0% found this document useful (0 votes)
7 views1,238 pages

Tesi Con Allegati

The document discusses the clinical impact of dosimetry in nuclear medicine therapy, focusing on 90Y-radioembolization (90Y-TARE) and Radioactive Iodine-I131 treatment (RAIT). It highlights the importance of personalized dosimetric evaluation for optimizing treatment outcomes and minimizing toxicity, as mandated by European Council Directive 2013/59. The PhD project aims to analyze dosimetric methods and their influence on treatment effectiveness for liver tumors and hyperthyroidism.
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF, TXT or read online on Scribd
0% found this document useful (0 votes)
7 views1,238 pages

Tesi Con Allegati

The document discusses the clinical impact of dosimetry in nuclear medicine therapy, focusing on 90Y-radioembolization (90Y-TARE) and Radioactive Iodine-I131 treatment (RAIT). It highlights the importance of personalized dosimetric evaluation for optimizing treatment outcomes and minimizing toxicity, as mandated by European Council Directive 2013/59. The PhD project aims to analyze dosimetric methods and their influence on treatment effectiveness for liver tumors and hyperthyroidism.
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF, TXT or read online on Scribd
You are on page 1/ 1238

UNIVERSITA’ DEGLI STUDI DI TORINO

Scuola di Dottorato in Scienze della Vita e della Salute


Dottorato in Fisiopatologia Medica

CLINICAL IMPACT OF DOSIMETRY IN NUCLEAR MEDICINE


THERAPY.

Tutor
Prof.ssa Désirée Deandreis
Prof. Gianni Bisi

CANDIDATA
Dott.ssa Monica Finessi

1
INDICE

CAPITOLO 1

1. INTRODUCTION. pag. 3

1.1 90Y-radioembolization (90Y-TARE). pag. 4


1.2 Radioactive Iodine-I131 treatment (RAIT). pag. 7

2. MATERIAL AND METHODS. pag. 10

2.1 90Y-radioembolization (90Y-TARE). pag. 10


2.2 Radioactive Iodine-I131 treatment (RAIT). pag. 15

3. RESULTS. pag. 17

3.1 90Y-radioembolization (90Y-TARE). pag. 17


3.2 Radioactive Iodine-I131 treatment (RAIT). pag. 21

4. DISCUSSION. pag. 30

5.CONCLUSIONS. pag. 35

6. REFERENCES. pag. 36

2
1. INTRODUCTION.

Dosimetric evaluation in nuclear medicine therapies is a crucial point and an actual issue.

The European Council Directive 2013/59 equalizes nuclear medicine therapy to

radiotherapy and, in particular, article 56 (1) describes the optimization principle with the

ALARA (as low as reasonably achievable) concept and states that “for all medical exposure

of patients for radiotherapeutic purposes, exposures of target volumes shall be individually

planned and their delivery appropriately verified taking into account that doses to non-

target volumes and tissues shall be as low as reasonably and consistent with the intended

radiotherapeutic purpose of the exposure”.

Dosimetric evaluation is routinely applied in external beam radiation therapy (EBRT)

through dosimetric planning by the medical physicist and verified during therapy, but it is

rarely performed in nuclear medicine therapy for several reasons, first because it is time

consuming and for the lack of evidence in standardized threshold values of absorbed dose

for efficacy and toxicity. Concerning the first point, dosimetric approach is not always

feasible, as it requires operator and specific faculties (whole-body counts or repeated scan

and sometimes blood samples over some days after radiopharmaceutical administration)

becoming a time-consuming procedure for both operator time and patient. For some

therapies, in fact, it is necessary to repeatedly scan the patient up to a week after the

administration, to trace the distribution in the body and calculate the permanence in the

various organs. Furthermore, the real advantages of dosimetric approach over empiric

approach, in several fields needs to be demonstrated.

Despite major limits of dosimetry, directive 2013/59 makes a nuclear medical therapy

based on fixed posology (empirical models) inadequate, and push towards a personalized

optimization based on dosimetry.

3
My PhD project was focused on dosimetric evaluation in radioembolization therapy for

primary and secondary unresectable liver tumor with 90Y microspheres (90Y-TARE) and 131I

therapy (RAIT) for hyperthyroidism in toxic adenoma (TA), toxic multinodular goiter (TMG)

and in Graves’ disease (GD), in order to evaluate the impact in clinical routine and in patient

outcome.

1.1 90Y-radioembolization (90Y-TARE).

Primary liver cancer is the fifth most common cancer and the second most frequent cause

of cancer-related death globally, accounting for 7% of all cancers. Hepatocellular carcinoma

(HCC) represents about 90% of primary liver cancers and constitutes a major global health

problem (2).

Patients with HCC are classified into five stages according to the Barcelona-Clinic Liver

Cancer (BCLC) classification (0, A, B, C and D) with an established treatment recommended

(2).

Early stage liver cancer patients can benefit from curative treatments such as resection,

liver transplantation or ablation (2). The intermediate-stage patients are most likely to

benefit intra-arterial treatments such as trans-arterial chemoembolization (TACE) and/or

90Y-TARE or external-beam radiation therapy (EBRT) (2), instead in case of advanced stage,

systemic therapy with Sorafenib in mainly indicated.

During the past two decades, 90Y-TARE has emerged as a safe and efficacious treatment

modality for unresectable primary and secondary liver tumours (2). The rationale of this

treatment is based on the fact that tumoral liver lesions are generally vascularized via the

hepatic artery, whereas healthy liver is almost excluded from arterial vascularization and

blood is prevalently supplied via the portal vein. This phenomenon leads to the possibility

4
to deliver radioactive microspheres to the tumor through trans-arterial administration in

order to irradiate locally the lesion.

Yttrium-90 (90Y) is a pure beta-emitting radionuclide with a physical half-life (T 1/2) of 64.2

hours. About 94% of the 90Y radiation dose is delivered during the first 11 days following

treatment (3).

The 90Y maximum and mean energies are respectively 2.26 and 0.926 MeV while the

maximum tissue penetration depth is 11 mm (mean penetration is 2.5 mm). 1 GBq of 90Y

distributed in 1 kg of tissue delivers a total dose of 50 Gy/kg in tissue (4).

Two types of 90Y-microspheres are commercially available: resin microspheres (SIR-

Spheres®; SIRTeX Medical, Lane Cove, NSW, Australia) and glass microspheres

(TheraSphere®; Nordion, Ottawa, Ontario, Canada) with some different characteristics. The

main differences (4) are the size of microspheres (20 and 60 μm of resin type vs 20–30 μm

of glass one), the number of spheres per vial (40-80 million vs 1.2-8 million) and the spheres

specific activity (40-70 vs 2500 Bq per sphere). This means that an higher number of

particles are infused with 1 GBq of resin microspheres compared to the same activity of

glass microspheres, thus leading to a potential higher embolic effect. Lastly, in case of resin

microspheres, the activity into the vial can be fractionated in more than one patient, while

in case of glass microspheres a single vial is use for a single patient.

Therapy session is preliminary simulated by means of two procedures: diagnostic

angiography and diagnostic scintigraphy by intra-arterial administration of 99mTc labelled

macroaggregate albumin (99mTc-MAA) that should mimic the vascular distribution pattern

of 90Y microspheres. The simulation is performed by acquisition of planar and tomographic

images by SPECT/CT that allows tumour and healthy liver uptake assessment, detection

and quantification of possible lung shunt fractions and gastrointestinal shunts.

5
Furthermore, pre-therapeutic scintigraphy is used for determining dosimetry in the frame

of individualized treatment planning.

Radioembolization is most successful when tumoral dose is optimized and non-target

deposition is minimized. Different dosimetric methods are proposed to quantify the activity

to deliver to the tumor. Three methods are proposed by resin microspheres manufactures

(5): the empirical method that is based only on tumor volume (the larger the tumor burden,

the higher the recommended activity), the body surface area (BSA) method that

incorporates also body surface area, assuming a correlation between BSA and tumor

volume and the multi-compartimental MIRD macrodosimetry or partition model, that

hypotizes that the three compartments involved in radioembolization are distinguishable

between them.

For glass spheres only non-compartmental MIRD macrodosimetry method is proposed,

that is slightly simplified, assuming homogeneous activity distribution in the liver, tumor

and lung (if any shunting occurs).

According to the manufacturers, the recommended absorbed dose of glass spheres to the

target should be 120 Gy for the entire involved lobe with a maximum lung doses of 30 Gy,

without constraint for normal liver. Usually, and especially in trials, it is recommended to

deliver an absorbed dose of 80–150 Gy to the injected lobe, site of disease.

Recent developments may allow for more precise individualized dosimetry (6). Despite

personalized precision dosimetry is essential to improve patient outcomes, it has not been

incorporated into the recently published and ongoing randomized clinical trials for 90Y

TARE.

In order to determine the effect of a treatment on both tumors and normal tissues and to

compare different radiation therapies, it is essential to evaluate the biological effects by

6
applying the linear-quadratic principle (LQ). This includes the calculation of the biological

effective dose (BED), which represents the dose producing the same biological effect

obtained with various dose rates and time radiation distributions. For BED evaluation it is

essential to know the absorbed dose deliver to the tumor. The first aim of this PhD project

was to investigate the influence of different dosimetric methods on BED calculation (the

correlation between absorbed dose and BED is not linear) in order to make a future

comparison between TARE and other radiation therapies, in particular in term of healthy

liver toxicity (4).

1.2 Radioactive Iodine-I131 treatment (RAIT).

Thyrotoxicosis is a clinical condition characterized by high serum free triiodothyronine (fT3)

and free thyroxine (fT4) (7). Hyperthyroidism can be either overt or subclinical. Overt

hyperthyroidism is characterized by low serum thyroid-stimulating hormone (TSH)

concentrations and raised fT3 and fT4 levels while, in contrast, in subclinical

hyperthyroidism are still normal (8).

The prevalence of hyperthyroidism is 1.2–1.6% (0.5–0.6% overt; 0.7–1.0% subclinical) (7–

9), with an increased incidence of mild hyperthyroidism in iodine-deficient areas (8,10) and

it can be sustained by different clinical conditions such as Graves’ disease (GD), toxic

multinodular goiter (TMG) or toxic adenoma (TA).

Graves’ disease is an organ-specific autoimmune disease more frequent in women with a

population prevalence of 1–1.5%. It is caused by the presence of thyrotropin receptor

antibodies (TRAb) that stimulate the thyroid-stimulating hormone (TSH) receptor (TSHR)

(7), leading to hyperfunction and goiter (9).

7
Toxic multinodular goiter and toxic adenoma are relatively common findings in iodine-

deficient areas accounting for 50% of all cases of hyperthyroidism (8), with a predominant

incidence in elderly patients. TMG often occurs in patients with a history of nontoxic goiter

that may develop autonomous growth and function over time; also somatic mutations of

TSHR and/or Gsα gene that lead to autonomy have been described (11–13).

Treatment choice is based on biochemical, clinical evaluation including neck ultrasound and

thyroid scintigraphy in order to confirm hyperthyroidism status, to define the cause and to

exclude thyrotoxicosis secondary to thyroiditis, iodine-induced and drug-induced thyroid

dysfunction, and factitious ingestion of excess thyroid hormones (8).

Therapy options for hyperthyroidism include antithyroid drugs (ATDs), RAIT and surgery.

According to recent American Thyroid Association (ATA) guidelines (7) in GD all therapeutic

options are indicated: despite in the past in the United States, RAIT has been the first

therapy option, in recent years shows a reduction in trend use of RAIT in favour of ATDs

administration (7). ATDs like propylthiouracil (PTU), carbimazole (CBZ) and methimazole

(MMI) are used as a first line therapy to reduce thyroid hormone synthesis and to obtain

remission that is defined as a euthyroid status for one year after ATDs cessation (14). If

remission is not achieved after 12-18 months (9), defined as the optimal duration of ATDs

regimen, or in case of relapse after drugs cessation, definitive approaches such as RAIT and

thyroidectomy are indicated. In case of TMG or TA, spontaneous remissions rarely occur

after ATDs, so early definitive approaches are preferred (14).

Thyroidectomy is an effective treatment for large TMG or in case of suspicious nodules.

Despite it represents the latter choice for therapy for other causes of hyperthyroidism,

sometimes it can be preferred as definitive approach to avoid exposure to ATDs or RAIT

8
(15) or in case of intolerance of ATDs. However thyroidectomy does not exempt to

complications related to specific surgical approach (9).

RAIT with 131I is a safe and generally well tolerated treatment for hyperthyroidism since

1940’s (16). The goal of RAIT is to achieve a non-hyperthyroid status, which can be

euthyroid or hypothyroid (16) providing a sufficient radiation dose in the thyroid

administering either a fixed or a calculated activity by dosimetric methods (7,17). A meta-

analysis published in 2009 (17) compared the effect of fixed versus calculated activity of

RAI in hyperthyroidism and resulted in an equally successful treatment outcome, despite

randomized trials are still required to define the best treatment approach.

RAIT’s complications are rare, except for those related to orbitopathy, that must be

carefully investigated and treated following indications of EUGOGO guidelines (18); thyroid

storm occurs only rarely after RAIT (19,20).

RAIT timing and purpose may be different according to different clinical indication. In case

of GD, RAIT is a very effective treatment with the goal to achieve hypothyroidism,

otherwise, in case of TMG or TA, the goal of RAIT is the rapid and durable elimination of

the hyperthyroid state, preferably reaching an euthyroid status. As a second goal, it is

possible to improve mechanical issues (i.e. dysphagia, dyspnea) reducing the volume of

toxic thyroid nodule(s) and/or thyroid goiter (21,22).

In case of GD, ATA guidelines (7) and European Association of Nuclear Medicine (EANM)

guidelines (16) define as goal of therapy the obtainment of an hypothyroid status either

administering a fixed activity or by a dosimetric approach considering both thyroid size and

RAI uptake. Regardless treatment approach, in GD RAIT goal strongly depends on

administered activities ranging from 61% success with 200 MBq to 86% with 580 MBq (7).

9
In case of TMG or TA, both ATA (7) and EANM (16) guidelines indicate as a goal the

restauration of euthyroidism, avoiding hyporthyroidism, either with fixed activity or by

dosimetric approach. Literature data reported in patients with nodular goiter a response

of 50%–60% after 3 months and 80% after 6 months (22,23) with a prevalence of

hypothyroidism of 3% and 64% at 1 and 24 years respectively (24).

The aim of this study was to analyse the outcome of RAIT in a large series of patients treated

according to a dosimetric approach in our institution between 2000 and 2018 and to

identify clinical variables associated to patient’s outcome.

2. MATERIAL AND METHODS.

2.1 90Y-radioembolization (90Y-TARE).

Twenty-nine consecutive patients with unilobar HCC (BCLC-B, Child score ≤ B7) treated

between November 2014 and May 2016 (median age 62, range 48-75) were included in the

study. Fifteen patients hospitalized at the Nuclear Medicine Department of Mauriziano

Hospital were treated with resin microspheres; fourteen patients hospitalized at the

University Nuclear Medicine Department of Città della Salute e della Scienza were treated

with glass microspheres. According to the manufacturers, the prescribed dose of glass

spheres was 120 Gy for the entire lobe with maximum lung doses of 30 Gy, without

constraint for normal liver; for the resin spheres our aim was to deliver 120 Gy to lesions

and a maximum of 40 Gy to healthy parenchyma. The activities to be administered were

calculated according to the mono-compartimental method for glass micropsheres and

according to partitional model for the resin ones. The mean injected 90Y activity was: 2.6

GBq (range 1.3 – 4.1 GBq) and 1.5 GBq (range 0.8 – 2.7 GBq) for glass and resin spheres

respectively.

10
A simulation was performed prior to injecting microspheres by infusion of 99mTc-MAA for

both groups. Two total body planar images (anterior and posterior) and a tomographic

exam were acquired. The SPECT-TC images were corrected by attenuation and scatter

(Siemens SymbiaIntevoT2, IterativeFlash3Dreconstruction algorithm) for the patients

treated with resin microspheres, while SPECT acquisition was performed and corrected

only by attenuation (GE Varicam, GE Xeleris3 workstation) for the patients treated with

glass microspheres. From the planar images, without attenuation correction, the lung shunt

(L) was calculated as the ratio between the total lung counts and the sum of the total liver

and lung counts.

Regardless of the manufacturer suggestions, the predicted tumor and healthy liver average

doses were calculated with three different methods for all the patients. The first method

was based on the recommendations provided by the American Association of Physicists in

Medicine (AAPM) (25) that suggest to draw a region of interest (ROI) on the anterior and

posterior planar images encompassing the tumor. The same ROI must then be moved

across the normal liver, on a region with a relatively uniform activity uptake (Fig. 1).

Fig 1. Example of planar images with ROIs encompassing the tumour and the same ROIs over the healthy

liver.

The dose to normal liver (NL) was then calculated as (25):

11
49.38 (Gy  kg/GBq) is equal to the product k<E>t1/2/ln2 with k a constant to yield the

dose in desired units and <E> the average energy emitted for nuclear transition; A is the

activity to be administered; L is the lung shunt fraction; mNormalLiver and mTumor are the mass

of normal liver and tumour respectively and T/N is the tumour-to-normal tissue ratio. T/N

was calculated from the counts of the ROIs drawn on planar images: T/N = (Counts Tumor /

mTumor) / (CountsNormalLiver / mNormalLiver). mNormalLiver and mTumor were obtained by means of

computed tomography (CT) images.

Whereas the tumour (T) dose was (25):

The second method was the multi-compartimental MIRD one (5,26) using SPECT-CT

corrected images. Two volumes of interest (VOIs), defining the tumour and the normal

liver, were drawn on images in order to estimate uptakes and volumes (Fig. 2). The masses

were obtained by multiplying the volumes by the density (1.03 g/cm3). The dose fraction

accumulated in the tumor (fractional tumor uptake) was (26):

where TLR has the same meaning as T/N, but calculated through VOI values. For the normal

liver, the fractional uptake was:

12
Accordingly, the mean doses for tumor and healthy liver were respectively (26):

and

Fig 2. Example of VOIs (tumour and normal liver uptake) on the tomographic images.

The third method, the Voxel-based method, also uses the SPECT-CT 3D corrected matrix. A

MATLAB® (Mathworks) code was developed by medical physicist at our departments.

Convolution calculations were adopted: for each target voxel i, the mean absorbed dose

(Di) from N surrounding source voxels along the three major axis was calculated as the

product between the cumulated activity in the voxel k and the S factor according to the

MIRD schema (27,28):

13
Where S factor is the absorbed dose to the target voxel per unit of cumulated activity in

the source voxel. k = 0 is the contribution of self-irradiation.

The cumulated activity was equal to the integral of the activity over the time. Due to the

permanent trapping of the microspheres by the liver (no biological clearance), for 90Y

radioembolization only one 99mTc-MAA SPECT is needed and is:

where 1.443 is the inverse of ln2, Ak is the initial activity (corrected for the lung shunt) into

the voxel k and t1/2 is the 90Y physical half-life. The S values were obtained from the on-

line free database http://www.medphys.it/ for the specific voxel size values (resin spheres:

4.8 mm; glass spheres: 3.45 mm) (29). The contributions of the 5 closest voxels (N = 5) were

considered.

Biological effective dose (BED) was calculated from the average absorbed dose D to

tumours and to the healthy parenchyma obtained with the three different dosimetric

methods according to the formula (30):

(9)

where Teff and Trep are the halftimes for 90Y decay and repair damage. α/β is assumed to be

2.5 Gy for the normal tissue and 10 Gy for the tumour; T eff = Tphysical = 64.2 h and Trep =

2.5 h for normal liver, 1.5 h for tumour. D is the average dose allowing a fair comparison

between the dosimetric methods.

14
Statistical comparisons between absorbed doses (D and BED) calculated according to the

three dosimetric methods were carried out with the Mann-Whitney two tails test

(significance level of 5 %).

2.2 Radioactive Iodine-I131 treatment (RAIT).

A total of 424 consecutive patients referred to our department for RAIT between 2000 and

2018 (121 men and 303 women) for hyperthyroidism related to GD (n=150), TMG (n=213)

and TA (n=61) with a minimum of 12 months follow-up were included in the study.

RAI administered activity (A0) was calculated, after ADT 7-15 days withdrawal, in all patients

according to the formula proposed by Snyder et al. (31) taking into account the

recommended absorbed radiation dose to target (DT), the thyroid mass in g (m0), maximum

rate of thyroid RAI uptake (Umax) and effective half-life in the target tissue (T1/2 eff):

(DT ⋅ m0)

A0 = 5,829 ⋅

(Umax ⋅ T1/2 eff).

Dose to target was established according to EANM guidelines (16) on the basis of both

patient’s clinical condition and presence/absence of ophthalmopathy after careful

evaluation of disease activity by an experienced ophthalmologist.

According to EANM guidelines (16) DT with the aim to restore euthyroidism is 150 Gy, in

patients with GD; in case of TMG or TA recommended doses to achieve ablation are 150-

300 Gy and 300-400 Gy, respectively.

Thyroid mass was calculated considering a density of 1 g/ml and by the sum of volume of

lobes or nodes using 99mTc-pertechnetate scintigraphy. For 99mTc-pertechnetate scan a

15
scintillation camera equipped with a low-energy, high-resolution, parallel-hole collimator

was used.

Maximum rate of thyroid RAI uptake (Umax) and effective half-life in the target tissue (T1/2

eff) were assessed by daily (6-24-48-72-96h) uptake measurement after administration of 2

MBq of 131I using a detector with sodium iodide crystal of 5 cm diameter and 5 cm depth

(2×2 inches). The fraction of the administered activity stored in the target mass at 6-24-48-

72-96h after 131I administration was considered the maximum rate of thyroid RAI uptake

and calculated by the count rates measured for the tracer activity prior the administration

and for the activity in the target tissue after the administration at established time points

(32). Effective half-life in the target tissue was calculated on at least three radioiodine

uptake measures (4 to 6 h, 24 to 48 h and 96 h) (32).

All the patients with the following data available were considered for analysis: age at time

of treatment, ATDs duration and posology, thyroid function assessed by TSH and fT4

evaluation at time of treatment and after 6 and 12 months follow-up at our center after

RAIT, absorbed dose and dimensional variation of target mass from baseline to 6- and 12

months follow-up assessed by neck ultrasound. Unfortunately, TRAb level at time of

treatment was not available in all patients, in particular in GD patients, so was not included

in our analysis.

Thyroid function was assessed by measurement of TSH and fT4 by a chemiluminescent

immunometric assay (DiaSorin, Saluggia, Italia). Normal values range for TSH were 0.25-3.5

UI/L, for fT4 7.8-19 ng/L respectively. Serum fT3 was measured using a radioimmunologic

assay (DiaSorin, Saluggia, Italia) with normal range between 2.2-4.4 ng/L.

After RAIT, all patients without contraindications were medicated with beta-adrenergic

blocking agents (propranolol) to prevent tachyarrhythmia, especially in elderly, and in

16
patients at high risk of development/worsening of orbitopathy prophylactic steroids oral

administration were administered, according to EUGOGO guidelines (33).

Response at 6 and 12 months was considered in case of euthyroidism condition with TSH

and fT4 plasma levels in the range of normality, subclinical hypothyroidism with TSH above

the upper normal limit with fT4 in the range of normality or overt hypothyroidism as TSH

above the upper normal limit with fT4 < 7.8 ng/L. Absence of response was considered in

case of subclinical hyperthyroidism with suppressed TSH values with normal fT4 or overt

hyperthyroidism with suppressed TSH and fT4 > 19 ng/L.

For descriptive statistics, the median (range) was used for continuous variables, while the

categorical ones were described by their relative/absolute frequencies. For the inferential

approach, the Mann-Whitney test was used for continuous covariates, while the

associations of 6 and 12 months response to RAIT were investigated by the Fisher’s exact

test. Two full series of univariate/multivariate binary logistic regression models were used

to estimate the potential impact of different predictors (independent variables) such as

disease duration, administered dose, TSH plasma levels, total administered activity on the

6 and 12 months response (dependent variables), respectively. All reported p-values were

obtained by the two-sided exact method, at the conventional 5% significance level. Data

were analyzed as of May 2019 by R 3.5.2 (R Foundation for Statistical Computing, Vienna-

A, http://www.R-project.org).

3. RESULTS.

3.1 90Y-radioembolization (90Y-TARE).

Figure 3 shows the absorbed doses and BEDs obtained. A summary of the mean values can

be seen in Table 1.

17
Tab. 1 Summary of average doses and BEDs for T and NL for both types of microspheres.

For resin microspheres, no statistical significant difference between MIRD and Voxel

methods was found (p-values: 0.48 and 0.52 for tumour and healthy parenchyma doses

respectively; 0.51 and 0.60 for corresponding BEDs). AAMP doses were discordant with

those obtained according to the MIRD and Voxel methods (p-values< 0.01). Furthermore,

tumour BEDs were much higher (from 65% to 400%), while the normal liver BEDs were

much lower (from – 90% to – 42%). The calculated tumour-to-normal tissue ratios on planar

images were on average 14 times greater than those obtained on SPECT-CT images.

A good correlation was observed between the BED values estimated with Voxel method

and those estimated with the MIRD one (Fig. 3) (Pearson correlation coefficient r = 0.96 for

normal liver and 0.99 for tumour). MIRD values were approximately 10% lower than Voxel

values (mean ± st.dev, NL: -7 ± 15 %; T: -12 ± 10 %).

18
Fig. 3 Correlation between Voxel dosimetry and MIRD method BED values for normal liver and tumours for

resin microspheres.

For glass microspheres, no significant statistical differences between MIRD and Voxel

methods were observed either (p-values: 0.05 and 0.51 for tumour and healthy

parenchyma doses respectively; 0.05 and 0.53 for corresponding BEDs), while for tumours

there were significant dose differences between AAPM and the other two methods with a

spread range of values as shown in Fig. 4 (p-values: 0.01 for both absorbed dose and BED).

Lower discrepancies were found for NL with no significant statistical difference (p-values >

0.05). For this type of microspheres, the T/N ratios on the planar images were on average

4 times higher than T/N ratios on tomographic images. A good correlation was observed

between the BED values estimated with both MIRD and Voxel methods (Fig. 5), through

slightly better in the case of the tumour (r = 0.72 for normal liver and 0.94 for tumour).

The results of this study have been published in 2016 in Physica Medica Journal (attached

file A) (4).

19
Fig. 4 Tumour and normal liver absorbed doses and biologically effective doses (BEDs) for resin and for glass

microspheres.

20
Fig. 5 Correlation between Voxel dosimetry and MIRD method BED values for healthy liver and tumours for

glass microspheres.

3.2 Radioactive Iodine-I131 treatment (RAIT).

A total of 424 patients with hyperthyroidism were included in this retrospective study (GD

n = 150; TMG n = 213; TA n = 61). In the entire population, median TSH level, median fT4,

median ATD duration and median RAI administered activity were 0.24 mcU/ml (0.01-1.11),

12.0 pg/ml (9.6-14.2), 24 months (12-60) and 520 MBq (444-600), respectively. Patients

characteristics are summarized in Table 2.

21
Tab 2. Baseline characteristics of the 424 patients included in the study [median(interquantile
range)]

Variable Value

Median Age (yrs) 63 (51.3-71.1)

Sex

Male 121 (28.5%)

Female 303 (71.5%)

Diagnosis

Graves’ disease (GD) 150 (35.4%)

Toxic multinodular goiter (TMG) 213 (50.2%)

Toxic adenoma (TA) 61 (14.4%)

Thyroid status

Subclinical Hyperthyroidism 324 (76.4%)

Overt Hyperthyroidism 97 (22.9%)

Missing 3 (0.7%)

Laboratory at treatment

Median TSH (UI/L) 0.24 (0.01-1.11)

Median fT4 (ng/L) 12.0 (9.6-14.2)

Dimensional US assessment (mm)

Thyroid size at treatment 45 (39-53)

1yr- Thyroid size 33 (24-43)

Nodule size at treatment 25 (17-34)

1yr- Nodule size 19 (12-28)

22
ATD

Median duration (months) 24 (12-60)

Median posology (mg) 5 (2.5-10)

RAIT (median value)

Median activity administered (MBq) 520 (444-600)

Median dose to target (Gy) 334 (244-428)

An overall response rate of 78.7% and 83% was observed at 6 and 12 months, respectively.

In GD group (n=150, 31 male and 119 female), 105 patients (70.5%) presented subclinical

hyperthyroidism and the remaining 45 patients overt hyperthyroidism, with a median TSH

0.01 mcUI/ml (0.004-1.31), a median ATD duration from diagnosis of 48 months (24-84),

median ATD posology per day of 7.5 mg (5-10) and median lobe size of 42 mm (36-50).

Median 131I A0 was 520 MBq (445-600), with a median DT of 336 Gy (277-416). Six months

after RAIT 75.2% of patients were considered responders (65.1% of patient presented overt

hypothyroidism, 5.4% subclinical hypothyroidism, 4.7% euthyroid status), while remaining

24.8% of patients were considered no-responders (16.1% of patient presented overt

hyperthyroidism and 8.7% subclinical hyperthyroidism status). Twelve months after RAIT

79.7% of patients were considered responders (70.6% of patients presented overt

hypothyroidism, 7.0% euthyroid and 2.1% subclinical hypothyroidism status), while

remaining 20.3% of patients were considered no-responders (16.1% of patients presented

overt hyperthyroidism and 4.2% subclinical hyperthyroidism). At the end of 12 months

follow up, 16% of patients (n= 24), required a further dose of 131I for persistent

hyperthyroidism.

23
In TMG group (n=213, 65 male and 148 female), 169 patients (80.1%) presented subclinical

hyperthyroidism before treatment, while the remaining 44 patients overt hyperthyroidism,

with a median TSH 0.336 mcUI/ml (0.02 – 1.13), median ATD duration from diagnosis of 22

months (10-36), median ATD posology per day of 5 mg (2.5-7.5) and median lobe size of 46

mm (40-56). Median 131I A0 was 520 MBq (444-600), with a median DT of 355 Gy (247-464).

Six months after RAIT 78.3% of patients were considered responders (59.4% of patients

presented euthyroidism, 10.2% overt hypothyroidism and 8.7% subclinical

hypothyroidism), while remaining 21.7% of patients were considered no-responders

(11.6% of patients with persistent subclinical hyperthyroidism and 10.1% in overt

hyperthyroidism status); 12 months after RAIT 82.7% of patients were considered

responders (61.9% of patients presented euthyroidism, 17.3% overt hypothyroidism and

3.5% subclinical hypothyroidism status), while remaining 17.3% of patients were

considered no-responders (12.4% of patients with overt hyperthyroidism and 4.9%

subclinical hyperthyroidism). At the end of follow up 3.7% of patients (n= 8), required a

further dose of 131I for persistent hyperthyroidism.

In TA group (n=61, 25 male and 36 female), 50 patients (82.0%) presented subclinical

hyperthyroidism before treatment, while 11 remaining patients presented with overt

hyperthyroidism, with a median TSH 0.19 mcUI/ml (0.01 – 0.87), median ATD duration from

diagnosis of 12 months (6-24), median ATD posology per day of 5 mg (2.5-7.5) and median

node size of 30 mm (22-37). Median A0 was 445 MBq (370-555), with a median DT of 241

Gy (172-338). Six months after RAIT 88.5% of patients were considered responders (70.5%

of patients presented euthyroid, 13.1% overt hypothyroidism and 4.9% subclinical

hypothyroidism), while remaining 11.5% of patients were considered no-responders (4.9%

of patients with subclinical hyperthyroidism and 6.6% overt hyperthyroidism status); 12

24
months after RAIT 93.2% of patients were considered responders (67.8% of patients

presented euthyroidism, 16.9% overt hypothyroidism and 8.5% subclinical

hypothyroidism), while remaining 6.8% of patients were considered no-responders (5.1%

of patients presented overt hyperthyroidism and 1.7% subclinical hyperthyroidism). At the

end of follow up 3.2% of patients (n= 2), required a further dose of 131I for persistent

hyperthyroidism. Response and patients’ characteristics according to different subgroups

are summarized in table 3.

Tab 3. Outcome at 6 and 12 months of the entire cohort divided by etiology groups.

GD TMG TA
Number of patients 150 213 61
Male 31 65 25
Female 119 148 36
Clinical presentation
Overt hyperthyroidism 45 44 11
Subclinical 150 169 50
hyperthyroidism
Median age (range) at 50 (15-86) 67 (32-91) 66 (30-83)
treatment
Median baseline TSH 0.01 mcUI/ml 0.336 mcUI/ml 0.19 mcUI/ml
(0.004-1.31) (0.02-1.13) (0.01-0.87)
Median ATD duration 48 months (24- 22 months (10- 12 months (6-
from diagnosis 84) 36) 24)
Median ATD posology 7.5 mg (5-10) 5 mg (2.5-7.5) 5 mg (2.5-7.5)
per day
Median target size 42 mm (36-50) 46 mm (40-56) 30 mm (22-37)
Median administered 520 MBq (445- 520 MBq (444- 445 MBq (370-
activity 600) 600) 555)

25
Median Dose to target 336 Gy (277-416) 335 Gy (247-464) 241 Gy (172-
380)
6-mo assessment result
Response 75.2% 78.3% 88.5%
Euthyroidism 4.7% 59.4% 70.5%
Overt hypothyroidism 65.1% 10.2% 13.1%
Subclinical 5.4% 8.7% 4.9%
hypothyroidism
24.8% 21.7% 11.5%
No-response 16.1% 10.1% 6.6%
Overt hyperthyroidism 8.7% 11.6% 4.9%
Subclinical
hyperthyroidism
12-mo assessment
result 79.7% 82.7% 93.2%
Response 7.0% 61.9% 67.8%
Euthyroidism 70.6% 17.3% 16.9%
Overt hypothyroidism 2.1% 3.5% 8.5%
Subclinical
hypothyroidism 20.3% 17.3% 6.8%
16.1% 12.4% 5.1%
No-response 4.2% 4.9% 1.7%
Overt hyperthyroidism
Subclinical
hyperthyroidism

Regardless hyperthyroidism etiology, in the whole 424 patients cohort, response group

compared to no-response group at 6 months presented higher median TSH baseline values

(0.36 vs 0.08 mcUI/ml, p<0.001) (Fig.6), lower ATD duration (24 vs 36 months, p=0.004)

(Fig.7), lower ATD posology (5 vs 7.5 mg/die, p=0.014) (Fig.8) and lower DT (327 vs 373 Gy,

p=0.003) (Fig.9). No statistical differences were found between groups in dimensional

variation of target size. At 12 months, response group compared to no-response group

26
presented higher median TSH baseline values (0.34 vs 0.08 mcUI/ml, p=0.002) (Fig.6) and

lower ATD duration and posology (24 vs 32 months, p=0.043 and 5 vs 7.5 mg/die, p=0.005)

(Fig. 7, 8). No statistical differences were found between groups in D T and in dimensional

variation of target mass.

Fig.6: Response group compared to no-response group, at 6 and 12 months, presented higher
median TSH baseline values (0.36 vs 0.08 mcUI/ml, p=0.001 and 0.34 vs 0.08 mcUI/ml, p=0.002,
respectively).

Fig.7: Response group compared to no-response group, at 6 and 12 months, presented lower ATD
duration (24 vs 36 months, p=0.004 and 24 vs 32 months, p=0.043, respectively).

27
Fig.8: Response group compared to no-response group, at 6 and 12 months, presented lower ATD
posology (5 vs 7.5 mg/die, p=0.014 and p=0.005, respectively).

Fig.9: Response group compared to no-response group at 6 months presented lower DT (327 vs 373
Gy, p=0.003).

The multivariate binary logistic model on the whole cohort identified as independent risk

factors for no-response both at 6 and 12 months , longer ATD duration (OR 1.01, p<0.001)

and OR 1.01, p=0.002 respectively), and higher ATD posology (OR 1.08, p=0.010) and OR

1.10, p=0.005 respectively) (Tab 4).

In particular, risk factors for no-response in GD group were longer ATD duration both at 6

and 12 months (OR 1.01, p=0.04)OR 1.01, p=0.026 respectively) and higher ATD posology

(OR 1.08, p=0.037(OR 1.09, p=0.059 respectively). In TMG group longer ATD duration both

28
at 6 (OR 1.01, p=0.005) and at 12 months (OR 1.01, p=0.012) and in TA group only higher

ATD posology at 6 months (OR 1.28, p=0.06) were identified as risk factors for no-response.

Tab 4: Multivariate logistic models to estimate the potential impact of different predictors on
response in the entire population.
OR 95% CI P value model
accuracy
6 months outcome 81.5%
ATD duration (months) 1.01 1.00-1.01 <0.001
ATD posology (mg) 1.08 1.02-1.14 0.010
TSH (mUI/l) 0.67 0.46-0.96 0.030
Age (>60 yrs) 1.66 0.89-3.11 0.115
12 months outcome 83.6%
ATD duration (months) 1.01 1.00-1.01 0.002
ATD posology (mg) 1.10 1.03-1.17 0.005
TSH (mUI/l) 0.70 0.48-1.02 0.061
Age (>60 yrs) 1.74 0.88-3.42 0.111

In these series, considering both TMG and TA group, there is a marginal, despite no

significant, trend of association between hypothyroidism onset post-RAIT and ATD duration

and ATD posology at 6 and 12 months, respectively; furthermore, subclinical

hyperthyroidism at treatment compared to overt hyperthyroidism showed a trend of

association with hypothyroidism onset both at 6 (p=0.029) and 12 months (p=0.1).

The results of this study have been presented as oral presentation (OP25) at 14th AIMN

congress (34) (attached file B)and as e-poster at annual 32nd EANM congress (EP0596) (34)

(attached file C).

29
4. DISCUSSION

This PhD project focused on clinical impact of dosimetry in nuclear medicine therapy

confirms the pivotal role of dosimetric evaluation in nuclear medicine therapy.

In case of 90Y-TARE, microsphere manufacturers have suggested various dosimetric

approaches, based on the body surface area of the patient and hepatic tumour involvement

(resin microsphere) or a mono-compartimental method, without distinguishing between

lesions and healthy liver tissue (glass microsphere). Three dosimetric methods that

distinguish between tumours and normal liver tissue were selected for this project: AAPM

recommendations, multi-compartimental MIRD and convolution based Voxel dosimetry.

All these methods employ MIRD formalism for absorbed doses evaluation, but they use

different methods to estimate volume of interest and uptake quantification. The first

method only requires planar images and can be used in departments in which no

tomographic images or attenuation corrected ones are available. MIRD and Voxel methods

are based on tomographic SPECT images.

The important point is to establish an available method to predict outcome. Some studies

have reported correlations between absorbed doses and clinical results. Ho et al. (35)

developed the partition model that subdivide lung, tumour and normal liver into separate

compartment and stated that it can predict complication rate, response rate and survival.

In a retrospective analysis of 20 arterial territories treated in 10 HCC patients using

SPECT/CT partition model, Kao et al. (36) observed that 100% tumour response could be

achieved when the predicted mean tumour dose was at least 91 Gy, without significant

toxicities and highlighted the importance of having a personalized dosimetric approach.

Chiesa et al. (37) suggested that the evaluation of dose distribution at voxel level outdoes

mean dose approach. Garin et al. (38) calculated tumour and healthy liver doses using a

30
quantitative analysis of 99mTc-MAA in 36 consecutive patients with HCC treated with glass

microspheres and found a strong correlation between response and tumour absorbed dose

and a relationship between survival and tumour absorbed dose. Another study conducted

by Garin at al. (38) in 71 inoperable HCC patients treated with glass microspheres showed

that dosimetry based on 99mTc-MAA SPECT/CT imaging was able to predict response and

survival.

For a comparison between results of the treatment between TARE and other radiation

therapies, it’s useful to employ the biological effective dose (BED) (39). This represents the

dose producing the same biological effect under various irradiation conditions.

The comparison between the three different dosimetric methods gave similar results for

the doses (absorbed and biological effective) of both volumes of interest (tumours and

healthy parenchyma) and similar results were obtained for resin and glass microspheres.

This study found a strong relationship between BED values estimated with Voxel dosimetry

and those estimated with the MIRD method (r = 0.96 and r = 0.72 for normal liver and r =

0.99 and r = 0.94 for tumour in case of resin and glass microspheres respectively). Instead

AAPM method appears to be less reliable.

In case of RAIT, the results of this project confirmed the effective and safe role of RAIT in

hyperthyroidism according to the literature data: only 8% of patients (n=34) requires a

second 131I administration mostly in GD group (16% vs 3.7% and 3.2% for TMG and TA,

respectively).

In case of GD, at 12 months follow-up, 79.7% of patients were considered responders,

according to previous published data. A prospective randomized trial published in 2015 (40)

comparing 91 GD patients outcome after administration of 550 and 1110 MBq of 131I,

presented a 1-yr therapeutic success of 84.6%, regardless the administered activity.

31
Another previous randomized trial published in 2012 (41) investigated the effectiveness of

2 fixed RAI doses, 370 MBq in 76 patients and 555 MBq in 52 patients respectively, and

found a similar remission rate in both groups (73.7% and 80.8%, respectively). A more

recent study (42) comparing empiric and calculated 131I activity, reported for 57 patients

with GD an overall success rate of 91%.

In case of TMG or TA, 82.7% and 93.2% of patients were considered as responders at 12

months follow-up assessment respectively. Our data agree with the results of previous

published studies. Reiners et al. (43) in 2012, stated that the rate of RAIT success in case of

TA ranges from 85% to 100%; moreover another study found a success rate of 93% one

year after treatment in patients with TMG (42). ATA guidelines (7) reported a resolution of

hyperthyroidism in case of TMG in 80% of patients at 6 months, similar to our data.

In our study overt hypothyroidism, requiring replacement therapy with l-thyroxine, occurs

1 year follow-up in 70.6% of cases in GD, 17.3% in TMG and 16.9% in TA group, confirming

literature data (7,44).

Furthermore, despite no significant, a trend of association was found between

hypothyroidism onset and ATD duration and posology, as previously suggested by other

authors (45).

In case of TMG and TA, 10.1% and 17.3% and 13.1% and 16.9% of patients experienced

overt hypothyroidism at 6 and 12 months follow up, respectively: these data, compared to

literature reported results, are concordant in case of TA (16,43), while are slightly higher

for TMG (7). In our study, higher incidence of hypothyroidism in case of TMG could be

explained by higher median administered DT (355 Gy, range 247-464 Gy) according to

dosimetric evaluation compared to recommended doses suggested by guidelines (16).

Substantial differences were also found in median DT both in case of TA and GD compared

32
to guidelines: in case of TA median DT was lower compared to EANM’s suggestions, while

in case of GD it was higher. These results may suggest that in case of TA response could be

achieved even with lower dose, allowing a reduction of both absorbed dose to critical

organs and days needed to respect radioprotection rules. On the contrary, higher median

DT founded in case of GD could indicate that in case of more aggressive GD, even with

ocular disease, higher doses are necessary to obtain hypothyroidism, that in clinical

practice represents the goal of treatment. On the other hand, higher median DT in case in

GD in our patient series could be explained by a sort of iodine resistance induced by long

term ATD treatment (median ATD 48 months). These results must be confirmed by large

prospective studies and must be correlated by clinical data such as disease duration and

activity.

Duration and posology of ATDs, PTU or MMI, were identified in this study as predictive

factors of treatment failure both in Grave’s disease, toxic multinodular goiter and toxic

adenoma. In our study patients dismissed ATDs at least 7-15 days before treatment. Long

pretreatment period of treatment with ATDs may have several explanations, first patient’s

reticence to perform RAIT or delayed sending of the patient to the nuclear medicine by

endocrinologist specialist.

ATDs are employed in the treatment management of hyperthyroidism, also as a “pre-

medication” prior RAIT to restore an euthyroidism or, at least, to maintain a subclinical

hyperthyroidism condition to prevent post-treatment thyrotoxicosis especially in elderly

patients with concomitant cardiovascular disease or with orbitopathy. Possible

interference of long-lasting ADT treatment on RAIT efficacy is well recognized. Long

pretreatment period with ATDs, in particular Carbimazole, could decrease iodine uptake

with a higher risk of treatment failure, despite underlying mechanism is not fully

33
understood. In particular, it reduces the cell damage produced by synthesis of oxygen free

radicals subsequent to RAI administration (46). Also pretreatment with PTU is associated

with an higher risk of RAIT failure (47–49). Furthermore, Santos et al. (50) suggested that

PTU administration should be avoided in patients with Graves’ disease before RAIT because

could lead to higher risk of treatment failure compared to methimazole administration or

any therapy (p<0.05). A systematic review published in 2007 (20) compared the rates of

treatment failure and the short and long term side effects in patients with hyperthyroidism

treated with RAI with or without adjunctive ATDs and found out that the risk of treatment

failure defined as persistent or recurrent hyperthyroidism or need for further RAI

treatment was significantly higher in adjunctive ATDs group compared with control

(p=0.006); no significant differences were found between different ATDs.

Other studies not only found increased failure rates with prior ATDs, but also increased

incidence of hypothyroidism in those who were successfully treated (45,51): our study

covers a follow-up period of 6-12 months for each patients, so no data are available

regarding late onset hypothyroidism.

Despite the directive 2013/59 EURATOM underlines the necessity of dosimetric assessment

and the results of this PhD project confirm its pivotal role on nuclear medicine therapy,

dosimetry presents several controversies extensively discussed in a recent literature review

published as first author (52). Dosimetric assessment, in fact, is not always feasible, as it

requires operator and specific faculties, and when available, being a time-consuming

procedure for both operator time and patient. Furthermore, among different therapies,

different methodologies are proposed in the literature, according to patient preparation

type of dosimetry and a standardization is still needed, also taking into account what is

34
feasible in each center, as previous published in a literature review published in 2019 (52)

(attached file D)

5. CONCLUSIONS

These results of analysis, for both 90Y -TARE and RAIT, underline the fundamental role of

dosimetric approach that, together with correct patients’ selection and preparation, lead

to a better outcome of nuclear medicine therapies. In particular, for 90Y-TARE the AAPM

method appears to be less accurate than MIRD and Voxel ones. These last two methods

seem to be more suitable for accurate dosimetry for 90Y -TARE. For RAIT, the results of

retrospective analysis, not only confirms that RAIT is a safe and effective treatment for

hyperthyroidism of both autoimmune and nodular etiology, but also that a more

aggressive, older and uncontrolled disease revealed by low TSH levels, longer duration and

higher posology of ATD is associated to worse response.

The directive 2013/59 EURATOM defines all nuclear medicine application for therapeutic

purpose as a form of radiotherapy and underlines the need of both justification and

optimization of these procedures with dedicated dosimetric protocol: the results of this

project confirms the necessity of dosimetric evaluation not only in term of efficacy but also

in term of safety of the treatment. To optimize the clinical impact of dosimetric evaluation

in nuclear medicine therapy, however, randomized studies are required to allow a

standardization of dosimetry protocols to optimize not only activity to be administered, but

also patient’s outcome.

35
REFERENCES.

1. European Commission. Council Directive 2013/59/Euratom of 5 December 2013. Off J Eur Union.

2014;(December 2003):1–73.

2. Galle PR, Forner A, Llovet JM, Mazzaferro V, Piscaglia F, Raoul JL, et al. EASL Clinical Practice

Guidelines: Management of hepatocellular carcinoma. J Hepatol. 2018;69(1):182–236.

3. Tong A, Kao Y, Too C, Chin K, Ng D, Chow P. Yttrium-90 hepatic redioembolization: clinical review

and current techniques in interventional radiology and personalized dosimetry. Br J Radiol.

2016;89:20150943.

4. Gallio E, Richetta E, Finessi M, Stasi M, Pellerito RE, Bisi G, et al. Calculation of tumour and normal

tissue biological effective dose in 90 Y liver radioembolization with different dosimetric methods.

Phys Medica. 2016 Dec;32(12):1738–44.

5. Giammarile F, Bodei L, Chiesa C, Flux G, Forrer F, Kraeber-bodere F, et al. EANM procedure guideline

for the treatment of liver cancer and liver metastases with intra-arterial radioactive compounds. Eur

J Nucl Med Mol Imaging. 2011;38(7):1393–406.

6. Salem R, Padia SA, Lam M, Bell J, Chiesa C, Fowers K, et al. Clinical and dosimetric considerations for

Y90: recommendations from an international multidisciplinary working group. Eur J Nucl Med Mol

Imaging. 2019 May 16;

7. Ross DS, Burch HB, Cooper DS, Greenlee MC, Laurberg P, Maia AL, et al. 2016 American Thyroid

Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of

Thyrotoxicosis. Thyroid. 2016;26(10):1343–421.

8. Leo S De, Lee SY, Braverman LE, Unit E, Sciences C. Hyperthyroidism. Lancet. 2016;388(10047):906–

18.

9. Kahaly GJ, Bartalena L, Hegedüs L, Leenhardt L, Poppe K, Pearce SH. 2018 European thyroid

association guideline for the management of graves’ hyperthyroidism. Eur Thyroid J. 2018;7(4):167–
36
86.

10. Vejbjerg P, Knudsen N, Perrild H et al. Lower prevalence of mild hyperthyroidism related to a higher

iodine intake in the population: prospective study of a mandatory iodization programme. Clin

Endocrinol (Oxf). 2009;71:440–45.

11. Gozu H, Lublinghoff J, Bircan R, Paschke R. Genetics and phenomics of inherited and sporadic

nonautoimmune hyperthyroidism. Mol Cell Endocrinol. 2010;322:125–34.

12. Tonacchera M, Chiovato L, Pinchera A, Agretti P, Fiore E, Cetani F, et al. Hyperfunctioning Thyroid

Nodules in Toxic Multinodular Goiter Share Activating Thyrotropin Receptor Mutations with Solitary

Toxic Adenoma. J Clin Endocrinol Metab. 1998;83(2):492–8.

13. Vicchio T, Giovinazzo S, Certo R, Cucinotta M, Micali C, Baldari S, et al. Lack Of Association Between

Autonomously Functioning Thyroid Nodules And Germline Polymorphisms Of The Thyrotropin

Receptor And Gαs Genes In A Mild To Moderate Iodine-Deficient Caucasian Population. J Endocrinol

Invest. 2017;37:625–30.

14. Cooper DS. Antithyroid Drugs. N Engl J Med. 2005;352:905–17.

15. Bartalena L, Chiovato L, Vitti P. Management of hyperthyroidism due to Graves’ disease: frequently

asked questions and answers (if any). J Endocrinol Invest. 2016;39(10):1105–14.

16. Stokkel MPM, Handkiewicz Junak D, Lassmann M, Dietlein M, Luster M. EANM procedure guidelines

for therapy of benign thyroid disease. Eur J Nucl Med Mol Imaging. 2010;37(11):2218–28.

17. De Rooij A, Vandenbroucke J, Smit J, Stokkel M, Dekkers O. Clinical outcomes after estimated versus

calculated activity of radioiodine for the treatment of hyperthyroidism: systematic review and meta-

analysis. Eur J Endocrinol. 2009;161(5):771–7.

18. Bartalena L, Baldeschi L, Dickinson AJ, Eckstein A, Kendall-Taylor P, Marcocci C, et al. Consensus

statement of the European group on Graves’ orbitopathy (EUGOGO) on management of Graves’

orbitopathy. Thyroid. 2008;18(3):333–46.


37
19. McDermott M, Kidd G, Dodson LJ, Hofeldt F. Radioiodine-induced thyroid storm. Case report and

literature review. Am J Med. 1983;75:353–9.

20. Walter MA, Briel M, Christ-Crain M, Bonnema SJ, Connell J, Cooper DS, et al. Effects of antithyroid

drugs on radioiodine treatment: systematic review and meta-analysis of randomised controlled

trials. BMJ. 2007;334(7592):514.

21. Bonnema S, Bertelsen H, Mortensen J, Andersen P, Knudsen D, Bastholt L, et al. The feasibility of

high dose iodine 131 treatment as an alternative to surgery in patients with a very large goiter:

effect on thyroid function and size and pulmonary function. J Clin Endocrinol Metab.

1999;(84):3636–41.

22. Nygaard B, Hegedus L, Ulriksen P, Nielsen K, Hansen J. Radioiodine therapy for multinodular toxic

goiter. Arch Intern Med. 1999;159:1364–8.

23. Erickson D, Gharib H, Li H, Van Heerden J. Treatment of patients with toxic multinodular goiter.

Thyroid. 1998;8:277–82.

24. Holm L, Lundell G, Israelsson A, Dahlqvist I. Incidence of hypothyroidism occurring long after iodine-

131 therapy for hyperthyroidism. J Nucl Med. 1982;23:103–7.

25. Dezarn W, Cessna J, DeWerd L, Feng W, Gates V, Halama J, et al. Recommendations of the American

Association of Physicists in Medicine on dosimetry, imaging and quality assurance procedures for

90Y microsphere brachytherapy in the treatment of hepatic malignancies. Med Phys.

2011;38(8):4824–45.

26. Gulec S, Mesoloras G, Stabin M. Dosimetric techniques in 90Y-microsphere therapy of liver cancer:

the MIRD equation for dose calculations. J Nucl Med. 2006;47(7):1209–11.

27. Chiesa C, Mira M, Maccauro M, Romito R, Spreafico C, Sposito C, et al. A dosimetric treatment

planning strategy in radioembolization of hepatocarcinoma with 90Y glass microspheres. Q J Nucl

Med Mol Imaging. 2012;56:503–8.

38
28. Pacilio M, Ferrari M, Chiesa, C, Lorenzon L, Mira, M, Botta F, et al. Impact of SPECT corrections on

3D-dosimetry for liver transarterial radioembolization using the patient relative calibration

methodology. Med Phys. 2016;43(7):4053–64.

29. Lanconelli N, Pacilio M, Lo Meo S, Botta F, Di Dia A, Aroche A, et al. A free database of radionuclide

voxel S values for the dosimetry of nonuniform activity distribution. PhysMedBiol. 2012;57(2):517–

33.

30. Cremonesi M, Chiesa C, Strigari L, Ferrari M, Botta F, Guerriero F, et al. Radioembolization of hepatic

lesions from a radiobiology and dosimetric perspective. Front Oncol. 2014;4(Aug 19):210.

31. Snyder W, Ford M, Warner G, Watson S. “S,” absorbed dose per unit cumulated activity for selected

radionuclides and organs. MIRD Pam No 11, Soc Nucl Med New York, NY. 1975;

32. Hänscheid H, Canzi C, Eschner W, Flux G, Luster M, Strigari M, et al. 2013 EANM Dosimetry

Committee Series on Standard Operational Procedures for Pre-Therapeutic Dosimetry II. Dosimetry

prior to radioiodine therapy of benign thyroid diseases. Eur J Nucl Med Mol Imaging. 2013;40:1126–

1134.

33. Bartalena L, Baldeschi L, Boboridis K, Eckstein A, Kahaly GJ, Marcocci C, et al. The 2016 European

Thyroid Association/European Group on Graves’ orbitopathy guidelines for the management of

graves’ orbitopathy. Eur Thyroid J. 2016;5(1):9–26.

34. 14th National Congress of the Italian Association of Nuclear Medicine and Molecular Imaging

(AIMN). Clin Transl Imaging. 2019;7(S1):1–138.

35. Ho S, Lau W, Leung T, Chan M, Johnson P, Li A. Clinical evaluation of the partition model for

estimating radiation doses from yttrium-90 microspheres in the treatment of hepatic cancer. Eur J

Nucl Med. 1997;24(3):293–8.

36. Kao Y, Hock Tan A, Burgmans M, Irani F, Khoo L, Gong Lo R, et al. Image-guided personalized

predictive dosimetry by artery-specific SPECT/TC partition modelling for safe and effective 90Y

39
radioembolization. J Nucl Med. 2012;53(4):559–66.

37. Chiesa C, Maccauro M, Romito R, Spreafico C, Pellizzari S. Need, feasibility and convenience of

dosimetric treatment palnning in ,iver selective internal radiation therapy with 90Y microspheres:

the experience of the National Tumor Institute of Milan. Q J Nucl Med Mol imaging. 2011;55(2):168–

97.

38. Garin E, Lenoir L, Rolland Y, Edelin J, Mesbah H, Laffont S, et al. Dosimetry based on 99mTc-MAA

SPECT/CT based dosimetry accurately predicts tumour response and survival in HCC patients treated

with 90Y-loaded glass microspheres: preliminary results. J Nucl Med. 2012;53(2):255–63.

39. Strigari L, Sciuto R, Rea S, Carpanese L, Pizzi G, Soriani A, et al. Efficacy and toxicity related to

treatment of hepatocellular carcinoma with 90Y-SIR spheres: radiobiologic considerations. J Nucl

Med. 2010;51(9):1377–85.

40. Sapienza MT, Coura-Filho GB, Willegaignon J, Watanabe T, Duarte PS, Buchpiguel CA. Clinical and

dosimetric variables related to outcome after treatment of graves’ disease with 550 and 1110 MBq

of 131I: Results of a prospective randomized trial. Clin Nucl Med. 2015;40(9):715–9.

41. Santos R, Romaldini J, Ward L. A randomized controlled trial to evaluate the effectiveness of 2

regimens of fixed iodine (131I) doses for Graves disease treatment. Clin Nucl Med. 2012;37:241–4.

42. Vija Racaru L, Fontan C, Bauriaud-Mallet M, Brillouet S, Caselles O, Zerdoud S, et al. Clinical

outcomes 1 year after empiric131I therapy for hyperthyroid disorders: Real life experience and

predictive factors of functional response. Nucl Med Commun. 2017;38(9):756–63.

43. Reiners C, Schneider P. Radioiodine therapy of thyroid autonomy. Eur J Nucl Med. 2002;29(Suppl

2):S471-8.

44. Stan MN, Durski JM, Bahn RS, Bhagra S, Thapa P, Brito JP, et al. Cohort Study on Radioactive Iodine–

Induced Hypothyroidism: Implications for Graves’ Ophthalmopathy and Optimal Timing for Thyroid

Hormone Assessment. Thyroid. 2012;23(5):620–5.

40
45. Ceccarelli C, Bencivelli W, Vitti P, Grasso L, Pinchera A. Outcome of radioiodine-131 therapy in

hyperfunctioning thyroid nodules: a 20 years’ retrospective study. Clin Endocrinol (Oxf ).

2005;62:331–5.

46. Walter MA, Christ-Crain M, Schindler C, Müller-Brand J, Müller B. Outcome of radioiodine therapy

without, on or 3 days off carbimazole: A prospective interventional three-group comparison. Eur J

Nucl Med Mol Imaging. 2006;33(6):730–7.

47. Hancock LD, Tuttle RM, LeMar H, Bauman J, Patience T. The effect of propylthiouracil on subsequent

radioactive iodine therapy in Graves’ disease. Clin Endocrinol (Oxf). 1997;47(4):425–30.

48. Imseis RE, Vanmiddlesworth L, Massie JD, Bush AJ, Vanmiddlesworth NR. Pretreatment with

propylthiouracil but not methimazole reduces the therapeutic efficacy of iodine-131 in

hyperthyroidism. J Clin Endocrinol Metab. 1998;83(2):685–7.

49. Tuttle RM, Patient T, Buss S. Treatment with Propylthiouracil before Radioactive Iodine Therapy Is

Associated with a Higher Treatment Failure Rate Than Therapy with Radioactive Iodine Alone in

Graves’ Disease. Thyroid. 1995;5(4):243–7.

50. Santos RB, Romaldini JH, Ward LS. Propylthiouracil reduces the effectiveness of radioiodine

treatment in hyperthyroid patients with Graves’ disease. Thyroid. 2004;14(7):525–30.

51. Lewis A, Rea T, Atkinson B, Bell P, Courtney H, Mccance D, et al. Outcome of 131 I therapy in

hyperthyroidism using a 550MBq fixed dose regimen. Ulster Med J. 2013;82(2):85–8.

52. Finessi M, Liberini V, Deandreis D. Dosimetrically Determined Activities in Advanced Differentiated

Thyroid Carcinoma – Controversies. Q J Nucl Med Mol imaging. 2019;63(3):258–66.

41
Physica Medica 32 (2016) 1738–1744

Contents lists available at ScienceDirect

Physica Medica
journal homepage: http://www.physicamedica.com

Original paper
90
Calculation of tumour and normal tissue biological effective dose in Y
liver radioembolization with different dosimetric methods
Elena Gallio a,⇑, Elisa Richetta b, Monica Finessi c, Michele Stasi b, Riccardo Emanuele Pellerito d,
Gianni Bisi c, Roberto Ropolo a
a
S.C. Fisica Sanitaria, A.O.U. Città della Salute e della Scienza, Corso Bramante 88/90, 10126 Turin, Italy
b
S.C. Fisica Sanitaria, A.O. Ordine Mauriziano, via Ferdinando Magellano 1, 10128 Turin, Italy
c
S.C. Medicina Nucleare U, A.O.U. Città della Salute e della Scienza, Corso Bramante 88/90, 10126 Turin, Italy
d
S.C. Medicina Nucleare, A.O. Ordine Mauriziano, via Ferdinando Magellano 1, 10128 Turin, Italy

a r t i c l e i n f o a b s t r a c t

Article history: Purpose: Radioembolization with 90Y microspheres is an effective treatment for unresectable liver
Received 17 June 2016 tumours. Two types of microspheres are available: resin (SIR-SpheresÒ) and glass (TheraspheresÒ). The
Received in Revised form 27 October 2016 aim of this study is to compare biological effective dose (BED) values obtained with three different
Accepted 28 October 2016
dosimetric methods.
Available online 18 November 2016
Methods: 29 HCC patients were included in this study: 15 were treated with resin(mean injected activity
1.5 GBq, range 0.8–2.7 GBq) and 14 with glass microspheres (2.6 GBq, range 1.3–4.1 GBq). Average doses
Keywords:
to tumours and normal liver tissues were calculated with AAPM, multi-compartmental MIRD and Voxel-
Yttrium-90
BED
based methods and consequently the BED values were obtained. Planar images were used for the AAPM
Dosimetry method: 99mTc-MAA SPECT-CT attenuation and scatter corrected images (resin) and 99m Tc-MAA SPECT
Microspheres attenuation corrected (glass) were employed for the other two methods.
Results: Regardless of type of microspheres, both for tumours and normal liver tissues, no significant sta-
tistical differences were found between MIRD and Voxel for both doses and BED values. Conversely AAPM
gave discordant results with respect to the other two methods (Mann-Whitney p-values 6 0.01). For resin
spheres the calculated tumour-to-normal tissue ratios on planar images were on average 14 times greater
than those obtained on SPECT-CT images, while they were 4 times greater on glass. A linear correlation
was observed between MIRD and Voxel BEDs.
Conclusions: The AAPM method appears to be less precise for absorbed dose and BED estimation, while
MIRD and voxel based dosimetry are more confident each other.
Ó 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

1. Introduction radioembolization (TARE) or external beam radiation therapy


(EBRT) [1]. During the past two decades, radioembolization with
Hepatocellular carcinoma (HCC) represents the sixth most microspheres of Yttrium-90 (90Y) has emerged as a safe and effica-
prevalent neoplasm and the third most common cause of cancer cious treatment modality for unresectable primary and secondary
death worldwide. Patients with HCC are stratified according to out- liver tumours [2]. The rationale of this treatment is based on the
come and treatment indication [1] as established by the Barcelona fact that tumoral liver lesions are generally vascularized via the
Clinic Liver Cancer (BCLC) classification. hepatic artery, whereas healthy liver is almost excluded from
Early stage liver cancer patients can benefit from curative treat- arterial vascularization and blood is supplied via the portal vein.
ments such as resection, liver transplantation or ablation [1]. The Yttrium-90 is a pure beta-emitting radionuclide with a physical
intermediate-stage patients will undergo intra-arterial treatments half-life (t1/2) of 64.2 h. About 94% of the 90Y radiation dose is
such as transarterial chemoembolization (TACE) and/or delivered during the first 11 days following treatment [3].
The 90Y maximum and mean energies are respectively 2.26 and
0.926 MeV while the maximum tissue penetration depth is 11 mm
(mean penetration is 2.5 mm). 1 GBq of 90Y distributed in 1 kg of
⇑ Corresponding author.
tissue delivers a total dose of 50 Gy/kg in tissue [4].
E-mail address: [email protected] (E. Gallio).

http://dx.doi.org/10.1016/j.ejmp.2016.10.023
1120-1797/Ó 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.
E. Gallio et al. / Physica Medica 32 (2016) 1738–1744 1739

Two types of 90Y-microspheres are commercially available: method for glass micropsheres and according to partitional model
resin microspheres (SIR-SpheresÒ; SIRTeX Medical, Lane Cove, for the resin ones. The mean injected 90Y activity was: 2.6 GBq
NSW, Australia) and glass microspheres (TheraSphereÒ; Nordion, (range 1.3–4.1 GBq) and 1.5 GBq (range 0.8–2.7 GBq) for glass
Ottawa, Ontario, Canada) that have some different characteristics. and resin spheres respectively.
The main differences [3] are the size of microspheres (20–60 lm A simulation was performed prior to injecting microspheres by
of resin type versus 20–30 lm of glass one), the number of spheres infusion of 99mTc-MAA for both groups. Two total body planar
per vial (40–80 million versuss 1.2–8 million) and the specific images (anterior and posterior) and a tomographic exam were
activity of spheres (40–70 vs 2500 Bq per sphere). This means that acquired. The SPECT-TC images were corrected by attenuation
more particles are infused with 1 GBq of resin microspheres than and scatter (Siemens SymbiaIntevoT2, IterativeFlash3Dreconstruc-
with the same activity of glass microspheres, thus leading to a tion algorithm) for the patients treated with resin microspheres,
potential embolic effect [5]. Lastly, only in case of resin, the activity while SPECT acquisition was performed and corrected only by
into the vial can be divided for more than one patient [6]. attenuation (GE Varicam, GE Xeleris3 workstation) for the patients
The therapy session is preliminary simulated by means of two treated with glass microspheres. From the planar images, without
procedures: diagnostic angiography and intra-arterial administra- attenuation correction, the lung shunt (L) was calculated as the
tion of 99mTc labelled macroaggregate albumin (99mTc-MAA) that ratio between the total lung counts and the sum of the total liver
should mimic the vascular distribution pattern of 90Y microspheres and lung counts.
[7]. The simulation is performed with planar and tomographic Regardless of the manufacturer suggestions, the predicted
images and is essential for evaluating tumour and healthy liver tumour and healthy liver average doses were calculated with three
uptake, possible lung shunt fractions and for excluding gastroin- different methods for all of the patients. The first method was
testinal shunts. Simulation is also used for determining dosimetry based on the recommendations provided by the American Associ-
in the frame of individualized treatment planning. ation of Physicists in Medicine (AAPM) [11] that suggest to draw a
The activity to be injected can be calculated conventionally region of interest (ROI) on the anterior and posterior planar images
according to manufacturers suggestions. Three methods are pro- encompassing the tumour. The same ROI must then be moved
posed by manufactures for resin microspheres: the empirical across the normal liver, on a region with a relatively uniform activ-
method, the body surface area (BSA) method and the partition ity uptake. An example is reported in Fig. 1.
one, while only the mono-compartimental method is proposed The dose to normal liver (NL) was then calculated as [11]
for the glass type [6]. Most of these methods do not allow discrim-
ination between tumour and healthy parenchyma unless a person- 49:38ðGy  kg=GBqÞ  AðGBqÞ  ð1  LÞ
DNormalLiv er ðGyÞ ¼ ð1Þ
alized dosimetric approach is carried out. mNormalLiv er ðkgÞ þ T=N  mTumour ðkgÞ
Tong et al. [3] reported no correlations between the activities
prescribed by BSA methodology and tumour-to-normal liver ratios 49.38 (Gy  kg/GBq) is equal to the product k<E>t1/2/ln2 with k a
(TLR) or percentage tumour involvement. constant to yield the dose in desired units and <E> the average
In order to determine the effect of a treatment on both tumours energy emitted for nuclear transition; A is the activity to be admin-
and normal tissues and to compare different radiation therapies, it istered; L is the lung shunt fraction; mNormalLiver and mTumour are the
is essential to evaluate the biological effects by applying the linear- mass of normal liver and tumour respectively and T/N is the
quadratic (LQ) model [8]. This includes the calculation of the bio- tumour-to-normal tissue ratio. T/N was calculated from the counts
logical effective dose (BED) [9], which represents the dose produc- of the ROIs drawn on planar images: T/N = (CountsTumour/mTumour)/
ing the same biological effect obtained with various dose rates and (CountsNormalLiver/mNormalLiver). mNormalLiver and mTumour were
time radiation distributions. For BED evaluation it is essential to obtained by means of computed tomography (CT) images.
know the absorbed dose. Our aim was to investigate the influence
of different dosimetric methods on BED calculation (the correlation
between absorbed dose and BED is not linear) in order to make a
future comparison between TARE and other radiation therapies,
in particular in term of healthy liver toxicity. In literature are
reported some dosimetric methods comparisons. For example,
Bernardini et al. [10] investigated the difference in term of activity
to be administered between two different body surface area meth-
ods and the MIRD one (Committee on Medical Internal Radiation
Dose) even though BSA methods do not consider the actual uptake
of organs.

2. Materials and methods

Twenty-nine patients suffering from hepatocellular carcinoma


were included in the study. Fifteen patients hospitalized at the
Nuclear Medicine Department of Mauriziano Hospital were treated
with resin microspheres; fourteen patients hospitalized at the
University Nuclear Medicine Department of Città della Salute e
della Scienza were treated with glass microspheres. According to
the manufacturers, the prescribed dose of glass spheres was
120 Gy for the entire lobe with maximum lung doses of 30 Gy,
without constraint for normal liver. While for the resin spheres
our aim was to deliver 120 Gy to lesions and a maximum of
40 Gy to healthy parenchyma [3,7]. The activities to be adminis- Figure 1. Example of planar images with ROIs encompassing the tumour and the
tered were calculated according to the mono-compartimental same ROIs over the healthy liver.
1740 E. Gallio et al. / Physica Medica 32 (2016) 1738–1744

Whereas the tumour (T) dose was [11]: In Gulec’s paper [12] the mean beta particle energy was
0.9348 MeV per disintegration, instead the AAPM recommenda-
49:38ðGy  kg=GBqÞ  AðGBqÞ  ð1  LÞ
DTumour ðGyÞ ¼ tions report 0.9267 MeV. So the product k<E>t1/2/ln2 is equal to
1
ðmNormalLiv er ðkgÞ
þ T=N  mTumour ðkgÞÞ
T=N 49.82 Gykg/GBq which is approximated to 50 Gy  kg/GBq.
T The third method, the Voxel-based method, also uses the
¼  DNormalLiv er ð2Þ
N SPECT-CT 3D corrected counts matrix. A MATLABÒ (Mathworks)
code was developed at our departments. Convolution calculations
The second method was the multi-compartimental MIRD one
were adopted: for each target voxel i, the mean absorbed dose
[12,6] using SPECT-CT corrected images. Two volumes of interest
(Di) from N surrounding source voxels along the three major axis
(VOIs), defining the tumour and the normal liver, were drawn on
was calculated as the product between the cumulated activity A ~k
images in order to estimate uptakes and volumes (Fig. 2). The
masses were obtained by multiplying the volumes by the density in the voxel k and the S factor according to the MIRD schema
(1.03 g/cm3). The dose fraction accumulated in the tumour (frac- [2,13]:
tional tumour uptake) was [12]:
X
N
Di ¼ ~ k  Sk
A ð7Þ
TLR  mTumour
fractional uptakeTumour ¼ ð1  LÞ ð3Þ k¼N
ðTLR  mTumour þ mNormalLiv er Þ
where TLR has the same meaning as T/N, but calculated through VOI S factor is the absorbed dose to the target voxel per unit of cumu-
values. For the normal liver, the fractional uptake was: lated activity in the source voxel.
The cumulated activity was equal to the integral of the activity
mNormalLiv er over the time. Due to the permanent trapping of the microspheres
fractional uptakeNormalLiv er ¼ ð1  LÞ
ðmTumour  TLRÞ þ mNormalLiv er by the liver (no biological clearance), for 90Y radioembolization
ð4Þ only one 99mTc-MAA SPECT is needed and A ~ k is:

Accordingly, the mean doses for tumour and healthy liver were ~ k ¼ 1:443  Ak  t1=2 ð90 YÞ
A ð8Þ
respectively [12]:
where 1.443 is the inverse of ln2, Ak is the initial activity (corrected
Gy  kg AðGBqÞ  fractional uptakeTumour for the lung shunt) into the voxel k and t1/2 is the 90Y physical half-
DTumour ðGyÞ ¼ 50 ð5Þ
GBq mTumour ðkgÞ life. The S values were obtained from the on-line free database
http://www.medphys.it/ for the specific voxel size values (resin
and spheres: 4.8 mm; glass spheres: 3.45 mm) [14]. The contributions
Gy  kg AðGBqÞ  fractional uptakeNormalLiv er of the 5 closest voxels (N = 5) were considered.
DNormalLiv er ðGyÞ ¼ 50 ð6Þ Biological effective dose (BED) was calculated from the average
GBq mNormalLiv er ðkgÞ
absorbed dose D to tumours and to the healthy parenchyma
obtained with the three different dosimetric methods according
to the formula [7]:
 
D  T rep
BED ¼ D  1 þ ð9Þ
ðT rep þ T eff Þ  a=b

where Teff and Trep are the halftimes for 90Y decay and repair dam-
age. a/b is assumed to be 2.5 Gy for the normal tissue and 10 Gy
for the tumour; Teff = Tphysical = 64.2 h and Trep = 2.5 h for normal
liver, 1.5 h for tumour. D is the average dose allowing a fair compar-
ison between the dosimetric methods.
Our dosimetric gold standard is the MIRD method because and
it’s suggested to ENAM guidelines [6]. It is also confirms by papers
in literature. Dieudonné et al. [15] reports that the average
absorbed dose calculated with this method is consistent with that
one estimated by kernel convolution [15]; Petitguillaume et al. [16]
indicates the good accordance with Monte Carlo simulations.
Statistical comparisons between doses (D and BED) calculated
according to the three dosimetric methods were carried out with
the Mann-Whitney two tails test (significance level of 5%).

3. Results

Fig. 3. shows the absorbed doses and BEDs obtained. A summary


of the mean values can be seen in Table 1.
For resin microspheres, no statistical significant difference
between MIRD and Voxel methods was found (p-values: 0.48 and
0.52 for tumour and healthy parenchyma doses respectively;
0.51 and 0.60 for corresponding BEDs). AAMP biological effective
doses were discordant with those obtained with the other two
methods (p-values <0.01): tumour BEDs were much higher (from
Figure 2. Example of VOIs (tumour and normal liver uptake) on the tomographic 65% to 400%), while the normal liver BEDs were much lower (from
images. – 90% to – 42%). The calculated tumour-to-normal tissue ratios on
E. Gallio et al. / Physica Medica 32 (2016) 1738–1744 1741

Figure 3. Tumour and normal liver absorbed doses and biologically effective doses (BEDs) for resin and for glass microspheres.

planar images were on average 14 times greater than those and 0.99 for tumour). MIRD values were approximately 10% lower
obtained on SPECT-CT images. than Voxel values (mean ± st.dev, NL: 7 ± 15%; T: 12 ± 10%).
A good correlation was observed between the BED values esti- For glass microspheres, no significant statistical differences
mated with Voxel method and those estimated with the MIRD between MIRD and Voxel methods were observed either for
one (Fig. 4) (Pearson correlation coefficient r = 0.96 for normal liver tumour and healthy parenchyma doses (p-values: 0.05 and 0.51
1742 E. Gallio et al. / Physica Medica 32 (2016) 1738–1744

Table 1
Summary of average doses and BEDs for T and NL for both types of microspheres.

Resin Spheres
Mean value ± 1 st.dev
Dose Tumour (Gy) BED Tumour (Gy) Dose Normal Liver (Gy) BED Normal Liver (Gy)
MIRD 189 ± 96 290 ± 202 48 ± 17 87 ± 44
Voxel 169 ± 84 249 ± 167 44 ± 14 78 ± 34
AAPM 558 ± 297 1455 ± 1301 18 ± 11 24 ± 18
Glass Spheres
Mean value ± 1st.dev
Dose Tumour (Gy) BED Tumour (Gy) Dose Normal Liver (Gy) BED Normal Liver (Gy)
MIRD 275 ± 164 504 ± 484 75 ± 42 184 ± 169
Voxel 188 ± 107 294 ± 237 60 ± 16 119 ± 44
AAPM 901 ± 831 4219 ± 5362 60 ± 40 138 ± 130

Figure 4. Correlation between Voxel dosimetry and MIRD method BED values for normal liver and tumours for resin microspheres.

respectively) and for corresponding BEDs (p-values: 0.05 and on average 4 times higher than T/N ratios on tomographic images.
0.53). Instead for tumours significant dose differences between A good correlation was observed between the BED values esti-
AAPM and the other two methods were found with a spread mated with both MIRD and Voxel methods (Fig. 5), through
range of values as shown in Fig. 3 (p-values: 0.01 for both slightly better in the case of the tumour (r = 0.72 for normal liver
absorbed dose and BED). Lower discrepancies were found for NL and 0.94 for tumour). In Table 2 Pearson correlation coefficients
with no significant statistical difference (p-values >0.05). For this between the methods are reported for the two types of
type of microspheres, the T/N ratios on the planar images were microspheres.

Figure 5. Correlation between Voxel dosimetry and MIRD method BED values for healthy liver and tumours for glass microspheres.
E. Gallio et al. / Physica Medica 32 (2016) 1738–1744 1743

Table 2
Summary of the Pearson correlation coefficients between the three methods for both types of microspheres.

Resin Spheres
MIRD – Voxel MIRD – AAPM Voxel – AAPM
Tumour D 0.99 0.27 0.18
BED 0.99 0.21 0.12
Normal Liver D 0.97 0.77 0.78
BED 0.96 0.75 0.78
Glass Spheres
MIRD – Voxel MIRD – AAPM Voxel – AAPM
Tumour D 0.94 0.35 0.20
BED 0.94 0.24 0.15
Normal Liver D 0.76 0.29 0.19
BED 0.72 0.54 0.46

4. Discussion study by Garin at al. [24] in 71 inoperable HCC patients treated


with glass microspheres showed that dosimetry based on 99mTc-
Transarterial radioembolization with 90Y microspheres is a safe MAA SPECT/CT imaging was able to predict response and survival.
and effective treatment for unresectable primary and secondary For a comparison between results obtained with different treat-
liver tumours. The aim of TARE is to selectively deliver a high- ments, i.e. TARE and other radiation therapies, it’s useful to employ
dose radiation into the target lesion while keeping radiation into the biological effective dose (BED) [8,9]. This parameter represents
the healthy liver parenchyma at tolerable levels in order to min- the dose producing the same biological effect under various irradi-
imise the side effects [17]. Consequently in order to increase effec- ation conditions. The external beam radiation therapy (EBRT) limit
tiveness and optimize the treatment, personal dosimetry is for treating hepatocellular carcinoma is liver toxicity when the
mandatory, as several authors have pointed out in literature dose absorbed by normal liver parenchyma is greater than 35 Gy
[3,17,18]. [17]. Fox et al. [25] found that the non-uniformity of microspheres
Microsphere manufacturers have suggested various dosimetric dose deposition spares regions of parenchyma, increasing its toler-
approaches, based on the body surface area of the patient and ance with respect to EBRT. Dose distribution around a microsphere
hepatic tumour involvement (resin microsphere) or a mono- exhibits an extreme dose gradient of more than 5 orders of magni-
compartimental method, without distinguishing between lesions tude in 2 mm [7]; instead with EBRT a larger part of healthy par-
and healthy liver tissue (glass microsphere). Three dosimetric enchyma is exposed to significant doses [25].
methods that distinguish between tumours and normal liver tissue BED formula for spatially uniform absorbed dose [7] was used
were selected for this study: AAPM recommendations, multi- in this study; the average dose was used in the calculation because
compartimental MIRD and convolution based Voxel dosimetry. it’s the sole dosimetric parameter that can be found out from all
All these methods employ MIRD formalism for absorbed doses three methods.
evaluation but they use different methods to estimate volume of The MIRD and Voxel dosimetric methods gave similar results
interest and uptake quantification. The first method only requires for the doses (absorbed and biological effective) to the volumes
planar images and can be used in departments in which no tomo- of interest (tumours and healthy parenchyma) for resin and glass
graphic images or attenuation corrected ones are available. MIRD microspheres. We also found a strong correlation between BED val-
and Voxel methods are based on tomographic SPECT images. ues estimated with Voxel dosimetry and those estimated with the
Monte Carlo simulation can also be used [16,19] but it requires MIRD method (r = 0.96 and r = 0.72 for normal liver and r = 0.99
a lot of human resources and lengthy calculations. Ljungberg and and r = 0.94 for tumour in case of resin and glass microspheres
Sjögreen-Gleisner [19] stated that a full Monte Carlo simulation respectively). Instead AAPM method appears to be less reliable.
may be justified when the particle range is much longer than the Significant statistical differences were found (p-values 6 0.01). In
spatial resolution of the SPECT-CT images. For 90Y, this condition addition we observed a much wide spread of tumour BEDs, larger
is not verified for some clinical SPECT systems, for which the pixel for glass microspheres (Fig. 3).
size is approximately 3–5 mm. These results could be at least partly explained by the applica-
The calculation of tumour and normal liver absorbed doses tion of AAPM method on planar images instead of tomography
enables us to study correlations between treatment outcomes. images. Potential necrotic masses within the tumours are not
Some studies have reported correlations between absorbed doses detected thus leading to a possible miscalculation of the actual
and clinical results. Ho et al. [20] developed the partition model mass of the tumour. Additionally self-absorption is not take into
that subdivides lung, tumour and normal liver into separate com- account. On the other hand, SPECT-CT or SPECT corrected images
partment and stated that it can predict complication rate, response overcome many of the technological limitations of planar images
rate and survival. In a retrospective analysis of 20 arterial territo- thus allowing more accurate measurements of dosimetric parame-
ries treated in 10 HCC patients using SPECT/CT partition model, ters [3]. 99mTc-MAA SPECT acquisitions for glass spheres were
Kao et al. [21] observed that 100% tumour response could be corrected only by attenuation, while for resin spheres both
achieved when the predicted mean tumour dose was at least attenuation and scatter correction were applied. In literature both
91 Gy for resin microspheres, without significant toxicities and scatter and attenuation corrections are suggested in order to
highlighted the importance of undertaking a personalized dosimet- improve dosimetric accuracy, but there is still much debate on
ric approach. Chiesa et al. [22] suggested that the evaluation of their influence [26]. Actually in our results the variability of BEDs
dose distribution at voxel level outdoes mean dose approach. Garin seems slightly lower in the case of resin spheres, further research
et al. [23] calculated tumour and healthy liver doses using a quan- is required in order to reach any definitive conclusion.
titative analysis of 99mTc-MAA in 36 consecutive patients with HCC The MIRD method foresees a uniform activity distribution and
treated with glass microspheres and found a strong correlation therefore uniform doses. In our results MIRD dose values showed
between patient response and tumour absorbed dose. Another a good linear correlation with the Voxel dosimetry that takes
1744 E. Gallio et al. / Physica Medica 32 (2016) 1738–1744

inhomogeneity into account. This probably reflects the fact that it [10] Bernardini M, Smadja C, Faraggi M, Orio S, Petitguillaume A, Desbrée A, et al.
Liver selective internal therapy with 90Y resin micropsheres: comparison
is impossible to detect non-uniform distribution at clinical voxel-
between pre-treatment activity calculation methods. Phys Med 2014;30
size level. Radiopharmaceuticals are often distributed heteroge- (7):752–64.
neously within a voxel; and even voxel-level adsorbed doses may [11] Dezarn WA, Cessna JT, DeWerd LA, Feng W, Gates VL, Halama J, et al.
not reflect the real biologic effect. This problem potentially can Recommendations of the American Association of Physicists in Medicine on
dosimetry, imaging and quality assurance procedures for 90Y microsphere
be addressed using subvoxel models of tissue [27] and so micro- brachytherapy in the treatment of hepatic malignancies. Med Phys 2011;38
dosimetry is required [28]. Moreover, good agreement between (8):4824–45.
MIRD and Voxel enables us to use the multi-compartimental [12] Gulec SA, Mesoloras G, Stabin M. Dosimetric techniques in 90Y-microsphere
therapy of liver cancer: the MIRD equation for dose calculations. J Nucl Med
method safely in departments in which Voxel dosimetry is not 2006;47(7):1209–11.
implemented (perceptual dose differences at approximately [13] Pacilio M, Ferrari M, Chiesa C, Lorenzon L, Mira M, Botta F, et al. Impact of
10% were observed). SPECT corrections on 3D-dosimetry for liver transarterial radioembolization
using the patient relative calibration methodology. Med Phys 2016;43
However only with Voxel dosimetry is it possible to calculate (7):4053–64.
the BED for each voxel in order to obtain a more accurate assess- [14] Lanconelli N, Pacilio M, Lo Meo S, Botta F, Di Dia A, Aroche AT, et al. A free
ment of BED and a biologically effective dose volume histogram database of radionuclide voxel S values for the dosimetry of nonuniform
activity distribution. Phys Med Biol 2012;57(2):517–33.
(BVH). From BVH it is possible to evaluate the normal tissue com- [15] Dieudonné A, Garin E, Laffont S, Rolland Y, Lebtahi R, Leguludec D, et al.
plication probability (NTCP), TD50/5 and TD5/5 for carrying out an Clinical feasibility of fast 3-dimensional dosimetry of the liver for treatment
accurate comparison with external beam radiation therapy. planning of hepatocellular carcinoma with 90Y-microsphers. J Nucl Med
2011;52(12):1930–7.
[16] Petitguillaume A, Bernardini M, Hadid L, de Labriolle-Vaylet C, Franck D,
Desbrée A. Three-dimensional personalized Monte Carlo dosimetry in 90Y resin
5. Conclusions
microspheres therapy of hepatic metastases: nontumoral liver and lungs
radiation protection considerations and treatment planning optimization. J
Personalized dosimetry in radioembolization with Yttrium-90 is Nucl Med 2014;55(3):405–13.
[17] Mosconi C, Cappelli A, Pettinato C, Golfieri R. Radioembolization with Yttrium-
strongly recommended. Absorbed and biologically effective doses
90 microspheres in hepatocellular carcinoma: role and perspectives. World J
were calculated with three different dosimetric methods for Hepatol 2015;7(5):738–52.
tumours and healthy liver parenchyma. The AAPM method appears [18] Stabin MG. Update: the case for patient-specific dosimetry in radionuclide
to be less accurate than MIRD and Voxel ones. These last two meth- therapy. Cancer Biother Radiopharm 2008;23(3):273–84.
[19] Ljungberg M, Sjögreen-Gleisner K. The accuracy of absorbed dose estimates in
ods seem to be more suitable for accurate dosimetry for TARE. tumours determined by quantitative SPECT: a Monte Carlo study. Acta Oncol
2011;50(6):281–9.
[20] Ho S, Lau WY, Leung TW, Chan M, Johnson PJ, Li AK. Clinical evaluation of the
References partition model for estimating radiation doses from yttrium-90 microspheres
in the treatment of hepatic cancer. Eur J Nucl Med 1997;24(3):293–8.
[1] Forner A, Llovet JM, Bruix J. Hepatocellular carcinoma. Lancet [21] Kao YH, Hock Tan AE, Burgmans MC, Irani FG, Khoo LS, Gong Lo RH, et al.
2012;379:1245–55. Image-guided personalized predictive dosimetry by artery-specific SPECT/TC
[2] Chiesa C, Mira M, Maccauro M, Romito R, Spreafico C, Sposito C, et al. A partition modelling for safe and effective 90Y radioembolization. J NuclMed
dosimetric treatment planning strategy in radioembolization of 2012;53(4):559–66.
hepatocarcinoma with 90Y glass microspheres. Q J Nucl Med Mol Imaging [22] Chiesa C, Maccauro M, Romito R, Spreafico C, Pellizzari S, Negri A, et al. Need,
2012;56:503–8. feasibility and convenience of dosimetric treatment planning in liver selective
[3] Tong AK, Kao YH, Too CW, Chin KF, Ng DC, Chow PK. Yttrium-90 hepatic internal radiation therapy with 90Y microspheres: the experience of the
radioembolization: clinical review and current techniques in interventional National Tunor Institute of Milano. Q J Nucl Med Mol Imaging 2011;55
radiology and personalized dosimetry. Br J Radiol 2016;89:20150943. (2):168–97.
[4] Kennedy A, Nag S, Salem R, Murthy R, McEwan AJ, Nutting CW, et al. [23] Garin E, Lenoir L, Rolland Y, Edelin J, Mesbah H, Laffont S, et al. Dosimetry
Recommendations for radioembolization of hepatic malignancies using based on 99mTc-MAA SPECT/CT based dosimetry accurately predicts tumour
yttrium-90 microsphere brachytheraphy: a consensus panel report from the response and survival in HCC patients treated with 90Y-loaded glass
radioembolization brachytherapy oncology consortium. Int J Radiat Oncol Biol microspheres: preliminary results. J Nucl Med 2012;53(2):255–63.
Phys 2007;68(1):13–23. [24] Garin E, Lenoir L, Edelin J, Laffont S, Mesbah H, Porée P, et al. Boosted selective
[5] Garin E, Rolland Y, Laffont S, Edeline J. Clinical impact of 99mTc-MAA SPECT/CT- internal radiation therapy with 90Yloaded glass microspheres (B-SIRT) for
based dosimetry in the radioembolization of liver malignancies with 90Y- hepatocellular carcinoma patients: a new personalized promising concept. Eur
loaded microspheres. Eur J Nucl Med Mol Imaging 2016;43:559–75. J Nucl Med Mol Imaging 2013;40(7):1057–68.
[6] Giammarile F, Bodei L, Chiesa C, Flux G, Forrer F, Kraeber-Bodere F, et al. EANM [25] Fox RA, Phil D, Klemp PFB, Egan G, Mina LL, Burtn MA, et al. Dose distribution
procedure guideline for the treatment of liver cancer and liver metastases with following selective internal radiation therapy. Int J Radiat Oncol Biol Phys
intra-arterial radioactive compounds. Eur J Nucl Med Mol Imaging 2011;38 1991;21:463–7.
(7):1393–406. [26] Pacilio M, Chiesa C, Ferrari ME, Botta F, Lorenzon L, Mira M, et al. Previsional
[7] Cremonesi M, Chiesa C, Lo Strigari L, Ferrari M, Botta F, Guerriero F, et al. dosimetry based on 99mTc-MAA SPECT for radioembolization of liver lesions
Radioembolization of hepatic lesions from a radiobiology and dosimetric with 90Y-loaded microspheres: impact of attenuation correction, scatter
perspective. Front Oncol 2014;4:210. correction and calibration. Eur J Nucl Med Mol Imaging 2015;42(1):S233.
[8] Strigari L, Sciuto R, Rea S, Carpanese L, Pizzi G, Soriani A, et al. Efficacy and [27] Dewaraja YK, Frey EC, Sgouros G, Brill AB, Robenson P, Zanzonico PB, et al.
toxicity related to treatment of hepatocellular carcinoma with 90Y-SIR spheres: MIRD pamphlet No. 23: quantitative SPECT for patient-specific 3-dimensional
radiobiologic considerations. J Nucl Med 2010;51(9):1377–85. dosimetry in internal radionuclide therapy. J Nucl Med 2012;53(8):1310–25.
[9] Dale R, Carabe-Fernandez A. The radiobiology of conventional radiotherapy [28] Kennedy AS, Nutting C, Coldwell D, Gaiser J, Drachenberg C. Pathologic
and its application to radionuclide therapy. Cancer Biother Radiopharm response and microdosimetry of 90Y microspheres in man: review of four
2005;20(1):47–51. explanted whole livers. Int J Radiat Oncol Biol Phys 2004;60(5):1552–63.
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138
https://doi.org/10.1007/s40336-019-00318-3

14th National Congress of the Italian Association


of Nuclear Medicine and Molecular Imaging
(AIMN)

Rimini (Italy), 11–14 April 2019

123
S2 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

ORAL SESSIONS

Friday 12 April, 2019

Cardiology (OP 01–07)


Neurology (OP 08–14)

Saturday 13 April, 2019


Oncology (OP 15–21)
Radionuclide Therapy (OP 22–28)

POSTERS

Cardiology
Neurology
Oncology: Brain
Oncology: Head-Neck
Oncology: Lung
Oncology: Endocrine e Neuroendocrine
Oncology: Gastroenterology
Oncology: Breast
Oncology: Female Pelvis
Oncology: Prostate
Oncology: lymphoproliferative disorders
Oncology: Melanoma
Oncology: Sarcoma
Paediatrics
Endocrinology
Gastroenterology
Pneumology
Nephro-Urology
Orthopedics
Inflammation and Infection
Lymphoscintigraphy and Radio-Guided Surgery
Physics
Dosimetry
Radiopharmaceuticals and Radiochemistry
Molecular Imaging and preclinical Imaging
HTA
Technicians and Nurses Session

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S3

FROM SCIENCE TO KNOWLEDGE: OUR ANSWERS TO HEALTH NEEDS

Dear Colleagues,

Welcome in Rimini!

AIMN is finally entering the world of the ‘‘control rooms’’ of the Ministry of Health: we are among the Societies accredited
for the national Guidelines. This is a real step forward to bring our methods into the LEAs, but will require an increase in
expertise not only from the heads of Scientific Societies or leaders of individual Services, but from each of us, too.
Our medical branch is experiencing a wonderful time of scientific and technological growth. Words like artificial intel-
ligence and radiomics are thrilling us, but all this has a cost and the current rules for medical devices involves the use of
rigorous methods, such as HTA evaluations, for their introduction. There are still many challenges for the correct use of
PET, conventional investigations and radiometabolic therapy in diagnostic pathways. These challenges can be faced and
won only through cultural growth and the help of those who have always been next to us, as AIFM and GICR, but also of
other Scientific Societies. Nuclear Medicine must be considered essential for the health of the citizen and supported by the
national health system. What better formative moment, to give the right answers in this historical time both for technology
and laws, if not that of the National Congress?
The program. The opening day is expected to be a scientific update of specific competence of some GdS (Focus on) that are
similar to the ‘‘pre-congress’’ of international conferences. For the following days, three courses have been developed, two
of which are strictly clinical and one that includes transversal subjects (Radiopharmacy, Physics, HTA) and innovative or
niche topics, but with potential for growth. Many non-nuclear editors, speakers and moderators (almost a third of the
total…) and many Scientific Societies have enthusiastically accepted our invitation and will give a certain added value to
this Congress. In addition, among the speakers of our branch, coming from all over our country, there are not only well
‘‘known’’ names, but also young nuclear physicians who have a high professional value. I’m afraid it will not be easy to
decide which scientific session to follow…
Like all the national Congresses, there are Plenary sessions which, for the proposed topics, represent a formative moment
of great relevance. I also invite you to attend the Industry Symposia: equally in line with current updating needs.
Finally, if we have maintained (essential for their future profession) the ‘‘Young area’’ for specializing physicians, some
changes have been introduced compared to previous years. The mid-morning break can be useful for going to the
exhibition or looking at a poster. The ‘‘Highlights’’ include three young nuclear doctors who will have to explain to us the
best they have learned and experienced. Impossible not to go and listen to them.

I wish you a good Congress!


Franca Chierichetti

123
S4 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

ORAL PRESENTATIONS OP02


Left ventricular dyssynchrony parameters measured
OP01 by phase analysis of post-stress and resting gated 13N-
The potential and the accuracy of [18F]FDG-PET/CT NH3 PET/CT myocardial perfusion imaging
in the diagnosis of IE compared to duke
echocardiographic criteria A. Mazzoletti1, D. Albano1, M. Bonacina1, E. Cerudelli1, F. Dondi1,
R. Durmo1, M. Gazzilli1, L. Camoni1,
F. Bertagna1, C. Tinoco Mesquita2, R. Giubbini1
M. Gazzilli2, R. Durmo2, D. Albano1, M. Bonacina2,
E. Cerudelli2, F. Dondi2, A. Mazzoletti2, F. Bertagna2, 1
Department of Nuclear Medicine, University of Brescia, Spedali
R. Giubbini2
Civili of Brescia, Brescia, Italy. 2Universidade Federal Fluminense,
1 Niteròi, Rio de Janeiro, Brazil
Medicina Nucleare, ASST Spedali Civili di Brescia, Brescia, Italy.
2
Medicina Nucleare, Università di Brescia, Brescia, Italy Background-aim: The relationship between perfusion pattern and
stress-induced changes in left ventricular mechanical dyssynchrony
Background-aim: In the latest update of the European Society of
(LVMD) has been previously described with controversial results on
Cardiology (ESC) guidelines echocardiography, contrast-enhanced
stress-rest perfusion imaging studies. No previous examinations
CT, radiolabelled leucocyte SPECT/CT and [18F]FDG-PET/CT are
considering LVMD parameters have been performed with 13N-am-
been included in the diagnostic flow chart for the management of
monia positron emission tomography/computed tomography (13N-
infective endocarditis (IE). The aim of this study is to analyze the
NH3 PET/CT). The aim of the study is to assess the relationship of
diagnostic accuracy of [18F]FDG-PET/CT in the detection of IE.
perfusion pattern with stress-induced changes in LVMD on 13N-NH3
Methods: We retrospectively analyzed a series of 105 patients
PET/CT after regadenoson stimulation and at rest.
(M:F = 54:51, mean age 62 years, median age 53 years, range 18–88,
Methods: In this retrospective study we enrolled 69 patients (43 men
40 with native valve NVE, 50 with prosthetic valve PVE and 20 with
and 26 women; average age 64.5 ± 11.6) who underwent stress-rest
cardiovascular implantable electronic device CIED) who underwent
13N-NH PET/CT from January 2014 to October 2018 at our
[18F]FDG-PET/CT scan for suspicious of IE. PET/CT images were
department. People with left bundle branch block, ventricular pacing
analyzed qualitatively and semi-quantitatively by measuring maxi-
and myocardial necrosis were excluded. We divided our population in
mum and mean standardized Uptake Value (SUVmax and SUVmean)
two groups considering imaging results: patients with reversible
of the suspected lesion.
myocardial perfusion defects at stress (Ischemic group, n = 23) and
These results were compared with the echocardiographic (trans-tho-
patients without myocardial reversible perfusion defects (non-is-
racic TT and trans-esophageal TE) findings and the clinical final
chemic groups, n = 46). We evaluated epidemiological/clinical
diagnosis.
characteristics (age, sex, obesity evaluated as BMI [ 30, history of
Results: Comparing PET/CT report and clinical final diagnosis
hypertension, diabetes, hyperlipidemia, kidney failure, smoker, car-
revealed a Sensitivity of 60%, Specificity of 96%, Negative Predictive
diac arrhythmias and previous revascularization), main imaging
Value of 71%, Positive Predictive Value of 93% and of Accuracy
features (summed stress score, summed rest score, summed difference
79%. These results reach levels of Accuracy equal to 95%, Sensitivity
score, LV ejection fraction) and LVMD parameters: phase standard
of 91%, Specificity of 100%, Negative Predictive Value of 92% and
deviation (PSD) and phase histogram bandwidth (PHB), both assessed
Positive Predictive Value of 100% in presence of adequate prepara-
after-stress and at rest.  PSD (post-stress PSD-rest PSD) and  PHB
tion to reduce the physiological myocardial uptake of [18F]FDG (a
(post-stress PHB-rest PHB) were calculated to measure stress-induced
low carbohydrate, high protein and high fat (LCHPHF) diet starting
changes in LVMD.
72 h before the examination).
Results: Considering the epidemiological/clinical features, no sig-
The echocardiograph findings, according to Duke criteria, showed a
nificant differences were present between two groups, except of male
Sensitivity of 64%, Specificity of 30%, Negative Predictive Value of
sex, history of diabetes and previous revascularization that were
47%, Positive Predictive Value of 47% and Accuracy of 47%. The
higher in ischemic-group (p value 0.013; p value 0.04; p value 0.04
echocardiograph accuracy in the detection of IE is considerable
respectively).
reduced in presence of PVE due to the artefacts.
There were no significant differences in the LV dyssynchrony
PET/CT has shown greater accuracy than the echocardiograph in
parameters (PSD post-stress, PSD at rest, PHB post-stress, PHB at
the evaluation of the response of antimicrobial therapy (97% vs 62%)
rest) between post-stress and at rest in both groups.
and in the study of CIED infections or local device infection.
Mean post stress LVMD parameters were significantly higher in
Furthermore, PET/CT confirmed its ability to identify extra-car-
ischemic group than non-ischemic (PSD post-stress 6.47 ± 4.28 vs
diac sites of [18F]FDG uptake in patients with other diseases (3 cases
4.35 ± 1.79, p value 0.005; PHB post-stress 27.65 ± 19.59 vs
of pneumonias, 5 of vasculitis, 2 of vascular prosthesis infections, 4 of
17.86 ± 7.75, p value 0.004). There was no statistical relevance in the
spondylodiscitis, 1 of mediastinitis). In two cases PET/CT allowed to
evaluation of the same variables at rest comparing the ischemic cohort
diagnose unknown tumors.
of patients to the non-ischemic one.  PSD was significantly higher
Conclusions: Our preliminary results suggest the high accuracy of
in ischemic patients (- 0.55 ± 1.89 vs 0.82 ± 2.43, p value 0.02)
[18F]FDG-PET/CT in the diagnosis and follow-up of IE on NVE,
while  PHB wasn’t statistically relevant.
PVE and CIED; PET/CT ability to provide other diagnoses and/or
Conclusions: In conclusion, with this study we have demonstrated
incidental diagnosis.
that LVMD parameters (PSD, PHB and  PSD) were significantly
However, according to ESC guidelines, is essential the complemen-
higher in the ischemic patients compared to non-ischemic, while there
tary use of echocardiograph, PET/CT and a multi-modality imaging
were no significant differences in each cohort between stress and rest
approach.
evaluation. Ammonia-PET/CT were performed immediately during
regadenoson stress induction and this may explains why myocardial
dyssynchrony after stress increases in ischemic patients.

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S5

OP03 OP04
How appropriate is MPI in a clinical setting Preliminary evaluation of stress myocardial blood flow
pattern in patients with apical hypertrophic
E. Milan2, F. Linguanti5, F. Dondi4, A. Giorgetti3, cardiomyopathy candidate to be enrolled
R. Campini1, G. Smania2, R. Sciagrà5, A.Gimelli3,
P. Calza1, R. Giubbini4
in the carapace study

1
Nuclear Medicine Unit-ICS Maugeri-IRCCS Veruno (NO), Veruno, A. Kokomani1, C. Fumagalli2, F. Tutino1, A. Ciaccio1,
Italy. 2Nuclear Medicine Unit ULSS2 Marca Trevigiana Treviso, R. Di Dato1, G. Puccini1, I. Olivotto2, P.G. Camici3,
Treviso, Italy. 3Nuclear Medicine Unit, CNR/Fondazione Monasterio R. Sciagrà1
Pisa, Pisa, Italy. 4Nuclear Medicine Unit, University of Brescia, 1
Brescia, Italy. 5Nuclear Medicine Unit, University of Firenze, Nuclear Medicine Unit, Careggi University Hospital, Florence, Italy.
2
Florence, Italy Referral Center for Cardiomyopathies, Careggi University Hospital,
Florence, Italy. 3Vita Salute University and Scientific Institute San
Background-aim: The appropriate use of imaging techniques is a Raffaele, Milan, Italy
crucial issue.
The Italian Group of Nuclear Cardiology (GICN) developed an APP, Background-aim: Microvascular dysfunction (MVD) plays a major
named NUCARDIAPPR, to promote appropriate selection of patients role in the pathophysiology of hypertrophic cardiomyopathy (HCM).
for MPI by referring cardiologists. So far there is no clear demonstration that medical therapy can
AIM of the study was to test the clinical applicability and efficacy favorably affect HCM through an improvement in MVD. The
of the NUCARDIAPPR algorithm in 5 series of consecutive patients. CARAPACE study financed by the Italian Ministry of Health is
Methods: Indications for testing were evaluated and recorded in 5 specifically focused on assessing the effect of therapy on global
different nuclear cardiology laboratories. The indications for testing myocardial blood flow (MBF) in HCM.
were classified as appropriate (A), potentially appropriate (PA) or During the patient screening for potential enrolment in the CAR-
rarely appropriate (RA) according to the APP definitions. APACE trial, we encountered a quite high proportion (30%) of
SPECT results were classified as: normal (N), abnormal in presence subjects with the apical pattern of HCM. Because scanty data are
of fixed defect related to previous necrosis (FD), abnormal in pres- available about MBF behavior in these patients, we found reasonable
ence of an ischemic pattern (I), abnormal in presence of both fixed to control their stress MBF pattern, and to compare it with that of the
and reversible defects (FD ? I). typical septal HCM, in order to exclude a potential selection bias in
Results: The appropriate/inappropriate prescriptions of stress-rest the CARAPACE cohort.
SPECT for 498 consecutive patients (age 68 ± 9.8 year; 71% men) Methods: In our database we collected the data of 12 patients, 10
were evaluated. males and 2 females (median age 44, interquartile range 26–60) with
On average, there were 440 (88.35%) A, 30(6.02%) PA and 28 confirmed diagnosis of apical HCM, who had undergone stress
(5.62%) RA prescriptions. The proportion of A, PA and RA indica- quantitative 13NH3 positron emission tomography (PET) in our
tions by centre was: Centre 1 A 106 (91.38%), PA 4 (3.45%), RA 6 Nuclear Medicine Department. Regional perfusion analysis, stress
(5.17%); Centre 2 A 86 (86%), PA 10 (10%), RA 4 (4%); Centre 3 A MBF, and stress transmural perfusion gradient (TPG = subendocar-
87 (87%), PA 8 (8%), RA 5 (5%); Centre 4 A 121(90.97%), PA 6 dial/subepicardial MBF) were assessed using the Pcard tool of the
(4.51%), RA 6 (4.51%); Centre 5 A 40 (81.63%), PA 2 (4.08%), RA 7 Pmod processing platform. The data were compared with our his-
(14.28%). torical database of HCM patients.
The rate of A, PA, and RA was not statistically different in the 5 Results: Regional perfusion analysis visually demonstrated apical
Centers (|2 = 13.32). However, the proportion of tests with A indi- hypoperfusion in 10 of 12 patients with wide perfusion defect in 3
cation was higher in 4 centers (three academic hospital and one patients. Taking as reference our recently published prognostic clas-
general hospital) in comparison to a tertiary center (|2 = 9.1; sification in global stress MBF tertiles, the values were in the highest
p = 0.01) where a great number of scan are prescribed by nonhospital tertile (C 2.14 mL/min/g) for 3 patients, in the middle tertile (1.54 to
cardiologists or other specialists. 2.13 mL/min/g) for 5 patients, and in the lowest tertile (B 1.53 mL/
Distribution of A, PA and RA request according with the cate- min/g) for 4 patients. The apical stress TPG was abnormal (\ 1) in 5
gories evaluated was: diagnosis of myocardial ischemia A 213 (91%), patients and normal in 7 patients. There was no correlation between
PA 8 (3.42%), RA 13 (5.55%); Risk stratification A 196 (85.96%), PA the global stress MBF and abnormal apical stress TPG.
18 (7.89%), RA 14 (6.14%); Preop. risk assessment for non-cardiac Conclusions: The apical variant of HCM shows often as expected
surgery A 12 (75%), PA 3 (18.75%), RA 1 (6.25%); Evaluation regional stress hypoperfusion of the apex in the visual perfusion
efficacy of medical therapy A 6 (85.71%), PA 1 (14.28%), RA 0; analysis. Like in the more frequent septal HCM, the global stress
Congestive heart failure A 13 (100%), PA 0, Ra 0. MBF values are heterogeneous and quite homogeneously distributed
The rate of N SPECT was higher in patients with a RA pre- within the established spectrum, without correlation between global
scription (11 (39%)), conversely both the groups with A or PA MBF values and visual detection of perfusion defects. We also did not
indications showed higher incidence of abnormal SPECT scan (295 register any correlation between global stress MBF values and the
(67%) and 22 (73%), respectively). finding of an abnormal apical TPG. All these data are in agreement
Conclusions: NUCARDIAPPR is a reliable and a useful tool that can with those observed in the classical septal HCM, and therefore sug-
help physicians in clinical daily practice. Preliminary results gest that patients with apical HCM can be enrolled for the
demonstrate that the great majority of MPI studies were appropriate. CARAPACE trial without introducing any selection bias.
No significant difference was found in the participating centers,
except one whose referrals are on ambulatory surveillance by cardi-
ologists with less professional contacts with Nuclear Cardiology labs.

123
S6 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

OP05 OP06
FGD PET/CT accuracy for diagnosis of infective valve ECG-Gated myocardial perfusion SPECT
endocarditis after dynamic exercise stress test and rest: failure mode
and effect analysis
C. Altini2, L. Leccisotti3, M. Lavalle3, F. Giovannenze1,
G. Scoppettuolo1, A. Giordano2 C. Spadavecchia1, P. Gandolfo3, I. Redaelli1, V. Salvatore3,
1
G. Albini3, A. Bergantin1, S. Papa2
Institute of Infective Diseases, Università Cattolica del Sacro Cuore,
Rome, Italy. 2Institute of Nuclear Medicine, Università Cattolica del 1
Cyberknife Unit, Imaging Department, Centro Diagnostico Italiano
Sacro Cuore, Rome, Italy. 3Nuclear Medicine Unit and PET-CT S.p.A., Milan, Italy. 2Imaging Department, Centro Diagnostico
Center, Fondazione Policlinico Universitario A.Gemelli IRCCS, Italiano S.p.A., Milan, Italy. 3Nuclear Medicine Unit, Imaging
Rome, Italy Department, Centro Diagnostico Italiano S.p.A., Milan, Italy
Background-aim: The diagnosis of infective valve endocarditis Background-aim: A Failure Mode and Effect Analysis (FMEA) was
(IVE) is challenging since initial echocardiography and/or cultures conducted as a proactive risk assessment method applied to ECG-
result normal or inconclusive in almost 30% of cases. Recently, FDG gated myocardial perfusion SPECT after dynamic exercise stress test
PET/CT has emerged as a useful non-invasive imaging technique in and rest, representing the examination with the highest risk in nuclear
patients with inflammatory and infectious conditions. The aim of this medicine.
study was to investigate the accuracy of FDG PET/CT in the diag- Methods: A multidisciplinary team was assembled, including nuclear
nosis of patients with IVE. medicine physicians, medical physicists, technicians and a nurse.
Methods: FDG PET/CT scans performed from April 2012 to July The various sub-processes of the whole examination were detailed to
2018 in patients suspected of having IVE were analysed. In order to generate the process tree from medical counseling to medical report
reduce physiological glucose uptake of the myocardium, patient delivery. For each sub-process, failure modes together with their
instructions included a low-carbohydrate diet for 24 h before the scan potential root causes and effects were outlined. Current process
and fasting for at least 12 h before the study. Standard whole body controls were identified: procedures or mechanisms currently in place
scan was performed * 60 min after FDG injection. FDG uptake in to prevent or reduce the cause likelihood from happening.
valve and paravalvular areas was considered to be abnormal if the Every failure was rated based on its severity (S), occurrence
uptake was confirmed in uncorrected PET images. The visual analysis (O) and detectability (D), ranging from 1 to 4 according to the US
defined whether PET/CT was positive/negative. The valve-to-back- Department of Veterans Affairs of Health Care System scales.
ground ratio (TBR) was calculated dividing the valve area SUVmax Each sub-process was scored by means of the risk probability
by the right atrial blood SUVmax. Whole body acquisition was per- number (RPN = O 9 S 9 D), thus leading to the identification of the
formed to detect septic metastases. The final diagnosis of definite IVE main weaknesses of the entire process.
was defined by histopathology and culture of surgical specimens or by To provide an action plan were reconsidered the sub-processes
the expert team opinion according to the data collected during a without any currently existing control and giving one of the following
minimum 3-month follow-up. scores: RPN [ 24 (chosen as the half of the maximum RPN obtained)
Results: Thirty-eight patients (23M, 70 ± 13 years) with suspected or medium–high severity and occurrence (S [ 2, O [ 2).
IVE were included in the analysis (6 patients with native valve, 17 Results: The complete process resulted in the identification of 105
patients with biological valve and 15 patients with mechanical valve). sub-processes. The maximum RPN score obtained was 48 and the
FDG PET/CT was performed at a median of 15 days after start of threshold of 24 was exceeded just in 6 cases in the phases of medical
antibiotic therapy. Median time from valve replacement was counseling, dynamic exercise stress test and tomographic acquisition,
13 months. Suppression of myocardial FDG uptake was achieved in while 64% and 14% of the sub-processes showed S [ 2 and O [ 2
24 (63%) patients (19 complete and 5 partial suppression). Abnormal respectively. More frequent potential causes of failure turned out to
FDG uptake in the valve area was found in 16/38 patients (42%). IVE be related to inattention, hurry and lack of systematic existing
was confirmed in 14 patients (37%) according to reference standard. controls.
FDG PET/CT was positive in 2 patients without a final diagnosis of The most critical failure mode effects consisted of poor quality
IVE (5%), probably as a consequence of inflammatory reactions to examination and patient health endangered due to outside vein or
foreign materials. Conversely, PET/CT was negative in 2 patients incorrect waiting time between injection and acquisition or insuffi-
with a diagnosis of definite IVE (5%), likely as a result of small cient patient monitoring during tomographic acquisition.
vegetations or the effect of antibiotic treatment. Sensitivity, speci- An action plan including scheduled outcome measures was
ficity, PPV, NPV and accuracy for the diagnosis of IVE were 88, 91, structured aiming at improving detectability through the introduction
88, 91 and 89%, respectively. In patients with definite IVE, mean of specific controls and reducing the occurrence. Main actions
valve SUVmax and TBR were 4.7 ± 2.3 and 1.97 ± 0.9, respec- included the introduction of an independent second check for some
tively. Septic emboli were identified in 2 patients (5%) with definite specific sub-processes.
IVE. Conclusions: FMEA analysis proved itself to be a useful and realistic
Conclusions: The results of our study show that FDG PET/CT offers approach to identify, eliminate or compensate for failure modes.
high diagnostic accuracy for patients with suspected IVE. In addition, On the basis of the results obtained, new strategies and additional
FDG PET/CT can help to identify the presence of septic emboli. safety measures were proposed to mitigate the risk of these failures
Finally, SUV measurement could be a reproducible quantitative and improve quality management workflow.
parameter useful for assessing the efficacy of therapy in the follow- Future perspectives include the reduction of the total RPN index
up. through the scheduled action plan and a new analysis of the focusing
sub-processes.

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S7

OP07 OP08
Advance texture analysis: a new step in imaging of IE? Metabolic dysfunctions associated with psychosis
in bipolar disorder
R. Zanca2, A. Marciano2, F. Bartoli2, R. Doria3, U. Conti1,
E. Lazzeri2, P.A. Erba2 G. Marotta2, G. Delvecchio1, A. Pigoni1, G. Mandolini1,
1
V. Ciappolino1, L. Oldani1, D. Madonna1, M. Grottaroli1,
Division of Cardiology, University of Pisa and AOUP, Pisa, Italy. C. Altamura1, P. Brambilla1
2
Regional Center of Nuclear Medicine, Department of Translational
Research and New Technology in Medicine, University of Pisa and 1
Department of Neurosciences and Mental Health, Fondazione
AOUP, Pisa, Italy. 3Unit of Infectious Diseases, University of Pisa IRCCS Ca’ Granda Ospedale Maggiore Policlinico, University of
and AOUP, Pisa, Italy Milan, Milan, Italy. 2Department of Nuclear Medicine, Fondazione
Background-aim: [18F]FDG-PET/CT has been recently introduced IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
in the diagnostic algorithm for the diagnosis of infective endocarditis Background-aim: Bipolar disorder (BD) is a common psychiatric
(IE). [18F]FDG PET/CT positivity at the valve site, which is a major disorder characterized by severe recurring mood swings, which sub-
criteria of the 2015 ESC criteria, is generally characterized by visual stantially reduced the functioning and quality of life of these subjects.
analysis. The advantage of semiquantitative assessment is still matter Psychotic symptoms are a common feature in Bipolar Disorder (BD),
of discussion. In this study we aim to apply advanced texture features especially during manic phases, and are associated with a more severe
analysis, which application has been mainly focused on cancer course of illness. However, not all bipolar subjects experience psy-
imaging, to IE. chosis during the course of their illness, and this difference often
Methods: In this work we prospectively evaluated a series of guides assessment and pharmacological treatment. In this context, the
[18F]FDG PET/CT (Discovery 710 GE) in 101 patients aim of the present study is to elucidate, for the first time, the meta-
(M:F = 58:43, mean age 73 ± 10 years, median age 76, range 44–86) bolic dysfunctions associated with psychosis in a group of bipolar
with suspected IE (NVE = 12, PVE biological = 63 and PVE patients with and without psychotic symptoms, using FDG-PET.
mechanical = 31) between January 2012 to August 2018 in our center Methods: Fifty BD patients with psychosis and 40 BD without
to define different pattern of uptake, semiquantitative parameters psychosis were recruited at the Department of Neurosciences and
(TGV, SUVmax, SUVmean, SUVsd, TLA) as well as advanced Mental Health. All BD patients fulfilled the diagnostic criteria of the
texture features. To this aim extracted we used LIFEx package from Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR).
semiautomatically segmented PET images. Results were compared to PET scans were obtained with a Biograph Truepoint 64 PET/CT
patients’ features including type of valve prosthesis, microbiology scanner at the Nuclear Medicine Department.
and biochemical markers. Presence and duration of antimicrobial The statistical analyses were performed using Statistical Parametric
treatment and steroids at the time of PET/CT was also considered. Mapping (SPM12, Wellcome Department of Cognitive Neurology,
Statistical analysis was performed with JMP Statistical Discovery tm London, UK). PET images were co-registered to individual volu-
Results: Texture features analysis allowed to identify a different signa- metric T1-weighted MR images. The T1-series images were
ture based on the type of prosthesis (NVE, PVE biological and segmented according to GM, white matter and cerebrospinal fluid
mechanical, in particular with HISTO_ENTROPY/ENERGY, SHA- tissue probability maps to generate the normalization deformation
PE_VOLUME/COMPACITY, GLCM_ENERGY/CORRELATION/ field into the MNI space to be applied to the co-registered FDG-PET
ENTROPY, GLRLM_GLNU/RLNU, NGLDM_COARSENESS, scan. Then the normalized PET images were smoothed with a 10 mm
GLZLM_GLNU/ZLNU features), uptake pattern (HISTO_KURTOSIS/ isotropic Gaussian filter to increase the signal-to-noise ratio and to
ENTROPY/ENERGY, SHAPE_VOLUME/COMPACITY/ENERGY, account for subtle variations in anatomic structures.
GLCM_CONTRAST/CORRELATION/ENTROPY, GLRLM_GLNU/ Results: Compared to HC, BD patients with psychosis showed
RLNU, NGCDM_COARSENESS, GLZLM_HGZE/SZHGE/LZHGE/ decreased glucose metabolism in superior, middle and inferior
GLNU/ZLNU), semiquantitative parameters (SUVmax, SUV std and occipital gyri in the left hemisphere, and inferior temporal and
TLG) and microbiology (blood culture negative patients as compared occipital gyri and lingual gyrus in the right hemisphere as well as
with other stains: MSSA, E. faecalis, Streptococcus and other Staphy- increased glucose metabolism in fusiform gyrus and insula in the left
lococcus (GLRLM_SRE/LRE/GLNU/RP, NGLDM_RP/CONTRAST/ hemisphere (p \ 0.01 cFWE corrected).
LZE, GLZLM_ LZLGE)). Antimicrobial treatment and its duration as Compared to HC, BD patients without psychosis showed decreased
well as steroids use seems not to have an impact on texture features glucose metabolism in middle occipital gyri in the left hemisphere,
parameters. and superior occipital gyrus in the right hemisphere, as well as
Conclusions: Texture features analysis demonstrated a specific sig- increased glucose metabolism in insula and inferior temporal gyrus in
nature in patients with PVE as compared to NVE and in blood culture the left hemisphere as well as insula and middle and inferior temporal
negative IE. gyri in the right hemisphere (p \ 0.01 cFWE corrected).
The direct comparison between the two patient groups showed that
BD patients with psychosis showed decreased glucose metabolism in

123
S8 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

right fusiform gyrus compared to BD patients without psychosis OP10


(p \ 0.01 cFWE corrected). Flutemetamol amyloid PET/CT and CSF amyloid load
Conclusions: This study suggests that metabolic alteration in brain
networks involved in emotions are a key feature of BD, regardless the in differentiating neuropathological entities
presence of psychosis. The metabolic reduction in fusiform gyrus is of Alzheimer disease
associated with the presence of lifetime psychotic symptoms in BD,
ultimately leading towards the idea that the fusiform gyrus might be E. Carapelle2, C. Mundi2, C. Avolio1, S.G. Modoni3
considered a putative biomarker of psychosis. This research may help
1
clinicians in identifying more effective therapeutic and rehabilitation Department of Medical and Surgical Sciences, University of Foggia,
practices for BD patients by creating neurobiological models of Foggia, Italy. 2Department of Neuroscience, Foggia University
psychiatric illness, which may ultimately shape new therapeutic Hospital, Foggia, Italy. 3Department of Nuclear Medicine, Foggia
interventions. University Hospital, Foggia, Italy
Background-aim: According the IWG-2 criteria, instrumental and
biological markers can anticipate clinical diagnosis of Alzheimer’s
OP09 disease (AD) by approximately 20 years and could improve in vivo
A new quantitative method to evaluate F-DOPA pet diagnostic accuracy and its outcome. According 2018 NIA-AA
Research Framework, AD is a pathophysiologically defined entity
images in patients with extrapyramidal disease throughout its continuum and we can define neuropathological pro-
files based on the combination of different biomarkers.
P. Bianchi3, R. Cappuccio1, E. Lorenzini2, A. Nieri3, Methods: 28 patients with probable cognitive decline were consec-
F. Buffoni3, P. Bertolaccini3 utively selected during output patient visit. According NINCDS-
ADRDA criteria, 18 patients were considered possible early-AD
1
BMV S.r.L, Florence, Italy. 2Department of Health Physics, patients. These patients underwent lumbar puncture and 18F-
Ospedale Apuano-Asl Toscana Nord-Ovest, Massa, Italy. 3Nuclear Flutemetamol PET.
Medicine Unit, Ospedale Apuano-ASL Toscana Nord-Ovest, Massa, According CSF analysis, patients were divided in:
Italy 1) AD: 181p-Tau [ 61 pg/ml and IATI \ 1.2 (CSF ?).
Background-aim: Parkinson’s disease (PD) is a neurodegenerative 2) SNAP: 181p-Tau \ 61 pg/ml (CSF -).
disorder due to progressive loss of dopaminergic neurons in the According combination between PET and CSF profile, we
substantia nigra. Accurate and early diagnosis of PD is not only obtained:
challenging but also important for patient care. The correct differ- 1) AD: Group with levels 181p-Tau [ 61 pg/ml and IATI \ 1.2
ential diagnosis of this disease with parkinsonian syndromes (PS) or (CSF ?) and positive images for -amyloid uptake in 18F-
with essential tremor (ET) is a diagnostic dilemma, considering that Flutemetamol PET (PET ?).
only PD is responsive to treatment with levodopa. Nuclear medicine 2) AP (Alzheimer’s pathophysiology): Group with levels 181p-
can help neurologists to reach this differential diagnosis. The fluoro- Tau \ 61 pg/ml and IATI [ 1.2 (CSF) and positive images for -
18-deoxyphenyl-alanine (F-DOPA) is a positron emission tomogra- amyloid uptake in 18F-Flutemetamol PET (PET ?).
phy tracer with selective in vivo affinity to the basal ganglia, due to 3) SNAP (Suspected non-Alzheimer’s pathophysiology): Group
the specific metabolism of substantia nigra. In F-DOPA-based PET with levels 181 P-Tau \ 61 pg/ml and IATI [ 1.2 (CSF -) and
imaging, diagnosis is mainly conducted through qualitative and semi- negative images for -amyloid uptake in 18F-Flutemetamol PET
quantitative analysis of F-DOPA uptake in basal ganglia. (PET -).
Aim of this study is create and validate a new method to evaluate For statistical analysis, PET images were processed by SPM12.
concentration of tracer in basal ganglia to allow an accurate and early The interaction between CSF and PET was studied in the three patient
diagnosis of presynaptic dopaminergic neuronal damage. cohorts using ANOVA. Statistically significant tests had pFWE value
Methods: We used a multiple 3D-Convolutional-Neural-Network of \ 0.05 at the cluster level.
model followed by a typical Artificial Neural Network (ANN) Results: AD, AP and SNAP group were homogeneous for age,
3-layers stadium for final classification, called BrainNNet (patent education and scores on principle neuropsychological tests but not for
pending), to extract characterizing features from PET-slices and CSF -amyloid level and showed significant differences in the pat-
classify them. We trained the network on 121 F-DOPA exams of terns of accumulation of cerebral -amyloid in PET images, in
patients with movement disorders. Scoring of the network is per- particular:
formed on 25% (31 exams) of reshuffled-per-each-epoch training set. AD vs AP: significant accumulation of cerebral -amyloid in left
Final testing is executed on a set of 17 exams. hippocampal region in AD. The involvement of this area is charac-
Results: The confusion matrix analysis conducted on 31 exams teristic of patients with a typical clinical presentation of AD.
scoring-set showed 14 true positive, 16 true negative and 1 false AP vs AD: significant accumulation of cerebral -amyloid in
negative that is an accuracy of 97% and a sensitivity of 93% with a mesial frontal regions in AP.
classification error of 3%. Calculated AUC valued was 0.989. AD vs SNAP and AP vs SNAP: significant accumulation of
Conclusions: Results obtained are largely encouraging in continuing cerebral -amyloid in different cortical regions.
tests of these new quantitative methods in imaging analysis. Follow- This result is not surprising, also according the new criteria SNAP
up of patients in the next two years will allow us to consolidate ANN is a syndrome defined by normal levels of amyloid biomarkers
results, basing on a well-defined set of normal cases. (CSF -/PET -), but with a neurodegeneration patterns. In fact,
10–30% of people clinically diagnosed as AD by experts, do not show
neuropathological changes of AD during autopsy.
Conclusions: SNAP remains today a nosological entity that is not yet
well defined.
In both cases, several studies have shown that SNAP pathogenesis is
related to the deposition of tau fibrils, which justify brain neurode-
generation; small quantities of amyloid would drive tauopathy,

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S9

causing tau spread in all cortex. The use of tau-PET could explain reduction of glucose consumption was obtained when comparing
SNAP etiopathogenesis. SNAP to CG (posterior cingulate, and precuneus).
The use of 18F-Flutemetamol PET imaging, based on the corre- Conclusions: SNAP patients showed a significant hypometabolism in
lation between Aß1-42 in CSF and brain, could recognize AD parietal and limbic cortices as compared to CG subjects. The pattern
different neuropathological profile in the very early stage of disease observed is similar but more limited as compared to that observed in
and so could useful to understand AD etiology, currently unknown. AD subject. These similarities may explain the clinical symptoms in
SNAP subjects. According to cerebrospinal fluid data available in our
study cohort, tau pathology may be related to cortical dysfunction in
these areas.
OP11
Brain metabolic patterns in patients with suspected
non-Alzheimer’s pathophysiology (SNAP)
OP12
and Alzheimer’s disease (AD): is [18F] FDG a specific
Metabolic signature of core features in patients
biomarker in these patients? with in dementia with Lewy bodies (DLB): a project
A. Chiaravalloti1, G. Barbagallo3, A. Martorana2,
of the European DLB consortium
A.E. Castellano4, O. Schillaci1
S. Raffa12, A. Chincarini14, M. Brendel8, A. Rominger8,
1
Department of Biomedicine and Prevention, University Tor Vergata, R. Bruffaerts7, R. Vandenberghe7, M.G. Kramberger6,
Rome, Italy. 2Department of Systems Medicine, University of Roma M. Trost6, V. Garibotto11, N. Nicastro9, G.B. Frisoni13,
Tor Vergata, Rome, Italy. 3Institute of Neurology, University Magna A.W. Lemstra1, J. Van Der Zande1, A. Pilotto16,
Graecia of Catanzaro, Catanzaro, Italy. 4IRCCS Neuromed, Pozzilli, A. Padovani15, S. Garcia-Ptacek10, I. Savitcheva10,
Italy M.A. Ochoa-Figueroa5, A. Davidsson4, V. Camacho17,
E. Peira8, D. Arnaldi3, M. Bauckneht12, M. Pardini3,
Background-aim: Suspected non-Alzheimer’s pathophysiology G. Sambuceti12, D. Aarsland2, F. Nobili3, S. Morbelli12
(SNAP) describes a clinical entity where older adults with or without
subtle cognitive decline have one of markers of neurodegeneration 1
Alzheimer Center and Department of Neurology, VU University
(i.e. neuronal injury marker), but are negative for test for brain Medical Center and Neuroscience Campus, Amsterdam, The
amyloid (Aß) pathology [i.e. cerebrospinal fluid (CSF) assay and Netherlands. 2Centre for Age-Related Medicine (SESAM), Stavanger
positron emission tomography (PET)] and have not been diagnosed University Hospital, Stavanger, Norway; Wolfson Centre for Age-
with a specific neurodegenerative disorder. The correct identification Related Diseases, King’s College London, London, UK. 3Clinical
of SNAP is crucial, since it has been reported to affect up to 23% Neurology, Department of Neuroscience (DINOGMI), University of
healthy individuals and is not characterized by a significant pro- Genoa, Genoa, Italy. 4Department of Clinical Physiology, Institution
gression of cognitive impairment. Our study uses [18F] FDG PET in of Medicine and Health Sciences, Linköping, Sweden. 5Department
the evaluation of patients with SNAP, subjects with Alzheimer’s of Clinical Physiology, Institution of Medicine and Health Sciences,
disease (AD) and healthy controls with the aim to detect different Linköping, Sweden and Department of Diagnostic Radiology,
metabolic patterns in brain glucose consumption. CSF amyloid-ß1–42 Linköping University Hospital, Linköping, Sweden. 6Department of
(Aß1–42) was used as a marker of amyloid and CSF tau was used as a Neurology, University Medical Centre, Ljubljana, Slovenia.
marker of neuronal injury, in order to differentiate AD and SNAP. 7
Department of Neurosciences, Faculty of Medicine, KU Leuven,
Methods: The present study was conducted on 43 newly-diagnosed Leuven, Belgium; Department of Neurology, University Hospitals
AD patients according to the NINCDS-ADRDA criteria and 15 SNAP Leuven, Leuven, Belgium. 8Department of Nuclear Medicine,
patients. AD patients were recruited after a detailed clinical assess- University of Munich, Munich, Germany. 9Department of Psychiatry,
ment including a thorough medical history, neurological examination, University of Cambridge, UK. 10Division of Clinical Geriatrics,
and laboratory testing according to a standardized protocol reported in Center for Alzheimer Research and Department of Radiology,
other studies previously published from our group. Selection of SNAP Karolinska Institutet, Stockholm, Sweden. 11Division of Nuclear
subject was conducted with CSF parameters as reported in other Medicine and Molecular Imaging, Geneva University Hospitals and
previous studies among clinically normal articipants aged [ 65 years NIMTLab, Geneva University, Geneva, Switzerland. 12IRCCS
SNAP group was defined by the absence of CSF amyloid marker and Ospedale Policlinico San Martino, Genoa, Italy, Nuclear Medicine
presence of CSF neuronal injury marker, with or without subtle Unit, Department of Health Sciences, University of Genoa.
cognitive decline. Thirty-four chemotherapy-naı̈ve subjects (males 13
LANVIE (Laboratoire de Neuroimagerie du Vieillissement),
20; females 14; mean age 71 ± 8 years) undergoing an [18F] FDG Department of Psychiatry, Geneva University Hospitals, Geneva,
PET/CT and found to be completely negative for various diseases Switzerland. 14National Institute of Nuclear Physics (INFN), Genoa
were enrolled in the study and served as the control group (CG), as section, Genoa, Italy. 15Neurology Unit, University of Brescia,
proposed in other previous studies from our group in this field. Sta- Brescia, Italy. 16Neurology Unit, University of Brescia, Brescia, Italy.
tistical parametric mapping 12 (SPM12) implemented in Matlab 17
Servicio de Medicina Nuclear, Hospital de la Santa Creu i Sant Pau,
2018a was used for analysis of PET scans in this study. Universitat Autònoma de Barcelona, Barcelona, Spain
Results: As compared to SNAP, AD subjects showed a significant
hypometabolism in a wide cortical area that involves the right frontal, Background-aim: To identify brain regions whose metabolic
parietal and temporal lobes (right superior temporal gyrus, right impairment contributes to DLB clinical core features expression and
middle frontal gyrus and right postcentral gyrus). We did not find any to assess the influence of severity of global cognitive impairment on
area of increased [18F] FDG uptake when subtracting SNAP to AD the DLB hypometabolic-pattern.
subjects. As expected, when compared to CG, AD subjects showed a Methods: We took advantage of the functional imaging repository of
significant reduction of [18F] FDG in brain in a wide cluster that the European DLB consortium, a multicenter DLB patients cohort.
involved frontal, temporal parietal and limbic cortex. A more limited Brain FDG-PET and information on the clinical core features
(Parkinsonism = PARK, Visual hallucinations = VH, cognitive

123
S10 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

fluctuations = CFL, and REM Sleep Behavior Disorders = RBD) areas (BA) using Pickatlas toolbox and intensity normalization was
according to DLB diagnostic criteria were available in 171 patients performed using pons as reference. SPM12 multiple regression was
(93 males, age 73.4 ± 7.0; MMSE score 22.2 ± 4.7). A brain par- used to find age and gender effects on CMRglc. Besides, correlation
cellation based on principal component analysis was carried out to and linear regression analyses were performed using SPSS software to
take into account regions relevant to the local data variance. Then a investigate age-related effects, gender differences and interaction
linear regression model was applied to generate core feature-specific between age and gender on CMRglc changes.
patterns and scores, corrected for the main confounding variables Results: SPM analysis demonstrated a significant negative correlation
(Age, Gender, Education, MMSE), and Center). Finally, a regression between age and CMRglc involving frontal lobes bilaterally, espe-
to the locally-normalized intensities was performed to generate an cially medial frontal cortices, insular regions bilaterally, several areas
MMSE-sensitive map capturing the effect of severity of cognitive of temporal lobes, including hippocampi, and few regions of parietal
impairment. lobes (p \ 0.0001 family-wise-error-corrected). No significant cor-
Results: PARK has a negative correlation with bilateral parietal, relation was found in occipital lobes and in primary sensory-motor
precuneus, and anterior cingulate metabolism. VH have a negative cortex. No positive correlation was found. This pattern was similar
correlation with bilateral dorsolateral-frontal cortex, posterior cingu- both in males and females although with wider clusters of negative
late, and parietal metabolism. RBD has a negative correlation with correlation with age in females. SPSS analysis confirmed previous
bilateral parieto-occipital cortex, precuneus, and ventrolateral frontal SPM results, both using anatomical and Brodmann areas (p \ 0.001).
metabolism. These three core features shared a positive correlation There was a significant interaction effect between gender and age on
with metabolism in the medial temporal lobe, orbitofrontal cortex, the combined CMRglc of anatomical ROIs (F(94, 54) = 1.79,
cerebellum, brainstem, basal ganglia, thalami, and sensorimotor cor- p = 0.01, Wilks’ X = 0.243, partial g2 = 0.757). CMRglc of poste-
tex. CFL have a negative correlation with bilateral occipital rior cingulate and some parieto-temporal areas, including
metabolism and positive correlation with parietal lobes metabolism. hippocampi, resulted lower in females as compared to males.
The p value for each pattern were: PARK = 0.0011, VH = 0.0001; Conclusions: Our study demonstrated age-related metabolic reduc-
CFL = 0.0001; RBD = 0.0002. MMSE positively covaried with tions in frontal, especially medial, insular, hippocampal cortices,
metabolism in left superior frontal gyrus, bilateral-parietal cortex, and more evident in female than in male subjects. Thorough knowledge of
left precuneus, and negatively with metabolism in insula, medial age- and gender-related CMRglc changes is critical for accurate
frontal gyrus, hippocampus in the left hemisphere and in right detection of abnormal findings and for investigating metabolic alter-
cerebellum. ations in neurological disorders.
Conclusions: The present study directly addresses in the largest
cohort of DLB patients ever reported a common disease severity-
graded and core feature-specific metabolic signatures thus providing a
deeper insight into the interplay between topography of neurode- OP14
generation and clinical presentation. Semi-quantification and grading of amyloid PET
(AMY-PET): a project of the European Alzheimer
disease consortium (EADC)
OP13
Evaluation of age-related metabolic changes in healthy S. Capitanio13, E. Peira16, S. Morbelli15, M. Pardini14,
M. Bauckneht13, J. Arbizu10, M.C. Branco3, K. Busing12,
subjects: an Italian brain 18F-FDG PET study A. De MendonÇa11, M. Didic25, M. Dottorini22, S. Engelborghs23,
C. Ferrarese7, G. Frisoni18, V. Garibotto17, E. Guedj1, L. Hausner5,
M. Allocca6, V. Berti6, F. Linguanti6, M.L. Calcagni4, J. Hugon2, S. Deleye4, P. Mecocci24, M. Musarra9, M. Queneau20,
A. Cistaro8, U.P. Guerra2, F. Nobili1, S. Pappatà3, M. Riverol6, I. Santana19, U.P. Guerra8, F. Nobili 21, A. Chincarini16
S. Sestini5, D. Volterrani7, R. Di Dato6, F. Tutino6,
A. Ciaccio6, E.M. Abenavoli6, A.L. Martini6, V. Vergura6, 1
AP-HM, Hôpital de la Timone, Nuclear Medicine Department and
R. Sciagrà6 Aix-Marseille Université, CNRS, Ecole Centrale Marseille, UMR
1
7249, Institut Fresnel, Marseille, France. 2Center of Cognitive
Clinical Neurology, Department of Neuroscience (DINOGMI), Neurology and Inserm U942 Lariboisière Hospital AP-HP University
University of Genoa, Genoa, Italy. 2Department of Nuclear Medicine, Paris Diderot, 75010, Paris, France. 3CIBIT, Institute for Nuclear
Poliambulanza Foundation, Brescia, Italy. 3Institute of Biostructure Sciences Applied to Health (ICNAS-P), and Institute for Biomedical
and Bioimaging, CNR, Naples, Italy. 4Institute of Nuclear Medicine, Imaging and Life Sciences (IBILI), Faculty of Medicine, University
Fondazione Policlinico Universitario Agostino Gemelli, Università of Coimbra, Coimbra, Portugal. 4Department of Cognitive Neurology,
Cattolica del Sacro Cuore, Rome, Italy. 5Nuclear Medicine Unit, UZ Leuven, Leuven, Belgium. 5Department of Geriatric Psychiatry,
U.S.L. Toscana Centro, Prato, Italy. 6Nuclear Medicine Unit, Central Institute of Mental Health, Medical Faculty Mannheim,
University Hospital Careggi, Florence, Italy. 7Nuclear Medicine Unit, University of Heidelberg, Mannheim, Germany. 6Department of
University Hospital of Pisa, Pisa, Italy. 8Positron Emission Neurology, Clinica Universidad de Navarra, University of Navarra,
Tomography Centre IRMET S.p.A., Turin, Italy Pamplona, Spain. 7Department of Neurology, San Gerardo Hospital;
Background-aim: 18F-Fluorodeoxyglucose (FDG) positron emission School of Medicine and Surgery and Milan Center for Neuroscience
tomography (PET) has been extensively used to detect metabolic (NeuroMI), University of Milano-Bicocca, Monza, Italy. 8Department
alterations in several neurological diseases vs. normal aging. Our of Nuclear Medicine, Poliambulanza Foundation, Brescia, Italy.
9
aims were to evaluate age-related changes in cerebral metabolism rate Department of Nuclear Medicine, San Gerardo Hospital, Monza,
of glucose (CMRglc) in a cohort of healthy subjects, and to assess the Italy. 10Department of Nuclear Medicine, Clı́nica Universidad de
effect of gender. Navarra, University of Navarra, Pamplona, Spain. 11Faculty of
Methods: Brain 18F-FDG-PET scans of 152 subjects (67/84 M/F, Medicine, University of Lisbon, Lisbon, Portugal. 12Institute of
20–84 y.o) were selected from the Italian Normative Database of the Clinical Radiology and Nuclear Medicine, Universitätsmedizin
Italian Association of Nuclear Medicine. Regions of interest (ROI) Mannheim, Medical Faculty Mannheim, Heidelberg University,
were drawn over all grey matter anatomical regions and Brodmann Mannheim, Germany. 13IRCCS Ospedale Policlinico San Martino,

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S11

Genoa, Italy. 14IRCCS Ospedale Policlinico San Martino, Genoa, negative/positive contrast both with different tracers and with dif-
Italy; Department of Neuroscience (DINOGMI), University of Genoa, ferent quantifiers. No correlation was observed between scan quality
Genoa, Italy. 15IRCCS Ospedale Policlinico San Martino, Genoa, and latitude. The latitude distribution tended to cluster in the mild
Italy; Nuclear Medicine Unit (DISSAL), University of Genoa, Genoa, negative to borderline region. Considering the distribution of the
Italy. 16Istituto Nazionale di Fisica Nucleare, Sezione di Genova, binary reading on ELBA-SUVr scatter-plot we found that pure classes
Genoa, Italy. 17Laboratory of Neuroimaging and Innovative nicely clustered in the lower-left and upper right quadrant respec-
Molecular Tracers (NIMTlab), Nuclear Medicine and Molecular tively, whereas intermediate classes tended to aggregate near both
Imaging Division, University Hospitals and University of Geneva, transition regions.
Geneva, Switzerland. 18Laboratory of Neuroimaging of Aging We constructed and validated a linear map between different tracers.
(LANVIE), University Hospitals and University of Geneva, Geneva, Conclusions: We confirmed that different tracers and quantifiers are
Switzerland; Department of Internal Medicine, University Hospitals equivalently discriminating for binary evaluation. However, we pro-
and University of Geneva, Geneva, Switzerland. 19Neurology posed and validated the integration of both visual reading and
Department, Centro Hospitalar e Universitário de Coimbra, Coimbra, different quantifiers in a more robust framework thus bridging the gap
Portugal; Faculty of Medicine, University of Coimbra, Coimbra, between a binary and a user-independent continuous scale.
Portugal. 20Nuclear Cardiology, Centre Cardiologique du Nord
(CCN), Paris, France. 21Nuclear Medicine Unit (DISSAL), University
of Genoa, Genoa, Italy, Department of Neuroscience (DINOGMI),
University of Genoa, Genoa, Italy. 22Nuclear Medicine, ‘‘S. Maria OP15
della Misericordia’’ Hospital, Perugia, Italy. 23Reference Center for Preliminary results on circulating tumor cells
Biological Markers of Dementia (BIODEM), Institute Born-Bunge, in metastatic NSCLC patients candidate
University of Antwerp, Antwerp, Belgium; Department of Neurology
to immunotherapy
and Memory Clinic, Hospital. 24Section of Gerontology and
Geriatrics, Department of Medicine, University of Perugia, Perugia,
Italy. 25Service de Neurologie et Neuropsychologie, Pôle de A. Castello3, S. Monterisi1, L. Toschi2, F. Grizzi1, S. Rossi2,
neurosciences cliniques, AP-HM Timone, Aix Marseille Université, D. Qehajaj1, G. Finocchiaro2, G. Veronesi5, D. Rahal4, E. Lopci3
INS UMR_S 1106, 13005, Marseille, France 1
Immunology and Inflammation, Humanitas Clinical and Research
Background-aim: To compare and integrate visual reading with Hospital, Rozzano, Milan, Italy. 2Medical Oncology, Humanitas
semiquantification of AMY-PET data based on different methods for Clinical and Research Hospital, Rozzano, Milan, Italy. 3Nuclear
a multi-parametric grading of AMY-PET data. Medicine, Humanitas Clinical and Research Hospital, Rozzano,
Methods: We retrospectively enrolled three cohorts of cognitively Milan, Italy. 4Pathology, Humanitas Clinical and Research Hospital,
impaired patients who underwent to 18Florbetaben (53 subjects), Rozzano, Milan, Italy. 5Thoracic Surgery, Humanitas Clinical and
18Flutemetamol (62 subjects), 18Florbetapir (60 subjects) PET/CT Research Hospital, Rozzano, Milan, Italy
respectively, in 6 European centres belonging to the EADC (European
Alzheimer Disease Consortium). The 175 scans were visually classified Background-aim: Our aim was to investigate circulating tumor cells
as positive/negative following approved criteria and further classified (CTCs) in patients with non-small cell lung carcinoma (NSCLC)
with a 5-step grading as negative, mild negative, borderline, mild candidate to immunotherapy and correlate findings with clinical and
positive, positive by 5 independent readers, blind to clinical data. Scan metabolic parameters.
quality was also visually assessed and recorded. Semiquantification was Methods: Overall, 17 patients (11 male, 3 female) affected by
based on two quantifiers: the standardized uptake value (SUVr) and the metastatic NSCLC and referred for immunotherapy were prospec-
ELBA method, an SUVr-independent approach designed to capture tively enrolled. All patients underwent FDG PET before treatment
intensity distribution patterns rather than actual counts in predefined and CTCs detection from whole blood drawn at baseline. The trial has
regions. Visual reading was considered as the gold standard. However, been approved by the IRB. For CTCs, isolation was carried out with
the binary reading is too coarse to link visual assessment to the semi- the ISET method. The presence of CTCs was compared with age,
quantification, we therefore resorted to the 5-step grading. gender, smoking status, histologic subtype, previous chemotherapy,
Relationship between visual grading and quantification: we used a PDL-1 expression, Performance status, and semi-quantitative
sigmoid model, whose parameters were fit on both z-score quantifier parameters on PET, including SUVmax, SUV mean, metabolic tumor
values (direct model, grading vs. quantifiers) and on the raw quanti- volume (MTV) and total lesion glycolysis (TLG).
fiers data (inverse model, quantifiers vs. grading). The direct model Results: CTCs were identified in 10 out of 17 patients (59%). At
was used to evaluate the relationship between the visual grading and baseline, mean number of CTCs was 3 (range 1–7). We found a
the semi-quantification methods. The inverse model was used to significantly lower number of CTCs in patients who had previously
estimate the between-tracers mapping. undergone chemotherapy (p = 0.031), whereas no further correlations
Grading consistency: We looked for patterns in the visual between CTCs and clinicopathologic characteristics were observed.
assessment by grouping subjects with similar average gradings. These According to semi-quantitative parameters on FDG PET, patients
were plotted versus their average quantifier score, defined as the with an extended tumor burden, expressed by TLG and MTV, were
group mean score on the first PCA axis (PCA on the z-scored SUVr associated with a higher number of CTCs (p = 0.011 and p = 0.004,
and ELBA). For each group we calculated the ‘‘evaluation latitude’’, respectively). Likewise, patients with a higher SUVmean value
that is the maximum range of visual gradings received by any member resulted having a higher CTCs count (p = 0.04).
of the group. Then, we looked at relationships between discrepancies Conclusions: In our cohort, the presence of CTCs seems to be
on the grading (latitude) with semi-quantification and the binary associated with metabolic parameters on FDG PET and is influenced
reading. Relationship between scan quality on one side and quan- by previous chemotherapy.
tification and evaluation latitude on the other was also evaluated. Acknowledgements: The authors thank AIRC (Associazione Italiana
Results: There was no significant difference among models (direct, per la Ricerca sul Cancro) for the support on research with the grant
z-score), both with respect to quantifiers and with respect to tracers. Nr. 18,923. ISET machine is available at Humanitas Research
The transition region width was very similar among tracers, showing Hospital thanks to a grant from LILT (Lega Italiana per la Lotta
that there is no substantial difference in assessing the contro i Tumori).

123
S12 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

OP16 sample, unbalance of G categories) advocate the need of a strong


Explorative texture analysis on dual tracer 68GA- validation on larger prospective cohorts.
DOTATOC and 18F-FDG PET/CT for preoperative
risk evaluation in pancreatic neuroendocrine neoplasms
OP17
5 1 6 1 4
P. Mapelli , M. Salgarello , S. Partelli , S. Pasetto , P. Rancoita , Planning PET-CT vs standard PET-CT fused
F. Muffatti3, J. Doraku1, V. Andreasi6, L. Gianolli2, M. Falconi6, with planning CT in head and neck radiotherapy:
M. Picchio5 volumetric and dosimetric implications
1
Department of Nuclear Medicine, IRCCS Sacro Cuore Don Calabria
Hospital, Negrar, Italy. 2Nuclear Medicine Department, IRCCS San S. Di Biase4, L. Rampin2, A.M. Maffione2, F. Perrotti3, G. Pavanato3,
Raffaele Scientific Institute, Milan, Italy. 3Pancreatic Surgery Unit, G. Grassetto2, G. Montesi3, E. Bellan1, A. Ferretti1, D. Genovesi4,
Pancreas Translational and Clinical Research Centre, IRCCS San G. Mandoliti3, D. Rubello2
Raffaele Scientific Institute, Milan, Italy. 4University Centre of 1
Statistics in the Biomedical Sciences, Vita-Salute San Raffaele Santa Maria della Misericordia Hospital, Medical Physics Unit,
University, Milan, Italy. 5Vita-Salute San Raffaele University, Milan, Rovigo, Italy. 2Santa Maria della Misericordia Hospital, Nuclear
Italy; Nuclear Medicine Department, IRCCS San Raffaele Scientific Medicine Unit, Rovigo, Italy. 3Santa Maria della Misericordia
Institute, Milan, Italy. 6Vita-Salute San Raffaele University, Milan, Hospital, Radiotherapy Unit, Rovigo, Italy. 4SS. Annunziata Hospital,
Italy; Pancreatic Surgery Unit, Pancreas Translational and Clinical Department of Radiotherapy-G. D’annunzio University, Chieti, Italy
Research Centre, IRCCS San Raffaele Scientific Institute, Milan, Italy Background-aim: 1 To evaluate target volume variances with the
Background-aim: The aim of the present study is to carry on an introduction of a new planning PET-CT (pPET-CT) acquisition
explorative assessment of texture features, obtained from 68Ga- comparing with standard PET-CT (sPET-CT) fused with planning CT
DOTATOC and 18F-FDG PET/CT images that might define a pre- (pCT) for radiotherapy (RT) purpose.
operative risk profile in patients affected by pancreatic 2 To evaluate the dosimetric impact of an automated SUV threshold
neuroendocrine neoplasms (PanNENs). based delineation method on pPET-CT compared to manually based
Methods: Retrospective study including 43 patients (27 males, 16 delineation method on sPET-CT fused with pCT (sPET-CT/pCT)in
females; mean age: 57.7 years, range 15–84) undergoing both to head and neck (H&N) RT.
68
Ga-DOTATOC and to 18F-FDG PET/CT before surgery for Pan- Methods: Thirteen H&N cancer patients underwent to a pPET-CT
NEN between 2011 and 2017 (Sacro Cuore Don Calabria Hospital, performed by a classical H&N PET protocol (matrix 400 9 400 and
Negrar; San Raffaele Scientific Institute). For all patients histological 6 min bed) and a diagnostic CT without IV contrast enhancement
and follow-up data were available. PET/CT scans were qualitatively (120 kV, 200 mAs, pitch 1.0) in treatment radiotherapy set-up (flat
interpreted. Texture analysis (TA) was applied to PET images of both couch and personalized mould). All patients also underwent to a
scan; volumetric region of interests (VOIs) were drawn on positive sPET-CT that was co-registered and fused with a pCT using a rigid
findings and Chang-Gung Image Texture Analysis (CGITA) software algorithm.
package was used for statistical radiomics metrics. Selected texture 1 Gross tumor volumes (GTVs) were delineated using an automated
features from both scans (intensity variability-IV; size zone vari- threshold method at 50% of the intra-lesion SUV max (t50%GTV),
ability-SZV; Zone percentage-ZP; Entropy; Homogeneity, both on pPET-CT and co-registered sPET-CT/pCT. GTVs differences
Dissimilarity; Coefficient of Variation) were analysed with appro- were analyzed in terms of volumetric absolute values, Jaccard Index
priate regression models to evaluate their possible role in predicting (JI), DICE similarity index (DSI) and distances from centroids to
tumour characteristics (size, grade G 2 vs 1, Ki-67 B 3 vs [ 3, evaluate shift errors due to the co-registration.
lymphnode invasion, angioinvasion). Bonferroni’s correction was 2 On sPET-CT/pCT, GTVs were manually delineated (mGTV).
applied to account for multiple testing. P-values less than 0.05 were Clinical target volumes (CTVs) were obtained adding an isotropic
considered to be significant. margin of 1 cm respecting anatomical boundaries; a margin of 3 mm
Results: 12 patients had G1, 28 G2 and 3 had G3 PanNEN with was added for planning target volumes (PTVs).
median Ki-67 index of 5% (range 1–65) and median diameter of IMRT plans were generated in the following two steps:
25 mm (range 8–95). 68Ga-DOTATOC TA: SZV, Entropy and IV 2a Plans were optimized on the PTVs generated from the mGTV
were significantly positively predictive for tumour dimension then the coverage of the PTVs deriving from t50%GTV on pPET-CT
(p = 0.0008, p \ 0.0001 and p = 0.0043, respectively), but only SZV was assessed in terms of target coverage and conformity index (CI),
and Entropy remained significant also when adjusting for multiple without a plan re-optimization.
testing (p = 0.0116, p = 0.0001 and p = 0.0595, respectively). ZP and 2b Plans were optimized on PTVs deriving from t50%GTV on
Homogeneity were significantly positively predictive for G pPET-CT to evaluate organs at risk (OAR’s) dose differences com-
(p = 0.0089; p = 0.0265) but not confirmed after p-value adjustment pared to plans optimized on sPET-CT/pCT.
(p = 0.1243; p = 0.3714, respectively). Results: 1 The volumetric analysis showed a mean JI of 0.2 (0–0.5),
18F-FDG TA: IV and SZV were significantly positively predictive for mean DSI of 0.3 (0–0.7) between t50%GTV on pPET-CT vs
tumour dimension (p = 0.0001 and p = 0.0020, respectively) also t50%GTV on sPET-CT/pCT. Mean distance between centroid was
when adjusting for multiple testing (p = 0.0013 and p = 0.0277, 0.9 cm. Moreover, mGTVs were larger than pPET-CT t50%GTV in
respectively); IV was also positively predictive for angioinvasion the totality of cases (mean: 13.5 cc vs 3.1 cc).
(p = 0.0361) although not confirmed after p-value adjustment 2 Planning evaluation:
(p = 0.5059). 2a In all cases a decrease of CI (mean reduction 18%, range
Conclusions: This explorative analysis suggests that specific texture 7–35%) of PTVs deriving from t50%GTV on pPET-CT introduced
features derived from preoperative 68Ga-DOTATOC and 18F-FDG into the plans optimized on sPET-CT/pCT, was observed; although, in
PET/CT could non-invasively predict specific tumour characteristics. 10/13 cases a good coverage was obtained.
The retrospective nature of the study and its limitations (i.e. small 2b On plans optimized on pPET-CT, a slightly dose reduction,
almost to one of OARs, was observed in all cases.

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S13

Conclusions: Shift errors, related to the rigid image fusion process predictive value and accuracy of PET/CT for BM were 52, 98, 97, 65
between sPET-CT and pCT, negatively influenced concordance with and 74%; for GI 64, 91, 69, 90 and 85% and for GI excluding diabetic
target volumes obtained on pPET-CT. An adequate coverage of patients 78, 92, 72, 94 and 89%. Besides, 18F-FDG PET/CT allowed
pPET-CT volumes in plans optimized sPET-CT/pCT volumes despite to upstage 21 cases detecting sites of involvement not identified with
lower CI and a small reduction of dose to OAR’s in pPET-CT plans CT and downstage 2 cases showing suspected lymph nodes at CT not
were reported. Based on these preliminary evaluations, pPET-CT FDG-avid.
could be considered an optimization in RT workflow for H&N cancer Conclusions: We have demonstrated that 18F-FDG pathological
management to reduce image fusion uncertainties and to standardize uptake in MCL occurred in almost all patients, with excellent
delineation. detection rate in nodal and splenic disease better than CT.
About the accuracy of PET in the evaluation of BM and GI
involvement, seems to be crucial the selection of patients excluding
all conditions potentially affecting the organ uptake and using specific
OP18 criteria for the evaluation of these districts. With these precautions,
Diagnostic and clinical impact of staging 18F-FDG PET/CT showed good specificity for BM and GI evaluation.
PET/CT in mantle cell lymphoma: a bicentric Moreover, we have also shown that PET/CT altered the manage-
ment and therapeutic approach as compared with CT in about 20% of
experience
the cases.
D. Albano5, P. Ferro1, G. Bosio4, F. Fallanca1, A. Re2, A. Tucci2,
A.J.M. Ferreri3, P. Angelillo6, M. Adavastro6, L. Gianolli1,
M. Picchio1, F. Bertagna5, R. Giubbini5 OP19
1
Quantitative analysis of FDG PET/CT: an experience
Department of Nuclear Medicine, San Raffaele Scientific Institute,
Milan, Italy. 2Division of Hematology, Spedali Civili, Brescia, Italy.
with partial volume effect correction in the evaluation
3
Lymphoma Unit, Department of Onco-Haematology, IRCCS San of receptor subtypes of breast carcinoma
Raffaele Scientific Institute, Milan, Italy. 4Nuclear Medicine, Spedali
Civili Brescia, Italy. 5Nuclear Medicine, University of Brescia and L. Fantechi3, S. Chiacchio3, A. Giuliano2, G. Manca3, F. Betti3,
Spedali Civili, Brescia, Italy. 6Strategic Research Program on CLL, C. Scatena1, F. Di Martino2, D. Volterrani3
Università Vita-Salute San Raffaele and IRCCS Ospedale San
1
Raffaele, Milan, Italy Department of Molecular Pathology/University Hospital of Pisa,
Pisa, Italy. 2Health Physics Unit/University Hospital of Pisa, Pisa,
Background-aim: Mantle Cell lymphoma (MCL) is an aggressive
Italy. 3Nuclear Medicine Unit/University Hospital of Pisa, Pisa, Italy
B-cell non Hodgkin’s lymphoma that typically presents with
advanced-stage disease and extranodal involvement, with a Background-aim: Quantitative parameters derived from FDG PET/
predilection for the bone marrow (BM) and gastrointestinal (GI) tract, CT have been frequently used as prognostic factors in different
where routine conventional imaging such as computed tomography cancers. However, such measurements can be burdened by the limited
(CT) may have some limitations. For this reason, a correct and early spatial resolution and the sub-optimal signal-to-noise ratio affecting
identification of initial stage can be crucial because affecting patient PET images. Thus, several factors can limit the accurate quantitative
management and therapeutic choice. The diagnostic accuracy of evaluation of PET findings. Partial volume effect (PVE) is one of the
staging 18F-FDG PET/CT in MCL has not yet well investigated. The main factors that degrade spatial resolution and can affect the results
aim of this bicentric retrospective study was to investigate the utility of quantitative analysis on PET images.
of staging 18F-FDG PET/CT in assessing nodal disease and splenic The aim of this study was to perform a quantitative analysis of breast
disease compared to CT, BM involvement compared to BM biopsy, cancer through a radiomic approach on PVE corrected data.
and GI involvement compared to GI endoscopy in a large sample of Methods: Fifty-six female patients aged C 18 years were enrolled
patients affected by MCL. The second point was to investigate the before surgical therapy for a cT2-cT4 or cT1N ? breast cancer. No
possible clinical impact of PET/CT. radiotherapy or chemotherapy was performed before.
Methods: Between January 2007 and January 2018, 122 patients with All patients underwent a FDG PET/CT by using a Discovery PET/CT
histologically proven MCL were retrospectively included from two 710 scanner (GE Healthcare, Milwaukee, USA). PET data were
Nuclear Medicine Centers. The inclusion criteria were histological acquired according to a standard protocol starting 60 min after tracer
confirmation of MCL and availability of BM biopsy, GI endoscopy administration (3.7 MBq/kg). Attenuation correction was performed
and baseline PET/CT in all patients. The diagnostic accuracy in using LD-CT.
nodes, spleen, BM and GI and clinical impact of 18F-FDG-PET/CT Axial images were corrected voxel-by-voxel for PVE using an
were calculated. PET/CT findings were considered positive for BM iterative post-reconstruction method based on the measured system
involvement in the presence of isolated/multiple focal uptake in the Point Spread Function. On PET images each tumor lesion underwent
bone marrow that could not be explained by benign findings on the segmentation using an Advantage 4.6 GE workstation. A manually
underlying CT images and/or diffuse BM uptake superior to the liver adapted threshold method has been employed to delimit each lesion
with or without sites of intense focal uptake (excluding possible (L) from healthy tissue. An area of background (BK) was manually
interfered factors); for GI involvement in the presence of iso- selected, within the healthy breast tissue.
lated/multiple focal uptake in the GI district. To describe the breast carcinoma of each subject five image
Results: All patients had abnormal FDG uptakes showing the pres- descriptors were evaluated:
ence of at least one hypermetabolic lesion consistent of MCL, with SUVmean(L); SUVmean(L) normalized to SUVmean(BK)
the exception of one case. PET/CT results, compared to CT, detected (SUVmean(L)-norm); Total Lesion Glycolysis (TLG); SUVmean(L)-
more nodal and/or splenic lesions in 26/122 patients, showing in 18 norm multiplied by Metabolic Tumor Volume (MTV); SUV-
cases nodal disease in both sides of the diaphragm, in 2 cases mean(BK). These quantitative data were used as input features for
extranodal lesions and in 3 cases splenic disease not recognized by two-class and multiclass support vector machine classifications.
CT. The sensitivity, specificity, positive predictive value, negative

123
S14 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

After surgery/biopsy, tumors were subdivided according to the Protocol was as follows: i.v administration of 5 MBq/kg of 64Cu-
luminal classification of receptor subtypes (A, B HER2-, B HER2?, PSMA-617; 1 h whole body scan with 3 min/bed position and a late
HER2, TN) of breast carcinoma. scan of the pelvis after diuretic administration using PET/CT tomo-
Results: A positive correlation was found between Ki67 and both graphs (Siemens Biograph Hi-Rez). Imaging results were compared
SUVmean(L) (p = 0.007, r = 0.376) and SUVmean(L)-norm to 18F-Choline PET and verified by magnetic resonance, histologi-
(p = 0.003, r = 0.414). Positive correlation trends were found cally or on follow-up. The clinical impact of 64Cu-PSMA was
between Ki67 and other image descriptors, except for SUVmean(BK), discussed in a multidisciplinary setting.
but no significant correlation emerged. Results: An interim analysis was performed on first 50 patients
Image descriptors were used to discriminate among all tumor luminal enrolled into the study with an evaluable clinical follow-up. All
subtypes, but AUC values were not statistically different. When a patients presented a BCR after primary surgery with a progressive
two-class discrimination was performed (luminal-A subtype versus PSA value rising. At the time of 64Cu-PSMA PET, PSA values
the others and TN subtype versus the others) better classification ranged from 0.20 ng/ml to 3.2 ng/ml with a median value of 0.64 ng/
performances were achieved. Especially when considering SUV- ml. Patients after restaging underwent to secondary treatment (target
mean(L)-norm and SUVmean(BK) as input features, AUC was 0.81 radiotherapy or surgery as appropriate). Patients based sensitivity
for TN subtype versus the others and 0.89 for luminal A subtype resulted 60% for 18F-choline and 94% for 64Cu-PSMA respectively.
versus the others. 64Cu-PSMA identified 45% more lesion compared to 18F-choline.
Conclusions: In conclusion, after PVE correction a good correlation Small local recurrence (up to a minimum of 3 mm) were identified by
of SUVmean(L) and SUVmean(L)-norm values with Ki67 was found. 64Cu-PSMA in 60% of cases vs only 20% identified by 18F-choline.
By means of this radiomic approach, SUVmean(L)-norm and SUV- Node metastasis sensitivity resulted 15% vs 35% for 18F-choline and
mean(BK) seem to be promising in discriminating Luminal-A and TN for 64Cu-PSMA while, surprisingly 15% of bone lesions evidenced at
from the other subtypes. More data are needed, but the results of this 64Cu-PSMA PET were missed by 18F-choline. Also, specificity
study underline the need of strategies to improve quantification in the resulted better with 64Cu-PSMA differentiating aspecific nodal and
perspective of a reliable radiomic analysis. bone uptake in more than 5% of cases. In more than 90% of cases
64Cu-PSMA PET changed clinical management guiding treatment
choice and allowing a target therapy.
Conclusions: 64Cu-PSMA PET is a feasible imaging with higher
OP20 sensitivity than 18F-Choline PET significantly impacting on clinical
Role of 64CU-PSMA PET in the early diagnosis management and guiding target therapy. A future role of 64Cu-PSMA
of prostate cancer recurrence: preliminary results as theranostic agent is worth exploring.
on a cohort of 50 patients

R. Sciuto1, S. Rea1, S. Annunziata1, A. Annovazzi1, R. Pasqualoni1, OP21


S. Bergomi1, L. Romano1, C. Mazzone1, G. Sanguineti2, M. Gallucci3 The potential role of dynamic PET with 13N-ammonia
1
Nuclear Medicine Unit, IRCSS Regina Elena National Cancer
for evaluating response to sorafenib in advanced HCC
Institute, Rome, Italy. 2Radiotherapy Unit, IRCSS Regina Elena patients
National Cancer Institute, Rome, Italy. 3Urology Unit, IRCSS Regina
Elena National Cancer Institute, Rome, Italy V. Scolozzi7, S. Taralli7, G. Bencivenga8, F.R. Ponziani1,
A. Nicoletti1, A.M. De Gaetano4, C. Gulli’2, A. Capotosti3,
Background-aim: Prostate-specific membrane antigen (PSMA) tar-
L. Indovina5, M. Pompili1, M.L. Calcagni6
geted positron emission tomography (PET) is an emerging prostate
cancer imaging method, which has been reported to have a higher 1
Division of Internal Medicine, Gastroenterology and Hepatology,
sensitivity and specificity than the currently approved PET imaging
Fondazione Policlinico Universitario A. Gemelli IRCCS-Catholic
agents (18F or 11C-Choline). PSMA ligands bind to the surface
University of the Sacred Heart, Rome, Italy. 2General Diagnostic and
receptor and are internalized within cells. Due to their small size,
Interventional Radiology, Fondazione Policlinico Universitario A.
unbound ligands are rapidly cleared by the body, leading to high
Gemelli IRCCS-Institute of Radiology, Catholic University of the
tumor to background ratio. Nowadays the most investigated PET
Sacred Heart, Rome, Italy. 3Institute of Physics, Catholic University
tracers are labelled with 68Gallium. Recent studies on small series of
of the Sacred Heart, Rome, Italy. 4Institute of Radiology, Catholic
prostate cancer patients have demonstrated the potential of 64Cu-
University of the Sacred Heart, Rome, Italy. 5Medical Physics Unit,
labeled PSMA ligand in patients with recurrent disease and in
Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
selected patients for primary staging with progressive local disease. 6
Nuclear Medicine Unit, Fondazione Policlinico Universitario A.
64Cu-PSMA may also offer the possibility of pre-therapeutic
Gemelli IRCCS-Institute of Nuclear Medicine, Catholic University of
dosimetry in the theranostic approach. The aim of this study is to
the Sacred Heart, Rome, Italy. 7Nuclear Medicine Unit, Fondazione
investigate the diagnostic role of 64Cu-PSMA PET on a large cohort
Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. 8PET-CT
of prostate cancer patient with early recurrence of disease and low
Center, Fondazione Policlinico Universitario A. Gemelli IRCCS,
PSA values.
Rome, Italy
Methods: The study was approved by IFO Ethical Committee and
designed as prospective clinical trial on a cohort of 162 patients with Background-aim: Sorafenib is an anti-angiogenetic drug currently
prostate cancer restaging for biochemical recurrence (BCR), sub- adopted as the standard of care for patients with advanced hepato-
jected to PET with Cu64PSMA and followed up with a 2-year follow- cellular carcinoma (HCC). Due to its poor tolerability, the narrow
up. The primary endpoint is to verify the diagnostic accuracy of PET therapeutic effect and the high costs, to early identify those patients
with 64CuPSMA in the early identification of prostate cancer recur- who can benefit from Sorafenib treatment is of paramount impor-
rences with low PSA values compared to standard 18F-Choline PET. tance. Since HCC is characterized by high vascularisation and
All patients enrolled into the study underwent to 64Cu-PSMA PET at Sorafenib acts right on angiogenesis, the aim of our preliminary study
a maximum time distance of two months from 18F-choline PET. was to investigate the potential role of PET with 13N-ammonia, a

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S15

perfusion tracer, for evaluating response to Sorafenib in advanced of 55 kBq/kg intravenously every 28 days for a maximum of 6 cycles
HCC patients. (median 3.5, range 1–6). 34/57 patients were previously treated with
Methods: Five male patients (mean age: 67.2 ± 6.2 years) with docetaxel; 35/57 patients underwent 4 or more treatments (22/57
advanced HCC were evaluated. All patients underwent contrast-en- underwent six cycles of treatment).
hanced (c.e.) CT and dynamic PET with 13N-ammonia (acquisition Results: Overall, 237 administrations were performed in 57 patients.
lasting 20 min; 370 MBq) before (baseline) and 2 months after (post- Mean sPSA at enrolment was 373 ng/ml. Baseline pain score, hae-
therapy) the beginning of Sorafenib treatment. For each patient, moglobin, white blood cells and platelets counts were 3.7 ± 2.68,
quantitative analysis was performed: VOIs were drawn on the 12.3 ± 1.41 g/dl, 7.6465 ± 2.30617/mmc and 276.482 ± 105.67298/
descending aorta (input function), on up to six HCC lesions and on mmc, respectively. 34/57 patients experienced a condition of pain
two normal liver areas using baseline and post-therapy c.e. CT, and relief/stabilization and reduced pain drugs intake, whereas 23/57 had
transferred on baseline and post-therapy PET, respectively. K1 (ml/ mildly worsening pain. Interestingly, the percentage of patients
min/g) and k2 (min-1) parameters were estimated using 1-tissue showing a reduction in sPSA values increased linearly with the number
compartment model. For each patient, percentage changes of K1 and of 223Ra-Cl2 administrations (R2 = 0.9975, P = 0.0319). sALP values
k2 in HCC lesions ( K1 and  k2) between baseline and post- dropped more significantly in patients receiving more administrations
therapy PET were correlated to clinical and CT response evaluation (79% after 4, 63% after 5 and 71% after 6 cycles). None suffered from
according to RECIST criteria, used as standard assessment. anorexia; delay in treatment for toxicity occurred only in 1 patient;
Results: HCC lesions (n = 22) showed higher median K1 and k2 diarrhoea occurred in 10/57 (17.5%) cases. After last treatment, 41
values than normal liver both at baseline PET (0.70 vs 0.42, p = 0.01 patients had mild-moderate anaemia whereas only one patient had
and 0.15 vs 0.05, p = 0.0005, respectively) and at post-therapy PET severe haemoglobin reduction (i.e. between 6.5 and 7.9 g/dl); 11/15
(0.57 vs 0.29, p = 0.002 and 0.11 vs 0.03, p = 0.0001, respectively). patients with moderate-severe anaemia were previously treated with
At standard response assessment, 3/5 patients were classified as docetaxel (mean haemoglobin levels at baseline and after last admin-
‘‘disease control’’ (2 with stable disease and 1 with partial response) istration were 11.73 ± 1.38 g/dl and 10.54 ± 1.96 g/dl, P \ 0.001).
and 2/5 patients as ‘‘no disease control’’ (both in progression). At Mild-moderate thrombocytopenia occurred in 9 patients.
post-therapy PET, all 5 patients showed a reduction in K1 value; the Conclusions: 223Ra-Cl2 can be safely used, leading mainly to
magnitude of changes was greater in patients who achieved disease mild/moderate haematological toxicity (more frequently in patients
control than in those with no disease control (mean  K1 = - 35.3% previously treated with docetaxel). This approach allowed to reach
vs -11.4%). Regarding k2, 4 patients (3 disease control, 1 in pro- significant pain relief with reduction of pain drug consumption and
gression) showed a reduction in k2 value, whereas in one patient (in biomarkers decrease in the majority of patients with a favourable
progression) an increase was observed; overall, a greater change in k2 hematologic toxicity profile; in particular, in our experience ALP
was found in patients who achieved disease control than in those who values decreased earlier than PSA values.
did not (mean  k2 = - 33.3% vs - 6.8%).
Conclusions: From our preliminary results, dynamic PET with 13N-
ammonia seems a promising and feasible imaging tool for evaluating
response to Sorafenib in patients with advanced HCC. After treat- OP23
ment, changes in quantitative parameters, represented by K1 and k2, Initial experience with 177Lutetium peptide receptor
are in line with standard response assessment. Further larger studies radionuclide therapy for pediatric patients
are needed to confirm our results and to investigate whether perfusion
with relapsed/refractory metastatic high-risk
changes identified by 13N-ammonia may predict tumour response,
aiming to early select patients with ‘‘no control disease’’ candidates to neuroblastoma
Sorafenib discontinuation.
M. Pizzoferro2, M. Longo1, M.F. Villani2, B. Cassano1, M.G. Cefalo3,
S. Annalisa3, A. Castellano3, M.C. Garganese2

OP22 1
Medical Physics Unit, IRCCS Bambino Gesù Children’s Hospital,
Effectiveness, safety and haematological toxicity Rome, Italy. 2Nuclear Medicine Unit, IRCCS Bambino Gesù
of 223Ra-Cl2: a single centre experience Children’s Hospital, Rome, Italy. 3Oncology Unit, IRCCS Bambino
Gesù Children’s Hospital, Rome, Italy
R. Laudicella1, F. Minutoli1, A.D. Comis1, H. Lanzafame1, B. Background-aim: Treatment of relapsed/refractory metastatic high-
Catalfamo1, F. Panasiti1, C. Mantarro1, B. Pagano1, S. Baldari1 risk neuroblastoma (rrmHRNBL) after multimodality therapy remains
a clinical challenge with no effective salvage therapies. In selected
1
Unit of Nuclear Medicine, Department of Biomedical and Dental patients with evidence of cellular expression of somatostatin receptor
Sciences and of Morphofunctional Imaging, University of Messina, (SSTR) 177Lutetium Peptide Receptor Radionuclide Therapy (177Lu
Messina, Italy PRRT) is emerging as a new targeted therapy option. We report our
initial experience based on this theranostic approach in two heavily
Background-aim: 223Ra-Cl2 is an alpha emitter radiopharmaceutical
pretreated pediatric patients with rrmHRNBL.
approved for treatment of symptomatic bone metastases in adults with
Methods: Two patients affected by rrmHRNBL, previously treated
castration-resistant prostate cancer (CRPC), in absence of any visceral
according to SIPEN HRNB 01 protocol including 131I MIBG as
metastases. The aim of this study was to describe our experience in
second line treatment, showed expression of SSTR in disease sites
this cohort of patients evaluating the effectiveness, safety and
assessed by molecular imaging. 4 cycles of PRRT (Lutathera) were
haematological toxicity of 223Ra-Cl2 treatment.
administered in each patient for palliative intent after ethical com-
Methods: We retrospectively evaluated fifty-seven patients (mean
mittee approval. Recommended administration procedure was applied
age 72.8 ± 7.3 years, range 57–89) treated in our centre. CT scan and
and haematological exams were performed. An individualized
bone scan were performed at enrolment. Complete blood counts,
dosimetry for bone marrow and kidneys was assessed based on blood,
serum alkaline phosphatase (sALP), prostatic specific antigen (sPSA)
whole-body images and organ-based analysis.
and pain score were evaluated at baseline and before each 223Ra-Cl2
administration. 223Ra-Cl2 was administered at the therapeutic activity

123
S16 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

Results: Two heavily pretreated patients (12 and 19 year-old) with (Ct) and CEA levels were assessed before and after treatment. In
rrmHRNBL received 4 cycles of palliative PRRT (4.4 GBq in the 1st selected cases, the radiobiological a parameter was calculated using a
cycle in the younger patient, 7.4 GBq per administration in the other simplified linear quadratic model (LQM).
cycles). For the cycle of 4.4 GBq, the absorbed doses to bone marrow Results: A total of 11 TARE procedures were performed without any
and kidneys were 0.22 and 0.88 Gy, respectively. For the single adverse events (4 bilobar treatments and 3 unilobar treatments). The
cycles of 7.4 GBq, the absorbed doses to bone marrow and kidneys mean injected activity was 936 ± 464 MBq. On CT at 4 months after
ranged from 0.12 to 0.36 Gy and from 0.83 to 1.12 Gy, respectively. treatment, we observed 2 CR (21.8%) and 5 PR (71.4%). A significant
The absorbed doses were below the dose limits for the individual mean reduction of the treated tumor volume was also found
patient, without significant acute toxicity attributed to PRRT. No (21.6 ± 20.2 ml pre-TARE vs 2.1 ± 1.8 ml post-TARE; p = 0.002).
regression of disease was obtained but early symptoms improvement Serum Ct showed a significant reduction at 1 month after TARE
(pain and/or dyspnea relief) was registered in both patients. In the (2982 vs 2657 ng/L; p \ 0.02) and after 4 months of follow-up (2982
younger patient, all disease sites in the thorax had SSTR uptake; over vs 2687 ng/L; p \ 0.04). In addition, mean CEA levels decreased at
the 4 cycles we observed a heterogeneous response to 177Lu PRRT one month after TARE although not statistically significant (151 vs
with evidence of a slow but progressive disease extension in the chest 111 lg/L; p = 0.08). The average absorbed dose to the tumor and to
despite the presence of some areas of tracer uptake reduction. In the the healthy liver based on post-TARE 3D dosimetry resulted
second patient the multiple sites of disease located in thorax and 239 ± 173 Gy and 43 ± 9 Gy, respectively. A significant direct
abdomen had SSTR uptake; over the 4 cycles nodular lesions showed relationship between the logarithm of tumor absorbed dose and its
a slight variability in number and uptake intensity. volumetric reduction was observed (r2 = 0.49; p \ 0.03). The mean
Conclusions: Our preliminary experience suggests that 177Lu PPRT value of the estimated radiobiological a parameter was
might be a new valuable tool for palliative intent in pediatric patients 0.013 ± 0.007 Gy-1.
affected by rrmHRNBL. The main observed advantages are favorable Conclusions: In our preliminary experience, TARE with Y90
radiation safety profile, improvement of quality of life with symptoms microspheres seems to be an effective and safe option for the treat-
relief, short duration of hospitalization, limited prescribed days of ment of LM in patients with advanced MTC. The number of objective
isolation after therapy and rapid reintegration into daily life. Our responses and the reduction of tumor volumes and of serum Ct sup-
clinical results reflect cellular heterogeneity and aggressiveness of port this hypothesis. Moreover, the applied radiobiological model
rrmHRNBL. Clinical trials in larger patient cohorts is warranted for suggests the good radiobiological sensibility of LM from MTC sup-
evaluation of response to 177Lu PPRT and for defining new combined ported by their remarkable hypervascularity. However, more data are
therapy based on distinct molecular targets. needed to assess the long-term effects of TARE and the impact of this
approach on the overall survival of these patients.

OP24
Preliminary experience of transarterial OP25
radioembolization for the treatment of liver metastases Outcome analysis after radioactive iodine-I131
from medullary thyroid cancer: dose–response treatment in 424 patients with hyperthyroidism
relationship and estimate of the radiobiological a
M. Finessi1, A. Bisceglia2, R. Passera1, R. Rossetto Giaccherino2,
parameter G. Castellano1, G. Bisi1, D. Deandreis1

T. Depalo3, G. Boni3, I. Bargellini1, L. Puleo4, F. Bianchi3, 1


Nuclear Medicine Unit, Department of Medical Sciences, University
G. Lorenzoni1, E. Bozzi1, F. Guidoccio3, A. Faranda3, of Turin, AOU Città della Salute e della Scienza, Turin, Italy. 2Unit of
A.C. Traino2, R. Cioni1, R. Elisei4, D. Volterrani3 Endocrinology, Diabetology and Metabolism, Department of Medical
1
Sciences, University of Turin, AOU Città della Salute e della Scienza,
Department of Vascular and Interventional Radiology, University Turin, Italy
Hospital of Pisa, Pisa, Italy. 2Division of Health Physics, University
Hospital of Pisa, Pisa, Italy. 3Regional Center of Nuclear Medicine, Background-aim: 131I therapy (RAIT) represents a curative treat-
University Hospital of Pisa, Pisa, Italy. 4Unit of Endocrinology, ment for hyperthyroidism in toxic adenoma (TA), toxic multinodular
Department of Clinical and Experimental Medicine, University goiter (TMG) and in Graves’ disease (GD) in case of not controlled
Hospital of Pisa, Pisa, Italy hyperthyroidism or disease recurrence after initial treatment with
antithyroid drug (ATD) treatment. According to guidelines both
Background-aim: Liver metastases (LM) occur in 45% of patients dosimetric or empiric approach can be used. The aim of our study is
with advanced medullary thyroid cancer (MTC). In some cases, LM to search for variables correlated with patient’s outcome in a dosi-
cannot be treated with surgery or RFA/TACE, especially when a metric based approach.
multifocal and a bilobar extension is present. Aim of this study is to Methods: We retrospectively analyzed 424 patients with hyperthy-
investigate the efficacy of transarterial radioembolization (TARE) in roidism referred to our department for RAIT between 2000 and 2018
patients with LM from MTC. (121 men and 303 women; TMG n = 213, GD n = 150, TA n = 61).
Methods: Seven patients (6 M and 1 F; mean age 56 ± 10 years) All patients underwent dosimetric approach by daily (6–24–48–72–
with predominant liver disease from MTC, previously selected by 96 h) uptake measurement after administration of about 2 MBq of
MRI or CT scans, underwent a pre-TARE planning angiography 131
I. Outcome was assessed at 6 and 12 months (m) and defined as
followed by a liver perfusion study with Tc99m-MAA SPECT/CT. response in case of euthyroidism and subclinical/overt hypothy-
TARE procedure with Y90 resin microspheres was performed roidism and no-response in case of persistent subclinical/overt
7–14 days later and the administered activity was determined using hyperthyroidism. Association between outcome and baseline TSH
the BSA method. Post-TARE Y90-PET/CT was performed within values, ATD duration and posology, absorbed dose and dimensional
24 h. Post-treatment 3D dosimetry based on Y90-PET/CT allowed to pre-post therapy reduction of target mass assessed by ultrasound was
calculate tumor average absorbed dose. Response to TARE was based evaluated by Mann–Whitney test. Risk factors for response vs no-
on mRECIST criteria. Tumor volumes based on CT, serum calcitonin response outcome were analyzed by binary logistic regression model.

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S17

Results: At 6 and 12 months an overall cure rate of 78.7% and 83% endpoints included best overall response (OR), objective response
was observed, respectively. TSH baseline values were higher in 6 m rate (ORR) (both RECISTv1.1, centrally assessed) and change from
and 12 m response group compared to 6 m and 12 m no-response baseline in diarrhoea and flushing. Safety included incidence of
group (median 0.36 vs 0.08 mcUI/ml, p \ 0.001 and 0.34 vs nephro-, haemato- and hepatotoxicity; vomiting during infusion.
0.08 mcUI/ml, p \ 0.001 respectively). ATD duration and posology Results: Enrolment terminated early (insufficient recruitment). Of 40
were lower in 6 and 12 m response group compared to 6 and 12 m no- patients enrolled, 39 had GEP-NET and one had lung-NET (full
response group (24 vs 36 months, p \ 0.004 and 5 vs 7.5 mg/die, analysis set [FAS]: GEP-NET n = 23, lung-NET n = 1). Median
p \ 0.014; 24 vs 32 months, p \ 0.043 and 5 vs 7.5 mg/die, (range) LAN overall exposure (GEP-NET, FAS): 37.0 (16.7–90.0)
p \ 0.005 respectively). Finally dose to target (DT) was significantly months. PFS rate (GEP-NET, FAS): 91.7% [95% CI: 53.9–98.8]. Best
lower in 6 m responder compared to 6 m no responder group (327 vs OR (GEP-NET, FAS): 34.8% partial response, 60.9% stable disease,
373 Gy, p \ 0.003). No statistical differences were found between 4.3% PD. ORR at time of last LAN–PRRT cycle (GEP-NET, FAS):
DT at 12 m and dimensional variation of target mass both at 6 and 27.3% [95% CI: 13.2–48.2]. Most patients with GEP-NET had stable/
12 m. Multivariate logistic models identify longer ATD duration and improved diarrhoea (15/16) and flushing (16/16) at the end of the last
higher ATD posology as independent risk factors for no-response in LAN–PRRT cycle (FAS). Few toxicities reported; no safety issues
GD group (ATD duration 6 m-OR 1.01, p \ 0.04; 12 m-OR 1.01, identified.
p \ 0.026 and posology 6 m-OR 1.08, p \ 0.037; 12 m-OR 1.09, Conclusions: Effectiveness data were encouraging in this selected
p \ 0.059), in TMG group (ATD duration: 6 m-OR 1.01, p \ 0.005; population. In clinical practice, LAN use is considered before, during,
12 m-OR 1.01, p \ 0.012) and in TA group (ATD posology: 6 m OR and after PRRT.
1.28, p \ 0.06). Sponsored by Ipsen
Conclusions: Our data suggest that a more aggressive, older and  2019 American Society of Clinical Oncology, Inc. Reused with
uncontrolled disease revealed by longer duration and higher posology permission. This abstract was accepted at the 2019 ASCO Annual
of ATD and low TSH levels is correlated to worse response. For these Meeting. All rights reserved.
reasons RAIT therapy has to be considered earlier in patients man-
agement to allow better outcome and avoid ATD toxicity. Impact of
dosimetry on clinical outcome needs further evaluation.
OP27
PRRT in patients with neuroendocrine tumor:
a standardized and simplified dosimetric approach
OP26
Lanreotide autogel/depot before, during, E. Tonini1, S. Di Biaso1, L. Manco1, A. Barboni1, A. Turra1, L.
and after peptide receptor radionuclide therapy Uccelli2, S. Panareo2, C. Cittanti2, I. Santi2, I. Rambaldi2, L. Lodi2,
in advanced neuroendocrine tumours: data E. Zappaterra2, S. Zaccaria2, S. Romani2, E. Govoni2, S. Bertelli2,
from the prelude study D. Bortolotti2, M. Bartolomei2
1
Medical Physics Unit, Sant’Anna University Hospital, Ferrara, Italy.
V. Prasad11, R. Srirajaskanthan5, C. Toumpanakis8, C.M. Grana3, 2
Nuclear Medicine Unit, Sant’Anna University Hospital, Ferrara,
S. Baldari12, T. Shah7, A. Lamarca10, F. Courbon4, K. Scheidhauer9,
Italy
E. Baudin1, X. Truong Thanh2, H. Aude2, L. Bodei6
Background-aim: Since July 2018, Neuroendocrine Tumour (NET)
1
Gustave Roussy, Villejuif, France. 2Ipsen, Boulogne-Billancourt, patients are being treated with peptide receptor radionuclide therapy
France. 3IRCCS Istituto Europeo di Oncologia, Milan, Italy. 4IUCT (PRRT) at Arcispedale Sant’Anna of Ferrara, according to the
Oncopole, Toulouse, France. 5King’s College Hospital NHS ‘‘FENET 2016’’ protocol, that includes the use of 177Lu-DOTATOC.
Foundation Trust, London, UK. 6Memorial Sloan Kettering Cancer For all enrolled patients, a dosimetric evaluation is performed, in
Center, New York, NY, USA. 7Queen Elizabeth Hospital, order to obtain a patient-tailored treatment and to comply with the
Birmingham, UK. 8Royal Free Hospital, London, UK. 9Technical regulations 2013/59/EURATOM, that fixes safety protection stan-
University München, Klinikum r.d. Isar, Munich, Germany. 10The dards for avoiding dangers caused by exposure to ionizing radiation.
Christie NHS Foundation Trust, Manchester, UK. Despite dosimetric evaluation should be considered mandatory, it
11
Universitätsklinikum Ulm, Ulm, Germany. 12University of Messina, is a time-consuming process, not always routinely applicable. The
Messina, Italy aim of the present study is to propose a shorter but complete dosi-
metric procedure, able to provide significant data for an accurate
Background-aim: 177Lu-DOTATATE, a peptide receptor radionu-
evaluation of each individual patient. In this regard, the accuracy of
clide therapy (PRRT), is licensed for gastroenteropancreatic (GEP)
the absorbed dose assessment is strongly correlated to the accuracy in
neuroendocrine tumours (NETs). PRELUDE is the first international,
determining the volumes of interest.
multicentre, retrospective study with central radiology reading to
Methods: Patients are treated with systemic administration of a
describe lanreotide autogel (LAN) use with 177Lu-PRRT (LAN–
cumulative activity between 18.5 and 27.7 GBq. The treatment is
PRRT) in advanced NETs.
fractionated in 5 cycles, each of them ranging from 3.7 to 5.55 GBq,
Methods: PRELUDE (NCT02788578) was an international, retro-
with a time interval between the cycles equal to 2 months.
spective, non-comparative analysis of medical records of patients
Dosimetric evaluation is performed after the 1 cycle to modulate the
receiving LAN–PRRT, and B 12 months follow-up with LAN only.
activity of the further 2, 3 and 4 and cycles and, then, it is repeated
Key inclusion criteria: metastatic/locally advanced, grade 1/2,
after the 5 cycle to assess the variation in term of uptake volume,
somatostatin receptor positive GEP or lung-NET; progressive disease
absorbed dose and BED on target lesions and critical organs. Patient
(PD) in the year prior to LAN–PRRT start; C 1 LAN injection
imaging with SPECT-CT is collected at 1, 24, 48, 72, 96 h after
8 weeks before the first LAN–PRRT cycle; continuous LAN use
177Lu-DOTATOC administration. Subsequently, in order to speed up
during LAN–PRRT; cumulative PRRT activity C 500 mCi. Primary
the dosimetric method, we decided to conduct the analysis with
endpoint: progression-free survival (PFS) rate at the end of the last
SPECT-CT after 1, 24 and 48 h; in this perspective, the cumulated
LAN–PRRT cycle (RECISTv1.1, centrally assessed). Secondary

123
S18 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

activities (obtained with 3 acquisitions) has been compared to the Enrolled patients undergone to standard Ra-223 treatment (six Ra-223
ones obtained performing 5 acquisitions. injections of 55 kBq/kg every 4-week). Physical dosimetry is per-
For imaging elaboration, the MIM software is used by an auto- formed at each radium administration according to protocol recently
mated workflow that allows to contour the volume of interest (VOI) published on SPET/CT calibration (Pacilio et al. 2016). Collection of
regarding tumour lesions, kidneys and bone segments on sequential blood samples and cell cultures are performed at consecutive times:
fused images and co-registered using a non-rigid registration algo- before the 223RaCl2 treatment (T0), after 7 days (T1), 30 days (T2)
rithm. The MIM software allows to obtain a complete report of the after the first treatment and finally at month 6 (T3) corresponding to
data correlating volume, total counts and counts per ml in function of the end of the therapy. Haematological toxicity parameters (blood cell
acquisition time, for each selected VOI. Then, starting from images count) have been weekly monitored during therapy until to one month
counts, it is possible to obtain activity corrected for scatter, attenua- after the end of 6^ cycle and analysed along with doses to blood and
tion and partial volume effects. Finally, the absorbed dose and the non-target tissues.
BED in the selected VOI can be computed through OLINDA 2.0 Results: The preliminary results on five patients evidenced that target
software. doses ranged from 0.001 Gy to 43.7 Gy (median 30.1 Gy) and a
Results: At present, the dosimetric evaluation concerning the first dose–response correlation was observed on target lesions predicting
cycle is available. The mean absorbed dose in kidneys for the selected objective response with a threshold of 20 Gy.
patients are 3.1 Gy, with a standard deviation of 0.8 Gy, while the The administration of 223RaCl2 produces a high dose dependent
BED is equal to 3.4 ± 0.9 Gy, with effective half time equal to increase of the number of dicentrics. Chromosome damage in PBL
42.0 ± 5.4 h and a time a disintegration time of 2.1 ± 0.4 s. (non-target tissue) is dose dependent and increases with the estimated
Conclusions: The final aim of this work is to ensure a dosimetric dose both in terms of dicentric yield and of complexity of the damage.
evaluation to all patients undergoing PRRT. MIM software has Dicentric distribution showed a progressive increase of complex
allowed us to standardize the method by working accurately and with damage which accumulates during the therapy reaching the highest
a great saving of time. The data obtained, related to changes in vol- value after the completion of the therapy (T3).The increase of chro-
ume and uptake, are translated into user-friendly graphs that show an mosome damage (almost double) observed between T1 and T2 is not
easier and more complete evaluation. due to an 223RaCl2 addition dose, suggesting that circulating lym-
phocytes were exposed to an extra dose by the emissions from the
target organs.
Conclusions: These preliminary results may have a relevant clinical
OP28 impact due to two main implications: 1. predictive role of dosimetry,
Correlation between physical dosimetry, biological for both clinical outcome and biological effect, is expected to allow a
effects and clinical toxicity in metastatic prostate personalized treatment that is still missing worldwide for a-emitters;
2. biological effects need to be clearly elucidated before an extensive
carcinoma patient treated with radium—223:
a-emitters clinical use.
preliminary results

R. Sciuto4, S. Rea4, R. Pasqualoni4, A. Annovazzi4, P. Iannantuono4,


S. Bergomi4, A. Testa2, V. Dini3, L. Strigari1 POSTERS
1
Laboratory of Medical Physics and Expert Systems Unit -IRCSS PO001
Regina Elena National Cancer Institute, Rome, Italy. 2ENEA-
Casaccia, Rome, Italy. 3ISS-Rome Italy. 4Nuclear Medicine Unit-
Comparison of myocardial perfusion scores [SSS/SRS]
IRCSS Regina Elena National Cancer Institute, Rome, Italy and extent calculated from manufacturer’s normal
Background-aim: Alpha-Targeted Therapy is emerging as a
database provided by QPS versus institutional
promising new modality for treatment of a variety of malignancies. personalized normal database
However, the delivery of the a-particle energy to the cancer cells
without toxicity to healthy tissues has still been the challenge and the A. Ghilardi1, G. Medolago2, D. Bianchi2, L. Pozzi1, N. Brambati1,
limiting factor. Radium-223 (Ra-223) is the first targeted alpha A. Bruno1
therapy for the treatment of patients (Pts) with metastatic castration
1
resistant prostate cancer (mCRPC) with symptomatic bone metastases ASST-PG23, Bergamo, Italy. 2Humanitas Gavazzeni, Bergamo, Italy
(BM) and no known visceral metastatic disease. The standard activity
Background-aim: In SPECT semiquantitative analysis of myocardial
(six Ra-223 injections of 55 kBq/kg every 4-week) may not be the
perfusion [SSS/SRS scores] proved to be important for diagnosis of
most appropriate therapy for each patient considering the wide dif-
coronary artery disease[CAD]. Most laboratories use pre_installed
ference in clinical presentation of mCRPC. In addition a-emitters
database provided with quantitative software package. However
radiobiological effects are not well known at today. A personalized
characteristics of Manufacturer’s normal database [M-NDBs], created
treatment schedule based on 3D alpha dosimetry could allow an
from patients with a low likelihood of cardiac disease [\ 5%], often
increase in efficacy and a reduction in toxicity.
don’t fit Institutional local population: use of an inappropriate data-
Methods: A Phase II feasibility study on 15 mCRPC patients was
base could influence performance of any quantitative software. Indeed
designed with the following aims: - to validate the actual methodol-
studying normal population in different geographic areas significant
ogy for dosimetric evaluation for alpha therapy in patients undergoing
physical differences may be found. Hence the need to create an
radium-223 chloride (223RaCl2) therapy in mCRPC; - to correlate the
Institutional local database [I_NDB] for each/many laboratories.
effective dose to target and non-target tissue and clinical outcome; -
Aim: We evaluated the effect of body mass index [BMI] as a sig-
to correlate the red marrow dose and the radiation-induced chromo-
nificant variable in diagnostic performance on quantitative
some damage in terms of number of dicentrics and of micronuclei
myocardial perfusion SPECT results using QPS M_NDB versus
induction in peripheral blood lymphocytes (PBL) after 223RaCl2
I_NDB.
treatment.
Methods: Forty male_patients [45 ? 10yrs] and forty female_pa-
tients [40 ? 12 years] scheduled for Tc99m-Sestamibi SPECT during

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S19

2013-2016 period were selected to generate a gender specific I_NDB decrease), non-responders (no HR increase and BP decrease) was
using Cedars Sinai Suite AutoQuant[PFQ]. All patients referred in 0.67, 0.86, 1.31 respectively.
suspicion of CAD with a pretest low likelihood of cardiac disease [at Patients were categorized as: (1) ischemia/hemodynamic responder,
least 1 risk factor] had BMI [ 30; underwent stress exercise on a (2) ischemia/hemodynamic non-responder, (3) no ischemia/hemody-
bicycle ergometer; Gated_SPECT was performed using double-head namic responder, (4) no ischemia/hemodynamic non-responder.
Siemens Symbia-S equipped with LEHR collimators. Myocardial Patients who responded to vasodilator stress as evidenced by hemo-
Perfusion scores [SSS,SRS,SDS] and coronary territory exten- dynamic changes or ischemia had lower SRR-Lung values (0.80, 1.12
t[LAD,LCx,RCA] were calculated both at stress and rest using QPS. and 0.79, respectively) than the group that did not respond (2.46). No
Exclusion criteria were diabetes, ECG abnormalities[LBBB, PM] and significant differences were found using SRR-Liver.
history of CAD [revascularization, infarction]. Conclusions: SRR-Lung could be a method to identify patients with
Results: In males only SDS differed significantly [p \ 0.03] between sub-maximal dipyridamole response, thus potentially improving the
M_NDB and I_NDB [2.4 vs 3.5 mean values respectively]; perfusion overall accuracy of dipyridamole stress Tc-99m MPI.
defect extent PDEx was larger as Total Value both at stress and rest
[0.017, 0.002]; specifically in RCA territory [p \ 0.011] at stress and
LCx [p \ 0.002]at rest.
In females SRS [p \ 0.043] and SDS [p \ 0.043] were significantly PO003
different between M_NDB and I_NDB. As regards coronary territo- Vascular and plaque-specific 18-F-NAF uptake predict
ries PDEx was larger in LAD both at stress [p \ 0.027] and rest the atherosclerotic plaque evolution
[p \ 0.02]; and LCx at rest [p \ 0.047].
Conclusions: In our experience I_NBD, as compared to M_NDB,
F. Fiz4, S. Morbelli3, A. Piccardo2, M. Bagnasco1, G. Sambuceti3
seem to better identify extent and severity of perfusion defects in a
specific subgroup of patients with BMI [ 30. In particular significant 1
Department of Internal Medicine, University of Genoa, Genoa, Italy.
differences were observed in myocardial segments/coronary territo- 2
Nuclear Medicine Deaprtment, Ospedali di Galliera, Genoa, Italy.
ries in which soft tissue attenuation is relevant: inferior/inferolateral 3
Nuclear Medicine Unit, Department of Health Sciences, University
in males and anteroseptal wall in females.
of Genoa, Genoa, Italy. 4Nuclear Medicine Unit, Department of
Radiology, University of Tübingen, Tübingen, Germany
Background-aim: 18-F-NaF-PET/CT (NaF-PET) has been proposed
PO002 as a tool to evaluate microscopic ongoing calcium deposition within
Evaluation of splenic switch-off in dipyridamole stress the atherosclerotic plaque (AP). However, it is unknown whether
Tc-99m tetrofosmin myocardial scintigraphy: NaF-PET uptake can predict whether the degree of calcification
within the AP will increase. In this study, we compared AP tracer
a multicenter study uptake to its calcification rate on subsequent NaF-PETs.
Methods: 56 patients (25 females, mean age 71 ± 8 years) were
P. Ferro3, D. Albano4, O. Kamel Hasan2, F. Bertagna1, L. Camoni4, retrospectively enrolled. Each patient had undergone 2 consecutive
R. Giubbini1, R. Beanlands5, B. Chow5 NaF-PET for clinical reasons (spaced 11 ? 2 months apart). A VOI,
1
including the entire abdominal aorta, was drawn: mean SUV in this
Medicine Department, Brescia University, Brescia, Italy. 2Nuclear VOI was normalized for blood pool to obtain a target-to-background
Medicine Department, London Health Center, London, UK. 3Nuclear ratio (TBRmean). An Agaston-like calcium score (CS) was calculated
Medicine Department, San Raffaele Hospital, Milan, Italy. 4Nuclear on the plaques within the entire abdominal aorta using a semi-auto-
Medicine Department, Spedali Civili, Brescia, Italy. 5University of mated software tool.
Ottawa, Heart Institute, Ottawa, Canada Moreover, up to five representative AP were chosen for each patient.
Background-aim: Inadequate pharmacologic stress and response On each one, a VOI was defined semi-automatically, in which
affect overall accuracy of myocardial perfusion imaging (MPI) for the TBRmean, mean density (HU) and CS were calculated. These values
detection of CAD. Previous magnetic resonance and positron emis- were compared with the corresponding ones on the subsequent NaF-
sion tomography studies have demonstrated that splenic switch-off PET.
(SSO) can be a useful tool to evaluate vasodilator response. The aim Results: CS increased in all subjects (on average 1.2 ± 1.1% per
of this study is to assess the possible role of splenic response in month). There was a direct correlation between aorta TBRmean and
dipyridamole stress Tc-99m MPI. the monthly CS increase (R = 0.79, p \ 0.001).
Methods: 164 patients (72 female, mean age 68 years) who had 199 plaques were identified; baseline plaque TBRmean was corre-
undergone dipyridamole stress Tc-99m MPI were retrospectively lated with percent increase of HU (R = 0.68, p \ 0.01) as well with
analyzed. Splenic, hepatic and lung tracer activity were measured, that of CS (R = 0.89, p \ 0.001). Plaques with a TBRmean \ 1.2
and the splenic response ratio (SRR) was calculated (spleen stress/ presented no increase in HU or in CS.
BKG stress)/(spleen rest/BKG rest). BKG was defined as the tracer Conclusions: Measurement of uptake within the aortic wall or in the
activity either in the liver (SRR-Liver) or in the lungs (SRR-Lung). single plaque can depict ongoing calcium deposition and thus predict
Patients were further categorized based on ECG ischemic changes, the calcification velocity within vascular lesions. 18-F-NaF-PET/CT
vasodilator hemodynamic response (increase in heart-rate (HR) and could represent a new window in estimating the atherosclerotic pla-
decrease blood-pressure (BP)), and scintigraphy results (ischemic vs que evolving potential.
non-ischemic).
Results: Mean SRR-Lung in responder patients (HR increase and
blood-pressure BP decrease), partial responders (HR increase or BP

123
S20 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

PO004 disease. Bone scan scintigraphy could be proposed as integral part of


Importance of cardiological nuclear medicine a new algorithm for the non invasive early diagnosis of CA as just
proposed by Gillmore et al. (2016) and in the future it is possible that
in patients with multiple tumors, a revolution the need for invasive endomyocardial biopsy will be limited to rare
in the choice of therapy after amyloidosis diagnosis exceptions.

L. Cosma1, V. Frantellizzi1, M.S. De Feo1, A. Matto1, L. Civitelli1,


G. De Vincentis1
PO005
1
Nuclear Medicine Unit, Department of Radiological Sciences, Cardiotoxicity in breast cancer patients: the role
Oncology and Anatomical Pathology, Sapienza University of Rome, of gated myocardial perfusion SPECT
Rome, Italy
Background-aim: Cardiac amyloidosis (CA) is an infiltrative disease M. Bonacina3, F. Elisei2, S. Morzenti1, E. De Ponti1, C. Landoni3,
characterized by the extracellular deposition of fibrils, amyloid, in the M. Arosio2, C. Crivellaro3
heart. The vast majority of patients with CA have one of two types:
1
transthyretin amyloid (ATTR) and immunoglobulin light chain Medical Physics, ASST-Monza, San Gerardo Hospital, Monza, MB,
associated amyloid (AL), that have different prognosis and thera- Italy. 2Nuclear Medicine Department ASST-Monza, San Gerardo
peutic options. ATTR CA is further divided into two forms: the Hospital, Monza, MB, Italy. 3Nuclear Medicine, University of
hereditary form (m-TTR) and the acquired form (wt-TTR). CA is Milano-Bicocca, Milan, Italy
often underdiagnosed and even if histological analysis of endomy- Background-aim: Patients undergoing chemotherapy (CHT) for
ocardial tissue is the gold standard for the certain diagnosis, it has its breast cancer (BC) need a monitoring of cardiac function due to the
limitations because it is an invasive technique. Nuclear medicine now possible onset of cardiotoxicity. Cardiotoxicity may occur with heart
plays a key role on the early and accurate diagnosis of this disease, failure but is often asymptomatic and is detectable only by assessing
including the peculiar ability to distinguish between the two types. an increase in cardiac volumes: left ventricular end-diastolic (LV-
We report the case of an 83-year old male affected by prostatic car- EDV) and end-systolic (LV-ESV) volumes and/or by a reduction of
cinoma, carcinoma of the cecum and kidney cancer submitted to bone the left ventricular ejection fraction (LV-EF). The primary purpose of
scan to detect bone metastasis, presenting a myocardial uptake of the study was to evaluate the role of gated SPECT myocardial per-
99mTC-HMPD (hydroxymethylene diphosphonate), very suggestive fusion imaging in this area. Dosimetric evaluation was also assessed.
of ATTR CA. The diagnosis permitted to modify the previous treat- Methods: Seventeen BC patients (mean age 55.93 ± 11.04 years)
ment plan. with invasive ductal carcinoma HER2 ? treated with surgery and
Methods: In 2018 this patient, referred to our center presenting PSA with an anthracycline-based adjuvant CHT, were enrolled. The trend
level elevation, underwent bone scintigraphy to exclude the presence of cardiac function was assessed by evaluation of LV-EF, LV-EDV
of bone metastases. The patient received 740 MBq of 99mTc-HMDP and LV-ESV using gSPECT in baseline conditions and at 12, 15 and
intravenously. Whole body scan was obtained 2 h after injection. 52 weeks during treatment and then at 6, 12, 24 and 48 months during
After the whole body scan, showing intense and homogeneous follow-up. Each patients was studied 15-20 min after injection of
myocardial uptake of 99mTc HMDP, a myocardial single photon 555 MBq of 99mTc-Tetrofosmin with gSPECT (16 frames/cardiac
emission computed tomography (SPECT) study was acquired. Planar cycle) using an Infinia Hawkeye IV gamma-camera. Dosimetry was
image were analyzed and cardiac retention was assessed both semi- assed according to ICRP reports.
quantitatively using the visual scoring (score = 0 absent cardiac Results: Two out of the 17 patients enrolled left the protocol: one
uptake and normal bone uptake; score = 1 mild cardiac uptake infe- because of a second tumor and the other due to the appearance of
rior to bone uptake; score = 2 moderate cardiac uptake accompanied cardiotoxicity. 15 patients completed the study: mean LVEF at
by attenuated bone uptake; score = 3 strong cardiac uptake with mild baseline was 70.67 ± 5.68. The greatest modification occurred after
absent bone uptake) and quantitatively (ROI drawn over the heart, 15th week of treatment, when mean LV-EF showed a significant
copied and mirrored over the contralateral chest) to calculate a heart decrease to 65.67 ± 8.27, while mean LV-EDV and mean LV-ESV
to contralateral ratio (H/CL ratio). Quantitative myocardial uptake increased from 73.60 ± 16.72 up to 84.73 ± 21.11 and from
was also performed using the quantitative SPECT protocol. 21.93 ± 7.17 up to 30.27 ± 14.16, respectively. All parameters
Results: Scintigraphic findings revealed a very intensive tracer uptake progressively returned similar to baseline values at the final exami-
in the heart region compared to bone tissue (score 3). The (H/CL) nation (after 48th month): mean LV-EF 70.20 ± 5.65, LV-EDV
ratio was 1.9. These findings were suggestive of CA and with high 73.40 ± 16.15 and ESV 22.07 ± 7.50. In one case cardiotoxicity
probability of the ATTR form. The oncologic patient in hor- occurred at 15th week: LV-EF decreased from 69 to 47%, LV-EDV
monotherapy with bicalutamide and triptorelin after the diagnosis af increased from 92 up to 142 ml and LV-ESV from 28 up to 75 ml.
ATTR CA, without doing endomyocardial biopsy, and after the dif- According to our image protocols, effective dose for gSPECT was
ferentiation of m-TTR from wt-TTR with genetic testing, could 3.83 mSv (ICRP 106). The use of gSPET instead of MUGA
modify the previous therapy and start a new cardiological treatment (6.47 mSv–ICRP 80) allowed a dose effective saving of 2.64 mSv/
plan. each control with a total saving of 21.12 mSv/patient.
Conclusions: The patient, without a previous history of cardiac dis- Conclusions: Although the small sample size, gSPECT was
ease, after our contribute to the diagnosis of CA, started a specific demonstrated an applicable tool for monitoring cardiac function and it
therapy for this condition taken advantage of it. Early diagnosis of CA correctly identify BC patient with cardiotoxicity. gSPECT also
has important clinical, therapeutic and prognostic implications and allowed a significant radiation dose saving compared to MUGA: this
with improving therapies on the horizon, an accurate diagnosis, is particularly relevant in cardiotoxicity studies that require repeated
including the ability to distinguish between AL CA from ATTR CA, and close evaluations.
is becoming paramount and could improve the survival of this

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S21

PO006 PO007
Role of somatostatin receptor and FDG imaging A semiquantitative score for cardiac transthyretin
in capturing plaque inflammation: a PET/CT analysis, amyloidosis
corroborated by clinical data
S. Gusella 3, A. Spimpolo 3, F. Girardi 3, C. Campi 3, P. Zucchetta
3
3 1 3 4
A. Nieri , F. Fiz , M. Bauckneht , E. Giovannini , M. Parasiliti , C. Calore 1, C. Briani 2, F. Bui 3, D. Cecchin 3
Caprino2, M. Albertelli2, S. Capitanio3, F. Ticconi3, M. Riondato4, 1
S. Raffa3, G. Sambuceti3, D. Ferone2, A. Ciarmiello4, S. Morbelli3 Department of Cardiac, Thoracic and Vascular Sciences, University
of Padua, Padua, Italy. 2Department of Neurosciences, University of
1
Department of Radiology, University of Tuebingen, Tübingen, Padua, Padua, Italy. 3Nuclear Medicine Department, University-
Germany. 2Endocrinology, Department of Internal Medicine, San Hospital of Padua, Padua, Italy
Martino Hospital, University of Genoa, Genoa, Italy. 3Nuclear Background-aim: Cardiac transthyretin amyloidosis (CATTR) is an
Medicine Unit, Department of Health Sciences, San Martino Hospital, underdiagnosed condition commonly leading to heart failure with
University of Genoa, Genoa, Italy. 4Nuclear Medicine Unit, preserved ejection fraction which requires, to be confirmed,
Sant’Andrea Hospital, La Spezia, Italy endomyocardial biopsy (EMB). Despite optimal sensitivity and
Background-aim: Several studies demonstrated that atherosclerosis- specificity, EMB is considered an expensive, invasive and risky
related vascular inflammation can be measured by means of 18F-FDG procedure. In light of the recent development of possible specific
PET. However background (i.e. muscular/myocardial) 18F-FDG transthyretin (TTR) therapies, it is of paramount importance to early
signal spillover or interference with patients’ comorbidities such as and noninvasively identify CATTR patients. Although scintigraphy
diabetes may hamper signal semiquantification. Up-regulation of with 99mTc-bisphosphonates has proven to be an accurate tool for
somatostatin receptor subtype-2 occurs on the surface of activated CATTR detection, wide consensus on scans semi-quantification still
macrophages and it has been suggested that PET imaging of lacks. Qualitative visual assessment of myocardial uptake with
somatostatin receptor distribution may also capture vascular inflam- Perugini 4-points scale (score 0, absent cardiac uptake and normal
mation (in absence of relevant interference related to background bone uptake; score 1, mild cardiac uptake, inferior to bone uptake;
uptake). score 2, moderate cardiac uptake accompanied by attenuated bone
Aim: To compare regional vascular distribution and biological uptake; score 3, strong cardiac uptake with mild/absent bone uptake)
determinants of visible calcium load, as assessed by computed represents—to our knowledge—the most widely used methodology.
tomography and plaque inflammations as assessed by both 68Ga- The aim of this study was to overtake the qualitative analysis by using
DOTATOC and 18F-FDG-PET in the same group of patients. a semi-quantitative approach to easily and objectively classify the
Methods: The study included 27 patients with neuroendocrine tumors degree of myocardial amyloid involvement in suspected CATTR
who underwent 18F-FDG and 68Ga-DOTATOC-PET for clinical patients.
reasons (12 males, mean age 69.4 ± 8.03 range 56–87). Cardiovas- Methods: We retrospectively evaluated 8674 99mTc-bisphosphonate
cular-risk stratification was performed according to a simplified (HMDP or DPD) scans performed for oncological staging or
version of the Framingham model including age, diabetes, smoking, rheumatologic evaluation at the University-Hospital of Padua,
systolic blood pressure and body mass index (BMI). Aortic uptake of Department of Medicine, Nuclear Medicine Unit, between January
both 18F-FDG and 68-Ga-DOTATOC was measured by drawing 2012 and December 2016 in order to identify patients showing car-
regions of interest comprising the entire aorta on each slice of the diac radiotracer uptake. Cardiac uptake, firstly assessed qualitatively
transaxial PET/CT, then SUVmean for the whole aorta was computed using the visual score of Perugini et al., was secondly evaluated using
and normalized to blood activity thus obtaining the aortic target-to- a new heart-to-soft tissue (mid-thigh) semi-quantitative ratio (HTR,
background ratio (TBRmean). With the aim of taking into account the heart to thigh ratio).
presence and degree of aortic hot spots, aortic SUVmax was also A group of 456 healthy controls (HC) with no cardiac uptake (visual
recorded and normalized on blood-pool activity (TBRmax). Finally score 0) has been used as reference.
the degree of arterial calcification (AC) was measured using a soft- ROC curves were created in order to determine the cut-off value
ware program providing Agatston-like scores. Differences in mean better discriminating between HC and patients (P). The cut-off were
values and linear regression analysis were tested for AC, TBRmean then used to classify 27 patients (D) considered doubtful using the
and TBRmax and cardiovascular risk-factors. P value of 0.05 was Perugini qualitative score.
considered statistically significant. Results: 68/8674 (0.7%) patients (52M/16F) aged 79 ± 7 years
Results: Aortic TBRmax was significantly higher on 68Ga-DOTA- showed significant cardiac uptake of 99mTc-bisphosphonates on visual
TOC than 18F-FDG-PET images (p \ 0.0007) while no difference inspection. 43 (63%) were assigned a visual score 1, 18 (27%) a score
were highlighted for TBRmean. Similarly, no correlation was high- 2 and 7 (10%) a score 3. HC and D groups resulted statistically
lighted between TBRmean values and calcium score for both tracers. different from P (p-value \ 0.0001) and from each other (p-value =
AC was dependent upon age, while it was not influenced by all the 0.019). The cut-off that better discriminates between HC and P was
remaining determinants of cardiovascular risk. Framingham risk score 4.285. 3/27 (11%) doubtful patients showed HTR values greater than
correlated with both TBRmean (p \ 0.05). Finally only TBRmax of the cut-off value and have been reclassified.
68
Ga-DOTATOC (and not of 18F-FDG) was higher in diabetics with Conclusions: The proposed HTR and the obtained cut-off proved to
respect to the remaining patients. be an easy method to quantify the cardiac uptake of 99mTc-
Conclusions: Correlations of both tracers uptake upon ongoing bio- bisphosphonates.
logical determinants of vascular damage/inflammation confirm that Although a good correlation between our method and the score pro-
PET might provide several different windows on plaque pathophys- posed by Perugini et al. was showed, the former could offer a more
iology. In this framework 68Ga-DOTATOC vascular signal quantitative approach than visual analysis alone and an applicable
demonstrated to better capture the presence of arterial hot spots and tool in doubtful cases. Further investigations, including genetic
was able to better highlight plaque inflammation in diabetic patients. analysis, will be needed to help identify amyloid subtypes namely
wild-type ATTR (ATTRwt) or genetic ATTR, the latter susceptible of
therapeutic options.

123
S22 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

PO008 99mTc-DPD scintigraphy has to be considered as a part of a com-


99mTc-DPD in amyloidotic cardiomyopathy: posite diagnostic tool, in a selected population in which the last
diagnostic doubt is the differentiation between ATTR and AL.
comparison with NT-proBNP serum levels The future goals will be the enrolment of a greater number of
patents with score 1-2 (for increasing the power and statistical sig-
R. Piva2, C. Aprile4, M. Marenco3, L. Lodola3, G. Palladini1, nificance of 99mTc-DPD scintigraphy), to test this method in the
G. Cavenaghi3 characterization of light chain related amyloidosis and to assess the
prognostic value of Perugini score 2 versus score 3.
1
Amyloidosis Research and Treatment Center, Foundation IRCCS
Policlinico San Matteo, Pavia, Italy. 2Foundation IRCCS Policlinico
San Matteo, Diagnostic Medicine Department, Nuclear Medicine
Unit, Pavia, Italy. 3Foundation IRCCS Policlinico San Matteo, PO009
Diagnostic Medicine Department, Nuclear Medicine Unit, Pavia, Clinical impact of motion artifacts on regional
Italy. 4National Center for Oncological Hadrontherapy (CNAO), myocardial blood flow with [13N]ammonia PET/CT
Pavia, Italy
Background-aim: Myocardial infiltration is the worst prognostic L. Camoni2, S. Cavuto1, R. Rinaldi2, D. Albano2, M. Bonacina3,
factor in patients affected by systemic amyloidosis. The most frequent R. Durmo3, F. Bertagna3, R. Giubbini3
types of systemic amyloidosis associated with cardiologic dysfunction
are transthyretin-related amyloidosis (ATTR) and immunoglobulin 1
Clinical Trials and Statistics Unit, Azienda USL-IRCCS di Reggio
light chains amyloidosis (AL). Emilia, Reggio Emilia, Italy. 2Nuclear Medicine Unit, Spedali Civili
We aimed to verify the usefulness of 99mTc-3,3-diphosphono-1,2- di Brescia, Brescia, Italy. 3Nuclear Medicine Unit, Università di
propanodicarboxylic acid (99mTc-DPD) in detection and etiologic Brescia, Brescia, Italy
differentiation of ATTR from AL, that are mandatory for appropriate
clinical management of amyloidotic cardiomyopathy (AC). Background-aim: Dynamic positron-emission-tomography/com-
Methods: We recruited 74 patients with histologically proven cardiac puted-tomography(PET/CT) is considered the gold standard non-
amyloidosis, who had been referred for evaluation to the Amyloidosis invasive technique for measuring myocardial blood flow (MBF)
Research and Treatment Center of Pavia. in vivo despite this, the motion artifacts are a problem during PET/CT
All patients underwent a complete diagnostic evaluation including scans for quantification of MBF. The aim of this study was to quantify
immunofixation electrophoresis of serum and urine, serum free light the prevalence of body motion in a clinical setting and evaluate the
chain assay, echocardiography, cardiac magnetic resonance and bone effects of motion on MBF and coronary flow reserve (CFR).
scintigraphy. Methods: A cohort of 60 sequential stress/rest PET/CT, injected with
Patients were scanned 5 min and 3 h after intravenous injection of 370 MBq of [13N]Ammonia, was analyzed for patient motion (120
700 MBq 99mTc-DPD. datasets in total) and MBF. Each exam was performed at rest and after
Myocardial uptake was qualitatively scored from 0 to 3 according regadenoson induced hyperemia. The exams were acquired on a GE
to Perugini grading (0: absence of cardiac uptake and normal bone Discovery690 scanner in list mode over 10 min. Stress and rest
uptake; 1: mild cardiac uptake \ bone; 2: moderate cardiac uptake images were reconstructed into 32 dynamic frames (24 9 10 s,
associated to attenuated bone uptake; 3: strong cardiac uptake with 4 9 30 s, 4 9 60 s), corrected for attenuation correction and recon-
mild/absent bone uptake). Heart retention (HR%), whole-body structed using ordered subsets expectation maximization (3 iteration–
retention (WB) and their ratio (H/WB) were semi-quantitatively 24 subsets–filter cut-off 6 mm–Hanning filter). The data were ana-
evaluated from region-of-interest (ROI), drawn over planar images. lyzed and corrected for motion by Corridor 4DM. The motion
Bone scans were performed in a total of 74 patients, 17 with AL artifacts and direction of motion were recorded for each affected
and 57 with ATTR. frame.
Serum assay of NT-proBNP and troponin-I were also performed. Results: Between the 1920 stress frames, 491 were corrected for
Results: Final diagnosis of cardiac involvement was confirmed in all motion artifacts (25.6%). The directions of the motion were cranial
the patients under study. for 213 frames, caudal for 230, anterior for 37 and posterior for 11.
ATTR patients were characterized by a moderate/strong cardiac Between the 1920 rest frames, 73 were corrected (3.8%). The direc-
uptake (7/57 had score 2; 50/57 score 3), while AL patients showed tions of the motion were cranial for 42‘ caudal for 18, anterior for 8‘
absent/mild uptake (10/17 score 0; 5/17 score 1; 2/17 score 2). We posterior for 5. The whole sample, considering the four directions, has
found a perfect match between, respectively, scintigraphic score 3 and a quadratic mean motion ± standard deviation of 5.49 ± 2.06 mm.
patients with ATTR and scintigraphic score 0/1 and AL patients. The The MBF of the stress PET/CT of the was statistically significant for
subpopulation with Perugini score 2 included both ATTR and AL the left anterior descending artery (LAD), for the right coronary artery
subjects. (RCA) and for the global MBF (TOT) (p \ 0.05) but not for the left
Sensitivity of visual scoring in ATTR and AL patients was 100% circumflex artery (LCX) (p = n.s.). In the three coronary territories
and 42% respectively. there’re no statistically significant difference (p = n.s.). The CFR was
Specificity and negative predictive value could not be evaluated statistically significant for LAD and TOT (p \ 0.05), but not for the
because of the high prevalence of disease in this preselected LCX and RCA. (p = n.s.).
population. The difference between with motion correction (MC) and without
HR and H/WB were significantly higher in ATTR patients has a wide range from -72% to ? 228% for MBF and CFR. The
(p \ 0.0001, U Mann–Whitney Test). confidence intervals at 95% (95% CI) for stress LAD, LCX and RCA
On the other side, the organ dysfunction markers were higher than were: 0.0868 (0.0566|0.1170), 0.000167 (- 0.0289|0.0292), - 0.0648
normal values but with no significant differences in the two (- 0.1078|- 0.0219), respectively. The rest 95% CI of LAD, LCX
subgroups. and RCA were respectively: - 0.0162 (0.0549|0.0225), - 0.007
Conclusions: 99mTc-DPD scintigraphy is confirmed to be a useful (- 0.0227|0.0086), - 0.0592 (- 0.1362|0.0178). The CFR 95% CI
tool for ATTR diagnosis, while its function in the differentiation of were 0.1397 (0.0745|0.2049), 0.0238 (- 0.0244|0.0720), 0.00667
AL from non–AC remains to be ascertained. (- 0.0772|0.0906) for LAD, LCX and RCA, respectively.

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S23

After MC five LAD territories modified the CFR from \ 2 ml/ 9/62 patients. PET has detected 108 positive vascular lesions in 28
min/T to [ 2 ml/min/T. Appling the MC to the RCA territories three patients with a median SUVmax value of 2.8 (range 1.1–7.0).
cases changed the CFR from [ 2 ml/min/T to \ 2 ml/min/T. In positive PET patients, mean CRP value was 7.92 mg/L (range
Conclusions: Motion artifacts frequently occur in stress/rest 0.03–39.60), mean ESR value was 21 mm/1 h (range 1–73) and mean
[13N]Ammonia-PET/CT, mainly with caudo-cranial direction and PTX3 value (13/28 patients) was 5.69 ng/ml (range 2.16–15.70). In
wide variability. If this artifacts aren’t corrected, they can introduce negative PET patients, median CRP was 8.99 mg/L (range
statistically significant difference in the quantification of MBF and 0.30–65.50; p-value: 0.421), mean ESR value was 28 mm/1 h (range
CFR, with errors up to 228%. 2–78; p-value 0.195) and mean PTX3 (18/34 patients) value was
7.74 ng/ml (range 2.93–22.70; p-value 0.132).
Conclusions: Functional characterization of the arterial lesions by
PET/CT provide additional information in TA over disease activity
PO010 measures, mainly based on systemic inflammation. Further prospec-
Functional characterization vascular lesions by FDG tive study is necessary to correlate FDG PET uptake with MRI
PET/CT provides additional information over clinical enhancement in vascular lesions, and to clarify the clinical relevance
and the predictive value of this imaging approach for the disease
assessment in Takayasu arteritis patients
progression and the best treatment strategy.
E. Incerti4, F. Fallanca4, U. Pajoro4, E. Tombetti1, M. Papa7,
G. Ironi5, E. Baldissera2, F. De Cobelli8, L. Gianolli4,
A.A. Manfredi3, M. Picchio6 PO011
1
Which coronary artery is more frequently affected
Department of Biomedical and Clinical Sciences, ‘‘L. Sacco’’
Hospital, Milan, Italy. 2Unit of Internal Medicine and Clinical
in smoker and non-smoker patients with coronary
Immunology, IRCCS San Raffaele Scientific Institute, Milan, Italy. artery disease?
3
Unit of Internal Medicine and Clinical Immunology, IRCCS San
Raffaele Scientific Institute, Milan, Italy/Vita-Salute San Raffaele N. Quartuccio3, M. Siracusa3, R. Ricapito3, R. Laudicella2,
University, Milan, Italy. 4Unit of Nuclear Medicine, IRCCS San L. Sturiale2, A. Arnone3, C. Caruso1, S. Baldari2, G. Arnone3
Raffaele Scientific Institute, Milan, Italy. 5Unit of Nuclear Medicine,
1
IRCCS San Raffaele Scientific Institute, Milan, Italy/Unit of Cardiology Unit, ARNAS PP.OO. ‘‘Civico, Di Cristina e
Radiology and Experimental Imaging Center, IRCCS San Raffaele Benfratelli’’, Palermo, Italy. 2Department of Biomedical and Dental
Scientific Institute, Milan, Italy. 6Unit of Nuclear Medicine, IRCCS Sciences and Morphofunctional Imaging, Nuclear Medicine Unit,
San Raffaele Scientific Institute, Milan, Italy/Vita-Salute San University of Messina, Messina, Italy. 3Nuclear Medicine Unit,
Raffaele University, Milan, Italy. 7Unit of Radiology and ARNAS PP.OO. ‘‘Civico, Di Cristina e Benfratelli’’, Palermo, Italy
Experimental Imaging Center, IRCCS San Raffaele Scientific
Background-aim: Smoking is a well-recognized risk factor for
Institute, Milan, Italy. 8Unit of Radiology and Experimental Imaging
coronary artery disease (CAD). However, to our knowledge, no study
Center, IRCCS San Raffaele Scientific Institute, Milan, Italy/Vita-
in literature has ever investigated which vessel is more frequently
Salute San Raffaele University, Milan, Italy
affected in patients with smoking history. The aim of this observa-
Background-aim: Takayasu arteritis (TA) is a rare, chronic and tional study was to examine the frequency of involvement of the main
large-vessel granulomatous disease of unknown etiology, affecting coronary arteries in smokers and non-smokers.
the aorta and its major branches. The disease typically presents at less Methods: 146 consecutive patients (mean age 65.8 years; M 121; F
than 40 years of age and affecting prevalently young women. The first 25) with cardiac single-photon emission computed tomography
goal of therapy is prevent progression of inflammatory vascular (SPECT) scans suggestive of CAD and positive coronarography
lesions. Disease activity evaluation is currently defined according to (performed within 3 months) were retrieved from the hospital data-
National Institutes of Health (NIH) criteria and it is thus very bases of two nuclear medicine departments. Patients were divided in
important for therapeutic decision. The aim of this study is to verify if two groups: non-smokers (n = 58) and smokers (including ex-smok-
activity PET measures and functional lesion characterisation provide ers; n = 88). Coronarography was used as standard of reference to
additional information in TA patients. establish the involvement of main coronary arteries (left anterior
Methods: A retrospective monocentric study on 62 patients with TA descending artery = LAD, left circumflex = LCx and right coronary
according to American College of Rheumatology Criteria was per- artery = RCA). Difference on frequency of involvement of each
formed at the IRCCS San Raffaele Hospital from April 2013 to April coronary artery between the two groups was assessed by means of Chi
2017 (56 women and 6 men; mean age: 48 years, range 18–81 years). square test (p \ 0.05).
All patients underwent FDG PET/CT and magnetic resonance Results: Involvement of LAD was more frequent in smokers com-
imaging (MRI) examinations, with a median interval of 1 month pared to non-smokers (p \ 0.001), being affected in 63 out of 88
(range 0–6 months). All vascular lesions in PET/CT was evaluated smokers (71.6%) and in 25 out of 58 non-smokers (43%), whereas
with both qualitative (positive/negative, visual scale 0-3, uptake involvement of LCx occurred more frequently in non-smokers than
aspect) and semi-quantitative (maximum standardized uptake value— smokers (46% vs. 31%, respectively; p = 0.039). No significant dif-
SUVmax) methods. Correlation of PET evaluation versus serum ference in frequency of involvement between the two groups was
biomarkers values as C-reactive protein (CRP), erythrocyte sedi- found for RCA (54.5% of smokers vs. 55.2% of non-smokers;
mentation rate (ESR) and pentraxin 3 (PTX3) was also performed. p = ns).
Results: PET was positive in 28/62 patients and negative in 34/62 Conclusions: LAD seems to be the most commonly affected coronary
patients, but all patients showed at least one vascular lesions at MRI. artery in smokers with CAD and its involvement in this group of
Visual scale analysis showed score 3.0 ([ liver uptake) in 22/62, 2.0 patients appears to be significantly more frequent than in non-
(= liver uptake) in 7/62, 1.0 (\ liver uptake) in 14/62, and 0 (no smokers. Conversely, LCx seems to be more frequently involved in
uptake) in 19/62 patients. Aspect of FDG uptake was focal in 8/62, non-smokers compared to smokers. Due to the small size of this study
widespread inhomogeneous in 25/62 and widespread homogeneous in sample, these findings should be confirmed in larger investigations.

123
S24 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

PO012 ZLNU and the Agatston score in asymptomatic plaques were found
Evaluation of [18F]NAF uptake in symptomatic (r = 0.7 and p = 0.05 and r = 0.78 and p = 0.02, respectively).
Contralateral 50% asymptomatic plaque and 50% symptomatic
and asymptomatic carotid artery plaques plaques share common features not present in the other asymptomatic
and determination of predictive pattern of vulnerable plaques. This may prelude potential plaque evolution, therefore we
plaque: preliminary results are currently follow up the patient to test this possibility.
Conclusions: These preliminary data suggest a possible use of
R. Zanca2, M. Mari3, N. Belcari1, M. Ferrari3, R. Berchiolli3, [18F]NaF-PET/CT such as texture features, to characterize the
P.A. Erba2 heterogeneity of atheromatous lesions potentially predicting asymp-
tomatic carotid plaque evolution causing unexpected cerebro-vascular
1
Department of Physics, University of Pisa, Pisa, Italy. 2Regional accidents.
Center of Nuclear Medicine, Department of Translational Research
and New Technology in Medicine, University of Pisa and AOUP,
Pisa, Italy. 3Vascular Surgery Unit Department of Translational PO013
Research and New Technologies in Medicine, University of Pisa and
AOUP, Pisa Italy [18F] FBB cortical uptake is not related to the age
of onset of Alzheimer’s disease
Background-aim: Indications to surgical intervention in patients
with carotid artery stenosis is a topic under constant debate, above all
in symptomatic patients. Recently, the use of [18F]NaF has been A. Chiaravalloti1, G. Barbagallo5, A.E. Castellano6, M. Ricci3,
suggested to detect microcalcifications in the arterial wall, a feature G. Ciccariello6, F. Ursini2, N. D’ascenzo4, Q. Xie4, O. Schillaci1
closely associated with macrophage accumulation and inflammation. 1
In this small series of patients we aim to perform a proof of concept Department of Biomedicine and Prevention, University Tor Vergata,
study on the feasibility of [18F]NaF imaging in patients with symp- Rome, Italy. 2Department of Health Sciences, University of
tomatic carotid stenosis. Therefore, we performed [18F]NaF-PET/CT Catanzaro ‘‘Magna Graecia’’, Catanzaro, Italy. 3Department of
just before carotid endarterectomy and correlate imaging and surgical Radiological, Oncological and Pathological Sciences, Sapienza
findings. University of Rome, Italy. 4Huazhong University of Science and
Methods: Between January and July 2018 we evaluate 10 patients Technology, Wuhan, China. 5Institute of Neurology, University
with symptomatic carotid stenosis between 50–90% (mean age Magna Graecia of Catanzaro, Catanzaro, Italy. 6IRCCS Neuromed,
71 ± 13 years, range 51–84). Patients underwent echo-color Doppler, Pozzilli, Italy
angioCT and [18F]NaF-PET/CT within 7-days interval. Time of PET/ Background-aim: To investigate the relationships between amyloid
CT from symptoms onset and surgery varied from 1 to 8 weeks. burden in brain and the age of onset of Alzheimer’s disease (AD),
Whole-body [18F]NaF-PET/CT (Discovery710 GE) was assessed by exploring the differences between patients with early onset of Alz-
visual analysis, semiquantitative parameters (MTV, SUVmax, SUV- heimer’s disease (EOAD, aged B 65 years) and patients with late
mean, SUVsd, TLA) and texture features to better characterized onset of Alzheimer’s disease (LOAD, aged [ 65 years).
lesion heterogeneity as compared to the contralateral normal/sub- Methods: We examined 60 patients with clinical diagnosis of Alz-
critical site. For this evaluation we used the LIFEx package from heimer’s disease according to NINCDS-ADRDA criteria. Of them 22
semiautomatically segmented PET and CT images. were EOAD, and 38 were LOAD. All of them underwent a brain
Results: Several features have been identify comparing homolateral Positron Emission Tomography (PET) scan 90 min after the injection
carotid artery stenosis to contralateral vessel (HISTO: KURTOSIS/ of 4-[(E)-2-[4-[2-[2-(2-fluoranylethoxy)ethoxy]ethoxy]phenyl]ethenyl]-
ENTROPY/ENERGY, GLRLM: SRE/LRE/GLNU/RP, NGLDM N-methylaniline ([18F] FBB); 300 ± 10 MBq). Qualitative analysis of
CONTRAST, GLZLM : LZE/LZHGE/GLNU/ZLNU, GLCM : PET data was positive for increased amyloid burden in brain in all the
CONTRAST/DISSIMILARITY). Figure 5 shows the correlogram of AD subjects. Relationships between amyloid burden in brain and age of
the extracted features. onset of AD were assessed by means of Statistical Parametric Mapping
Considering the ultrasound and clinical characteristics of the plaques, (SPM) version 12, with the use of age as regression factor and sex,
in contralateral 50% asymptomatic carotid stenosis we observed 16 Mini-Mental State Examination (MMSE) as covariates in the regression
features meaningful for unsteable plaque (SUVmean, SUVstd, analysis. Moreover, a two-sample t test was used for comparison
SUVmax, HISTO KURTOSIS/ENTROPY/ENERGY, GLCM between EOAD and LOAD subjects.
CONTRAST/DISSIMILARITY, GLRMLRE/LGRE/HGRE/SRLGE/ Results: There were no significant differences [18F] FBB uptake
LRLGE/LRHGE, GLZLM HGZE/SZLGE). The values of GLCM- between EOAD and LOAD patients. Multiple regression analysis did
DISSIMILARITY are significantly higher in symptomatic patients not show any significant correlation between age of onset and brain
with carotid plaque [ 50%. So we can hypothesize how this feature, amyloid deposition in AD subjects.
can be a marker of plaques with tendency to instability but can also Conclusions: In our study population, age of onset is not related to
correlate with the percentage of stenosis. SUVmax values as well as brain amyloid burden in AD patients. Other factors may be involved
the features of HISTO-KURTOSIS e GLRLM-LRHGE, are signifi- in explaining the clinical differences between EOAD and LOAD
cantly different in patients treated with statins as compared to statin- patients.
naive. A significant correlation between HISTO-KURTOSIS and
plaque volume in symptomatic patients, GLZLM-GLNU/GLZLM-

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S25

PO014 PO015
Erdheim–chester disease with infratentorial Cortical response to levodopa in Parkinson’s disease
leukoencephalopathies: brain FDG-PET, bone patients with dyskinesias
scintigraphy and whole-body FDG-PET
G. Marotta2, F. Turco3, A. Canessa3, C. Olivieri3, N. Pozzi1,
1 2 3
G. Marotta , L. Chiapparini , G. Cavalli , T. Langella ,2 C. Palmisano1, G. Arnulfo1, J. Volkmann1, G. Pezzoli4, I.U. Isaias1
A. Venerando2, G. De Luca3, S. Raspante2, B. Pollo2, G. Lauria2, 1
M.G. Cangi3, S. Gerevini3, A. Botturi2, L. Dagna3, D. Pareyson2, Department of Neurology, University Hospital Wuerzburg and
E. Salsano2 Julius-Maximillian-University, Wuerzburg, Germany. 2Department of
Nuclear Medicine, Fondazione IRCCS Ca’ Granda Ospedale
1
Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Maggiore Policlinico, Milan, Italy. 3Fondazione Europea di Ricerca
Nuclear Medicine Department, Milan, Italy. 2Fondazione IRCCS Biomedica, Milan, Italy. 4Parkinson Institute ASST G. Pini-CTO,
Istituto Neurologico Carlo Besta, Milan, Italy. 3IRCCS Ospedale San Milan, Italy
Raffaele, Milan, Italy Background-aim: Levodopa-induced dyskinesias are a common and
Background-aim: Erdheim–Chester disease (ECD) is a rare non- disabling side effect of dopaminergic therapy in Parkinson’s disease
Langerhans cell histiocytosis likely under-diagnosed as cause of adult (PD), but their neural mechanisms in vivo are still poorly understood.
infratentorial leukoencephalopathies. In this study, we evaluated Besides striatal pathology, the importance of cortical dysfunction has
radiological and nuclear medical imaging of ten patients presenting been increasingly recognized. The supplementary motor area (SMA)
with prominent infratentorial leukoencephalopathy of unknown origin in particular, may have a relevant role in dyskinesias onset given its
who were most often diagnosed with ECD. involvement in endogenously generated actions. The aim of the
Methods: Seven males and three females; mean age at clinical onset present study was to investigate the levodopa-related cortical
was 49.6 years (range 38–59); cerebellar ataxia with or without other excitability changes along with the emergence of levodopa-induced
neurological symptoms was the only or the main clinical manifesta- peak-of-dose dyskinesias in subjects with PD.
tion. Eight patients had white matter focal supratentorial Methods: Thirteen patients without dyskinesias and ten with dyski-
abnormalities, in addition to the infratentorial white matter changes, nesias received 200/50 mg fast-acting oral levodopa/benserazide
and six out of eight patients had spinal cord lesions. following overnight withdrawal (12 h) from their dopaminergic
All ten patients underwent one or more conventional brain MR medication. For each patient, the most dopamine-depleted hemisphere
imaging studies, bone scintigraphy, whole-body FDG-PET and brain was identified, based on the density of dopamine reuptake transporters
FDG-PET. (DAT) at the striatal level measured with FP-CIT SPECT.
Results: MRI showed supratentorial involvement (deep cerebral We targeted transcranial magnetic stimulation to the supplementary
white matter, corona radiata, and internal capsule) in eight patients motor area, ipsilateral to the most dopamine-depleted striatum defined
and involvement of the hypothalamic–pituitary axis in all patients. with FP-CIT SPECT, and recorded transcranial magnetic stimulation-
Thoraco-abdominal CT showed periaortic sheathing in two patients. evoked potentials with high-density electroencephalography before
Brain FDG-PET showed hypermetabolism in the infratentorial lesions and at 30, 60, and 180 min after levodopa/benserazide intake.
in one patient, and in the region of sella turcica in another patient. Results: The striatal DAT binding values decreased significantly in
In eight patients (none of whom complained of bone pain), 99mTc all patients, with no difference between the two groups.
bone scintigraphy showed a symmetric diaphyseal and metaphyseal Clinical improvement from levodopa/benserazide paralleled the
radiotracer uptake in the long bones of the legs; in four of these increase in cortical excitability in both groups. Subjects with dyski-
patients, plain X-ray films showed osteosclerotic lesions in the long nesias showed higher fluctuation of cortical excitability in comparison
bones of the legs. to non-dyskinetic patients, possibly reflecting dyskinetic movements.
Whole-body FDG-PET including distal extremities revealed PD with dyskinesias showed a greater increase of Immediate
increased glucose uptake in the long bones of the legs in five patients. Response Area (IRA) at 30 min ( %IRA30_off) and 60 min
In the remaining two patients with normal 99mTc bone scintig- ( %IRA60_off) after levodopa intake, while suffering from dyski-
raphy, no abnormality was found either on plain X-ray films and in nesias. Also of relevance, at 180 min (when levodopa was still
whole-body and brain FDG-PET, while CT scan demonstrated pul- beneficial, but levodopa-induced dyskinesia were no longer present,
monary fibrosis in one. the IRA measurements ( %IRA180_off) did not significantly differ
In eight patients, ECD was confirmed by bone scintigraphy, between the two groups.
pathological data, or both. Two ECD patients treated with vemu- We did not find a significant correlation between  % IRA-
rafenib showed a marked improvement of neurological symptoms and max_off and age, disease duration, disease severity (UPDRS-III score
brain MRI abnormalities at 1 year follow-up. at meds-off), dyskinesias severity, or density of DAT at a striatal
Conclusions: Adult patients with prominent infratentorial leukoen- level.
cephalopathies of unknown origin should undergo investigations Conclusions: In this study PD with dyskinesia displayed an imme-
aimed at unveiling ECD, including bone scintigraphy and whole-body diate hypersensitivity of SMA, possibly sustaining dyskinetic
FDG-PET. The early diagnosis allows starting disease-modifying movements. Dynamic changes in SMA excitability emerged rapidly
therapies of an otherwise life-threatening disease. within the first 30 min following levodopa intake and closely paral-
leled clinical responsiveness to levodopa, but did not correlate with
striatal DAT density, which was similar in subjects with or without
dyskinesias.
Together with endogenous brain oscillation, levodopa-related
dynamics of brain state could influence the therapeutic response of
neuromodulatory interventions.

123
S26 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

PO016 levels correlated with NAWM volume (r = 0.81; p = 0.01). The


Amyloid PET as a marker of normal-appearing white multiple regression analysis showed CSF Aß levels as the best pre-
dictor of NAWM volume (r = 0.81; p = 0.007).
matter early damage in multiple sclerosis: correlation Conclusions: We found a lower WM-SUV in damaged WM (DWM)
with CSF -amyloid levels and brain volumes compared to normal appearing WM (NAWM) in all patients. A
decreased NAWM-SUV in active compared to non-active group was
G. Marotta1, A.M. Pietroboni2, T. Carandini2, A. Colombi2, observed. CSF Aß concentration was a predictor of both NAWM-
C. De Cicco3, D. Galimberti2, E. Scarpini2 SUV and NAWM volume. The correlation between CSF Aß levels
and WM-SUV suggests that the predictive role of Aß may be linked
1
Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, to myelin early damage and may reflect the disease activity and the
Nuclear Medicine Department, Milan, Italy. 2Neurodegenerative clinical progression.
Diseases Unit, University of Milan, Centro Dino Ferrari, Fondazione
IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy.
3
Ospedale di Cremona, ASST Cremona, Cremona, Italy
PO017
Background-aim: Multiple sclerosis (MS) is the most common Structural and metabolic cerebral alterations
chronic inflammatory disease of the central nervous system (CNS),
whose demyelination is the pathological hallmark. between elderly bipolar disorder and behavioral
Positron emission tomography (PET) with ß-amyloid tracers is a variant frontotemporal dementia: a combined MRI-
promising tool to evaluate white matter (WM) damage and repair. PET study
Aims of the current study are: (1) to assess amyloid uptake in WM
of MS patients, dividing patients in accord to their disease activity; G. Marotta1, G. Delvecchio4, G.M. Mandolini4, A. Arighi2,
(2) to investigate possible correlations between amyloid uptake and C. Prunas4, M.C. Mauri4, A.M. Pietroboni2, C. Cinnante3,
CSF Aß levels, brain volumes, and clinical markers of disease F.M. Triulzi3, E. Scarpini2, C. Altamura4, P. Brambilla4
progression.
Methods: Twelve patients were divided according to their disease 1
Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico,
activity in the last year before the recruitment: 8 patients were con- Department of Nuclear Medicine, Milan, Italy. 2Fondazione IRCCS
sidered active, whereas 4 patients were judged stable, with no Ca’ Granda Ospedale Maggiore Policlinico, University of Milan,
evidence of acute inflammation (non-active MS). Centro Dino Ferrari, Neurodegenerative Diseases Unit, Milan, Italy.
All patients underwent lumbar puncture, brain MRI and 18F-Flor- 3
Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico,
betapir PET. Neuroradiology Unit, Milan, Italy. 4Fondazione IRCCS Ca’ Granda
FLAIR-weighted images and SUV-PET images were coregistered Ospedale Maggiore Policlinico, University of Milan, Department of
to individual volumetric T1-weighted images. Lesions were seg- Neurosciences and Mental Health, Milan, Italy
mented by the lesion growth algorithm as implemented in the LST
toolbox version 2.0.15 for SPM. Background-aim: Elderly Bipolar Disorder (BD) and Behavioral
Using the WM and GM probability map of segmentation of the Variant of Frontotemporal Dementia (bvFTD) may exhibit similar
individual lesion-filled T1-images, we extracted the mean SUV of symptoms and both disorders are characterized by selective abnor-
each patient’s total WM and GM by the coregistered SUV-PET malities in cortical and subcortical regions that are associated with
images. cognitive and emotional impairments.
The ROI representing NAWM was calculated by subtracting the Aim of the study was to investigate common and distinct neural
DWM ROI from the total WM ROI. substrates of BD vs bvFTD by coupling, magnetic resonance imaging
GM was evaluated also using the Siemens PET Amyloid Plaque (MRI) and positron emission tomography (PET).
Quantification software of the package Molecular Imaging Methods: 3T MRI and FDG-PET scans were acquired for 16 elderly
Neurology. BD patients, 23 bvFTD patients with mild cognitive impairments and
Results: Concerning the GM tracer uptake, all patients were cate- 68 healthy controls (48 for PET and 20 for MRI analyses).
gorized as amyloid negative by quantitative cut-off. Concerning the MR images were acquired using a 3-Tesla Philips Achieva MRI
WM tracer uptake, DWM-SUV was lower compared to NAWM-SUV scanner. PET scans were obtained with a Biograph Truepoint 64 PET/
(1.032 ± 0.112 vs. 1.128 ± 0.122; p = 0.0005) in each subject. CT scanner. For VBM analyses, all T1-weighted images were seg-
When dividing patients according to their disease activity (active mented and Dartel tools were then used to determine the nonlinear
group vs. non-active), we found a reduced NAWM-SUV in active deformations for registering the GM and white matter images of all
group compared to non-active group (1.077 ± 0.119 vs. subjects, and the resulting images were spatially normalized into the
1.231 ± 0.023; p = 0.028), whereas no significant differences in MNI space and smoothed with an 6-mm Gaussian filter. For PET
DWM-SUV were observed. NAWM-SUV correlated with both total analyses, all FDG-PET images were subjected to affine and nonlinear
WM volume (r = 0.73; p = 0.006) and NAWM volume (r = 0.82; spatial normalization into the MNI space with SPM12 using the
p = 0.01), but not with DWM volume (r = -0.45; p [ 0.05) in all MS dementia-optimized brain FDG-PET template and smoothed with an
patients. 8-mm Gaussian filter. Inference on the GM volumes and metabolic
Focusing on the active group, CSF Aß levels were lower in patients differences between groups was made using double-sided t-tests with
with WM-SUV less than 1.05 compared to those with WM-SUV a threshold of p \ 0.001.
greater than or equal to 1.05 (698.8 ± 32.57 vs. 1033 ± 226.4; Results: BD and bvFTD patients exhibit different localization of gray
p = 0.029). CSF Aß levels correlated with NAWM-SUV (r = 0.79; matter (GM) reductions in the lateral prefrontal cortex (PFC), with the
p = 0.017). In particular, the lower the CSF Aß concentration the first group showing GM decrease in the ventrolateral PFC and the
lower the tracer uptake in the NAWM. The linear regression analysis latter group showing GM reduction in the dorsolateral PFC and
showed CSF Aß levels as a predictor of NAWM-SUV (r = 0.79; unique alterations within the orbitofrontal cortex. The bvFTD group
p = 0.01). NAWM-SUV correlated with NAWM volume (r = 0.82; also displayed unique volumetric shrinkage in regions within the
p = 0.01). The multiple regression analysis showed NAWM volume temporo-parietal network together with greater metabolic impair-
as the best predictor of NAWM-SUV (r = 0.87; p = 0.007). CSF Aß ments within the temporal cortex and more extensive volumetric and

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S27

metabolic abnormalities within the limbic lobe. Finally, while the BD Conclusions: The role of primary visual cortex area for the differ-
group showed greater GM volumes in caudate nucleus, bvFTD sub- entiation between blink and pursuit visual behavior seems to be
jects displayed lower metabolism. important and our model could help clinicians to evaluate if visual
Conclusions: This MRI/PET study explored structural and functional fixation response supports or not the diagnosis of MCS.
abnormalities in bvFTD and elderly BD patients, with the final aim of
identifying the specific biological signature of these disorders, which
might have important implications not only in prevention but also in
differentiating diagnosis and treatment. PO019
18F-Florbetaben PET/CT for clinical assessment
of Alzheimer’s disease in a multidisciplinary team
PO018 study: value into anti-amyloid clinical trials and new
Visual fixation in disorders of consciousness: imaging analysis method for amyloid regional burden
a combined analysis with flash visual evoked potentials, quantification
MRI and PET to support differential diagnosis
P. Alongi9, D.S. Sardina4, S. Gilberto2, R. Coppola5, S. Scalisi9,
1 2 2 2 V. Puglisi1, A. Arnone8, G. Di Raimondo1, V. Alaimo6, G. Russo7,
G. Marotta , D. Sattin , D. Rossi Sebastiano , L. D’incerti , D.
A. Stefano7, R. Giugno3, T. Piccoli2, M. Midiri10, L. Grimaldi5
Guido2, S. Tirelli2, A. Bersano2, D. Duran2, S. Ferraro2, L. Minati2,
A. Nigri2, S. Bianchi Marzoli3, C. Rosazza2, M. Leonardi2 1
Department of Neurology, G.Giglio Institute, Cefalù, Italy.
2
1 Department of Biomedicine and Clinical Neuroscience, University
Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico,
of Palermo, Palermo, Italy. 3Department of Computer Science,
Nuclear Medicine Department, Milan, Italy. 2Fondazione IRCCS
University of Verona, Verona, Italy. 4Department of Mathematics and
Istituto Neurologico Carlo Besta, Milan, Italy. 3IRCCS Istituto
Computer Science, University of Catania, Catania, Italy. 5Department
Auxologico Italiano, Neuro-Ophthalmology Unit, Milan, Italy
of Neurology, G.Giglio Institute, Cefalù, Italy. 6Department of
Background-aim: One of the major challenges for clinicians who Radiological Sciences, G.Giglio Institute, Cefalù, Italy. 7Institute of
cure patients with Disorders of consciousness concerning the detec- Molecular Bioimaging and Physiology, National Research Council
tion of signs of consciousness to differentiate patients in Vegetative (IBFM-CNR), Cefalù, Italy. 8Nuclear Medicine School, University of
State (VS) from those with minimal consciousness (MCS). Recent Firenze, Italy. 9Nuclear Medicine Unit, Department of Radiological
studies showed as visual responses to tailored stimuli seem to be one Sciences, G.Giglio Institute, Cefalù, Italy. 10University of Palermo,
of the first evidence revealing that one patient is changing from one Palermo, Italy
state to another one. The aim of this cross-sectional study is to ana-
Background-aim: We assessed the impact of 18F-Florbetaben
lyze the visual system in a selected group of patients in order to find
(FBB)-PET using a new processing imaging algorithm in correlation
useful markers for clinical classification of participants showing
with clinical data, neuropsychological assessment and cerebrospinal
visual fixation ability.
fluid (CSF) analysis on the diagnosis of AD in a clinical setting and
Methods: Flash visual evoked potentials (fVEPs), structural 3T
potential inclusion in clinical trials.
magnetic resonance imaging (sMRI) and FDG-PET were analyzed in
Methods: Seventy-seven patients with clinical evidence of dementia
58 inpatients. Forty-two (72%) patients out of 58 showed only visual
according to ENS-EFNS criteria, undergoing diagnostic FBB-PET
blink reflex in the Coma Recovery Scale-Revised visual function
were retrospectively evaluated by a multidisciplinary team (MDT).
subscale, twelve (21%) visual pursuit and four (7%) fixation scores.
FBB-PET results were correlated with clinical, cognitive status, CSF
For FDG-PET, SUV maps were coregistered using SPM12 to indi-
analysis and other imaging. FBB-PET images were processed with
vidual volumetric T1 series, which were segmented to generate the
SPM and converted in standard space (MNI space) by normalizing
normalization deformation field to be applied to the coregistered
them with tissue probability map as template. AAL atlas was used to
FDG-PET scan. The general linear model was used to perform a
mask each regional VOI followed by extraction of SUVR, normalized
voxel-by-voxel univariate statistical test for groups comparison: a
on the cerebellar gray matter. The regional SUVR and scores from
two-sample t-test was conducted between patients with the visual
clinical and cognitive tests were used to create ROC curves and obtain
blink response only and patients with visual pursuit. The voxel-based
the best thresholds for the clinical diagnosis. Leave-one-out cross-
statistical analysis was performed by applying a threshold of
validation was carried out to validate the results.
p \ 0.001 and considering clusters of at least 100 voxels.
Results: An elevated amyloid burden was detected at FBB-PET scan
Results: A significant difference was also found between the two
in 45/77 patients with dementia. Diagnostic integration with FDG-
groups (voxel threshold = p \ 0.001 FDR-corrected) considering
PET, clinical data and CSF protein levels was possible in a soubgroup
FDG-PET data. The cluster was composed of 389 voxels and it was
of 44 out of 77 patients. Of them 26/44 patients presented elevated
localized in the right calcarine cortex (Brodmann area 17) and in the
amyloid burden at FBB-PET. Finally, 22 out of 26 patients FBB-PET
neighboring right lingual gyrus cortex (areas 18/19).
positive were classified by MDT as AD, the remaining 4 as vascular
The relationships between instrumental data (fVEPs, sMRI, PET) and
or FTD. Among the variables ordered by AUC, FBB and FDG PET,
sociodemographic variables and presence of visual blink to threat or
CDR value 1, CSF Tau and p-tau levels showed the best true positive
visual pursuit responses were fitted in univariate and multivariable
and true negative rates (FBB-PET: AUC = 0.85, Se 0.91, Sp 0.79;
logistic regression models to predict visual pursuit behavior finding
FDG PET: AUC = 0.76, Se 0.86, Sp 0.67; CDR 1 AUC 0.72, Se 0.75,
specific cut-off values. An AUC = 0.902 was found using tailored
Sp 0.67; CSF-Tau: AUC = 0.75, Se 0.84, Sp 0.64; CSF p-TAU AUC
cut-off values. Finally, a qualitative test of the best predictive model
0.66, Se 0.72, Sp 0.65). At semi-quantitative evaluation of FBB-PET,
was made on four patients with visual fixation revealed in 3/4 patients
a SUVR value of 1.006 in the inferior frontal cortex and of 1.03 in the
a good probability to predict if fixation data could support/correlate to
precuneus region were the best cutoff SUVR value and showed a
visual pursuit behavior or not, reducing diagnostic error using stan-
good correlation with the diagnosis of AD (inferior frontal cortex
dard assessment scale only (25% in our small sample).
AUC 0.883; precuneus region AUC 0.826). By using two-tailed
Pearson correlation between SUVR values of all brain region and

123
S28 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

neuropsychological tests, we found a significant moderate inverse group, we documented that iRBD patients showed increased FDG
correlation especially for inferior frontal cortex and Attentive-mem- uptake compared to PD patients in the midbrain and pons, cerebellum,
ory test (R = -0.455; p = 0.008), Rey Auditory-verbal learning Test lentiform nucleus and claustrum, and in frontal and temporal lobes.
(R = - 0.459; p = 0.006), Corsi-Span Test (R = - 0.408; Conversely, PD patients did not show areas with increased FDG
p = 0.017), Raven Test (R = - 0.405; p = 0.022). An inverse cor- uptake compared to iRBD patients. Considering the AD and DLB
relation was also found between precuneus brain region and Raven groups, when comparing iRBD to DLB group we documented that
Test (R = - 0.420; p = 0.017) and rolandic operculum region and iRBD patients showed increased FDG uptake in temporal, parietal,
Rey Auditory-verbal learning Test (R = - 0.426; p = 0.012), Atten- and occipital lobes than DLB, whereas iRBD patients showed glucose
tive-memory test (R = - 0.477; p = 0.005) and Corsi-Span Test relative hypometabolism compared to DLB patients in frontal and
(R = - 0.427; p = 0.012). Based on FBB-PET positivity followed by limbic lobes. Finally, iRBD patients showed reduced FDG uptake in
other necessary characteristics for inclusion criteria 13 patients have the frontal lobe and increased FDG uptake in limbic, temporal and
been successfully enrolled in clinical trials using innovative mono- parietal lobes compared to AD patients .
clonal antibodies therapy Conclusions: This study documented the alteration of brain [18F]FDG
Conclusions: Amyloid-PET, especially when using SPM normalized uptake in iRBD patients compared to controls, as expected in the
SUVR analysis, confirms high predictive power for the differential early stages of neurodegeneration. However, the pattern of cerebral
diagnosis of dementia over FDG-PET, neuropsychological tests and [18F]FDG uptake found in iRBD patients resulted different from that
CSF analysis. When evaluating patients with dementia, however, a presented by AD, DLB or PD patients. These findings further support
multidisciplinary approach is crucial for the final classification of the hypothesis that iRBD may represent a very early stage of neu-
patients with AD and potential inclusion in clinical trials. rodegeneration in which unspecific biomarkers changes occur.

PO020 PO021
Cerebral glucose metabolism in idiopathic REM sleep Clinical progression over 1-year in mild cognitive
behavior disorder is different from Tau-related and a- impairment subjects with low ß-amyloid neocortical
synuclein-related neurodegenerative disorders: a brain retention levels
[18F]FDG PET study
A. Ciarmiello3, E. Giovannini3, M. Riondato3, G. Giovacchini3,
5 5 2 1 5
C. Liguori , R. Ruffini , E. Olivola , A. Chiaravalloti , F. Izzi , O. Ferrando3, M. De Biasi1, C. Passera1, S. Pastorino3, A. Mannironi2,
A. Stefani4, M. Pierantozzi3, N.B. Mercuri3, N. Modugno2, P. Lazzeri3, A. Tartaglione1
D. Centonze2, O. Schillaci1, F. Placidi5 1
Memory Center, La Spezia, Italy. 2Unit of Neurology, S. Andrea
1
Department of Biomedicine and Prevention, University Tor Vergata, Hospital, La Spezia, Italy. 3Unit of Nuclear Medicine, S. Andrea
Rome, Italy. 2IRCSS Neuromed, Pozzilli, Italy. 3Neurology Unit, Hospital, La Spezia, Italy
Department of Systems Medicine, University of Rome ‘‘Tor Background-aim: The rate of clinical progression in mild cognitive
Vergata’’, Rome, Italy. 4Parkinson’s Disease Centre, Neurology Unit, impairment (aMCI) subjects with low amyloid burden is unknown.
Department of Systems Medicine, University of Rome ‘‘Tor The primary aim of the study was to perform a 1-year follow-up on
Vergata’’, Rome, Italy. 5Sleep Medicine Centre, Department of rate of cognitive decline in aMCI with low amyloid retention level.
Systems Medicine, University of Rome ‘Tor Vergata’’, Rome, Italy The secondary objective was to compare the rate of cognitive decline
Background-aim: REM behavior disorders (RBD) is a sleep para- in low amyloid positive and negative subjects.
somnia, characterized by the pathological lack of atonia during REM Methods: In this prospective phase III trial (EudraCT 2015-001184-
sleep associated with enacting dreams. Several longitudinal studies 39), 32 participants with aMCI underwent clinical, neuropsycholog-
revealed that patients affected by idiopathic RBD (iRBD) trend to ical and PET amyloid imaging tests. Study participants were followed
convert to a-synucleinopathies at follow-up. Although several efforts for 1 year to assess changes in global cognition and amyloid burden.
have been spent to predict the phenoconversion of RBD to a-synu- PET images were scored as positive (Aß ?) for amyloid retention
cleinopathies, we do not currently have instruments able to identify using a standardized uptake value ratio C 1.3, measured in grey
which neurodegenerative disorder underlies iRBD condition. This matter, at baseline scan. The Mattis Dementia Rating Scale (MDRS)
study aimed at evaluating brain glucose metabolism, measured by was used to assess clinical longitudinal changes of cognitive
[18F]FDG-PET, in patients affected by iRBD in order to find possible impairment.
similarities and differences to Parkinson’s Disease (PD), Lewy Body Results: Amyloid positive subjects showed greater clinical worsening
Dementia (DLB), Alzheimer’s Disease (AD), and controls. on MDRS score (p = 0.03). Aß- showed no significant changes on
Methods: Differences in brain [18F]FDG uptake were analyzed using MDRS scores over 1 year. Among 13 subjects with cognitive dete-
statistical parametric mapping (SPM8) implemented in Matlab rioration 11(85%) had positive amyloid scan and 2 (15%) were Aß-
R2012b among iRBD, PD, DLB, AD, and controls. whereas in MDRS- group 5 (26%) were Aß ? and 14 (74%) were
Results: Fifty-four iRBD, 28 PD, 10 DLB, 55 AD, and 35 controls Aß - (|2 = 10.5;P = 0.001). Aß positivity identified individuals with
were included in this study. over-time progression (Sensitivity = 85%, Specificity = 74%,
When comparing iRBD to controls, we documented that iRBD PPV = 69%, NPV = 88%).
patients showed glucose relative hypometabolism in a wide cluster Conclusions: This study demonstrates that, aMCI cognitive decline
including BA 7, 19, and 37, owing to precuneus, superior parie-tal can be predicted at low retention amyloid level and above the
lobule and middle temporal gyrus. Conversely, iRBD patients showed threshold of SUVr = 1.3 the rate of decline is increased. Detection of
increased FDG uptake in several BA compared to controls, owing to low amyloid deposition may help in selecting target population for
temporal lobe, limbic lobe, and frontal lobe and in the brainstem. preventive therapeutic interventions and to design treatment trial.
Thereafter, we compared iRBD patients to patients affected by
different neurodegenerative processes. When comparing iRBD to PD

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S29

PO022 late-scan at 50 min). PET/CT images were analyzed visually and


Impact of tracer retention level on visual classification semiquantitatively. For visual analysis, three physicians with different
experience scored tracer uptake on the 18F-Florbetapir early-phase
of amyloid PET images and 18F-FDG images in 10 cortical regions (bilateral frontal, tem-
poral, parietal, occipital, posterior cingulate/precuneus) using a four-
E. Giovannini1, G. Giovacchini1, E. Borsò1, P. Lazzeri1, V. Duce1, point scale (0 = no reduction, 1 = slight, 2 = moderate, 3 = severe
O. Ferrando1, A. Ciarmiello1 reduction), and 18F-Florbetapir late-phase in the same cortical
regions using a three-point scale (0 = normal, 1 = abnormal with
1
Unit of Nuclear Medicine, S. Andrea Hospital, La Spezia, Italy minor plaques, 2 = abnormal with major plaques). We used SPM12
Background-aim: Our aims were to test inter-rater agreement and for semiquantitative analysis applying a ROI-based correlation anal-
concordance between visual and semiquantitative scoring at different ysis (considering precuneus as target region and normalized for the
amyloid retention levels in Mild Cognitive Impairment (MCI) mean global binding), a covariance-analysis taking precuneus as
patients. target and a comparison of global DMN (Deafult Mode Network).
Methods: A sample of 71 amnestic MCI patients (AGE Results: Inter-reader agreement was very high (Cohen’s kappa 0.762
73.96 ± 7.35 years, MMSE 24.23 ± 5.33, CDR-SOB 2.16 ± 2.14) for 18F-FDG, 0.775 for 18F-Florbetapir early-phase and 0.794 for
underwent 18F-florbetaben PET/CT and clinical assessment. Amyloid late-phase). Regional visual scores of early-phase and 18F-FDG were
positivity was assessed by semiquantitative approach by means of significantly correlated (r = 0.867, p \ 0.001). Also ROI-based
previously published threshold (SUV C 1.3). Images were visually analysis, global brain visual analysis and DMN comparison revealed
scored as positive or negative by three independent, certified readers concordant results between 18F-Florbetapir early and 18F-FDG-PET/
blinded to neuropsychological result. Fleiss kappa coefficient was CT, especially at parietal and precuneus regions (p \ 0.001).
used to test inter-reader concordance on the whole population and on Conclusions: 18F-Florbetapir early-phase scans significantly corre-
3 subgroups with low (SUVr \ 1.1), medium (SUVr [ 1.1 \=1.5) late on quantitative and visual images with 18F-FDG-PET/CT scans,
and high (SUVr [ 1.5) Aß burden. suggesting that amyloid tracer could potentially be used as
Results: Fleiss’s kappa statistic was k = 0.86, P \ 0.00001 on the biomarkers in place of 18F-FDG.
whole sample. By evaluating the groups with different Aß burden
separately, the inter-raters agreement changed according to tracer
retention levels (k = 0.85, P = 0.0001; k = 0.48, P = 0.0001; PO024
k = 0.98; P = 0.00001; for low, medium and high subgroup respec-
tively). In medium MCI group, 9% of subjects scored as negative on Comparison of semiquantitative analysis methods
visual assessment were classified amyloid positive on semiquantita- of dopaminergic brain imaging
tive threshold whereas we did not find discrepancies in low and high
amyloid retention groups. R. Durmo1, B. Paghera1, D. Albano1, M. Bonacina1, M. Gazzilli1,
Conclusions: Inter-raters agreement of visual detection of amyloid E. Cerudelli1, F. Dondi1, A. Mazzoletti1, L. Camoni1, F. Bertagna2,
positivity is high in low and high retention levels group but reduces in R. Giubbini2
the range of SUVr [ 1.1 \=1.5), in these cases the support of semi-
1
quantitative analysis would be necessary to reduce the risk of amyloid Nuclear Medicine, Spedali Civili Brescia, Brescia, Italy. 2Nuclear
positivity misclassification. Medicine, University of Brescia and Spedali Civili Brescia, Brescia,
Italy
Background-aim: Brain single photon emission computed tomog-
PO023 raphy (SPECT) with 123I-Ioflupane is the most common technique to
Preliminary study of correlation between brain glucose differentiate degenerative parkinsonian syndromes from non-degen-
erative parkinsonism. Visual assessment of reconstructed images is
metabolism (18F-FDG) and cerebral blood flow considered sufficient for the diagnosis, but the availability of semi-
with amyloid tracers (18F-florbetapir) in clinical quantitative methods have the potential to improve diagnostic
routine accuracy (pointing out subtle changes that can elude human eye).
Moreover, quantification potentially allows to follow disease pro-
D. Albano4, B. Paghera3, C. Rodella1, R. Durmo4, M. Bonacina4, gression, the effects of neuroprotective drugs and to evaluate
E. Premi2, M. Gazzilli4, E. Cerudelli4, A. Mazzoletti4, F. Dondi4, relationships with measurable clinical parameters such as classifica-
F. Bertagna4, A. Padovani2, R. Giubbini4 tion of the stage disease. The aim of our study was to compare the
performances of two different semiquantitative methods of analysis
1
Health Physics Department, Spedali Civili, Brescia, Italy. data in the same population: one based on 2D ROI analysis (DaTS-
2
Neurology Unit, Department of Clinical and Experimental Sciences, CAN 3-2 software; GE Healthcare) and the other one based on 3D
University of Brescia, Brescia, Italy. 3Nuclear Medicine, Spedali VOI method (the basal ganglia V2 software, BasGan).
Civili Brescia, Brescia, Italy. 4Nuclear Medicine, University of Methods: Two hundred fifty patients (146 male; 104 female; median
Brescia and Spedali Civili Brescia, Brescia, Italy age 65, range 40–86) referred to our Nuclear Medicine Department to
undergo a 123I-Ioflupane SPECT for an unclassified parkinsonian
Background-aim: Amyloid PET tracers are lipophilic and charac- syndrome were retrospectively evaluated. All patients underwent a
terized by an elevated first-pass influx rate (K1). Early amyloid PET baseline clinical examination by a movement disorder specialist
may provide valuable K1-related information. Several pharmacoki- before imaging. After at least 2 year of follow up a new clinical
netic studies indicate that K1 reflects regional cerebral blood flow, revaluation was made. SPECT images were visually assessed by a
which is closely related to glucose metabolism. nuclear medicine physician expert in neuroimaging. The patient data
This prospective study compare the performance of 18F-Florbetapir- were processed using two commercial programs to determine the
PET/CT early acquisitions to 18F-FDG-PET/CT in a clinical setting. relative uptake in the striatum: (1) DaTSCAN 3-2 software (GE
Methods: We included 15 patients who underwent 18F-FDG-PET/ Healthcare Xeleris workstation), an 2D operator depending software
CT and a dual-time 18F-Florbetapir-PET/CT (1-6 min early-scan and

123
S30 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

and (2) the free software Basal-Ganglia Matching-Tool v.2 (BasGan sampled for the analysis of the DAT1 gene expression and methy-
v2, Windows workstation) operator free 3D automatically software. lation degree on Peripheral blood lymphocyte (PBL) cells. In more
A comparison of the results from the programs was performed, detail, the degree of methylation of a fragment of about 300 bp at the
together with a comparison with the visual assessment. ROC curve level 5 ‘of the UTR region of the first exon DAT-1 (SLC3A6), with
analysis was performed to find the cut-off value with the best accu- transcription regulator function, in PBL of patients with de novo
racy for every methods to predict the final diagnosis. diagnosis of PD was investigated and compared with data obtained
Results: At the visual analysis, 123I-Ioflupane striatal uptake was from an equivalent healthy subjects group. This evaluation has been
normal in 63/250 patients (25%) and abnormal in 187/250 patients made prior to any specific medical treatment, in drug-naive patients,
(75%) with a mild, medium or severe unilateral/bilateral decreased to avoid any possible pharmacologic interpherence and modulation on
striatal uptake. Visual analysis showed a Sensitivity of 96.9%, DAT1 gene expression. In addition, the degree of DAT1 mRNA
Specificity of 100%, Positive Predictive Value of 98.5%, Negative transcription was quantified. The central nervous system DAT
Predictive Value of 89.4% and accuracy of 97.7% for degenerative imaging was achieved with DATscan and obtained data were coupled
parkinsonism. The mean caudate-occipital uptake ratio with DaTS- with those derived from the 123I-MIBG imaging.
CAN3-2 was 3.21 ± 0.65 for the right caudate and 3.22 ± 0.64 for Results: The degree of DAT1 gene methylation is confirmed strongly
the left; while with the BasGan 3,18 ± 0.97 for the right and correlated with age and disease severity, underlining how this
3.15 ± 0.96 for the left respectively. Putamen/occipital mean uptake mechanism influences the individual phenotype during the course of
ratio with the DaTSCAN3-2 was 2.62 ± 0.69 for the right and whole life.
2.6 ± 0.72 for the left putamen; the BasGan was respectively This study showed a tendency to the correlation between DAT1 gene
2.07 ± 1.01 for the right and 2.09 ± 1.00 for the left side. The ROC methylation and putaminal dopaminergic depletion at neuro-recep-
curve showed a sensitivity of 80,6% and specificity of 71.9% with the torial imaging that offers speculative hypotheses of scientific
BasGan software and a sensitivity of 78,1% and specificity of 69.8% deepening. Preliminary evidence of increased gene expression in
with the DaTSCAN3-2 software. AUC for BasGan software was Parkinson’s lymphocytes would suggest that the reduction of circu-
0.827 for the caudate and 0.915 for the putamen. AUC for the lating catecholamines may support an up-regulation of peripheral
DaTSCAN3-2 software was 0.805 for caudate and 0.894 for putamen. DAT aimed to increasing neurotransmitter reuptake. Depletion of the
No statistical difference between the two methods was found transporter on the circulating lymphocytes, however, which cannot be
(p = 0.081 for the caudate and p = 0.1 for the putamen). correlated with the degree of nigrostriatal depletion, leads to the
Conclusions: The two semiquantitative methods provide very robust suspicion that the two phenomena, even with the same trend, are not
results for routine evaluation of 123I-Ioflupane scans and they are correlated and therefore subject to different regulatory mechanisms.
both remarkably accurate. Conclusions: This result, providing a missing link between genome
and environment, would support the hypothesis that, despite a clear
correlation between lymphocyte protein and nigrostriatal protein
evident at the peripheral molecular level, it represents an evidence of
PO025 the development of the phenomenon in the same direction.
Correlation between neuroreceptorial DAT/MIBG
imaging and DAT gene methylation in Parkinsonian
syndromes PO026
Multidisciplinary approach on dementia diagnosis: our
M. Pontico2, V. Frantellizzi2, N. Locuratolo1, F. Fattapposta1,
G. De Vincentis2
experience

1
Department of Neurology and Psychiatry, Sapienza University of G. Grassetto4, M. Ceci1, F. Fordiani3, P. Amista’3, R. L’erario2,
Rome, Rome. 2Nuclear Medicine Unit, Department of Radiological P. Dalsanto1, M.C. Marzola4, S. Chondrogiannis4, L. Rampin4,
Sciences, Oncology and Anatomical Pathology, Sapienza University A.M. Maffione4, D. Rubello4
of Rome, Rome 1
Geriatric Unit, Hospital Rovigo, Rovigo, Italy. 2Neurology Unit,
Background-aim: Parkinson’s disease is a progressive neurodegen- Hospital Rovigo, Rovigo, Italy. 3Neuroradiology Section, Hospital
erative disease characterized by a heterogeneous and complex Rovigo, Rovigo, Italy. 4Nuclear Medicine Department, Hospital
syndromic picture whose etiopathogenesis, currently unknown, it is Rovigo, Rovigo, Italy
believed to be supported by complex multifactorial environmental
and genetic interactions. In a large majority of parkinsonian syn- Background-aim: To evaluate the efficacy of multidisciplinary
dromes, the risk of developing neurodegeneration is linked, in approach in dementia diagnosis.
addition to genetic factors, to environmental events occurring during Methods: Since May 2017 in Rovigo Hospital it has been constituted
development or in advanced stages of life, responsible for increased a multidisciplinary ‘‘dementia’’ group (MG) that meets monthly. The
susceptibility to the disease. The study of the dopaminergic nigros- group is composed by geriatrics, neurologist, neuroradiologists and
triatal degeneration, crucial event of the motor phenomenology of PD, nuclear medicine physicians and discuss about patients with suspected
is currently supported in vivo by functional neuroimaging provided by dementia or MCI already submitted to clinical and biochemical
DATScan. This study focused on the evaluation of the relationships examination (Vitamin B12, folate, TSH), Geriatric Assessment
between the degree of DAT gene methylation at the peripheral level (MMSE, Clock drawing test, ADL, IADL) and Brain Morphological
and nigrostriatal presynaptic DAT protein expression to determine the examination (CT or RMI).
potential correlation between peripheral and central neurodegenera- Results: From May 2017 until November 2018 the MG discussed 55
tion indicators. patients, 28 male and 27 female, mean age 71, mean MMSE 20.55,
Methods: 12 patients recently diagnosed with idiopathic PD were mean ADL 5, mean IADL 3.5. A secondary dementia was excluded in
submitted to 123I-FP-CIT brain SPECT and 123I-MIBG myocardial all patients by morphological and biochemical examinations. The
SPECT, obtained in a timeframe of no more than 2 months. Previ- multidisciplinary group reached the diagnosis at the first discussion in
ously, at the time of the clinical diagnosis, each subject was blood 31/55 patients without the need of further examinations. In 10/31
primary dementia (PD) was excluded (cases of psychiatric or

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S31

paraneoplastic conditions). In the others PD diagnosis was reached not clarified by Q analysis. Furthermore, only SQ could suggest the
(vascular, neurodegenerative or mixed conditions). In 24/55 MG diagnosis of PNFA in the remaining 2/17 cases. Finally, in the
determined the need of further examinations (MRI in patient with patients classified as PNFA or SVA, also based on clinical and
doubtful CT result, brain FDG-PET, DaTscan, amyloid-PET, EEG, MMSE signs, a progression to FTD could be hypothesized, while in
liquor analysis, 2nd level neuropsychological tests). At the re-evalu- those patients classified as LPA a relation to AD could be suggested.
ation MG reached the diagnosis in 10 patient. The others 14 require Conclusions: This study seems to confirm the usefulness of FDG-
follow-up. PET in diagnosing PPA variants already in an early stage as well as in
Conclusions: The multidisciplinary meeting let to share the point of suggesting the development in FTD or AD in uncertain cases. SQ
view of the different physicians allowing a deeper knowledge of each analysis proved to give a significantly increment of Q analysis per-
single case and a better interpretation of the examinations, especially formance in our cases, permitting to achieve the most appropriate
the functional ones. In our experience multidisciplinary approach let disease classification, thus suggesting that the combined use of the
to avoid expensive further examinations in about half of cases. two procedures of analysis represents the most valid tool for the best
interpretation of FDG-PET images in PPA patients. A larger series of
cases monitored in a long clinical and instrumental follow up are
necessary to confirm these data.
PO027
Qualitative (Q) and semiquantitative (SQ) brain 18F-
FDG PET analyses in primary progressive aphasia
PO028
(PPA) variants
Value of brain F18-FDG PET/CT in antiphospholipid
S. Nuvoli2, M.R. Piras1, S. Contu2, B.L.J. Pung2, G. Tanda2,
syndrome associated chorea: a case report
A. Marongiu2, A. Spanu2, G. Madeddu2
F.M. Fringuelli2, S. Luzzi1, G. Biscontini2, C. Rinaldi1, G. Garraffa2,
1
Unit of Neurology, Department of Medical, Surgical and A. Palucci2, L. Burroni2
Experimental Sciences, University of Sassari, Sassari, Italy. 2Unit of 1
Nuclear Medicine. DPT of Medical, Surgical and Experimental Department of Experimental and Clinical Medicine, Polytechnic
Sciences. University of Sassari, Sassari, Italy University of Marche, Ancona, Italy. 2Nuclear Medicine Unit,
Ospedali Riuniti ‘‘Torrette’’, Ancona, Italy
Background-aim: The differential diagnosis of PPA variants repre-
sents a critical problem since logopenic aphasia (LPA) might progress Background-aim: Antiphospholipid syndrome (APS) is character-
to Alzheimer disease (AD) and progressive non-fluent aphasia ized by arterial and/or venous thrombosis in the presence of
(PNFA) and semantic variant (SVA) to fronto-temporal dementia antiphospholipid antibodies. Central nervous system (CNS) involve-
(FTD). We evaluated the usefulness of both Q and SQ analyses of ment is one of the most common clinical manifestations of APS, and
18F-FDG PET images in the differentiation of PPA variants. includes arterial and venous thrombotic events, psychiatric features
Methods: We retrospectively enrolled 35 consecutive patients, 18 and a variety of other non-thrombotic neurological syndromes.
with clinical symptoms of aphasia but with normal MMSE and with Chorea is a rare non-thrombotic neurological manifestation of APS.
unclear classification of PPA variants (Group A); 17 patients with Brain magnetic resonance imaging (MRI) can be of help in detecting
clinical and MMSE signs attributable to PPA and with mixed cerebrovascular lesions but often yields negative results in APS
symptoms for early AD and FTD (Group B). All patients underwent patients. Previous ECD-TC99 m SPECT studies revealed decreased
brain 18F-FDG PET/CT analyzing the images by both Q and QL brain blood flow in APS with a history of thrombotic events. There
methods, the latter using an automated analysis program that produces were still non-objective methods qualified to detect the early CNS
brain metabolic z score region map, and comparing each patient with involvement in APS.
age matched control group. Methods: A 68-years-old woman with APS and clinical history of
Results: Q analysis visualized hypometabolism areas of different deep venous thrombosis and pulmonary embolism was admitted to
degree, irregularly widespread or localized in different cortical our hospital for subacute onset of involuntary, uncoordinated move-
regions, in most cases bilaterally and in prevalence in the left hemi- ments Neurological evaluation revealed generalized chorea in
sphere. SQ analysis evidenced z score highest value in different areas absence of focal signs. The antiphospholipid antibodies were mea-
permitting to identify those with the major pathological involvement. sured, including IgG/IgM to cardiolipin and 2-Glycoprotein I
In particular, in Group A patients, Q and QL analyses were concor- (2GPI).
dant to achieve a correct diagnosis in 8/18 (44.4%) cases as 4 LPA Results: Traditional brain CT scan was normal and brain MRI
and 4 PNFA. In the other 10/18 (55.6%) patients, only SQ analysis revealed only a nuanced hypointensity of the basal ganglia of indef-
could be useful for the most appropriate diagnosis as LPA in 5 cases inite meaning. The antiphospholipid antibodies values showed a
and as PNFA in the remaining five cases, one of the latter wrongly significant increase of Cardiolipin (IgG [ 640 and IgM [ 300;
classified as LPA at Q analysis. In Group B patients, both analyses n.v. \ 10) and 2GPI (IgG [ 867 and IgM [ 300; n.v. \ 10). Brain
were concordant in 9 (52.9%) patients classifying 5/17 cases as PNFA F18-FDG PET/CT showed a significant reduction in glucose meta-
and 4/17 cases as LPA. In other 4/17 patients with difficulties in bolism in both hemispheres and thalami, with increased metabolism
discriminating LPA from PNFA at Q analysis, a correct classification of the caudate nuclei and precentral giri.
of PNFA could be permitted only by SQ analysis. Moreover, in 1 of Conclusions: Our findings suggest that F18-FDG PET/CT can detect
17 cases, SQ was able to change the classification from LPA to PNFA brain metabolic alterations in PAPS associated chorea and can be of
as well as it could permit to classify as SVA a further 1 of 17 cases value as diagnostic hallmark.

123
S32 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

PO029 PO030
Comparision of available semiquantitative softwares Idiopathic normal pressure hydrocephalus
for DAT SPECT with or without Parkinsonism: 123I-ioflupane scan
(DaTscan)—preliminary data
L. Turchetta1, G.P. Annunziata1, D. Scala1, V. Ippolito1, I. Valenti1,
F. Favarulo1, I. Sepe1, M. Catalano1 I. Bossert2, N.G. Pozzi4, D. D’ambrosio1, C. Vellani2, M. Todisco3,
1
R. Zangaglia3, B. Minafra3, G. Trifirò2, C. Pacchetti3
UOC Medicina Nucleare, AORN A. CARDARELLI, Naples, Italy
1
Background-aim: 123I-Ioflupane imaging provides display of Medical Physics Unit, ICS Maugeri SpA SB IRCCS, Pavia, Italy.
2
dopamine neurons density in the substantia nigra that can be affected Nuclear Medicine Unit, ICS Maugeri SpA SB IRCCS, Pavia, Italy.
3
in patients (pts) with Parkinson disorders. Beyond qualitative visual Parkinson and Movement Disorder Unit, National Neurological
assessment, various semiquantitative methods based on manual or Institute Foundation ‘‘C. Mondino’’ IRCCS, Pavia, Italy. 4Parkinson
automated delineation of regions of interest (ROI) or volumes of and Movement Disorder Unit, National Neurological Institute
interest (VOI) are available. These methods allow to calculate Foundation ‘‘C. Mondino’’ IRCCS, Pavia, Italy; Department of
parameters as caudate to background ratio, putamen to background Neurology, University Clinic and JMU Wuerzburg, Germany
ratio and putamen to caudate ratio, representative of disease severity. Background-aim: Idiopathic normal pressure hydrocephalus (iNPH)
In our institute semiquantitative evaluation was performed using both is a complex syndrome encompassing ventriculomegaly, cognitive
DaTquant and Basal Ganglia softwares. The aim of the study is to decline, gait impairment and incontinence that occurs in elderly
evaluate whether the two software are equivalent in the quantification population. Clinically, it can closely mimic parkinsonism and cause
of nigrostriatal degeneration so that data obtained with different misdiagnosis and mistreatment. Our aim was to investigate the
algorithms can be compared in order to achieve a standardization of pathophysiology of iNPH by evaluating conventional imaging of
benchmark values. dopamine transport with 123I-ioflupane single-photon emission com-
Methods: 105 consecutive pts (mean age 68.68 ± 8.41; 64 male, puted tomography (DaTscan) in its different clinical presentations
mean age 68.41 ± 8.95; 41 female mean age 69.10 ± 7.58) with (i.e. iNPH with high gait control disorder but without parkinsonism
symptoms related to parkinson were investigated with 123I-FB-CIT (iNPH-wp) vs.iNPH with parkinsonism (P)—like forms).
Single photon emission tomography (SPECT) during one year period. Methods: We enrolled 56 consecutive and radiologically-confirmed
SPECT imaging was performed 4 h after intravenous injection of iNPH patients (35 men and 21 women, mean age 76.3 years, range
185 MBq 123I-ioflupane. A total of 128 views of 50 s each over 360 62–87 years).
degrees were acquired on a 128 9 128 matrix. Data reconstruction Every patient underwent a clinical examination by an expert neurol-
was performed using filtered backprojection with Butterworth filter ogist, applying UPDRS and iNPH scale. Differences in age and
5.0, power of 7 and no attenuation correction was applied. SPECT UPDRS scores were evaluated using a t-test.
images were analyzed visually according to a predefined five point All patients performed a DaTscan acquisition using a GE Infinia
ranking scale of dopaminergic nerve cell degeneration (from normal Hawkeye 4 gamma camera and a LEUHR fan beam collimator (90
to burst striatum). Qualitative analysis showed a regular 123I-Ioflu- projections, 30 s/projection).
pane distribution in 44 pts and a lower DaT uptake in the entire Qualitative analysis of DATscan reconstructed images was per-
striatum in 17 pts and limited to putamina in 44 pts. Semiquantitative formed by using a GE Xeleris Workstation.
evaluation with automated volume of interest (VOI) using DaTquant Results: Thirty-eight patients showed a iNPH-wp phenotype, while
and Basal Ganglia software was performed too. Several numeric 18 showed a PD-like phenotype. UPDRS baseline score was higher in
parameters such as caudate to background ratio (C/Br), putamen to P-like than in iNPH-wp (26.2 vs 12.8, p = 2 9 10E-05), while no
background ratio (P/Br) and putamen to caudate ratio (P/Cr) of both significant differences were noted in population’s age (77.1 years vs
sides were generated. All data were statistically analyzed using IBM 75.8 years, p = 0.2).
SPSS statistics 19 software for Windows. Only, five patients had a normal DaTscan (3 iNPH-wp and 2 P-like
Results: No significant differences between the two semiquantitative phenotypes).The remaining 51 patients had a reduced striatal uptake.
analysis methods expressed by a Pearson linear correlation signifi- Semi-quantitative analyses are still ongoing.
cance of 0.01 was found. This significance level was verified in all Conclusions: Our data suggest that subjects with iNPH can present
ratios, C/Br, P/Br and P/Cr obtained with the two softwares, showing altered dopamine reuptake transporter density, thus resembling the
that both systems are equivalent. molecular findings in PD. Comparative molecular imaging studies are
Conclusions: Computer-based analysis of Dopamine transporter ongoing and will support the differential diagnosis. At present, a
imaging (DaTscan) can aid in image interpretation. DaTquant or collaborative and inter-disciplinary approach is recommended for
Basal Ganglia softwares are equivalent in semiquantitative ratio cal- these patients care.
culation in pts with Parkinson’s disease and Parkinson’s plus
syndromes. In our population both semiquantitative methods are
sensitive enough to detect degeneration of the dopaminergic system
giving reliable numeric marker in interpretation of 123I-ioflupane
studies.

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S33

PO031 brain injury); (2) to investigate the relationship between the CC


Excitability of the supplementary motor area depends integrity and the brain metabolism.
Methods: A sample of 52 patients (29 VS, 23 MCS) with DOC,
on subcortical damage in Parkinson’s disease caused by TBI or HBI, was selected among a larger database col-
lected during CRC-Start Up Coma Research Centre.
G. Marotta4, S. Casarotto1, F. Turco2, A. Comanducci1, A. Perretti3, We assessed the diagnostic accuracy of the CC and SWM integrity,
G. Pezzoli5, M. Rosanova1, U.I. Isaias2 using diffusion tensor imaging (DTI) and structural magnetic reso-
nance imaging (sMRI), in a sample of DOC individuals, well-
1
Department of Biomedical and Clinical Sciences L. Sacco, balanced for diagnosis and etiology. CC DTI-derived measures were
University of Milan, Milan, Italy. 2Department of Neurology, correlated with the brain metabolism in a sub-cohort of 29 patients,
University Hospital, Wurzburg, Germany. 3Fondazione Europea di computed with FDG-PET. Mean SUV for both hemispheres were
Ricerca Biomedica, Milan, Italy. 4Fondazione IRCCS Ca’ Granda calculated using regions of interest masks produced with the AAL
Ospedale Maggiore Policlinico, Nuclear Medicine Department, atlas.
Milan, Italy. 5Parkinson Institute ASST G. Pini-CTO, Milan, Italy Results: Our results showed that the CC macrostructural DTI-derived
Background-aim: SMA is a crucial component of the basal ganglia- measures discriminate between diagnosis and correlate with the
thalamocortical circuit model. A reduction of supplementary motor clinical status of DOC patients irrespective of the etiology. Moreover,
area (SMA) activity follows the typical dopaminergic impairment the CC DTI-derived measures strongly correlate with the metabolism
within the basal ganglia that characterizes PD. of the right hemisphere, while no correlation emerged with the left
In this study we aimed at testing whether an acute levodopa admin- hemisphere metabolism. No significant diagnostic accuracy emerged
istration has measurable and specific cortical effects possibly related for the CC sMRI evaluation and the SWM measures.
to striatal dopaminergic deficit. Conclusions: Our results indicate that: (1) the degree of the inter-
Methods: In thirteen PD patients, we measured the electroen- hemispheric anatomical disconnection is a marker of the level of
cephalographic responses to transcranial magnetic stimulation (TMS/ consciousness independently from the type of brain injury; (2) CC
EEG) of the SMA and superior parietal lobule before and after an alterations might be the consequence of the reduced brain
acute intake of levodopa whether these neurophysiological effects metabolism.
parallel the asymmetry of akinetic-rigid symptoms and the corre- Remarkably, our results suggest that the functional interplay between
sponding dopaminergic striatal innervation loss. 123I-FP-CIT SPECT the two hemispheres is tightly linked to the level of consciousness.
were performed to identify the more affected and the less affected
brain side in each patient, according to the dopaminergic innervation
loss of the putamen. PO033
Cortical excitability changes before and after an acute intake of
levodopa were computed and compared between the more and the 123I-FP-CIT semi-quantification on a large cohort
less affected brain side at the single-patient as well as at the group of patients using a novel approach
level.
Results: We found that levodopa intake induces a significant increase S. Berti2, A. Spimpolo2, S. Gusella2, D. Poggiali2, R. Simeone2,
(P \ 0.01) of cortical excitability nearby the SMA in the more S. Sestini1, F. Bui2, D. Cecchin2
affected brain side, greater (P \ 0.025) than in the less affected brain
side. Notably, cortical excitability changes nearby the superior pari- 1
Department of Diagnostic Imaging, Nuclear Medicine Unit, N.O.P.,
etal lobule were not statistically significant. S. Stefano, U.S.L. Toscana Centro, Prato, Italy. 2Nuclear Medicine
Conclusions: These results strengthen the idea that dysfunction of Department, University-Hospital of Padua, Padua, Italy
specific cortico-subcortical circuits may contribute to pathophysiol-
ogy of PD symptoms. Most important, they support the use of Background-aim: [123I]FP-CIT SPECT imaging (DaTSCAN) is of
navigated TMS/EEG as a non-invasive tool to better understand the great value in differentiating degenerative forms of parkinsonism
pathophysiology of PD. (Parkinson’s disease, Progressive Supranuclear Palsy, Lewy Body
Dementia, Multiple System Atrophy) from non-degenerative parkin-
sonisms (drug-induced parkinsonism, vascular parkinsonism) or
Essential Tremor. Qualitative visual analysis of striatal uptake is the
PO032 most common approach in clinical practice. The need for semi-
Disorders of consciousness patients quantitative analysis has led to the development of many semi-
quantification methods and softwares (DatView, DaTQUANT, SPM,
and interhemispheric anatomical disconnection BasGan, etc.). The aim of this study is to validate a new automatic
method for the quantitative assessment of [123I]FP-CIT SPECT
G. Marotta1, S. Ferraro2, A. Nigri2, S. Nava2, C. Rosazza2, D. Sattin2, developed at the University-Hospital of Padua.
D. Sebastiano Rossi2, M.G. Bruzzone2, M. Leonardi2, A. Redolfi2, Methods: Data of 543 patients (293 M, 250 F, mean age 75 years)
L. D’incerti2, R. Benti1 who underwent DaTSCAN between 2006 and 2009 at the Nuclear
Medicine Department of The University-Hospital of Padua were
1
Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, qualitatively analyzed and categorized as pathological or non-patho-
Nuclear Medicine Department, Milan, Italy. 2Fondazione IRCCS logical. Reconstructed and realigned data have been automatically
Istituto Neurologico Carlo Besta, Milan, Italy analyzed by two different programs of semi-quantification: a ‘‘two
Background-aim: In disorder of consciousness (DOC) patients, box method’’ (2BM) by Tossici-Bolt and coworkers and a new
corpus callosum (CC) and subcortical white matter (SWM) integrity method (PD system) based on the automatic identification of image
were showed to discriminate between diagnostic categories. The aims centroids and thresholding of striatal regions.
of the study were: (1) to clarify the link between the integrity of CC Results: The qualitative analysis of PD db patients resulted in 118
and of SWM and the clinical status in DOC patients, disentangling the non-pathological scans (39 M, 79 F, mean age 73 years) and 396
role played by the different brain injuries (traumatic or hemorrhagic pathological scans (255 M, 141 F, mean age 76 years). The [123I]FP-
CIT average striatal uptake levels of non pathological subjects was

123
S34 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

2.69 and 12.59 with PD system and 2BM respectively. Among the PO035
pathological subjects, the [123I]FP-CIT average striatal uptake level Contribution of statistical maps of hypometabolism
obtained was 1.77 and 8.07 for PD system and 2BM respectively.
Both tested methods demonstrated a statistically significant and relative hypermetabolism in the differential
(p \ 0.05) difference between positively and negatively judged diagnosis of degenerative Parkinsonisms
subjects.
Conclusions: This study allowed us to test two different methods (a G. Puccini3, S. Ramat2, R. Di Dato3, A. Kokomani3, R. Calabretta3, F.
new one and a reference one) for semi-quantification of [123I]FP-CIT Tutino1, C. Polito2, G. Lombardi2, M.T. De Cristofaro1, A.P. Passeri3,
on a large cohort of subjects. The new method (PD system), as the S. Sorbi2, V. Berti3, R. Sciagrà3
2BM, was able to automatically differentiate between non-patholog-
1
ical and pathological subjects with a very good level of accuracy. The Nuclear Medicine Unit, AOU Careggi, Florence, Italy. 2Neurology 1
proposed method could be useful to assist the visual analysis of Unit, AOU Careggi, Florence, Italy. 3Nuclear Medicine Unit, AOU
DaTSCAN in clinical practice especially in case of interpretation by Careggi, Florence, Italy
less experienced physicians.
Background-aim: The role of FDG-PET in the differential diagnosis
between degenerative Parkinsonisms is clinically consolidated. Most
recent guidelines attribute to the FDG-PET voxel-based analysis a
PO034 crucial value, recommending adding it to the qualitative visualization
18F-FDG and 18F-flutemetamol PET in differential of the images. The aim of our study was to evaluate the contribution
of statistical maps of both hypometabolism and relative hyperme-
diagnosis of dementia tabolism in increasing the diagnostic accuracy and confidence in the
evaluation of patients with degenerative Parkinsonisms, in both expert
F. Calabria3, R. Tavolaro3, A. Bruni1, A. Petrone2, A. Bagnato3 and non-expert readers.
Methods: We analyzed a group of 83 patients with a clinically
1
Centro Regionale di Neurogenetica, ASP CZ, Lamezia Terme, Italy. confirmed diagnosis of degenerative Parkinsonism (56 PD, 10 PSP, 9
2
Department of Neurology, ‘‘Annunziata’’ Hospital, Cosenza, Italy. MSA, 8 CBS) who had undergone FDG-PET for disease assessment.
3
Department of Nuclear Medicine and Theranostics, Mariano Santo All PET scans were acquired, according to the EANM guidelines,
Hospital, Cosenza, Italy using a scanner PET/CT Gemini TF. In order to obtain hypometa-
Background-aim: 18F-flutemetamol PET has emerged as powerful bolism and relative hypermetabolism maps a voxel-based analysis has
tool in diagnosis of amyloid related dementia. On the other hand, 18F- been set using SPM12. After spatial normalization, a two-sample
FDG PET still can play a role in depicting other neurodegenerative t-test was used to compare each patient with an internal database of 30
kinds of dementia. Our aim was to investigate the association of both control subjects with no neurodegenerative disease. Age and gender
tracers in a population with unclear clinical diagnosis between atyp- were used as nuisance variables. Hypo- and hypermetabolism maps
ical Alzheimer Diseases and Frontotemporal dementia. were obtained setting the threshold at p \ 0.001 non-corrected, and
Methods: During 2017 we examined 29 patients for differential have been used as an aid to the qualitative visualization of the FDG-
diagnosis between atypical Alzheimer Disease and Frontotemporal PET images for the assignment of each patient to a specific degen-
dementia. All patients were examined by means of both 18F- erative parkinsonism by 4 readers (2 experts and 2 non-experts).
flutemetamol and 18F-FDG brain PET scans. Readers first had to evaluate only qualitative images, indicating the
Results: Among examined patients, a positive 18F-flutemetamol PET most likely diagnosis and their level of confidence. Then they add the
and positive 18F-flutemetamol PET were documented in 21/29 visualization of hypometabolism maps, confirming or changing the
patients. 3/29 patients presented positive 18F-flutemetamol PET and assignment, and indicating the confidence. Finally the maps of
negative 18F-FDG PET. Therefore, in 24/29 (82%) patients a sup- hypermetabolism were visualized. Statistical analyses were per-
posed diagnosis of amyloid related dementia was done. In 3/29 (11%) formed using software SPSS, setting significance at p \ 0.01.
patients positive 18F-FDG PET but negative 18F-flutemetamol PET Results: Regarding the non-expert readers evaluation, we found a
allowed to diagnose Frontotemporal dementia. Finally, 2/29 (7%) statistically significant increase in global diagnostic confidence from
patients presented both negative 18F-flutemetamol PET and 18F-FDG 77.7% (qualitative visualization) to 83.7% (hypometabolism maps) to
PET; a clinical diagnosis of depression was done. 88.3% (hypermetabolism maps). Non-expert readers had a statisti-
Conclusions: As expected, 18F-flutemetamol PET helped to diagnose cally significant increase in diagnostic confidence in all groups
amyloid related dementia in all cases with positive 18F-flutemetamol (highest level of confidence in MSA group). Non-expert readers
PET. On the other hand, the pattern of deficit distribution in patients increased in correctly classified patients from 61.4%, to 74.7%, and to
with positive 18F-FDG PET and negative 18F-flutemetamol PET 81.9%, respectively.
allowed to correctly identify patients with Frontotemporal dementia. For the expert readers evaluation, we obtained a statistically signifi-
Both negative 18F-flutemetamol and 18F-FDG PET scans help to cant increase in global diagnostic confidence from 80.6%, to 87.1%
consider clinical suspicion of other diseases. and to 90.8%, respectively, and an increase in correctly classified
In differential diagnosis between unclear atypical Alzheimer disease patients from 85.5%, to 91.6%, and to 91.6%, respectively.
and Frontotemporal dementia, the association of both 18F- Conclusions: The use of hypometabolism and hypermetabolism
flutemetamol PET and 18F-FDG PET could help clinical differential maps, in conjunction with qualitative image assessment, increased the
diagnosis. confidence in the classification of patients for both expert and non-
expert readers.
In non-expert readers, both hypometabolism and hypermetabolism
maps help increasing accuracy and getting closer to the results of the
expert readers.
For expert readers hypometabolism maps but not hypermetabolism
maps increase the accuracy. The most difficult classification for both
expert and non-expert readers was CBS, in which the diagnostic
accuracy has not been increased by the analysis of the maps, due to

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S35

the characteristic pattern heterogeneity. Furthermore, in our group of PO037


patients, the typical asymmetric distribution of metabolic alterations Correlation between CSF and PET amyloid burden
often was not evident.
in patients with suspected AD: Florence experience

G. Puccini1, C. Polito2, G. Lombardi2, M. Nerattini3, B. Nacmias2,


PO036 M.T. De Cristofaro3, A. Passeri3, S. Sorbi2, R. Sciagrà3, V. Berti3
Impact of 18F-labelled beta-amyloid PET tracers
1
on differential diagnosis of uncertain cases in a clinical Nuclear Medicine Unit, AOU Careggi, Florence, Italy. 2Neurology 1
Unit, AOU Careggi, Florence, Italy. 3Nuclear Medicine Unit, AOU
routine setting Careggi, Florence, Italy

C. Cittanti2, D. Gragnaniello1, I. Rambaldi2, P. Milani1, I. Santi2, Background-aim: Given the increasing role of biomarkers in the
S. Panareo2, L. Uccelli2, M. Caracciolo2, S. Seno2, L. Urso2, diagnosis and management of Alzheimer’s Disease (AD), a greater
M. Bartolomei2 understanding of the different information obtained by 18F--amy-
loid tracers PET (AmyPET) and cerebrospinal fluid (CSF) biomarkers
1
Neurology Unit, Department of Neuroscience and Rehabilitation, determination is necessary.
S.Anna University Hospital, Ferrara, Italy. 2Nuclear Medicine Unit, Methods: We selected a series of 34 patients (mean age: 67 ± 9; F:M
Department of Oncology, S.Anna University Hospital, Ferrara, Italy 20:14) who underwent both AmyPET (25% Florbetapir; 37% Flor-
betaben; 38% Flutemetamol) and CSF biochemical determination of

Background-aim: In the last years PET using various 18F-labelled -amyloid 1–42 (CSF-A), total tau, and tau phosphorylated between
tracers for brain beta-amyloidosis (FLA-PET) has been developed and 2015–2018. Demographic, genetic and clinical data were collected.
become available for clinical practice. But despite its widespread use CSF levels were considered quantitatively and as ? or - (?:CSF-
in scientific investigations, studies in clinical routine settings are still A \ 600 pg/ml). PET scans were acquired, according to the EANM
limited. So, the aim of our study was to investigate the impact of guidelines, using a PET/CT Gemini TF. AmyPET were visually and
FLA-PET in patients with clinical suspicion of dementia but not semi-quantitatively analyzed. For the semi-quantitative analysis, PET
univocal interpretation after 18F-Fluordesoxyglucose PET (FDG- scans were co-registered with the corresponding low-dose CT, then
PET). corrected for atrophy and spatially normalized into Montreal Neuro-
Methods: All study subjects were referred from the departments of logical Institute space. Using MarsBaR software we extracted the
Neurology, Geriatrics and Internal Medicine with clinical suspicion of mean uptake values of 9 regions of interest (ROIs): Dorso-lateral
dementia due to neurodegenerative disease. After undergoing an prefrontal cortex (DLPFC), Medial-prefrontal cortex, Orbito-frontal
FDG-PET, all patients were discussed in our multidisciplinary board cortex, Occipital cortex, Precuneus, Temporo-lateral cortex, Tem-
of neurodegenerative disorders where an additional FLA-PET was poro-medial cortex, Posterior cingulate cortex (PCC) and Striatum,
recommended due to uncertainty on the final diagnosis. Before FLA- bilaterally. The standard uptake values ratio (SUVr) was calculated
PET execution the most probable diagnosis as well as potential dif- for each ROI using pons as reference region. Statistical analyses were
ferential diagnosis were recorded. FLA-PET images were visually performed using SPSS (significance at p \ 0.05).
interpreted and classified on a ‘‘binary’’ scale as amyloid-positive or - Results: We found statistically significant differences in all regional
negative. Finally, clinical diagnoses were compared before and after SUVr between AmyPET ? and AmyPET - patients (Precuneus
FLA-PET. showed the greatest and most significant difference). The best cut-off
Results: A total of 86 patients (age 67.2 ± 8.3) examined from for AmyPET ?/AmyPET - separation has been identified as 0.7.
September 2015 to October 2018 were included in the study. Visual Only DLPFC, precuneus and lateral temporal SUVr values showed
analysis of FLA-PET images allowed to identify 37 subjects (43%) significant differences between CSF-A? and CSF-A- patients.
with a positive study for brain amyloid deposition and 49 patients Statistically significant correlation between CSF-A and all regional
(57%) with a negative investigation. After FLA-PET a final clinical SUVr values was observed (Precuneus and DLPFC showed the best
diagnosis could be achieved in about 84% of all former uncertain correlation, Striatum showed the worst). 27/34 patients resulted
cases. Moreover FLA-PET changed the most likely prior diagnosis in AmyPET ? and 13/34 resulted CSF-A ? . Negative concordant
27% of all cases. In particular the highest impact on the change of the cases (AmyPET-; CSF-A-) were 7, whereas positive concordant
most likely diagnosis was observed in distinguishing Alzheimer’s cases (AmyPET ? ;CSF-A ?) were 15. All 12 discordant cases
dementia (AD) from Fronto-temporal dementia (FTLD), where FLA- were AmyPET ? and CSF-A-. The comparison between concor-
PET resulted in a change of the most probable prior diagnosis in 36% dant -, concordant ? and discordant groups showed statistically
of cases. significant differences among all groups regarding CSF-A. ROIs
Conclusions: In our preliminary experience FLA-PET shows a high SUVr showed statistically significant difference in concordant ? vs
incremental value in establishing the final clinical diagnosis in concordant - and concordant - vs discordant; in concordant ? vs
patients with suspected dementia when FDG-PET is inconclusive. discordant, precuneus showed lower SUVr values in discordant as
The differentiation between AD and FTLD resulted in the most fre- compared to concordant ?, although not significant.
quent change in diagnosis and this aspect should be taken into account Conclusions: Several regions can be used to semi-quantify AmyPET,
when establishing the diagnostic flow-chart of patients with suspected although the Precuneus appears to be the most useful region for
cognitive impairment. However larger clinical trials are needed to both ± identification and CSF correlation. PCC, instead, has not
assess the role of this approach on patient management, pending the proved to be very useful: perhaps it is difficult to automatically cal-
availability of specific therapies for neurodegenerative diseases culate SUVr in this region due to its small size, position and limited
treatment. spatial resolution. In our population, all 12 discordant cases (PET ?/
CSF-) were confirmed as true AmyPET ? to clinical diagnosis,
suggesting a better performance of AmyPET than CSF determination
in patients with suspected AD. Our results support the fact that the
two markers reflect two different parameters in the continuum of the
pathological process of accumulation of cerebral amyloid plaques.

123
S36 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

PO038 PO039
Effects of bariatric surgery on brain glucose The comparison of 18F-FET and 18F-choline
metabolism and cognitive function: insight in patients with newly diagnosed low-grade gliomas:
from dynamic FDG PET/CT study a pilot study

G. Aghakhanyan2, G. Daniele1, A. Dardano1, L. Fantechi2, M. Hodolič1, A. Mišir Krpan2, A. Golubić3, M. Žuvić3, M. Baučić2,
M. Gennaro2, S. Caputo2, F. Betti2, L. Antonacci2, L. Giusti1, G. Mrak4, J. Nemir4, D. Huić3
A. Ciccarone1, F. Santini1, G. Ceccarini1, F. Guidoccio2,
S. Mazzarri2, S. Del Prato1, D. Volterrani2 1
Nuclear Medicine Department, Faculty of Medicine and Dentistry,
Palacký University, Olomouc, Czech Republic. 2Department of
1
Department of Clinical and Experimental Medicine, University of Oncology, University Hospital Centre, Zagreb, Croatia. 3Department
Pisa, Pisa, Italy. 2Regional Center of Nuclear Medicine, University of Nuclear Medicine and Radiation Protection, University Hospital
Hospital of Pisa and Department of Translational Research on New Centre, Zagreb, Croatia. 4Department of Neurosurgery, University
Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy Hospital Centre, Zagreb, Croatia
Background-aim: We aimed to evaluate the impact of bariatric Background-aim: Low grade gliomas (LGG) account for app. 15%
surgery (RYGB) on the brain glucose metabolism and the interplay of all gliomas, with incidence rate of 1/100,000 persons per year.
between gut hormones/metabolomics, cerebral metabolic rate of Although traditionally considered benign, most LGG gradually
glucose (CMRGlu) and cognitive function. evolve into high grade tumours. Within 5 years it will happen in app.
Methods: Thirteen morbidly obese subjects with normal glucose half of the patients.
tolerance (BMI 46 ± 4.9 kg/m2; HbA1c 40.1 ± 5.9 mmol/mol; age The diagnosis of LGG is challenging. Functional Magnetic Reso-
42.4 ± 9.8 years) planned for RYGB surgery were recruited. The oral nance Imaging (fMRI) results are often inconclusive, ambiguous or
glucose tolerance test (OGTT) was performed, followed by 60 min indeterminate. The definitive diagnosis can only be achieved by brain
FDG dynamic PET study. Continuous blood samples were drawn biopsy, which is invasive, sometimes inaccessible, associated with
before and at 30, 60, 90, and 120 min for glucose, insulin, GLP, VIP, sampling errors because of tumours heterogeneity.
GIP and C-peptide measurements. The same venous blood samples Hence, functional imaging modalities are needed in addition to
were used for calculating radioactivity concentration in plasma. structural information and pathohistological findings.
Fasting blood samples for metabolomics (leptin, brain derived neu- Because of low uptake of radiotracer in normal brain parenchyma,
rotrophic factor, BDNF) were also collected and the homeostasis fluoromethyl-(18F)-dimethyl-2-hydroxyethyl-ammonium chloride
model assessment of insulin resistance (HOMA-IR) was calculated as (18F-FCH) has proven to be a good alternative in diagnostic centres
an index of insulin resistance. The influx constant (Ki) and MRGlu where O-(2-[18F]-fluoroethyl)-L-tyrosine (18F-FET) is not available.
were then quantified using the two tissue compartment Patlak 18F-FET has the advantage of displaying a higher tumour-to-back-
approach with an imaged-derived input function (PMOD). Subse- ground ratio and of not accumulating in inflammatory lesions. On the
quently, the parametric CMRGlu images were created and spatially other hand, 18F-FCH is more widely available.
normalized in MNI space. The paired t-test and Spearman rank cor- No study has been published on the use of 18F-FCH and 18F-FET
relation were applied to assess changes and associations of voxel-wise Positron Emission Tomography (PET/CT) in the primary diagnosis of
CMRGlu and metabolomics. All patients underwent a battery of LGG. Therefore, the objective of this pilot study was to improve
neuropsychiatric tests (MMSE, MoCA, Token test, TMT, etc.) to diagnostic accuracy of primary diagnosis of LGG with choosing the
assess cognitive function in several domains, before and 6 months appropriate PET radiopharmaceutical.
after RYGB. Methods: This pilot study comprised 7 patients (age 37-80 years)
Results: Six months after RYGB a significant BMI reduction with suspected LGG, diagnosed with 3T MRI and/or stereotactic
(p \ 0.001) was achieved. Post-OGTT GLP1 was increased brain biopsy. After MRI and/or stereotactic brain biopsy all patients
(p \ 0.01) as well as GIP (p \ 0.01). The HOMA-IR dropped sig- underwent 18F-FCH PET/CT and 18F-FET PET/CT. Interval
nificantly 6 m after RYGB (p = 0.02). Either whole brain and region- between 18F-FCH PET/CT and 18F-FET PET/CT scan was maxi-
selective CMRGlu decreased 6 m after surgery (15.9 ± 4.6 to mum one week. Scans were performed 20 min after intravenous
10.5 ± 5.1 lmol/min/100 ml; p \ 0.01). Voxel-wise paired analysis injection of 185 MBq 18F-FCH or 18F-FET.
displayed clusters of decreased CMRGlu 6 m after RYGB (p = 0.005, One up to two weeks after PET/CT scanning patients underwent
kE [ 50, uncorrected) in the wide-spread brain regions. In addition, surgery.
we found a significant positive relationship between CMRGlu and Pathohistological results were compared with 18F-FCH PET/CT
HOMA-IR. and 18F-FET PET/CT findings.
All patients at baseline presented MMSE and MoCA scores in the Results: Six out of seven patients with suspected LGG had full
normal range. However, 6 months after RYGB, the cognitive domains imaging diagnostics with final pathohistological finding after surgery:
examined showed a trend of global improvement. MMSE score Two patients were diagnosed with diffuse astrocytoma (grade II).
increased statistically significantly (p \ 0.002) as well as MoCA Both patients had negative 18F-FCH and positive 18F-FET scan
score (p \ 0.005). (SUVmax. 2.0 and SUVmax. 2.8).
Conclusions: After bariatric surgery, there are several modifications Two patients were diagnosed with glioblastoma multiforme. Both
of multiple factors that play a role in the so-called ‘‘intestinal-brain patients had positive 18F-FCH (SUVmax. 3.9) and 18F-FET (SUV-
cross-talk’’, in CMRGlu and in cognitive function. CMRGlu of max 3.1) PET/CT.
morbidly obese subjects is abnormally enhanced in response to One patient had negative results for both PET/CT scans and was
insulin. Bariatric surgery seems to reverse this insulin-mediated signal diagnosed with focal cortical dysplasia.
dysfunction and could produce significant CNS effects decreasing Patient who entered this study the last had negative 18F-FCH scan
brain glucose over-consumption and promoting potential neuropro- and positive 18F-FET scan (SUVmax. 2) but has no final pathohis-
tective effects. tological finding yet.
Conclusions: Preliminary results based on a small number of patients
showed that appropriate radiopharmaceutical should be chosen before

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S37

performing PET/CT in patients with newly diagnosed LGG. 18F-FCH Although F18-FDG PET/CT is not recommended for the primary
seems not to be appropriate tracer in patients with newly diagnosed detection of breast cancer, it may play a role in the detection of local
LGG. Both tracers, 18F-FCH and 18F-FET, seems to be appropriate recurrence or distant metastases in the setting of locally advanced
in primary diagnosis of high-grade gliomas. The study is ongoing. breast cancer when other imaging modalities are equivocal or con-
founding. There are several entities within the breast that will show
increased FDG-activity on PET/CT with F18-FDG. These include
acute and chronic inflammation, physiologic lactation, and benign
PO040 focal breast masses including fat necrosis.
Clinical utility of amyloid PET imaging Methods: We studied a 47-year-old woman with an history of nipple
in the diagnostic pathway of Alzheimer’s disease sparing right mastectomy.
Subsequently, she showed pathological lymphadenomegaly in the left
axilla diagnosed to control BREAST-RMI. Then, left axillary lym-
A. Baldoncini3, G. Montelatici3, V. Rossi3, M. Agnolucci3, P. Zolo1,
phadenectomy was performed.
A. Tiezzi2, F. Redi2
At histological examination only 1/11 lymph nodes was found for
1 massive metastasis site and to complete the restaging, a whole body
Malattie Neurodegenerative, Istituto di Riabilitazione SMP, Agazzi,
FDG PET-TC was performed.
Arezzo, Italy. 2UOC Neurologia e Neurofisiopatologia, Ospedale San
Results: FDG PET/CT images documented up-take (SUV max 3.15)
Donato, Arezzo, Italy. 3UOSD Medicina Nucleare, Ospedale San
in the right breast region at the surgical scar; suspect finding for
Donato, Arezzo, Italy
neoplastic lesions and therefore deserving of diagnostic investigation.
Background-aim: Alzheimer’s Disease (AD) is the most common Therefore a breast ultrasound was performed on the right retroareolar
cause of dementia in the elderly. Definitive diagnosis of AD can only area (1.2 cm) revealing hypoechoic mass, referable to cicatricial
be achieved by postmortem brain examination. Recently in vivo - outcome (fat necrosis).
amyloid plaques biomarkers, such as the increase of tracer retention Conclusions: Fat necrosis has increased FDG uptake secondary to the
on amyloid PET scan or the reduction of A42 in CSF, have been presence of metabolically active inflammatory cells in early stages of
introduced as add-on to clinical testing into the AD diagnostic the process. Fat necrosis of the breast is often hypermetabolic on PET/
workflow. CT and may show intense FDG activity in the setting of transverse
The aim of the present study is to evaluate the impact of amyloid PET rectus abdominis myocutaneous (TRAM) flap reconstruction if the
scan in the assessment of patients referred to Arezzo Hospital’s fat-rich tissue is damaged intraoperatively. The presentation of a
CDCD (Centro Disturbi Cognitivi e Demenze) for clinical suspicion patient with a history of breast cancer status after mastectomy, pal-
of AD. pable mass, and increased activity on PET/CT may be concerning,
Methods: A total of 54 subjects with a)progressive Mild Cognitive although this entity is more likely to be fat necrosis than recurrent
Impairment (37%), b)possible AD with atypical symptoms (43%), tumor. Mammography is more specific, although ultrasound is still a
c)early (\ 65 years) diagnosis of dementia with atypical onset (20%) very important tool in making the diagnosis-increased echogenicity of
were scheduled for amyloid PET-CT scan from september 2017 to subcutaneous tissue. In patients operated by nipple sparing mastec-
march 2018. Patients were injected with 370 MBq of 18F-Florbetaben tomy the possibility of up-takes compatible with fat necrosis should
or 185 MBq of 18F-Flutemetamol and subsequently scanned after an be considered in PET evaluation.
uptake time of 90 min. Images were interpreted by a certified nuclear
physician and reported as positive or negative for amyloid deposits in
the gray matter, according to qualitative visual criteria.
Results: 33 patients were found to have a positive PET scan (60%), PO042
while 21 (40%) were negative. Low-dose molecular breast imaging: correlation
Patient with negative PET scan where clinically reassessed and with mammographic, sonographic and histopatho-
classified as normal i.e. without AD or other dementia types (28%),
non progressive MCI (36%) or dementia other than AD (36%).
logical features of suspicious breast lesions
Conclusions: Amyloid PET scan is a useful tool for the assessment of
patients with clinical suspicion of AD; in particular the high negative S. Chiacchio3, G. Angelini2, D. Mazzotta2, M. Moretti2, C. Scatena5,
predictive value of the test allows for an early discrimination of A. Al Sharif1, R. Morganti6, S. Caputo3, G. Manca3, E. Rossetti4,
healthy controls and other forms of dementia. A.G. Naccarato5, M. Roncella4, C. Marini2, D. Volterrani3
All the above offers the possibility of a more accurate and specific 1
intervention, rehabilitation and assistance Department of Radiology and Nuclear Medicine, University of
Jordan, Amman, Jordan. 2Departmental Section of Radiological
Senology, AOU Pisana, Pisa, Italy. 3Nuclear Medicine Department,
AOU Pisana, Pisa, Italy. 4Operative Unit of Senology, AOU Pisana,
PO041 Pisa, Italy. 5Section of Pathology, Department of Surgery, AOU
PET-CT in nipple sparing mastectomy: a case report Pisana, Pisa, Italy. 6Section of Statistics, University of Pisa, Pisa, Italy
Background-aim: Current imaging guidelines recommend multi-
G. Biscontini2, D. Morichetti1, G. Garraffa2, F.M. Fringuelli2, modality imaging, Molecular Breast Imaging (MBI) with 99mTc-
A. Palucci2, L. Burroni2 Sestamibi is an adjunct technique often employed when magnetic
resonance imaging (MRI) is not available. The purpose of this study is
1
Cytology Unit, Ospedali Riuniti ‘‘Torrette’’, Ancona, Italy. 2Nuclear to retrospectively compare the performance of low-dose MBI with
Medicine Unit, Ospedali Riuniti ‘‘Torrette’’, Ancona, Italy digital mammography (DM) and DM ? ultrasound (US), and to
assess their diagnostic value.
Background-aim: The shift from modified radical mastectomy to
Methods: We retrospectively reviewed fifty patients for the period
skin-sparing and nipple-sparing mastectomy offers new options for
May 2015-May 2017. High risk patients (BRCA-mutated and/or with
immediate breast reconstruction. Tissue expansion is no longer cru-
breast cancer familiarity); patients with suspicious breast lesions on
cial, especially with the advent of prepectoral reconstruction.

123
S38 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

US and/or on DM, who also underwent MBI, were included in the Correlation, and Coarseness_NGLDM were selected, while Model 4
study. Imaging findings were correlated with the histopathological included also for estrogen receptors, type of NAC, Ki67, and
results. Low-dose MBI was interpreted in conjunction with DM ? GLNU_GLZLM. The AUCs were 0.71, 0.72, 0.70, and 0.73 for Models
US and qualitatively evaluated as positive (focally moderate or with 1, 2 3 and 4, respectively.
marked increased uptake), or negative (completely negative or with Conclusions: This study confirmed the major role of tumour
mild uptake). molecular subtype and age in the prediction of pCR to NAC and
Results: Low-dose MBI demonstrated the highest sensitivity (86.4% suggested that radiomics features could have a role in prediction of
vs 83.1% by DM ? US and 67.8% by DM); a particularly low dose of pCR to NAC in locally advanced breast cancer patients. A larger
MBI was able to identify 6 new cases [ductal carcinoma in situ population is required to furtherly investigate and assess the predic-
(DCIS) and occult lesions in patients with dense breasts]. MBI sen- tive role of the advanced imaging features in this clinical setting.
sitivity is superior or equal to DM and DM ? US in all breast cancer
categories classified according to invasiveness, molecular subtype,
breast density and lesion size. Low-dose MBI suffered from lowest
specificity (45.4% vs 54.6% by DM ? US and 72.7% by DM). PO044
Conclusions: Low-dose MBI has a clinical value as adjunct imaging The value of preoperative molecular breast imaging
technique that improves cancer detection in patients with non-con- for the size assessment of invasive carcinoma and ductal
clusive DM and US. Further studies will be necessary to improve test
carcinoma in situ
specificity in this group of patients.
S. Galassi1, M.L. Stazza1, M. Rondini1, A. Lazzarato1, S. Nuvoli1,
G. Madeddu1, A. Spanu1
PO043
1
Advanced imaging features derived from 18F-FDG Unit of Nuclear Medicine, Department of Clinical, Surgical and
Experimental Sciences, University of Sassari, Sassari, Italy
PET/CT for pathological complete response prediction
in breast cancer patients undergoing neoadjuvant Background-aim: Molecular Breast Imaging (MBI) with the tech-
netium-labelled cationic lipophilic radiotracers has proved to be able
chemotherapy to play an important complementary role to conventional imaging
procedures in the diagnosis of primary breast cancer as well as in the
L. Antunovic5, R. De Sanctis4, F. Gelardi2, L. Cozzi2, M. Kirienko2, preoperative local staging of disease. MBI also demonstrated a high
A. Sagona3, C. Tinterri3, R. Torrisi4, A. Santoro4, R. Zelic1, accuracy in the identification of residual disease following neoadju-
M. Sollini2, A. Chiti2 vant therapy. The aim of the present study was to assess the value of
1
preoperative MBI for the size assessment of invasive carcinoma and
Clinical Epidemiology Unit, Department of Medicine Solna, ductal carcinoma in situ (DCIS) in patients with newly diagnosed
Karolinska Institutet, Stockholm, Sweden. 2Department of primary breast cancer.
Biomedical Sciences, Humanitas University, Milan-Rozzano, Italy. Methods: A consecutive series of 190 patients (age: 31–78 years)
3
Department of Breast Surgery, Humanitas Clinical and Research with newly diagnosed primary breast cancer scheduled to surgery was
Center-IRCCS, Rozzano, Milan, Italy. 4Department of Medical retrospectively reviewed. Prior to surgery, all patients underwent
Oncology and Hematology, Humanitas Clinical and Research Center- MBI, in both craniocaudal and mediolateral oblique projection (600 s/
IRCCS, Rozzano, Milan, Italy. 5Department of Nuclear Medicine, view), using a high-resolution semiconductor-based device for
Humanitas Clinical and Research Center-IRCCS, Rozzano, Milan, imaging acquisition. MBI data were correlated with surgical
Italy histopathological findings. Pearson’s correlation coefficient was cal-
Background-aim: The aim of the study was to evaluate the role of culated to assess differences in tumor size between MBI and
radiomics features obtained from baseline 18F-FDG PET/CT in histopathological examination. Concordance was defined as a differ-
combination with clinical data in the prediction of pathological ence B 0.5 cm between MBI and pathology.
complete response (pCR) after neoadjuvant chemotherapy (NAC) in Results: At surgery, 108 out of 190 patients had an invasive primary
locally advanced breast cancer patients. tumor (invasive ductal: 95 cases, invasive lobular: 7 cases, mucinous:
Methods: Seventy-nine patients (mean age 50.7 years, SD 11.93) 3 cases, other types: 3 cases) with a median tumor size of
with breast cancer who were treated with NAC and underwent staging 1.80 ± 1.83 cm at histopathological analysis and 1.90 ± 1.94 cm at
18F
-FDG PET/CT (January 2010–January 2018) were retrospectively MBI (r = 0.986, p \ 0.00001) which over-estimated lesion size in
selected. An experienced nuclear medicine board certified specialist 8/108 cases. Thirty-five/190 patients had a DCIS with median tumor
defined the volume of interest (VOI) on primary tumour lesion. The size of 1.60 ± 1.23 cm at histopathological analysis and
extraction of radiomics features (first-, second- and higher-order) was 2.15 ± 1.50 cm at MBI (r = 0.629, p \ 0.00005). In this group of
performed using a dedicated software (LifeX). Clinical data, tumour patients, lesion size was overestimated at MBI in 11 cases and
histological characteristics and radiomics features were analysed underestimated in one. The remaining 47/190 patients had an invasive
using multiple logistic regression models. Two different approaches tumor (invasive ductal: 41 cases, invasive lobular: 6 cases) and an
for model building were used: as main analysis, a complete-case associated DCIS component. In 38 of these 47 cases, the DCIS
approach was performed; in the sensitivity analysis, the missing data component was marginal; median tumor size was 1.5 ± 1.18 cm at
were imputed using the multiple imputation chained equation and two histology and 1.85 ± 1.16 cm at MBI (r = 0.921, p \ 0.00001)
thresholds (Model 3 and 4, respectively) were used for predictor which overestimated lesion size in 10 cases and underestimated in one
selection. pCR was the primary endpoint. case. In the remaining 9/47 patients, the DCIS associated to the
Results: pCR was achieved in 19 patients. Two models were built invasive tumor was extensive and MBI gave an accurate size defi-
within the complete-case approach, a simple model including age and nition of both components in 7/9 cases, overestimating in one case
molecular subtype (Model 1) and a more complex model which and underestimating in the remaining case.
entailed also radiomics features (correlationGLCM, coarsenessNGLDM, Conclusions: MBI proved a reliable diagnostic tool in the preoper-
and GLNUGLZLM, Model 2). For the Model 3 age, molecular subtype, ative assessment of tumor size in patients with newly diagnosed

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S39

primary breast cancer. MIBI lesion size strongly correlated with 0.0058). In the bioptic subgroup (n = 10) SUVmax (p = 0.0094),
histological findings mainly in pure invasive carcinomas. Lesion size SUVmean40 (p = 0.0107), SUVmean50 (p = 0.0094), SUVmean60
overestimation was more frequent in DCIS. However, the size of (p = 0.0154) correlated with tumour vascularization.
extensive DCIS component associated to invasive carcinomas was Conclusions: 18F-FAZA PET/CT is a reliable method to assess
correctly predicted in a high percentage of cases. These data seem to tumour hypoxia in HGG as supported by the correlation between
suggest a wider application of MBI in the surgical planning of breast imaging parameters, CA-IX and vascularization. The methodological
cancer patients. However, they need to be confirmed in larger need of subdividing the population into surgical and bioptical speci-
prospective studies. mens might have hampered the statistical power of the study,
although it has been necessary to guarantee homogeneity within each
population.
PO045
18F-FAZA PET/CT in high-grade glioma to assess
PO046
tumour hypoxia before treatment and correlation
with hypoxia immunohistochemical markers Non invasive determination of IDH mutation status
in high-grade gliomas: utility of ADC maps and (18F)-
P. Mapelli4, F. Fallanca1, M. Callea2, V. Bettinardi1, P. Rancoita3, DOPA PET/TC
E. Incerti1, A. Compierchio1, M. Vuozzo1, C. Monterisi1, M. Terreni2,
C. Doglioni2, L. Gianolli1, M. Picchio4 L. Picori1, P. Feraco2, D. Donner1, S. Agostini1, F. Chierichetti1
1 1
Nuclear Medicine Department, IRCCS San Raffaele Scientific Department of Nuclear Medicine, Santa Chiara Hospital, Trento,
Institute, Milan, Italy. 2Pathology Unit, IRCCS San Raffaele Italy. 2Department of Radiology, Santa Chiara Hospital, Trento, Italy
Scientific Institute, Milan, Italy. 3University Centre of Statistics in the
Background-aim: The brain tumors new classification (2016 WHO)
Biomedical Sciences, Vita-Salute San Raffaele University, Milan,
distinguishes diffuse gliomas based on the molecular characteristics
Italy. 4Vita-Salute San Raffaele University, Milan, Italy; Nuclear
of isocitrate dehydrogenase (IDH) in IDH-mutated, IDH-wild type
Medicine Department, IRCCS San Raffaele Scientific Institute Milan,
(WT) and not otherwise specified. The evaluation of IDH mutation
Italy
status has diagnostic, prognostic and therapeutic implications. The
Background-aim: To investigate the correlation between 18F-FAZA aim of this study is to evaluate whether the analysis of ADC maps and
PET data and hypoxia immunohistochemical (IHC) markers in (18F)-fluorodihydroxyphenylalanine (18F-DOPA) can non-invasively
patients with high-grade glioma (HGG). predict the IDH mutation status.
Methods: Prospective single Centre clinical study including 17 pts Methods: Conventional MRI and ADC maps of 16 patients (11-M,
with brain MRI suggestive for HGG, who underwent pre-treatment 5-F) with histological diagnosis of high-grade diffuse glioma (G-III,
18F-FAZA PET/CT. The following 18F-FAZA PET-derived param- G-IV) and evaluation of IDH mutation status (9-MUT, 7-WT), were
eters have been derived: maximum standardized uptake value retrospectively evaluated. All MRI were performed on a 1.5T MR
(SUVmax), mean standardized uptake value (SUVmean) and meta- scan (ge-optima 450). In order to place the ROIs on the solid com-
bolic tumour volume (MTV) at different thresholds of 40%, 50%, ponents of the lesion, the ADC maps were elaborated and co-
60%, hypoxic volume (HV) estimated by applying different positivity registered with the T2w and c.e.T1w images. Then 4-5 ROIs were
thresholds to tumour to blood ratio (1.2, 1.3, 1.4), thus obtaining placed for each tumor and the ADC-mean values were calculated,
HV1.2, HV1.3, HV1.4. 10/17 pts underwent stereotactic biopsy and choosing the lowest values for each patient.
7/10 underwent craniotomy for surgical lesion excision. IHC analysis The same procedure was performed with PET/CT scan (Siemens,
were performed considering the following markers: hypoxia inducible Biograph 64) using (18F)-DOPA as tracer.
factor 1a [HIF-1a], Carbonic Anhydrase IX [CA-IX] and Glucose We placed (VOIs) in the same area where was applied the ROIs in
Transporter-1 [GLUT-1]; tumor angiogenesis and proliferative index RM scan in both groups of patients in order to calculate the SUV
have been evaluated. Anti CA-IX, GLUT-1 and HIF-1a antibodies mean values between IDH-MUT and IDH-WT.
have been used and a semiquantitative scoring system with five cat- To compare the ADCmean and SUVmean values between IDH-
egories (0 = 0%, 1 B 10%, 2 = 11–25%, 3 = 26–50% and MUT and IDH- WT we performed Student’s ‘‘t’’ test, considering
4 = 51–75%) has been applied to evaluate the extent of their significant value of p \ 0.05 in both groups.
expression. Anti-CD31 antibody has been used to assess tumour Results: The ADCmean values in IDH-WT patients
vascularity and Ki-67 to evaluate tumour proliferation. Evaluation of (0.86 9 10-3 mm2/s ± 0.06) were lower than those of IDH-MUT
immunomarkers expression was independently performed by two patients (1.24 9 10-3 mm2/s ± 0.19) with difference between the
expert pathologists blinded to PET results analysis. PET-derived two groups significant for p \ 0.01. The value of ADC C 1.01 9
parameters were evaluated and compared with anatomopathological 10-3 mm2/s can be considered as a ‘‘cut-off’’ to differentiate the
features by using Spearman’s correlation coefficient. mutation status.
Results: 18F-FAZA showed one lesion in 15/17 pts and multiple The ratio between tumor to background in PET/CT scan in IDH-WT
lesions in 1/17 pts. According to WHO classification, 12/17 pts had group was (2.59 9 10-3 mm2/s ± 0.448), higher than the group of
grade IV glioma, 5/17 had grade III glioma. For HIF-1 a the fol- IDH-MUT (1.9 9 10-3 mm2/s ± 0.533), with a significative
lowing score/number of pts have been observed: 0/1, 1/15, 2/1. For p \ 0.05.
CA-IX: 0/3, 1/8, 2/2, 3/3 and 4/1. Finally, for GLUT-1, 0/1, 1/2, 2/6, Conclusions: In the standard routine MR and PET are already
3/6 and 4/2 were reported. Mean Ki-67 value was 19% (range: assessed to evaluate brain tumors but they are both of limited value if
3-40%). Bioptical and surgical samples have been considered sepa- advanced techniques are not applied and if there is no integration of
rately for analysis. In the surgical subgroup (n = 7) CA-IX correlated anatomical and functional data. In our experience adding quantitative
with all PET parameters as follow: SUVmax (p = 0.0002), SUV- data such as ADC to conventional MR and semi-quantitative analysis
mean40 (p = 0.0058); SUVmean50 (p = 0.009), SUVmean60 to PET with aminoacid tracers like DOPA is necessary for a better
(p = 0.0153), MTV40-50-60 (p = 0.0424), HV 1.2-1.3-1.4 (p = comprehension of tumor nature. In the era of molecular imaging this

123
S40 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

is a novel approach that could be introduced as a non-invasive marker PO048


of specific genomic patterns. 18F-FET PET/CT in the management of patients
with brain tumor

PO047 M. Colandrea2, I.M. Milanesi6, E. Lamperti5, M. Schiariti4, S. Alessi3,


Target volume definition with 68GA-DOTATOC-PET/ M.E. Ferrari1, S.M. Baio2, S.L.V. Fracassi2, L. Gilardi2, P.A. Rocca2,
CT and MRI for patients with meningiomas G. Manfrinato2, L.L. Travaini2, A. Silvani5, L. Fariselli6, P. Ferroli4,
A.S. Cascio2, S. Papi2, M. Fiorenza2, C.M. Grana2
M. Colandrea3, C. Garibaldi4, M.E. Ferrari2, A. Iannalfi1, S. Pesente5, 1
European Institute of Oncology, Medical Physics, Milan, Italy.
S.M. Baio3, S.L. Fracassi3, L. Gilardi3, A.P. Rocca3, L.L. Travaini3, 2
European Institute of Oncology, Nuclear Medicine, Milan, Italy.
G. Manfrinato3, D. Militano3, S. Papi3, A.S. Cascio3, M. Cremonesi2, 3
European Institute of Oncology, Radiologist, Milan, Italy. 4Istituto
C.M. Grana3 Neurologico Besta, Neurosurgeon, Milan, Italy. 5Istituto Neurologico
1 Besta, Oncologist, Milan, Italy. 6Istituto Neurologico Besta, Radiation
Centro Nazionale di Adroterapia Oncologica CNAO, Radiation Oncologist, Milan, Italy
Oncology, Pavia, Italy. 2European Institute of Oncology, Medical
Physics, Milan, Italy. 3European Institute of Oncology, Nuclear Background-aim: Increased amino acid transport in brain tumour
Medicine, Milan, Italy. 4European Institute of Oncology, Radiation cells results from overexpression of the transporter systems and is
Research, Milano, Italy. 5Tecnologie Avanzate T.A. s.r.l. Research related to alterations in the tumour vasculature and cell proliferation.
and Development, Udine, Italy Radiolabelled amino acids offer significant improvement in the
diagnostic evaluation of cerebral tumours in comparison with con-
Background-aim: To investigate the potential impact of 68Ga- ventional anatomical imaging. Moreover 18F-fluoroethyl tyrosine
DOTATOC PET/CT in addition to standard morphological imaging (18F-FET) PET is useful for the noninvasive differentiation of tumor
(MRI and CT) in gross tumour volume (GTV) delineation in patients and nontumoral processes, as tumors have significantly higher uptake
affected by skull base meningiomas and treated with particle therapy. than non-neoplastic tissue. Recent studies suggest that radiolabelled
Methods: Sixteen patients (median age 51.4 years) with skull base amino acids could be superior to FDG in differentiating tumour and
meningiomas underwent 68Ga-DOTATOC PET/CT for target tumor inflammation.
delineation followed by constract-enhanced (CE) MRI and CT for The aim is to present our experience with 18F-FET PET as diagnostic
treatment planning with particle therapy. GTV for treatment was tool in the initial staging of suspected glioma (for guiding biopsy or
defined on the CE-MRI fused to the simulation CT (CTsim) inte- when biopsy is not feasible) or for differentiation of glioma recur-
grating information from the PET/CT. Three methods to delineate the rence from radionecrosis.
PET volume were evaluated: manual (PETman), semiautomatic (42% Methods: So far, we performed PET/CT with 18F-FET in 30 pro-
threshold of SUVmax, PETSUV42%) and an automatic adaptive gressive patients (11 women and 19 man; median age 49.77 yrs).
thresholding method incorporating PET reconstruction parameters Group A: 21 out 30 patients affected by brain tumors (1 GI, 7 GII, 8
(PETauto) (iTA, TA, Udine). PETman volumes were delineated by GIII, 5 GIV according to WHO 2016) and already treated with sur-
the same nuclear medicine physician, while PETSUV42% and gery and radio-chemotherapy. These patients presented a doubtful
PETauto volumes were determined by medical physicists. The PET/ MR imaging during follow up and were evaluated by 18F-FET PET
CT, CE-RMI and CTsim were co-registered with a deformable image in order to better define the nature of the lesions.
registration algorithm using the MIM Software (v. 6.1) and tumor Group B: 9 out 30 patients presented a doubtful MRI suspicious
volumes and positions were determined. The overlapping region of for brain disease; they received 18F-FET PET in the initial staging for
MRI and PETman resulted in GTVcommon. guiding biopsy or when biopsy is not feasible.
Results: The brain lesions had a median SUVmax of 12.1 ± 6.8 Manually drawn regions of interest over areas of maximal FET
(range 3.2–32.6). Overall, the GTV-MRI was larger than GTV-PET- uptake were used to calculate tumor to background ratios (TBRmax).
man in 7 patients (43.8%), smaller in 6 (37.5%) and almost the same in Moreover, MRI and PET images were fused using an Advantage
3 (18.8%). The median value of the different volumes were: GTV- Windows Workstation (GE Healthcare) in order to have precise
MRI = 14.3 ± 37.2 cc, GTV-PETman = 14.4 ± 47.0 cc, GTVcom- localization of uptakes.
mon = 12.2 ± 33.6 cc, GTV-PETSUV42% = 8.3 ± 18.3 cc, GTV- Results: 23 patients underwent 0–40 dynamic 18F-FET PET scans
PETauto = 11.3 ± 26.2 cc. As expected, volumes determined by the and 7 patients received a 20–40 min scan. TBRmax was assessed in
fixed threshold technique were always smaller than GTV-PETman the 20–40 min summation images in all patients, as well as in sum-
( = - 51.0 ± 32.7%) and GTV-PETauto ( = - 21.5 ± 12.7%) mation images from 5–20 min in 23 patients: no differences between
since they do not take into account variations in tumor heterogeneity. early and late images in terms of TBRmax was found.
The largest differences were observed for lesion showing a high SD of Group A: 17 out 21 patients had positive PET consistent with
SUV. The median difference between GTV-PETman and GTV- recurrent disease (TBRmax [ 1.6), 1 patient with suspected recur-
PETauto was 39.6 ± 29.5%. rence (TBR max [ 1.52) and 3 had negative PET consistent with
Conclusions: 68Ga-DOTATOC-PET/CT seems to improve the target radiation necrosis (no focal uptake). Moreover in 1 patient with two
volume delineation in skull base meningiomas, often leading to a MRI lesions, PET discovered a third area of pathological uptake. 2
reduction of GTV compared with results from MRI. The automatic out 17 positive patients are still in good clinical conditions (false
adaptive thresholding delineation method may provide robust and positive PET?), 3 in stable disease, 2 in progression disease, 4 died
reliable tool to help physician in segmenting PET images, reducing and 6 are lost at follow-up. The patient with doubtful PET is in
inter- and intra-observer variability. stable disease. 2 out 3 PET negative patients are still in follow-up
while 1 died after 7 months (false negative PET?).
Group B: 6 out 9 patients had positive PET suspicious for glioma.
To date, 3 have died (1 GII, 1 GIV and 1 without histological data)
and 3 are lost at follow-up (between them 1 GIII). 3 out 9 patients had

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S41

negative PET, in 1 patient biopsy revealed gliosis and 2 are lost at Cancer Institute, Rome, Italy. 5Pathology Unit, IRCCS Regina Elena
follow-up. National Cancer Institute, Rome, Italy. 6Radiology and Diagnostic
Conclusions: 18F-FET PET/CT is feasible and gives clear informa- Imaging Unit, IRCCS Regina Elena National Cancer Institute, Rome,
tion. Moreover, the fusion of functional and morphological images Italy
allows a better definition of areas of uptake and has the potential to
Background-aim: Cartilaginous bone tumors represent a wide vari-
impact on the management of patients with glioma. 18F-FET PET/CT
ety of neoplasms ranging from benign to extremely aggressive
allows a conclusive recognition of recurrence or radiation necrosis
malignant lesions. Unlike other tumors, the biopsy cannot easily
and is a useful tool for guiding biopsy or helping in the diagnosis
distinguish benign lesions from low-grade chondrosarcoma (LGCS)
when biopsy isn’t possible.
and among different grade of chondrosarcoma, sometimes not
allowing to choose the best therapeutic approach. Aim of the study
was to evaluate the ability of 18F-FDG PET/CT to differentiate
PO049 chondroma (Ch) from chondrosarcoma (CS) and to predict CS his-
tological grade as compared to biopsy and CT imaging.
Metastatic melanoma response to combination therapy
Methods: 18F-FDG PET/CT of 95 patients with chondroid lesions (35
with BRAF and MEK inhibitors: a FDG PET/CT study Ch and 60 CS) were retrospectively evaluated.
Results: A concordance between the preoperative biopsy and the final
L. Burroni1, G. Biscontini1, F.M. Fringuelli1, G. Garraffa1, histological grade was observed overall in 78.3% of patients, the
A. Palucci1 lowest accuracy (58.6%) was for the diagnosis of intermediate/high
grade CS (G2/G3, IHGCS). According to the criteria of maximum
1
Nuclear Medicine Unit, Ospedali Riuniti ‘‘Torrette’’, Ancona, Italy sensitivity and specificity, SUVmax cut-off points were respectively
2.4 to discriminate Ch vs LGCS (sensitivity 0.79, specificity 0.74), 3.7
Background-aim: Melanoma is a highly metastatic neoplasm of the
to differentiate LGCS vs IHGCS (sensitivity 0.83, specificity 0.84)
skin that has risen in incidence among white population over the past
and 7.7 to differentiate IHGCS vs de-differentiated CS (sensitivity
few decades. FDG PET/CT has become a cornerstone for staging
0.92, specificity 0.9). The radiological aggressiveness score
disease, assessing therapy and determining prognosis in patients solid
(AgSCORE), calculated as the sum of several radiologic features at
malignancies, included advanced melanoma. Combination therapies
co-registered CT scan, also showed a high accuracy to differentiate
for the treatment of metastatic melanoma are a matter of debate
between LGCS and IHGCS (cut-off = 4; sensitivity 0.76; specificity
nowadays. We studied the early changes on FDG PET/CT for patients
0.9). An even higher accuracy (Sensitivity 0.91; Specificity 1) were
with BRAF-mutant melanoma receiving BRAF and MEK inhibition
observed in those cases in which both SUVmax and AgSCORE were
therapy.
concordant.
Methods: Nine patients with advanced BRAF-mutant metastatic
Conclusions: Results in this large series of patients suggest a
melanoma were included. All patients received combination BRAF
potential role of 18F-FDG PET/CT for histological grading of carti-
and MEK inhibitors for the treatment of metastatic melanoma. In all
laginous tumors, and in particular to discriminate LGCS vs IHGCS,
patients FDG PET/CT scans were performed at baseline and 1 month
thus helping the clinician toward the best patient management.
post treatment. All images were assessed visually to identify sites of
increased uptake and SUVmax measures were calculated. HRCT was
also performed in all patients.
Results: The baseline PET/CT scan demonstrated multiple metastatic PO052
lesions in all patients. At follow-up 2 patients had a complete
Clinical and prognostic role of 18F-FDG PET/CT
response, 3 had stable disease and 4 had progressive disease. In
patients with progressive disease CT responses and clinical conditions in pediatric Ewing sarcoma
have discouraged the execution of the follow-up PET/CT.
Conclusions: Due to its ability in detecting metabolic changes before F. Dondi3, D. Albano2, M. Bonacina3, R. Durmo3, M. Bertoli2,
anatomic alterations take place, FDG PET/CT can be a powerful tool E. Cerudelli3, M. Gazzilli3, A. Mazzoletti3, F. Bertagna1,
in personalized treatment management in advanced melanoma. In two C. D’ippolito4, R.F. Schumacher4, R. Giubbini1
cases with complete response, PET/CT played a significant role in
1
patient monitoring and prediction of treatment response. In particular, Nuclear Medicine, Spedali Civili di Brescia and Università degli
change in SUVmax for the least responsive tumor and baseline per- Studi di Brescia, Brescia, Italy. 2Nuclear Medicine, Spedali Civili di
formance may be useful prognostic indicators for progressive-free Brescia, Brescia, Italy. 3Nuclear Medicine, Università degli Studi di
survival in patients with BRAF-mutant melanoma. Brescia, Brescia, Italy. 4Oncoematologia Pediatrica e Trapianto di
Midollo Osseo Pediatrico, Spedali Civili di Brescia, Brescia, Italy
Background-aim: Ewing sarcoma (ES) is one the most common
PO051 pediatric bone sarcomas with aggressive behaviour and suboptimal
prognosis. Imaging with 18F-FDG PET/CT could be a valuable tool to
18F-FDG PET/CT in the evaluation of cartilaginous
select patients with worst outcome. There are several studies
tumors of bone: the added value of tumor grading regarding the role of PET/CT in the staging and/or restaging of ES but
they focus on heterogeneous population (mixed adults and paedi-
A. Annovazzi3, V. Anelli6, C. Zoccali4, N. Rumi1, A. Persichetti4, atrics; mixed bone and soft tissue sarcomas) and the results are
M. Novello5, R. Sciuto3, V. Ferraresi2, R. Biagini4 controversial. The aim of our study is to evaluate the diagnostic
accuracy of staging and restaging PET/CT and investigate a possible
1
Department of Radiology, Catholic University of the Sacred Heart, prognostic role of PET/CT parameters in pediatric ES.
Rome, Italy. 2First Division of Medical Oncology, IRCCS Regina Methods: We retrospectively included 17 patients (14 male, 3
Elena National Cancer Institute, Rome, Italy. 3Nuclear Medicine females; mean age 11) who underwent a total of 27 18F-FDG PET/CT
Unit, IRCCS Regina Elena National Cancer Institute, Rome, Italy. in our department. Among 27 PET studies, 10 were performed for
4
Oncological Orthopaedics Unit, IRCCS Regina Elena National staging purpose before any treatment and 17 after primary therapy to

123
S42 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

evaluate treatment response and/or relapse. The PET images were response to neoadjuvant-chemotherapy defined by the histological
analyzed visually and semi-quantitatively by measuring the maximum percentage of tumor necrosis or by MRI evaluation.
mean standardized uptake value body weight (SUVmean), maximum Methods: Patients have been enrolled from June 2010 to November
SUV (SUVmax), lean body mass (SUVlbm), body surface area 2016 according to the following inclusion criteria: (a) biopsy-proven
(SUVbsa), metabolic tumor volume (MTV) and total lesion glycolysis bone or soft tissue sarcoma; (b) 18F-FDG-PET/CT at baseline within
(TLG) of the hypermetabolic lesion. The Kaplan–Meier method was 4 weeks before the start of neoadjuvant-chemotherapy (PET1);
used to estimate the progression-free survival (PFS) and overall sur- (c) 18F-FDG-PET/CT 6 weeks after the start of neoadjuvant-
vival (OS) times. chemotherapy (PET2); (d) radical therapy after neoadjuvant-
PET/CT results were compared with other conventional imaging (CI, chemotherapy (surgery and/or radiation therapy); (f) evaluation of the
computed tomography and/or magnetic resonance) results. response to therapy assessed by percentage of necrosis in the resected
Results: Among 10 PET/CT scans performed for staging, 9 were tumor or by MRI evaluation at the end of neoadjuvant-chemotherapy.
positive showing the presence of at least one hypermetabolic lesion Standardized Uptake Value (SUV)max, SUVmean, SUVpeak,
consistent with disease (average SUVmax 10,6; SUVmean 7,8; Metabolic Tumor Volume (MTV) and Total Lesion Glycolysis (TLG)
SUVlbm 8,1; SUVbsa 3; MTV 199 and TLG 2281) and 1 had neg- of the primary tumor were calculated for PET1 and PET2. Changes
ative PET/CT. therein between PET1 and PET2 parameters were also calculated as
CI and PET/CT were concordant in 8 cases and discordant in 2 cases; follow: =[(PET1–PET2)/PET1] 9 100. All primary lesions were
in these two patients PET/CT were false negative due to the presence evaluated to assess the response to neoadjuvant-chemotherapy.
of lung nodules under the minimal resolution power. Clinical and Responders to therapy were considered patients with a necro-
PET/CT features did not correlate with survival outcome (PFS, OS), sis C 95% in the resected tumor or patients with complete
Of 17 PET/CT scans performed for restaging, 9 were positive disappearance of the lesion at the MRI performed after the completion
(average SUVmax 5,5; SUVmean 3,9; SUVlbm 4,4; SUVbsa 1,5; of neoadjuvant-chemotherapy and before radiation therapy.
MTV 55,9 and TLG 255) while 8 were negative. CI and restaging Results: Thirty-four patients were enrolled: 10 females; 24 males;
PET/CT were concordant in 9 cases and discordant in 8. PET was median age = 15.1 years. Fifty percent (17/34) of patients had
superior to CI in 5 cases (1 true positive, 4 true negative) and inferior Osteosarcoma, 38.2% (13/34) Ewing Sarcoma, 5.9% (2/34) Liver
in 3 cases (2 false negative and 1 false positive). Sensitivity, speci- Embryonal Sarcoma and 5.9% (2/34) Synovial Sarcoma. Mean fol-
ficity, positive predictive value, negative predictive value and low-up was 38.8 months (range 16.3-84.1). Twenty-three percent (8/
accuracy of FDG-PET/CT were 73%, 80%, 89%, 57%, 75%. 34) of patients died from cancer-related causes while 23.5% (8/34)
After a median follow-up of 20 months, relapse/progression of were alive with disease and 53% (18/34) had no evidence of residual/
disease occurred in 8 patients with an average time of 11.75 months recurrent disease. Considering the response to neoadjuvant-
and death occurred in 5 patients with an average time of 13.2 months. chemotherapy 32.3% of patients (11/34) were classified as respon-
A positive FDG PET/CT was significantly associated with shorter OS ders, while 67.7% of patients (23/34) were classified as non-
compared to unremarkable PET/CT scan (p = 0.047), not with PFS. responders.
Instead, other semiquantitative PET features were not correlated with Primary objective: the univariate analysis demonstrated an associa-
outcome. tion between all PET2-parameters and DFS (PET2-SUVmax
Conclusions: With this study we demonstrated that 18F-FDG PET/CT p = 0.0113; PET2-SUVpeak p = 0.0111; PET2-SUVmax/SUVmean-
showed a good diagnostic performance in pediatric Ewing sarcoma, liver p = 0.03; PET2-SUVpeak/SUVmean-liver p = 0.032; PET2-
better than conventional imaging, especially in restaging, except for SUVmax/SUVmax-liver p = 0.04; PET2-SUVpeak/SUVmax-liver
pulmonary micrometastases. Only restaging PET/CT was signifi- p = 0.035; PET2-MTV p = 0.033 and PET2-TLG p = 0.005). It was
cantly correlated with OS. No other PET/CT features correlated with also assessed a significant correlation between  TLG (p = 0.036)
PFS or OS. Semiquantitative analysis does not provide additional and DFS. No significant association was observed between PET1
prognostic information. parameters and  SUV parameters with OS and DFS.
Secondary objective: no significant correlation was observed
between response to therapy and PET1-parameters, PET2-parameters
and changes therein.
PO053 Conclusions: According to our data, 18F-FDG-PET/CT performed
18FDG PET/CT performed early during neoadjuvant- six weeks after the start of neoadjuvant-chemotherapy proved to be an
chemotherapy to predict outcome in paediatric sarcoma early predictor of patients’ outcome since all PET-2 parameters
(SUVmax, SUVmean, SUVpeak, MTV, TLG) and  TLG were
patients. Results of a prospective single-center trial
significantly associated with disease-free survival.
G. Polverari1, J. Calais3, L. Du2, G. Li2, N. Federman4, S. Fanti1,
J. Czernin3, F. Ceci3
PO054
1
Metropolitan Nuclear Medicine of Bologna, University of Bologna, FDG PET/CT as indicator of progression free survival
Bologna, Italy. 2UCLA Johnson Comprehensive Cancer Center
Biostatistics, Los Angeles (CA), USA. 3UCLA Nuclear Medicine,
short-term in Ewing sarcoma
Los Angeles (CA), USA. 4UCLA Pediatrics Oncology, Los Angeles
(CA), USA V. Vergura1, A. Kokomani1, F. Linguanti1, M. Allocca1,
E. Abenavoli1, V. Berti1, M. Matteini1, D. Greto2, L. Livi2,
Background-aim: This is a prospective, single-center trial approved V. Briganti1, R. Sciagrà1
by the local ethics committee (UCLA-IRB#10-000246) in pediatric
patients with high grade bone or soft tissue sarcoma. The primary 1
Nuclear Medicine Unit, Careggi University Hospital, Florence, Italy.
objective was to evaluate the relationship between 18F-FDG-PET/CT 2
Radiotherapy Unit, Careggi University Hospital, Florence, Italy
parameters at baseline and early during neoadjuvant-chemotherapy
with overall survival (OS) and disease-free survival (DFS). The Background-aim: In a recent publication (J CANCER 2017;15:
secondary aim was to evaluate if 18F-FDG-PET/CT can predict the 2892–2898) a baseline SUVmax [ 11.6 is reported as negative pre-
dictor of Overall Survival (OS) and Progression Free Survival (PFS)

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S43

in long term follow up on 28 patients with Ewing sarcoma (ES). This Results: According to histological response, all patients were cate-
study tested a SUVmax cut-off, identified using recursive partitioning gorized into responders (tumor necrosis [ 90%, n. 15) and non-
analysis (RPA), to evaluate its predictive efficacy in short-term PFS responders (tumor necrosis \ 90%, n. 20). Six out of 41 patients
(first relapse). (14,6%) have not undergone surgical treatment. Repeated measures
Methods: We retrospectively analyzed a database of 27 patients with ANOVA showed mean affect across time with significant reduction of
ES (16 men; 11 women; mean age: 16.7 years; 7 and 10 respectively SUVmax at t1 (p \ 0.0001) and t2 (p \ 0.01). The level of tumor
in IIA and IIB stage; 3 and 7 respectively in IVA and IVB stage, 12 necrosis showed positive relationship with the delta changes of
with and 15 without metastasis at staging) who underwent baseline SUVmax at t1 (p = 0.007, r = 0.5) and t2 (p = 0.006, r = 0.5) for the
and end of treatment FDG PET in our Unit of Nuclear Medicine. primary lesion. Similar association was observed between the level of
SUVmax [ 8, identified using recursive partitioning analysis (RPA), tumor necrosis and the  SUVmax for the surrounding soft tissue.
was considered as cut-off value as suggested by the reported article. A  SUVmax cut-off of 4.7 at t1 and of 7.5 at t2, were able to predict
The median follow-up was 8 months. responders (tumor necrosis [ 90%) with a sensitivity of 0.8 and 0.77
Results: Only 4 of 27 patients had SUVmax [ 8 at staging and all and a specificity of 0.78, and 0.72, respectively. The OS and EFS
demonstrated recurrences or metastases during follow up (positive analysis conducted in the whole cohort determined the median time of
predictive value, VPP 100%). Most patients (23 of 27) had SUV- progression-free survival was around 19.8 months. Median time to
max \ 8, of these 8 had metastasis and 15 no metastasis (negative EFS was 34.4 months. OS and EFS were significantly different in
predictive value, VPN 65%). responders and non-responders.
Conclusions: The study apparently shows that a SUVmax of the Conclusions:  SUVmax after neoadjuvant and adjuvant
primary lesion at baseline FDG PET/CT \ 8 has a just a fair negative chemotherapy seems to act as a metabolic predictor of histological
predictive value for PFS during a short term follow up. SUVmax [ 8 response, stratifying, with good sensitivity and specificity, treatment
was detected in just four cases and in all coincided with a bas short- responders from non-responders.  SUVmax was also predictive of
term prognosis. EFS and OS and may be a useful prognostic biomarker for OS and
ES.

PO055
Metabolic predictors of treatment response in patients PO056
with osteosarcoma and Ewing’s sarcoma Role of 18F-FDG PET/CT in target delineation
of lymph nodes in patients candidate to IMRT
G. Aghakhanyan4, T. Neri3, L. Caponi4, L. Coccoli3, F. Guidoccio4, for nasopharynx carcinoma
S. Chiacchio4, S. Caputo4, F. Betti4, L. Antonacci4, A. Franchi2,
G. Casazza3, R. Capanna1, I. Paglianiti4, D. Volterrani4 P. Moda1, A.R. Marsella2, R. Marchese2, G. Silvano2, F. Lauriero1
1
Orthopedic Oncology, University Hospital of Pisa, Pisa, Italy. 1
Nuclear Medicine Unit, PET/CT Centre, Hospital ‘‘G. Moscati’’,
2
Pathology Unit, University Hospital of Pisa, Pisa, Italy. 3Pediatric Taranto, Italy. 2Radiotherapy Unit, Hospital ‘‘G. Moscati’’, Taranto,
Oncology, University Hospital of Pisa, Pisa, Italy. 4Regional Center Italy
of Nuclear Medicine, University Hospital of Pisa and Department of
Translational Research on New Technologies in Medicine and Background-aim: Radiation therapy is the main treatment choice for
Surgery, University of Pisa, Pisa, Italy nasopharynx carcinoma (NPC).
Because of the proximities of many critical organs in the head and
Background-aim: To determine the relationship of serial [18F]FDG neck, intensity-modulated radiation therapy (IMRT) is the preferred
uptake in the primary tumor with a histologic response and event-free modality for accurate irradiation of target volumes, including the
survival in pediatric and young adult patients with osteosarcoma (OS) primary gross tumor volume (GTV) and the positive cervical lymph
and Ewing’s sarcoma (ES). nodes (GTV-N), sparing organ at risk.
Methods: Since September 2006 to August 2018, forty-one patients There is no consensus to include cervical lymph nodes (CLNs)
(34 males; median age, 21.7 years; age range 3–44 years) with OS MRI negative in CTV/GTV IMRT planning. Aim of this study is to
and ES from a single institution (Pediatric Onco-Haematology Unit, evaluate the role of 18F-FDG PET/CT in patients affected by NPC
University Hospital of Pisa), who underwent serial [18F]FDG PET/ and candidate to IMRT who have small CLNs that appear negative on
CT imaging, including baseline (t0), after neoadjuvant (t1) and MRI scans.
adjuvant chemotherapy (t2) were recruited. All patients were subdi- Methods: 14 patients (8 female, 6 male), mean age 53 years (range
vided into 5 subgroups: localized ES, metastatic ES at the diagnosis, 17–81 years), underwent both imaging modality (MRI and PET/CT)
plurimetastatic ES at the diagnosis (Very High Risk Group), localized for initial staging before IMRT planning.
OS and metastatic OS. For all time-points, the serum lactate dehy- All patients performed a 18-FDG PET/CT scan with immobilization
drogenase (LDH) and alkaline phosphatase (ALP) activities, the PET- of the head district, fasted for at least 6 h and with plasma glu-
derived parameters, such as maximal standardized uptake value cose \ 200 mg/dl, 60 min after intravenous injection of 4 MBq/kg
(SUVmax) for the principal lesion and the surrounding soft tissue 18F-FDG. Images analysis was carried out visually and by semi-
compartment and the postoperative histologic data, such as tumor quantitative determination calculating the maximum standardized
grading and tumor response (percentage of tumor necrosis), were uptake value (SUV Max). Positivity was considered if: abnormal
collected. Repeated measures ANOVA, linear regression and/or increased FDG uptake was greater of the surrounding background and
Pearson correlation analysis were applied between quantitative, the SUV max was [ 2.5.
ordinary and delta-encoded variables, as appropriate. Overall survival MRI images of head and neck district were acquired with a 1.5 T
(OS) and event free survival (EFS) was calculated using non para- scanner with contrast enhancement and T1 -T2 sequence. MRI criteria
metric Kaplan–Meier test determining the time to event from the first for positive lymph nodes were: diameter [ 10 mm, or capsular
[18F]FDG PET/CT scan until the event or last follow-up. The sur- invasion, or cluster or string-like distribution, or central necrosis. We
vival distributions were compared with logrank test. The significance focused our attention to solitary and negative CLNs with
level was set at or below 5% in all analysis.

123
S44 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

5 mm \ diameter \ 10 mm found at different levels from clear 7 patients (average SUVmax 16.5; range 12.5–22), lymph node
metastatic CLNs. metastasis in 6 patients (average SUVmax 11.4; range 4.2–18.8) and
Ultrasonography guided fine needle aspiration cytology (US- distant metastasis in 4 patients (2 in liver: SUVmax 13.7 and 8.6
FNAC) was performed in all positive 18F-FDG PET/CT CLNs with respectively; 1 in lung: SUVmax 12.4; 1 multiple bone metastasis).
MRI negative. US-FNAC and 18F-FDG PET/CT results were com- Conclusions: Head and neck MMs are 18F-FDG avid tumors; 18F-
pared to evaluate diagnostic accuracy. FDG PET/CT could be a valuable imaging for staging, re-staging and
Results: 22 MRI negative CLNs were solitary and most of them follow up of patients.
located at level II with a mean maximum diameter B 10 mm. 18F-
FDG PET/CT imaging identified 10 positive on 22 MRI negative
CLNs, with a mean SUV max of 8.7 (range 2.5–18.2). US-FNAC
results confirmed metastasis in 8 of the 10 18F-FDG PET/CT posi- PO058
tive, showing an accuracy of 80% for distinguishing malignant lymph Radiomics analysis of 18F-FDG PET/CT images:
nodes. The remaining 2 lymph nodes were cytopathological classified preliminary results in patients with head and neck
as lymphadenitis. The PPV (positive predictive value) of 18F-FDG
cancer
PET/CT was also 80%. Lymph nodes confirmed as pathological were
subsequently delineated and treated as GTV-N with 66–70 Gy/30-35
fractions. With a median follow-up of 18 months no relapse was M. Larobina4, L. Murino5, R. Solla4, R. Fonti4, B. Salvatore4,
observed by MRI and 18F-FDG PET/CT. A. Brunetti3, S. Del Vecchio3, A. Cuocolo3, L. Mansi1, L. Pace2
Conclusions: Locoregional relapse is one of the undesirable even- 1
tuality for NPC patients treated with IMRT. Nodal staging with 18F- Centro Interuniversitario di Ricerca per la Sostenibilità (CIRPS),
FDG PET/CT compared to MRI has higher accuracy in the evaluation Rome, Italy. 2Dipartimento di Medicina e Chirurgia, Università di
of occult metastasis in small CLNs. Therefore, diagnosis based on the Salerno, Salerno, Italy. 3Dipartimento di Scienze Biomediche
nodal size could be no more reliable, resulting in misdiagnosis of Avanzate, Università di Napoli ‘‘Federico II’’, Naples, Italy. 4Istituto
metastatic CLNs. When using IMRT, correct diagnosis and accurate di Biostrutture e Bioimmagini-CNR, Naples, Italy. 5Istituto per le
targeting of metastatic CLNs is crucial for the local control of the Applicazioni del Calcolo-CNR, Naples, Italy
disease and survival. Background-aim: To evaluate the usefulness of 18F-FDG-PET/CT
texture analysis in the staging and prediction of outcome in a group of
patients with head and neck cancer.
Methods: We retrospectively evaluated twenty-two patients with
PO057 head and neck cancer (15 male, 7 female; mean age
18F-FDG PET/CT in head and neck mucosal melanoma 60.7 ± 11.0 years). Patients underwent whole-body 18F-FDG PET/
CT at diagnosis and were subsequently treated with radiotherapy
R. Durmo1, D. Albano1, M. Bonacina1, M. Gazzilli1, E. Cerudelli1, alone or combined with chemotherapy. Only the primary tumors were
F. Dondi1, A. Mazzoletti1, F. Bertagna2, R. Giubbini2 considered for the radiomics analysis. Starting from PET images,
lesions were segmented using a 40% SUVmax threshold. For each
1
Nuclear Medicine, Spedali Civili Brescia, Brescia, Italy. 2Nuclear lesion the metabolic tumor volume (MTV), and parameters such as
Medicine, University of Brescia and Spedali Civili Brescia, Brescia, SUVmax, SUVmean, total lesion glycolysis (TLG), and a total of sev-
Italy enteen textural features were calculated. Five textural features derived
from the intensity-histogram of the lesion volume: standard deviation,
Background-aim: Mucosal melanoma (MM) represents about 1.3%
skewness, kurtosis, coefficient of variation, area under cumulative
of all melanomas and it is a rare disease with a very poor prognosis,.
SUV-volume histogram curve (AUC-SHC) were calculated using an
The nasal cavity, paranasal sinuses, and oral cavity are the most
in-house software written in IDL (Exelis Visual Information Solu-
common locations. MMs are now recognized to have distinct
tions, Inc.) also used for the MTV calculation. Twelve textural
molecular alterations and different clinical behaviour compared to
features derived from the three-dimensional grey levels co-occurrence
cutaneous or uveal melanomas showing a greater tendency to
matrix: uniformity, entropy, correlation, contrast, homogeneity,
metastasize and poorer prognosis. The aim of our retrospective study
variance, sum mean, dissimilarity, cluster shade, cluster tendency,
was to evaluate glucidic metabolic behaviour and imaging findings of
max probability, inverse variance were calculated using the Matlab
head and neck MMs studied with 18F-fluorodeoxyglucose positron-
(The MatWorks, Inc.) function cooc3D.m. Texture features were
emission tomography/computed tomography (18F-FDG PET/CT).
normalized as Z-scores and four distinctive groups of features were
Methods: Between 2005 and 2018 thirty patients (21 female, 9 male,
identified using hierarchical clustering approach. Four features were
average age 65.8 years, range 20–87 years) with histologically-con-
selected, each to be representative of a group: skewness, homo-
firmed diagnosis of head and neck MM underwent 18F-FDG PET/CT
geneity, AUC-SHC, and dissimilarity. Conventional PET parameters
(16 staging; 14 re-staging; patients of restaging group underwent
such as SUVmax, SUVmean, MTV, and TLG, and the four represen-
more than one PET/CT). A total of 60 PET/CT images were quali-
tative features above selected were evaluated in relation to patient
tatively and semi-quantitatively analyzed by measuring the maximum
clinical data that comprised: age, clinical stage, tumor grade, and
standardized uptake value (SUVmax). No patients was affected by
follow-up, with the ANOVA test. Overall survival was estimate using
primary melanoma in any other site at the time of diagnosis.
Kaplan–Meier analysis and Cox regression.
Results: Twenty-seven MMs were located in the nasal cavity and/or
Results: MTV, homogeneity and dissimilarity mean values showed a
ethmoidal/maxillary sinus while 3 in the oral cavity. All MMs of
statistically significant difference with respect to clinical stage
patient who underwent PET/CT for staging were 18F-FDG avid at the
(p \ 0.05). TLG and skewness mean values showed a statistically
site of primary tumor (average SUVmax 14.4; range 5.25–30.5); five
significant difference with respect to tumor grade (p \ 0.05). For the
patient showed also cervical lymph nodes involvement (average
prediction of overall survival none of the textural features were
SUVmax 5.9; range 4.77–6.6) and one patient showed axillary lymph
retained in the multivariate analysis, and only TLG and MTV were
node positivity (SUVmax = 4.77); no distant metastasis were found.
held in the model. Overall survival was significantly better in patients
In the group of patients who underwent 18F-FDG-PET/CT for re-
with an MTV \ 9.27 mL (p \ 0.05).
staging and/or follow up, primary site recurrence was demonstrated in

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S45

Conclusions: The preliminary results of this study suggest that con- SUV-max and MTV for the prediction of 2-year mortality shows
ventional PET parameters and textural features can be useful in the respective AUCs of 0.68 (95% CI 0.51-0.85) and 0.69 (0.53-0.84).
evaluation of head and neck cancer patients. Conclusions: MTV and SUVmax are the only two PET parameters
which are prognostic for OS and DFS in patients with pleomorphic
lung carcinoma, and that they have similar discriminatory ability.
PO059
Pleomorphic lung carcinoma: pattern of molecular
PO060
imaging
Prognostic value of intratumoral heterogeneity based
L.L. Travaini3, M.E. Ferrari2, M. Colandrea3, L. Gilardi3, S.L. on fractal geometry analysis in operated NSCLC
Fracassi3, P.A. Rocca3, S.M. Baio3, G. Manfrinato5, G. Buonsanti3, patients
M. Barberis4, L. Spaggiari6, P. Maisonneuve1, C.M. Grana3
1
A. Castello2, C. Russo3, F. Grizzi1, D. Qehajaj1, E. Lopci2
Division of Epidemiology and Biostatistics, European Institute of
Oncology IRCCS, Milan, Italy. 2Medical Physics Department, 1
Department of Immunology and Inflammation, Humanitas Clinical
European Institute of Oncology IRCCS, Milan, Italy. 3Nuclear and Research Hospital, Rozzano (MI), Italy. 2Department of Nuclear
Medicine Division, European Institute of Oncology IRCCS, Milan, Medicine, Humanitas Clinical and Research Hospital, Rozzano (MI),
Italy. 4Pathology Unit, European Institute of Oncology, Milan, Italy. Italy. 3Michele Rodriguez Foundation, Milan, Italy
5
Residency Program in Nuclear Medicine, University of Milan, Italy.
6
Thoracic Surgery Department, European Institute of Oncology Background-aim: To determine the heterogeneity of glucose uptake
IRCCS, Milan, Italy applying fractal analysis on 18F-FDG PET/CT images in patients
with non-small cell lung carcinoma (NSCLC) before surgery, and to
Background-aim: Pleomorphic lung carcinoma is a rare form of lung assess whether this heterogeneity was associated with disease-free
cancer usually correlated with poor prognosis. Early recognition of survival (DFS).
patients could help the surgeon/oncologist to choose a more person- Methods: 18F-FDG PET/CT scans of 113 patients prior surgery were
alized treatment. The aim of this retrospective study was to assess the retrospectively revised. PET DICOM images were analyzed for
impact of metabolic features by fluorine-18 fluorodeoxyglucose PET/ fractal geometry using a ad-hoc software to automatically determine
Computed Tomography ([18F]FDG-PET/CT) in the prediction of the following indexes: (a) mean intensity value (MIV), (b) standard
overall survival (OS) and disease free survival (DFS) in a series of deviation (SD), (c) relative dispersion (RD), (d) three-dimensional
patients with pleomorphic lung carcinoma submitted to radical (3D) histogram of the fractal dimension (3D HIST FR DIM), and
surgery. (e) fractal dimension in 3D (3D-FD). All the fractal indexes were
Methods: We designed the analysis of consecutive patients referred subsequently compared with metabolic parameters and DFS.
to our hospital for staging of lung cancer. Inclusion criteria comprised Results: We found a significant correlation between 3D-FD and
age older than 18 years, diagnosis of pleomorphic lung carcinoma SUVmax, SUVmean, MTV, and TLG. Additionally, positive corre-
(WHO 2017) and staging by [18F]FDG-PET/CT performed less than lations between MIV, SD and all metabolic parameters were also
45 days from surgery. Metabolic parameters [maximum standardized detected. Patients with high 3D-FD tumor (C 1.62) showed signifi-
uptake value (SUVmax), mean standardized uptake value (SUV- cantly higher values of SUVmax, SUVmean, MTV, and TLG than
mean), metabolic tumor volume (MTV), total lesion glycolysis and those with lower 3D-FD.
tumor/no tumor] were determined on [18F]FDG-PET/CT images. The In univariate analysis, 3D-FD and TLG resulted significantly asso-
SUV threshold for tumor segmentation was defined as the 41% of the ciated with DFS (p = 0.04 and p = 0.03, respectively). These findings
SUVmax of the lesion. OS and DFS curves were plotted using the were confirmed on log-rank test. On multivariate analysis, among age,
Kaplan–Meier method and the log-rank test was used to assess dif- stage disease, histotype, 3D-FD, and metabolic parameters, only 3D-
ferences in survival. Univariate and multivariable Cox proportional FD was identified as independent prognostic factor for DFS
hazard regression adjusted for pathological stage (stage I, stage II, (p = 0.032; HR 0.418, 95% CI: 0.189–0.926).
stages III-IV) was used to assess the association between PET 3D-FD was different between adenocarcinoma and squamous cell
parameters and survival. We performed receiver operating charac- carcinoma (1.60 vs 1.88, p = 0.014), and 3D-FD value was found
teristic (ROC) curve analysis to illustrate the performance, measured higher in advanced stage disease.
with the area under the curve (AUC) of [18F]FDG-PET/CT param- Conclusions: Metabolic heterogeneity determined applying fractal
eters as predictors of mortality or tumor recurrence at 2 years. principles on PET images can be considered as a novel imaging
Results: The study included 49 patients equally distributed in stage I, biomarker for survival in patients with NSCLC.
II and III–IV with a mean aged = 64.8 ± 9.4 years. We found no The Italian Association for Research on Cancer (AIRC – Associ-
significant differences between [18F]FDG-PET/CT parameters and azione Italiana per la Ricerca sul Cancro) is acknowledged for the
tumor stage, indicating that cancers have highly intensive uptake also support on research with the grant nr. 18923.
at initial stage. The two most important prognostic [18F]FDG-PET/
CT parameters for OS at univariate and multivariable analysis were
MTV (p = 0.03) and the SUVmax (P = 0.07). The ROC analysis of

123
S46 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

PO061 PO062
Predictive and prognostic role of metabolic response Emergencies on 18F-FDG PET/CT with contrast agent
in patients with stage III NSCLC treated
with neoadjuvant chemotherapy M. Leporace1, F. Calabria1, A. Lanzillotta1, A. Bagnato1
1
Department of Nuclear Medicine and Theranostics, Mariano Santo
A. Castello2, L. Toschi3, S. Rossi3, G. Finocchiaro3, F. Grizzi1,
Hospital, Cosenza, Italy
D. Qehajaj1, D. Rahal4, E. Lopci2
Background-aim: 18F-FDG PET/CT in oncological patients can be
1
Department of Immunology and Inflammation, Humanitas Clinical performed with contrast agents administration, providing a better
and Research Hospital, Rozzano (MI), Italy. 2Department of Nuclear definition of tumor size and borders and optimal characterization of
Medicine, Humanitas Clinical and Research Hospital, Rozzano (MI), brain lesions, hepatic metastases and/or peritoneal carcinomatosis.
Italy. 3Department of Oncology, Humanitas Clinical and Research Currently, a significant part of 18F-FDG PET/CT scans are developed
Hospital, Rozzano (MI), Italy. 4Department of Pathology, Humanitas worldwide with iodinated contrast agents administration. The aim of
Clinical and Research Hospital, Rozzano (MI), Italy our study was to show and discuss some emergency cases we
encountered in our clinical practice with contrast enhanced 18F-FDG
Background-aim: Treatment of locally advanced (stage III) NSCLC
PET/CT.
still remains a challenge for clinicians, as patients at the same stage
Methods: From January 2017 to October 2018, we examined 300
and with same treatment experienced different outcomes. Our study
oncological patients with 18F-FDG PET/CT with iodinated contrast
aimed to assess the predictive and prognostic role of 18F-FDG PET/
and oral agents.
CT in stage III NSCLC candidates to neoadjuvant chemotherapy.
Results: Among examined patients, 7/300 (2.3%) presented a vas-
Methods: Overall, 66 stage III NSCLC patients treated with induc-
cular or parenchymal disease presenting as emergency case, needing
tion chemotherapy from March 2013 to December 2017, were
acute surgical and/or pharmacological treatment. In particular, we
retrospectively identified. Inclusion criteria comprised: age [ 18
documented 1 case of deep vein thrombosis, 4 cases of pulmonary
years, diagnosis of locally advanced NSCLC (stage IIIA/IIIB) eligible
embolism and 2 cases of arterial aneurysm, splenic and pancreatic,
for neoadjuvant treatment, patients undergoing 18F-FDG PET/CT
respectively.
scan prior to and following chemotherapy. Response assessment were
Conclusions: Our preliminary data suggest that physicians cannot
evaluated according to the RECIST 1.1 and EORTC criteria. 18F-
exclude, in clinical practice with contrast enhanced 18F-FDG PET/
FDG PET/CT parameters analyzed comprised: maximum and mean
CT, the detection of an emergency clinical case during a scan per-
standardized uptake value (SUVmax and SUVmean), metabolic
formed for oncological purpose. In our series, a low but significant
tumor volume (MTV), total lesion glycolysis (TLG), and the per-
percentage of examined patients was affected by an acute vascular
centage changes () between two consecutive scans. We
accident, particularly pulmonary embolism. In this scenario, a vas-
distinguished metabolic parameters for primary tumor (T) and for
cular radiologist with skill in oncological field could be the best
regional lymph nodes (N). All clinical variables and metabolic
option to include in contrast enhanced 18F-FDG PET/CT evaluation.
parameters were compared to treatment response and correlated to
PFS and OS, based on a median follow-up of 9.4 months.
Results: Post-induction therapy SUVmax_T, SUVmean_T, MTV_T,
and TLG_T varied significantly between responders and non-re- PO063
sponders (6.6 vs 13.8 p = 0.001, 4.2 vs 8.1 p \ 0.001, 6 vs 17.9
Predictive role of 18F-FDG PET/CT in lung cancer
p = 0.002, 24.1 vs 136.3 p \ 0.001, respectively). Likewise, per-
centage changes ( _T) were significantly different between the two patients undergoing immunotherapy
groups (p \ 0.001). Along with primary tumor, also post-SUV-
max_N, post-SUVmean_N, and post-TLG_N (p = 0.024, p = 0.015, C. Lea1, F. Stefano2, P. Giulia2, L. Evangelista1
p = , p = 0.024, respectively), as well as all percentage changes
1
( _N) were different between responders and non-responders. Nuclear Medicine and Molecular Imaging Unit, Veneto Institute of
RECIST 1.1 and EORTC response classifications were discordant in Oncology IOV-IRCCS, Padua, Italy. 2Oncology 2 Unit, Veneto
27 patients (40.9%; | = 0.265, p = 0.003). On multivariate analysis, Institute of Oncology IOV-IRCCS, Padua, Italy
post-TLG_N resulted an independent predictor for both PFS and OS.
Background-aim: The purpose of the present study was to assess the
Surgery and RECIST 1.1, instead, were predictors for PFS and OS,
predictive role of 18F-FDG PET/CT for the evaluation of response to
respectively.
immunotherapy in patients affected by metastatic lung cancer.
Conclusions: Several metabolic parameters may differentiate
Methods: From a mono-institutional database, data for 25 patients
responders from non-responders following neoadjuvant chemotherapy
(median age 68 years; range 37–77) with metastatic lung cancer were
in stage III NSCLC. As compared to RECIST 1.1, EORTC seems to
retrospectively retrieved. All patients were treated with Nivolumab
be more appropriate for evaluation therapeutic response. Finally,
(therapeutic scheme: 240 mg every 2 weeks). PD-L1 expression was
post-TLG_N have a significant prognostic information.
available in 14/25 patients. All patients underwent 18F-FDG PET/CT
The Italian Association for Research on Cancer (AIRC—Associ-
before immunotherapy. Whole-body maximum standardized uptake
azione Italiana per la Ricerca sul Cancro) is acknowledged for the
value (SUVmaxwb), metabolic tumor volume (MTVwb) and total
support on research with the grant nr. 18923.
lesion glycolysis (TLGwb) were obtained as the sum of SUVmax,
MTV and TLG in all metabolic lesions. The best response to therapy
was considered in terms of partial response (PR), stable disease (SD)
and progressive disease (PD), based on clinical and radiological fol-
low-up.
Results: 18F-FDG PET/CT was positive in 23/25 patients (80%). The
majority of them had a pathological 18F-FDG uptake in lung, lymph
nodes and bones. SUVmaxwb, MTVwb, TLGwb were higher in patients
with a PD-L1 expression than those without. Sixteen patients had a

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S47

response to therapy (PR ? SD), while 9 did not (PD). SUVmaxwb Results: According to the pre-PET likelihood of malignancy, 47
was significantly higher in patients without a response to therapy than (13.2%) patients were at low, 277 (78%) at intermediate and 31
those with a response to immunotherapy (median: 63.56 vs. 22.13; (8.8%) at high risk of malignant SPN. Conversely, based on the post-
t-student test: p = 0.006). Similarly, also TLGwb and MTVwb were PET likelihood of malignancy, 85 (23.9%) were at low, 123 (34.6%)
higher in non-responder than the counterpart, although not statisti- at intermediate and 147 (41.5%) at high likelihood of malignant SPN.
cally significant. However, the difference was more evident in women Based on the standard of reference, 175 patients had a benign and 180
than men (median SUVmaxwb in responders and no-responders for a malignant SPN. In overall patients, the NRI was 78% (z = 10.0;
women and men: 39.88 vs. 85.89 and 21.92 vs. 51.67, respectively). p \ 0.0001) Out of 126 patients at intermediate pre-PET likelihood of
Conclusions: The entire tumor burden evaluated by 18F-FDG PET/ malignancy who had a benign SPN, 47 (37%) shifted in the low post-
CT can be predictive of response to immunotherapy in patients with PET likelihood. Moreover, out of the 151 patients at intermediate pre-
metastatic lung cancer. A large prospective multicenter trial is war- PET likelihood of malignancy who had a malignant SPN, 111
ranted in order to definitively assess the meaning of 18F-FDG PET/CT (73.5%) shifted in the high post-PET likelihood.
as a guide for immunotherapies. Conclusions: This study demonstrates that patients with a malignant
SPN are better stratified by an algorithm including 18F-FDG PET/CT
imaging than using only clinical/morphological variables. In fact, a
substantial number of patients considered at intermediate pre-PET
PO064 likelihood of malignancy are re-classified as at high or low risk, based
The role of 18F-FDG PET/CT over clinical data on the PET findings.
in patients with single pulmonary nodule (SPN): results
from the italian tailored assessment of lung
indeterminate accidental nodule (Italian) multicenter PO065
trial Radiomic features to differentiate lymphomas
from thymic mediastinal masses on baseline imaging
L. Evangelista16, L. Pace13, L. Mansi2, S. Pellegrino12, S. Del
Vecchio12, G. Pepe4, L. Basso10, D. Ripani15, M. Tredici7, A. M. Kirienko1, G. Ninatti1, L. Cozzi3, N. Gennaro4, F. Ricci2,
Chiaravalloti14, G. Storto3, L. Guerra8, L. Pavanello1, D. D’arienzo5, C. Carlo Stella1, P. Zucali2, A. Chiti1, M. Sollini1
P. Miletto9, A. Cuocolo12, A. Lambertini11, M. Spadafora6
1
1
Department of Biomedical Sciences, Humanitas University, Pieve
Azienda Universitaria Integrata di Verona, Verona, Italy. 2Centro Emanuele, Milan, Italy. 2Department of Oncology and Hematology,
Universitario di Ricerca per lo Sviluppo Sostenibile, Naples, Rome, Humanitas Cancer Center, Humanitas Clinical and Research Center,
Italy. 3CROB-IRCCS; Rionero in Vulture, Potenza, Italy. 4Humanitas Rozzano, Milan Italy. 3Radiotherapy, Humanitas Cancer Center,
di Milano, Milano, Italy. 5Medicina Futura Acerra, Napoles, Italy. Humanitas Clinical and Research Center, Rozzano, Milan, Italy.
6
Ospedale del Mare, Napoles, Italy. 7Ospedale di Bolzano, Bolzano, 4
Training Program in Radiology, Humanitas University, Pieve
Italy. 8Ospedale San Gerardo-AAST Monza, Monza, Italy. 9Ospedale Emanuele, Milan, Italy
san Giuseppe Moscati, Avellino, Italy. 10SDN-IRCCS, Napoles, Italy.
11
Università degli Studi di Bologna, Bologna, Italy. 12Università degli Background-aim: The present study aimed at evaluating the ability
Studi di Napoli ‘‘Federico II’’, Naples, Italy. 13Università di Salerno, of computed tomography (CT) radiomic features to classify anterior
Salerno, Italy. 14Università Tor Vergata di Roma, Roma, Italy. mediastinal masses as lymphomas or thymic neoplasms.
15
Universita’ Cattolica di Roma, Rome, Italy. 16Veneto Institute of Methods: A cohort of 110 patients (M:F = 47:63, median age 47.5,
Oncology IOV-IRCCS, Padua, Italy range 35–62) diagnosed with either thymic neoplasia or lymphoma
with at least one mediastinal localization [ 4 cm in size, and with
Background-aim: This study assessed the additional role of 18F- baseline non-contrast-enhanced CT imaging available at our institu-
FDG PET/CT over clinical/morphological data in the definition of tion, was retrospectively studied. The cohort was divided into a
likelihood of malignancy in patients with SPN. training and a validation group. Radiomic textural features (n = 41)
Methods: The study population included 355 consecutive patients were extracted using the LIFEx package. CT images were manually
with one or more SPN previously identified by CT images, defined as segmented using Eclipse software. Statistical analysis was performed
lung nodule with a size B 3 cm who were send to 18F-FDG PET/CT using the R platform. Imaging features were used as predictors in
for the characterization of the nodule/nodules. Patients with prior linear discriminant analysis (LDA) with backward stepwise variable
cancer history and those candidates to 18F-FDG PET/CT for the insertion to classify the lesions as lymphomas or thymic neoplasms.
staging of lung cancer were excluded. SPN malignancy risk was Additionally, an LDA model was built including radiomic and clinical
calculated by using the Brock University cancer prediction equation variables (age and sex). Pathology was used as reference standard.
(as pre-PET probability of malignancy) and the Herder Solitary Scoring metrics included sensitivity, specificity, accuracy and anal-
Pulmonary Nodule Malignancy Risk Calculator (as post-PET proba- ysis of the receiver operating characteristic (ROC) curves in terms of
bility of malignancy). According to the pre-PET and post-PET area under the curve (AUC).
likelihood of SPN malignancy, patients were classified into low- Results: Fifty-seven patients (27 males, 30 females) were affected by
likelihood (\ 5%), intermediate-likelihood (5–65%), and high-like- thymic neoplasia (3 thymic carcinoma, 54 thymoma) and 53 (20
lihood ([ 65%) subsets. The difference between correct and incorrect males, 33 females) by lymphoma (39 Hodgkin’s Lymphoma, 12 non-
reclassification according to patient outcome was defined as the net Hodgkin’s Lymphoma, 2 ns), median age of 61 (range 48-70) and 36
reclassification improvement (NRI). Final diagnosis of SPN was (range 26-46) years, respectively. LDA considering radiomic
established by histopathology and/or by other imaging data at follow- parameters only, selected 12 CT radiomic features. In the training
up. Assuming independence between individuals with benign or group, sensitivity, specificity, accuracy and AUC of the model
malignant SPN and following McNemar’s logic for significance resulted 0.85 ± 0.06, 0.94 ± 0.04, 0.90 ± 0.06 and 0.94 ± 0.06,
testing in correlated proportions, a simple asymptotic test for the null respectively; in the validation group, sensitivity, specificity, accuracy
hypothesis of NRI = 0 was used (z test). and AUC resulted 0.73 ± 0.07, 0.83 ± 0.05, 0.77 ± 0.07 and
0.85 ± 0.06, respectively. LDA derived from clinical ? radiomic

123
S48 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

parameters selected 1 clinical variable (age) and 8 radiomic features. Constrast_NGLDM (CI 0.52–0.85; P = 0.048) and 0.71 for
In this model, in the training group sensitivity, specificity, accuracy LZE_GLZLM (CI 0.55–0.87; P = 0.014). Considering CT features
and AUC resulted 0.80 ± 0.07, 0.94 ± 0.04, 0.87 ± 0.06, the areas under the ROC curves for the ability to predict response
0.94 ± 0.07, respectively, while in the validation group the same were for 0.67 for SRHGLE_GLRLM (CI 0.5–0.84; P = 0.071) and
metrics resulted 0.73 ± 0.08, 0.89 ± 0.05, 0.80 ± 0.08 and 0.69 for SZE_GLZLM (CI 0.51–0.86; P = 0.045).
0.91 ± 0.08, respectively. Conclusions: Textures in baseline 18F-FDG PET/CT scans, mea-
Conclusions: CT radiomic features have the potential to differentiate sured by Volume_SHAPE, Correlation_GLCM, Contrast_NGLDM
at baseline between lymphomas and thymic masses, sparing the use of and LZE_GLZLM, on PET images and SRHGLE_GLRLM and for
invasive diagnostic procedures. SZE_GLZLMN on CT images are associated with no response to
neoadjuvant chemotherapy in stage IIIA NSCLC. This association
suggests that textural image features may provide predictive infor-
mation that offer promise for personalized medicine in which patients
PO066 might be stratified before therapy, with the potential to reduce inef-
Radiomics analysis with 18F-FDG PET/CT fective treatments
for prediction of response to neoadjuvant
chemotherapy in stage IIIA non-small cell lung cancer
PO067
A. Lorenzoni2, M. Imbimbo3, A. Capozza1, C. Chiesa1, G. Marina3, Prediction of response to immune checkpoint inhibitor
A. Alessi1, E. Seregni1
therapy by FDG PET
1
PET Unit, Istituto Nazionale dei Tumori, Milan, Italy. 2PET Unit,
Istituto Nazionale dei Tumori, Milan, Italy. 3Unit of Thoracic K. Massri1, L. Dellavedova1, R. Stoico1, A. Calcagno2, L. Maffioli1
Oncology, Istituto Nazionale dei Tumori, Milan, Italy 1
Nuclear Medicine Department, ASST Ovest Milanese, Legnano
Background-aim: Stage IIIA non-small cell lung cancer (NSCLC) (MI), Italy. 2Oncology Department, ASST Ovest Milanese, Legnano
comprises an heterogeneous group of cancers. In potentially (MI), Italy
resectable disease neoadjuvant chemotherapy, aiming at improving
surgical resection rates, can be offered. However about half of these Background-aim: The purpose of this study was to determine the
patients do not obtained adequate response and sequential radiother- clinical usefulness of PET-CT in evaluating the response to Immune
apy (RT) is often administered, resulting in an undertreatment. Checkpoint Inhibitor Therapy (ICT) in patients with metastatic mel-
Nowadays there are no clinical, histological nor imaging character- anoma or lung cancer. We compared the results with the standard
istics that can predict which patients may benefit from neoadjuvant evaluation made with CT-scan.
chemotherapy. The aim of our retrospective study was to determine Methods: We prospectively collected data from 43 patients with
the association of textural features derived from baseline18F-FDG metastases (21 with melanoma and 22 with lung cancer). All patients
PET/CT images and induction chemotherapy response in stage IIIA underwent 18F-FDG-PET imaging at baseline and 4 months after ICT
NSCLC. treatment. FDG-PET response was assessed by three criteria: Total
Methods: Forty-one patients (mean age 65y; 32 men, 9 women) who Lesion Glycolysis (TLG), EORTC criteria and PET Response Criteria
underwent pre-treatment 18F-FDG PET/CT were enrolled. Response in Solid Tumors (PERCIST). We compared these results with those
was assessed by CT according to RECIST criteria. The volume of obtained by diagnostic CT imaging with Response Evaluation Criteria
interest (VOI) of the primary tumor lesion was semi-automatically in Solid Tumors (RECIST 1.1). We used the SUL peak (Standard
defined on PET images with a threshold of 40% of the SUVmax using Uptake Lean Body Mass) to assess the study by the PERCIST criteria.
a commercial software (PET VCAR, GE Healthcare, Waukesha, WI, Then, we measured the SUVmax to assess the response following the
USA). If the VOI did not cover the tumour visually, threshold was EORCT criteria. TLG was calculated as: TLG = mean SUV 9 MTV
lowered; when the VOI incorporated adjacent structures, manual (cm3).
adjustment was employed. Textural features were calculated on both ROC analysis and Spearman’s test were calculated to define the
CT and PET images within the same VOI. Features were extracted response to therapy: SUL peak, SUVmax and TLG were compared to
using the LifeX package and included first order (conventional indi- percentage change in the sum of the longitudinal diameter (SLD) in
ces, histogram- and shape-based parameters) and second and high target lesion from a CT scans.
order features. Statistical analysis was performed using the R plat- Results: TLG showed the strongest correlation to SLD (R = 0.936,
form. Radiomic features (45 for CT and 47 for PET images) were p = 0.003), compared to SUV max (R = 0.827, p = 0.009) and SUL
compared in non-responders (stable disease/progressive disease) and peak (R = 0,818 p = 0.010). Two-tailed p-values \ 0.05 were con-
responders (complete response/partial response) groups. Areas under sidered statistically significant.
the receiver-operating-characteristic (ROC) curves were calculated to To predict progression on CT-scans, ROC analysis showed the best
assess the accuracy in predicting response to neoadjuvant results for TLG in comparison with the other criteria: area under the
chemotherapy curve (AUCs) resulted between 0.78 and 1.0. TLG had the highest
Results: According to CT RECIST, there were 16 non-responders and value of 1.0 (95% confidence interval (CI) 0.71–1).
25 responders. Response to induction chemotherapy was not associ- Conclusions: The present study demonstrates that to evaluate ICT
ated with SUV parameters, MTV, and TLG. Considering PET response in patients with metastatic cancer, criteria based on TLG
parameters the areas under the ROC curves for the ability to predict allow to obtain better results than those obtained by PERCIST and
response were 0.6 for Volume_SHAPE (CI 0.5–0.83; P = 0.08), 0.71 EORTC criteria.
for Correlation_GLCM (CI 0.55–0.87; P = 0.024), 0.69 for

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S49

PO068 comparable PTV’s Homogeneity and Conformity Index. The use of


The use of perfusion SPECT to preserve functional lung perfusion SPECT would allow clinicians to potentially reduce lung
toxicity, permitting a dose escalation.
in radiotherapy planning for NSCLC patients

G. Rovera2, M. Zollino1, A. Giordano2, V. Valenza2


PO069
1
Foundation University Hospital A. Gemelli IRCCS, Rome, Italy. Post-treatment evaluation of patients with small-cell
2
Nuclear Medicine Unit, Department of Diagnostic Imaging, lung cancer: prognostic role of 18F-FDG PET/CT
Radiation Oncology and Hematology, Foundation University Hospital
A. Gemelli IRCCS, Rome, Italy
C. Altini1, A. Niccoli Asabella1, T. Masi1, N. Addante1, A. Di Palo1,
Background-aim: Single Photon Emission Computed Tomography/ G. Sigrisi1, A. Cimino1, M. Fanelli1, G. Rubini1
Computed Tomography (SPECT/CT) can be used to avoid the high
perfusion areas in radiotherapy planning for non-small-cell lung 1
Nuclear Medicine Unit, Interdisciplinary Department of Medicine,
cancer (NSCLC) patients not eligible for surgery, in order to poten- University of Bari ‘‘Aldo Moro’’, Bari, Italy
tially reduce lung toxicity. The aim of this study is to compare two
different 3D-conformal treatment plans, with and without SPECT/CT Background-aim: To determine the prognostic value of post-treat-
data. ment 18F-FDG PET/CT in patients with Small-cell Lung cancer
Methods: SPECT/CT perfusional scans were performed in nine (SCLC).
patients using the Siemens Symbia Intevo tomograph after intra- Methods: Forty-eight patients (40 males and 8 females; mean age
venous injection of 148 MBq of 99mTc-labeled macroaggregated 64.48 years, range 48-86) with histologically proven SCLC and post-
albumin, using low energy - high resolution collimators. Projections treatment 18F-FDG PET/CT scan were retrospectively reviewed.
were acquired with step and shoot method at discrete 3 angular 32/48 (66.7%) had the SCLC peripherical form while 16/48 (33.3%)
intervals with each camera head rotating through 180 for a total of 60 had the central form; 14/48 (29.2%) performed combined Chemo-
views (30 s). Images were acquired with a 128 9 128 matrix and a Radiotherapy treatment while 34/48 (70.8%) had chemotherapy only.
zoom factor of 1.00. All scans were carried out with free breathing, Presence of primary tumour (T), pathological lymph-nodes (N) and
and had sufficient coverage to include the total lung volume. The CT metastasis (M) was evaluated for each patient. The clinical endpoints
and SPECT scans were co-registered for the purposes of attenuation were overall survival (OS) and progression-free survival (PFS) and
correction and a more precise anatomical localization of scintigraphic the last follow-up was in January 2018. The survival time was esti-
findings. mated using Kaplan–Meier method, and the difference between
SPECT images were used to define dysfunctional lung regions, groups was assessed using log-rank tests. A multiple Cox’s propor-
caused by tumor or other conditions such as chronic obstructive tional hazard model was performed for 18F-FDG PET/CT results and
pulmonary disease. Functional lung volumes were classified in three clinical variables (age B 65 years/[ 65 years, male/female and cen-
groups according to their relative tracer uptake in SPECT/CT images: tral/peripheral SCLC). p \ 0.05 was considered statistically
Low Perfusion (LP 0–40%), Medium Perfusion (MP 40–70%) and significant.
High Perfusion (HP 70–100%). Results: All 18F-FDG PET/CT resulted positive for at least one
Two different 3D-conformal plans, with co-planar e non co-planar pathological lesion. 41/48 (85.4%) patients were positive for T and
fields, were simulated: one according to non-functional lung infor- 7/48 (14.6%) were negative; 28/48 (58.3%) were positive for N and
mation (Anatomic Plan, A), the other one using the SPECT perfusion 20/48 (41.7%) were negative; 9/48 (18.8%) were positive for M and
area geometries (Functional Plan, F). Each plan was performed with 39/48 (81.3%) were negative. At the end of the follow-up 39/48
Varian Eclipse treatment plan System and calculated with Anisotropic (81.3%) patients were alive while 9/48 (18.8%) were dead. Median
Analytical Algorithm (version 10.0.28) and the total dose delivered OS was 20 months (range 5-128), median PFS was 22 months (range
amounted to 50,4 Gy in 28 fractions. 2-128). We compared OS and PFS for the T, N and M. OS resulted
Results: A Dose-Volume Histogram (DVH) was used to evaluate the statistically different for N (log rank = 7.819; p = 0.005) and M
dose to the target and to the organs at risk. F plans produced a sig- parameters (log rank = 9.609; p = 0.002). Mean OS in N negative
nificant reduction of dose in HP areas, in particular the V20Gy HP patients was 121 months, while in N positive patients was 67 months;
values were reduced from 15% to 8% (p = 0.046), while the V20Gy mean OS in M negative was 98 months, 49 months in M positive.
homolateral HP values decreased from 38% to 22% (p = 0.028) and PFS resulted statistically different for N (log rank = 5.446; p = 0.02)
the Dmean homolateral HP varied from 16 to 12 Gy (p = 0.039). The and M parameter (log rank = 1.021; p \ 0.001). Mean PFS in N
reductions of V20Gy HP and V20Gy homolateral HP areas were about negative patients was 87 months, while in N positive patients was
50% (from 46 to 60%). Finally, there were no significant differences 34 months; mean PFS in M negative was 68 months, 18 months in M
in the heart Dmean, V38Gy and V42Gy, esophagus Dmean, V35Gy and positive. Cox’s analysis showed statistical significance only for N
V50Gy, spinal canal Dmax and Planning Target Volume (PTV) parameter (HR = 11.66).
Homogeneity and Conformity Index. Conclusions: Post-treatment 18F-FDG PET/CT is a fundamental tool
Conclusions: With Functional Plans, it is possible to avoid HP areas in the post-treatment evaluation of SCLC patients. In particular, the
and reduce dose in the HP regions of healthy lung, especially in identification of lymph-nodes involvement is related to a poorer
homolateral lung. This goal is achieved without worsening DVH’s prognosis in term of OS and PFS.
constrains in Spinal Canal, Esophagus and Heart, and with

123
S50 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

PO070 PO071
Visual versus quantitative evaluation glucose FDG Italian multicentre study on the utility of FDG-PET/CT
uptake in patients enrolled in a ‘‘coordinated in small cell lung carcinoma
and complex ambulatory care path’’ (PACC)
N. Quartuccio9, L. Evangelista6, F. Caobelli2, C. Altini13, A.
2 2 2
V. Vergura , F. Linguanti , E. Abenavoli , A.M. Grosso , 3 Lambertini8, I. Schorlin14, C.E. Popescu7, S. Margotti16, L. Cuppari6,
L. Voltolini4, R.M. Piperio1, C. Gallini2, V. Briganti2, R. Laudicella3, A.N. Asabella13, G.M. Lima8, S. Pacella7, L.
M. Matteini2, E. Costanzo2, L. Vaggelli2, R. Sciagra’2 Sturiale3, A. Vento3, D. Cardile3, A. Ciaccio12, A. Kokomani12, F.
Linguanti12, G. Di Pierro15, S. Scalisi4, F. Scalorbi5, S. Panareo17, A.
1
Interventional Pulmonology, Careggi University Hospital, Florence, Cistaro16, S. Baldari3, S. Fanti8, G. Rubini13, P. Alongi4, O.
Italy. 2Nuclear Medicine Unit, Careggi University Hospital, Florence, Schillaci10, A. Chiaravalloti11, W.G. Young Aimn1
Italy. 3Pulmonary Pathophysiology, Careggi University Hospital, 1
Florence, Italy. 4Thoracic Surgery, Careggi University Hospital, AIMN (Italian Association of Nuclear Medicine), Milan, Italy.
2
Florence, Italy Clinic of Radiology and Nuclear Medicine, University Hospital
Basel, University of Basel, Basel, Switzerland. 3Department of
Background-aim: In our hospital a ‘‘Coordinated and Complex Biomedical and Dental Sciences and Morphofunctional Imaging,
Ambulatory Care Path’’ (PACC) multidisciplinary group, made up of Nuclear Medicine Unit, University of Messina, Messina, Italy.
expert specialists, was established for the pulmonary nodule (PN) 4
Department of Radiological Sciences, Nuclear Medicine Service,
treated in day service. According to the diagnostic path, oncologists Fondazione Istituto G. Giglio, Cefalu. Italy. 5Division of Nuclear
normally send patients to fluorine-18-deoxyglucose ([18F]-FDG) Medicine, European Institute of Oncology, Milan, Italy. 6Nuclear
positron emission tomography/computed tomography (PET/CT) Medicine and Molecular Imaging Unit, Veneto Institute of Oncology
when PN presents uncertain morphological characteristics on CT. IOV, IRCCS, Padua, Italy. 7Nuclear Medicine Department, Niguarda
This study analyzed the diagnostic accuracy of maximum standard- Ca’ Granda Hospital, Milan, Italy, Milan, Italy. 8Nuclear Medicine
ized uptake value (SUVmax) compared to visual qualitative analysis Department, S.Orsola-Malpighi Hospital, University of Bologna,
in FDG PET/CT made by expert specialists for the evaluation of Bologna, Italy. 9Nuclear Medicine Unit, ARNAS PP.OO. ‘‘Civico, Di
solitary PN in patients enrolled in PACC. Cristina e Benfratelli’’, Palermo, Italy. 10Nuclear Medicine Unit,
Methods: Retrospective analysis of 113 consecutive PACC patients Department of Biomedicine and Prevention, University Tor Vergata,
submitted to PET/CT between January 2017 and August 2018 for PN Rome, Italy. 11Nuclear Medicine Unit, Department of Biomedicine
evaluation. PN were visually evaluated for location, size, and quali- and Prevention, University Tor Vergata, Rome, Italy; IRCCS
tative distribution of radiopharmaceutical uptake, and semi- Neuromed, Pozzilli (IS), Italy. 12Nuclear Medicine Unit, Department
quantitative analysis with SUVmax calculated and compared to of Experimental and Clinical Biomedical Sciences ‘‘Mario Serio’’,
SUVmax on a liver region of interest. PN with SUVmax higher than University of Florence, Florence, Italy. 13Nuclear Medicine Unit,
SUVliver were classified as malignant. The PET/CT results were Department of Interdisciplinary Medicine, University of Bari ‘‘Aldo
correlated with other predictors of malignance (age, gender, smoking Moro’’, Bari, Italy. 14Nuclear Medicine Unit, Ospedale di Circolo e
status, PN size and location). The definitive diagnosis was established Fondazione Macchi di Varese, Varese. 15Oncology Unit, University
by histopathology or by clinical/radiological follow-up for at least one of Florence, Florence, Italy. 16Positron Emission Tomography Centre,
year. IRMET S.p.A., Affidea, Turin, Italy. 17Unit of Nuclear Medicine,
Results: 20 of the 113 patients presented metastatic pulmonary Department of Diagnostic Imaging, S. Anna University Hospital,
nodules and were excluded from further analysis. Of the remaining Ferrara, Italy
93, 79 (86%) patients had malignant PN, whereas 14 (15%) patients
had benign PN. The average PN diameter was 31.40 ± 20.3 mm Background-aim: Small cell lung cancer (SCLC) is an uncommon
(range: 5.6–100 mm), and nodule diameter correlates significantly and dramatically aggressive type of lung cancer (accounting for
with malignancy (Spearman Rho = 0.346; p \ 0.001). 15–20% of all pulmonary neoplasms) with median survival less than
In visual analysis there were 77 true-positive (VP), 4 false-positive 1 year. Since SCLC presents high rate of recurrences locally or
(FP), 10 true-negative (VN), and 2 false-negative (FN). In semi- regionally it is important to discriminate between presence and
quantitative analysis there were 69 VP, 7 FP, 7 VN, and 10 FN. absence of active metabolic disease after initial treatment in order to
The sensitivity of PET/CT for diagnosing of malignant PN was address the correct patient management. The aims of this work were:
significantly greater for visual analysis than for semi-quantitative (1) the evaluation of prognostic information provided by [18F]FDG-
analysis (97% vs. 87%, respectively, p \ 0.05). PET/CT findings, including semiquantitative FDG-derived parame-
Specificity and accuracy were lower with SUVmax (71% and 93% ters, in terms of overall survival (OS) and progression-free survival
vs. 50% and 81%, respectively). (PFS) in patients with SCLC at restaging after treatment and (2) the
FN results were more frequent using SUVmax than visual analysis assessment of the additional value of [18F]FDG PET/CT compared to
(10 vs. 2 respectively). NPV for visual analysis showed a trend to be conventional imaging.
higher than for SUVmax (83% vs. 41%, p = 0.05). Methods: Databases of 10 Italian nuclear medicine departments were
Conclusions: Although FDG PET/CT demonstrates an accurate interrogated to identify patients with history of SCLC and an avail-
diagnostic role in detecting lung cancer within PN, FN may occur able [18F]FDG-PET/CT scan at restaging after chemotherapy,
because of small PN dimensions or low FDG uptake in some radiotherapy or chemo-radiotherapy. [18F]FDG-PET/CT scans were
malignant lung neoplasms. The current results indicate that within a examined to identify presence of local lymph node or distant recur-
multidisciplinary group made up of expert specialists, visual analysis rences. For each lesion, maximum and mean standardized uptake
performed by an experienced observer can be superior to the finding (SUVmax and SUVmean) were calculated and volume-based meta-
of a SUVmax lower or equal than liver uptake, particularly in small bolic parameters [Metabolic tumor volume = MTV and Total lesion
lesions or PN with non-focal morphological appearance. glycolysis = TLG] were derived using commercial software gener-
ating an isocountour volume of interest (VOI) by means of a threshold
of 40% of the maximum pixel activity. Univariate and multivariate
analyses were used to investigate the relationship between outcome

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S51

(OS and PFS) and patient variables. Kaplan–Meier curves were 18F-FDG-PET/CT findings, after at least 90 days of PT, where
computed to assess the impact of metastatic lesions detected by dichotomized in favorable (no significant uptake) and unfavorable
[18F]FDG PET/CT on OS and PFS. Significance of difference (focal uptake or rim plus focal uptake corresponding to site of original
between the curves was assessed by Cox regression analysis lesion).
(p \ 0.05). Additional findings by other imaging (high-resolution In 7 patients (58.3%), there was no evidence of pathological areas,
CT), carried out within 3 months from [18F]FDG PET/CT, were expression of complete response.
retrieved. Diagnostic agreement was evaluated comparing the number In the remaining 5 patients (41.7%) there was residual disease, 3
of metastases depicted by each the imaging modality in a patient- of which with equivocal CT scan due to evidence of post-ablation
based analysis. mass larger than original lesion (metastatic lesions 20%; primary
Results: Amongst a total of 164 patients with SCLC, patients with malignancies 80%), and therefore 4 of them were retreated with PT
evidence of metastatic lesions at PET imaging presented a signifi- and 1 with radiotherapy.
cantly shorter OS (p value \ 0.039) and PFS (p value \ 0.001) With a median follow-up of 12 months no relapse was observed
compared to patients without lesions. At univariate analysis, PFS by 18F-FDG PET/CT.
resulted significantly shorter in patients with presence of metastases at Pre-PT SUV max (cut-off 4) ad lesion size (cut-off 2 cm) were not
PET imaging (p \ 0.001). Conventional imaging was available in 119 associated with risk of recurrence (P = 0.55).
patients. In 52 (43.7%) cases PET/CT and CT demonstrated the same Conclusions: PET/CT is crucial for disease initial staging to deter-
number of lesions. In 35 (29.4%) cases PET/CT showed additional mine if PT should be performed.
lesions compared to CT, whereas in 32 patient (26.9%) CT evidenced It is also useful to determining the appropriateness of treating pul-
more lesions than PET/CT. monary malignancies by restaging patients, because early detection of
Conclusions: Evidence of metastatic lesions at [18F]FDG PET/CT recurrence is important to allow for PT retreatment or other
imaging at restaging has a strong influence on OS and PFS of patients treatments.
with SCLC. [18F]FDG PET/CT and CT seem to be complementary PET/CT has proven to be more accurate in detecting residual or
imaging modalities in patients with metastatic SCLC. recurrent disease compared with CT alone in the follow-up period.

PO072 PO073
Role of 18F-FDG PET/CT in patients treated One year experience with SPECT/CT: pictorial essay
with percutaneous pulmonary tumor ablation
F. Calabria2, M. Leporace2, A. Lanzillotta2, A. Bagnato1
1 2 2 2
P. Moda , A. Briatico Vangosa , D. Monaco , E. D’ettorre , 1
F. Lauriero1 Department of Nuclear Medicine and Theranostics, Mariano Santo
Hospital, Cosenza, Italy. 2Department of Nuclear Medicine and
1
Nuclear Medicine Unit, PET/CT Centre, Hospital ‘‘G. Moscati’’, Theranostics, Mariano Santo Hospital, Cosenza, Italy
Taranto, Italy. 2Radiology Unit, Hospital ‘‘G. Moscati’’, Taranto, Italy Background-aim: Single Photon Emission Computed Tomography/
Background-aim: Percutaneous thermal ablation (PT) is a potentially Computed Tomography (SPECT/CT) with CT scanner of newer
curative option for patients with primary malignancies or metastatic generation is a recent addition in the diagnostic panorama of hybrid
lesions in the lung that cannot undergo other treatments, for comor- imaging. In fact, novel hybrid SPECT/CT scanners allow higher
bidity reasons, or because they refuse surgery. quality anatomic imaging, which can significantly improve functional
The aim of this study was to evaluate the utility of 18F-FDG PET/CT data. Our aim was to describe a 1-year-experience with a SPECT/CT
in the initial staging and restaging of patients treated with PT. scanner of newer generation in the department of nuclear medicine of
Methods: 12 patients (4 females and 8 males), mean age 73 years our regional hospital.
(range 58-84 years), with CT evidence of suspicious pulmonary Methods: From October 2017 to October 2018 we performed
lesions, underwent simultaneously needle biopsy and PT (7 primary SPECT/CT scans in 84 patients examined by 131I whole body scans,
malignancies and 5 metastatic lesions) and followed for 12 months 99mTc-MDP bone scans and parathyroid imaging with 99mTc-MIBI.
after treatment. The SPECT and CT images were acquired during a single, approxi-
All patients, fasted for at least 6 h and with plasma glu- mately 40-min-long imaging session.
cose \ 200 mg/dl, underwent to a baseline PET/CT total body Results: Higher quality anatomic imaging, and higher soft-tissues/
60 min after intravenous injection of 4 MBq/kg 18F-FDG. bone contrast provided by the CT component of the exam signifi-
Images analysis was carried out visually and by semiquantitative cantly improved diagnostic accuracy in selected cases. In particular,
determination calculating the maximum standardized uptake value the added value of CT allowed to identify false positive cases in
(SUV max) of each lesion. 99mTc-MDP bone scans (osteophytosis and fractures, lytic lesions
The unidimensional maximum diameter of the lesion was recorded non tracer-avid), false positive cases with 131I whole body scan
on diagnostic CT scan before PT. (bronchiectasis 131I-avid and other inflammatory findings) while
All patients were re-examinated after at least 90 days, to limit parathyroid imaging was improved with the exact localization of
false positive results due to inflammation, to evaluate structural parathyroid adenomas, presenting as foci of focal uptake at SPECT
appearance of the lung lesions after PT and, when available, the SUV imaging. In a single case examined by 99mTc-MDP bone scan for
max in postablation scans. restaging prostate cancer, a focal area of uptake, higher than sur-
Association of SUV max and lesion size with local recurrence was rounding background of radio-urine, was detected in the left lateral
calculated with Chi2 Test. wall of the bladder; SPECT/CT allowed to recognize this finding as
Results: All 12 patients had single area of pathological FDG uptake associated to a bladder lesion with calcifications: histological exam
in the lungs at baseline PET/CT examination (2.3 \ SUV max \ diagnosed bladder cancer.
15.7), and subsequently underwent to CT guided PT after evaluation Conclusions: Our pictorial essay provides interesting cases showing
of tumor size (8 mm \ size \ 35 mm; mean diameter 20.33 mm) the usefulness of SPECT/CT. SPECT/CT provides complementary,
and distance from thoracic surface for correct length needle selection. not redundant, information because sites of abnormal tracer uptake on

123
S52 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

the SPECT images can be anatomically localized on CT, anatomic of renal toxicity in re-challenge patients is not higher than previously
abnormalities on the CT images can draw attention to subtle abnor- reported.
malities of tracer uptake on SPECT, a lesion discovered on a
preceding diagnostic imaging study can be shown to precisely match
the area of abnormal radiopharmaceutical uptake on SPECT, and
combined SPECT/CT can improve test specificity by reducing the PO075
uncertainties associated with low-resolution SPECT alone. Our data Complete response in a pancreatic NEN with liver
and collection of clinical cases eloquently show how hybrid imaging metastasis after PRRT in association with lanreotide
with SPECT/CT can be a valid support for nuclear physicians during
autogel/depot
the routinely activity of traditional nuclear imaging of a regional
hospital.
R. Laudicella2, F. Minutoli2, R. Filice2, L. Baratto1, A. Vento2,
S.A. Pignata2, D. Cardile2, B. Pagano2, S. Baldari2
1
PO074 Division of Nuclear Medicine and Molecular Imaging, Department
PRRT retreatments: renal function evaluation of Radiology; Stanford University; Stanford, CA (USA). 2Unit of
Nuclear Medicine, Department of Biomedical and Dental Sciences
and Morphofunctional Imaging, University of Messina, Messina Italy
A. Vento1, R. Laudicella1, F. Minutoli1, A.D. Comis1, R. Filice1,
S.A. Pignata1, F. Quattrocchi1, A. Campennı̀1, S. Baldari1 Background-aim: Therapeutic options in progressive neuroendocrine
neoplasm (NEN) are quite limited. Peptide receptor radionuclide
1
Department of Biomedical and Dental Sciences and Morpho- therapy (PRRT) with somatostatin analogues is an effective treatment
Functional Imaging, Nuclear Medicine Unit, University of Messina, option in patients with pancreatic NEN (pNEN) with unre-
Messina, Italy sectable liver metastases.
Methods: We present a case of a 73-year-old male patient, reporting
Background-aim: Peptide receptor radionuclide therapy (PRRT) is a
the sudden appearance of rapidly escalating symptoms characterized
well-established option for patients with metastatic and/or inoperable
by asthenia, nausea and vomiting; the instrumental investigations—
neuroendocrine neoplasms (NEN). Nevertheless, due to the mainly
ultrasound (US), contrast-enhanced CT (eCT), PET with 68Ga-
renal excretion of the tracer, renal toxicity is the most restrictive
DOTATOC and 18F-FDG—in association with the laboratory data
factor over time. We retrospectively evaluated the renal toxicity of
(high chromogranin A level), supported the diagnostic hypothesis
PRRT salvage therapy in patients affected by NEN.
confirmed later on histological examination, of G2-pNEN (Ki67 =
Methods: 10 patients (7 male and 3 female, mean age 56,7y, range
3.5%) with infiltration of peripancreatic adipose tissue, vascular
43-75) with NEN (4 pancreatic, 2 ileal, 2 of unknown origin, 1
invasion and neoplastic thrombosis even in the lienal vein. Surgical
meningioma and 1 pulmonary) with progressive disease, who had
treatment—pancreatic tail resection and splenectomy—was per-
benefit from previous PRRT (at least stable disease, according to
formed, but after 6 months the presence of hepatic localizations was
RECIST 1.1 criteria), were selected for re-treatment. 8/10 suffered
observed. The patient (ECOG PS = 0) underwent PRRT with 177Lu-
from comorbidities (6 hypertension, 4 diabetes, 2 dyslipidemia). The
DOTATOC intravenous infusion administered every 6 to 8 weeks, in
cohort underwent at least two PRRT (range 2–4) between 01.02.2006
association with somatostatin analogues—Auto-gel/Depot lanreotide
and 01.10.2017 with high activities of 90Y-, 177Lu- and/or 111In-
(LAN) 120 mg subcutaneous—every 28 days.
labelled peptides. Totally were administered 83 cycles (41, 21, 21
Results: In the presented clinical case, 16 months after the end of 5
with 90-Yttrium, 177-Lutetium and 111-Indium, respectively) and the
cycles of PRRT (cumulative activity equal to 27.97 GBq, activity
activity range for each cycle was 0.93–7.4 GBq (1.11–2.405 GBq,
range 3.75–7.3 GBq) we observed complete response (CR) to treat-
1.75–7.4 GBq, 0.93–7.4 GBq for 90Y, 177Lu, 111In, respectively).
ment with disappearance of documentable disease in instrumental
Intravenous infusion of amino acids was administered at each cycle of
investigations (US, post-dose scintigraphy, eCT, PET 68Ga-DOTA-
PRRT in order to reduce tubular peptide’s uptake, minimizing renal
TOC), laboratory value (Chromogranin A normalized), clinical
impairment. Renal function was assessed trough 99mTc-DTPA GFR
observation (disappearance of the symptomatology associated with
measurements. We compared GFR % variations after each PRRT and
weight gain) in the absence of hematological and renal toxicity.
for each radiopharmaceutical. GFR values before the beginning and
Conclusions: At the state of the art, the CR in patients with NEN is
after last PRRT were also compared.
sporadic and in most series completely absent. Data from literature
Results: Baseline GFR ranged from 50 to 113 ml/min (mean value
show better results in pNENs (CR in 8% of cases—Sansovini et al.,
82,9 ml/min) and from 40 to 152 ml/min at last follow-up (mean
2013) [1]. We also believe that the reduced lesion load at enrollment
value 72.9 ml/min). According to Cyto-toxic criteria (CTC), at
and the therapeutical association between PRRT and Autogel/Depot
baseline 4/10 patients had grade 1 and 6/10 had grade 2 nephrotox-
LAN can contribute to mantain the complete response of our case
icity. At last follow-up, we did not record any case of severe
report PRRT.
nephrotoxicity (grade 3–4) otherwise 9/10 had grade 2 (moderate
Reference
nephrotoxicity). At baseline, according to chronic kidney disease
[1] Sansovini M, Severi S, Ambrosetti A, Monti M, Nanni O, Sarnelli
classification (CKD), 5/10 had normal GFR value, 3/10 had stage 2
A, Bodei L, Garaboldi L, Bartolomei M, Paganelli G. Treatment with
and 2/10 had stage 3. At last follow-up, 3/10 had still normal GFR
the radiolabelled somatostatin analog Lu-DOTATATE for advanced
value, 2/10 had stage 2, 5/10 had stage 3 toxicity. In our cohort, we
pancreatic neuroendocrine tumors. Neuroendocrinology.
did not record any grade 4 (severe impairment) or 5 toxicity (renal
2013;97(4):347–54. https://doi.org/10.1159/000348394. Epub 2013
failure). No statistically significant difference of GFR before and after
May 22. PubMed PMID: 23392072.
treatments was found; no statistically significant difference between
GFR% variations before and after treatments using different radio-
pharmaceuticals was found. Interestingly, renal toxicity trend seems
to reduce with progressive PRRT.
Conclusions: PRRT salvage therapy is a tolerable and feasible option
in patients with a good response after initial therapy. The occurrence

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S53

PO076 PO077
Incremental value of SPET/CT in disease staging Preoperative risk assessment in pancreatic
after ablative treatment of glandular residues neuroendocrine neoplasms: role of dual tracer 68GA-
with radioiodine in patients with differentiated thyroid DOTATOC and 18F-FDG PET/CT
carcinoma
P. Mapelli5, M. Salgarello1, S. Partelli6, J. Doraku1, F. Muffatti3,
2 2 2
A. Muni , H. Rouhanifar , L. Tommasi , E. Pomposelli , 2 S. Pasetto1, P. Rancoita4, V. Andreasi6, L. Gianolli2, M. Falconi6,
M. Muratori2, R. Russo2, G. Cuccu2, D. Valentini1 M. Picchio5
1
1
Health Physic Unit ‘‘SS. Antonio e Biagio e C. Arrigo’’ Alessandria Department of Nuclear Medicine, IRCCS Sacro Cuore Don Calabria
Hospital, Alessandria, Italy. 2Nuclear Medicine Unit ‘‘SS.Antonio e Hospital, Negrar, Italy. 2Nuclear Medicine Department, IRCCS San
Biagio e C. Arrigo’’ Alessandria Hospital, Alessandria, Italy Raffaele Scientific Institute, Milan, Italy. 3Pancreatic Surgery Unit,
Pancreas Translational & Clinical Research Centre, IRCCS San
Background-aim: Patients with thyroid differentiated carcinoma Raffaele Scientific Institute, Milan, Italy. 4University Centre of
treated with radioiodine for the ablation of thyroid residues after Statistics in the Biomedical Sciences, Vita-Salute San Raffaele
surgery are usually subjected, after 4–7 days from the administration University, Milan, Italy. 5Vita-Salute San Raffaele University, Milan,
of radioiodine, to a total body scintigraphy, exploiting the residual Italy; Nuclear Medicine Department, IRCCS San Raffaele Scientific
radioactivity for the staging of the disease after treatment. Commonly Institute, Milan, Italy. 6Vita-Salute San Raffaele University, Milan,
the images are integrated with planar projections on the neck, site of Italy; Pancreatic Surgery Unit, Pancreas Translational and Clinical
thyroid residues, and eventually on those parts of the body that show Research Centre, IRCCS San Raffaele Scientific Institute, Milan, Italy
indeterminate accumulations of radioiodine.
Methods: For 2 years now, our nuclear medicine service has a Background-aim: To investigate the predictive role of 68Ga-
modern SPET/CT tomograph that allows hybrid imaging with DOTATOC and 18F-FDG PET/CT derived parameters in patients
tomographic techniques. In his time we have assessed how the new affected by pancreatic neuroendocrine neoplasms (PanNENs) candi-
techniques are able to increase the diagnostic accuracy of post- date to surgery, in order to delineate a possible imaging risk profile,
treatment scintigraphy in patients with differentiated thyroid with specific focus on lymphnodal status and histological features of
carcinoma. aggressive behaviour.
From 1 January to 31 October 2018 we treated 112 patients with Methods: This is a retrospective study including 61 patients (38
radioiodine, 95 of whom were admitted for the ablation of glandular males, 23 females; mean age: 58.4 years, range 15–84), who under-
residues after total thyroidectomy for differentiated thyroid carci- went both to 68Ga-DOTATOC and to 18F-FDG PET/CT before
noma. The staging scintigraphy after therapy was performed on each surgery for PanNEN between 2011 and 2017, at Sacro Cuore Don
of these patients 3–6 days after administration of the therapeutic dose Calabria Hospital, Negrar and San Raffaele Scientific institute, for
of radioiodine (30–130 mCi). The total body examination was inte- whom histological and follow-up data were available. The PET/CT
grated with a SPET/CT study aimed at the neck and/or in the areas in scans were interpreted with both qualitatively (positive vs. negative)
which accumulations of radioiodine of uncertain pathological attri- and semi-quantitatively measurements as follow: maximum and mean
bution were detected. standardized uptake value (SUVmax and SUVmean) for both 18F-
Results: Of the 95 patients with thyroid residue 14 of them have FDG and 68Ga-DOTATOC PET/CT, metabolic tumour volume
shown on the SPET/TC the presence of metastases that were undis- (MTV) and tumour lesion glycolysis (TLG) for 18F-FDG PET/CT
covered and undetectable to simple planar images because they were and 68Ga-DOTATOC-avid tumour volume (DOTATOC-TV) and
68
hidden by the metabolic activity of glandular residues. To categorise, Ga-DOTATOC tumour lesion (DOTATOC-TL) for 68Ga-DOTA-
12 metastases were found in the lymph nodes of the neck, 1 case of TOC PET/CT. Receiver Operating Characteristics (ROC) curve
infiltration of the trachea and 1 cerebral metastasis which, on planar analysis was used to investigate the performance of several PET
images, had been mistaken for skin contamination. parameters in predicting tumour status or characteristic. For each PET
Conclusions: From our experience, 14.7% of patients undergoing parameter, the optimal cut-off was derived; logistic regression anal-
ablative treatment of thyroid residues show unknown metastases on ysis was then used to assess whether the PET parameters categorized
the SPET/TC prior to treatment which are difficult to detect with only with the optimal cut-off could significantly predict the corresponding
planar images, especially when neck glandular residues are abundant. tumour status or characteristic.
The SPET/TC is also able to detect distant metastases with greater Results: According to the 2010 WHO classification, 18 patients had
accuracy than is possible with only total body images. G1, 39 G2 and 4 had G3 PanNEN. The mean Ki-67 index was 7.1%
(range 0.9–65). DOTATOC-TV and DOTATOC-TL significantly
discriminated between pT3 or pT4 PanNEN versus pT1 or pT2, as
well as 18F-FDG SUVmax, MTV and TLG. 68Ga-DOTATOC
SUVmean was able to significantly predict a Ki-67 [ or B 2;
moreover it was predictive for lymphnodal involvement with a

123
S54 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

threshold of 17.5 and correspondent sensitivity and specificity of 79% organized in a sinusoidal way associated to foci of extramedullary
and 65.7%, respectively (p = 0.0216). Patients with 68Ga-DOTATOC erythropoiesis suggestive of hemangioma.
SUVmean B 17.5 also showed better disease-free survival (42.9 vs Conclusions: Hemangioma represents a rare condition and may be
50.5 months). 18F-FDG MTV and TLG were predictors for confused with malignant tumours at CT images leading to subsequent
angioinvasion; cut-off thresholds, sensitivity and specificity were and useless adrenalectomy. In fact there are no characteristic signs on
7.98, 68%, 76.6% (p = 0.011) for MTV and 32.4, 68%, 80% radiological studies for adrenal hemangioma. Dual tracer PET/CT
(p = 0.0051) for TLG. using 18F-FDG and 68Ga-DOTANOC demonstrated to be very
Conclusions: Dual tracer imaging performed with both 68Ga-DOTA- informative in the preoperative characterization of indeterminate
peptides and 18F-FDG provides relevant information in regard of adrenal masses.
tumour behaviour and aggressiveness, thus definitely implementing
the diagnostic preoperative work-up.
PO079
18F-Choline PET/CT incidental thyroid uptake
PO078 in patients studied for prostate cancer purpose
18F-FDG and 68GA-DOTANOC PET-CT-negative,
histopathology-proven hemangioma of adrenal gland D. Albano1, R. Durmo1, M. Bonacina1, E. Cerudelli1, M. Gazzilli1,
in a patient with suspicious for malignancy AT CT F. Dondi1, A. Mazzoletti1, F. Bertagna1, R. Giubbini1
1
C. Fuccio1, M. Ullo1, G. Collina3, A. Rastelli4, P. Castellucci2, Nuclear Medicine, University of Brescia and Spedali Civili Brescia,
F. Ottalevi1, W. Siquini5, A. Berbellini6, B. Rossi1 Brescia, Italy

1
Background-aim: Thyroid incidental uptake is defined as a thyroid
Department of Nuclear Medicine, AV5, C.G. Mazzoni Hospital, uptake newly and incidentally detected by imaging techniques per-
Ascoli Piceno, Italy. 2Department of Nuclear Medicine, Sant’Orsola- formed for an unrelated purpose and in particular for non-thyroid
Malpighi Hospital, Bologna, Italy. 3Department of Phatology, AV5, diseases and it may be a dilemma. The aim of this study was to
C.G. Mazzoni Hospital, Ascoli Piceno, Italy. 4Department of establish the prevalence and the pathological nature of thyroid inci-
Radiology, AV3, Macerata Hospital, Macerata, Italy. 5Department of dental uptake among patients studied with 18F-choline-PET/CT.
Surgery, AV5, Madonna del Soccorso Hospital, San Benedetto del Methods: We have retrospectively evaluated 368 patients who
Tronto, Italy. 6Medea Center, Macerata, Italy underwent 18F-choline PET/CT for prostate cancer, both for staging
Background-aim: Benign adrenal lesion (tumours, cysts and pseu- or restaging purposes, from June 2016 to September 2018. The PET
docysts) are a heterogeneous group of relatively uncommon entities images were analyzed visually and semi-quantitatively by measuring
that may represent a challenge for radiologists and pathologists. We the maximum standardized uptake value (SUVmax) and the mean
present a case report describing the potential role of PET imaging in a SUV (SUVmean) of the thyroid gland and of the thyroid inciden-
patient with an adrenal lesion suspicious for malignancy at CT taloma; every thyroid focal tracer uptake deviating from physiological
images. distribution and background was considered as suggestive of inci-
Methods: A 65 years old patient affected by melanoma of left leg dentaloma. Final diagnosis of thyroid incidentaloma was obtained by
underwent whole body c.e. CT to stage the disease. CT showed a cytological examination performed after ultrasonography guided fine
nodular lesion in the right adrenal gland showing a ring enhancement needle aspiration or by histological examination after surgery.
in the arterial phase and subsequent centripetal and homogeneous Results: Average SUVmax and SUVmean of thyroid gland in
enhancement in the portal and equilibrium phase with a radiodensity, patients without focal thyroid uptake were 3 ± 1 (range 1.1–5) and
respectively, of 153HU and 120 HU. The diagnostic interpretation 1.8 ± 0.6 (0.8–3.2) respectively. Among 368 patients, a focal inci-
was uncertain; the radiologist firstly suspected an hypervascular pri- dental uptake was identified in 9 cases (2.4%) and 8 underwent further
mary lesion. CT images also described a small nodule in the right investigations to determine the nature. Two incidentalomas were
lung and hypertrophy of the left adrenal gland. In order to better classified as malignant (thyroid carcinoma), whereas 5 were benign (3
characterize the lesion, patient underwent laboratory tests and PET nodular hyperplasia, 1 follicular adenoma, 1 Hurtle cell adenoma) and
studies with 18F-FDG and DOTA-peptides and, finally, laparoscopic 1 indeterminate at cytological examination. Of 2 incidentalomas
surgery of the right adrenal gland. which resulted malignant at histological examination after surgery,
Results: The laboratory tests only showed high values of 17-OH- one was a papillary thyroid carcinoma (pT2 acc. AJCC 8th edition).
progesterone ([ 30 nmol/L; normal value \ 6.06) and slight increase and the other tall cells variant papillary carcinoma (pT1bN0 acc.
of 17-beta-estradiol (60 pg/ml; normal range 20–40) and AJCC 8th edition).
androstenedione (2.6 ng/ml; n.v. \ 1.52 ng/ml) (suggestive of a In malignant lesions SUVmax were 9.6 and 4.5 respectively and
congenital adrenal hyperplasia but not able to exclude an underlying SUVmean 5.3 and 2.9. Average SUVmax and SUVmean of benign
tumour). 18F-FDG PET/CT resulted negative for malignancy; in lesions were 4.9 and 3.2 and of indeterminate lesion 5 and 3
particular no significant incremental uptake was seen in the right respectively.
adrenal respect to contralateral gland (SUVmax right adrenal = 3.0; Conclusions: 18F-choline-PET/CT focal incidental thyroid uptake
SUVmax left adrenal 2.2). A PET study with 68Ga-DOTANOC (one may be a relevant diagnostic reality which requires further investi-
week later) was performed with the same negative results (SUVmax gations and affects management especially considering that, despite
right adrenal = 23; SUVmax left adrenal 28). After surgery, the prevalence of benign lesions, also malignant nodules were found.
pathology revealed a nodular lesion composed by capillaries

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S55

PO080 PO081
Prognostic role of metabolic 18F-FDG PET/CT Is dual tracer PET/CT a prognostic biomarker
in adrenocortical carcinoma in the PRRT enrollment of GEP-NET patients?

R. Durmo1, D. Albano1, D. Cosentini3, M. Bonacina1, M. Gazzilli1, S.A. Pignata1, A. Campennı̀1, F. Minutoli1, R. Laudicella1,
E. Cerudelli1, F. Dondi1, F. Bertagna2, A. Mazzoletti1, A. Berruti3, A. Comis1, R. Filice1, B. Catalfamo1, F. Panasiti1, S. Baldari 1

R. Giubbini2
1
Nuclear Medicine Unit, Department of Biomedical and Dental
1 2
Nuclear Medicine, Spedali Civili Brescia, Brescia, Italy. Nuclear Sciences and Morphofunctional Imaging, University of Messina,
Medicine, University of Brescia and Spedali Civili Brescia, Brescia, Messina, Italy
Italy. 3Oncology Department, University of Brescia and Spedali Civili
Background-aim: Collecting the information provided in both SSTR
Brescia, Brescia, Italy
and FDG PET/CT in patients affected by gastroenteropancreatic
Background-aim: Adrenocortical Carcinoma (ACC) is a rare and neuroendocrine tumors (GEP-NETs), in 2017, Chan et al. developed a
aggressive malignancy with poor 5-year survival rates. Although the single parameter grading scheme as known as the NET-PET grade.
role of 18F-FDG PET/CT in the management of ACC has not been The aim of the study is to evaluate the feasibility of NET-PET grade
fully investigated, it has been increasingly used in detection, staging scheme as a prognostic biomarker in metastatic GEP-NETs patients
and follow-up. FDG-PET metabolic parameters have been shown to undergoing peptide-radionuclide-receptor-therapy (PRRT).
have a significant prognostic impact in other solid tumors that can Methods: Overall, 31 GEP-NETs metastatic patients (13F and 18 M,
guide optimal patient treatment. Our aim was to determine whether mean age 61 years, range 27–80) who underwent both 18F-FDG and
68
metabolic PET/CT parameters could play a role as prognostic markers Ga-DOTATOC PET/CT prior PRRT, were included in the analysis.
in patients affected by ACC. Following tumors embryonic origin, the patients were divided into
Methods: We conducted a retrospective study of 21 patients (8 men, two groups: foregut-GEP-NETs (17/30 patients, all affected by pan-
13 female, average age: 48, range 16–65) with a histological diag- creatic-NET) and midgut-GEP-NETs (14/30 patients).
nosis of primary ACC who underwent 18F-FDG PET/CT (from Moreover, according to the WHO 2010 GEP-NET classification,
August 2014 to September 2018) prior to any treatment, followed by the patients were divided into three groups: G1 (Ki67 \ 3), G2 (Ki67
chemotherapy with or without surgery. PET images were qualitatively from 3 to 20), and G3 (Ki67 [ 20).
and semi-quantitatively analyzed by measuring the maximum stan- According to visual evidence scale (ve) of NET-PET grade, we
dardized uptake value body weight (SUVmax), lean body mass divided the patients into five groups (P1 indicating purely SSTRI-avid
(SUVlbm), body surface area (SUVbsa), metabolic tumor volume of disease without FDG uptake in any lesions and P5 indicating the
the primary lesion (MTV), total lesion glycolysis (TLG) of the pri- presence of significant FGD ve ?/SSTRI ve-).
mary lesion, whole body MTV (MTVwb) and whole body TLG Based on dual-tracer PET/CT’ visual evidence, the patients were
(TLGwb). Clinical variables such as age, sex and clinical stage were stratified into three groups: the first group of patients will suitable for
also assessed. treatment with 177Lu-DOTATOC alone (p1-p4a); in the second group,
177
For the entire population, receiver operating characteristic (ROC) Lu-DOTATOC may have a role in the treatment of patients, but
curve analysis was used to identify the optimal cutoff point of they should have other therapy (p4b); in the third group, the subjects
semiquantitative parameters in order to interpret the results of pro- may not derive adequate tumor control from PRRT and should have
gression free survival (PFS) and overall survival (OS).The Kaplan– systemic chemotherapy (p5).
Meier method and Log-rank test were used to perform univariate To demonstrate 177Lu-DOTATOC uptake in the three main
survival analysis. lesions, post-therapeutic Whole-Body Scan (pt-WBS) was obtained
Results: At a median follow-up of 14 months (range 2–50 months), three days after PRRT.
relapse or progression of disease occurred in 16 patients with an Results: Applying the WHO 2010 classification, 5 subjects were in
average time of 11 months (range 1–33 months) from the baseline the G1 group, 18 subjects were in the G2 group (among them, 7 had
PET/CT; death occurred in 10 cases with an average time of 9 months Ki67 [ 10) and, finally, 5 patients were in G3 group.
(range 2–21). All PET/CT showed the presence of FDG avid lesion Among 31 patients, the NET-PET grade was P1 in 12 patients, from
consistent with ACC. Average SUVmax, SUVlbm, SUVbsa, MTV, P2 to P4a in 18 patients, P4b in 0 patient and P5 in 1 patient,
TLG, MTVwb and TLGwb were 24.74 (range 4.4–40), 12,7 (range respectively.
4.08–28.5) 4.4 (range 1.42–9.22), 236.8 (range 3.5–886.1), 1894.1 The current guidelines indicate chemotherapy for G3 patients.
(range 17.5–2225.9), 312.8 (average 3.5–895.8) and 2726.3 (range By contrast, according to the NET-PET stage G3 patients were
17.5–9612.6) respectively. In univariate analysis, considering cutoff classified as P2a (2/5), p2b (2/5) and p3a (1/5) grade.
value derived from ROC curve (SUVmax:11, SUVlbm:8.9, Following assessment of NET-PET grade, therefore, the G3
SUVbsa:6.7, MTV:79.9, TLG:424.6, MTVwb:119.8 and patients underwent PRRT.
TLGwb:2698.7) showed that baseline PET/CT metabolic parame- Assessing 177Lu-DOTATOC biodistribution, pt-WBS was per-
ters were not associated with PFS and OS (P [ 0.05 for all). formed 3 days after PRRT: all G3 patients exhibited intense 177Lu-
Conclusions: ACC is an intensely FDG-avid tumour and 18F-FDG DOTATOC uptake in the main lesions.
PET/CT may provide critical information for determining the Conversely, PRRT failed in 1 midgut-NET G2 patient (Ki67 =
appropriate treatment course. The prognostic value of SUV, MT- 12%): based on NET-PET grade assessment, this patient was P5.
V and TLG in pretreatment is still undetermined and it does not seem Conclusions: Our experience suggests that the NET-PET grade can
to be useful to predict patients prognosis. Further studies with large be a reliable support tool for the decision of the treatment strategy of
sample of patients would been needed to confirm or contradict our GEP-NETs, especially in G3 patients.
evidence. Achieving a more accurate assessment of subjects with metastatic
GEP-NETs, NET PET score can identify the patients that might
benefit from PRRT or who should undergo chemotherapy.

123
S56 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

PO082 maintaining therapy in GEP-NETs patients. We wish to stress the


Peptide receptor radionuclide therapy and somatostatin importance of the maintenance of ‘‘cold’’ SSA after PRRT and to
respect the SSA administration timing during the PRRT protocol.
‘‘cold’’ analogues therapy in the treatment of GEP-NET
patients: our center’ experience

S.A. Pignata1, L. Sturiale1, R. Laudicella1, F. Quattrocchi1, PO083


A. Vento1, H. Lanzafame1, C. Mantarro1, B. Pagano1, D. Cardile1, Can texture analysis be used for a vivo ‘‘imaging
S. Baldari1 biopsy’’ in neuroendocrine tumors? A first step
1 feasibility study with 68GA-DOTATOC PET/CT
Nuclear Medicine Unit, Department of Biomedical and Dental
Sciences and Morphofunctional Imaging, University of Messina,
Messina, Italy V. Liberini5, B. De Santi1, E. Gallio4, E. Pilati5, M. Finessi5,
M. Bellò5, M.G. Papotti2, F. Maletta2, M. Volante3, G. Bisi5,
Background-aim: The aim of the study is investigating the benefit of F. Molinari1, D. Deandreis5
the combined and maintenance SSA-administration in Gastroen-
teropancreatic neuroendocrine tumors (GEP-NETs) patients that 1
Biolab, Department of Electronics and Telecomunications,
underwent peptide-receptor-radionuclide-therapy (PRRT). Politecnico di Torino, 10129, Turin, Italy. 2Department of Oncology,
Methods: We retrospectively reviewed the records of 40 metastatic Pathology Unit Molinette Hospital, University of Turin, Italy.
and symptomatic GEP-NETs patients (18F and 22 M; mean age 3
Department of Oncology, Pathology Unit San Luigi Hospital,
57.3 years; range 30–78), admitted to our Nuclear Medicine Unit University of Turin, Italy. 4Medical Physics Unit, Department of
from 01.11.2008 to 01.02.2017 Radiology, AOU Città della Salute e della Scienza, Turin, Italy.
Of 40 patients enrolled, 17 had pancreatic-NET (p-NET), 23 had 5
Nuclear Medicine Unit, Department of Medical Sciences, University
midgut-GEP-NETs (2 duodenal-NETs, 17 small-intestinal-NETs, 4 of Turin, Italy
colorectal-NETs).
Furthermore, following WHO 2010 GEP-NET classification they Background-aim: Neuroendocrine tumors (NET) are an heteroge-
were divided into three group: G1 (Ki67 \ 3%, 8 patients), G2 (Ki67 neous group of malignancies with a varied histology, localization and
from 3 to 20%, 32 patients) and G3 (1 well-differentiated p-NET with behavior. Differentiation grade according to Ki67 index is one of the
Ki67 = 30%). most important factors to predict tumor aggressiveness and its
All GEP-NET patients underwent PRRT, combined SSA-therapy, assessment often relays on a single biopsy of primary tumor or sec-
and maintenance SSA-therapy. ondary lesion.
The long-acting SSA-therapy was administered by injection every However, differentiation grade can be underestimated or it can be
28 days. variable among lesions in a metastatic setting.
68
The PRRT protocol involved 4 cycles of 200 mCi of 177Lu- Ga-DOTA-peptide PET/CT appears to be a non-invasive imag-
DOTATOC at least 8 weekly intervals. ing method to assess tumor differentiation and aggressiveness.
All patients, therefore, received SSA as a combination therapy Application of image analysis and identification of texture features
with PRRT and ‘‘cold’’ SSA administration was discontinued 14 days could be useful for a deeper characterization of the tumor.
before 177Lu-DOTATOC administration and carried out again The objective of this study was to evaluate the feasibility of a
14 days later. In this way, the patients had two ‘‘cold’’ SSA injection radiomic approach in NET through the analysis of image textural
between two PRRT. features at 68Ga-DOTATOC PET/CT and evaluating their correlation
This point represents the main difference with respect to current with the histological NET grading system.
principal guidelines that recommend discontinuation of 4 weeks. Methods: We retrospectively analyzed a cohort of 20 treatment-naı̈ve
Our decision was supported by both favorable post-therapy Whole patients, who came to our observation to perform a staging PET/CT
Body scan radiopharmaceutical biodistribution and literature data, as with 68Ga-DOTATOC for NET disease. In all cases, the differentia-
already demonstrated. tion grade of primary tumors assessed by biopsy was available and
Results: The median follow-up period from the beginning of treat- patients were divided into 3 groups (15/20: Ki67 index \ 3—G1
ment was 43.6 months (range 15–116 months). group; 4/20: Ki67 index [ 3 and \ 20—G2 group; 1/20: Ki67
In our cohort of patients, we observed that the mean PFS was index [ 20—G3 group).
35 months (range 7–111): at last follow-up, 10 out of 40 patients Using the open source software LIFEx, we performed texture analysis
(25%) had visual evidence of disease progression at the radiological on a volume of interest (VOI) of the biopsy site lesion (in our study
and/or molecular imaging assessment. corresponding to the primary lesion), outlined manually by an expert
Interestingly, of 5 p-NET patients, 2 had Ki67 = 6%, 3 had operator. Manual VOIs were then refined by fixed threshold of 20% of
Ki67 = 15%. the maximum SUVmax.
In the midgut-NETs group, 4 patients had a Ki-67 B 3. Only one Statistical analysis (MANOVA and linear regression) was used to
of them had Ki67 [ 10%. correlate textural features (GLCM_Homogeneity, GLCM_Entropy,
Noteworthy, the mean OS was 45.6 months (range 15–116) and, to GLRLM_Short-Run Emphasis, GLRLM_Long-Run Emphasis,
date, data were not sufficiently mature to provide an estimate of the GLZLM_Low Gray-level Zone Emphasis, GLZLM_High Gray-level
median OS. Zone Emphasis, SUVmax, HISTO Entropy and HISTO Energy) with
Furthermore, we observed that there was a mortality rate of 10% in histological data (including grading and Ki67 index).
p-NET patients (4/17 patients, three of them had a Ki67 B 10%). Results: Among the 20 analyzed patients, the primary NET location
On the other hands, all midgut-NETs patients still alive (the mean was duodenal (3/20 pt), midgut (4/20 pt), pancreatic (10/20 pt) and
OS was 47 months, range 19–113). bronchial (3/20 pt) respectively.
Finally, all patients had stable/improved carcinoid syndrome MANOVA analysis showed that the parameters vectors of analyzed
symptoms; few toxicities reported; no safety issues identified. textures (the parameters all together) are able to differentiate the
Conclusions: Our experience suggests and confirmed the clinical patient into three groups according to the Ki67 index value found on
benefit of combination therapy (’’cold’’ SSA plus PRRT) and the the primitive lesion, as mentioned before.

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S57

A linear correlation between the Ki67 index and texture features Results: Therapy was well tolerated in all patients and none presented
was found only for the HISTO Energy and the GLRLM Long-Run acute side effects. No problems in vial manipulation, dose prepara-
Emphasis features (p-value B 0.05) of VOIs with threshold of 20%, tion, administration and radiation protection issues occurred.
but not for manual VOIs. No significant long-term hematologic toxicity was seen.
Conclusions: The findings of this study, although preliminary, show We have the follow up of 20 patients (median 5 months; range
that textural features analysis with 68Ga-DOTATOC PET/CT is 1 month-6 years,): CT, MRI or PET (with 68Ga-DOTATOC or with
feasible. 18F-FDG) showed stable disease in 13 patients and progression in 7
A future prospective study with a larger and homogeneous cohort for cases.
tumor grading and primary lesion site is necessary to identify the Conclusions: Our experience shows the feasibility of PRRT in
package of most ‘‘robust’’ texture features, which will allow us to patients with relapsed/metastatic paraganglioma, with stable disease
capture a different biological behavior of the various lesions (primi- in two-thirds of cases.
tive and metastatic).

PO085
PO084 131
I-SPECT/CT in neck lymph node metastasis
Peptide receptor radionuclide therapy (PRRT) detection in patients with differentiated thyroid
in paraganglioma: the European institute of oncology carcinomas (DTC) in long-term follow-up
experience
A. Marongiu1, S. Nuvoli2, I. Gelo2, L. Mele2, B. Piras2, M.L. Stazza2,
G. Manfrinato1, L. Gilardi1, S.M. Baio1, M. Colandrea1, S. Galassi2, G. Madeddu2, A. Spanu2
S.L. Fracassi1, P.A. Rocca1, L.L. Travaini1, A. Cascio1,
R. Mei1, C.M. Grana1 1
Unit of Nuclear Medicine, Department of Clinical, Surgical and
Experimental Sciences, University of Sassari, Sassari, Italy. 2Unit of
1
Nuclear Medicine Division, European Institute of Oncology, Milan, Nuclear Medicine, Department of Clinical, Surgical and Experimental
Italy Sciences, University of Sassari, Sassari, Italy
Background-aim: Paragangliomas are rare neuroendocrine tumors Background-aim: The prognostic importance of regional lymph
arising from neural crest progenitors located outside of adrenal gland. node metastases in DTC is controversial even if it is generally
The clinical presentation is variable and is attributed to hemodynamic accepted that their presence, especially if in bilateral regions, corre-
and metabolic actions of the catecholamines produced and secreted by lates with tumor recurrences and with adverse prognosis, in particular
these tumors. in older age group. Thus, their identification is mandatory to achieve
Surgical resection is the treatment of choice and it can be used as a early the most appropriate treatment. We further investigated the
curative treatment for recurrent or limited metastatic tumors. In usefulness of 131I-SPECT/CT with diagnostic dose in neck lymph
patients with metastatic disease in whom surgery may not be feasible, node metastasis detection in DTC patients in long term follow-up.
radiofrequency ablation, external radiation and therapy with 131I- Methods: We retrospectively evaluated 215 consecutive DTC
MIBG or 177Lu- or 90Y-labeled somatostatin receptors can be used. patients already submitted to total thyroidectomy and radioiodine
The aim of our study is to evaluate the European Institute of therapy, all of them with ascertained radioiodine avid foci in the neck
Oncology experience in the treatment of paraganglioma patients with at 131I-SPECT/CT during long-term follow-up; at surgery, 62
Peptide Receptor Radionuclide Therapy (PRRT). patients were classified at high risk (H), 61 at low risk (L), 92 at very
Methods: We retrospectively analysed 33 patients with a histological low risk. All patients underwent 131I-whole body scanner (WBS)
diagnosis of paraganglioma that were referred to our Institution from followed by SPECT/CT 48 h after an orally radioiodine administered
1993 to 2018. Sixteen were male and 19 female and in six the dose of 185 MBq, using a hybrid variable dual head gamma camera,
pathology had a familiar origin. In 21 patients the disease at the time including a low dose-x-ray, and equipped with high energy, parallel
of diagnosis was localized in head and neck, in 13 in pelvis and only hole collimators.
in 1 in abdomen. Thirty had surgical removal of the tumor and in 5 Results: SPECT/CT detected 456 iodine avid foci in the neck in the
cases surgery was not performed. 215 patients, while WBS evidenced 323 foci in 161/215, patients all
Twenty-two received therapies like external radiotherapy, somato- also identified by SPECT/CT.WBS classified as residues 262/323 foci
statin analogue administration, chemotherapy, liver termoablation and and as unclear 61 foci. SPECT/CT confirmed 253/262 foci as residues
treatment with 131I-MIBG for relapse or metastatic localizations but correctly characterized the remaining 9 cases as 8 neck lymph
before PRRT. node metastases and 1 physiologic structure. Moreover, SPECT/CT
Pretreatment evaluation was performed with whole body CT (15 appropriately characterized the 61 foci unclear at WBS as 18 lymph
pts), MRI (14), scan with 111In-pentetreotide (24), 131I-MIBG (5), node metastases, 24 residues and 19 iodine avid physiologic struc-
PET scan with 18F-FDG (4), 68Ga-DOTA-peptides (8), 18F-DOPA tures. In 73 patients, SPECT/CT also detected 133 occult foci at
(2) in different combination. In almost all cases the morphological WBS, among whom 54 cases with foci completely occult at WBS,
evaluation was concordant with the functional imaging findings. characterizing these as 59 residues and 74 lymph node metastases.
Thirty patients performed PRRT, thirteen with 177Lu-DOTA- Globally, SPECT/CT identified 100 metastatic foci as neck lymph
TATE, 8 with 90Y-DOTATOC, 9 with a combination of 177Lu- node metastases in 54 patients (23 H, 11L, 20VL), while WBS evi-
DOTATATE and 90Y-DOTATOC. Nine patients had 6 or more denced 26 (p \ 0.0001) in 22 cases, in part wrongly classified as
cycles of therapy with 177Lu-DOTATATE, 1 patient had 6 cycles of residues and in part as unclear foci. Twelve VL patients, seven of
therapy with 90Y-DOTATOC and 2 patients 6 cycles of therapy with whom with lymph nodes near submandibular glands, had thyroglob-
177Lu-DOTATATE and 90Y-DOTATOC; the others 18 received less ulin undetectable or \ 2.5 ng/ml and were T1aN0M0. Globally,
than 6 cycles of therapy. SPECT/CT obtained an incremental value than WBS in 43.2% of
cases, a more correct patient classification changing therapeutic
approach in 27.4% of cases and contributed to avoid unnecessary

123
S58 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

therapies in presence of single foci of physiologic uptakes not clas- cases with radiological/biochemical NEN suspicion. PET/CT was
sified by WBS in 7% of cases. also useful to evaluate therapy response and follow-up, accordingly to
Conclusions: 131I-SPECT/CT proved a reliable tool in detecting and its use in sporadic NEN.
characterizing neck lymph node metastases in DTC patients in long- PET and CI were concordant in almost half of the pts. Lesions
term follow-up improving WBS performance, including the inter- dimension and tumour differentiation may explain the observed dis-
pretation of unclear foci, and reducing the false positive results. The cordant findings. Finally, being a whole body imaging procedure,
role of SPECT/CT appears particularly significant in patients with PET/CT is a valuable tool for MEN-1 SD pts screening considering
WBS inconclusive, VL, T1aN0MO and with undetectable or very low their higher risk of developing other primitive tumors.
thyroglobulin levels.

PO087
PO086 Is 68GA-DOTANOC PET/CT useful in patients
Is 68GA-DOTANOC PET/CT useful in patients referred for suspected NEN relapse?
with men-1 syndrome?
D. Calabrò2, S. Telo2, E. Tabacchi2, L. Zanoni2, D. Campana1,
2 2 2 1 2
D. Calabrò , S. Telo , E. Tabacchi , D. Campana , L. Zanoni , N. Brighi3, S. Fanti2, V. Ambrosini2
S. Fanti2, V. Ambrosini2
1
Internal Medicine, S. Orsola-Malpighi Hospital, Bologna, Italy.
1 2
Internal Medicine, S. Orsola-Malpighi Hospital, Bologna, Italy. Nuclear Medicine, S. Orsola-Malpighi Hospital, Bologna, Italy.
2 3
Nuclear Medicine, S. Orsola-Malpighi Hospital, Bologna, Italy Oncology, S. Orsola-Malpighi Hospital, Bologna, Italy
Background-aim: To retrospectively evaluate the role of 68Ga- Background-aim: To retrospectively assess the potential role of
68
DOTANOC PET/CT (SA-PET) in patients (pts) with MEN1-syn- Ga-DOTANOC PET/CT in patients (pts) with an oncological his-
drome (SD) and the concordance with conventional imaging (CI). tory of previous neuroendocrine neoplasm (NEN) and referred for
Methods: Pts undergoing SA-PET at our center are included in an suspected relapse.
electronic archive (EC:131/2017/O/Oss) and those carrying MEN1 Methods: Data of pts undergoing 68Ga-DOTANOC PET/CT were
SD studied between September 2017 and July 2018 were included in prospectively collected in an electronic archive (EC:131/2017/O/
the analysis. PET/CT results were compared to previous PET/CT Oss). Pts with an oncological history of previous NEN and referred
scans and CI (CT, RM, US) when available. for suspected NEN relapse between September 2017 and August 2018
Results: Among 466 pts undergoing SA-PET, 25 had genetic con- were included. Suspicion of NEN relapse was based on either
firmation of MEN-1 SD (5,4%). Indication to PET/CT was: equivocal morphological imaging (CT, MRI, US), clinical symptoms
(i) radiological/biochemical suspicion of new neuroendocrine tumors and laboratory data (increased NEN markers, e.g. chromogranin A) or
(NEN) and (ii) restaging of known NEN lesions. their combination. When PET/CT was positive, the confirmed relapse
PET/CT was positive in 5/6 pts (83.3%) studied for suspected new was described as local (at the primary tumour site) or diffuse. PET/CT
NEN localization. In 4/5 pts, CI imaging was available: in 3/4 pts was performed according to EANM guidelines.
(75%), PET/CT and CI were concordant (lesions site and number) Results: Among 479 pts studied with PET/CT, 29/479 pts (6%) were
while in 1/4 pts CI detected 3 additional liver lesions. The single PET- referred for suspected NEN relapse: PET/CT resulted positive in
negative case showed a positive CT scan (duodenal lesion under PET 11/29 pts (38%).
spatial resolution). Equivocal conventional imaging findings were observed in 25/29
Nineteen/25 pts (76%) were studied for restaging (9 interim, 9 FU, (86%) pts.
1 after surgery). PET/CT was positive in 14/19 pts (74%), showing PET was positive in 11/25 (44%) cases (including three cases
stable disease (SD) in 10/14 pts (71%) and disease progression (PD) presenting also with increased markers and one symptomatic pt). In
in 4/14 pts (29%). In 10/14 pts (71%) CI imaging was available: in 2/11 pts (18%) PET/CT showed local recurrence on the surgical
4/10 pts (40%) CI and PET/CT were concordant (site and number), in resection shear. In 9/11 (82%) pts, distant metastasis were found: 5/9
2/10 pts (20%) PET/CT revealed more lesions than CI (sub-centi- pts (55%) with nodal involvement only and 4/9 pts (45%) with
metric abdominal nodes in one case and multiple pancreatic lesions) widespread disease (3 liver, 2 bone, 1 peritoneum). In 11/25 (44%)
while in 3/10 pts (30%) CI demonstrated the presence of lesions PET/CT was negative: 3/11 lung nodules (\ 1 cm), 1/11 lung nod-
missed at PET/CT (in 1/3 hepatic lesion, 1/3 lymph nodes, 1/3 pan- ule [ 1 cm (FDG positive), 2/11 suspicious liver lesions (negative at
creatic lesions). PET and CI detected different lesions sites in one FDG PET), 2/11 surgical shear, 1/11 auditory canal level, 1/11 sus-
patient. pected lymph node, 1/11 suspected local relapse (poorly differentiated
PET/TC was negative in 5/19 (26%) pts; CI was available in 3/5 parotid carcinoma). PET/CT was inconclusive in 3/25 (12.5%:
cases: in 2/3 pts CI detected more lesions (one pancreatic and one mediastinal lymph nodes, auditory canal, uncinate process).
liver lesion), in 1/3 pts PET and CI were both negative. PET/CT was negative in 4/29 cases (14%) studied for increased
Clinical FU was available in 4/25 pts (16%): 2/4 pts with negative markers alone.
PET were addressed to FU, SD demonstrated on PET/CT indicated no Conclusions: In pts with suspected NEN relapse, 68Ga-DOTANOC
therapy modification in 1/4 pt, 1/4 pt with PD on PET/CT started SA PET/CT was positive in approximately one-third of cases studied for
therapy. Of note, in the latter case pathological uptake was demon- suspected relapse based on equivocal conventional imaging findings
strated on two additional left breast lesions that were later diagnosed and in few cases with associated clinical symptoms or increased
as breast cancer. markers. When suspicion was based on the mere detection of
Conclusions: The role of SA-PET/CT in MEN-1 SD pts is still increased markers, PET/CT was always negative. In the majority of
debated. Although limited by the paucity of collected cases, our data pts, relapse occurred as metastatic disease, mostly in lymph nodes.
show that PET/CT was overall accurate for the detection of NEN
lesions, resulting positive in 75% of cases. PET/CT was more fre-
quently positive in the MEN subgroup studied for suspected new
NEN lesions as compared to reported PET positivity in non-MEN

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S59

PO088 compared to radiolabelled glucose; however 18F-FDG PET exami-


Role of dual tracer PET imaging with 68GA- nation added useful informations in patient with moderate-low
differentiated neoplasms, but could be probably safely omitted in
DOTATOC and 18F-FDG in pancreatic patients who present a G1 tumor,.
neuroendocrine tumor staging

P. Guglielmo3, P. Mapelli4, S. Partelli5, C. Canevari1, F. Muffatti2,


P. Magnani1, V. Andreasi5, F. Fallanca1, L. Gianolli1, M. Falconi5, PO089
M. Picchio4 Correlation between 68Ga-DOTATOC PET/CT
semiquantitative parameters and pathological grading
1
Nuclear Medicine Department, IRCCS San Raffaele Scientific in NETs
Institute, Milan, Italy. 2Pancreatic Surgery Unit, Pancreas
Translational and Clinical Research Centre, IRCCS San Raffaele
Scientific Institute, Milan, Italy. 3University of Milan Bicocca, Milan, M. Spallino2, G. Cabrini2, L. Monaco3, D. Zanni1, M. Cuzzocrea3,
Italy. 4Vita-Salute San Raffaele University, Milan, Italy; Nuclear C. Dolci2, A.F. Scarale2, E. Gay2, C.E. Popescu2, R. Sara2,
Medicine Department, IRCCS San Raffaele Scientific Institute, M.C. Pelle2, E. Preza3, M. Milella2, C. Rossetti2
Milan, Italy. 5Vita-Salute San Raffaele University, Milan, Italy; 1
Pancreatic Surgery Unit, Pancreas Translational and Clinical Medical Physics Department, ASST Niguarda Hospital, Milan, Italy.
2
Research Centre, IRCCS San Raffaele Scientific Institute, Milan, Italy Nuclear Medicine Department, ASST Niguarda Hospital, Milan,
Italy. 3Nuclear Medicine Department, University Milan Bicocca,
Background-aim: Pancreatic neuroendocrine neoplasms (panNENs) Milan, Italy
represent a worldwide increasing tumor, due to the improved inci-
dental detection even of small pancreatic lesions. A correct and Background-aim: In this study we aimed to quantify the expression
accurate initial staging is crucial for determining the most appropriate of somatostatin receptors (SSTRs) in Neuroendocrine Tumors (NETs)
management of these patients. Nuclear medicine imaging offers using the semiquantitative parameter SUV (Standardized Uptake
valuable tools for staging, such as PET with 18F-FDG and with 68Ga- Value) of [68Ga]DOTA(0)-Phe(1)-Tyr(3)-octreotide (DOTATOC)
DOTA conjugated peptides. Despite no commonly recognized clini- PET/CT; we compared tumor uptake with its pathologic grade, given
cal indications have been established yet, the use of both radiotracers the fact that the presence of cell surface receptors seems to depend on
might be useful for staging purposes. Aim of the present study is to tumor cell differentiation.
evaluate the potential synergic role of dual tracer PET study, using Methods: 68Ga-DOTATOC PET/CT scans of 53 patients (27 males,
both 68Ga-DOTATOC and 18F-FDG, performed in a cohort of 26 females; 10/53 NET stage I, 4/53 stage II, 6/53 stage III, 33/53
patients referred to our hospital with cytologically proven or suspi- stage IV) were evaluated to identify semiquantitative parameters SUV
cious panNENs at common imaging. max and SUV mean of a main tumor lesion, defined as the largest
Methods: In this retrospective study, patient population consisted of and/or the lesion with the highest pathological radiotracer uptake (15/
32 subjects (17 males, 15 females; mean age 60.7 year-old) who 53 liver, 14/53 pancreas, small intestine 13/53, 8/53 lymph nodes,
underwent to double-tracer PET imaging using either PET/CT 2/53 bone, esophagus 1/53). According to the WHO Grading System,
(n = 49) or PET/MRI (n = 15). Nine/32 underwent to surgical neoplastic tissue was graded in low (G1; 30/53 patients), intermediate
resection, whereas in the remaining 23/32 only a cytological sample (G2; 17/53 patients) and high grade (G3; 6/53 patients) referred to a
of the primary tumor was available for analysis. For each PET range of Ki-67 index or mitotic rate (\ 3%, 3–20%, [ 20%,
examination, the sites of increased abnormal uptake were depicted respectively). SUV max and SUV mean values of main lesions were
and classified as T, N or M and then a head-to-head comparison separately correlated to pathologic grades G1, G2 and G3 (using one-
between the entity of uptake of the two radiotracers site-by-site was way analysis of variance ANOVA) and to well differentiated (G1 and
performed. Furthermore, SUVmax and the SUVmean of all sites with G2) and poorly differentiated G3 (using Student t-test), with a p
increased uptake, for both radiotracers, have been derived. No sur- value B 0.05.
vival analysis was carried on, due to the short follow-up period [mean Results: Using ANOVA test, mean values of SUV max for G1, G2
5.2 months (range 10-0.1 months)]. and G3 groups were 28.45 ± 19.67, 30.81 ± 25.06, 14.93 ± 13.71
Results: 16 patients had a G1 grade, 8 had a G2 tumors and 2 pre- respectively (F 1.30, p 0.28); mean values of SUV mean were
sented a G3 panNEN; in 6 patient the result of the biopsy was 7.49 ± 3.75, 7.46 ± 3.40, 6.16 ± 3.58 respectively (F 0.35, p 0.70).
negative or inadequate. 68Ga-DOTATOC PET could detect 25 pri- Using Student t-test, mean values of SUV max for well and poorly
mary sites (T), 8 lymph nodes (N), 8 liver metastases, 4 bone lesions differentiated tumors were 29.30 ± 21.53 and 14.93 ± 13.71
and 1 intestinal lesion; 18F-FDG PET could depict 7 T, 4 N and 4 respectively (T 1.59, p 0.12); mean values of SUV mean were
liver metastases. Therefore 68Ga-DOTATOC highlighted more 7.48 ± 3.59 and 6.16 ± 3.58 respectively (T 0.86 p 0.39).
lesions than 18F-FDG in the whole population (25 vs 7 T; 8 vs 4 N Conclusions: Our results did not show a statistically significant
and 13 vs 4 distant metastases). 18F-FDG PET was negative in all correlation between PET semiquantitative values SUV max and SUV
patients having G1 tumors. Conversely, when only patients with G2 mean and histological grade of NETs, nevertheless we observed a
or G3 tumor are considered, 18F-FDG PET could detect a higher reduction of main lesions radiotracer uptake in poorly differentiated
number of lesions, some of them not visible at 68Ga-DOTATOC PET tumors compared to well differentiated forms, maybe reflecting a
(pancreatic lesion, lymph node and a liver metastasis). Considering lower expression of SSTRs. These results deserve to be further
PET/CT scans with 68Ga-DOTATOC, mean SUVmax of T sites was investigated with analyses in larger series of patients with more
66.2 and mean SUVmean was 40.6. Mean SUVmax of N localizations homogeneous lesions; correlation with specific Ki-67 values should
was 48.4 and mean SUVmean was 29.0. For M sites, mean SUVmax also be explored.
was 46.9 and mean SUVmean was 30. Analyzing PET/CT using 18F-
FDG, mean SUVmax of the primary sites was 5.4 and the mean
SUVmean 3.2.
Conclusions: According to this retrospective cohort, 68Ga-DOTA-
TOC has a higher sensitivity and accuracy in panNENs staging

123
S60 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

PO090 PO091
Lesion dosimetry in metastatic thyroid cancer treated Impact of 68Ga DOTATOC PET/CT in the therapeutic
with 131I: methodology and preliminary dose–response management of neuroendocrine tumors
results
E. Pilati1, M. Finessi1, R. Passera1, V. Liberini1, C. De Angelis2,
2 1 1 1
V. Garbaccio , E. Richetta , M. Poli , A. Pecora , E. Garnero , 2 E. Arvat3, A. Piovesan3, M. Gallo3, L. Ciuffreda4, N. Birocco4,
A. Sandri2, A. Codegone2, V. Pirro2, D. Deandreis3, R.E. Pellerito2, A. Ponzetti4, M.P. Brizzi5, D. Campra6, G. Giraudo7, M. Bello’1,
M. Stasi1 G. Bisi1, D. Deandreis1
1
1
Medical Physics Department, A.O. Ordine Mauriziano Umberto I, Nuclear Medicine Unit, Department of Medical Sciences, University
Turin, Italy. 2Nuclear Medicine Department, A.O. Ordine Mauriziano of Turin, AOU Città della Salute e della Scienza di Torino, Turin,
Umberto I, Turin, Italy. 3University Nuclear Medicine, Department of Italy. 2Gastroenterology Unit, Department of General and Specialist
Medical Sciences, University of Turin, Città della Salute e della Medicine, AOU Città della Salute e della Scienza di Torino, Turin,
Scienza di Torino, Turin, Italy Italy. 3Oncological Endocrinology Unit, Department of Medical
Sciences, University of Turin, AOU Città della Salute e della Scienza
Background-aim: Metastatic differentiated thyroid cancer (MDTC) di Torino, Turin, Italy. 4Medical Oncology, Department of Medical
is generally treated with high 131I activity, but some patients despite Oncology, University of Turin, AOU Città della Salute e della
a preserved 131I uptake still have a poor prognosis. With standard Scienza di Torino, Turin, Italy. 5Medical Oncology, Department of
fixed 131I activity approach lesion absorbed dose can’t be estimated. Oncology, University of Turin, AOU San Luigi Gonzaga, Orbassano,
European (EU 59/2013) Directive requires a personalized dosimetry. Turin, Italy. 64th General Surgery, Department of Surgical Sciences,
Aim of this study is to show post therapy dosimetric methodology and University of Turin, AOU Città della Salute e della Scienza di Torino,
preliminary dose–response results in a group of metastatic patients. Turin, Italy. 71st General Surgery, Department of Surgical Sciences,
Methods: Lesion dosimetry was performed on 10 MDTC patients University of Turin, AOU Città della Salute e della Scienza di Torino,
(July 2016–June 2018). The SPECT-CT (Siemens Symbia Intevo T2) Turin, Italy
was calibrated with a spheres phantom filled with liquid 131I
(13 MBq/ml) to evaluate counts/MBq, partial volume effect (PVE) Background-aim: PET/CT imaging with somatostatin receptor–tar-
and dead time corrections. After 131I administration (mean ± 1 SD geted (SSRT) ligands labeled with 68Ga has shown superior accuracy
7.2 ± 2.4 GBq, range 3.7–11.1 GBq) 4 SPECT-CT images (64 in detecting and staging neuroendocrine tumors (NETs) compared to
views, 256 9 256, ITSCAC) were acquired (4, 24, 48, 96 h p.a.). standard imaging modalities. The aim of this study was to assess the
Applying the calibration counts were converted into activity and then impact of 68Ga DOTATOC PET/CT in the therapeutic management
time-integrated to calculate the dose (MIRD sphere model). Mean of patients with NETs in our clinical practice.
doses were evaluated for 32 lesions (8 visceral, 24 skeletal); among Methods: We retrospectively evaluated 137 consecutive patients (73
them, for 20 lesions (4 visceral, 16 skeletal), when a further radio- men, 64 women; median age 62 years; range 18–83 years) with NETs
iodine treatment was available, clinical response was investigated (45.3% GEP, 14.6% lung, 15.4% other or unknown, 24.7% missing)
(evaluation of SPECT-CT images and blood parameters: TSH, AbTg, referred to our department from February 2017 to August 2018 to
HTG). Outcome was defined as complete response (CR), partial perform 68Ga DOTATOC PET/CT scan. Clinical indications for PET/
response (PR) (together indicated as responding R), stable disease CT scan acquisition were: staging or occult primary tumor (n = 46,
(SD) and progressive disease (PD) (indicated as not responding NR). 33.6%), restaging (n = 81, 59.1%) and surveillance (n = 10, 7.3%);
ROC analysis was performed. 39 (28.5%) patients underwent also 18F-FDG PET/CT to assess FDG
Results: SPECT-CT calibration factors (1.4 kcts/MBq), PVE avidity for high-grade NETs. Median follow-up after 68Ga DOTA-
(130 ml: 100%, 11 ml: 75%, 5.5 ml: 58%, 1.1 ml: 6%) and dead-time TOC PET/CT was 6.4 months (range 1-14 months).
correction (up to 17% of counts loss) were obtained. Mean accuracy The impact of the exam on the clinical management was evaluated on
was (- 15%) and (- 13%) for activity and dose respectively. Dose the basis of clinicians decisions after performing 68Ga DOTATOC
varies among patients and lesions (range 0.1–189 Gy/GBq). Uptake PET/CT: indication for locoregional therapies (surgery for primary
seems to decrease in following treatments (when dosimetry was occult and interventional locoregional treatment), indication/change
repeated): 2.2 Gy/GBq to 0.1 Gy/GBq for 1 lymph node and from for systemic therapies such as increase in somatostatin analogues
10.2 Gy/GBq to 4.6 Gy/GBq for 1 bone metastasis. This could con- posology or new therapeutic protocol, peptide receptor radionuclide
firm the need to increase the activity in the first treatment. Doses therapy (PRRT) or association of locoregional plus systemic
(mean ± 1 SD) for the different response groups were SD treatment.
71 ± 26 Gy, PD 81 ± 44 Gy, PR 186 ± 232 Gy; only 1 lesion Results: According to histopathologic data available from 59.8%
showed a CR (45 Gy) and due to the poor statistics was excluded patients (n = 82), 29.2% had G1, 27.7% G2, and 2.9% G3 NETs
from the analysis. When doses were related to NR and R groups respectively. In patients with known or suspected NETs, 31.4%
76 ± 35 Gy and 168 ± 220 Gy mean value were obtained respec- (n = 43) presented with locally advanced and 20.4% (n = 28) with
tively (independent samples t-test p = 0.27). ROC curve analysis metastatic disease; 65% of patients were under treatment with
showed AUC 0.64 ± 0.13 and sensitivity and a specificity equal to 76 somatostatin analogues and 16.8% received other therapies before
and 67 respectively (threshold dose 75 Gy). PET such as chemotherapy, PRRT or interventional locoregional
Conclusions: Post therapeutic lesion dosimetry in MDTC patients treatment. 68Ga DOTATOC PET/CT was positive in 62.8% of
can be performed with SPECT-CT. This approach requires good patients (n = 86). In particular, the primary lesion was positive in
synergy among different operators (physicist, nuclear medicine 53.4% of patients (n = 46), allowing the identification of occult pri-
physicians, technicians) and is feasible and accurate. Dosimetric mary lesion in all patients with suspected NET (n = 7), the
information is a powerful tool to improve the clinical strategy (i.e. identification of lymph nodes and distant metastases in 24.8%
higher activity iodine therapy, alternative treatments). Dose–response (n = 34) and in 32.8% (n = 45) of them, respectively, with upstaging
correlation must be further investigated in terms of lesion type and in 27% of patients (n = 37). 18F-FDG PET/CT was positive in 23
higher administered activity. patients (23/39). 68Ga DOTATOC PET/CT findings influenced the
therapeutic management in 37,9% of patients (n = 39, p = 0.024):

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S61

30.8% of patients were sent to locoregional therapies (surgery or PO093


interventional locoregional treatment), 46.2% to systemic therapies In-111-pentetreotide as a turning point in the targeted
(chemotherapy, introduction or increase posology of somatostatin
analogues), 10.3% to PRRT and 12.8% to locoregional plus systemic therapy of G3: a case report
treatment.
Conclusions: In accordance to previously published data, our data L. Turchetta1, G.P. Annunziata1, V. Ippolito1, M. Catalano1
confirm the pivotal role of 68Ga DOTATOC PET/CT in staging and
1
restaging NETs and underline the usefulness of this imaging tech- UOC Medicina Nucleare, AORN A. CARDARELLI, Naples, Italy
nique in the clinical management of these patients. Background-aim: According to World Health Organization (WHO)
2017 classification, high grade pancreatic neuroendocrine tumors
(pNET) are classified into two subgroups based on ki 67 immunos-
PO092 taining: well differentiated NET (WDNET) with KI67 \ 55% and
poor differentiated NEC (PDNEC) characterized by KI 67 [ 55%.
Added value of 18F-FDG PET/CT compared to receptor This new classification, come from a better knowledge of NET
imaging in lung neuroendocrine tumors pathological characteristics and tumor behavior, could change thera-
peutic management and improve patient care.
F. Linguanti1, V. Berti1, V. Vergura1, A. Kokomani1, M. Allocca1, Methods: A 57-year-old man affected by pNET previous classified as
E. Abenavoli1, M. Matteini1, L. Vaggelli1, V. Briganti1, R. Sciagra’1 NEC G3(Chromogranin ?, Synaptophysin ?, CD56 ? and Ki67 =
50%) according to WHO 2010 and with liver metastasis visualized at
1 CT has been underwent 18-FDG-PET-CT. PET scan confirmed
Nuclear Medicine Unit, Careggi University Hospital, Florence, Italy
pancreatic tail uptake (SUVmax 3.0) and V, VI, IV and VIII hepatic
Background-aim: This study analyzes the capability of 18F-FDG- segment uptake (SUV max 3.8)
PET/CT to characterize neuroendocrine tumors (NETs) of the lungs, According to current guidelines, the patient started chemotherapic
in order to demonstrate whether 18F-FDG-PET uptake is related to regimen with Cisplatinum and Etoposide (6 cicles) showing
Ki67 index in pulmonary NETs. stable disease at ad interim CT after three months.
Methods: We analyzed 42 patients with pulmonary NET, including At the end of the therapy, 18-FDG-PET-CT was performed again
typical carcinoid (TC), atypical carcinoid (AC), small cell lung cancer and it showed an increase of SUV max value at hepatic lesions and
(SCLC) and large cell neuroendocrine carcinoma (LCNEC). Of them, new hepatic lesions too. The multidisciplinary NET team decided to
37 underwent both 18F-FDG-PET/CT and receptor scintigraphy with perform 111In Pentetreotide (Octreoscan) scintigraphy because of the
111In-pentetreotide, whilst 5 underwent only 18F-FDG-PET/CT. disease progression shown in PET imaging and clinical worsening of
Acquisitions were performed 4 h and 24 h after injection for receptor the pt with persistent abdominal pain, nausea and mild impairment of
scintigraphy with 111In-pentetreotide and 1 h after injection for 18F- liver function.
FDG-PET/CT. Tumor/non-tumor ratio was measured at each time Octreoscan showed high score uptake (3–4) at multiple hepatic
point and percent difference was calculated in receptor scintigraphy lesions and at pancreas tail.
with 111In-pentetreotide (4–24%T/NT). FDG uptake was measured Therefore the pt began Octreotide LAR (30 mg i.m./28 days) and
as the ratio between SUV max and SUV liver. Results were correlated everolimus (10 mg/day) combined therapy.
with Ki67 percent index in histological response. Nonparametric Results: Immediate clinical improvement was observed and 3 months
correlation analysis was performed using SPSS software. P \ 0.05 after CT and PET-CT showed partial lesions regression (decreased in
was considered significant. volume, number and Suv value).
Results: Highly differentiated pulmonary NETs (TC and AC) showed Two years later, Octreoscan wasn’t changed, confirming long term
high 111In-pentetreotide uptake. With increasing Ki67 percent index, disease stability.
in agreement with higher malignancy and tumor dedifferentiation, the At present the pt is alive without notable symptoms. Thanks to this
percentage of tumors with high 111In-pentetreotide uptake progres- combined therapy with somatostatin analogue and everolimus based
sively reduced (p \ 0.02). on Octreoscan data, the pt obtained a 24 months progression-free
In contrast, 18F-FDG PET/CT showed higher 18F-FDG uptake in survival and a 32 months total survival from diagnosis.
poor differentiated NETs (p \ 0.001). In highly differentiated NETs, Conclusions: The case report shows high In-111Pentetreotide SPECT
18F-FDG-PET/CT uptake showed a different behavior in TC versus diagnostic performance in characterizing the biological heterogeneity
AC: absent or low uptake in TC and moderate uptake in AC (median of G3 NET and the ability to lead to the best suitable therapy.
SUV TC = 1.20; median SUV AC = 2.5). Pt’s pathological analysis with 50% Ki67 value falls in a range
Conclusions: Receptor imaging is important to characterize highly common to WDNET and PDNEC.
differentiated pulmonary NETs. The role of 18F-FDG-PET/CT is Therefore in order to establish the more appropriate targeted
acknowledged in poorly differentiated NETs, as defined by tumor therapy that could increase the global survival, a better knowledge of
proliferation (mitotic count [ 10 mm2 and Ki67 \ 5%). Our results the biological characteristics of the tumor is fundamental, especially
demonstrate the added value of 18F-FDG-PET/CT to characterize SSR density on tumor cells surface, coming from scintigraphic
tumors with intermediate spectrum of proliferation (AC: mitotic count imaging.
2–10 mm2; 5% \ Ki67 \ 20%). Even though with some overlapping Future studies will establish clinical and therapeutic impact of
features, integration of receptor and metabolic imaging is helpful in nuclear imaging data in the two subgroups of NET G3.
pulmonary NETs characterization, reflecting differences in clinical
behavior and prognosis.

123
S62 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

PO094 Conclusions: Our preliminary data evidenced that tumor uptake on


Correlation of somatostatin receptor-2 expression SSTR2-imaging correlate with SSTR2-expression on IHC but show
SSTR2 imaging superiority in receptors density identifying.
with 111IN-pentetreotide uptake Upcoming studies will take SSTR2-expression into account for more
and immunohistochemical in lung neuroendocrine detailed thoracic NET analysis.
tumors

L. Turchetta2, G.P. Annunziata2, D. Scala2, S. Campione1, PO095


V. Pellecchia1, V. Ippolito2, I. Valenti2, M. Catalano2, F. Favarulo2
Comparison between the 7th and 8th edition
1
UOC Anatomia Patologica, AORN A.Cardarelli, Naples, Italy. of the AJCC TNM staging system for differentiated
2
UOC Medicina Nucleare, AORN A.Cardarelli, Naples, Italy thyroid cancer and clinical and prognostic impact:
Background-aim: Somatostatin radiolabelled analogues imaging a single center experience
with 111In -Pentetreotide (Octreoscan) or 68Ga-peptides, is ‘‘standard
of care’’ in diagnostic management of Neuroendocrine Tumors (NET) M. Bertoli2, D. Albano2, M. Bonacina1, D. Rexhep1, E. Cerudelli1,
Efficacy of biotherapy performed with somatostatin analogues M. Gazzilli1, F. Dondi1, A. Mazzoletti1, A. Peli2, R.T. Giubbini1,
depends on the somatostatin receptors (SSTRs) density on tumor cells F. Bertagna1
surface. Low grade NETs show high SSTRs density while high grade
NETs show low SSTRs density. On the other hand literature evi- 1
Medicina Nucleare/Università degli Studi di Brescia/ASST Spedali
dences that poorly differentiated tumor can express these SSTRs with Civili di Brescia/Brescia, Italy. 2Medicina Nucleare/ASST Spedali
various density grade, so that somatostatin analogues therapy could be Civili di Brescia/Brescia, Italy
proposed for high grade tumors too.
Pathological exame and receptorial nuclear imaging can highlight Background-aim: Aim of our study was to compare patients with
receptors density. Immunohistochemistry (IHC) is able to measure differentiated thyroid cancer (DTC) previously treated with total
density of SSTRs subtype, proliferation index and synaptophysin and thyroidectomy and radioiodine (RAI) therapy before and after
chromogranin positivity. Octreoscan allows to evaluate SSTRs den- restaging according to 8th AJCC TNM staging system by disease
sity through a qualitative analysis based on uptake score from 0 to 4 outcomes.
(Krenning score). Methods: We included 981 DTC patients who underwent total thy-
The aim of the study is to find the correlation between HIC SSTRs roidectomy and RAI therapy from January 1997 to December 2003 in
expression and 111In-Pentetreotide score in thoracic NET, because of our department. We declassified them according to the 8th TNM/
a limited number of studies about this topic. AJCC edition and compared with the 7th edition focus on the main
Moreover the authors highlight the possible prognostic signifi- clinical features and disease outcome.
cance of the IHC expression of SSTR2 subtypes and scintigraphy Results: Using the 8th edition, patients classified as T1 or T2 passed
positivity. from 634 to 843 and patients classified asT3 from 319 to 122.
Methods: 32 Patients (pts) with average age of 57.5 with histological Considering patients classified as T1-T2 acc. 8th edition, T1-T2 acc.
confirmed thoracic NETs were retrospectively selected from 2017 to 7th edition and T3 acc. 8th edition, we didn’t find any statistically
2018. 26 pts met the following enrollment criteria: available Octre- significant difference in terms of first dose of RAI administrated,
oscan, tissue for pathological review and follow-up data. Pathological median age, gender and antithyroglobulin levels before RAI
samples included 16 well differentiated lung NET,(typical and atyp- (p [ 0.05). Instead, the total number of RAI treatments (p \ 0.01),
ical lung carcinoid) and 10 lung NEC (small and large cell).Well Tg level at ablation (p \ 0.01) and disease free survival (p \ 0.05)
differentiated NETs were treated with somatostatin analogues. were significantly different in T1–T2 group according to 8th edition
Patients received intravenous injection of 220 MBq of 111In-pente- than T1–T2 according to 7th edition. These evidences was not con-
treotide (Mallinckrodt Pharmaceuticals) 4 h and 24 h before whole firmed comparing T1–T2 acc. 8th edition and T3 acc. to 8th edition
body scans, static and SPECT images. Concentrated ABCam Primary (p [ 0.05).
monoclonal antibodies IgG type directed against the 2A receptor When switched to the 8th edition, 947 patients were classified as
(UMB1) of the somatostatin has been used for IHC. SSTR2 s-ex- stage I or stage II compared to 710 according to 7th edition. Among
pression was scored using a four-point scale: Score 0 absence of these two groups any statistically significant difference were found in
immunoreactivity. Score 1 pure cytoplasmic immunoreactivity, both first dose of RAI, median age, distribution of sex, antithyroglobulin
focal and diffuse. Score 2 membranous reactivity in less than 50% of levels before RAI, total numbers of RAIs, Tg levels before RAI and
tumor cells, regardless of cytoplasmic staining. Score 3 circumfer- disease free survival.
ential membranous reactivity in more than 50% of tumor cells, Conclusions: With the 8th AJCC TNM staging system, a significant
independently of the presence of cytoplasmic staining. Score 3 or 2 number of patients have been downstage despite patients classified as
were evaluated as positive cases. Pts with positive SSTR2-imaging T1–T2 with this new classification seem to have a similar behavior
(score C 2),negative SSTR2 imaging, positive SSTR2 immunoreac- and outcome compared to T3. Moreover T1–T2 acc. to 8th edition
tivity (score C 2), absence of a immunoreactivity were compared. look like more aggressive and with worse prognosis than ‘‘old’’ T1–
Results: UMB1 positivity was observed in 12 pts and UMB nega- T2 acc. to 7th edition.
tivity in 14 pts. In our opinion RAI therapy should be still consider in this group of
Octreoscan scores were [ 2 in 14 pts and no uptake was observed in patients.
12 pts. Therefore in 24 pts imaging and pathological data were con-
cordant and discordant in 2 pts. No concordance was observed in two
pts affected by small cell cancer with uptake score 2 at scintigraphy
and no receptors expression at IHC. Overall concordance of data
UMB1 versus scintigraphy was 92%. All pts treated with Octreotide
were responsive and had stable disease at follow-up.

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S63

PO096 early individuate RAI-refractory DTC patients, proving to be an


SEMI-quantitative analysis of 18F-FDG PET/CT excellent diagnostic and prognostic tool even in this kind of patients.
concurrent with first 131I therapy in high-risk
differentiated thyroid cancer patients. Preliminary
results PO097
Suspected secondary findings in 131I whole body
A. Rizzo 1, G. Perotti 1, L. Zagaria 1, C. Altini 1, S. Annunziata 1, scintigraphy post I131 therapy: preliminary single-
M. Salvatori 1 center experience with SPECT/CT
1
Nuclear Medicine Unit, Department of Diagnostic Imaging, D. Calabrò1, E. Lodi Rizzini1, C. Scampoli2, E. Tabacchi1,
Radiation Oncology and Hematology, Foundation University Hospital L. Zanoni1, P. Zagni1, F. Monari2, M. Levorato1, S. Fanti1
A. Gemelli, IRCCS, Rome, Italy
1
Background-aim: In 2015 ATA Guidelines for adult patients with Nuclear Medicine, S. Orsola-Malpighi Hospital, Bologna, Italy.
2
differentiated thyroid cancer (DTC) defined four categories to classify Radiation Oncology Center S.Orsola-Malpighi, Bologna, Italy
radioiodine-refractory patients. Two out of four categories include Background-aim: To evaluate the role of additional SPECT/CT to
presence of metastatic tissue which does not concentrate radioiodine planar post I31 therapy whole body scintigraphy (WBS) in well dif-
at the first post-therapeutic whole-body scan (TxWBS) and uptake of ferentiated thyroid cancer and relapse when suspected secondary
radioiodine in some lesions but not in others. findings are detected. Secondary aim is to evaluate which factor may
The purpose of the present study was to evaluate the performance of better predict malignancy in order to understand when it is useful to
18
F-FDG PET/CT (PET/CT) concurrent with first radioiodine therapy further investigate a WBS finding with SPECT/CT.
(RAI) in high risk differentiated thyroid cancer (DTC) patients. Par- Methods: Among the patients (pts) who underwent 131I WBS after
ticularly, we analysed the value of semi-quantitative PET/CT values radio metabolic therapy between May 2016 and September 2018,
to predict, after surgery, radioiodine-refractory DTC distant those with a report describing 131I avid suspected secondary findings
metastases. at SPECT/CT images were retrospectively reviewed. Results were
Methods: From October 2017 to October 2018, we performed 197 compared with the available further investigations, such as 18F-FDG
first RAI. All patients were classified both by using AJCC 8th edition/ PET/CT or biopsy, in order to characterize the benign or malignant
TNM classification system and ATA 2015 Risk Stratification System. nature of the I131 avid findings. Among the malignant cases, stage
We prospectively selected patients classified as high risk by ATA (according to the American Thyroid Association Classification),
2015 Risk Stratification System (gross extra-thyroid extension, T4 presence of risk factors (differentiation, vascular and extracapsular
any N any M, M1 any T any N), submitted to total thyroidectomy and invasion, resection margins, local infiltration, b-RAF mutation, mul-
first RAI treatment. tifocality), thyroglobulin values (both basal and stimulated; hTg) were
13 DTC patients [M:F = 6:7; mean age: 49.8 ± 15.2; 5 classic analyzed.
papillary thyroid cancer and 8 DTC with aggressive histological Results: Among the 457 pts who underwent 131I WBS after radio
variants] responding to the inclusion criteria were analysed. All metabolic therapy, in 75/457 pts SPECT/CT was performed and in
included patients, in hypothyroidism condition, were submitted to 58/75 (77%) pts SPECT/CT scans showed suspected secondary
PET/CT about three months after surgery and within one week from findings: in 32/58 (55%) cases lymph nodes (25/32 laterocervical,
RAI (administered activity 6.08 ± 1.14 GBq); TxWBS was per- 6/32 mediastinal, 1/32 abdominal), in 11/58 (19%) bone lesions, in
formed 3 days after RAI. 8/58 (14%) lung nodules, in 1/58 (2%) hepatic lesion, in 7/58 (12%)
The analysis of PET/CT and TxWBS images was performed only lesions with unclear anatomical correspondence. Nineteen/58 pts
on distant metastases. Loco-regional lymph-node metastases were not (33%) underwent to 18F-FDG PET/CT after WBS in suspicion of
evaluated to avoid the risk of false positive PET/CT results due to the poor differentiation : in 12/19 pts (63%) PET was positive and con-
recent surgery. cordant (in terms of lesions’ number and site) with WBS; in 7/19 pts
Qualitative analysis was performed comparing in the same (37%) PET/CT was negative (probably well differentiated lesions); in
metastasis the different uptake of 18F-FDG and radioiodine. 2/7 PET negative pts biopsy confirmed the malignancy of the lesions.
Semi-quantitative analysis [standard uptake value (SUV), qPET, Among the 14/58 pts with confirmed secondary lesions, stage, risk
metabolic tumor volume (MTV) and total lesion glycolysis (TLG)] factors and hTG levels were evaluated:
was performed only on PET/CT target lesions, defined as the hottest - 1/14 (7%) pts was stage I, 9/14 pts (64%) were stage II, 4/14 pts
lesion for each organ in every patient. (29%) were stage III;
Receiver Operating Characteristics (ROC) curve analysis was used - 7/14 (50%) had no risk factors, 1/14 pts had only one risk factor
to identify a potential cut-off for semi-quantitative parameters in and 6/14 pts showed more than 2 risk factors;
order to predict radioiodine uptake. - basal hTG values were available in 11/14 pts: 9/11 (82%)
Results: The qualitative analysis of PET/CT and TxWBS images showed hTg [ 5 ng/mL, 2/11(18%) hTg between 0,2 and 1 ng/mL;
showed negative concordance in 4 patients and positive concordance in the remaining 3/14 pts, AbTg values were positive.
in 2 patients. In 7 patients, PET/CT and TxWBS mismatched lesions - stimulated hTG (recombinant TSH) values were available in
were observed (2 lesions revealed only by TxWBS, 4 lesions only by 13/14 pts: in 10/13 (77%) stimulated hTG was [ 10 ng/mL while in
PET/CT, 3 lesions by both exams). 3/13 (23%) pts between 1 and 5 ng/mL. In one pt, AbTg values were
The target lesions with no radioiodine uptake showed to semi-quan- positive.
titative PET/CT analysis a value of SUVmax and qPET greater than Nine/14 pts (64%) were treated for primary carcinoma while 10/14
11.35 (AUC = 0.9, p \ 0.001) and 4.56 (AUC = 0.9, p \ 0.001) (71%) pts for recurrence/residual disease at least once (2 or more
respectively. MTV and TLG thresholds were not able to predict which cycles) and were retreated for persistent high hTg levels.
lesions had no RAI uptake. Six/58 (10%) pts underwent to further investigation (CT or biopsy)
Conclusions: Despite the small number of selected cases, this pre- and resulted falsely positive: all these pts showed basal hTG
liminary work showed that PET/CT, performed concurrently with the levels \ 1 ng/mL and stimulated hTG levels \ 10 ng/mL.
first RAI in high-risk DTC patients, could be a promising method to

123
S64 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

Conclusions: SPECT/CT has an additional diagnostic value to planar PO099


WBS after I131 radio metabolic therapy in pts with well-differenti- The prognostic role of FDG PET/CT before combined
ated thyroid carcinoma. Although biased by the paucity of cases, this
analysis demonstrates that it is useful to perform SPECT/CT even in radio-chemotherapy in anal cancer patients
those pts with low stage and few risk factors, especially if basal hTg is
measurable and TSH values are suppressed. Further analyses on lar- D. Ripani2, L. Leccisotti1, S. Manfrida1, R. Barone3, L. Tagliaferri1,
ger population are warranted to search for possible predictive factors. M.A. Gambacorta2, V. Privitera2, V. Masiello1, V. Rufini2,
V. Valentini2, A. Giordano2
1
Diagnostica per Immagini, Radioterapia Oncologica and Ematologia
PO098 Department, Fondazione Policlinico Universitario A. Gemelli IRCCS,
A prospective trial for the evaluation of esophageal Rome, Italy. 2Diagnostica per Immagini, Radioterapia Oncologica
cancer patients: fluorodeoxyglucose (FDG) positron and Ematologia Department, Università Cattolica del Sacro Cuore -
Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
emission tomography (PET)/computed tomography 3
Radius S.r.l., Budrio (BO), Italy
(CT) vs. contrast enhancement (C.E.)CT VS. FDG PET/
Background-aim: Pre-treatment prognostic factors able to accurately
C.E.CT identify patients with anal squamous cell carcinoma (SCC) at high
risk of recurrence who may benefit from optimized treatment are still
P. Reccia1, L. Evangelista1, M. Burei1, L. Cuppari1, R. Alfieri3, lacking. Therefore, the aim of this study was to assess the prognostic
S. Galuppo2, A.R. Cervino1 value of FDG PET/CT parameters measured before combined radio-
chemotherapy (RCT).
1
Nuclear Medicine and Molecular Imaging, Veneto Institute of Methods: Consecutive pts with anal SCC undergoing staging FDG
Oncology IOV-IRCCS, Padua, Italy. 2Radiation Oncologist, Veneto PET/CT from May 2011 to February 2018 and treated with combined
Institute of Oncology IOV-IRCCS, Padua, Italy. 3Surgery Oncology RCT were retrospectively reviewed. The following PET/CT param-
Unit, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy eters were calculated: SUVmax, SUVpeak, SUVmean, metabolic
Background-aim: The present study was conceived on a population tumor volume (MTV) and total lesion glycolysis (TLG) of primary
of esophageal cancer patients who have been undergoing FDG PET/ tumor (T) and all involved loco-regional lymph-nodes (N); SUV
CT and c.e.CT in a single session, both at initial staging and after mean, MTV and TLG were measured by using a threshold of 40% of
more than 4 weeks from the end of neoadjuvant treatment. The SUVmax. Whole-body (WB) MTV and WB TLG were calculated as
prospective trial was approved by our institutional Ethical Committee. the sum of the MTV and TLG values of all lesions in each pt. The
Herein, we reported the preliminary data about the comparison of endpoints were overall survival (OS), disease specific survival (DSS),
diagnostic performance among PET/CT, c.e.CT, PET/c.e.CT and disease free survival (DFS), local relapse free survival (LRFS),
histology, after neoadjuvant therapy. metastatic free survival (MFS) and colostomy free survival (CFS).
Methods: The multidisciplinary team of our Institute started the Univariate survival analysis with Kaplan–Meier curves was per-
recruitment from January 2012. After concomitant neoadjuvant formed to allow between-group comparison. Median split was used to
therapy, a whole-body PET/CT scan followed by a three-phases neck- turn continuous variables into dichotomous variables. P-values (Log-
thorax-abdomen c.e.CT, in a single session, was performed in all Rank test) were corrected for multiple comparisons using the Ben-
patients. Four specialized physicians (two radiologists and two jamini–Hochberg method. A logistic regression model was developed
nuclear medicine specialists) read the images, separately. The addi- for the multivariate analysis. Fivefold cross-validation was also per-
tional value provided by PET/c.e.CT over of PET/CT and c.e.CT formed to prevent overfitting. The area under the receiver operating
separately performed, was obtained by comparing the data with characteristic (ROC) curve (AUC) was used to quantify the predictive
histology. accuracy.
Results: A total of 35 patients were prospectively collected for the Results: Fifty-nine pts (39 F; 63 ± 11 years) were included in the
end-point of the study. The imaging co-registration (PET and c.e.CT) study: 49 (83%) pts were in advanced stage (cT3-4 any N; cT2N ?).
was good in 89% of patients, discrete in 8% and scarce in only 1%. Combined RCT was administered mainly using mitomycin C and
The combination of PET/c.e.CT for the primary tumor was able to 5-fluorouracil. RT was delivered with a simultaneous-integrated boost
reduce the rate of false negative (FN) findings otherwise reported by (SIB-IMRT) with 44-55.8 Gy; according to initial disease presenta-
PET/CT alone (from 4 to 0%). Furthermore, the combined images, tion and response to combined treatment a sequential boost was added
improved the detection of lymph node metastases, by reducing the FN in 43 pts (73%). The median follow-up period was 28 months. OS,
rate and FP rate, respectively for PET/CT and c.eCT (89% vs. 44% DSS, DFS and CFS were 83, 90, 71 and 78% respectively. Colostomy
and 69% vs. 13%, respectively). Finally, PET/c.eCT reduced the FP rate was 22% (13 pts). Twelve (20%) pts relapsed locally after
rate of c.e.CT for the identification of distant metastases (from 22 to treatment while 3 (5%) pts had a systemic recurrence. Univariate
6%). analysis showed that T-TLG C 117, WB-TLG C 139 and WB-
Conclusions: FDG PET/c.e.CT represents an accurate and feasible MTV C 19 cm3 were significantly related to worse OS, DSS and
imaging method to predict the pathological stage of patients with lower CFS. Furthermore, T-MTV C 15 cm3 was significantly related
esophageal cancer. to worse DFS and lower CFS. Finally, T-TLG and WB-TLG values
above the median resulted significantly related to worse DFS. Logistic
regression model showed that stage, age, T-SUVpeak, T-TLG and
WB MTV are statistically significant (p \ 0.05) predictors of OS
(AUC = 0.935, fivefold-cv AUC = 0.80 ± 0.09).
Conclusions: Higher pre-treatment MTV and TLG values predict
worse outcome. These results, which need a validation in a
prospective study, suggest that measurement of baseline metabolic
tumor burden may provide helpful biomarkers for pt stratification and
personalised treatment in anal cancer.

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S65

PO100 PO101
18F-FDG PET/CT in predicting outcome Effectiveness and safety of 90-yttrium
of the neoadjuvant treatment in locally advanced rectal radioembolization in liver tumors: improvement
cancer from multimodality imaging analysis

R.V.A. Vicinelli3, E. De Bernardi3, R.M. Niespolo4, A. Scarabelli3, A. Di Palo2, C. Ferrari2, A. Niccoli Asabella2, V. Lavelli2, P. Caputo2,
E. De Ponti1, C. Dolci3, S. Terravazzi4, C. Landoni3, L. Guerra2, G. Sigrisi2, G.V. Difonzo2, G. Ranieri1, C.D. Gadaleta1, G. Rubini2
C. Crivellaro3
1
Diagnostic and Interventional Radiology Unit with Integrated
1
Medical Physics, ASST-Monza, San Gerardo Hospital, MB, Italy. Section of Translational Medical Oncology-National Cancer Research
2
Nuclear Medicine Department ASST-Monza, San Gerardo Hospital, Centre, IRCCS Istituto Tumori ‘‘Giovanni Paolo II’’ Bari, Italy.
MB, Italy. 3Nuclear Medicine, University of Milano-Bicocca, Milan, 2
Nuclear Medicine Unit, Interdisciplinary Department of Medicine-
Italy. 4Radiotherapy Department, ASST-Monza, San Gerardo University of Bari ‘‘Aldo Moro’’, Bari, Italy
Hospital, MB, Italy
Background-aim: Trans-Arterial-Radioembolization (TARE) using
Background-aim: The aim of this study was to evaluate the role of 90-Yttrium microspheres (90Y-spheres) is a well-established therapy
baseline 18FDG PET/CT in predicting the histopathological response option in primary or secondary liver malignancies.
to neoadjuvant chemo-radiotherapy treatment in rectal cancer corre- To date, there is not a consensus in reference imaging method for the
lating metabolic and geometric-shape features of primary lesion with evaluation of the extent of liver disease after TARE. Morphological,
tumor regression grade (TRG) and presence of recurrence. metabolic and perfusion tumor characteristics, provided by contrast-
Methods: Sixty-one patients with rectal cancer and candidates to enhanced CT (CECT)/trans-arterial CECT (arterial-CT), PET/CT and
neoadjuvant chemo-radiotherapy (nCRT) followed by surgery, 99mTc-MAA-SPECT/CT, can highlight different but equally impor-
underwent an 18F-FDG PET/CT scan before treatment. All rectal tant aspects of the same disease. We present our multimodality
lesion were contoured using PETVCAR, obtaining the following imaging analysis approach in which the TARE planning derived from
parameters: maximum and mean standard uptake values (SUVmax the different pre-treatment imaging modalities.
and SUVmean), metabolic tumor volume (MTV), total lesion gly- Methods: From May 2016 to March 2018, 54 patients (mean age
colysis (TLG), histogram-intensity features and geometric-shape 69 years, range 38–84) were evaluated as potentially candidates for
features. TARE: 34/54 (63%) hepatocellular carcinoma (HCC), 18/54 (34%)
Histopathological response on surgical samples was assessed using liver metastasis (LM), 2/54 (3%) cholangiocarcinoma. All patients
Mandard grading system, classified as responders (TRG 1–2) and were preliminary subjected to 18F-FDG-PET/CT (in FDG-avid
non-responders (TRG 3–4). All patients underwent to clinical follow- tumors) or 18F-FCH-PET/CT (in well-differentiated HCC) and an
up. Extracted metabolic parameters were compared to tumor regres- abdomen CECT for staging liver disease and to detect the target
sion grade (TRG) and to the presence of recurrence, by using tumor, both with metabolic and morphological data. Moreover, during
Kruskal–Wallis test. the angiographic work-up, arterial-CT was acquired, outlining the
Results: Out of 61 patients, 36 resulted to be histopathologic perfusion territories of the hepatic artery branches. Finally, 99mTc-
responders to nCRT (TRG1-2), while the remaining 25 resulted non- MAA-SPECT/CT was performed as TARE simulation. Subsequently,
responders (TRG [ 3). nuclear physician together with radiologist provided an off-line fusion
Significant differences between responders and non responders were imaging registration of arterial-CT, 99mTc-MAA-SPECT/CT and
found for MTV (mean 26.4 and 45.3 respectively p = 0.01), TLG PET/CT exams on a dedicated workstation in order to integrate vol-
(mean 187.9 and 459.7 respectively p = 0.007), 3 histogram-intensity ume with perfusion and metabolic target lesion data. When needed,
features (Hist-variation p = 0.015, Hist-standard deviation p = 0.015, the angiographic work-up and 99mTc-MAA-SPECT/CT simulation
His-Entropy p = 0.028) and 3 geometrical-shape features (Surface were repeated. Mean and max counts in 99mTc-MAA-SPECT/CT
p = 0.02, Surface to volume ratio p = 0.010 and Compactness and volumes in arterial-CT, both for lesion and healthy perfused liver,
p = 0.009). Median follow-up resulted 5.25 years (range 0.9–9.6); were considered to calculate the injected activity. After TARE, 90Y-
22/61 (36%) patients had recurrence. Histopathological responders PET/CT was performed to confirm the preliminary simulation.
had a better DFS (p = 0.003). MTV (p = 0.02), Surface (p = 0.04), Results: In 21/54 (38%) patients, PET/CT information guided the
Sup/vol (0.024) and Compactness (p = 0.0121) were correlated to the treatment in the most metabolically active area of the target lesion. In
presence of recurrence. No significant differences were found for 5/54 (9%) patients, arterial-CT identified more extensive liver
SUVs. involvement with widespread microscopic disease, not detected at
Conclusions: In locally advanced rectal cancer patients submitted to staging imaging; they resulted not eligible for TARE. In 7/54 (13%)
nCRT, MTV, TLG and some textural/geometric-shape features cases, there was discordance between 99mTc-MAA-SPECT/CT and
extracted from FDG uptake of the primary tumor, are promising in arterial-CT results and the angiographic work-up was repeated. The
predicting histological response and recurrences. Larger studies with remnant cases demonstrated a good match between different imaging
independent testing database are needed to clarify the role of these methods. In all cases the 90Y-PET/CT post-TARE confirmed the
metabolic features to realize a personalized medical treatment. preliminary radiopharmaceutical distribution.
Conclusions: The multimodality imaging analysis based on the
integration of different information develops a ‘‘disease liver map’’
which consider morphologic, metabolic and perfusion aspects. Our
experience demonstrates that this approach allow to optimize treat-
ment efficacy (directing more precisely to the target lesion with a
better selectivity) and safety (avoiding irradiation to the healthy
liver).

123
S66 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

PO102 allows a better management of HCC patients, avoiding an over-


18F-FCH-PET/CT early response in hcc patients treatment in patients in complete response or conversely early treat
those, particularly with multifocal disease, that need to complete the
treated with 90Y-trans-arterial-radioembolization treatment in the other lobe.

C. Ferrari2, A. Niccoli Asabella2, A. Di Palo2, P. Caputo2,


A. Cimino2, V. Lavelli2, S. Sisto2, G. Ranieri1, C.D. Gadaleta1,
G. Rubini2 PO103
Treatment of hepatic tumour with 166HO-spheres
1
Diagnostic and Interventional Radiology Unit with Integrated selective internal therapy (SIRT): preliminary
Section of Translational Medical Oncology-National Cancer Research
Centre, IRCCS Istituto Tumori ‘‘Giovanni Paolo II’’ Bari, Italy. experience at National Cancer Institute of Milan
2
Nuclear Medicine Unit, Interdisciplinary Department of Medicine,
University of Bari ‘‘Aldo Moro’’, Bari, Italy M. Maccauro1, C. Spreafico1, S. Bhoori1, C. Chiesa1, T. Cascella1,
G. Aliberti1, A. Marchiano1, E. Seregni1, V. Mazzaferro1
Background-aim: Hepatocellular carcinoma (HCC) is a common
cause of cancer related mortality. Among the therapeutic procedures, 1
Fondazione IRCCS Istituto nazionale Tumori, Milan, Italy
Trans-Arterial-Radioembolization (TARE) with 90Yttrium-micro-
spheres has demonstrated high efficacy across the whole spectrum of Background-aim: To evaluate safety, efficacy and toxicity of the
HCC from early to advanced stages. intra-arterial injection of 166Ho microspheres (Terumo) in HCC and
Diagnosis and treatment response evaluation in HCC patients is cholangiocarcinoma (ICC).
mainly performed with contrast-enhanced Computed Tomography Methods: From May 2018 to September 2018, 2 patients with
(ceCT), based on RECIST criteria. However, morphological changes unresectable HCC and 1 patient with ICC able to undergo angiog-
on CECT could be not detected before 3 months. raphy were treated with 166Ho-Spheres SIRT. All patients had pre-
The aim of this study was to assess the reliability of 18F-FCH- treatment evaluation including : CT scan, a-fetoprotein (AFP) levels,
PET/CT in the early response evaluation to TARE compared to ceCT, liver function tests, 99mTc- macroaggregated albumin (99mTc-
in well-differentiated HCC patients. MAA) SPECT/TC scan, liver Magnetic Resonance (MR) and
Methods: 20 patients (mean age 72.4 years, range 53–84) affected by angiography to define the vascular anatomy.
unresectable well-differentiated HCC and treated with TARE, per- Two were a multifocal HCC patients with Child A, and with Bilirubin
formed 18F-FCH-PET/CT and ceCT before and after 1 month from 0.40 mg/dL and 0.81 mg/dL respectively, another was a ICC patient
treatment. Radiologic response assessment was performed according with Bilirubina 0.75 mg/dL. The average tumour sizes of all patients
to RECIST criteria as: Complete Response (CR), Partial Response was 11.7 cm. A standard lobar treatments for 166Ho-Quirem Spheres

(PR), Stable Disease (SD), and Progressive Disease (PD). The were performed (patients median age 63).
semiquantitative analysis, by using SUVmax variation (%), was The therapeutic activity was calculate in order to give an average
evaluated to establish PET/CT response assessment as following: CR whole liver absorbed dose of 60 Gy, as per IFU. A MR was per-
(absence of lesions), PR (SUVmax reduction [ 25%), PD (SUVmax formed the day after the SIRT, a SPECT/CT was performed the fifth
increase [ 30%) and SD (no PR or PD). CR ? PR patients were day after. Urine collect was performed for 5 day after the
considered responders, while SD ? PD were no responders. The administration.
agreement between the two imaging methods was calculated by using To assess tumour response CT scan and biochemical markers were
Cohen’s K. performed at 1 month and every 3 months post therapy.
Results: 13/20 (65%) patients had multifocal HCC at baseline CT and Results: All procedures were safe, without major complications.
18F-FCH-PET/CT, while 7/20 (35%) had a single lesion (mean Median follow-up was 4 months. The overall median dose delivered
diameter 46 mm, range 35–80). According to RECIST: 3/20 (15%) was 60 Gy to the target lobe, 262 Gy to the tumour. A typical dose
patients were classified as CR, 5/20 (25%) PR, 9/20 (45%) SD, 3/20 given was either 4,3 GBq. About radiation safety dose rate, T0 con-
(25%) PD. According to semiquantitative 18F-FCH-PET/CT analysis: tact of administration box 200–300 uSv/h, T0 @ 1 m right side 20
8/20 (40%) patients were considered CR, 7/20 (35%) PR, 2/20 (10%) uSv/h, t = 24 h @ 1 m right side 11 uSv/h, Urine excretion in 72 h is
SD, 3/20 (15%) PD. In particular, in 7/20 (35%) patients 18F-FCH- 1/10000.
PET/CT and ceCT showed discordant response: CR vs SD in 3/7 According to RECIST and CHOI criteria a partial response was
(42%) patients (single lesion), PR vs SD in 4/7 (57%) patients (3 observed in all patients. No bilirubina change, pulmonary toxicities
multifocal and 1 single lesion). PD was detected in both imaging and none life threatening were observed
modalities. The agreement between the two imaging methods was fair Conclusions: To be conclusive we need a larger patients series and a
(k = 0.364, 95% IC 0.070–0.657). longer follow, but a 166Ho-Spheres SIRT seems to be a safe thera-
Conclusions: Our preliminary results demonstrated that 18F-FCH- peutic option for advanced-intermediate HCC and ICC. In next future
PET/CT is a reliable method to the early evaluation of patients with we will have the opportunity to use a Holmium scout dose is expected
unresectable well-differentiated HCC who underwent to TARE. This to improve the treatment planning

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S67

PO104 PO105
Dosimetry data and efficacy of transarterial Preliminary experience of the hepatic transarterial
radioembolization in patients with unresectable administration of HO166-PLLA microspheres
intrahepatic cholangiocarcinoma in patients with liver metastases from colorectal cancer

T. Depalo3, G. Boni3, I. Bargellini1, G. Lorenzoni1, F. Guidoccio3, T. Depalo3, G. Boni3, I. Bargellini1, E. Bozzi1, F. Bianchi3,
E. Bozzi1, E. Fiorelli3, L. Caponi3, A.C. Traino2, R. Cioni1, R. Cervelli1, F. Guidoccio3, R. Viglialoro3, A. Giuliano2,
D. Volterrani3 F. Di Martino2, A.C. Traino2, R. Cioni1, D. Volterrani3
1 1
Department of Vascular and Interventional Radiology, University Department of Vascular and Interventional Radiology, University
Hospital of Pisa, Pisa, Italy. 2Division of Health Physics, University Hospital of Pisa, Pisa, Italy. 2Division of Health Physics, University
Hospital of Pisa, Pisa, Italy. 3Regional Center of Nuclear Medicine, Hospital of Pisa, Pisa, Italy. 3Regional Center of Nuclear Medicine,
University Hospital of Pisa, Pisa, Italy University Hospital of Pisa, Pisa, Italy
Background-aim: Transarterial radioembolization (TARE) is an Background-aim: Transarterial radioembolization (TARE) is an
option of treatment in patients with unresectable intrahepatic option of treatment for several liver malignancies. Recently, new
cholangiocarcinoma (ICC). Aim of this study was to investigate poly-L-lactic acid (PLLA) microspheres labelled with Holmium-166
patient outcome after TARE and the relationship with tumor absorbed (Ho166) have been introduced in clinical practice. Ho166 is a high-
dose. TARE efficacy has been also analyzed in terms of radiobio- energy -emitting isotope with  emission and paramagnetic prop-
logical sensibility. erties. Aim of this study is to assess the feasibility, efficacy and safety
Methods: Since 2012 up to now, patients with unresectable ICC of TARE with Ho166-PLLA microspheres in patients with liver
underwent pre-TARE planning angiography and Tc99m-MAA metastases (LM) from colorectal cancer (CRC).
SPECT/CT. TARE procedure with Y90 resin microspheres was per- Methods: Two patients with multiple LM from CRC, who encoun-
formed 7–14 days later followed by PET/CT within 24 h. The tered a previous liver resection and at least two lines of
administered activity of Y90-microspheres was determined using the chemotherapy, were recruited. Patients, previously selected by MRI
BSA method. Post-treatment 3D dosimetry based on PET/CT images scan, underwent a pre-TARE planning angiography and Tc99m-MAA
was performed to calculate tumor absorbed dose. Response to TARE SPECT/CT in order to assess the lung shunt and to simulate the
was evaluated in terms of RECIST criteria and the reduction of the hepatic distribution of the activity. TARE with Ho166-PLLA
treated tumor volume was based on CT scan at 4–6 weeks after microspheres was performed 7-14 days later followed by SPECT/CT
treatment and then every 3 months. The radiobiological a parameter within 24–48 h. Administered activity was predetermined using a
of a simplified linear quadratic model (LQM) was estimated in standard approach, that included liver weight and whole liver dose
selected cases and the trend of tumor control probability (TCP) was (B 60 Gy). In one case, a lower whole liver dose (40 Gy) was con-
obtained. Overall survival (OS) and time-to-progression (TTP) after sidered due to high risk of liver failure. In each patient, two FDG
TARE were also assessed. PET/CT scans, before treatment and after 2 months from TARE, were
Results: Thirty-four TARE treatments were performed in 27 patients performed in order to evaluate the tumor metabolic response in terms
including bilobar treatments in 5 patients and retreatments in the same of SUVmax, SUVmean, MTV and TLG. VOIs including each
lobe in 2 patients because of local relapse. The mean injected activity hypermetabolic lesion (standard threshold of 42%) were drawn on
was 969 ± 330 MBq. In 29 procedures, where post-TARE Y90-PET/ PET/CT and referred on post-TARE SPECT/CT and the average
CT was performed, the average absorbed dose to the tumor and to the absorbed dose of each VOI was calculated. Moreover, after TARE
healthy liver resulted 123 ± 28 Gy and 49 ± 10 Gy, respectively. At (24-48 h), patients underwent 1.5T and 3T MRI of the abdomen (R2*
the best response on CT (128 ± 90 days after TARE), we observed 7 values from the multi-gradient echo sequences; parameters: TR =
PR (24.1%), 14 SD (48.3%) and 8 PD (27.6%). A significant volu- 43.8, first TE = 1.4100 16 echo-train, FA = 40). Tumor and healthy
metric reduction of the treated tumor was recorded (135 ± 164 ml liver distributions of Ho on R2* maps of MRI were compared with
pre-treatment vs 94 ± 117 ml post-treatment; p \ 0.05). No rela- average counts on post-TARE Ho166-SPECT in terms of lesion-to-
tionship between tumor absorbed dose and its volumetric reduction non lesion ratios (L/N).
was observed. A significant direct linear correlation between TTP Results: LM were treated with two administrations of Ho166-PLLA
(median of 7.3 months; IC 95% 2.2–14.1) and OS (median of microspheres in one patient and with one administration in the other
20.2 months; IC 95% 14.7–50.8) was found. OS was significantly one. No adverse events were observed after both treatments. A total of
higher in patients treated with TARE followed by chemotherapy than 10 separated liver regions were selected on pre-treatment PET/CT and
in patients who underwent only TARE (50.9 vs 16.4 months, on post-TARE SPECT/CT. A significant reduction of MTV (11.3 vs
p = 0.022). From the analysis of 23 procedures, where follow-up CT 3.5 cm3, p = 0.002), TLG (69.9 vs 15.5 g, p = 0.002), SUVmax (15.2
data were available, the a parameter resulted 0.006 ± 0.003 Gy-1. vs 5.8, p = 0.006) and SUVmean (9 vs 4.5, p = 0.006) was observed.
The curves of TCP suggest the need to increase tumor doses in order An inverse linear relationship was found between average absorbed
to improve the probability of tumor control. dose and SUVmax (r2 = 0.58, p \ 0.001) and between average
Conclusions: In our experience, TARE with Y90 microspheres is an absorbed dose and SUVmean (r2 = 0.65, p \ 0.005). A good corre-
effective option for patients with unresectable ICC. The application of lation was found also between mean L/N ratios obtained with MRI
radiobiological models suggests the need to increase tumor absorbed and SPECT/CT.
dose in order to improve outcome. Therefore, in our opinion the BSA Conclusions: TARE with Ho166-PLLA microspheres is a feasible
method is not the best approach to calculate the activity to be and safe alternative of intra-arterial therapy for hepatic malignancies.
administered. The low prevalence of objective response in our series In these first two patients, an effective metabolic response of LM from
supports this hypothesis. However, a parameter seems to be variable CRC at the first step of follow-up was observed. Further investiga-
in this tumor setting. Further evaluations are needed to establish tions are needed to evaluate the long-term efficacy of treatment.
which factors could affect the variability of the radiobiological TARE with Ho166-PLLA microspheres has also the potential
parameter. advantage of multi-modality imaging, combining SPECT and MRI.

123
S68 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

PO106 PO107
Clinical and prognostic role of 18F-FDG PET/CT Brown fat activation detection rate at 18F-FDG PET/
in recurrent endometrial carcinoma CT is significantly higher in sex hormone-depending
tumors compared to non sex hormone-depending
D. Albano1, M. Bonacina1, R. Durmo1, E. Cerudelli1, M. Gazzilli1, tumors in adult females
F. Dondi1, A. Mazzoletti1, F. Bertagna1, R. Giubbini1
1 M. Bonacina1, D. Albano2, M. Bertoli2, R. Durmo1, F. Dondi1,
Nuclear Medicine, University of Brescia and Spedali Civili, Brescia,
E. Cerudelli1, M. Gazzilli1, A. Mazzoletti1, F. Bertagna3, R. Giubbini3
Italy
1
Background-aim: Endometrial carcinoma (EC) is a common gyne- Medicina Nucleare, Università degli studi di Brescia, Brescia, Italy.
2
cological cancer with an overall good prognosis, except of cases of U.O. Medicina Nucleare, ASST Spedali Civili di Brescia, Brescia,
advanced EC or in presence of recurrence. Conventional imaging (CI) Italy. 3U.O. Medicina Nucleare, Università degli Studi di Brescia/
and tumor marker have limited accuracy for detecting recurrence in ASST Spedali Civili di Brescia, Brescia, Italy
these patients. The aim of this retrospective study was to assess the
Background-aim: Aim of our study was to compare brown fat (BF)
diagnostic performance, the prognostic value and the impact on
activation ratio detected with fluorine18-fluorodeoxyglucose positron
therapeutic management of 18fluorine-fluorodeoxyglucose positron
emission tomography/computed tomography (18F-FDG PET/CT) in
emission tomography/computed tomography (18F-FDG PET/CT) in a
sex hormone-depending tumors (SHDT) and non-sex hormone-de-
large sample of patients with suspected recurrent EC.
pending-tumors (NSHDT) in a large population of adult females.
Methods: We retrospectively evaluated 157 patients who had
Being SHDT correlated with higher sex hormones circulating levels, a
undergone surgery with/without adjuvant therapy for histologically
higher rate of BF detection in these tumors at FDG PET compared to
proven EC. All patients underwent restaging 18F-FDG PET/CT for
NSHDT could be a consequence of BF activation dependence on sex
suspected recurrence. Comparable CI (contrast-enhanced CT and/or
hormones.
magnetic resonance imaging) was available for 150 patients and was
Methods: Breast cancer, Ovarian cancer and Uterus cancer (both
compared to PET/CT results. The PET images were analyzed visually
endometrial and cervix) were considered SHDT; stromal tumors were
and semi-quantitatively by measuring the maximum standardized
included as supposed to be hormone-depending in these tissues. We
uptake value body weight (SUVmax), metabolic tumor volume
retrospectively included 538 18F-FDG PET/CT studies positive for
(MTV) and total lesion glycolysis (TLG).). For the entire population,
BF detection in adult females patients performed from 2005 to 2015,
receiver operating characteristic curve analysis was used to identify
extrapolated from a total amount of 10035 PET scans performed in
the optimal cutoff point of semiquantitative parameters in the light of
adult females. A |2 test was performed to anylize BF positive/BF
progression free survival (PFS) and overall survival (OS). A combi-
negative ratios in SHDT and NSHDT.
nation of clinical follow-up/imaging follow-up and/or histopathology
Results: Four thousands two hundred and one PET studies were
(when available) was taken as reference standard. PFS and OS were
performed in evaluation of SHDT, and 5834 in evaluation of NSHDT.
computed using Kaplan–Meier curves.
Among 4201 SHDT evaluated with FDG PET, 239 were positive for
Results: Seventy-nine patients (50.3%) had positive 18F-FDG PET/
BF detecion and 3962 were negative; among 5834 NSHDT evaluated
CT (average SUVmax 13.1) showing the presence of at least one
with FDG PET, 299 were positive for BF detection and 5535 were
hypermetabolic lesion consistent with local recurrence or metastatic
negative. BF detection rate was significantly higher in SHDT com-
lesion, while the remaining 78 (49.7%) were negative. Sensitivity,
pared to NSHDT (p \ 0.01).
specificity, positive predictive value, negative predictive value and
Conclusions: The significantly higher rate of BF detection in SHDT
accuracy of 18F-FDG-PET/CT were 96%, 99%, 99%, 96%, 97%
at FDG PET compared to NSHDT could support BF activation
respectively and were higher compared to CI (97, 62, 72, 96 and
depending on female sex hormone; further studies are needed taking
80%). CI and PET/CT were concordant in 120 patients and discordant
in account different phases in pathology management and sex hor-
in 30 patients. After a mean follow-up period of 39 months, relapse or
mone blocking therapy.
progression of disease occurred in 58 (37%) patients with an average
time of 22.1 months and death occurred in 37 (23%) patients with an
average time of 27.6 months. A positive 18F-FDG PET/CT was
significantly associated with shorter PFS and OS compared to unre- PO108
markable PET/CT scan, both at 3-year (PFS 37% vs 91% p \ 0.001;
18F-FDG PET/CT in preoperative nodal staging
OS 54% vs 98% p \ 0.001) and 5-year (PFS 27% vs 77% p \ 0.001;
OS 40% vs 92% p \ 0.001). Instead, SUVmax, MTV and TLG were of endometrial cancer: radiomics can improve
not correlated with outcome survival. 18F-FDG-PET/CT results had a sensitivity in detecting nodal metastases
significant impact on therapeutic approach in 33 patients: avoiding
unnecessary therapies in 28 cases and modifying therapeutic choice in C. Crivellaro4, A. Buda1, D. Vicini2, F. Elisei3, L. Guerra3,
5 cases. C. Landoni4, R. Fruscio2, E. De Bernardi5
Conclusions: 18F-FDG PET/CT showed a good diagnostic perfor-
mance in patients with suspected recurrent EC, superior than 1
Clinic of Obstetrics and Gynaecology, San Gerardo Hospital, Monza,
conventional imaging, and showed an important prognostic value in MB, Italy. 2Gynaecology, University Milano-Bicocca, Milan, Italy.
assessing the rate of PFS and OS. Moreover, PET/CT allowed for a 3
Nuclear Medicine, ASST-Monza, San Gerardo Hospital, Monza,
change in treatment decision in about 20% of cases. MB, Italy. 4Nuclear Medicine, University Milano-Bicocca, Milan,
Italy. 5University Milano-Bicocca, Milan, Italy
Background-aim: Sentinel lymph-node (SLN) biopsy ultrastaging,
able to identify micrometastatic deposits, increased false-negative
PET/CT findings in nodal staging of endometrial cancer patients.
Indeed, small metastatic LNs lesions may remain undetected by PET/
CT scan because of limited spatial resolution of the technique. The

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S69

aim of this study was to investigate if imaging features computed on MRI was performed after chemotherapy to evaluate response to
the primary lesion could improve sensitivity in detection of nodal treatment. After the surgery all patients underwent clinical and
metastases. diagnostic re-evaluations to plan if perform further treatment or fol-
Methods: Between January 2009 and August 2018, 115 women with low-up only. The minimum follow-up duration was 18 months.
histologically proven endometrial cancer who underwent preoperative The volume of the primary tumor was delineated on the PET images
18F-FDG PET/CT were retrospectively considered. SUV, MTV, by a single observer, applying a variable threshold of SUVmax,
TLG, geometrical shape, histograms and texture features were com- within a semiautomatic algorithm implemented in PET-VCAR soft-
puted inside tumour contours. In the first group of 86 patients (group ware (GE Healthcare Milwaukee, USA). On the volume of interest
1) association between imaging features and LN metastases was (VOI), 56 features were extracted by LIFEx free software. In order to
performed by univariate Mann–Whitney test and by neural network assess the association between the features and the outcomes
multivariate model. Univariate and multivariate models were assessed (chemotherapy response (outcome1) and treatment decision (out-
with leave one out on 20 training sessions and on a second group of come2)), Student t test or the Mann–Whitney test were performed,
testing 29 women (group 2). Combination between LN metastases according to variables distribution. We also evaluated the possible
visual detection results and radiomic analysis was also assessed. interaction between tumor histological subtypes (squamous- versus
Results: Sensitivity and specificity of LN visual detection were 50% adenocarcinoma), age of patients and the outcomes. Moreover, the
and 99% on group 1 and 33% and 95% on group 2, respectively. The role of significant features in the recurrence of disease was investi-
lower sensitivity of visual detection in group 2 is mainly related to the gated applying Cox regression analysis (DFS) in the subgroup of
higher rate of micrometastases respect to group 1 (25% vs 13%). A patient selected for FU only. Analyses were done using R software
unique heterogeneity feature computed on the primary tumour (the version 3.5.0
zone percentage of the grey level size zone matrix, GLSZM ZP) was Results: Considering pelvic MRI 17% patients resulted non-respon-
able to predict LN metastases better than any other feature or mul- ders to neo-adjuvant chemotherapy and 37% needed further treatment
tivariate model (sensitivity and specificity of 75% and 81% on group after surgery procedure. Both the outcomes were not significantly
1 and of 89% and 80% on group 2). Tumors with LN metastases associated with SUV parameters, MTV, age of patients nor histo-
generally demonstrated a lower GLSZM ZP value, i.e. by the co- logical subtypes. In the association analysis five features resulted
presence of high-uptake and low-uptake areas. The combination of significant (p \ 0.05) in predicting outcome1, in detail: Shape (vol),
visual detection and GLSZM ZP values in a unified framework Shape (#vx), NGLDM Coarseness, GLRLM_RLNU,
obtained sensitivity and specificity of 94% and 67% on group 1 and of GLZLM_GLNU.The same features were predictive of outcome2,
89% and 75% on group 2, respectively. except for NGLDM Coarseness and GLZLM_GLNU that have no
Conclusions: In preoperative PET/CT staging of endometrial cancer reached significance. While the feature GLZLM_SZHGE was sig-
patients, the computation of imaging features of the primary tumor nificantly associated only with outcome2. None of these features were
increased sensitivity for nodal staging and can be considered for a predictive of DFS
better treatment planning. Further studies on larger cohorts are Conclusions: These preliminary results suggest that radiomics can be
needed. applied also to gynecologic PET/CT. The features obtained on pre-
treatment PET can be associated with MRI to early provide further
information about the aggressiveness of the disease. Therefore, these
data can have a role in clinical practice, changing the treatment
PO109 planning or including further therapies after surgery. Prospective
Radiomic analysis of FDG PET/CT in locally advanced studies with increase number of patients are necessary to validate
cervical cancer: an innovative approach these features and to evaluate the role of radiomic analysis on post-
treatment PET.
F. Scalorbi3, A. Alessi3, F. Martinelli2, G. Argiroffi3, E. Maietti1,
A. Lorenzoni3, G. Bogani2, I. Sabatucci2, F. Raspagliesi2, E. Seregni3
1
PO110
Center for Clinical Epidemiology, University of Ferrara, Department
of Medicine, Ferrara, Italy. 2Gynecologic Oncology Unit, IRCCS
Prognostic value of [18F]fluorocholine PET parameters
Istituto Nazionale Tumori di Milano, Milan, Italy. 3S.C. Nuclear in metastatic castrate–resistant prostate cancer treated
Medicine and S.S PET, IRCCS Istituto Nazionale Tumori di Milano, with docetaxel
Milan, Italy
Background-aim: This is a monocentric retrospective study based on E. Quaquarini3, D. D’ambrosio4, F. Sottotetti2, F. Gallivanone1,
radiomic analysis of pre-treatment 18F-FDG PET/CT(PET) imaging M. Hodolic5, R. Palumbo2, C. Porta8, C. Canevari7, D. Presti2,
in locally advanced cervical cancer of uterus (FIGO IB2-IVa). The A. Bernardo2, G. Trifirò6
aim is to provide an additional diagnostic tool useful to predict 1
response to neoadjuvant chemotherapy and post-surgery treatment Institute of Molecular Bioimaging and Physiology, National
decision (follow up versus adjuvant therapy). Radiomic data analysis Research Council (IBFM-CNR), Milan, Italy. 2Medical Oncology
is a new promising method already applied in many neoplasms. This Unit, IRCCS ICS Maugeri SpA SB, Via Maugeri 10, Pavia, Italy.
3
is a quantitative, reproducible and effective imaging method that Medical Oncology Unit, IRCCS ICS Maugeri SpA SB, Via Maugeri
could be applied also in gynecologic tumors. 10, Pavia, Italy; University of Pavia, PhD in Experimental Medicine,
Methods: Thirty patients (mean age 46.2 years: range 25–77) with Pavia, Italy. 4Medical Physics Unit, IRCCS ICS Maugeri SpA SB,
bioptic diagnosis of cervical cancer carried out between 2013 and Via Maugeri 10, Pavia, Italy. 5Nuclear Medicine Research
2016 have been retrospectively evaluated. All patients have been Department, Iason, Graz Austria; Nuclear Medicine Department,
subjected to dose-dense platinum-based chemotherapy followed by Faculty of Medicine and Dentistry, Palacký University Olomouc,
surgical excision with histological confirmation carried out by the Czech Republic. 6Nuclear Medicine Unit, IRCCS ICS Maugeri SpA
same team of gynecologists and pathologists, at the IRCCS National SB, Via Maugeri 10, Pavia, Italy. 7Nuclear Medicine Unit, IRCCS
Institute of Tumour of Milan (INT). For each patient one PET and one San Raffaele Scientific Institute, Milan, Italy. 8Traslational Oncology
pelvic-MRI were performed at INT to plan the treatment. Another Unit, IRCCS ICS Maugeri SpA SB, Via Maugeri 10, Pavia, Italy

123
S70 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

Background-aim: The availability of new treatments for metastatic examination, and at least one negative biopsy were enrolled. The
castrate-resistant prostate cancer (mCRPC) patients increases the need cohort comprised patients with either an equivocal mpMRI (PIRADS
for reliable biomarkers to help clinicians to choose the better v2. B 2) or an absolute or relative contraindication to mpMRI. All
sequence strategy. In this study we explored the role of FCH PET/CT patients underwent whole body 68Ga-PSMA PET/CT 60 min after
as prognostic marker in patients with mCRPC by using accurate PET/ radiopharmaceutical injection (185–250 MBq). Focal PSMA uptake
CT biomarkers corrected for partial volume effect (PVE). superior to background activity was considered for the analysis and
Methods: This is a retrospective, observational trial conducted outlined for target biopsy. Semi-quantitative measures for all lesions
between March 2013 and August 2016. We enrolled patients with comprised SUVmax and SUVratio-to-background. Sensitivities,
mCRPC treated with three-weekly docetaxel after androgen depri- specificities, and accuracy were calculated compared to histopathol-
vation therapy who underwent FCH PET/CT before and after the ogy results.
therapy. Semi-quantitative indices such as maximum standardized Results: Overall, 624 consecutive patients were enrolled in our trial;
uptake value (SUVmax), mean standardized uptake value (SUVmean) from January to December 2017, 59 cases were referred to 68Ga-
corrected for partial volume effect (PVC-SUV), metabolically active PSMA PET/CT: 34 patients (57.6%) had already performed mpMRI
tumour volume (MATV) and total lesion activity (TLA) corrected for with either a negative result for PCa (n = 10) or positive mpMRI but
partial volume effect (PVC-TLA) were measured both in pre- and negative biopsy. In this subset of patients, 42 cases (71%) were
post-treatment FCH PET/CT scans for each lesion. Whole body addressed to 68Ga-PSMA PET/TRUS fusion biopsy that demonstrated
indices were calculated as sum of values measured for each lesion the presence of 27 malignant lesions (16 patients): 11 cases with GS 6
(SSUVmax, SPVC-SUV, SMATV, STLA). Progression free survival (3 ? 3), 14 cases with GS 7 (10 cases GS 3 ? 4; 4 cases GS 4 ? 3),
(PFS) and overall survival (OS) were considered as clinical endpoints. and 2 cases GS 10 (5 ? 5). Mean SUVmax for all PCa lesions
Univariate and multivariate hazard ratios for whole body FCH PET/ resulted statistically significantly higher than in benign lesions
CT indices were performed and p \ 0.05 was considered as (P \ 0.001). In particular, mean values for GS 6, GS 7 and GS 10
significant. resulted 7, 14 and 29, respectively. Also mean SUVratio-to-back-
Results: We enrolled 29 patients with a median age of 71 years old ground for PCa lesions resulted statistically significantly higher
(42-82); 84% had a bone and node-only disease, 17% a visceral (P \ 0.001) with GS 6, GS 7 and GS 10 having a mean SUVratio of
involvement. At a median follow-up of 6 years, mean PFS was 2.5, 5.4 and 9.6, respectively. ROC analysis performed for optimal
13.5 months (range 2.3–37.6 months) and mean OS was 37.0 months cut-off points demonstrated that a SUVmax [ 5.8 and a SUVra-
(4.7–66 months). Cox regression analysis showed a statistically sig- tio [ 2.2 could identify clinically significant PCa (GS C 7) with a
nificant correlation between PFS, SMATV (HR 1.019, 95% CI sensitivity of 93.7% in both cases.
1.06–1.09, p = 0.005) and STLA (HR 1.02, 95% CI 1.0–1.08, Conclusions: In patients with a high suspicion of cancer, despite
p = 0.012). No correlations between OS and FCH PET/CT parame- previously negative biopsy and/or mpMRI, 68Ga-PSMA PET/CT is
ters were defined probably due to the small sample size and the small still capable to detect malignant lesions and identify with a high
numbers of events. sensitivity clinically relevant PCa.
Conclusions: Semi-quantitative indices such as SMATV and STLA
at baseline have a prognostic role in patients treated with docetaxel
for mCRPC and they may be more useful than commonly used PET/
TC indices such as SUVmean and SUVmax. These results suggest a PO112
potential role of FCH PET/CT imaging in clinical decision-making. 64CU-PSMA physiological distribution assessed
Multicentre trials are urged to confirm these results. by PET/CT

F. Calabria3, R. Tavolaro3, M. Toteda3, S. Cardei3, G.L. Cascini2,


PO111 O. Schillaci1, A. Bagnato3
Potentials of 68GA-prostate specific membrane antigen 1
*Department of Biomedicine and Prevention, University ‘‘Tor
PET/CT for primary diagnosis of prostate cancer Vergata’’, Rome, Italy. **IRCCS INM Neuromed, Pozzilli (IS), Italy.
2
Department of Diagnostic Imaging, Nuclear Medicine Unit, Magna
E. Lopci1, G. Lughezzani4, A. Castello1, A. Saita4, P. Colombo2, Graecia University, Catanzaro, Italy. 3Department of Nuclear
N.M. Buffi4, N. Lo Iacono4, R. Hurle4, K. Marzo1, L. Leonardi1, Medicine and Theranostics, Mariano Santo Hospital, Cosenza, Italy
R. Peschechera4, A. Benetti4, S. Zandegiacomo1, L. Pasini4,
Background-aim: 64Cu-PSMA Positron Emission Tomography/
P. Casale4, L. Balzarini3, A. Chiti1, G. Guazzoni4, M. Lazzeri4
Computed Tomography (PET/CT) is becoming a promising diag-
1 nostic tool in the restaging of prostate cancer (PC) patients.
Nuclear Medicine, Humanitas Clinical and Research Hospital,
Theoretically, 64Cu-PSMA can be a valid tracer in imaging PC due to
Rozzano, Milan, Italy. 2Pathology, Humanitas Clinical and Research
its affinity for prostate cells; however, no data are reported about its
Hospital, Rozzano, Milan, Italy. 3Radiology, Humanitas Clinical and
physiological in vivo distribution. Our aim was to describe physio-
Research Hospital, Rozzano, Milan, Italy. 4Urology, Humanitas
logical 64Cu-PSMA distribution.
Clinical and Research Hospital, Rozzano, Milan, Italy
Methods: During 2017 we examined 46 PC patients by means of
Background-aim: The current study is designed to test the hypoth- 64Cu-PSMA PET/CT. Among them, we evaluated physiological
esis that prostate biopsy using 68Ga-PSMA PET/Trans Rectal tracer distribution in 20 patients with negative PET/CT scan for
Ultrasound (TRUS) fusion images may have a clinical impact in the secondary lesions. 64Cu-PSMA distribution was measured placing a
subset of patients with a high suspicion of prostate cancer (PCa), a spherical region of interest on target organs and with the calculation
previously negative biopsy and contraindications to or negative of maximum Standardized Uptake Values (SUVmax).
multiparametric MRI (mpMRI). Results: We observed physiological 64Cu-PSMA distribution, in
Methods: This prospective study started in April 2015 and was descending order of SUVmax, in the following organs: liver, gall-
emended in 2017 to include 68Ga-PSMA PET/CT in a selected sub- bladder, intestinal loops, pancreas, kidneys, stomach, salivary glands,
group of patients: men with persistently elevated PSA and/or PHI bladder, lachrymal glands, bone marrow, spleen, testicles, thyroid and
(prostate health index) suspicious for PCa, negative digital rectal

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S71

muscles. Faint uptake was observed in the brain. In a patient, lung HGB (mg/dl): 12.1 (11.6–13.1) Vs 11.5 (10.4–12.4); p: \ 0.001
64Cu-PSMA uptake was associated with pneumonitis PLT: 241.5 (207.2–268.8) Vs 177.5 (160.0–217.8); p: \ 0.001
Conclusions: The highest gradient of physiological uptake was GOT (UI/L): 17.5 (16.0–21.0) Vs 17.0 (16.0–21.0); p: 0.369
recorded in liver and biliary tract, due to the peculiar hepatic meta- GPT (UI/L): 12.0 (8.0–18.0) Vs 14.5 (9.8–18.2); p: 0.007
bolism of 64Cu-PSMA. Mild uptake was documented in exocrine LDH (UI/L): 383.0 (249.0–443.0) Vs 304.5 (195.2–437.8);
glands, probably due to their common embryologic origin. Bone p: \ 0.001
marrow usually presents low uptake, potentially allowing the recog- ALP (UI/L): 114.0 (87.5–225.5) Vs 76.0 (63.5–121.0); p: \ 0.001
nition of skeletal PC metastases. The finding of a pneumonitis 64Cu- PSA (UI/L): 47.2 (18.4–105.8) Vs 76.1 (20.7–248.8); p: \ 0.001.
PSMA avid can be linked to tracer uptake in inflammation; therefore, Conclusions: Our data confirm that in a ‘‘real life’’ setting (in a
this can lead in lack of specificity. population different in terms of age and comorbidities compared with
RCT), Ra-223 treatment was well tolerated and effective in mCRPC
patients. At the recommended dose, in a ‘‘real life setting’’ we con-
firmed the safety profile described in the literature. The fluctuation of
PO113 biomarkers (ALP and PSA) was as expected, and as previously
The administration of radium-223 dichloride in patients described confirming a good safety profile. The clinical outcomes
with castration resistant prostate cancer (MCRPC) recorded were consistent and overlapping with those reported in
randomized clinical trial. A prolonged follow-up is needed to defi-
and bone metastases is feasible and safe in ‘‘real-life’’
nitely evaluate long term survival outcomes.
setting: single-center experience

M. Mascia1, M. Marchioni3, M. Di Nicola3, A.D. Di Nicola1,


C. Villano1, L. Travascio1, L. Cindolo2 PO114
Sensitivity of [18F]fluoromethylcholine PET/CT to PSA
1
Department of Nuclear Medicine,’’Spirito Santo’’ Hospital, Pescara, over different plasma levels: a retrospective study
Italy. 2Department of Urology, ASL Abruzzo 2, Chieti, Italy.
3
Laboratory of Biostatistics, Department of Medical, Oral and
in a cohort of 192 prostate cancer patients
Biotechnological Science, ‘‘G. d’Annunzio’’ University, Chieti, Italy
E. Borso’1, G. Giovacchini1, E. Giovannini1, P. Lazzeri1,
Background-aim: Radiation therapy with Radium-223 dichloride M. Riondato1, R. Leoncini1, V. Duce1, M. Picchio2, A. Ciarmiello1
[Ra-223] has demonstrated ability to improve overall survival, to
reduce symptomatic skeletal events in men with castration-resistant 1
Unit of Nuclear Medicine, S. Andrea Hospital, La Spezia, Italy.
prostate cancer (CRPC) and bone metastases, showing a good safety 2
Vita-Salute San Raffaele University, Milan, Italy
profile. Herein, we report on the safety and feasibility of Ra-223
administration in mCRPC patients, in a ‘‘real life’’ setting. Background-aim: Several factors have been identified that predict
Methods: In this open-label, uncontrolled, non-randomized, phase IV positive [18F]fluoromethylcholine (FCH) PET/CT in prostate cancer
trial, Ra-223 was given to patients with CRPC and bone metastases in (PCa) patients undergoing PET/CT for biochemical failure. Among
4-week cycles. The patients were treated with injections of Ra-223 these factors, PSA is the single, most consistently factor associated
[55 kBq/kg body weight (BW)] every 4 weeks (Q4 W) for up to six with the prediction of positive FCH PET/CT. In this study, we wished
injections. Between January 2017 to May 2018 all the patients treated to confirm this finding and expand it in a large series of patients.
with Ra-223 were enrolled. Safety was determined via demographics, Methods: We retrospectively analyzed 192 PCa patients who were
comorbidities and clinical parameters, blood test and outcomes and recruited at the Nuclear Medicine Department of the S. Andrea
toxicity events. The Gleason score (GS) at the diagnosis was recor- Hospital of La Spezia, Italy from March 2013 to March 2018 and who
ded, the performance status was measured by the Eastern Cooperative underwent FCH PET/CT owing to biochemical failure after radical
Oncology Group (ECOG), the pain by the question 3 of Brief Pain prostatectomy.
Inventory scale (BPI) and Patients satisfaction, as well as fatigue and Results: Median trigger PSA was 2.57 ng/ml. The overall positive
use of oppioids were assessed. Treatment feasibility was evaluated by detection rate of FCH PET/CT was 60.9%. The percent of positive
the change in bone scans after 3 months and 6 months. scans was 30.5% for PSA \ 1 ng/ml, 59.4% (38/64) for PSA between
Results: Overall 43 patients 75.0 (IQR 67.7–79.5) years old as 1 and 5 ng/ml and 88.4% for PSA [ 5 ng/ml (P \ 0.001). At uni-
average, received the Ra-223. Patients previously treated with abi- variate regression analysis, high PSA levels, biochemical failure
raterone acetate, enzalutamide, or taxanes only or in combinations during anti-androgenic therapy (ADT) at the time of PET/CT and
were 41.9, 11.6 and 32.5%, respectively. All patients complained pain older age significantly (P \ 0.05) predicted positive FCH PET/CT. At
at the bone metastatic sites (median BPI 2.5, IQR 2.0–3.0). The multivariate regression analysis, only high PSA levels and biochem-
ECOG was [ 1 in 16.3%. Overall, the 74.1% of patients completed ical failure during ADT maintained the statistical significance
all the 6 cycles (median dose at the first cycle 4290 vs last cycle 4015 (P \ 0.05). However, when the analysis was restricted to patients
KBq). The median of the treatments carried out was 4.7 out of 6. The with PSA \ 1 ng/ml, PSA lost the statistical significance. ROC
9% of patients experienced clinical significant toxicity. Nausea, analysis revealed an area under the curve of 0.795. The PSA cut-off
anorexia, constipation and weight loss occurred in 30, 28, 17 and 18% value that best distinguished PET/CT-positive from PET/CT-negative
of the cases, although mainly during the first 12 weeks. At 3-month patients was 2.57 ng/ml. Sensitivity and specificity at this PSA value
bone scan showed stable disease and progression in 32 (74.4%) and 4 were, respectively, 66.7% and 76.0%.
(9.3%) of cases, respectively. However at 6 months bone scan showed Conclusions: This paper confirms that PSA robustly predicts positive
a progression in the 47.1% of patients. At the end of the scheduled PET/CT with radiolabeled choline. Unfortunately, this study also
treatments 31 patients completed the therapy (71.09%), 6 developed a confirms the limited sensitivity of FCH PET/CT for PSA \ 1 ng/ml,
clinical progression (13.95%), 6 died for causes not drug-related which currently represents the weakest point of the technique. Trigger
(13.95%). PSA represents a robust predictor of FCH PET/CT.
The changes in blood test were [Cycle 1 Vs Cycle 6]:
Weight (Kg): 78.0 (69.0–86.5) Vs 73.0 (67.0–87.0); p: \ 0.001

123
S72 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

PO115 Conclusions: PSMA-PET localizes prostate cancer in more than two-


Areas at risk for residual prostate cancer post-radical thirds of patients with biochemical persistence post-surgery with
implications for management. Mesorectal nodes, sub-aortic nodes and
prostatectomy uncovered by 68Ga-PSMA-11 PET bone are at high risk for disease persistence. Persistent lesions were
in a multicenter retrospective study already seen in more than one-third of patients on baseline PSMA-
PET. PSMA-PET identifies limitations of the current surgical
A. Farolfi7, W. Fendler5, D. Pianori2, F. Barbato5, V. Cervati7, approach and the histopathology reference standard.
M. Weber5, J. Calais1, H. Ilhan6, A. Afshar-Oromieh3, M. Eiber4,
K. Herrmann5, S. Fanti7
1
Ahmanson Imaging Translational Division, Department of PO116
Molecular and Medical Pharmacology, University of California Los Load of bone disease evaluated by a scintigraphic
Angeles (UCLA), Los Angeles, CA, USA. 2Department of method (MIRVIN software) as a survival predictor
Biomedical and Neuromotor Sciences, University of Bologna, in MCRPC patients
Bologna, Italy. 3Department of Nuclear Medicine, Heidelberg
University Hospital, Heidelberg, Germany. 4Department of Nuclear
Medicine, Klinikum rechts der Isar, Technical University, Munich, V. Frantellizzi1, M.D. Ippoliti1, S. Sollaku1, G. Brunotti1,
Germany. 5Department of Nuclear Medicine, University Hospital L. Civitelli1, G. De Vincentis1
Essen, Essen, Germany. 6Department of Nuclear Medicine, 1
University Hospital, LMU Munich, Germany. 7Metropolitan Nuclear Nuclear Medicine Unit, Department of Radiological Sciences,
Medicine of Bologna, University of Bologna, Bologna, Italy Oncology and Anatomical Pathology, Sapienza University of Rome,
Rome, Italy
Background-aim: Biochemical persistence after radical prostatec-
tomy (RP) in prostate cancer (PC) patients is associated with poor Background-aim: 90% of mCRPC expand to the bone. Bone
outcome. Positron-emission-tomography using small ligands for the metastases can be treated with 223Ra, an alpha-emitter. Bone pain
prostate specific membrane antigen (PSMA-PET) demonstrates high relief and increase of Overall Survival (OS) are associated to 6-cycles
accuracy for PC localization. We aim to define areas at risk for therapy’s administration. The percentage of bone disease is repre-
residual disease as well as the accuracy and impact on management of sented by the Bone Scan Index(BSI), evaluated with a specific
PSMA-PET in this setting. software. This value may associate to OS, then could be useful to
Methods: One hundred ninety-one (191) patients (median age stratify patients’ enrollment for 223Ra treatment. Basal BSI OS
67 years; range 47–87) were enrolled at 6 centers between August predictivity power evaluation is the primary end-point. The evaluation
2011 and May 2018 following these inclusion criteria: (a) RP as of BSI variations in the time course of therapy, the comparison
definitive therapy for PC; (b) persistently elevated post-operative PSA between BSI and 3-PS (prognostic score based on basal values of Hb,
levels with nadir C 0.1 ng/ml; (c) PSMA-PET performed within PSA and ECOG-PS) and the evaluation of BSI together with 3-PS in
12 months after RP. PET was read using PROMISE criteria. Lesions OS prediction are secondary end-points.
follow-up and management was recorded. PC was localized using a Methods: 127 patients treated with 223Ra were enrolled. Bone
standard template and detection rate, positive-predictive value (PPV), scintigraphies were collected before, during and after the therapy.
impact on management and inter-reader agreement was determined. Follow-up images were taken after 3 months, 6 months and 1 year.
In patients with additional PSMA-PET before RP (n = 33), rate of The images were processed by MIRVIN software developed by an
image-based PC persistence (detected before and after surgery) and engineering team in Sapienza for BSI calculation.
recurrence (detected after surgery only) was determined. Association Results: 546 scintigraphies, of which 127 basal, 211 intermediate, 87
between patient’s characteristics and presence of lesions was inves- final, 60 after 3 months, 38 after 6 months and 23 after one year, were
tigated by regression analysis. analyzed. 79 patients died during the evaluation period. Both the
Results: Median PSA nadir was 0.7 ng/ml; median recent PSA at the univariate (HR: 1.8, 1.61–2.02, p \ 0.001) and the multivariate (HR:
time of the PSMA-PET was 1.10 ng/ml. PSMA-PET localized PC in 1.82, 1.56–2.10, p \ 0.001) analysis -adjusted for BMI, age, Gleason
68.1% (130 of 191) patients with biochemical persistence post-RP. Score, number of previous systemic treatments, basal PSA, tALP, Hb,
Detection rate increased significantly with PSA nadir and recent PSA. PLT, ECOG-PS- confirm the OS prediction power of basal BSI. The
37.2% (71/191) patients had disease confined to the pelvis (Tr/N1) BSI variation trend over time is not significant as a OS predictor
while 30.9% (59 of 191) of patients had distant lesions (M1). Among (p = 0.36). BSI (AUC = 83%) is a better OS predictor than 3-PS,
patients with disease Tr/N1 45.1% (32/71) showed positive sub-aortic while BSI and 3-PS together have the best OS prediction power
or mesorectal lymph-nodes. In 45.4% (15/33) patients with PSMA- (AUC = 91%).
PET before and after RP, at least one lesion was already detected at Conclusions: Independently from previous systemic treatments’
baseline (PET persistence), 24% (8/33) had new appearance of number, the best OS for 223Ra-treated patients is obtained with
lesions. PSMA-PET PPV was 84.8%. Change in management after BSI \ 5%. According to EMA and AIFA directions, 223Ra treatment
PSMA-PET was recorded in 41.5% (54/130) patients with a positive should be started with advanced bone disease (C 6 metastases), with a
scan. Patients with PET Tr/N1 versus M1 disease had a higher pro- minor OS and less chances of receiving 6 223Ra administrations.
portion of local salvage therapy (17 of 27, 23.9% versus 10 of 27, New directions on treatment starting, based on disease percentage
16.9%). In the multivariate logistic regression analysis ISUP grade better than number of metastases, may be opportune. MIRVIN soft-
C 4 (OR = 2.31; CI 95% 1.09–4.87; p = 0.02) and T stage C 3a (OR ware could be useful in the stratification of patients’ enrollment for
3.29; CI 95% 1.16–9.32; p = 0.02) were significantly associated with 223Ra treatment, aiming an effectiveness’ increase and costs’
the presence of distant lesions. optimization.

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S73

PO117 PO118
223
Quality of life at baseline as overall survival predictor Radium therapy response assessment by pain
in MCRPC patients treated with 223radium response rate and disease control rate in patients
with castration resistant prostate cancer
V. Frantellizzi1, M.S. De Feo1, A. Matto1, G. Brunotti1, and symptomatic bone metastases
G. De Vincentis1
1 V. Lavelli1, C. Ferrari1, A. Niccoli Asabella1, G.V. Difonzo1,
Nuclear Medicine Unit, Department of Radiological Sciences,
A.G. Nappi1, A. Cimino1, A. Gaudiano1, G. Rubini1
Oncology and Anatomical Pathology, Sapienza University of Rome,
Rome, Italy 1
Nuclear Medicine Unit, Interdisciplinary Department of Medicine,
Background-aim: Bone metastases represent the end-stage for many University of Bari ‘‘Aldo Moro’’, Bari, Italy
patients with Castration Resistant Prostate Cancer (CRPC).
Background-aim: 223Radium (223Ra) has been shown to improve
223Ra-dichloride, a bone-targeting alpha particle emitter, is a vali-
overall survival (OS), to delay skeletal-related events and to reduce
dated treatment in CRPC patients with symptomatic bone metastases,
pain in patients with castration-resistant prostate cancer (CRPC) and
due to its palliative effect on bone pain and its significant improve-
bone metastases. Our retrospective, observational study aims to
ment of overall survival (OS).
evaluate Disease Control Rate (DCR), Pain Response Rate (PRR) and
The prognostic value of baseline data in predicting the survival
OS, in patients underwent 223Ra-therapy at Policlinic-University of
prolonging effect of 223Ra-dichloride therapy is continuously under
Bari.
investigation.
Methods: From February 2016 to April 2018, 24 patients (mean age
The aim of this study was to evaluate the impact of baseline
68 years, range 57–83) with symptomatic bone metastases of CRPC,
quality of life (QoL) on OS in mCRPC patients treated with 223Ra-
matching the approved inclusion criteria, were enrolled at our Nuclear
dichloride.
Medicine Department to underwent 223Ra-therapy. Among them, 14
Methods: 223Ra-dichloride (55 KBq/Kg 1q4wks for 6 cycles) was
patients who completed all six scheduled doses of therapy (55 kBq/
administered to 163 eligible consecutive symptomatic mCRPC
kg, 4 weeks intervals) were included in the analysis. The time from
patients in our Nuclear Medicine Unit from September 2013 to July
diagnosis of bone metastases was mean 35.4 months (range 13–72).
2018. Baseline QoL was assessed by asking patients to answer both
At the time of starting therapy, each patient had at least 6 bone
the European Organization for Research and Treatment of Cancer
metastases (tumor burden: 6–20 in 8/14; [ 20 in 6/14), assessed by
Quality of Life Questionnaire C30 (EORTC QLQ-C30) and the Bone
bone scintigraphy. Treatment response was evaluated by comparing
Metastasis Module (QLQ-BM22). Other baseline clinical data rele-
the number of lesions from pre-therapy to post-therapy bone
vant to the OS analysis (age, height, weight, PLT, ECOG
scintigraphy and classified in: complete response (CR), partial
Performance Status, Hb, PSA, tALP) have been taken into account.
response (PR), stable disease (SD) and progressive disease (PD). DCR
OS was established from the date of the first administration of 223Ra-
was calculated as the fraction of patients who had the best response
dichloride until the date of death from any cause. Data were retro-
rating (CR ? PR ? SD). PRR was also assessed both at the end of
spectively collected and summarized using descriptive statistics,
the treatment and at follow-up, using a quantitative pain scale (Brief
univariate analysis and multivariate analysis with Cox model.
Pain Inventory-Short Form). Finally, the OS was estimated using
Results: Among 163 patients (mean age 73 years), 89 (55%) com-
Kaplan–Meier method. The mean follow-up period was 8.86 months
pleted the 6 scheduled administrations, 48 patients (29%)
(5–21 months).
discontinued 223Ra treatment because of progression disease or
Results: At the end of treatment PR was observed in 2/14 (14.3%)
death, while 26 (16%) were still receiving 223Ra-dichloride therapy
patients, SD in 5/14 (35.7%) and PD in 7/14 (50%). No CR was
at the time of the analysis. The mean follow-up time from the first
observed in our sample. The DCR was 50%. At follow up assessment
223Ra-dichloride treatment was 11 ± 7 months (range
only 1/14 patients died. Although patients referred increasing pain in
1–32 months). Multivariate analysis has been performed. In the first
the first 3 months of 223Ra-therapy, probably due to ‘‘flare phe-
analysis, every single item of both EORTC QLQ-C30 and QLQ-
nomenon’’, PRR resulted 71% (10/14 patients) at the end of
BM22 questionnaire was individually taken into account to evaluate
treatment, while decreased to 35% (5/14) at follow-up. Mean OS after
the baseline QoL. In the resulting model, baseline patients’ weight,
223Ra-therapy was 634 days (IC 95%; range 615.79–653.21).
Hb, tALP and two EORTC QLQ-C30 items (PF2 = physical func-
Conclusions: 223Ra confirmed to be an important treatment option
tioning and DY = dyspnea) were significantly associated with OS
for patients with CRPC and symptomatic bone metastases. Our results
(PF2: HR = 0.972, CI 0.962–0.982, p \ 0.001; DY: HR = 0.992, CI
demonstrate that it is able to control the disease in a significant per-
0.985–0.999, p = 0.025). The second analysis was performed by
centage of patients and to extend survival with a favorable safety even
evaluating the baseline global-QoL as a single variable. In the final
in the presence of a high tumor burden. 223Ra-therapy has proved
model baseline patients’ Hb, tALP and baseline global-QoL showed a
also effective in pain control in the majority of patients for a mean
significant correlation with OS (global QoL: HR = 0.995, CI
period of 8 months.
0.992–0.998, p = 0.003).
Conclusions: The improvement of OS in patients with mCRPC
treated with 223Ra-dichloride is well established but the identification
of baseline variables that may predict the individual response to
treatment is a continuous challenge. The baseline QoL is significantly
correlated with OS, meaning that patients with better baseline QoL
are more likely to obtain a marked survival prolonging effect from
223Ra-dichloride therapy

123
S74 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

PO119 PO120
Role of 18F-FCH PET/CT semiquantitative analysis Which tools to use to evaluate pain exacerbation
to assess 223radium-dichloride therapy response during the 223RA treatment? A case report
in metastatic castration resistant prostate cancer
patients S.A. Pignata1, A. Comis1, R. Filice1, R. Laudicella1, F. Quattrocchi1,
A. Vento1, D. Cardile1, M.F. Martino1, S. Baldari1
C. Ferrari1, V. Lavelli1, A. Niccoli Asabella1, A.G. Nappi1, 1
Nuclear Medicine Unit, Department of Biomedical and Dental
G. Sigrisi1, P. Caputo1, N. Merenda1, G. Rubini1
Sciences and Morphofunctional Imaging, University of Messina,
1 Messina, Italy
Nuclear Medicine Unit, Interdisciplinary Department of Medicine,
University of Bari ‘‘Aldo Moro’’, Bari, Italy Background-aim: Radium-223 is an alpha emitter and calcium
mimetic bone-seeking agent approved for the treatment of symp-
Background-aim: To date there is not consensus about the most
tomatic bone metastases in castration-resistant prostate cancer
reliable diagnostic method in treatment response assessment in
(mCRPC).
patients with metastatic castration-resistant prostate cancer (mCRPC)
Patients with confirmed progressive mCRPC with two or more
underwent 223Ra-Dichloride Therapy. 99mTc-diphosphonate whole-
symptomatic bone metastases and no evidence of visceral metastases
body bone scintigraphy and whole-body CT scan are generally used
at imaging were eligible for the treatment.
to evaluate treatment efficacy. However, it has been postulated that
Interestingly, during registration trial, 223Ra showed better overall
fluorine-18 fluorocholine (18F-FCH) PET/CT may be also a useful
survival (OS) benefit vs placebo in mCRPC patients.
tool in the response evaluation. The purpose of our study was to
Unfortunately, it has not yet been codified an appropriate and
investigate whether 18F-FCH PET/CT semiquantitative parameters
acknowledged protocol for the assessment of patient during the 223Ra
are reliable to monitor response to 223Ra-Dichloride therapy in
therapy (clinical index, laboratory tests, and imaging): then there’s
mCRPC patients.
still the matter of the ongoing therapy assessment.
Methods: In a period of 21 months, from September 2016 to May
Methods: We report a clinical case of a 75 years patient affected by
2018, 24 consecutive patients (mean age 71.3 years, range 57–82)
mCRPC (Gleason 9, 5 ? 4) with PSA value of 62 ng/ml (\ 4.5),
with mCRPC referred to our Nuclear Medicine Department and
ALP value of 184 U/L (0–130), and symptomatic bone metastases
enrolled to underwent 223Ra-Dichloride Therapy. 10/24 patients,
that were enrolled for 223Ra treatment in December 2016.
who met the following selection criteria, were used for the analysis:
Before the 223Ra treatment, the patient received GnRH analog
(1) matched the approved inclusion criteria for the treatment; (2)
(Enantone), anti-androgen drug (Bicalutamide), blocks androgen
completed all six scheduled 223Ra-Dichloride doses (55 kBq/kg,
synthesis drug (Abiraterone) and 6 cycles of Docetaxel.
4 weeks intervals); (3) performed 18F-FCH PET/CT both at baseline
For the assessment or enrollment criteria, bone scan (‘‘Study
and 2 months after the end of treatment. Baseline and post-therapy
demonstrated abnormal uptake in several ribs, in the sternum, in right
18F-FCH PET/CT were performed with the same device in our
shoulder blade, in some vertebrae, and in the pelvis’’) and Computed
Department. A total of 30 lesions (the 3 most metabolically active
Tomography, CT, (to exclude the presence of visceral metastases)
metastases for each patient at baseline and post-therapy 18F-FCH
were performed.
PET/CT) were monitored and used for the semiquantitative analysis.
After checking the enrolment criteria, the patient received an
We assessed the following semiquantitative parameters: maximum
intravenous injection of 223Ra (at a dose of 55 kBq per kg of body
Standard Uptake Value (SUVmax), mean Standard Uptake Value
weight; in a total of 6 injections) every 4 weeks.
(SUVmean), minimum Standard Uptake Value (SUVmin), Metabol-
Results: Between the third and the fourth injection of 223Ra, a severe
ically Active Tumor Volume (MATV) and Total Lesion Activity
spine pain occurred to the patient.
(TLA). Student’s T-Test was used to evaluate whether a statistically
Before the pain exacerbation happened, the patient referred to feel so
significant difference existed between baseline and post-therapy 18F-
good that he went to the gym and had a hard workout.
FCH PET/CT semiquantitative parameters. P [ 0.05 was considered
Whole body scan (WBS) obtained 3 h after 99mTc-MDP injection
statistical significant.
using a dual-headed gamma camera (Brightview-X, Philips, Cleve-
Results: In baseline and post-therapy semiquantitative evaluation,
land) equipped with low-energy high-resolution parallel-hole
mean SUVmax changed from 7.10 to 5.7; mean SUVmean from 4.25
collimators.
to 3.22; mean SUVmin from 3.19 to 2.38; mean MATV from 19.66 to
WBS identified a decrease of uptake in known lesions and the
26.98; mean TLA from 76170.06 to 79014.27. Student’s T-Test
appearance of two ‘‘horizontal band shape’’ uptake areas in D10 and
showed a statistically significant difference for SUVmax (t = 2.042;
L4 vertebrae, respectively.
p = 0.05), SUVmean (t = 2.164; p = 0.04) and SUVmin (t = 2.749;
Those findings appeared compatible with osteoporotic vertebral
p = 0.01). No statistically significant difference was found for MATV
compression fractures (OVCFs) and CT confirmed that.
and TLA.
Following percutaneous vertebroplasty procedure and its conva-
Conclusions: Our experience demonstrates that 18F-FCH PET/CT,
lescence time, the patient completed the 223Ra treatments.
thanks to the semiquantitative evaluation, have an important role in
In the first follow-up, a reduction in pain, a decrease of PSA
the assessment of 223Ra-Dichloride treatment response. In particular
(58 ng/ml) and ALP (128 U/L) were observed.
among the PET/CT parameters considered in our study, the most
To date, the patient still alive with an OS of 24 months.
significant ones were SUVmax, SUVmean and SUVmin. A greater
Conclusions: According to the literature, during treatment with
number of patients would be necessary to confirm these preliminary 223
Ra, patients experience an improvement in their clinical condi-
data and to evaluate the prognostic significance of these semiquan-
tions: thus, the patients resume their lifestyle habits.
titative parameters.
It is important that the physician recommended what the patient can
do and how should do it.
This is especially appropriate for patients who have undergone
previous therapy with Abiraterone.

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S75

Finally, during 223Ra treatment, WBS and morphological imaging PO122


have proven to be an excellent tool for the interim evaluation of the Bone-dominant disease by 18F-choline PET/CT
mCRPC patient.
in recurrent prostate cancer patients

M. Rensi2, L. Cuppari1, F. Di Gregorio2, D. Capobianco2, M. Burei1,


PO121 L. Evangelista1
Investigation of diagnostic performance of texture
1
analysis applied to 68Ga-PSMA PET/CT and MP- Nuclear Medicine and Molecular Imaging Unit, Veneto Institute of
Oncology IOV-IRCCS, Padua, Italy. 2Nuclear Medicine Unit,
3TMRI in stratifying prostate cancer patient Azienda Sanitaria Universitaria Integrata, Udine, Italy

A. Savini1, M.L. Belli1, G. Feliciani1, F. Ferroni3, M. Celli2, Background-aim: The aim of the study was to assess the prediction
F. Matteucci2, D. Barone3, S. Severi2, A. Sarnelli1, G. Paganelli2 of bone-dominant disease by 18F-Choline PET/CT in recurrent
prostate cancer patients.
1
Medical Physics Unit, Istituto Scientifico Romagnolo per lo Studio e Methods: From two Italian institutional databases (Veneto Institute
la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. 2Nuclear Medicine of Oncology IOV-IRCCS, Padua and Hospital of Udine, Udine), data
Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei for 160 patients with prostate cancer undergoing 18F-Choline PET/
Tumori (IRST) IRCCS, Meldola, Italy. 3Radiology Unit, Istituto CT were collected. The inclusion criteria were: (1) the presence of a
Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) biochemical recurrence of disease (PSA value [ 0.2 ng/mL) after a
IRCCS, Meldola, Italy curative treatment (i.e. radical prostatectomy or radiotherapy); and (2)
a positive 18F-Choline PET/CT for bone disease. The exclusion cri-
Background-aim: In the management of prostate cancer patients, the teria were: (1) a negative PET/CT scan and (2) the presence of non-
prior knowledge of the ISUP score would be of great help in treatment bone disease at PET/CT scan. Categorical data were expressed as
decision (i.e. in deciding among active surveillance, curative surgery frequency (%) and continuous variable as median (range). Chi square
or radiotherapy). Combining available imaging modalities such as was used for the comparison between categorical variables. A P
multi-parametric magnetic resonance (mp-MRI) and 68Ga-PSMA value \ 0.05 was considered statistically significant.
PET/CT could improve the ISUP score prediction. In this study, we Results: Median age was 74 years (range 52–89). The median PSA
applied texture analysis to combined mp-MRI and 68Ga-PSMA PET/ value at the time of 18F-Choline PET/CT was 3.5 ng/mL (range
CT in order to discriminate prostate cancers with low ISUP scores (1 0.2–373). In particular, 90 (56.2%) had a PSA \ 5 ng/mL, while 70
vs 2 ?). (43.8%) had a PSA C 5 ng/mL. Gleason Score was ranged between
Methods: 10 patients with prostate cancer were enrolled to undergo 8–10 in the majority of patients (n = 71; 44.4%). Fifty-eight (36.3%)
mp-MRI and 68Ga-PSMA PET/CT. Ground-truth ISUP was deter- patients had a single bone lesion at PET/CT, while 102 showed
mined through TRUS biopsy and pathohistology after prostatectomy. multiple localizations. In this latter subset, 38 (37.3%) and 64 (62.7%)
An expert radiologist contoured prostate gland on T2w images reg- had \ 5 and C 5 lesions, respectively. Forty-seven patients (52.2%)
istered with Diffusion and Perfusion images. T2w images were co- with a PSA level \ 5 ng/mL had a single bone lesion at PET/CT,
registered with 68Ga-PSMA PET/CT by means of mutual-information conversely 59 (84.3%) subjects with a PSA C 5 ng/mL had multiple
algorithm. Contours on MRI were then transferred to the 68Ga-PSMA lesions at PET/CT (p \ 0.001), more often more than 5 lesions
PET/CT. Texture analysis was applied to the contoured volume on all (n = 41; 70%). Furthermore, among patients with single bone lesion
modalities in order to extract features to be correlated with ISUP (n = 58), the Choline uptake was localized in the pelvis (n = 19;
score. Inter-modality correlation of features was analyzed as well. 40%) in case of PSA \ 5 ng/mL and in the column (n = 7; 63.6%) in
Results: Patients were stratified into two groups. The first group case of PSA C 5 ng/mL.
included 6 patients with ISUP score equal to 1 (low risk). The second Conclusions: In recurrent prostate cancer patients, low PSA levels
group included 4 patients with ISUP score greater or equal to 2 (in- are frequently associated with a single bone lesion at Choline PET/CT
termediate to high risk). A total of 72 features were calculated for that would be treated with a local therapy. On the other hand, the high
each imaging modality. One feature was correlated with the ISUP level of PSA are more often associated with a widespread bone dis-
stratification for both T2w and PET-PSMA images (Wilcoxon test, ease at PET/CT that would be treated by a systemic or a targeted
p = 0.03). Furthermore, the feature resulted correlated between the therapy (i.e. 223Ra-dichloride).
two imaging modalities (PET and MRI) with a Spearman’s correla-
tion coefficient [ 0.7 and p = 0.05.
Conclusions: Texture analysis appears to be a promising methodol-
ogy for predicting ISUP score. Furthermore, it suggests that two PO123
different imaging modalities such as 68Ga-PSMA PET/CT and T2w Prognosis and therapy-based on 18F-Choline PET/CT
MRI may give correlated information about the prostate tumor. in recurrent bone-dominant prostate cancer patients

L. Cuppari1, M. Burei1, P. Reccia1, A.R. Cervino1, L. Evangelista1


1
Nuclear Medicine and Molecular Imaging Unit, Veneto Institute of
Oncology IOV-IRCCS, Padua, Italy
Background-aim: The aim of the study was to assess the prognostic
role and therapeutic choice based on 18F-Choline PET/CT findings in
recurrent bone-dominant prostate cancer patients.
Methods: From a mono-institutional database, data for 70 patients
with recurrent bone-dominant prostate cancer undergoing 18F-Cho-
line PET/CT were collected. The inclusion criteria were: (1) the

123
S76 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

presence of a biochemical recurrence of disease (PSA value [ 0.2 ng/ received an average of 4 injections. 2 patients haven’t concluded yet
mL) after a curative treatment (i.e. radical prostatectomy or radio- the treatment.
therapy), and (2) a positive 18F-Choline PET/CT for bone disease. The main cause of interruption of treatment was a rapid progression
The exclusion criteria were: (1) a negative PET/CT scan and (2) the of disease (38%), severe anaemia (38%) or thrombocytopenia (15%)
presence of non-bone disease at PET/CT scan. Chi square was used and major depression (9%).
for the comparison between categorical variables. Kaplan–Meier After the third injection we noted a reduction of the pain in the
analysis (i.e. log rank) was used for assessing the prognostic signifi- 53% of our patients.
cance of 18F-Choline PET/CT. A P value \ 0.05 was considered After two months from the last therapy we registered 8 deaths: 1 in
statistically significant. the group 1 (4%) and 7 in the group 2 (54%). The median overall
Results: Median age was 74 years (range 52–89). The median PSA survival was respectively of 7.4 and 5.4 months.
value at the time of 18F-Choline PET/CT was 4.3 ng/mL (range 15 patients in the group 1 are still in follow-up, with a good
0.2–300). Twenty-three (32.9%) patients had a single bone lesion at control of the pain in the 67% of them and a median of 7.2 months
PET/CT, while 47 showed multiple localizations. In this latter subset, from the last injection.
17 (36.2%) and 30 (63.8%) had \ 5 and C 5 lesions, respectively. Conclusions: A careful selection of the patients allows to complete
After PET/CT, all patients were send to a specific treatment (hor- the whole treatment and obtain the best response in reducing symp-
monal therapy in 49 patients, chemotherapy in 12, external-beam toms and improving overall survival.
radiotherapy in 7 and 223Radium in 2). In particular, 4/7 (57%) and Recent AIFA guidelines, delating the usage of Ra223 and selecting
2/7 (29%) undergoing radiotherapy has a single and \ 5 bone lesions more frequently end stage patients, could significantly decrease the
at Choline PET/CT, configuring the oligometastatic disease. Con- clinical effectiveness of this therapy.
versely, those patients (n = 30) with a widespread bone disease were
treated with systemic therapies (hormonal therapy in 18 and
chemotherapy in 9). The 5-year overall survival was significantly
worse in patients with more than 5 bone lesions at Choline PET/CT as PO125
68
compared to those with less than 5 lesions and a single lesion (10, 33 Ga-PSMA-11 PET/CT guided change management
and 65%, respectively; p \ 0.001). in patients with biochemical recurrence of prostate
Conclusions: In bone dominant recurrent prostate cancer patients,
cancer after radical prostatectomy and before adjuvant
18F-Choline PET/CT is able to guide to local or systemic therapies
and it can stratify the prognosis, based on the extension of skeletal or salvage radiotherapy
tumor burden.
D.G. Nicolotti1, E. Pilati1, R. Passera1, A. Maiorana1, R. Parise2, S.
Bartoncini2, A. Guarneri2, B. Lillaz3, A. Zitella3, M. Bello’1, G. Bisi1,
P. Gontero3, U. Ricardi2, D. Deandreis1
PO124
1
A real-life experience with RA223 in MCRPC Nuclear Medicine Unit, AOU Città della Salute e della Scienza di
Torino, Department of Medical Sciences, University of Turin, Turin,
E. Cossalter2, M.B. Panarotto2, M. Gazzilli3, M. Bonacina3, Italy. 2Radiation Oncology Unit, AOU Città della Salute e della
R. Durmo3, F. Dondi3, R. Giubbini1 Scienza di Torino, Department of Oncology, University of Turin,
Turin, Italy. 3Urology Unit, AOU Città della Salute e della Scienza di
1
Chair of Nuclear Medicine and Nuclear Medicine Unit, Brescia, Torino, Department of Surgical Sciences, University of Turin, Turin,
Italy. 2Nuclear Medicine Unit, Spedali Civili, Brescia, Italy. 3Nuclear Italy
Medicine University, Brescia, Italy Background-aim: 68Ga-PSMA-11 PET/CT is definitely establishing
Background-aim: Radium 223 dichloride (Ra223) is an alpha emitter itself as a tool of high diagnostic accuracy in the detection of prostate
and calcium mimetic with the capability of targeting osteoblastic cancer (PCa) recurrence and it is annovered in recent international
metastatic lesions. It is the first alpha emitter approved for treatment guidelines. However the definition of appropriateness and cost-ef-
of patients with symptomatic bone metastases from metastatic cas- fectiveness criteria in different clinical settings is still ongoing. The
trate-resistant prostate cancer (mCRPC). A complete therapy consists aim of this single Center study was to assess the impact of 68Ga-
of six cycles of injection every 28 days and it was demonstrated to PSMA-11 PET/CT on the management of PCa patients (pts) with
reduce symptoms and improve overall survival in these patients. persistence of disease or biochemical recurrence (BCR) after surgery,
This study describes our real-life experience on the usage of Ra223, with low PSA values, eligible to adjuvant (ART) or salvage radio-
paying particular attention in selecting patients with a high chance of therapy (SRT).
completing the whole treatment. Methods: PCa pts with BCR after surgery, PSA values between 0.2
Methods: Between July 2015 and October 2018, 42 patients were and 1.5 ng/ml and eligible to ART or SRT were prospectively
evaluated for radiometabolic therapy. We selected 38 patients with enrolled at our Center between November 2016 and November 2018.
mCRPC and no known visceral metastasis, while 4 received other All pts performed 68Ga-PSMA-11 PET/CT according to international
palliative radiometabolic treatment for the contraindications. All our procedure guidelines acquisition protocol. In case of PSA [ 1.5 ng/
38 patients had a permissive blood count cells (CBC) and more than ml, pts performed first radiolabeled Choline PET/CT and, if negative,
six metastases. The reported pain varied from moderate to severe. PSMA PET/CT. Clearly abnormal PSMA PET findings were con-
Alkaline phosphatase, CBC and clinical condition were evaluated sidered as true positive; dubious findings were monitored or
before every injection, after 2 weeks and 2 months after the last investigated with other imaging tools and defined as true positive or
injection. Totally we performed 190 treatments. PSA was evaluated at negative by a multidisciplinary consensus. In case of negative PET or
the beginning, after the third injection and 2 months after the end of prostatic bed relapse, pts were sent to standard ART or SRT. In case
therapy. of lymph node or distant metastases the therapeutic plan was based on
Results: 36 patients concluded the treatment: 23 patients (64%) PET findings. Associations between PET positivity and clinical pat-
received all the six cycles (group 1), while 13 patients (36%, group 2) terns were investigated by logistic regression analysis and Mann–

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S77

Whitney test and the percentage of pts in which PET results modified Methods: We retrospectively collected clinical data of 23 pts affected
the therapeutic planning was evaluated. by CRPC treated with Radium 223 for symptomatic bone mts at the
Results: One hundred and two pts were included in this clinical Nuclear Medicine Unit of University Hospital of Ferrara from July-15
setting and performed 68Ga-PSMA-11 PET/CT. Median age was 69 to November-18. Serum PSA, ALP and blood count were assessed
yrs (range 52–82), pathological T stage was C 3 in 39.2% every cycle at day1 and day14. To evaluate the efficacy of treatment,
(n = 40), \ 3 in 56.9% (n = 58), missing in 3.9% (n = 4) pts, ISUP at every visit we asked pts to report changes in bone pain compared to
Grade was C 3 (GS C 4?3) in 55.9% (n = 57), \ 3 (GS B 3?4) in baseline and it was classified as ‘increase’, ‘no change’, ‘decrease’ or
43.1% (n = 44), missing in 1% (n = 1) pts. Median PSA value at the ‘complete cessation’. To assess the therapeutic efficacy on bone
moment of PET was 0.54 ng/ml (range 0.2–8.9), median PSA dou- metastases in term of remission, stabilization or progression of dis-
bling time (DT) was 7.7 months (range 0.3–264.8) and median PSA ease, we performed a bone scan before Radium 223 treatment and at
velocity (VEL) was 0.4 ng/ml/yr (range 0-66.2). the end of 6 expected cycles. An informed consent was taken before
68
Ga-PSMA-11 PET/CT was positive in 31.4% (n = 32) cases, 50% the start of treatment.
(n = 16) in lymph nodes, 25% (n = 8) in the bone and only 25% Results: 23 pts underwent treatment with Radium 223 at 50 kBq/kg
(n = 8) in prostatic bed. i.v. every 4 weeks; 18 of 23 pts (78.3%) received all 6 expected
In the univariate logistic regression analysis also the ISUP infusions of radiotracer, 5 (21.7%) stopped the treatment for the
Grade C 3 was significant (p = 0.036), but in the multivariate model worsening of clinical conditions. Twelve pts were pre-treated with
the main determinant predictor for PET positivity was the patholog- less then 3 lines therapy (52%), 5 pts with 3 or more lines (21.7%).
ical T stage C 3 (OR 4.27; 95% CI 1.73–10.54; p = 0.002). The most common effects on blood were anemia (57% G1-2, 28%
Associations (Mann–Whitney test) were found with increasing pre G3), thrombocytopenia (42% G1, 14% G2), neutropenia (14% G2).
PET PSA value (p \ 0.001), shorter PSA DT (p = 0.006) and higher An increase of PSA value from 1st to 6th cycle was found in 14 of 18
PSA VEL (p = 0.001). pts (77.7%) with a median P-173 ng/ml. ALP value decreased in 15
A change management occurred in 75% (n = 24) of cases with of 18 pts (83.3%), with a median P of 63 U/L. No particular side
extra prostatic bed positive PSMA PET: in particular modification of effects hade been highlighted and the treatment was well tolerated. At
RT plans and/or stereotactic RT in 50% (n = 12) of these pts, antic- the 1st Radium 223 infusion, 16 pts (72%) were receiving nons-
ipation of hormone therapy in 25% (n = 6), salvage teroidal anti-inflammatory drugs (NSAIDs) ? opioid drugs for pain
lymphadenectomy in 12.5% (n = 3) and watch and wait in 12.5% relief, 4 pt (15%) only NSAIDs, 3 pt (14%) only opioid analgesic. 19
(n = 3), respectively. pts (86%) reported a decrease pain intensity since the 3rd cycle, also
Conclusions: These results suggest that 68Ga-PSMA-11 PET/CT is a confirmed after the last dose; 4 pts (14%) reported no appreciably
useful tool to guide the management of PCa pts with BCR and low change of pain. Analgesic drug dose was reduced in 14 of 23 pts
PSA levels with high impact in pts eligible to ART or SRT. Its (60.8%). Bone scan, performed 1 month after the end of treatment,
accuracy is significantly better if performed in case of more aggres- showed 2 PD (11.1%) and 6 SD (33.3%). Not SREs were observed
sive disease patterns. A standardized definition of these PCa features during the follow up.
should direct an appropriate patient selection to implement this tool in Conclusions: Radium 223 is well tolerated and effective in terms of
clinical practice in a cost-effective way. pain control and stabilization of bone disease. No PSA response was
detected while ALP levels significantly decreased. Not significant
bone marrow toxicity was shown. Acting on pain, a decrease of
antalgic therapy and an improvement of patient’s QoL were observed.
PO126
Efficacy of radium 223 in castration resistant prostate
cancer (CRPC) patients with painful bone metastases:
PO127
a retrospective study
Performance of (18)F-FCH PET/CT in patients
S. Panareo1, D. Scapoli2, F. Fiorica3, I. Santi1, I. Rambaldi1,
with PSA £ 1NG/ML and usefulness of PSA kinetic
C. Cittanti1, C. Ippolito4, A. Frassoldati2, M. Bartolomei1 indexes PSADT and PSAVE in the selection of patients
1
Nuclear Medicine Unit, Department of Oncology/Medicine- V. Landino1, A. Chiaravalloti1, D. Di Biagio1, A. Cimini1,
Specialistic, University, Hospital of Ferrara, Ferrara, Italy. 2Oncology O. Schillaci1
Unit, Department of Oncology/Medicine-Specialistic, University-
Hospital of Ferrara, Ferrara, Italy. 3Radiotherapy Unit, Department of 1
Department of Biomedicine and Prevention, University Tor Vergata,
Oncology/Medicine-Specialistic, University-Hospital of Ferrara, Rome, Italy
Ferrara, Italy. 4Urology Unit, Department of Surgery, University-
Background-aim: To investigate the performance of [18]F-fluoro-
Hospital of Ferrara, Ferrara, Italy
choline ([18]F-FCH) PET/CT in relation to the prostate-specific
Background-aim: Bone metastases (mts) represent a substantial antigen (PSA) kinetic indexes, PSA doubling time (PSAdt) and PSA
cause of morbidity in pts with CRPC with a high rate of related velocity (PSAve), in detecting recurrent prostate cancer (PC) in a
skeletal events (SREs) and of development of visceral metastases. selected population of patients treated with radical prostatectomy and
Radium 223 dichloride is an alpha emitter that selectively binds to with PSA B 1 ng/ml.
areas of increased bone turnover in bone mts and emits high-energy Methods: The study group comprised 41 patients (mean age
a-particles of short range. The ALSYMPCA study assessed the effi- 70 ± 7 years, range 59–83 years) who had been treated with radical
cacy of Radium 223 compared to placebo in terms of OS, time to first surgery 30 to 90 months previously and with biochemical failure
SRE and QoL in men with CRPC with symptomatic bone mts and (defined as a measurable serum PSA level) who were evaluated with
unknown visceral mts. The aim of our analysis is to evaluate the [18]F-FCH PET/CT. In order to establish the optimal threshold for
usefulness of Radium 223 in the control (bone and therapeutic effi- PSAdt and PSAve, the diagnostic performance of PSA, PSAdt and
cacy) of bone metastases. PSAve were compared by receiver operating characteristic curve
(ROC) analysis. A threshold of 6 months was selected for PSAdt; a

123
S78 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

threshold of 0.03 ng/ml/year was selected for PSAve on the basis of Different clinical stages of BCR were identified by referring
ROC curve analyses (see below). physicians and our cohort was grouped into three different categories,
Results: In the population examined, PSA (mean ± SD) was namely: (a) biochemical persistence (BCP) after RP in 13.5% (45/
0.79 ± 0.26 ng/ml (range 0.03–1 ng/ml) before PET/CT examina- 332) (subgroup 1), (b) first-time BCR in 44.9% (149/332) (subgroup
tion. PSAdt was 5.49 ± 5.35 months and PSAve was 2), and (c) PSA failure after salvage or hormonal therapy in 41.6%
0.17 ± 0.32 ng/ml per year. (138/332) (subgroup 3).
[18]F-FCH PET/CT was positive in 24 patients (58%). PSAve was Results: Primary objective: 68Ga-PSMA-11 PET/CT detection rate
0.48 ± 1.5 ng/ml/year in patients with a negative PET/CT scan and was 53.6% (CI 95% 48.1–59.1).
1.18 ± 3.06 ng/ml/year in patients with a positive PET/CT scan In a patient-based analysis, disease confined to pelvis (prostate bed
(P = 0.04); and PSAdt was 8 ± 5 months in patients with a negative and/or lymph-nodes) was detected in 24.7% of cases (82/332). The
scan and 4 ± 4 months in patients with a positive scan (P = 0.02). presence of at least one distant lesion was observed in 28.9% of cases
PSA values were not significantly different between patients with a (96/332).
positive and a negative PET/CT scan. PET/CT resulted in a sensitivity The detection rate in different subgroups was: subgroup
of 87.5%; specificity of 70%; positive predictive value of 75% and a 1 = 64.5%, subgroup 2 = 45.6%, and subgroup-3 = 58.7%.
negative predictive value of 82.4%. Secondary objectives:
For PSAdt B 6 months the detection rate (DR) was 87%, and for 1. In the multivariate Cox regression analysis, PSA (OR 3.304; CI
PSAve [ 0.03 ng/ml/year the DR was 80%. 95% 1.052–10.372; p = 0.041) and PSAdt (OR 0.807; CI 95%
Conclusions: The results of our study suggest that [18]F-FCH PET/ 0.720–0.907; p = 0.001) showed association with 68Ga-PSMA-
CT could be considered for the evaluation of patients with bio- 11PET/CT detection rate;
chemical recurrence of PC and with PSA levels below 1 ng/ml after 2. Correlative imaging (choline PET, mp-MRI, CT, bone
radical prostatectomy. Fast PSA kinetics could be useful in the scintigraphy) was available in 73.2% of patients (243/332). The mean
selection of these patients. time between 68Ga-PSMA-11 PET/CT and correlative imaging was
3.7 months. When 68Ga-PSMA-11 PET/CT was positive, correlative
imaging resulted negative in 83% of cases (108/130).
3. Mean follow-up was 15.3 months (range 9.8–25.3). Validation
PO128 of positive findings was available in the 59% of patients. Overall, 154
68
GA-PSMA-11 PET/CT in recurrent prostate cancer: patients were considered false negative, four false positive and 101
efficacy in different clinical stages of PSA failure true positive. Accordingly, the per-patient PPV was 96.2%, (CI 95%
95.60–96.70).
after radical therapy
Conclusions: Our data confirmed the efficacy of 68Ga-PSMA-11
PET/CT for detecting local vs systemic disease in PCa patients pre-
F. Ceci1, P. Castellucci1, G. Polverari1, T. Graziani1, A. Farolfi1, senting PSA failure after radical therapy.
F. Lodi1, S. Fanti1 Furthermore, 68Ga-PSMA-11 PET/CT detection rate is different
1
depending on the clinical stage (BCP vs first-time BCR vs PSA
Metropolitan Nuclear Medicine of Bologna, University of Bologna, failure after salvage therapy), and this information should be taken
Bologna, Italy into consideration by referring physicians.
Background-aim: The primary objective was the evaluation of 68Ga-
PSMA-11 PET/CT detection rate for identifying the site(s) of relapse
(disease confined to pelvis vs distant relapse) in a population with low
PSA values (0.2–2 ng/m), and assessing 68Ga-PSMA-11 PET/CT
PO129
performance at different clinical stages of biochemical recurrence Retrospective evaluation of 68gallium-PSMA-11
(BCR). and 11C-choline in two different cohorts of prostate
Secondary objectives were: cancer patients, with PSA values between 0.2–1.00 NG/
1. to evaluate the association of clinical/pathologic features and
68
Ga-PSMA-11 PET/CT detection rate;
ML after radical prostatectomy
2. the comparison of 68Ga-PSMA-11 PET/CT performance with
other imaging procedures performed during BCR. A. Farina1, I. De Nicola1, A. Lambertini1, F. Ceci2, P. Castellucci1,
3. to evaluate the positive predictive value (PPV) in a per-patient S. Fanti1
analysis. 1
Methods: This population was enrolled through an open-label, sin- Nuclear Medicine Department, Sant’Orsola-Malpighi Hospital,
gle-center, prospective registry study performed at the Nuclear University of Bologna, Bologna, Italy. 2UCLA Nuclear Medicine,
Medicine of the S.Orsola-Malpighi University Hospital of Bologna, Department of Molecular and Medical Pharmacology, University of
Italy and approved by Local Ethics Committee (Prot. PSMA-PROS- California Los Angeles (UCLA), Los Angeles, CA, USA
TATA; Eudract: 2015-004589-27 OsSC). Background-aim: The aim of this study was to assess the perfor-
The inclusion criteria were: (1) proven PCa, (2) radical prostatectomy mance of 68Ga-PSMA-11 PET/CT and 11C-Choline PET/CT in two
(RP) or radiotherapy as definitive therapy, (3) proven BCR, (4) PSA different cohorts of prostate cancer (PCa) patients with serum PSA
0.2-2 ng/ml, (5) age C 35 years, and (6) willing to sign an informed level range 0.2–1.00 ng/mL after radical prostatectomy (RP).
consent. Methods: All PCa patients referred to our center from February 2016
332 consecutive patients met inclusion/exclusion criteria and were to March 2018 were evaluated and two different cohort of patients
prospectively included. were retrospectively analysed according the following inclusion cri-
Mean PSA was 0.84 ng/ml (range 0.2–2 ng/ml), mean PSAdt was teria: (a) RP as primary therapy; (b) PSA between 0.2 ng/mL and
7.4 months (range 0.8–54.3 months), mean PSAvel was 0.98 ng/ml/ 1.00 ng/mL. One hundred twelve underwent 11C-Choline PET/CT
year (range 0.1–19.3 ng/ml/year). RP was the primary therapy in (mean PSA: 0.55 ng/mL, median PSA: 0.5 ng/mL) and were defined
97.9% (325/332) of patients. 75 out of 332 patients (22.5%) under- as Group A. One hundred and seventy-one patients underwent 68Ga-
went salvage therapies during BCR. PSMA-11 PET/CT (mean PSA: 0.51 ng/mL, median PSA: 0.49 ng/

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S79

mL) and were defined as Group B. All images were qualitatively treatment. Mean OS of Group A was better than Group B of
evaluated by at least 2 nuclear medicine physicians. The performance 10 months (short follow up limited a statistical evaluation)
of both PET/CT scan was evaluated as detection rate in a per-patients Conclusions: Our preliminary results show that patients with Bone
analysis. Scan Index \ 10% have more chances to complete all cycles of
Results: In Group A 11C-Choline resulted positive in 38/112 Ra223 therapy and to be responder patients. Elevated baseline BSI
(33.93%) of cases and negative in 74/112 (66.07%) of cases. In Group could be related to a worst outcome. Our data, as reported in litera-
B 68Ga-PSMA-11 imaging was positive in 85/171 (49.71%) of cases ture, confirmed that PSA isn’t a useful marker to predict disease
and negative in 86/171 (50.29%) of cases. progression. The evaluation of overall survival was limited due to a
Conclusions: Our single-center, retrospective analysis is consistent short follow up, but OS resulted better in patients with low BSI, thus
with the available data in current literature, as we observed in two in a less advanced state of the disease and able to complete all 6
different cohorts of patients that 68Ga-PSMA-11 PET/CT is more cycles of Ra223.
sensitive to detect PCa lesions than 11C-Choline PET/CT, especially
in recurrent PCa patients with low PSA levels.
PO131
Comparison of 68Ga-PSMA SUVmax and tumour
PO130
heterogeneity in DW-MRI
Radium-223-dichloride therapy in castration-resistant
metastatic prostate cancer: bone scan index evaluation M. Mottola2, F. Ferroni4, R. Togni1, A. Gherardi1, A. Turci2, M.
to predict therapy success Celli3, L. Fantini3, P. Caroli3, D. Barone4, G. Gavelli4, F. Matteucci3,
A. Bevilacqua1, G. Paganelli3
P. Ghedini1, V. Rossetti1, A. Franceschetto1, L. Massi1, A. Casolo1, 1
M. Nicolini3, R. Sabbatini2, N. Prandini1 Advanced Research Center on Electronic Systems for Information
and Communication Technologies ‘‘E. De Castro’’ (ARCES),
1
Nuclear Medicine, Azienda Ospedaliero-Universitaria Policlinico di University of Bologna, Bologna, Italy. 2Department of Electrical,
Modena, Modena, Italy. 2Oncology Unit, Azienda Ospedaliero- Electronic and Information Engineering ‘‘Guglielmo Marconi’’
Universitaria Policlinico di Modena, Modena, Italy. 3Oncology Unit, (DEI), University of Bologna, Bologna, Italy. 3Nuclear Medicine
Ospedale di Sassuolo, Sassuolo, Italy Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei
Tumori (IRST) IRCCS, Meldola, Italy. 4Radiology Unit, Istituto
Background-aim: Evaluation of Radium-223-Dichloride therapy Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)
response in patients with symptomatic bone metastases in castration- IRCCS, Meldola, Italy
resistant prostate cancer (mCRPC) in correlation with bone scan
index (BSI). Background-aim: 68Ga-PSMA is a labelled ligand to a membrane
Secondary Aim was to evaluate OS in subgroup of patients based on protein overexpressed in many prostate cancer cells and has raised its
BSI. interest to be highly specific in PET imaging for detection and staging
Methods: We retrospectively enrolled 20 patients addressed to our of prostate cancers. DW-MRI is a standard technique that provides
Nuclear Medicine Unit from 2014 to 2018 (age mean/range = 68.2/ quantitative information about tumour cellularity and tissue structure
58–78 years-old) with these inclusion criteria: (1) mCRPC patients is a useful tool for the detection and staging of prostate cancer in
with symptomatic bone metastases (2) Radium-223-Dichloride ther- clinical practice. This study investigates the correlation between
apy (1–6 cycle); when bone scan was available, BSI was measured SUVmax and tumour heterogeneity computed from DWI sequences.
and patient were divided in two subgroups: BSI \ 10% (Group A), Methods: 17 patients (age range 49–75 years; mean, 64.3 years) of a
BSI [ 10% (Group B). PSA, Alkaline phosphatase (ALP) and prospective study aiming at multi-cohort investigation for clinical
hemochrome values were measured before, previously each admin- impact of mp-3TMRI and 68Ga-PSMA PET/CT in diagnosis of
istration and at the end of therapy. Therapy evaluation, with clinical clinically-significant prostate cancer and presurgical staging. After
and radiological confirmation was classified as (CR), partial response co-registering MRI and PET sequences, Regions of Interest (ROIs)
(PR) or stable disease (SD). New radiological documented lesions or were manually delineated around prostate in MRI/T2 and the cancer
clinical progression were considered (PD). Delta-BSI was evaluated lesion in the dominant sequence (high values of DWI or T2). SUVmax
when post therapy scan was available. Follow-up (clinical and radi- was computed on PET images and 60%-threshold of SUVmax was
ological) was between 3 and 18 months (mean 12.2 months) and OS used for lesion contouring. A compound texture feature related to
was evaluated respectively for Group A and Group B tumour heterogeneity (Hc) was computed within prostate ROIs in
Results: (9/20) were responder patients in bone mets (PR, CR, SD); DWI and the outcome represented with colorimetric maps. The
(11/20) patients were reported to be PD. Considering responder highest regions were extracted by automatic contouring. Average Hc
patients subgroup, 6/9 showed an increasing PSA-trend, while 3/9 a (DWI) and SUVmax (PET) were computed on the co-registered slices
stable PSA trend. 100% of responders showed a significant decrease and the Spearman rank correlation (r) was assessed.
of ALP trend and all of them were responders also at imaging. Results: SUVmax ranges from [1.6–101.0] and Hc through
Baseline bone scan was available in 18/20 pts (2 pts had only Choline [37.9–50.6]. Regions highlighted by Hc are usually much greater than
PET scan). Among them, 5/18 could be classified in Group A (mean those detected by SUVmax thresholding and always include the region
BSI = 4.6%) and all of them showed PR, SD or CR. 13/18 could be outlined by radiologists. 13 patients show r C 0.7, 3 with r C 0.5 and
classified in Group B (mean BSI = 26.5%), and between them only 1 only with r C 0.25. For 11 patients (65% of cases) the amount of
4/13 were responder pts. Delta-BSI was increased more than 30% in PET slices pointing out malignant SUV peaks is greater than DWI
9/13 patients of Group B with PD, and reduced only in 3/4 of slices showing high Hc values, with Hc ROIs better depicting tumour
responder patient. In Group A, delta BSI showed a reduction in 3/5 extent. For 3 patients (17.5%) PET and Hc-DWI show equivalent
patients (about 50%) and a slight improvement in 2/5 pts. performance in tumour detection and in 3 cases only, Hc points out
Among pts in Group A, all of them completed all 6 cycles of more slices with suspect tumour ROIs. However, in all cases SUV and
Ra223, while only 6/13 pts in Group B completed all cycles of Hc show the same trend, with the highest values around central slices
and a much greater increasing rate for SUV.

123
S80 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

Conclusions: The outcomes of this study reveal a rank correlation Conclusions: Overall our patients, 5% (8/162) had 18F-FCH positive
between heterogeneity of cellularization and the expression of the pulmonary nodules: 14.3% (1/7) Pca metastasis, 42.8% (3/7) primary
membrane receptor of PSMA. The reason of such correlation requires lung cancer and 42.8% (3/7) benign etiology.
deeper investigations and could be confirmed after examining a wider The main limitation of our study is the relatively restricted number of
cohort. Hc result a promising compound feature for outlining patients with positive findings related to the low incidence of 18F-
malignant ROIs extent to be employed together with PET sequences FCH avid pulmonary nodules in Pca patients.
for validating tumour side. A deeper analysis is required for those few Nevertheless, our data suggest that detection of incidental
cases showing weak or even poor correlation between SUV and Hc. increased 18F-FCH avid pulmonary nodules is not specific but may
have significant impact on the patient management and should always
be reported, knowing that more than a half could represent malignant
etiology.
PO132
Occurence of 18F-FCH PET/CT positive pulmonary
lesions in patients affected by prostate cancer
PO133
1 1 2 2
P. Moda , A. Notaristefano , R. Leggieri , T. Iarussi , F. Lauriero 1 [18F]FMCH intratumor heterogeneity analysis
in patients with oligometastatic and multimetastatic
1
Nuclear Medicine Unit, PET/CT Centre, Hospital ‘‘G. Moscati’’, prostate cancer recurrence
Taranto, Italy. 2Thoracic Surgery Unit, Hospital ‘‘SS. Annunziata’’,
Taranto, Italy A. Marciano6, R. Zanca6, F. Di Martino3, C. Traino3, N. Belcari2,
Background-aim: 18F-FCH PET/CT might have the potential to F. Paiar4, F. Pasqualetti4, E. Neri5, S. Chiacchio6, F. Bartoli6,
identify other malignancies apart prostate cancer (Pca). M. Sollini1, P.A. Erba6
The aim of our study was to evaluate the occurrence of 18F-FCH 1
PET/CT positive pulmonary nodules in patients affected by Pca Department of Biomedical Sciences, Humanitas University, Milan,
during initial stadiation and restaging for biochemical recurrence. Italy. 2Department of Physics, University of Pisa, Pisa, Italy. 3Medical
Methods: 162 consecutive patients were retrospectively evaluated Physics Unit AOUP, Pisa, Italy. 4Radiation Oncology, Department of
with 18F-FCH PET/CT, 124 for restaging due to PSA increase and 38 Translational Research and New Technology in Medicine, University
patients for initial staging regarding extra prostatic extension risk. of Pisa and AOUP, Pisa, Italy. 5Radiology, Department of
Patient under hormone therapy did not stop it before PET imaging. Translational Research and New Technology in Medicine, University
We performed an early acquisition of the pelvic region 3–5 min of Pisa and AOUP, Pisa, Italy. 6Regional Center of Nuclear Medicine,
after intravenous injection of 4 MBq/Kg 18F-choline. After Department of Translational Research and New Technology in
30–45 min a Total-Body PET/CT examination was performed. Medicine, University of Pisa and AOUP, Pisa, Italy
Images analysis was carried out visually and the maximum stan- Background-aim: Restaging of patients with biochemical recurrent
dardized uptake value (SUV max) was calculated by semiquantitative prostate cancer (PCa) by [18F]FMCH allows the identification of two
determination. different group of patients with oligometastatic and multimetastatic
We compared SUV max values between malignant and benign disease, thus impacting in the subsequent treatment planning. Tex-
lesions with T-test. tural features advanced analysis has been used in several cancer for a
All patients exhibiting increased 18F-FCH avid pulmonary nod- more objective and quantitative evaluation. In this work we used
ules were then contacted and interviewed regarding the continuation radiomics analysis of [18F]FMCH PET/CT in patients with bio-
of their investigations: histopathological biopsy or CT follow-up. chemical recurrence of PCa after primary radical therapy with the
Results: Out of 162 patients, we identified 8 patients (5%) with hypothesis that oligometastatic and multimetastatic disease might
increased 18F-FCH avid pulmonary nodules (mean SUV max 4.1; present a specific radiomic signature.
range 2.0–7.1) and 11 patients (6.8%) with only morphological Methods: Within a prospective trial, we evaluated a series of 92
abnormalities. patients (mean age 73 ± 7 years, median age 73 years, range 55–85)
The clinical characteristics of the 8 patients (5%) with increased 18F- with recurrent PCa (median PSA at the time of [18F]FMCH PET/CT
FCH avid pulmonary nodules were the following: mean age 77 (range 5.2 ng/ml). Histology data and current treatment were recorded in all
56–89), median PSA level at PET/CT scan 186 ng/ml (range patients.
0.6–1000) and median Gleason score 7 (range 5–9). Whole-body PET/CT (GE Discovery ST) was acquired about 45 min
Seven of 8 patients, exhibiting increased 18F-FCH avid pul- after [18F]FMCH (4 MBq/kg of body weight) administration. Based
monary nodules, underwent to biopsy with the following on [18F]FMCH PET/CT results patients were classified in on Oligo-
histopathological findings: 4 patients had a primary lung cancer (2 metastatic (\ 3 lesions) or Multimetastatic ([ 3 lesions) disease. A
adenocarcinoma and 1 bronchioloalveolar carcinoma), 3 patients had total of 370 lesions were found and classified according to TNM in
benign lesions and 1 patient Pca metastasis. skeleton (n = 221), distant Ln (n = 81), regional Ln (n = 68), lesions
The remaining patient was only subjected to CT follow-up. not classified in the previous classes were excluded from the analysis.
None of the patients with only morphological abnormalities were Radiomics texture features were extracted using the LIFEx package
subjected to biopsy assessment and therefore it was not possible to from semiautomatically segmented PET and CT images. Statistical
determine the negative predictive value. analysis was performed with JMP Statistical DiscoveryTM. The
The positive predictive value for the patients with histopatholog- Spearman correlation coefficient two-sided Wilcoxon rank sum test or
ical findings was 57% (4/7). Kruskal–Wallis test were used and corrected for multiple testing
The patients with primary malignant lung lesions, as well as the using the Bonferroni–Holm method (significance level a = 0.05).
ones with benign lesions, had evidence of single pulmonary nodules, Multivariate analysis, Linear discriminant analysis and Principal
in comparison to the only one with Pca metastasis presenting multiple Components, was conducted splitting the dataset in the training,
lesions. validation and test subsets in order to apply the ‘‘lock box approach’’.
There was significant difference in median SUVmax values
between malignant and benign lesions (p value = 0.05).

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S81

Results: Patients with oligometastatic and multimetastatic recurrence LNM 2 (3 ± 2; 1–10). Median LNM size was 5 mm (5 ± 2.5; 2–10).
(both 3 and 5 lesions) presented different radiomics signature. On patient-based analysis, FACBC sensitivity, specificity, PPV, NPV
Radiomics features were also different among PCa subtypes (Gleason and accuracy for LNM were 50, 81, 90, 83 and 74% (vs CHOL: 50,
score), thus identifying more aggressive PCa. In addition, texture 70, 36, 81 and 65%). There were 10 discordant cases (14%): 1 CHOL
parameters showed ability in distinguishing among site of recurrence FN/FACBC TP, 7 CHOL FP/FACBC TN, 1 CHOL TN/FACBC FP, 1
being different in bone lesions recurrence, distant Ln recurrence and CHOL TP/FACBC FN. A not negligible n of equivocal score in TP
local Ln recurrence. Hormone-therapy impact on textural features was (5/9) and of faint/indeterminate uptake in TN group (only 30/44 non
assessed to identify texture features characterizing lesions indepen- avid) were observed.
dently from ongoing therapy. Validation and retesting of the model Conclusions: FACBC demonstrated ln sensitivity equal to CHOL
showed its stability with a difference in AUC of less than 15% in each with slightly better specificity, overall diagnostic performance and
classification studied. practical/technical advantages. Sensitivity is still inadequate com-
Conclusions: Our preliminary results after these first series of pared to PLND, suggesting that to date there is no metabolic tracer
patients showed that texture analysis of [18F]FMCH PET/CT is able ideal for preoperative ln staging. PET visual interpretation also relies
to characterize the heterogeneity of lesions in patients with recurrent more on reader experience than on unquestionable ln avidity, thus
PCa, more efficiently than the semi-quantitative indexes. Radiomic evaluation of semi-quantitative indices, as well as anatomical region-
analysis proved its ability in investigating lesions heterogeneity, based and uni/multivariate-regression to search for LNM predictive
providing imaging biomarker to be add to the current available to factors is a topic of ongoing work.
better characterize disease PCa burden and biological aggressiveness,
thus guiding patients’ treatment decision making.
PO135
Prognostic role of baseline 18F-FDG PET/CT metabolic
PO134
18 parameters in mantle cell lymphoma
F-Fluciclovine PET/CT for nodal staging high risk
prostate cancer: final results of a prospective trial D. Albano2, N. Bianchetti1, M. Bonacina2, R. Durmo2, E. Cerudelli2,
M. Gazzilli2, F. Dondi2, A. Mazzoletti2, A. Re1, A. Tucci1,
L. Zanoni2, C. Pultrone5, F. Giunchi3, C. Nanni2, I. Bossert1, F. Bertagna2, R. Giubbini2
A. Matti2, R. Schiavina5, M. Fiorentino3, L. Bianchi5, D. Romagnoli4,
C. Fonti2, F. Lodi2, E. Brunocilla5, A. Porreca4, S. Fanti2 Division of Hematology, Spedali Civili, Brescia, Italy. 2Nuclear
1

Medicine, University of Brescia and Spedali Civili, Brescia, Italy


1
Nuclear Medicine, Istituti Clinici Scientifici Maugeri, Pavia, Italy.
2 Background-aim: Mantle cell lymphoma (MCL) is an aggressive
Nuclear Medicine, Sant’Orsola-Malpighi Hospital, Bologna, Italy.
3 lymphoma subtype with aggressive behavior and high 18F-FDG-
Pathology, Sant’Orsola-Malpighi Hospital, Bologna, Italy. 4Urology,
avidity at fluorine-18-fluorodeoxyglucose positron emission tomog-
Abano Terme Hospital, Padua, Italy. 5Urology, Sant’Orsola-Malpighi
raphy/computed tomography (18F-FDG PET/CT); nowadays no
Hospital, Bologna, Italy
validated criteria for PET/CT in treatment evaluation and prediction
Background-aim: To evaluate 18F-fluciclovine PET/CT (FACBC- of outcome are currently available. The aim of this study was to
PET) diagnostic performance for preoperative lymphnode (ln) staging investigate whether the metabolic baseline PET/CT features may
in high risk prostate cancer (PCa). predict treatment response at end of treatment (eot) and prognosis in
Methods: A prospective monocentric study (granted by Programma MCL. Moreover, we evaluated also the possible prognostic role of
di ricerca Regione-Università GR Alessandro Liberati 2013) enrolled Deauville criteria.
a series of patients (pts) with biopsy-proven PCa, standard staging Methods: Between January 2007 and January 2018, 87 patients with
(including 11C-Choline PET/CT (CHOL PET)), eligible for pelvic ln histologically proven MCL were retrospectively enrolled; all patients
dissection (PLND), to undergo an investigational FACBC-PET underwent baseline 18F-FDG PET/CT and eotPET/CT after 6 cycles
(370Mbq, GE Discovery 690, 2 min/bed). Nodal uptake higher than of chemotherapy. The PET images were analyzed visually and semi-
surrounding background was reported by at least 2 readers (blinded to quantitatively by measuring the maximum standardized uptake value
CHOL PET results) using a visual 5-point scale: 1–2 probably neg- body weight (SUVbw), the maximum standardized uptake value lean
ative; 4–5 probably positive; 3 equivocal. Lesion site, size, SUV and body mass (SUVlbm), the maximum standardized uptake value body
TBRs were recorded. PET results were compared with PLND. The surface area (SUVbsa), lesion to liver SUVmax ratio (L-L SUV R),
following patients were excluded: 8 limited PLND; 3 intermediate lesion to blood-pool SUVmax ratio (L-BP SUV R), metabolic tumor
risk; 2 treated with radiotherapy; 4 found to be M1; 5 neoadjuvant volume (MTV) and total lesion glycolysis (TLG). EotPET/CT results
hormonal therapy. were visually interpreted according to the criteria of the Deauville-5-
Results: 94 pts underwent FACBC PET; 72/94 (77%) were included point-scale (DC). For the entire population, receiver operating char-
in the final analyses. Median age was 66y (mean 65 ± 6; 47–76), acteristic curve analysis was used to identify the optimal cutoff point
PSA 7,2 ng/ml (10 ± 8; 2.3–48.7). The majority presented: TRUS of semiquantitative parameters in the light of progression/relapse.
positivity (63%), cGS C 8 (88%), cT2 (79%), pGS C 8 (79%), pT3a Survival curves were plotted according to the Kaplan–Meier method.
(54%), ECE (76%), perineural invasion (89%), R0 (56%), negative Results: At a median follow-up of 40 months, relapse/progression
seminal vesicles (76%). Median time interval between CHOL/ occurred in 47 patients with an average time of 20.2 months and
FACBC was 1 day, FACBC/surgery 1 month. Open, laparoscopic or death in 23 patients with an average time of 30.5 months. Median
robotic surgery approach in 14, 5 and 81%; postsurgical complica- PFS and OS were 30 and 41 months. The estimated 2-year PFS and
tions occurred in 26%. Staging CT and MRI were available in 14 and OS rates were 52% and 82% respectively, while 3-year PFS and OS
45 pts: suspected LN metastases (LNM) were reported in 5 (4 TP) and rates were 48% and 72%, respectively. At eotPET/CT, 60 patients had
6 (3 TP) pts respectively. Median LNM predicted risk by Briganti complete response, 17 patients had partial response and 8 patients had
Nomogram was 19% (25 ± 19; 5–82). Observed LNM prevalence progression of disease. Two patients die before performing eotPET/
was 25% (pN1: 18 pts). Overall 1671 ln were retrieved, 45 (3%) LNM CT. There was a statistically significant difference between baseline
counted. Per pt, median n of removed ln was 22 (23 ± 10; 8–51), of MTV and TLG of response group (complete and partial response) and

123
S82 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

no response group at eotPET/CT (p 0.040, p 0.002). Other metabolic Results: We found that SUVmax values obtained with IEC and IRR
PET/CT parameters were not related to treatment response. EotPET/ are strictly correlated (IEC = 0.79*IRR; r2 = 0.98) for MLD values
CT results using Deauville criteria significantly correlated with PFS range 15-60 mm. For lesions with MLD below 15 mm a definite trend
(p \ 0.001), not with OS. MTV and TLG were demonstrated to be to a reduction of the correlation coefficient is observed, linked to the
independent prognostic factors for PFS (p 0.049 and 0.019); instead, more pronounced partial volume effect that characterizes IEC
the other metabolic parameters (SUVbw, SUVlbm, SUVbsa, L-L reconstruction. The coefficient seems independent from blood glucose
SUV R and L-BP SUV R) were not related to outcome survival. levels, but the small number of patients denied a significant statistical
Considering OS, none variable was significantly associated. result.
Conclusions: Metabolic tumor features (MTV and TLG) were sig- Conclusions: Our data support the hypothesis that, whenever nec-
nificantly correlated with response to treatment and long-term essary for forcibly comparing SUVmax values obtained from FDG-
outcome. Also eotPET/CT results (evaluated according to DC) is PET scan reconstructed with older and up-to-date reconstruction
significantly correlated with PFS. algorithms, the use of user-defined conversion factor introduce a
small, tolerable error.

PO136
SUVmax values obtained in FDG PET/TC PO137
with different reconstruction algorithm show Contrast enhanced CT and non-enhanced low-dose CT:
a constant-ratio relationship comparison between diagnostic contribute in staging
and restaging FDG-avid lymphomas
D. De Palma1, S. Casagrande1, C.L. Gobbo1, S. Scotti1, I. Schiorlin1,
C. Favaro1, M. Menzaghi1 I. Rambaldi6, L. Marchetti3, M. Caracciolo2, M. Tilli5, I. Marri5,
M. Giganti4, G. Benea1, M. Bartolomei6
1
Nuclear Medicine Unit, Tech Service Dept. ASST-Settelaghi,
1
Varese, Italy Department of Interventional and Diagnostic Radiology, Arcispedale
Sant’Anna, Via Aldo Moro 8, 44124, Ferrara, Italy. 2Department of
Background-aim: Quantification has been from the beginning one of
Morphology, Surgery and Experimental Medicine, Section of Nuclear
the cornerstone of Nuclear Medicine. The most popular quantitative
Medicine, University of Ferrara, Via Ludovico Ariosto 35, 44121,
tool in FDG-PET is the Standard Uptake Value (SUV). i.e. the tracer
Ferrara, Italy. 3Department of Morphology, Surgery and Experimental
concentration into a volume unit, expressed as MBq/g. SUV was first
Medicine, Section of Radiology, University of Ferrara, Via Ludovico
tested as a discriminator between malignant and benign lesions but,
Ariosto 35, 44121, Ferrara, Italy. 4Department of Morphology,
due to its limits for this purpose, its main use became the evaluation
Surgery and Experimental Medicine, Section of Radiology,
of therapy response during follow-up studies, expressed as SUV value
University of Ferrara, Via Ludovico Ariosto 35, 44121, Ferrara, Italy.
reduction ( SUV). There are many known factors that affect SUV 5
Department of Interventional and Diagnostic Radiology, Arcispedale
reproducibility, but one of the most intriguing is the reconstruction
Sant’Anna, Via Aldo Moro 8, 44124, Ferrara, Italy. 6Department of
algorithm. In fact, new software increases the image quality, but
Medical Sciences, Unit of Nuclear Medicine, Azienda Ospedaliero-
hamper the comparison of SUV values obtained in the same patient in
Universitaria, Arcispedale S. Anna, University of Ferrara, Ferrara,
different times or, in multi-centric studies, between patients studied in
Italy
different centers.
This is more worrying considering that PET raw data are normally not Background-aim: According to guidelines, staging of FDG-avid
saved on PACS, and is then impossible to change afterwards the lymphomas requires a PET-CT exam and a baseline contrast
reconstruction algorithm used enhanced CT (ceCT), both acquired in a single session.
This problem could theoretically be overcome if SUVs obtained This study aims to evaluate the incremental ceCT diagnostic value
with different algorithm, all others factors remaining unchanged, were compared to unhenanced low-dose CT (ueCT) included in PET-CT
linked by a constant ratio. We then tried to verify this hypothesis. study in staging, to establish the real diagnostic contribute of ceCT.
Methods: We retrospectively analyzed data from 29 patients with Methods: PET-ceCT were prospectively performed in 30 patients
malignant Lymphomas, enrolled in randomized double blind with FDG-avid lymphomas.
prospective studies, whose PET scans were reconstructed with two Two different radiologists evaluated ceCT and ueCT in a blinded
different algorithm: a classical OSEM 2D-iterative (IEC) and a TOF- manner.
based, parallaxis-error correction inclusive, resolution recovery Nodal and extranodal findings for each study were separately
(IRR). All studies were performed with a Siemens Biograph mCT compared with PET-CT results (gold standard). CT and PET findings
scanner, with four detector rings, a 40 slices CT, a TOF temporal were both classified according to revised Ann-Arbor classification.
resolution of 540 ps. Results: In 28 of 30 patients ceCT (93%) did not change Ann-Arbor
VOIs were manually drawn, on the IRR images, around the most stage assigned by low-dose ueCT-FDG-PET.
active lesions, visually detected with a SUV-based color scale, tracing Nodal findings were equally detected for both ceCT and ueCT.
an ellipsoid master VOI and applying an automatic edge detection at a In only two cases (7%) ceCT identified extranodal lesions (1
SUV threshold value of 2.5 MBq/g. The master VOI was then copied hepatic and 1 muscular sites) and correctly provided changes in Ann-
on the IEC image. Arbor stage than low-dose ueCT. However, in the latter two cases
We first checked the Gaussian/non-Gaussian data distribution by therapeutic strategy would not have been changed.
Kolmogorov–Smirnov test. A non-Gaussian distribution was Conclusions: PET-ueCT staging of FDG-avid lymphomas should be
observed, so we compare the two groups using Wilcoxon signed rank considered as primary imaging modality of choice.
test. Being them statistically different, we calculated the correlation Additional diagnostic value of ceCT is limited only in selected cases
between the SUVmax of the two groups. After, we further evaluate of extranodal disease and could be avoided in the majority of cases,
the weight of the glycemic levels (above/below 100 mg/dl) and of the particularly in younger patients in order to minimize radiation
lesion diameter after normalization to a spherical shape (MLD)

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S83

exposure and to reduce risk of allergic reaction or nephropathy due to on D5-D7 was significantly higher in patients who progressed to
iotinated Ct contrast agents. symptomatic MM (0.49 [IQR 0.44–0.53] vs 0.43 [IQR 0.37–0.48];
These sample results should be confirmed in a larger population in P = 0.014); median Grey-Level Run Length Matrix_Long-Run High
order to better detect patients most likely to benefit, particularly those Gray-level Emphasis (GLRLM_LRHGE), which is the distribution of
with extranodal disease. the long homogeneous runs with high grey-levels, calculated on iliac
crests was significantly higher in patients who progressed to symp-
tomatic MM (86.1 [IQR 62.5–105.7] vs 54.7 [IQR 40.7–77.2];
P = 0.022).
PO138 Conclusions: Advanced textural parameters may be useful to identify
Progression to symptomatic myeloma predicted subtle, otherwise visually undetectable, disease involvement of
by texture analysis-derived parameters in patients patient’s bone marrow with possible prognostic impact.
without focal disease at FDG-PET/CT

C. Caldarella5, D. Ripani4, T. Za1, V. De Stefano2, A. Giordano3 PO139


1
Standardization of MTV computation: acquisition time
Hematology Service, Fondazione Policlinico Universitario
A.Gemelli IRCCS, Rome, Italy. 2Institute of Hematology, Fondazione
and segmentation algorithm matter
Policlinico Universitario A.Gemelli IRCCS-Università Cattolica del
Sacro Cuore, Rome, Italy. 3Institute of Nuclear Medicine, Fondazione A. Borra4, F. Bergesio1, L. Guerra3, S.D. Morbelli4, G. Sambuceti4,
Policlinico Universitario A.Gemelli IRCCS-Università Cattolica del S. Chauvie2, A. Gallamini5
Sacro Cuore, Rome, Italy. 4Institute of Nuclear Medicine, Università 1
Cattolica del Sacro Cuore, Rome, Italy. 5Nuclear Medicine Unit and Medical Physics Department, S. Croce and Carle Hospital, Cuneo,
PET-CT Center, Fondazione Policlinico Universitario A.Gemelli Italy. 2Medical Physics Department, S.Croce and Carle Hospital,
IRCCS, Rome, Italy Cuneo, Italy. 3Nuclear Medicine Department, S. Gerardo Hospital,
Monza, Italy. 4Nuclear Medicine Unit, Department of Health
Background-aim: The role of FDG-PET/CT for disease staging and Sciences, University of Genoa, Genoa, Italy. 5Research, Innovation
to assess response to treatment in patients with multiple myeloma and Statistics Department, A Lacassagne Cancer Center, Nice, France
(MM) is well established. However in patients with smouldering MM
focal lesions are not always noticeable on FDG-PET/CT. Texture Background-aim: The aim of the present study was twofold: (1) to
analysis-derived parameters may improve the interpretation of PET/ compare two different methods for tumor segmentation, adopting
CT images. Aim of our study was to determine whether texture (a) a SUVmax absolute threshold of 2.5 (T2.5) or (b) a relative
analysis-derived PET parameters predict progression to symptomatic threshold of 41% of the SUV max (T41%), to compute metabolic
MM in patients without evidence of focal sites of 18F-FDG uptake at tumor volume (MTV); (2) to assess the influence of acquisition time
initial staging. on MTV computing with both methods in baseline staging with FDG-
Methods: Patients with smouldering MM undergoing FDG-PET/CT PET/CT in Hodgkin Lymphoma (HL).
for disease staging from May 2014 to February 2018 were retrospec- Methods: HL patients recruited in a European observational study
tively reviewed in order to retrieve those without evidence of focal sites aimed to assess the overall accuracy in predicting treatment outcome
of 18F-FDG uptake. For each patient D5-D7 and L2-L4 vertebral of dual-point PET/CT (DTP-PET) underwent dual-time image
bodies, as well as iliac crests and the proximal half of each femoral acquisition, at 60’ and 120’ after the administration of a single,
diaphysis were contoured by placing 3-dimensional VOIs on sagittal standard dose of 18F-FDG during HL staging and restaging. SUV-
and axial projections; a more accurate bone contour was obtained max, SUVmean and MTV were computed for all patients lesions in
applying a lower threshold value of 65 Hounsfield units on coregistered baseline FDG/PET-CT with petctviewer.org software using either
CT. A dedicated software (Lifex,http://www.lifexsoft.org) allowed to T2.5 or T41%. Only small or medium-sized focal lesion from ROIs
obtain for each VOI conventional parameters (SUVmax, SUVmean, not encompassing areas of physiological FDG uptake were selected
SUVpeak, MTV, TLG), first-order textural histogram and shape fea- for MTV calculation in baseline FDG-PET/CT.
tures (Skewness, Kurtosis, Entropy, Energy, Sphericity, Compacity), Results: Early images were acquired after a mean of 70 ± 20’ late
and advanced textural second-order features (Grey-Level Zone Length acquisition after a mean of 133 ± 19’ after FDG injection. A total of
Matrix [GLZLM], Grey-Level Run Length Matrix [GLRLM], Neigh- 33 lesions in 13 patients were evaluated. As expected, both SUVmax
borhood Grey-Level Different Matrix [NGLDM] and Grey Level Co- and SUVpeak increased at delayed acquisition. By contrast MTV
occurrence Matrix [GLCM]). Progression to symptomatic MM was values showed a divergent behavior according to the two methods
established based on clinical-laboratory symptoms/signs. used for tumor segmentation. In fact while  MTV computed with
Results: Thirty-two patients with smouldering MM and available T2.5 increased overtime, with a median ?21% value (P \ 0.04),
outcome information to determine progression to symptomatic MM MTV computed with T41% decreased (- 7%; P \ 0.002).
were included (16 m, 16f; mean age 62.6 ± 11.4 years): progression Conclusions: Depending on the threshold used for tumor segmenta-
to symptomatic MM occurred in 19/32 patients (59%) and they tion, opposite results in MTV computing were found in late (?120’)
needed to start disease specific treatment. Conventional parameters, compared to standard (?60’) image acquisition in DTP-PET: MTV
along with first-order textural histogram and shape features, did not increased on decreased overtime using T2.5 and T41% methods,
significantly differ between patients according to their progression to respectively. These results, though obtained in a limited series of
symptomatic MM; conversely, median Grey Level Co-occurrence patients suggest that both acquisition time and tumor segmentation
Matrix_Correlation (GLCM_Correlation), which measures the linear methods matter in MTV computation reproducibility.
dependency of grey levels on those of neighbouring pixels, calculated

123
S84 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

PO140 PO141
Diagnostic value of the CT portion of PET/CT studies Diagnostic accuracy of FDG PET/CT at the end
assessed by the clinical impact of incidental findings of treatment of hodgkin lymphoma in the HD0607 trial
in multiple myeloma patients
A. Buschiazzo3, F. Bergesio2, A. Bianchi3, M. Menga4, F. Fallanca1,
1 1 1 1
C. Ferrari , A.G. Nappi , N. Maggialetti , A. Niccoli Asabella , S. Chauvie2, A. Gallamini5, A. Biggi3
N. Merenda1, N. Addante1, L. Brunese1, G. Rubini1 1
Nuclear Medicine Department, IRCCS San Raffaele, Milan, Italy.
2
1
Nuclear Medicine Unit, Interdisciplinary Department of Medicine, Medical Physics Department, ASO Santa Croce e Carle, Cuneo,
University of Bari ‘‘Aldo Moro’’, Bari, Italy Italy. 3Nuclear Medicine Department, ASO Santa Croce e Carle,
Cuneo, Italy. 4Nuclear Medicine Department, Azienda Ospedaliera e
Background-aim: 18F-FDG-PET/CT is a useful tool to image Universitaria di Trieste, Trieste, Italy. 5Research, Innovation and
Multiple Myeloma (MM), to evaluate the extent of whole-body dis- Statistics Department A. Lacassagne Cancer Centre, Nice, France
ease and to distinguish between active or inactive disease after
therapy. The unenhanced CT portion may provide additional diag- Background-aim: Positron Emission Tomography-Computed
nostic information not apparent on PET. Tomography (PET-CT) is standard of care for remission assessment
The aim of this study was to evaluate the prevalence and the clinical in FDG-avid lymphoma. According to the Malignant Lymphomas
significance of incidental extra-skeletal findings (IF) from the inde- Imaging Working Group, Deauville score (DS) is recommended for
pendent reading of the unenhanced CT portion of PET/CT studies. PET/CT reporting. To date, however, few studies have focused on the
Methods: We selected an homogeneous cohort of 112 patients prognostic value of PET/CT when performed at the end of therapy in
affected by MM (66 men and 46 women; mean age 65.8 years), who patients with Hodgkin’s lymphoma (HL) using the recommended
underwent to 18F-FDG-PET/CT during their work-up at our Nuclear standard criteria. In this study we evaluated the accuracy of the DS in
Medicine Department from June 2016 to July 2017. the end of therapy evaluation of FDG-PET in the HD0607-trial.
The unenhanced CT portion of PET/CT was performed with the Methods: The multicenter trial HD0607 is focused on the clinical
following parameters: acquisitions from the skull to the mid-thigh impact of dose intensification performed early during treatment in a
(5–7 bed positions), 120 kV and mA with automatic modulation subset of poor prognosis, advanced-stage HL patients, defined as
system. All CT studies were retrospectively reviewed on a dedicated PET-positive after two courses of conventional ABVD. PET/CT was
workstation, with 3.75 slice thickness and equipped with MPR/VR performed at baseline (PET0), after two cycle of ABVD (PET2);
reconstructions, by an expert CT radiologist. PET2 positive patients (DS C 4) according to a review panel, pro-
Each IF, not related to MM, was categorized in a body region/ ceeded to escalated-BEACOPP regimen (experimental arm) while
system and classified according to MM-Reporting and Data System patients with a negative PET2 (DS \ 4) continue the conventional
(MM-RADS), a 5-point significance score system inspired by ABVD regimen (standard arm). Remission was assessed with a final
C-RADS, in which the score increases with the clinical significance of PET (EoT-PET) at the end of treatment in both arms.
IF. The study population of the present study consisted of a subset of 112
Results: 153 IF were detected in 112 patients (mean value 1.4). randomly chosen among the 782 advanced-stage HL included in the
53.6% of IF would have required further clinical investigation HD0607 study. EoT-PET, together with PET0 and PET2 scans, were
(MM3 ? MM4), of which 18.3% (28/153) of IF were potentially independently reviewed by two nuclear medicine physicians blinded
clinically significant (MM4) and categorized as follows: 9/153 (5.9%) to patient history, clinical data and treatment outcome. In each patient
in the abdomen (8 liver solid lesions [ 1 cm and 1 peritoneal carci- the location of the most active residual lesion in EoT-PET (reference
nomatosis), 8/153 (5.2%) in the lung (3 pulmonary nodules [ 1 cm, 3 lesion) was identified and visually scored according to DS; a con-
calcified pleural plaques [ 1 cm, 2 non-calcified pleural plaques [ sensus was reached in discordant cases. EoT-PET with DS C 4 was
1 cm), 6/153 (3.9%) in the cardiovascular system (aortic aneurysmal defined as positive.
dilatations), 3/153 (2.0%) in the gastrointestinal tract (2 rectal The results of EoT-PET were considered in term of sensitivity
thickening, 1 appendicular mucocele), 1/153 (0.7%) in the geni- (SE), specificity (SP), predictive positive value (PPV), negative pre-
tourinary system (1 kidney solid nodule [ 1 cm), 1/153 (0.7%) in the dictive value (NPV). Failure Free Survival (FFS) was calculated at
breast (1 breast solid nodule [ 1 cm). 3 years using the Kaplan–Meier method.
Conclusions: 18F-FDG-PET/CT is now considered the method of Results: 96/112 (86%) of EoT PET were negative and 16/112 (14%)
choice in MM. To date, co-registration CT images become diagnostic, were positive. The mean FFS after a 3 years follow up were 0.96 and
thanks to specific dose reduction protocols. 0.62 in EoT-PET negative and positive patients, respectively. SE, SP,
Our study showed that the independent reading of the unenhanced CT PPV and NPV were 0.61 (0.39–0.80), 0.98 (0.92–1.00), 0.88
portion of PET/CT studies found a considerable number of IF (1.4/ (0.62–0.98), 0.91 (0.83–0.96) respectively.
pts), probably due to the high mean age of MM patients. Conclusions: DS criteria are accurate to identify patients with a good
Particularly, the evidence that 18.3% (MM4) was severe enough to or bad prognosis at the end of treatment in the H0607 trial.
warrant significant change in the clinical management of patients,
leads us to believe that the combined radiologist-nuclear physician
report, may further improve the diagnostic value of 18F-FDG PET/
CT and the management of these patients.

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S85

PO142 PO143
Value of FDG-PET/CT radiomic features in predicting Evaluation of the prognostic role of interim pet in adult
response to nivolumab treatment in refractory hodgkin hodgkin lymphoma according to Deauville criteria
lymphoma patients and metabolic parameters

M. Sollini1, M. Kirienko1, L. Cozzi3, F. Ricci4, C. Torrisi5, S. Pacella4, C. Landoni4, C. Crivellaro4, E. De Ponti2, M. Arosio3,
J. Jandric2, C.C. Stella4, A. Chiti2 S. Bolis1, F. Elisei3, L. Guerra3
1 1
Department of Biomedical Sciences, Humanitas University, Pieve Haematology Department, ASST Monza, San Gerardo Hospital,
Emanuele, Milan, Italy. 2Department of Biomedical Sciences, Monza, Italy. 2Medical Physics Department, ASST Monza, San
Humanitas University, Pieve Emanuele, Milan, Italy; Nuclear Gerardo Hospital, Monza, Italy. 3Nuclear Medicine Department,
Medicine, Diagnostic Imaging Department, Humanitas Clinical and ASST Monza, San Gerardo Hospital, Monza, Italy. 4Nuclear
Research Center, Rozzano, Milan, Italy. 3Department of Biomedical Medicine, University of Milano Bicocca, Milan, Italy
Sciences, Humanitas University, Pieve Emanuele, Milan, Italy;
Background-aim: 18-Fluorodeoxyglucose (FDG) positron emission
Radiotherapy, Humanitas Cancer Center, Humanitas Clinical and
tomography/computed tomography (PET/CT) has become a very
Research Center, Rozzano, Milan, Italy. 4Department of Oncology
important tool for initial staging and for the response assessment in
and Hematology, Humanitas Cancer Center, Humanitas Clinical and
Hodgkin lymphoma (HL).
Research Center, Rozzano, Milan, Italy. 5Radiology, Humanitas
The interim-PET (i-PET) has also a prognostic role, because it has
Cancer Center, Humanitas Clinical and Research Center, Rozzano,
been demonstrated that patients with early response to therapy have a
Milan, Italy
better prognosis.
Background-aim: To assess the predictive role of positron emission This study aimed to explore the prognostic role of i-PET in
tomography (PET)-derived radiomic features in patients affected by patients with HL using the Deauville criteria and the SUVmax and
refractory Hodgkin Lymphoma (HL) undergoing nivolumab SUVpeak of the reference lesions; the results obtained with the
treatment. qualitative 5-PS and with the metabolic parameters (SUVmax and
Methods: We retrospectively evaluated HL patients who performed a SUVpeak) were respectively correlated to disease free survival (DFS)
PET/CT before the initiation of nivolumab in our institution. The and overall survival (OS).
volume of interest (VOI) of the target lymphnode (the largest in Methods: We retrospectively selected 83 patients (47 men, 36
transverse diameter and/or with the highest maximum standardised women; mean age 40 ± 14 years, range 20–73) with newly diag-
uptake value (SUVmax))—was semi-automatically defined on PET nosed HL, stage I-IV disease (7 stage I, 36 stage II, 21 stage III and 19
images with a threshold of 40% of the SUVmax using a commercial stage IV).
software (PET VCAR, GE Healthcare, Waukesha, WI, USA). The All patients underwent 18F-FDG PET/CT prior to treatment (baseline
features were extracted using LIFEx software. The dataset was ran- PET), after two cycles of chemotherapy (i-PET) and at the end of
domly split into training and validation sets. Combinations of imaging treatment. i-PET were qualitatively interpreted by two nuclear med-
features were used as predictors in linear discriminant analysis with icine physicians using the Deauville five-points scale with ‘‘the liver’’
direct variable insertion. The procedure was repeated for 100 cycles as threshold: PET/CT with a score of 1-3 were considered ‘‘negative’’
with different and independent case assignments. Treatment response and the others with a score of 4 or 5 ‘‘positive’’. Lesions with the
was assessed according to Lyric criteria. Patients were classified as highest FDG uptake on i-PET were selected as ‘‘reference lesions’’
responders (stable disease, partial or complete response) and non- and SUVmax and SUVpeak of this were calculated. All datasets were
responders (progressive disease). Scoring metrics included sensitivity, correlated with DFS and OS. ROC curves were analyzed in order to
specificity, accuracy and the analysis of the receiver operating char- find SUVmax and SUVpeak thresholds that better distinguish patients
acteristic curves in particular, the area under the curve (AUC). with good prognosis from the others. Kaplan–Meier method was used
Results: Thirty-six HL patients (M:F = 21:15) were analyzed. to evaluate DFS and OS.
Fourteen patients were classified as responders and 22 as non-re- Results: The median follow-up was 36 months for DFS and
sponders. Sensitivity, specificity, accuracy and AUC were 98%, 91%, 50 months for OS.
95% and 0.98 in the training and 75%, 66%, 72% and 0.69 in the i-PET scan resulted negative for 66 patients (79.5%) and positive for
validation sets. 17 patients (20.5%). The positive and negative predictive values of
Conclusions: These preliminary data suggest that pre-treatment PET/ i-PET for predicting treatment outcome were 47,0% and 93,9%,
CT textural features may predict response to Nivolumab in refractory respectively.
HL patients. An external validation analysis is planned. The DFS and OS for positive i-PET and negative i-PET were
58.2% and 96.7% (p \ 0.0001), and 70.6% and 98.5% (p \ 0.0001)
respectively.
Cuts-off of 3.3 for SUVmax and of 3 for SUVpeak distinguished
good responders from refractory patients and were also relevant for

123
S86 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

prognosis in terms of overall survival (OS) (p = 0.014 and p = 0.022, underscored in DS1. In the axillary lymph nodes many DS3 were up-
respectively). scored in DS4 for the poor surrounding background.
Conclusions: Interim PET/CT is a good predictor of outcome in Regarding the clinical impact analysis, the use of COL scale
patients with HL. changed the interpretation of the exam in two patients at the interim
Deauville criteria using a threshold of 3 better discriminated between evaluation: in one patient from positive to negative (DS4 with BN and
patients with poor prognosis and the others. Similarly, metabolic DS3 with COL), the EoT-FDG-PET was negative and the patient had
features of reference lesion (SUVmax \ 3.3 and SUVpeak \ 3) are not a recurrence. In the other patient from negative to positive (DS3
predictors of good prognosis in terms of overall survival (OS). with BW and DS4 with COL): the EoT-FDG PET was positive and
later the patient had a recurrence. In the EoT evaluation the COL
scale changed the interpretation of the exam in one patient, from
positive to negative (DS4 with BW and DS3 with COL) and the
PO144 patient did not have a recurrence.
The use of colour scale could improve both concordance Conclusions: In the evaluation of i- and EoT FDG PET scans in HL
and accuracy of Deauville score assignment at interim patients, the use of COL could increase both the accuracy and the
diagnostic confidence in DS. The improvement is particularly sig-
and end-of-treatment FDG PET in patients
nificant in the binaries DS 1, 2 or 3 vs. DS 4 or,5. Further studies are
with hodgkin lymphoma needed for the analysis of the clinical outcome of patients, especially
in other lymphoma populations.
A. Kokomani4, V. Berti4, G. Puccini4, R. Di Dato4, F. Tutino4,
A. Ciaccio4, V. Briganti4, F. Linguanti4, V. Vergura4, S. Kovalchuk2,
B. Puccini2, F. Mungai5, L. Rigacci3, A. Passeri4,
O.F. On Behalf Of Imaging Working Group1, R. Sciagrà4 PO145
Evaluation of PET/MR attenuation correction methods
1
Fondazione Italiana Linfomi, Alessandria, Italy. 2Haematology Unit, for multiple myeloma
Careggi University Hospital, Florence, Italy. 3Haematology Unit, San
Camillo Hospital, Rome, Italy. 4Nuclear Medicine Unit, Careggi
A. Spimpolo1, G. Maretto1, S. Berti1, V. Bodanza1, R. Simeone1,
University Hospital, Florence, Italy. 5Radiology Unit, Careggi
D. Cecchin1, F. Bui1, P. Zucchetta1
University Hospital, Florence, Italy
1
Background-aim: The 5-point Deauville scale (DS) is widely used to Nuclear Medicine Department, University-Hospital of Padua, Padua,
assess interim (i) and end-of-treatment (EoT) FDG PET metabolic Italy
response to chemotherapy in Hodgkin lymphoma (HL) patients,
Background-aim: MR-based attenuation correction (MRAC) of PET
though sometimes the correct assignment of the DS is difficult The
data in PET/MR systems is still a field of active research. MR-image
aim of our study is to evaluate the contribution of a colour scale in DS
intensities, in fact, are related to proton density and longitudi-
assignment in improving concordance, accuracy and prediction of
nal/transverse magnetization relaxation properties of objects, which in
patient outcome as compared to the black/white scale.
turn are not related to attenuation of ionizing radiation. Consequently,
Methods: We elaborated 219 images from a database of 119 patient
unlike PET/CT, spatially aligned CT data measuring radiodensity of
with HL, who underwent first line chemotherapy, i-FDG PET and
patients’ tissues are not available and extremely dense biological
EoT-FDG PET in our Nuclear Medicine Unit from 2010 to 2017.
tissues—such as cortical bone—might display the same signal of air,
Every image was anonymously saved in two colour scales: black and
despite the high attenuation power of the former in comparison to the
white inverse (BW) and Rainbow (COL) on a GE Xeleris Workstation
latter.
Console. For the concordance analysis 2 expert nuclear medicine
Recently, Siemens has implemented on its 3T Biograph mMR a new
physicians and 2 non-expert nuclear medicine residents evaluated the
bone-segmentation algorithm which adds bone information to the
images and assigned a DS score and a confidence level (0–100). In
standard 4-compartments sequence-based l-map. This method relies
discordant cases, a consensus on DS was established within expert
on an offline-constructed model including a set of pre-aligned MR
evaluators. All DS were then compared to lesion uptake ratio to
image and bone mask pairs for each major bone including left/right
mediastinal blood pool and liver uptake for the accuracy analysis. The
upper femur, left/right hip, spine and skull.
clinical impact analysis was performed on 94 patients with complete
The aim of the present study was to evaluate the impact of bone-
clinical information available at Haematology Unit, and who com-
modeling on SUV measurements of MRAC 18F-FDG-PET in bone
pleted the first-line treatment.
lesions and background regions of MM patients.
Results: The use of the COL scale, as compared with the BW scale,
Methods: 20 18F-FDG PET/MR studies (M = 12; F = 8;
increased the global concordance among readers in the DS assign-
61 ± 9 years) of patients undergoing examinations for MM staging
ment from 65 to 75% and the confidence level from 79 to 88%.
(12/20) or post-therapy follow up (8/20) were considered.
The percentage of correctly classified cases was 79% with the BW
For each study, standard CAIPIRINHA-/DIXON-based 4 compart-
scale and 88% with the COL scale. With the use of COL images, the
ments l-maps (air, soft tissue, lung, fat) and new 5-compartments (4
percentage of correctly classified cases among DS 1, 2 or 3 vs DS 4 or
plus bone) l-maps were used for MRAC of PET data.
5 improved from 73 to 88% and from 78 to 87%, respectively.
SUVmean and SUVmax of VOIs placed on femoral heads, subcu-
The percentage of the correctly classified cases among the main
taneous fat, third lumbar vertebra, liver, spleen, lungs and bone
lymph node regions with the use of COL scale improved from 82 to
lesions respectively were calculated on the reconstructed PET images.
88% in the neck lymph nodes; from 90 to 100% in the axillary lymph
Paired sample t-test (for normal data) or Wilcoxon signed rank test
nodes; from 78 to 88% in the mediastinal lymph nodes and from 52 to
(for non-normal data) were used to compare SUVmean of anatomical
84% in the abdominal-pelvis lymph nodes. In the neck and medi-
regions and SUVpeak of bone lesions in 4- and 5-compartments PET
astinal lymph nodes the DS3 were frequently underscored in DS2
studies respectively (a \ 0.05).
with the BW scale for the excessive surrounding background. For the
Results: 11/20 DIXON-based and 12/20 CAIPIRINHA-based l-maps
same reason, in the abdominal and pelvic lymph nodes the DS2 were
had bone-modeling errors. Significant differences were observed
between PETDIXON_bone-modeling and PETDIXON_no-bone average

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S87

SUVmean on left femoral head (0.473 vs 0.278; p = 0.0001), right (p \ 0.05). Besides, statistically significant differences were found in
femoral head (0.422 vs 0.246; p \ 0.05) and third lumbar vertebra SUVmean between BI and Lifex with SUV C 2.5 threshold, and
(1.254 vs 1.190; p \ 0.05). On CAIPI-based PET studies significant between Lifex and Accurate with SUV 2.5 threshold (p \ 0.05).
differences resulted in the same regions. A systematical but slight Among the not statistically significant differences in TMTV calcu-
underestimation of SUVpeak in PETDIXON_no-bone versus PETDIX- lations (p [ 0.1), the smallest difference for TMTV has been
ON_bone-modeling (1.32 vs 1.36; p \ 0.001) and PETCAIPI_no-bone versus 5.01 cm3 and it has been observed between Fiji and Lifex with
PETCAIPI_bone-modeling (1.27 vs 1.30 p = 0.001) was observed. threshold SUV C 41%. SUVmax appeared stable across the different
Conclusions: Bone-modeling provides systematically higher bone methods, with the smallest difference of 0.002 found between BI and
background SUVmean and bone lesions SUVpeak. However, the modest Accurate with SUV C 2.5 threshold. SUVmean appeared the less
magnitude of the observed differences would not presumably deter- stable value across the different methods, with the smallest difference
mine any clinical impact, considering that no lesion was missed out of 0.08 found between BI and Accurate. SUVpeak has been evaluated
on visual inspection of any reconstructed PET. only with BI and Accurate, and the smallest difference has been found
with threshold SUV C 2.5.
Conclusions: Differences between TMTV values can be found using
different softwares and different thresholds. Not all softwares are able
PO146 to perform all calculations. The fastest and most comprehensive
Comparison of three threshold methods with three software was BI with SUV C 41%. Although it is recommended to
different software algorithms for TMTV calculation: use the same software with the same threshold, if in need to use
different softwares, we suggest BI and Lifex with threshold SUV
a preliminary study in patients with Hodgkin
C 41%. SUV measurements, especially SUVmax and SUVpeak,
lymphoma appear stable across softwares, with the exception of BI vs. Accurate
with threshold SUV C 4.
A. Kokomani4, V. Berti4, G. Puccini4, V. Briganti4, R. Di Dato4,
A. Ciaccio4, F. Tutino4, F. Linguanti4, V. Vergura4, A. Passeri4,
B. Puccini2, S. Kovalchuk2, F. Mungai5, L. Rigacci3, R. Sciagrà4,
O.F. On Behalf Of Imaging Working Group1 PO147
Time-to-event prediction applying artificial intelligence
1
Fondazione Italiana Linfomi, Alessandria, Italy. 2Haematology Unit, on end-of-treatment FDG-PET/CT in diffuse large
Careggi University Hospital, Florence, Italy. 3Haematology Unit, San
Camillo Hospital, Rome, Italy. 4Nuclear Medicine Unit, Careggi
B-cell lymphoma
University Hospital, Florence, Italy. 5Radiology Unit, Careggi
University Hospital, Florence, Italy S. Annunziata2, A. Pelliccioni2, E. Maiolo1, A. Cuccaro1, S. Hohaus1,
A. Giordano2
Background-aim: The total metabolic tumor volume (TMTV)
assessed on baseline FDG-PET is becoming an important approach to 1
Institute of Hematology, Università Cattolica del Sacro Cuore,
tumor burden measurement, even if still not used in the clinical Rome, Italy. 2Institute of Nuclear Medicine, Università Cattolica del
practice. The aim of our study was to compare the reproducibility of Sacro Cuore, Rome, Italy
three different thresholds with three different software algorithms for
TMTV calculation at baseline FDG-PET in patients with Hodgkin Background-aim: In the era of personalized medicine, strong prog-
Lymphoma. nostic tools are needed in diffuse large B-cell lymphoma (DLBCL).
Methods: We retrospectively included 130 patients with histological FDG-PET/CT at the end of first line chemo-immunotherapy showed a
diagnosis of Hodgkin Lymphoma who had undergone baseline FDG- good prognostic power, in some papers improving the power of
PET at our Nuclear Medicine Department from 2010 to 2016. We clinical scores. Nevertheless, PET/CT parameters showed some lim-
used three different software algorithms for TMTV measurement: itations as sub-optimal prognostic accuracy, commonly considering
Beth-Israel (BI) plug-in for Fiji, Lifex and Accurate. For each soft- progression or death as binomial variables and analyzing them by
ware we measured TMTV with three fixed threshold methods: univariate analysis or multi-regression models (MRM). Recently,
SUV C 2.5, SUV C 4 and SUV C 41% of maximum. SUVmax, Artificial Intelligence methods (AI) as Neural Networks (NN) offer
SUVmean, and SUVpeak for each method were assessed. We used the possibility to predict time-to-adverse event as continuous variable
automatic calculation algorithms. Manual operations were required expressed in months. Aims of this study is to retrospectively evaluate
for the exclusion of brain, kidneys, bladder and other aspecific focal AI as NN for the prediction of the time to adverse events in the
uptake areas. The time of processing for each software and each follow-up by using end-of-treatment FDG-PET/CT in DLBCL.
method was considered. Methods: FDG-PET/CT at the end of first line chemo-immunother-
Results: BI was the only approach that allowed the definition of the apy for DLBCL were retrospectively evaluated by: visual methods as
area of segmentation (i.e. locoregional vs. disseminated disease) and International Harmonization Project (IHP) and Deauville Score (DS);
required less manual operations for TMTV calculation. The Lifex semi-quantitative parameters as SUVpeak, qPET (target SUVpeak to
found more aspecific ROIs than other softwares, was not able to liver SUVmean), MTV and TLG at different SUVmax thresholds
perform SUVpeak and was the most time-consuming. Accurate per- (40%, 60%, 80% of SUVmax). Progression during treatment and
formed a good automatic processing for the thresholds SUV C 2.5 relapse were considered as adverse events for the progression-free
and SUV C 4, but required manual ROI drawing for the method survival (PFS). The receiver operating characteristic approach was
SUV C 41% of maximum. For each software, threshold SUV C 2.5 applied to identify the optimal cut-point of PET/CT parameters with
was the most time-consuming. respect to adverse events. Positive predictive value (PPV) and nega-
Regarding TMTV calculation, statistically significant differences tive predictive value (NPV) for different PET results were calculated
were found between BI and Lifex using SUV C 2.5 threshold and using the presence of adverse events as reference standard. FDG-PET/
between BI and Accurate with SUV C 4 threshold (p \ 0.05). We CT parameters and time-to-event were considered as input variables
found statistically significant differences in SUVmax, SUVmean and and target variables respectively, for time-to-event prediction in both
SUVpeak values between BI and Accurate with SUV C 4 threshold MRM and NN models. A Multilayer perceptron with 3 layers was

123
S88 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

used as NN. NN analysis consisted in 10 hidden neurons. A corre- Results: The median of follow up was 25.5 months. Among 80
lation coefficient was calculated to show the power of MRM and NN patients, 18 died and 19 relapsed.
in time-to-event prediction. MRM and NN mean absolute error The mean ± standard deviation, median, and range of tMTV in non-
(MAE) in predicting time-to-event was calculated. relapsed vs relapsed patients were 314 ml ± 470, 107 ml (2–2067) vs
Results: Three hundred and eight patients were retrospectively 438 ± 435, 398 ml (22–1506) respectively (p value = 0.076). The
included. IHP, DS, qPET and TLG40 were prognostic factors for PFS mean ± standard deviation, median and range of tMTV in alive vs
by univariate analysis (p \ 0.05). Values of qPET 2.36 and TLG40 dead patients were 335 ml ± 487, 115 ml (2–2067) vs 716 ± 1368,
20.1 were the optimal cut-points with respect to PFS. PFS at 3 years 203 ml (22–5501) respectively (p value = 0.065). According to ROC
respectively were 96% for negative IHP versus 69% for positive IHP, analysis, a tMTV cut-off value of 400 ml showed a positive and
95% for DS 1–3 versus 61% in DS 4–5, 85% for DS 1–4 versus 20% negative predictive value of 33% and 88% for DFS and 30% and 84%
for DS 5. PFS PPV e NPV respectively were 40% and 82% for for OS respectively. Kaplan–Meier curves showed a DFS significantly
positive IHP, 55% and 83% for DS 4–5, 95% and 80% for DS 5, 89% different in patients with low vs high tMTV (p = 0.05). In the sub-
and 82% for positive qPET, 60% and 78% for positive TLG40. MRM group of 41 patients with MYC immunophenotypic evaluation, we
was not able to predict time-to-progression in months, showing a found that MYC negative patients with poor prognosis were associ-
correlation coefficient of 0.23. Conversely, NN showed a high cor- ated to high tMTV both for DFS (p = 0.0019) and OS (p = 0.02).
relation coefficient (0.93). MRM MAE was 85%, while NN MAE was Conclusions: In our study, we found that an optimal tMTV cut-off of
24%. Moreover, for a time-to-event shorter than 30 months, a linear 400 ml at baseline PET allows to exclude disease recurrence or exitus
relationship between FDG-PET/CT parameters and time-to-event was with a high NPV (84% for OS and 88% for DFS) in DLBCL patients.
evident and NN MAE was of 40%. For a time-to-event longer than High tMTV in MYC negative patients is associated with a worse
30 months, a non-linear relationship was evident and NN MAE was prognosis. If these results will be validated in a larger population,
of 16%. tMTV and biological markers of DLBCL, can be used as benchmark
Conclusions: Neural Networks allows end-of-treatment FDG-PET/ to stratify patients for novel or risk-adapted therapies.
CT in diffuse large B-cell lymphoma to predict the time to adverse
events as progression in the follow-up, improving over multi-re-
gression analysis. Neural Networks showed the presence of a non-
linear model in the relationship between FDG-PET/CT parameters PO149
and time-to-event, not previously described. total metabolic tumor volume (TMTV) and total lesion
glycolysis (TLG) are correlated with clinical outcome
and interim therapy response in hodgkin lymphoma
PO148
Total metabolic tumor volume (TMTV) at baseline M. Spallino4, M. Cuzzocrea4, E. De Ponti2, S. Bolis1, I. Casaroli1,
C. Landoni4, L. Guerra3
18-F-FDG PET/CT and MYC expression
for the assessment of clinical outcome and treatment 1
Hematology Department, San Gerardo Hospital ASST, Monza, Italy.
2
response in diffuse large B-cell lymphoma Medical Physics Department, San Gerardo Hospital ASST, Monza,
Italy. 3Nuclear Medicine Department, San Gerardo Hospital ASST,
M. Cuzzocrea4, M. Spallino4, E. De Ponti2, I. Casaroli1, S. Bolis1, Monza, Italy. 4Nuclear Medicine Department, University Milan
C. Landoni4, L. Guerra3 Bicocca, Milan, Italy

1
Background-aim: PET is commonly evaluated by visual analysis in
Hematology Department, San Gerardo Hospital ASST, Monza, Italy. Hodgkin’s lymphoma (HL) without resorting to semiquantitative/
2
Medical Physics Department, San Gerardo Hospital ASST, Monza, quantitative parameters as SUVmax, SUVpeak, TMTV and TLG.
Italy. 3Nuclear Medicine Department, San Gerardo Hospital ASST, Some recent papers showed that the TMTV and TLG assessed in
Monza, Italy. 4Nuclear Medicine Department, University Milan- baseline PET are correlated to prognosis and consequently could be
Bicocca, Milan, Italy used to optimize the treatment strategy, but published results are
Background-aim: Total Metabolic Tumor Volume (tMTV), assessed sometimes discordant. In this work we evaluate whether quantitative
at baseline PET, is a promising prognostic tool in Diffuse Large parameters in baseline PET are correlated to overall survival (OS),
B-cell Lymphoma (DLBCL), as reported by recent papers. An opti- disease-free survival (DFS) and treatment response in patients with
mal tMTV cut-off seems able to stratify patient in terms of prognosis, HL treated at the Hematology Division of San Gerardo Hospital in
even if published results are sometimes discordant. A growing interest Monza.
is emerging about the biological characteristics of DLBCL, that are Methods: 163 patients (94 men; mean age: 38 years, range 18–81)
potentially predictive biomarkers. We evaluate the prognostic value with newly diagnosed HL, disease stage I-IV (11 stage I, 49 stage IIA,
of tMTV at baseline PET, also combining immunophenotypic eval- 34 stage IIB, 33 stage III, 36 stage IV) referred to our Hospital
uation of MYC, in DLBCL patients. between 12/2005 and 12/2016 were retrospectively evaluated. We
Methods: We retrospectively evaluated 80 patients (48 men; mean calculated the semiquantitative parameters at baseline staging PET
age: 61 years, range 22–86) with newly diagnosed DLBCL, disease using the Beth Israel plugin for Fiji with a fixed threshold of 41% of
stage I-IV (8 stage I, 13 stage II, 19 stage III, 40 stage IV) referred to the maximum. Sum rank test was performed to evaluate statistical
our Hospital between april 2011 and october 2017. The tMTV at differences between the semiquantitative parameters in patients with
baseline PET was calculated using a fixed threshold of 41% of the different outcome (dead vs alive). Receiver operating characteristics
SUVmax. In a subgroup of 41 patients, we also evaluated phenotypic (ROC) analysis was performed to evaluate the best threshold of
expression of MYC (14 pos, 37 neg) with immunohistochemistry. quantitative parameters to discriminate good vs bad prognosis
Sum rank test was performed to evaluate statistical differences in patients.
tMTV in patients with different outcome. Receiver operating char- Results: Overall, baseline PET of 158/163 HL patients were evalu-
acteristics (ROC) analysis was performed to evaluate the best cut-off ated for quantitative parameters. Median follow up duration was
of tMTV to discriminate patients with good vs poor prognosis. 40 months, 5 patients died and 11 relapsed.

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S89

In dead and alive patients, median MTV values were 269.5 analysis (CGITA software, v. 1.4). An absolute rescaling method (0-
(87.3–546.5) vs 84.6 (3.5–590.9) (p = 0.036) respectively and median 25 SUV) was also applied. Then we used a Support Vector Machine
TLG values were 2772.1 (341.7–3724.1) vs 492.4 (15.5–4596.8) to classify single VOIs and to predict ML subtype from 108 texture
respectively (p = 0.029). According to ROC analysis, a TMTV cut- analysis features. Finally, we validated the model in order to assess
off value of 269.5 mL showed a sensitivity, specificity and accuracy the significance of the results.
respectively of 60, 88.2 and 87.3% to identify patients with good vs Results: 36 patients were enrolled in the study (9 each with DLBCL,
worse prognosis; the same figure for TLG were 60, 96.7 and 95.6% FL, HL, and MCL), and then we identified a total of 66, 86, 53, and
with a cut-off value of 2772.1. Kaplan–Meier curves showed an OS 144 VOIs for DLBCL, FL, HL, and MCL respectively. Machine
significantly different in patients with low and high TMTV (p = 0.05) learning method showed to accurately classify 52% of VOIs and 61%
and TLG (p \ 0.05). of patients. When we increased specificity of the classifier to predict
We classified patients with Deauville Score (DS) 1–2–3 at interim- ML subtype only in case of high agreement among VOIs we observed
PET (after 2 cycles) as responders and patients with DS 4–5 as non- an increase in the correct classification rate (up to 71% for patients).
responders. TMTV and TLG were good to discriminate responder vs We obtained a very high sensitivity for HL (90.5% of VOIs, and 9/9
non-responder patients with the sum rank test (p-value 0.07 and 0.05 patients correctly detected) and intermediate sensitivity rates for
respectively). DLBCL (42% of VOIs, 4/7 patients), yet with high specificity, over
No statistically significant difference was found comparing 80%; FL and MCL resulted to be the most difficult classes to
metabolic parameters relative to relapsed and non-relapsed patients. discriminate.
Conclusions: We demonstrated the correlation between baseline PET Conclusions: Adoption of a machine learning algorithm to predict
metabolic parameters and clinical outcome in terms of prognosis and ML subtype is feasible and achieves good accuracy with HL patients,
response to therapy defined by interim PET. These results are but FL and MCL subtypes are the most difficult categories to classify.
promising but confirmation in a larger series is requested, particularly Our initial results should be confirmed in larger patients series.
to increase patients with worse prognosis. If these results will be
validated in a larger population, TMTV and TLG, in addition to other
imaging parameters (interim PET), can be useful benchmark to
stratify patient prognosis and modulate the treatment strategy. PO151
Dopamine transporter imaging (DATScan) in suspected
tyrosine hydroxylase (TH) deficiency
PO150
18 S. Sollaku1, V. Frantellizzi1, J. Lazri1, L. Civitelli1, G. De Vincentis1
F-FDG in malignant lymphoma subtype: a PET/CT
based machine learning approach 1
Nuclear Medicine Unit, Department of Radiological Sciences,
Oncology and Anatomical Pathology, Sapienza University of Rome,
M. Casali5, A. Fama2, M. Bertolini4, S. Gianotti1, A. Ferrari2, Rome, Italy
E. Barbolini2, M. Iori4, M. Lippi1, F. Merli2, S. Luminari3, A. Versari5
Background-aim: Tyrosine hydroxylase (tyrosine 3-monooxyge-
1 nase) deficiency is associated with a broad phenotypic spectrum.
Department of Sciences and Methods for Engineering (DISMI),
Based on the severity of symptoms and signs as well as responsive-
University of Modena and Reggio Emilia, Modena, Italy.
2 ness to L-DOPA therapy, there are three clinical phenotypes variants:
Hematology, AUSL-IRCCS, Arcispedale S. Maria Nuova, Reggio
TH-deficient DOPA-responsive dystonia (mild form); TH-deficient
Emilia, Italy. 3Hematology, AUSL-IRCCS, Arcispedale S. Maria
infantile parkinsonism with motor delay (severe form); TH-deficient
Nuova, Reggio Emilia, Italy; 5. Dipartimento Chirurgico, Medico,
progressive infantile encephalopathy (very severe form). The aim of
Odontoiatrico e di Scienze Morfologiche con interesse
this report is to present a case of dopamine transporter imaging in an
Trapiantologico, Oncologico e di Medicina
early patient with suspected TH deficiency
Rigenerativa(CHIMOMO), University of Modena and Reggio Emilia,
Methods: A 14-year-old boy presented a parkinsonism developed
Italy. 4Medical Physics, AUSL-IRCCS, Arcispedale S. Maria Nuova,
during the last 2 years of life. On examination he suffered from
Reggio Emilia, Italy. 5Nuclear Medicine Unit, Azienda Unità
flapping tremor of the upper limbs, bradykinesia, bradypsychism,
Sanitaria Locale-Istituto di ricovero e cura IRCCS- Reggio Emilia,
remarkable hypomimia, mutism, dysphagia due to dystonia of the
Italy
tongue and behavioral change (hypochondria and obsessive con-
Background-aim: Malignant lymphomas (ML) are cancers of the ducts). Brain MRI was normal as well as an extensive neurometabolic
immune system and are characterized by enlarged lymphnodes that work-up. L-DOPA/Carbidopa treatment resulted in a dramatic but
typically spread across many different sites (VOIs). Diagnosis and incomplete improvement of clinical condition. Genetic work-up for
subtype definition are usually based on biopsy of a single tumor site, TH deficiency and primary and symptomatic early onset Parkinson
and actually more than 60 histologic ML subtypes are identified. disease are in course. The patient underwent DATScan (123I-FP-CIT)
Total body examinations with computed tomography (CT) and 18F- brain examination on a dual-head SPECT scanner equipped with
FDG-PET/CT are able to provide a comprehensive picture of the parallel hole collimators and image reconstruction was done on a
patient. Machine learning is one of the hottest topics in artificial Xeleris 3 Workstation (GE, Milwaukee). OSEM iterative recon-
intelligence and computer science. Our hypothesis is that a data-dri- struction (4 iteration, 10 subsets) was used and Chang attenuation
ven approach exploiting machine learning algorithms on features correction was applied. Images were smoothed using Butterworth
extracted from 18 F-FDG-PET/CT can be used to predict differential post reconstruction filter (CF = 0.5, Power = 10). The reconstructed
diagnosis of the main ML subtypes. images were registered with patient brain MRI exam for better visual
Methods: An equal number of patients with histologically confirmed reporting and segmentation. The measurements were qualitatively
Diffuse Large B Cell Lymphoma (DLBCL), Follicular Lymphoma evaluated by two experienced physicians and additional semi-quan-
(FL), Hodgkin Lymphoma (HL) and Mantle cell lymphoma (MCL) titative analysis of the patient data was done using DaTQuant
for whom a diagnostic FDG-PET exam was available were identified. software.
For each patient VOIs were segmented by an expert nuclear physician Results: SPECT reconstructed images showed severe uptake reduc-
(method based on 41% SUVmax threshold) to first perform texture tion of 123I-FP-CIT in the basal ganglia with relatively high

123
S90 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

abnormal background activity. Specific binding ratio was 1.32 for left clinical history of this last patient showed an absolute lack of response
striatum and 1.31 for right striatum. of NB to any kind of therapy and thus a really refractory illness.
Conclusions: To our knowledge, this is the first report of dopamin- Conclusions: The study demonstrated a significant regression of AIT
ergic presynaptic assessment in TH-deficiency. TH catalyzes the skeletal scoring, so that just 43% of the patients had SIOPEN scoring
initial and rate-limiting step in the synthesis of catecholamines, is C 3. However, in these few patients a remarkable difference in the
including dopamine. We suppose that dopamine level reduction could reduction of number of bone lesions could be observed, with a worse
lead to downregulation of pre-synaptic dopamine transporters, in outcome in the case with limited decrease in lesion number. This
order to assure adequate dopamine concentration in the synaptic cleft. study suggests that for the selection of patients to be submitted to
Unfortunately, no autopsies of individuals with any of the forms of VERITAS we should consider not only SIOPEN score but also the
TH deficiency have been reported. reduction of lesions, accordingly differentiating among the SIOPEN
poor responders cases with better prognosis (to be treated with the
standard HR-NB-2 protocols) vs. really refractory NB (to be sched-
uled for VERITAS).
PO152
Prognostic value of SIOPEN scoring and absolute
number of skeletal lesions variation at staging
PO153
and after induction treatment in 14 pediatric patients
MR apparent diffusion coefficient (ADC) and 123-I-
with HR-NB-1 protocol MIBG uptake in low risk neuroblastoma: an exemplar
A.L. Martini2, E.M. Abenavoli2, M. Allocca2, R. Di Dato1,
case report
A. Tondo3, C. Olianti2, R. Sciagra’2
E.M. Abenavoli1, A.L. Martini1, R. Di Dato1, A. Tondo2,
1
Nuclear Medicine Unit, University Hospital Careggi, Florence, Italy. A.L. Perrone3, C. Olianti1, R. Sciagra’1
2
Nuclear Medicine Unit, University Hospital Careggi, Florence, Italy. 1
3
Oncohematology Unit, Meyer Pediatric University-Hospital, Nuclear Medicine Unit, University Hospital Careggi Florence, Italy.
2
Florence, Italy Oncohematology Unit, Meyer Pediatric University-Hospital,
Florence, Italy. 3Radiology Unit, Meyer Pediatric University-
Background-aim: 123-I MIBG scintigraphy is a neuroblastoma (NB) Hospital, Florence, Italy
diagnostic test semi-quantified by the SIOPEN method and used to
stratify patients with good versus poor response to therapy. The aim Background-aim: The literature demonstrates that in neuroblastoma
of study is to compare the prognostic value of SIOPEN scoring and (NB), a common tumor in childhood, chemotherapy (CHT) usually
absolute number of skeletal lesions variation at the diagnosis and after reduces the size of the mass, but also that resistance can develop in
induction treatment. some pathological tumor clones.
Methods: 14 paediatric patients (HR-NB-1 protocol) referred to The change in the appearance of the original mass can be evaluated
Nuclear Medicine for I-123 MIBG scintigraphy (January 2009–April not only from the degree of 123I-MIBG uptake (value obtained by a
2018) were investigated by two 123I-MIBG scans for staging (STA) division between total counts of two ROI of the same size pointed
at diagnosis and for response evaluation after induction treatment respectively on the mass and on the liver), but also using the apparent
(AIT). The studies included 4 F and 10 M (mean age diffusion coefficient (ADC, which becomes higher in proportion to
4.14 ± 2.85 years at the first scintigraphy). The two I-123 MIBG cellular differentiation, and decreases in case of anaplasia), obtained
scans were scored by the SIOPEN methods, dividing the skeleton into from post processing MR and calculated for each voxel or ROI within
12 anatomical body segments. Skeletal MIBG involvement was NB
scored using a 0–6 scale: 0, no involvement; 1, one discrete lesion; 2, Methods: We report the case of a localized, unresectable, not dif-
two discrete lesions; 3, three discrete lesions; 4 more than 3 discrete ferentiated NB, in a little girl of 13 months, with negative bone
foci or a single diffuse lesion involving 50% of a bone; 5, diffuse marrow, not amplified NMYC oncogene, no genomic profile, VAM
involvement of 50% to 95% of the entire bone; 6, diffuse involvement within normal limits, but with hypertension, which was controlled
of the entire bone, with a maximum score of 72. A cut-off score using ACE-inhibitors.
of B 3 was the most useful predictor across trials to define good Results: Abdomen MR showed the presence of a heteroplastic lesion
responders (Eur J Nucl Med Mol Imaging. 2018 February; 45: localized in the epigastrial region with a size of 42*50*27 mm, and
292–305), and conversely to select patients with inadequate response ADC = 0.5, enclosing the celiac artery. The 123I-MIBG whole body
to chemotherapy (score C 3), who would be candidate to the VER- scan confirmed the diagnosis of abdominal lesion, showing a MIBG
ITAS protocol (metabolic therapy with 131I-MIBG, 12-18 mCi/pro avid area in the epigastrium characterized by radiotracer uptake twice
kg). that of the liver.
Results: Statistical analysis showed a significant (p \ 0.05) differ- After three months and four cycles of CHT (VP16, CARBO), the
ence between medium STA skeletal scoring and medium AIT skeletal child underwent again 123I-MIBG, which showed a reduction of the
scoring (STA score 16.57 ± 18.86 vs. AIT score 1.57 ± 2.50; uptake extent, but an increase in its intensity (mass/liver = 2.38–2.46
p = 0.008). The patients without skeletal lesions at STA (5 patients) vs. staging-MIBG mass/liver = 2). Post-treatment MR showed a dif-
had no lesions at AIT (no disease progression). The other patients ferent characterization of the primitive lesion, with ADC = 0.75, and
with skeletal lesions at STA (9 patients) had a reduction in number of a mild reduction of the mass size (42*44*27 mm).
lesions (average reduction 15 ± 17.80%), but without a complete For the absence of negative prognostic factors and the resolution
disappearance of skeletal involvement. In our cohort, STA skeletal of hypertension, it was decided to follow up the disease with short-
scoring was C 3 in 7 patients (50%). AIT skeletal scoring was C 3 in term re-evaluation as indicated in the low risk protocol.
3/7 (43%), who were than suitable for VERITAS. Among these 3 After two months, in the latest 123I-MIBG scintigraphy, lesion
poor responders, however, 2 patients had nevertheless a remarkable dimensions and uptake resulted clearly reduced (mass/liver = 1.07).
reduction in number of lesions ([ 75%), whilst only one patient The MR morphological pattern confirmed the reduction in the
showed a limited reduction in the number of lesions (= 45%. The mass size (34*42*24 mm), and the ADC index increased to 1.43. The

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S91

increase in the uptake in the first post-CHT 123I-MIBG could suggest for LINES NB, without significant difference in Kaplan-Meyer
the selection of a cellular clone with greater differentiation just before analysis, likely owing to the small cohorts.
the involution process, associated initially to just mild dimensional Conclusions: These data show a significant response to COJEC
response in first post CHT-RM, but later confirmed by the ADC particularly for SIOPEN scoring in HR NB, a significant response for
increase. PT in LINES and HR NB, and no significant response for soft tissue.
Conclusions: CHT is confirmed as first choice treatment of low risk Tumour reduction after induction-CHT is significant both as PT
NB with symptoms. Monitoring both MIBG uptake with semi- MIBG scoring and as volume reduction in WB-MRI scans. Overall
quantitative indexes and ADC could help predicting modifications of survival for LINES NB and HR NB in local experience is consistent
NB biological features, with possible interesting prognostic with literature results.
implications.

PO155
PO154 Tumor uptake and tumor necrosis evaluation at staging
Chemotherapy response in hr and lines neuroblastoma: FDG-PET in osteosarcoma and Ewing sarcoma:
SIOPEN scoring and scoring for primary tumour prognostic value of SUV
and soft tissue in MIBG scan and WB-MRI
R. Di Dato2, M. Allocca2, A.L. Martini2, A. Tamburini3,
C. Olianti1, M. Allocca1, R. Di Dato1, A.L. Martini1, C. Caporalini1, C. Olianti2, R. Sciagra’2
E.M. Abenavoli1, A.L. Perrone3, A. Tondo2, R. Sciagra’1
1
Anatomopathology Unit, Meyer Pediatric University-Hospital,
1
Nuclear Medicine Unit, University Hospital Careggi, Florence, Italy. Florence, Italy. 2Nuclear Medicine Unit, University Hospital Careggi,
2
Oncohematology Unit, Meyer Pediatric University-Hospital, Florence, Italy. 3Oncohematology Unit, Meyer Pediatric University-
Florence, Italy. 3Radiology Unit, Meyer Pediatric University- Hospital, Florence, Italy
Hospital, Florence, Italy
Background-aim: Osteosarcoma (OS), Ewing’s Sarcoma (ES) and
Background-aim: Accurate disease staging is essential to optimise rhabdomyosarcoma represent 13% of paediatric malignancies. Some
treatment in neuroblastoma (NB). Diagnostic iodine-123 (123I) or studies show that the 18FDG-PET parameters, including SUV
post-therapy iodine-131 (131I) labelled MIBG scintigraphy is rec- (Standardized Uptake Value) max and TV (Tumor Volume) of the
ommended to assess disease extent in accordance with International lesion, correlate with the histological result and predict prognosis.
NB Risk Group (INRG) guidance. The aim of this report is to evaluate The aim of this study is to assess the prognostic value of different
chemotherapy-response in term of (1) SIOPEN scoring (whole parameters at staging 18FDG-PET in patients with OS and ES.
skeleton), (2) soft tissues scoring and (3) primary tumour (PT) vari- Methods: We evaluated SUVmax and TV of primary lesion, SUVmin
ation between staging (STA) and after chemotherapy or induction and TV of necrosis in 48 patients with OS (26 patients) and ES (22
treatment (CH) and to evaluate the overall survival in two indepen- patients), age 4-29 years (mean 15.06 ± 5.8), who underwent staging
dent trial populations: High-Risk (HR) NB and Low and Intermediate 18FDG-PET. We drew ROIs on the lesion area of hyperactivity, and
Risk Neuroblastoma European Study (LINES) NB. on the necrotic area, measured longitudinal and transverse dimen-
Methods: We investigated 21 children with NB (June 2009/October sions, and calculated the respective TV approximating them to
2018) by 123I-MIBG scan and whole-body diffusion weighted MRI cylindrical or ellipsoid morphology. We also measured the SUV max
(WB-MRI) at STA and at CH. The study included 5 females and 16 of the lesion and the SUV min of the necrosis. We correlated these
males, mean age 3.47 ± 2.96 years at first scintigraphy (range data to the histological outcome (Huvos score for OS and Picci score
0–12 years). Of LINES patients 7/21 (33%) underwent VP/CARBO, for ES based on percentage of necrosis) and to the clinical course,
of HR-NB patients 14/21 (66%) underwent COJEC induction Che- dividing the studied population in poor and good responders.
motherapy. SIOPEN method scores skeletal disease extent within 12 Results: The two groups were not different for age distribution
body segments on a 0 to 6 scale giving a maximum score of 72. Soft (15.6 ± 6.0 years for OS and 14.5 ± 5.8 years for ES). Statistical
tissues (ST) other than the PT, i.e. lymph nodes, paraganglia, pul- analysis of the parameters showed a significant difference between
monary or hepatic metastasis, were scored in each body segment the OS group and the ES group for SUVmax, with a higher average
assigning the following scores: zero for no abnormality, one for a SUVmax of the lesion in the OS group (7.06 ± 3.82 in OS vs
solitary, two for 2 and three for [ 2 lesions. We considered also 4.43 ± 2.93 in ES, p \ 0.05). There was no significant difference
primary tumour presence or absence in MIBG scan and the variation between OS and ES groups for TV of the lesion, even if average TV
of tumour volume (TV) at STA and CH on WB-MRI scan as of OS was higher than ES (191.00 ± 266 cm3 in OS vs
response-to-CHT indexes. 124.94 ± 155 cm3 in ES). The mean percentage of necrosis as
Results: In HR-NB significant difference was found between STA compared to TV was 10% in OS and 6% in ES.
SIOPEN scoring and STA PT scoring vs. related CH scoring Non parametric tests demonstrated a significant difference in SUV-
(p \ 0.02 and p \ 0.05 respectively), while no significant difference max value of the lesion (p \ 0.05) and in SUVmin value of necrosis
was found for soft tissue scoring. In STA MIBG scan we found PT in (p \ 0.05) between good and poor responder clusters in ES group
21/21 patients (HR and LINES NB), while at CH MIBG scan we only. No significant statistical difference was found for the other
found PT in 13/21 patients with an overall tumour complete response parameters both in OS and ES: TV lesion, TV of necrosis, the per-
of 38% (4/7, 57% for LINES and 4/14, 29% for HR) (Chi square test centage of necrosis in the lesion. ROC analysis indicated for ES group
NS). In HR-NB CH WB-MRI, we found a significant PT volume a borderline significance of the area under the curve (0.79, p = 0.02),
reduction (p \ 0.02): median STA PT volume = 507.63 cm3; range both for SUVmax of lesion and for SUVmin of necrosis, with a
104–1202, vs. CH PT volume = 64 cm3; range 16–935. In LINES SUVmax cut off value of 3.2 (78% specificity and 77% sensitivity)
NB, only the reduction in PT score at CH MIBG vs. STA MIBG was and SUVmin cut off value of 0.85 (78% specificity and 85% sensi-
significant (STA median 1; range 1–3 vs. CH median 0; range 0–1; tivity), whereas there was no significance for OS.
p \ 0.05). Overall survival analysis showed 40% for HR NB and 86%

123
S92 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

Conclusions: In conclusion, our study showed a significant statistical DOPA PET/CT in detecting soft tissue and bone/bone marrow
difference between good and poor responders as regards lesion metastases was 85% and 95%; significantly higher (p \ 0.01) than
SUVmax and necrosis SUVmin in the ES group only. We did not find that 123I-mIBG WBS (41% and 93%).
a significant statistical difference for the other parameters in OS nor in After COJEC, 123I-mIBG WBS proved positive in 14 out of 18 HR-
ES. These results suggest that SUVmax could be proposed as prog- NB patients. 18F-DOPA PET/CT was positive in 17 patients. On the
nostic factor at the moment of diagnosis for ES patients only. PBA, the sensitivity of 123I-mIBG WBS and 18F-DOPA PET/CT in
detecting primary tumours, soft tissue metastases and bone/bone
marrow metastases was 72, 33, 38 and 83%, 75% and 54% respec-
tively. On the LBA, the sensitivity of 18F-DOPA PET/CT in
PO156 detecting soft tissue and bone/bone marrow metastases was 77% and
Diagnostic and prognostic role of 18F-DOPA PET/CT 86%; significantly higher (p \ 0.01) than that 123I-mIBG WBS (11%
in children affected by high risk neuroblastoma and 54%).
Over a median follow-up of 29.3 months, 7 disease progressions
undergoing HBNB02: comparison with 123I-MIBG
and 5 deaths occurred.
scan In our multivariate analysis, WBMB, evaluated after COJEC,
remained the only factor independently associated with PFS. Children
G. Ferrarazzo3, E. Lopci4, G. Morana5, M. Puntoni1, M. Conte7, with WBMB [ 7.5 had higher risk of disease progression than those
A. Cistaro8, P. Zucchetta6, M. Pescetto2, A. Garaventa7, G. Bottoni3, with WBMB B 7.5 [HR 12.6, 95% CI 1.35–117, p = 0.026]. No
M. Massollo3, A. Piccardo3 significant association was found between the considered risk factors
and OS.
1
Clinical Trial Unit, Scientific Directorate, E.O. Galliera Hospital, Conclusions: 18F-DOPA PET/CT is more sensitive than 123I-mIBG
Genoa, Italy. 2Department of Anesthesiology E.O. Ospedali Galliera, WBS to stage HR NB patients and to evaluate disease persistence
Genoa, Italy. 3Department of Nuclear Medicine E.O. Ospedali after COJEC. In time-to-event analyses, WBMB, evaluated after
Galliera, Genoa, Italy. 4Department of Nuclear Medicine Humanitas induction chemotherapy, remained the only risk factor independently
Clinical and Research Hospital, Genoa, Italy. 5Neuroradiology associated with disease progression.
Operative Unit, Istituto Giannina Gaslini, Genoa, Italy. 6Nuclear
Medicine Department, University Hospital, Padua, Italy. 7Oncology
Unit, Istituto Giannina Gaslini, Genoa, Italy. 8Positron Emission
Tomography IRMET S.p.A., Turin, Italy PO157
99m
Background-aim: 18F-DOPA PET/CT proved more sensitive than
Tc-HMDP SPECT/CT in patients with condylar
123I-mIBG scan to detect Neuroblastoma (NB) relapse. Moreover, hyperplasia: a methodological jungle in absence
the prognostic role of 18F-DOPA PET/CT at the time of recurrence of practice guidelines
has been validated by using a scoring system called whole body
metabolic burden (WBMB). However, 18F-DOPA PET/CT has never A. Rizzo2, L. Zagaria2, M. Todaro1, A. Giordano2, V. Valenza2
been tested as pivotal diagnostic tool to stage High Risk (HR) NB
patients and to evaluate treatment response after induction 1
Maxillofacial Surgery Unit, Foundation University Hospital A.
chemotherapy (COJEC). Gemelli, IRCCS, Rome, Italy. 2Nuclear Medicine Unit, Department
The aim of this study was to validate the diagnostic role of 18F- of Diagnostic Imaging, Radiation Oncology and Hematology,
DOPA PET/CT in children affected by HR-NB at the time of diag- Foundation University Hospital A. Gemelli; IRCCS, Rome, Italy
nosis. We also aim to investigate the ability of 18F-DOPA PET/CT to
evaluate the response to induction chemotherapy (COJEC). Lastly, we Background-aim: Condylar hyperplasia (CH) is a rare pathology
investigated the prognostic role of 18F-DOPA, at diagnosis and post affecting the mandibular condyle unilaterally and resulting in facial
COJEC, by using WBMB that was compared with progression free asymmetry. 99mTc-HMDP SPECT/CT is necessary for its diagnosis,
survival (PFS) and overall survival (OS) as well as to the mIBG its staging and to assess patient’s management. Several quantitative
SIOPEN score and semi-quantitative measurements of condylar 99mTc-HMDP
Methods: We prospectively enrolled 18 HR-NB patients (14 stage 4 uptake have been described in literature but neither Italian guidelines,
and 4 Stage 3). All patients underwent 18F-DOPA PET/CT and 123I- nor international ones, suggest a specific measurement method.
mIBG whole body scan (WBS) with SPECT/CT, before COJEC, Purpose of this study was to evaluate if there were differences in
within 10 days of each other. These procedures were repeated after percentage of radiopharmaceutical uptake in the hottest condyle
COJEC. 18F-DOPA PET/CT results were compared with those of comparing three out of the many methods reported in literature.
123I-mIBG scan. For each modality, a patient-based (PBA) and a Methods: From January 2018 to October 2018, we performed 99mTc-
lesion-based-analysis (LBA) was performed and the sensitivity cal- HMDP SPECT/CT in 18 patients (M:F = 9:9; median age: 17 IQR
culated. The standard of reference was based on clinical, imaging and 16–20) with suspected CH.
histological data. SPECT/CT was performed 2 h after intravenous injection of
Two groups of physicians separately calculated the SIOPEN and the 552 MBq (IQR 543–564) of 99mTc-HMDP.
WBMB scoring systems. Finally, the association of these two Fused images were analysed using three different methods:
parameters and the principal NB risk factors (age, stage, MYC regions of interest (ROI) were drawn around the whole condyle
amplification, LDH levels and catecholamine metabolites) with PFS summing consecutives axial SPECT frames (whole condyle method);
and OS was evaluated. a fixed-size ROI (1 cm2) was drawn in the centre of both condyles, in
Results: At the time of staging, 123I-mIBG WBS was positive in 17 the site of maximum 99mTc-HMDP uptake (max uptake region
out of 18 HR-NB patients. 18F-DOPA PET/CT was positive in all 18 method); volumes of interest (VOI) were drawn around the anatomic
patients. On the PBA, the sensitivity of 123I-mIBG WBS and 18F- condyles using the co-registered CT images (anatomic method). The
DOPA PET/CT in detecting primary tumours, soft tissue metastases percentage of radiopharmaceutical uptake in the hottest condyle was
and bone/bone marrow metastases was 83.3, 33.3, 66.7 and 94.4%, then calculated:
61.1% and 72.2% respectively. On the LBA, the sensitivity of 18F-

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S93

Whole condyle and max uptake region method: (total hottest Methods: We reviewed the records of 63 patients (F = 51, M = 12)
condyle counts/sum of both condyles total counts) 9 100%. affected by DTC. All patients underwent TRA within 3 months from
Anatomic method: (average hottest condyle counts/sum of both thyroid surgery, after either rhTSH-stimulation (Group A, n = 36) or
condyles average counts) 9 100%. L-T4 withdrawal (Group B, n = 27). Thirty-three patients were
Friedman and Wilcoxon tests were used to examine whether the treated with 2220 MBq (18 after rhTSH-stimulation) while 30
parameters were significantly different among the studied methods. patients were treated with 3700 MBq (18 after rhTSH-stimulation). A
In second instance, relying on literature data, the obtained per- post-therapy whole body scan (pT-WBS) was obtained 5 days after
centages were classified as positive for CH if higher than 55% and RAIT. All patients drank 1.5 L of water and took laxatives drug
McNemar test was used to find if there were significant differences 2 days before pT-WBS. Quantitative analysis was performed writing
among the methods. 7 region-of-interest (ROI) on abdomen in anterior–posterior views,
Results: The median percentage of 99mTc-HMDP uptake was 53.15% with different shapes, corresponding to liver (L), stomach (S),
(IQR 51.3–55.3) for whole condyle method, 54.85% (IQR 52.7–57.2) ascending-colon (AC), transverse-colon (TC), descending-colon
for max uptake region method and 53.6% (IQR 50.8–56.1) for ana- (DC), rectum (R), small-intestine (SI). For each region, we evaluated
tomic method. Comparison between the methodologies evidenced activity incorporated at pT-WBS as geometrical mean of anterior–
significant differences in the percentage of radiopharmaceutical posterior counts, corrected for background. To estimate the AAD, the
uptake in the hottest condyle (whole condyle method vs max uptake effective half-lives of 15.7 and 10.5 h were used for withdrawal and
region method, p \ 0.01; whole condyle method vs anatomic method, rhTSH patients, respectively, as already described. The AAD and
p = 0.05; max uptake region method vs anatomic method, p \ 0.01). average activity ratios between A and B Groups were estimated.
Placing 55% as the threshold to define a condyle as hyperplastic, Results: The AAD for L, S, AC, TC, DC, R, SI evaluated in Group B
whole condyle method showed 6/18 positives; max uptake region patients were higher than in Group A patients with ratio values of
method: 9/18 positives; anatomic method: 7/18 positives. The quali- 3.62, 4.16, 4.34, 3.19, 2.93, 3.66 and 3.48, respectively. In addition,
tative analysis showed no significant statistical differences between the average activities evaluated on L, S, AC, TC, DC, R, SI of Group
the three methods. B patients were significantly higher than in Group A patients with
Conclusions: 99mTc-HMDP SPECT/CT is a widely used method in p-values of 0.000, 0.000, 0.001, 0.000, 0.022, 0.007, 0.002, respec-
the evaluation of patients with facial asymmetry and suspected CH. tively. Finally, the lowest values of both AAD and average activity
Despite the small number of cases and the lack of follow up data, we for each region were observed in Group A patients treated with
evidenced several critical issues: 2220 MBq.
1. Absence of guidelines indicating the nuclear physician the best way Conclusions: As the efficacy of rhTSH-stimulation is equal to L-T4
to study these patients; withdrawal to obtain TRA, our data suggest a preference for rhTSH-
2. There is not a univocal way to interpret the data acquired from stimulation rather than L-T4 withdrawal since the AAD is signifi-
the exam; cantly lower than in patients treated in hypothyroidism. This reduces
3. The evaluation of the same patient with different methods the risk of both abdominal radio-induced secondary tumors and liver
highlights significant differences in percentage of uptake; dysfunction.
4. A 55% threshold may not be a valid cut-off to define a condyle
as pathologic for any measurement method.
PO159
Comparison between dual-phase and late-phase
PO158
imaging in the evaluation of hyperfunctioning
Comparing radioiodine abdominal absorbed dose
parathyroid glands
in differentiated thyroid cancer patients undergone
thyroid remnant ablation in either levo-thyroxine F. Dondi3, D. Albano2, R. Rinaldi2, M. Bonacina3, R. Durmo3,
withdrawal or after rhTSH stimulation E. Cerudelli3, M. Gazzilli3, A. Mazzoletti3, M. Bertoli2, F. Bertagna1,
R. Giubbini1
A. Campennı̀1, E. Amato1, R. Laudicella1, A.D. Comis1, A. Vento1, 1
R. Filice1, S.A. Pignata1, L. Sturiale1, A. Alibrandi3, R.M. Ruggeri2, Nuclear Medicine, Spedali Civili di Brescia and Università degli
L. Auditore1, S. Baldari1 Studi di Brescia, Brescia, Italy. 2Nuclear Medicine, Spedali Civili di
Brescia, Brescia, Italy. 3Nuclear Medicine, Università degli Studi di
1
Department of Biomedical and Dental Sciences and Morpho- Brescia, Brescia, Italy
Functional Imaging, Nuclear Medicine Unit, University of Messina, Background-aim: Hyperparathyroidism is a common endocrinologic
Messina, Italy. 2Department of Clinical and Experimental Medicine, disease that correlates with asymptomatic increase in serum calcium
Unit of Endocrinology, University of Messina, Messina, Italy. and PTH levels. Primary hyperparathyroidism (PHPT) is often caused
3
Department of Economical, Business and Environmental Sciences by a hyperfunctioning solitary parathyroid gland and surgical resec-
and Quantitative Methods, University of Messina, Messina, Italy tion is the standard therapy; minimally invasive parathyroidectomy is
Background-aim: In differentiated thyroid cancer (DTC) patients, now a widely established approach, therefore preoperative localiza-
radioactive iodine therapy (RAIT) is an important therapeutic tool for tion is nowadays mandatory.
both thyroid remnant ablation (TRA) and adjuvant treatment (AT). SPECT/CT with 99mTc SESTAMIBI is one of the most useful tool to
Two stimulation strategies can be used to perform RAIT: (I) Levo- correctly localize hyperfunctioning parathyroids. Routinely, this exam
Thyroxine (L-T4) withdrawal; (II) rhTSH-stimulation. The use of is performed with a dual-phase protocol with early and late acquisi-
rhTSH has been proven to be as effective as L-T4 withdrawal in tion and is based on the concept of differential wash out between
achieving both TRA and AT. Aim of the present work was to compare thyroid and parathyroid adenoma. This protocol is time consuming
radioiodine abdominal absorbed dose (AAD) among patients treated due to need to perform two SPECT acquisitions.
after either L-T4 withdrawal or rhTSH-stimulation.

123
S94 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

The aim of this study is to evaluate the diagnostic accuracy of a clinical indications: (i) suspicion of pancreas graft rejection (n = 9)
late-phase-only acquisition and compare it with a classical dual-phase based on hyperglycemia, abdominal pain and/or high amylase/lipase;
protocol. (ii) suspected lymphoproliferative disease (n = 1); (iii) oncological
Methods: We retrospectively evaluate 105 patients (82 females, 23 follow-up (1 melanoma and 1 solitary lung nodule).
male; mean age 62 ± 13 years) who performed SPECT/CT with Overall, the cohort included 9 patients suspected for acute pancreas
99m
Tc SESTAMIBI in our department from 2016 to 2018. graft rejection and 3 patients with other indications to 18F-FDG PET/
A combination of clinical/imaging follow-up and/or histopathology CT.
(when available) was taken into account as reference standard. All the PET/CT images were interpreted qualitatively (focal, diffuse
parathyroids dual-phase SPECT images were quantitatively evaluated homogenous, diffuse non-homogeneous; Visual scale: 0 = no uptake
in a blind way by two nuclear medicine specialists and then they were or less than the liver; 1 = liver uptake; 2 [ liver uptake) and semi
re-submitted in a different order to late-phase only. The possible role quantitatively with the assessment of the following parameters:
of CT images in the interpretation of images was also considered. maximum and mean Standardized Uptake Value (SUVmax and SUV
Sensitivity, specificity, positive predictive value (PPV), negative mean, respectively).
predictive value (NPV) and accuracy for dual-phase and late-phase Results: Acute graft rejection was diagnosed in 6 patients (REJ
images were calculated. group). In patients with no rejection (CTR group), final diagnoses
Results: There was an excellent agreement between the interpretation included normal findings (2), post-transplant lymphoproliferative
of dual-phase and late-phase images (k = 0.956, rho = 0.966); only in disease (1), chronic reactive lymphadenitis (1), pneumonia (1),
one case the two protocols were divergent. For the dual-phase pro- enteritis (1).
tocol we obtained a sensitivity of 90%, a specificity of 97%, a PPV of Visual scale showed a score of 2 in 7 patients (6 diffuse non-homo-
98%, a NPV of 83% and an accuracy of 92%; for late-phase protocol geneous and 1 diffuse homogenous) and a score of 0 in the remaining
a sensitivity of 90%, a specificity of 94%, a PPV of 97%, a NPV of 5 patients (qualitative tracer distribution not applicable). The diffuse,
83% and an accuracy of 91%. non-homogenous pattern tended to be more frequent in REJ vs. CTR.
CT images were crucial for study interpretation in a significant SUVmax and SUVmean were significantly higher in REJ vs. CTR
amount of patients for both protocols: in 40 patients (38%) of the (p = 0.036 and p = 0.029, respectively). Statistical significance was
dual-phase protocol and in 41 patients (39%) of late-phase protocol. lost when the analysis was restricted to REJ and CTR patients who
Conclusions: In conclusion, we have demonstrated that a late-phase- underwent 18F-FDG PET/CT for clinical suspicion of rejection. A
only 99mTc SESTAMIBI SPECT/CT is equivalent to a dual-phase subgroup of patients (n = 4) underwent a follow-up 18F-FDG PET/
imaging: it has good diagnostic performance in patients with hyper- CT after treatment of graft rejection. These scans showed a significant
parathyroidism and it doesn’t seems less accurate compared with a decrease both in SUVmax and SUVmean (p \ 0.05 for both com-
dual-phase protocol. This may lead to increased lab output and more parisons), which was consistent with the observed clinical response to
comfort for the patients. treatment.
Conclusions: 18F-FDG PET/CT SUVmax and SUVmean are very
promising in diagnosing acute pancreas rejection, although further
investigation is advocate because of the small sample size of the
PO160 present study. The significant decrease in SUV after treatment for
18
F-FDG PET/CT: a non-invasive way to assess rejection suggests that 18F-FDG PET/CT could be a useful tool for
pancreas graft rejection? monitoring response to treatment.

P. Mapelli5, G. Pepe2, C. Conte6, E. Falbo1, V. Paloschi1, R. Caldara1,


G. Dell’antonio3, C. Socci4, A. Secchi7, L. Gianolli2, M. Picchio5, PO161
P. Maffi1
Changes in bone density after 1 year of cross-sex
1
Department of Internal Medicine, Transplant Unit, IRCCS San hormonal treatment evaluated by dual-energy X-ray
Raffaele Scientific Institute, Milan, Italy. 2Nuclear Medicine absorptiometry
Department, IRCCS San Raffaele Scientific Institute, Milan, Italy.
3
Pathology Unit, IRCCS San Raffaele Scientific Institute, Milan, V. Lavelli1, A. Niccoli Asabella1, F. Duni1, A. Ungaro1, A.R. Pisani1,
Italy. 4Transplant Surgery Unit, Department of Surgery, IRCCS San S. Sisto1, G.V. Difonzo1, G. Rubini1
Raffaele Scientific Institute, Milan, Italy. 5Vita-Salute San Raffaele
University, Milan, Italy; Nuclear Medicine Department, IRCCS San 1
Nuclear Medicine Unit, Interdisciplinary Department of Medicine,
Raffaele Scientific Institute Milan, Italy. 6Vita-Salute San Raffaele University of Bari ‘‘Aldo Moro’’, Bari, Italy
University, Milan-Italy; 3) Department of Internal Medicine,
Transplant Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy. Background-aim: Gender dysphoria (GD) is defined as the suffer-
7
Vita-Salute San Raffaele University, Milan, Italy; Department of ance related to an incongruence between one’s experienced and one’s
Internal Medicine, Transplant Unit, IRCCS San Raffaele Scientific assigned gender of a duration of at least 6 months. Persons who
Institute, Milan, Italy experience gender-related distress might desire gender affirming
treatment with sex steroids. Sex steroids are also important determi-
Background-aim: Graft biopsy is currently the only available diag- nants of bone acquisition and bone homeostasis.
nostic tool for pancreas graft rejection, as no specific, non-invasive Osteoporosis is defined as a skeletal disease, characterized by low
tools are available for this purpose. The aim of the present study is to bone mass and micro architectural deterioration of bone tissue, with a
assess the role of 18F-FDG PET-CT in detecting and monitoring consequent increase in bone fragility and susceptibility to fracture.
pancreas graft rejection. Dual-energy X-ray absorptiometry (DXA) which provides fast
Methods: Retrospective study including 12 patients (6M and 6F; scanning, improved spatial resolution, applied to central and periph-
mean age at transplant: 45 ± 12 years) who underwent pancreas eral skeletal sites is currently used for detecting osteoporosis.
transplantation alone (PTA) or simultaneous pancreas-kidney trans- Cross-sex hormonal treatment (CHT) in transgender persons can
plant (SPK). Mean duration of diabetes was 24 ± 11 years. All affect bone mineral density (BMD). The aim of this study was to
patients underwent 18F-FDG PET/CT according to the following

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S95

investigate the first-year effects of CHT on BMD in transgender Conclusions: In our population we achieved a response to treatment
persons in 44/60 patients (73%) with a single 131I dose, in most cases using
Methods: A total of 34 patients aged from 19 to 66 years (mean lower administered activities than those currently used in our
35 years), 12 transwomen and 22 transmen, were included. All department with an empiric approach. Our results suggest that
patients completed the first year of CHT. Twenty-one of 34 patients (9 patients with a lower thyroid mass are more likely to respond to
transwomen and 12 transmen) underwent sex reassignment surgery treatment compared to those with higher thyroid mass.
(SRS). Transwomen (male-to-female transgenders) received estrogen
and anti-androgens, whereas transmen (female-to-male transgenders)
were treated with testosterone. A dual-energy X-ray absorptiometry
(DXA) (Unigamma Plus, L’ACN, Milano, Italy) was performed at PO163
18
baseline and after 1 year CHT to measure lumbar spine (LS) and F-FDG PET/CT can predict thyroid disfunction
femoral neck (FN). BMD, T-score and Z-Score before and after in patients treated with immunotherapy
1 year of CHT were measured.
Results: An increase of LS BMD was observed in 29 patients (85.2%)
P. Moda2, C. Pastore3, S. Pisconti3, M. Sciaraffia1, F. Lauriero2
and an increase of FN BMD was observed in 16 patients (47%).
In transwomen, the difference of LS BMD mean was 0.11 (std 0.25), 1
Endocrinology Unit, ‘‘SS. Annunziata’’, Taranto, Italy. 2Nuclear
the difference of FN BMD mean was 0.08 (std 0.32). In transmen, the
Medicine Unit, PET/CT Centre, Hospital ‘‘G. Moscati’’, Taranto.
difference of LS BMD mean was 0.08 (std 0.21), the difference of FN 3
Oncology Unit, Hospital ‘‘G. Moscati’’, Taranto, Italy
BMD mean was 0.20 (std 0.36).
There was no statistical significance of the LS BMD and FN BMD Background-aim: Immunotherapy (IT) agents have improved out-
differences between the two groups. comes in patients affected with a variety of malignancies.
Conclusions: DXA is a valid method to evaluate the effects of cross- It promotes immune responses by blocking programmed death-1
sex hormonal treatment in transgender persons. BMD increased receptor immune cells (PD-1) and inducing T-cell activation, prolif-
overall in both groups after 1 year of CHT. LS BMD increased more eration and cytokines production.
in transwomen, but FN BMD increased more in transmen. Aim of our study was to evaluate the role of 18F-FDG PET/CT in
the early evidence of immune-related thyroid disfunction (irTD)
compared with laboratory analysis.
Methods: A total of 18 patients (11 male and 7 female; mean age
PO162 63.6, range 38–81) (14 with advanced NSCLC and 4 with advanced
Efficacy of radioiodine treatment in patients melanoma) were treated with two immune checkpoint inhibitor
with Graves’ disease treated with dosimetric calculation antibody as second line therapy.
Laboratory results of thyroid function (TSH, FT3, FT4, Ab-Thy-
roperoxidase) were available before and during follow-up period.
M. Spallino2, R. Sara2, D. Zanni1, C. Dolci2, A.F. Scarale2,
All patients performed a 18-FDG PET/CT scan before and after
C.E. Popescu2, L. Monaco3, M. Cuzzocrea3, E. Preza3,
2–4 cycles of IT with the usually modality: fasted for at least 6 h and
M. Milella3, E. Gay3, G. Cabrini2, C. Rossetti4
with plasma glucose \ 200 mg/dl, 60 min after intravenous injection
1 of 3.7 MBq/kg 18F-FDG.
Medical Physics Department, ASST Niguarda Hospital, Milan, Italy.
2 Images analysis was carried out visually and by semiquantitative
Nuclear Medicine Department, ASST Niguarda Hospital, Milan,
determination calculating the maximum standardized uptake value
Italy. 3Nuclear Medicine Department, University Milan Bicocca,
(SUV Max) of thyroid gland.
Milan, Italy. 4Nuclear Medicine Department, ASST Niguarda
SUV max values were recorded on a excel table.
Hospital, Milan, Italy
Patients were divided in two groups: patients who developed irTD
Background-aim: Dosimetry-based radioiodine (131I) therapy in and those who did not.
Graves’ disease is not a standardized treatment. We prospectively Unpaired t-test was used to assess the significant differences
evaluated a series of patients treated in our Centre to test the efficacy between the two groups for SUV max parameter.
of the treatment and analysed the correlation between thyroid mass Relationship between development of irTD and number of cycles
and clinical outcome. of IT received was also tested.
Methods: We studied 60 patients (19 males, 41 females, median age Results: Patients were divided in two groups on the basis of the
49 years, range 24–84) with Graves’ disease treated from May 2017 thyroid testing review: patients who presented irTD (n = 7) and those
to May 2018; median follow-up after treatment was 8 months, range who did not (n = 11).
4–17. The dose of 131I to be administrated was established according All patients had normal TSH before starting IT
to 2012 EANM (European Association of Nuclear medicine) guide- Mean number of cycles of IT (each lasting 4 weeks) was 12.7
lines. We calculated thyroid mass by scintigraphy with a 40% (range 2–33)
threshold-method and considered 131I uptake values at 2, 24 and Patients who developed irTD received therapy for a longer period
144 h from administration of a 370 kBq 131I capsule, in order to (15.3 cycles) respect the ones who did not (11.1 cycles), but the trend
achieve for all patients a final absorbed dose of 300 Gy at the level of was not statistically significant.
the thyroid gland. Correlation between thyroid mass and clinical For the 7 patients who presented irTD (38.8%), the average serum
outcomes was evaluated with Student’s t test for unpaired data, with a TSH at time of follow-up 18F-FDG PET/CT was 8.02 lUI/ml with a
p value B 0.05 considered as significant. range of 4.8–14.58 lUI/ml (normal range 0.401–4.701 lUI/ml).
Results: After 131I treatment 8/60 patients (13%) were euthyroid and Ab-Thyroperoxidase were positive in 3 of 7 patients (42.8%).
36/60 (60%) were hypothyroid, thus classified as responders; 16/60 Diffuse increase of 18F-FDG uptake in the thyroid gland during IT
patients (27%) remained hyperthyroid, requiring further 131I (not was observed in 6 of 7 patients who developed irTD (Mean SUV max
responders). We found a significant difference in term of thyroid mass 5 ± SD 2.20), with abnormal TSH.
between the two groups of patients: 16.44 ± 9.40 (range 6.09–45.68) The remaining patient had no increase of 18F-FDG uptake in the
and 21.85 ± 7.47 (range 13–34.2) g in responders and not responders thyroid gland during follow-up, but only abnormal TSH.
respectively, t = 3.86, p value = 0.02.

123
S96 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

T-test comparing the two groups during therapy (patients who information on all the swallowing act until the stomach is filled. The
developed irTD and those who did not) showed significant differences evaluation of each segment, not only oral and pharynx, is fundamental
in SUV max of the thyroid gland (P = 0.0034). because it is related with DOSS and integrates the clinical evaluation,
Conclusions: 18F-FDG PET/CT can predict the development of irTD helping the physiatrist in the choice of the speech therapy.
such as thyroiditis and subsequent hypothyroidism before laboratory
testing.
Monthly thyroid testing must become a standard of care during IT.
Therefore, oncologists and endocrinologist can monitoring better PO165
clinical state of patients for insurgence of sign and symptoms of Dynamic oropharyngoesophageal scintigraphy
thyroiditis or hypothyroidism, starting a preventive therapy with beta- in patients with neurodegenerative diseases: additional
blockers or thyroid hormone replacement.
value of static images

C. Altini1, A. Niccoli Asabella1, A.G. Nappi1, A. Milano1, V. Buono1,


PO164 M. Zinfollino2, M.L. Fiorella2, G. Rubini1
Patients with neurodegenerative diseases candidates 1
Nuclear Medicine Unit, Interdisciplinary Department of Medicine,
to speech therapy: the role of oropharyngoesophageal University of Bari ‘‘Aldo Moro’’, Bari, Italy. 2Otolaryngology,
scintigraphy Department of Basic Medical Science, Neuroscience and Sensory
Organs, University of Bari ‘‘Aldo Moro’’, Bari, Italy
C. Altini1, A. Niccoli Asabella1, T. Magarò1, A. Gaudiano1, A.
Background-aim: To investigate the role of dynamic and static
Milano1, A. Pedana1, M. Zinfollino2, M.L. Fiorella2, G. Rubini1
oropharyngoesophageal scintigraphy (OPES) in patients with neuro-
1 logical disorders, evaluated using the Dysphagia Outcome and
Nuclear Medicine Unit, Interdisciplinary Department of Medicine,
Severity Scale (DOSS).
University of Bari ‘‘Aldo Moro’’, Bari, Italy. 2Otolaryngology,
Methods: We enrolled 32 neurological patients (14 women and 18
Department of Basic Medical Science, Neuroscience and Sensory
men; mean age 60 years, range 24–87) complaining of dysphagia
Organs, University of Bari ‘‘Aldo Moro’’, Bari, Italy
with diagnosis of amyotrophic lateral sclerosis (11/32 patients), bul-
Background-aim: to investigate the role of oropharyngoesophageal bar onset SLA (3/32), multiple sclerosis (8/32), Parkinson’s disease
scintigraphy (OPES) in patients with neurological diseases classified (4/32), spinocerebellar ataxia (2/32), neonatal brain disease (2/32) and
by the ‘‘Dysphagia Outcome and Severity Scale’’ (DOSS) and can- ataxic syndrome (2/32). All patients underwent OPES using a stan-
didates to speech therapy. dardized procedure (5 ml semiliquid bolus labeled with 37 MBq of
Methods: We enrolled 33 patients (15 women and 18 men, mean age 99mTc-nanocolloid; dynamic acquisition for 60 s). After the dynamic
59 years, range: 24–87) complaining of dysphagia with diagnosis of recording, 60-s static images were acquired immediately (static1),
amyotrophic lateral sclerosis (14/33), multiple sclerosis (9/33), after a swallowing of a semiliquid bolus not-labeled (static2) and after
Parkinson’s disease (4/33), spinocerebellar ataxia (2/33), neonatal a swallowing of water not-labeled (static3). Images were acquired
brain disease (2/33) and ataxic syndrome (2/33). All patients under- with patients face in an 80 projection in front of gamma-camera.
went OPES using a standardized procedure (5 ml semiliquid bolus Region of interests on the oral cavity and pharynx were drawn to
labeled with 37 MBq of 99mTc-nanocolloid; dynamic acquisition for collect data about Oral and Pharyngeal Transit Time (OTT’’ and
60 s). Images were acquired with patients face in an 80 projection in PTT’’), Oral and Pharyngeal Retention Index (ORI % and PRI %)
front of gamma-camera. ROIs on the oral cavity, pharynx, esophagus and Retention in oral cavity and pharynx on static images
and stomach were drawn to collect data about Oral, Pharyngeal and (%OralStatic1, %OralStatic2, %OralStatic3, %PharynxStatic1,
Esophageal Transit Time (OTT, PTT and ETT respectively), %PharynxStatic2 and %PharynxStatic3 respectively).
Esophagus-Gastric Transit Time (EGTT), Oral, Pharyngeal and Patients were divided into 2 groups: DOSS1 (moderate,
Esophageal Retention Index (ORI, PRI, and ERI respectively) and mild/moderate and mild dysphagia) which included 20/32 patients,
Esophageal Emptying Rate (EER). Patients were divided into 2 DOSS2 (normal or slight compromised swallowing) which included
groups: DOSS1 (moderate, mild/moderate and mild dysphagia) which 12/32 patients.
included 19/33 patients, DOSS2 (normal or slight compromised T-test was applied to compare DOSS with data obtained at
swallowing) which included 14/33 patients. Cohen’s test was applied dynamic and static OPES. P \ 0.05 was considered statistically
to compare OPES results with DOSS groups. significant.
Results: ORI was pathological in 8/19 pts of DOSS1 and non- Results: In DOSS1 mean values were: OTT00 = 1.7500 (range 0.500 –
pathological in the remnant, while it was non-pathological in all 14 300 ), ORI% = 14.32% (range 0.70–46.50%), %OralStatic1 = 5.56%
pts of DOSS2, showing fair agreement (k = 0.38). PRI resulted (range 0.28–16.40%), %OralStatic2 = 1.85% (range 0.14–4.79%),
pathological in 11/19 pts of DOSS1 and non-pathological in the %OralStatic3 = 1.39% (range 0.34–3.29%), PTT00 = 1.16 (range
remnant while it was pathological in 3/14 pts DOSS2 and non- 0.500 –500 ), PRI% = 27.53% (range 0.80–80.98%), %PharynxStat-
pathological in the remnant, showing fair agreement (k = 0.34). ERI ic1 = 2.42% (range 0.15–9.27%), %Pharynxstatic2 = 0.77% (range
resulted pathological in 17/19 pts of DOSS1 and non-pathological in 0.03–2.64%) and %Pharynxstatic3 = 0.5% (range 0.07–1.92%). In
the remnant while it was pathological in 7/14 pts of DOSS2 and non- DOSS2 mean values were: OTT00 = 1.7100 (range 100 –300 ), ORI% =
pathological in the remnant, showing moderate agreement (k = 0.41). 6.53% (range 1–13.50%), %OralStatic1 = 2.44% (range
EER resulted pathological in 15/19 pts of DOSS1 and non-patho- 0.68–5.08%), %OralStatic2 = 1.19% (range 0.30–3.01%),
logical in the remnant while it was pathological in 7/14 pts DOSS2 %OralStatic3 = 0.92% (range 0.24–2.32%), PTT00 = 1.7100 (range
and non-pathological in the remnant, showing fair agreement with 0.500 –1100 ), PRI% = 16.89% (range 2.70–73.10%), %PharynxStat-
DOSS (k = 0.29). OTT, PTT, ETT and EGTT showed no agreement ic1 = 1.28% (range 0.28–4.41%), %Pharynxstatic2 = 0.49% (range
with DOSS. 0.09–1.30%) and %Pharynxstatic3 = 0.31% (range 0.05–0.78%).
Conclusions: Dysphagia is a relevant problem in neurological T-test resulted statistically significant for ORI% (t = - 2.224;
patients. OPES is a simple and well tolerated procedure that provides p = 0.03) and for OralStatic1 (t = - 2.454; p = 0.02).

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S97

Conclusions: Both dynamic and static OPES are well tolerated and PO167
easily performed procedures even in patients with neurological dis- Value of 18F-FDG-PET/CT in patients with seminoma
orders. Performing static images provides important information to
complete the dynamic examination, using the unique administration and suspected recurrent disease
of the radiopharmaceutical, in order to better assess the degree of
dysphagia of patients with neurological diseases. F. Di Gregorio1, M. Rensi1, D. Capobianco1, F. Giacomuzzi1,
M. Povolato1, G. Ferretti1, M. Rossi1, O. Geatti1
1
Nuclear Medicine Unit, University/Hospital of Udine, Udine, Italy
PO166
Background-aim: Seminoma is the most common testicular cancer
The role of salivagram in ab ingestis pneumonia risk affecting younger male and has an excellent prognosis with a 5 year
in a group of SMA 1 patients survival rate over 90%. However, 20–30% of patients with seminoma
will develop metastatic disease. To date, Computed Tomography
P. Nicoletti1, B. Berti2, V. Fuoco1, L. Fanelli2, M. Pane2, V. Valenza1 (CT) is the imaging technique of choice for follow-up and restaging
the disease, but CT has the limitation of anatomical imaging and
1 sometimes provides equivocal findings. Although 18F-FDG PET/CT
Nuclear Medicine Unit, Department of Diagnostic Imaging,
Radiation Oncology and Hematology, Foundation University Hospital (PET/CT) is not routinely performed in patients with seminoma, its
A. Gemelli IRCCS, Rome, Italy. 2Paediatric Neurology Unit and prognostic value in the assessment of metastatic spread is well doc-
Nemo Clinic Center, Foundation University Hospital A. Gemelli umented in many forms of malignant tumors.
IRCCS, Rome, Italy Aim of this study is to assess the diagnostic performance and the
prognostic value of PET/CT in patients with seminoma and suspected
Background-aim: Spinal muscular atrophy (SMA) is a motor neuron recurrent disease at CT scan.
disease characterised by generalised muscle atrophy and weakness Methods: Retrospectively 24 patients affected by seminoma (age
resulting from the dysfunction of motor neurons in the ventral horn of range 28–60 years) with radiological suspicious of recurrence disease
the spinal cord caused by mutations of the SMN1 gene [5q13]. The were investigated. Inclusion criteria were suspicious CT findings. All
classification of SMA is based on the maximal motor function patients underwent PET/CT examinations within 3 months from CT.
achieved. SMA 1 is the most severe form including very weak infants PET/CT were performed on a Siemens Biograph LSO scanner 60 min
unable to sit unsupported. Progressive dysphagia due to masticatory after the IV administration of 18F-FDG. PET/CT results were com-
muscle weakness and pharyngeal swallowing problems is a frequent pared with imaging, histological examination and clinical evolution at
complication in SMA 1 resulting in aspiration and consequent pul- follow-up duration of 2 years.
monary infections. SMA standard of care recommend to perform Results: In 16 out of 24 patients with positive CT findings, PET/CT
deglutitory evaluation, shortly after diagnosis and during the follow- showed pathological FDG uptake. Recurrent lesions was confirmed in
up. Salivagram is an easily and safely conducted with relatively low 12 of 16 patients with pathological PET/CT findings, by means of
radiation exposure scintigraphic method that enables detection of histology in 8 patients and by other diagnostic imaging modalities or
salivary aspiration into the lungs in children. follow-up in 4 patients. 4 patients with false-positive PET/CT findings
Methods: In the last 4 months we enroled 7 pediatric patients with were related to the presence of inflammation. PET/CT showed no
SMA1, aged between 10 months and 12 years old, who underwent pathological FDG uptake in 8 out of 24 patients with positive CT
salivagram in our Institute. The exam was performed using 10 MBq findings. All of them were considered true negative because no evi-
of 99mTc-DTPA, administered orally in sublingual location, while dence of disease by histological examination or during follow-up was
the patient was lying supine on the imaging table. Continuous found. In detection of recurrent disease PET/CT showed a sensitivity
dynamic 15-s images were acquired for a total of 30 min, using a and a specificity of 100% and 67% respectively. PET/CT showed a
gamma camera with Low-Energy collimator positioned in anterior negative predictive value of 100% and a positive predictive value of
view. In case of pharyngeal stagnation (high risk condition for ab 75%.
ingestis), in absence of early aspiration signs, we acquired late static Conclusions: Our data show that PET/CT is a noninvasive useful
images up to 2 h to identify any late suction. diagnostic tool in patients with seminoma for the evaluation of sus-
Results: We identified swallowing deficiency (bolus loss from the pected recurrence disease at CT scan. In this setting of patients PET/
lips and or nasopharyngeal reflux) in 43% of pts; elevated pharyngeal CT provides valuable informations, especially in case of equivocal
stagnation in 71% of pts; aspiration (1 case intra-deglutition and 1 CT findings, with a good prognostic value.
case post-deglutition) in 28% of cases; absence of esophageal transit
in 57% of cases and gastroesophageal reflux disease (GERD) in 28%
of cases.
Conclusions: Salivagram is an easy, safe and non-invasive evaluation PO168
tool for children with swallowing difficulty such as in neuromuscular The usefulness and the accuracy of 18F-FDG PET/CT
diseases. In this group of SMA1 patients we are able to highlight the
presence of swallowing incoordination, pharyngeal stagnation and in the restaging of clear cell carcinoma patients
GERD, all conditions that leads to suction. Evaluating these risk after primary surgical treatment
conditions that leads to the development of aspiration pneumonia
(AP), we are able to identify patients who belong to different risk M. Gazzilli2, R. Durmo2, M. Bertoli1, D. Albano1, M. Bonacina2,
categories detecting patients who require parenteral nutrition. It E. Cerudelli2, F. Dondi2, A. Mazzoletti2, F. Bertagna2, R. Giubbini2
enables assessment of children at a high risk of AP at the onset of the
1
disease and during the clinical course of the disease. Medicina Nucleare, ASST Spedali Civili di Brescia, Brescia, Italy.
2
Medicina Nucleare, Università di Brescia, Brescia. Italy
Background-aim: In Europe, Renal Cell Carcinoma (RCC) repre-
sents 3% of all neoplasm. Prognosis in RCC depends on tumor extent,
presence of metastasis, age and co-morbidities. 18Fluorine-

123
S98 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

Fluorodeoxyglucose Positron Emission Tomography/Computed Results: Overall, 7 patients were included in the final analysis. In 5/7
Tomography 18F-FDG-PET/CT (18F-FDG PET/CT) has suboptimal pts (71%), diuretic administration was performed. In 5/7 pts (71%),
diagnostic performance in the initial staging of RC due to physio- RS was clearly positive: 2/5 (40%) pts had a functionally excluded
logical excretion of radiotracer in the kidney that can mask lesions kidney (wrinkle kidneys) while 3/5 (60%) pts showed a reduced renal
uptake. More than 30% of the patients with a locally confined disease function and obstacle to the ureteral outflow. In 2/7 pts (28.5%), RS
at diagnosis develop metastases after nephrectomy. demonstrated preserved bilateral renal function and a slight obstacle
The aim of our study is to establish the usefulness of 18F-FDG PET/ to the ureteral outflow.
CT in the restaging of clear cell renal (CCRC) carcinoma patients. All pts referred a previous radiological diagnosis of ureteral
Methods: From 2006 to 2017 we retrospectively analysed 54 patients involvement by endometriosis but only in 4/6 (50%) pts, previous
(Male 35, Female 19; median age 64 years; range 33–81 years) uroCT data were available:
affected by CCRC who underwent radical or partial nephrectomy. In 1/4 pt, uroCT showed a bilateral second/third grade
(According to AJCC 7th edition at stage 19 patients were T1; 7 hydroureteronephrosis with major involvement of the right uterus: RS
patients T2; 26 patients T3; 2 patients T4; according to Fuhrman excluded a bilateral function loss, showing only a slight obstacle to
grade: 1 patients was G1; 25 patients G2; 19 patients G3; 9 patients the right-ureteral outflow;
G4). All patients underwent 18F-FDG PET/CT for restaging purpose In 1/4 pt, uroCT reported a severe damage on the left kidney
with the suspect of clinical or radiological relapse. Patients with (wrinkle kidney) with corresponding severe functional loss at the RS;
positive 18F-FDG PET/CT results were considered as true- positives Two/4 (50%) pts showed monolateral first grade
(TP) if further evaluations confirmed the malignant nature of lesions hydroureteronephrosis: in one pt, RS demonstrated preserved bilateral
and false-positive (FP) if further evaluations showed no malignant renal function with slight monolateral obstacle to the ureteral outflow.
lesions. Patients with negative 18F-FDG PET/CT results were con- In the other case, a moderate bilateral loss of function with con-
sidered as true negative (TN) if further evaluations confirmed no comitant obstacle to the ureteral outflow was reported.
neoplastic lesions and false-negative (FN) if further evaluations Only in one case (1/7), follow-up data were available: this patient
showed malignant ones. underwent to a surgical intervention after the first renography and the
Results: 18F- FDG PET/CT was positive in 33 patients (61.1%) and following RS showed a complete functional recovery and the reso-
negative in 21 (38.8%). Sensitivity, specificity, positive predictive lution of obstacle of the ureteral outflow.
value (PPV), negative predictive value (NPV) and accuracy of F18- Conclusions: Ureteral endometriosis is quite rare but unfortunately, it
FDG PET/CT were 88.24, 85, 90.91, 80.95, 87.04 respectively. The is often asymptomatic and may lead to silent obstructive uropathy
most common site of lesions was mediastinal lymph nodes, lung, and, in some cases, to renal failure. Despite the small population, this
ipsilateral adrenal gland and bone. The lesion showed an intense 18F- analysis demonstrate the complementary role of RS and conventional
FDG uptake with a value of SUV max and SUV mean between 2.6 imaging, especially in determining whether anatomical damage has
and 16.1. already led to a functional loss, in order to define who is still sus-
Conclusions: Our preliminary study showed good sensitivity and ceptible to surgical treatment.
specificity of 18F-FDG PET/CT for the restaging of patients with
CCRC after primary surgical treatment, due to a high FDG uptake of
the lesions.
18F-FDG PET/CT could be useful in restaging patients with CCRC, PO170
detecting distant metastasis and in therapy monitoring. Diagnostic performances of [18F]FDG-PET/CT to assess
infected post traumatic non-unions

PO169 M. Sollini1, S. Chiola1, N. Trenti3, E. Malagoli5, M. Catalano4,


L. Di Mento5, A. Kirienko5, M. Berlusconi5, A. Chiti1, L. Antunovic2
Usefulness of Tc99m-MAG3 renal scintigraphy
in women with ureteral endometriosis 1
Department of Biomedical Sciences, Humanitas University, Pieve
Emanuele, Milan, Italy. 2Department of Nuclear Medicine,
D. Calabrò1, R. Bonfiglioli1, L. Zanoni1, M. Levorato1, S. Fanti1 Humanitas Clinical and Research Center-IRCCS, Rozzano, Milan,
Italy. 3Department of Radiology, Humanitas Clinical and Research
1
Nuclear Medicine, S. Orsola-Malpighi Hospital, Bologna, Italy Center-IRCCS, Rozzano, Milan, Italy. 4Department of Radiology,
Ospedale del Mare, Ponticelli, Naples, Italy. 5Trauma Center,
Background-aim: To assess the usefulness of TC99m-MAG3 renal
Humanitas Clinical and Research Center-IRCCS, Rozzano, Milan,
scintigraphy (RS) in women with radiological diagnosis of ureteral
Italy
endometriosis (both intrinsic and extrinsic).
Methods: Between June 2016 and October 2018, all patients (pts) Background-aim: Post-traumatic fracture non-unions occur in about
who underwent TC99 m-MAG3 renal scintigraphy for radiological 5% of patients who need to be re-operated. Infection is one of the
suspicion of ureteral involvement due to endometriosis were enrolled. major complications of fracture healing, especially in patients with
All renograms were retrospectively reviewed and, when available, open fractures. The presence of infection has a major influence on the
compared to following RS, to evaluate if any changes occured. Pre- patient management and surgical strategy. Pre-operative diagnosis of
vious conventional imaging data (in particular uroCT) were also infected non-unions is still a challenge. The aim of this study was to
collected and compared to RS in order to assess the concordance evaluate the diagnostic performance of [18F]FDG-PET/CT in sus-
between morphological and functional imaging in terms of damage. pected infected non-unions.
Tc99m-MAG3 renography was performed according to the EANM Methods: We retrospectively collected all patients who performed
guidelines. Diuretic administration was evaluated during the perfor- [18F]FDG-PET/CT for suspected infected non-union, scheduled for a
mance of the dynamic study. Renal functionality and obstructive surgical treatment in our trauma center from January 2011 to June
conditions were evaluated by visual assessment of renograms, split 2017. Demographics, clinical data, diagnostic examinations, labora-
uptake % and ERPF values (Mod. Gates methods), measured by a tory results, surgical reports, microbiological intraoperative findings
dedicated software. and patient outcome were analyzed. Overall, 47 patients with non-
union of the lower extremities were included in the present study.

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S99

[18F]FDG-PET/TC images were analyzed visually and semi-quanti- presence of infection. Autologous leukocyte scintigraphies were
tatively (i.e., target/background ratio) by one experienced nuclear evaluated visually and semiquantitatively. In three-phase bone scans,
medicine physician and one experienced musculoskeletal radiologist. regions of interest (ROIs) were delineated in the perfusion and blood-
Microbiological results on specimens collected during surgery were pool phase images, incorporating the entire prosthetic region and
used as reference standard to define the final diagnosis. [18F]FDG- applying an isocontour method (including only pixels within a
PET/TC sensitivity, specificity, positive predictive value (PPV), threshold of 40% of the maximum pixel activity within the ROI);
negative predictive value (NPV), accuracy, positive and negative corresponding mirror ROIs were placed on the healthy knee, making
likelihood ratio (LR ? and LR-, respectively) were calculated. minimal manual positioning corrections and applying the isocountour
Results: Intraoperative tissue cultures resulted positive for infection method. Perfusion (Pr) and Blood Pool (BPr) ratios were calculated
in 25 patients and negative in the remaining 22 cases. The pre-test by dividing the total ROI counts in the prosthetic knee for the ROI
probability was 53%. PET/CT images were visually scored as positive counts in the healthy knee; P/BP ratio was calculated as follows: P/BP
and negative in 30/47 and 17/47 cases, respectively. According to ratio = {[(Pr/BPr) 9 100] - 100}. Corresponding ROC curves for
final diagnosis PET/CT analysis correctly identified 23/25 patients as each semiquantitative parameter were generated to identify the opti-
infected, while excluded non-union infections in 15/22 cases. Sensi- mal cut-offs for predicting the results of the autologous leukocyte
bility, specificity, PPV, NPV and accuracy were 92, 68, 77, 88 and scintigraphy.
81% respectively. LR ? and LR- resulted 2.89 and 0.12, respec- Results: Autologous leukocyte scintigraphy identified 8 cases of
tively. The positive post-test probability was 77%. The combination septic loosening and 12 negative cases. The optimal cut-offs of Pr
of the visual approach and semi-quantitative analysis resulted in a (1.91), BPr (1.5) and P/BP ratio (25.20%) discriminated between
higher specificity (77%) but in a lower sensitivity (80%), with a high septic and aseptic loosening (respectively above and below the cut-off
positive post-test probability (80%) but a suboptimal negative post- values) with high accuracy (Pr: sensitivity = 100%, speci-
test probability (26%). ficity = 83.3%; BPr: sensitivity = 87.5%, specificity = 58.33%; P/BP
Conclusions: This study demonstrated that [18F]FDG-PET/CT may ratio: sensitivity = 100%, specificity = 100%).
be successfully used in the diagnosis of infected post traumatic non- Conclusions: Semiquantitative evaluation in three-phase bone scan
unions. The addition of semi-quantitative analysis to the visual may serve as a relevant tool in the assessment of suspected septic
approach improved specificity. loosening of knee prostheses. In our experience, P/BP ratio is the
semiquantitative parameter with the highest predictive power of
septic loosening. These findings warrant confirmation in larger patient
samples; furthermore we will assess whether the use of P/BP ratio
PO171 may anticipate the timing of differential diagnosis between septic and
A new semiquantitative parameter in three-phase bone aseptic loosening and influence clinical decision making.
scan to predict the findings of 99mTc-HMPAO-labeled
leukocyte scintigraphy in patients with knee
arthroplasty PO172
May the quantification of (99M)TC-HMDP bone
N. Quartuccio6, M. Siracusa6, R. Ricapito6, A. Arnone6, N. Galvano2, concentration with SPECT/CT be expression
R. Sciortino3, G. Calsabianca1, G. Piritore7, F. Terrazzino7,
D. Messana7, M.T. Arnone6, F. Midiri5, P. Alongi4, G. Arnone6
of the bone mineral density? Preliminary results

1
ANIO ONLUS, Palermo, Italy. 2Department of Orthopaedic Surgery D. Maccora5, L. Zagaria5, V. Scolozzi5, A. Rizzo5, S. Lello2,
(DICHIRONS), University of Palermo, Palermo, Italy. 3Department A. Capozzi2, A. Leone1, L. Indovina4, A. Capotosti4, G. Soraci3,
of Orthopaedic Surgery, Ospedale Civico ARNAS, Palermo, Italy. D. Smaniotto3, V. Valenza5
4
Department of Radiological Sciences, Nuclear Medicine Service, 1
Fondazione Istituto G. Giglio, Cefalù, Italy. 5Department of Radiol- Department of Diagnostic Imaging, Radiation Oncology and
ogy, DIBIMED, University of Palermo, Palermo, Italy. 6Nuclear Hematology, Foundation University Hospital A. Gemelli IRCCS,
Medicine Unit, ARNAS PP.OO. ‘‘Civico, Di Cristina e Benfratelli’’, Rome, Italy. 2Department of Woman and Child Health, Foundation
Palermo, Italy. 7Radiology Unit, ARNAS PP.OO. ‘‘Civico, Di Cris- University Hospital A. Gemelli IRCCS, Rome, Italy. 3Gemelli
tina e Benfratelli’’, Palermo, Italy Advanced Radiation Therapy Center, Department of Diagnostic
Background-aim: Interpretation of three-phase bone scan in patients Imaging, Radiation Oncology and Hematology, Foundation
with suspected loosening of knee prosthesis relies on the evaluation of University Hospital A. Gemelli IRCCS, Rome, Italy. 4Medical
asymmetry of counts in the flow and blood pool phase images Physics Unit, Foundation University Hospital A. Gemelli IRCCS,
between the prothesized and contralateral knee. In case of three-phase Rome, Italy. 5Nuclear Medicine Unit, Department of Diagnostic
bone scan pattern of loosening, autologous leucocyte scintigraphy is Imaging, Radiation Oncology and Hematology, Foundation
the gold standard non-invasive imaging method for distinguishing University Hospital A. Gemelli IRCCS, Rome, Italy
between septic and aseptic loosening. However, autologous leucocyte Background-aim: Single-photon emission computed tomography
scintigraphy is a more complex, expensive and longer exam compared (SPECT) lacks quantitative information on regional activity concen-
to three-phase bone scan. The aim of the present study was to predict tration (AC) of the injected tracer. Recently, a new methodology for
the results of autologous leukocyte scintigraphy by identifying in absolute quantification in SPECT has been introduced and applied in
three-phase bone scan cut-off values of count ratios between the different clinical environments. The evaluation of the skeletal con-
prosthetic knee and the ‘‘healthy’’ knee in perfusion and blood pool centration of 99mTc-HMDP in bone scintigraphy could be a promising
phases and the use of a new semiquantitative parameter, named approach to assess the bone metabolism. First object of the study was
perfusion-to-blood pool ratio (P/BP ratio). to determine AC in the healthy lumbar spine and femoral neck.
Methods: Twenty patients with history of unilateral knee arthroplasty Secondly, we aimed to correlate SPECT quantitative parameters with
underwent three-phase bone scan (after 1 year from arthroplasty) and data from CT and bone densitometry.
subsequently 99mTc-HMPAO-labeled leucocytes scintigraphy (within
an interval of 2 months), used as standard of reference to establish

123
S100 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

Methods: A retrospective analysis was performed on female patients aim is to assess the value of a Radiomic approach in discriminating
with breast cancer who underwent a bone scintigraphy and a bone patients affected by infection from patients affected by inflammation.
densitometry, both exclusively before treatment. Patients were Methods: For this study we selected patients with complications after
injected with 643.06 ± 67.71 MBq of 99mTc-HMDP (according to first reparative orthopaedic surgery, who had positive FDG PET CT
the body weight). A whole body planar imaging was performed 2 h and underwent surgery to remove PET suspicious areas. Micro-
after injection, followed by SPECT/CT of the lumbar spine and the DTTect system was used to collect and partially process removed
pelvis. For quantitative analysis a volume of interest (VOI) was tissues. Based on histology and microbial results, patients were
delineated on the lumbar spine (including L1–L4) and on the femoral assigned to the inflammation or infection class. FDG PET CT image
neck, in areas not affected by malignancy or any other bone diseases. analysis consisted in a first semi-automatic segmentation step using
AC (kBq/ml), SUV and Hounsfield units (HU) were extracted, using 3D Slicer software, carried out by an expert nuclear medicine
the reconstruction algorithm ‘‘xSPECT Bone’’ (Symbia Intevo, Sie- physician. A SUV over 3 g/ml was considered significant and was
mens). Lumbar and Femoral Bone mineral Density (BMD; g/cm2) included in further analysis. Shape based, intensity based and texture
were assessed by Dual energy X-ray absorptiometry (DEXA) (GE- based features were calculated using the PyRadiomics software.
Lunar Prodigy Advance). Bone densitometry was associated with Furthermore clinical features, age, gender and SUV, were added to
bone quality analysis, obtained at vertebral level through Trabecular the features set. Feature selection was carried out using a custom
Bone Score (TBS) Insight program to evaluate inner bone structure genetic algorithm. Features subsets, were scored by their classification
and integrity. Data were expressed in median values and standard accuracy using 3 different machine learning (ML) systems: kNN,
deviations. Parameters obtained with bone scintigraphy, CT and bone LDA and NaiveBayes classifier (NB). Models validation was carried
densitometry were correlated by Pearson correlation analysis. A p out by leave-one-out and, additionally, by 5- and 10-fold cross-vali-
value \ 0.05 was considered as statistically significant. dation (20 repetitions).
Results: Eight patients were included. AC measured in the lumbar Results: Totally 75 patients (32 women, 43 men) were included in the
spine was 50.41 ± 16.54 kBq/ml, which corresponded to SUVmean study. Histological and microbial results showed that 47 out 75
of 5.86 ± 1.00, SUVmax of 8.89 ± 1.57 and SUVmin of patients were positive for infection. Through PyRadiomics software
4.52 ± 0.74. The VOI analysis showed a CT value of 200.36 ± 15.02 196 features were extracted from CT and PET images for each
HU. The bone densitometry showed BMD of 1.01 ± 0.13 g/cm2 and patient. The features selection, carried out with a genetic algorithm,
TDS of 1.31 ± 0.08. Regarding the lumbar vertebrae, SUV did not showed 4 robust features one CT-based and three PET-based. These
correlate significantly with HU (p = not significant—NS) as well as were used for classification and the best diagnostic performance was
with BMD and TBS (p = NS, respectively). In the femoral neck, AC obtained, using the NB classifier with average accuracy of 86%.
amounted to 25.39 ± 10.28 kBq/ml, corresponding to SUVmean of Conclusions: This study suggested that ML systems applied to
2.88 ± 0.76, SUVmax of 4.28 ± 1.10 and SUVmin of 2.24 ± 0.56. Radiomic data from FDG PET CT can discriminate bone infection
CT value was 396.21 ± 69.62 HU and BMD was 0.79 ± 0.11 g/cm2. from inflammation.
In this case, no significant correlations were observed between SUV
and HU (p = NS) and between SUV and BMD (p = NS).
Conclusions: Although preliminary, our data exclude a correlation of
SUV with bone CT density and with BMD and TBS. The reason PO174
should be found in the different physiopathologic aspect that each Transthyretin cardiac amyloidosis and aortic stenosis:
examination represents: the bone scintigraphy is related to the in which patients we have to suspect a coexistence
osteoblastic activity, while data from CT and bone densitometry are
expression of the structural density. However, a larger population is
E. Cerudelli2, D. Albano1, M. Gazzilli2, M. Bonacina2, R. Durmo2,
required to explore further the potential value of SPECT quantitative
F. Dondi2, A. Mazzoletti2, F. Bertagna3, R. Giubbini3
parameters in the diagnosis and in the prognosis of the bone loss.
1
Spedali Civili di Brescia, Brescia, Italy. 2Università degli Studi di
Brescia, Brescia, Italy. 3Università degli Studi di Brescia e Spedali
PO173 Civili di Brescia, Brescia, Italy
A radiomic approach for successful distinction Background-aim: Degenerative aortic stenosis (AS) is the most
of infection versus inflammation in patients treated common valvular heart disease and can lead to a severe concentric
remodelling, diastolic dysfunction and atrial fibrillation. These find-
with reparative orthopaedic surgery: a pilot study ings can be seen also in wild type transthyretin (wt-TTR) cardiac
amyloidosis (TTR-CA), a restricted cardiomyopathy caused by the
N.C. D’amico2, P. Gandolfo5, G. Valbusa2, E. Grossi1, R. Armonino5, deposition of wt-TTR that carries a poor prognosis.
D. Fazzini3, G.M. Calori4, M. Colombo4, E. Mazza4, S. Papa2 TTR-CA can be accurately detected by a non-invasive technique like
1
a bone seeking radioisotope scintigraphy, such as technetium-99m-
Bracco Imaging S.p.A., Milan, Italy. 2Imaging Department, Centro 3,3-diphosphono-1,2 propanodicarboxylic acid (99mTc-DPD) with-
Diagnostico Italiano S.p.A., Milan, Italy. 3Radiology, Imaging out need of myocardial biopsies.
Department, Centro Diagnostico Italiano S.p.A., Milan, Italy. Several studies reported the coexistence of TTR-CA and low-flow-
4
Reparative Orthopaedic Surgery, ASST PINI-CTO, Milan, Italy. low gradient AS with normal left ventricle ejection fraction (LVEF)
5
Unit Nuclear Medicine, Imaging Department, Centro Diagnostico and underlined the importance of screening patients in whom there is
Italiano S.p.A., Milan, Italy a suspicion of concomitant severe AS and TTR-CA because of the
Background-aim: It has been demonstrated that FDG PET has a high different management and prognosis between patients with only AS
sensitivity but a low specificity in differentiating infection from or with both pathologies.
inflammation in patients with joint prosthesis implant (JP) or post- We decide to investigate the coexistence of AS and TTR-CA and
traumatic synthesis interventions (SI). This fact leads to a surgical and to identify clinical, echocardiographical and laboratoristic criteria
therapeutic overtreatment of patient affected by inflammation. Our which could rise the suspect of the coexistence of the two diseases.
Methods: We retrospectively analyze 81 patients (82 ± 7 years, 85%
men) that underwent 99mTc-DPD scintigraphy because of the suspect

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S101

of TTR-CA with or without moderate or severe AS by the transtho- SUV ratio was significantly associated with reduction of GC therapy
racic echocardiography: 8 patients with AS were classified as positive (p \ 0.001).
for TTR-CA (group 1 = 10%), 27 without AS were positive (group Conclusions: Vessels FDG uptake decreased significantly after the
2 = 34%) and 46 with AS were negative (group 3 = 57%). initiation of TCZ therapy in LVV patients showing a good metabolic
Results: Between patients with TTR-CA, with or without AS, the response. The reduction of FDG uptake is related to decrease of
prevalence of arrhythmia is very high (80%) and is more frequent to steroid therapy, confirming a reduction of disease activity. FDG-PET/
have a carpal tunnel syndrome surgery (20%) in anamnesis. CT could be used to evaluate treatment response in TCZ-treated
Patients with TTR-CA and AS by echocardiography, compared to patients.
patients with only AS, showed a significative higher thickness of the
interventricular septum (21.00 vs. 14.5 mm, p \ 0.01), LV posterior
wall (15.17 vs. 11.46 mm, p = 0.018) and lower e-wave deceleration
time (154.5 vs. 225.3 ms, p = 0.060). PO176
Patients with only TTR-CA, compared to patients with only AS, Deauville-score outperforms  SUVmax for end-of-
demonstrated a significant difference in the interventricular septum treatment evaluation of 18F-FDG PET in patients
(19.58 vs. 14.5 mm, p \ 0.001) and LV posterior wall thickness
with spondylodiscitis
(17.14 vs. 11.46 mm, p \ 0.001).
Comparing the level of N-terminal probrain natriuretic peptide
(NT-proBNP), patients with TTR-CA and AS expressed the highest V. Ceriani2, S. Capitanio4, M. Mikulska2, S. Tunesi3, R. Pincino3,
values, significantly different from the values of the other two groups L.A. Nicolini2, M. Pennone4, M. Bauckneht4, A. Borra2, S. Raffa2,
(1 vs. 2: 32918.00 vs. 9164.18 ng/dl, p = 0.006; 1 vs. 3: 32918.00 vs. C. Marini1, G. Sambuceti2, C. Viscoli2, S. Morbelli2
4690.25 ng/dl, p = 0.001). 1
Conclusions: In our study group Transthyretin cardiac amyloidosis CNR Institute of Molecular Bioimaging and Physiology, Milan,
has a prevalence of 15% in patients with moderate or severe aortic Italy. 2Department of Health Sciences, University of Genoa, Genoa,
stenosis. Both clinical and echocardiography criteria and plasma Italy. 3Infectious Disease Unit, Policlinico San Martino, Genoa, Italy.
4
levels of NT-proBNP can alert the clinician for suspect of the coex- Nuclear Medicine Unit, Policlinico San Martino, Genoa, Italy
istence of the two pathologies. Background-aim: Defining time frame of treatment discontinuation
is challenging in patients with spondylodiscitis as failure of therapy is
mainly based on clinical evaluation and markers of systemic
inflammation. 18F-FDG PET/CT (PET) has shown high sensitivity
PO175 and specificity for identifying early responders in the interim evalu-
Evaluation of treatment response to tocilizumab ation of patients empirically treated. However its value at the end of
with 18F-PET/CT in patients with large vessel vasculitis therapy is less established. We aimed to assess the added value of
FDG PET based on either  SUVmax or Deauville score (DS) at
E. Cerudelli2, G. Bosio1, D. Albano1, M. Gazzilli2, M. Bonacina2, Interim and end-of-therapy evaluation in patients with
R. Durmo2, F. Dondi2, A. Mazzoletti2, F. Bertagna3, R. Giubbini3 spondylodiscitis.
Methods: We retrospectively enrolled patients submitted to PET at
1
Spedali Civili di Brescia, Brescia, Italy. 2Università degli Studi di baseline and after therapy and whose CRP levels at the same time-
Brescia, Brescia, Italy. 3Università degli Studi di Brescia e Spedali points were available. SUVmax was measured both at baseline and
Civili di Brescia, Brescia, Italy after therapy and early and final-  SUVmax was computed. Interim
and end of treatment PET were also visually scored by means of the
Background-aim: 18F-Fluorodeoxyglucose positron emission 5-points DS. Linear regression analysis was performed to evaluate the
tomography (FDG-PET/CT) can be useful in the detection of the relationship between  SUVmax and DS on one side and inflam-
arterial wall inflammation in patients affected by large-vessel vas- matory indexes at each time point. Finally, Interim and final SUVmax
culitis (LVV) as Takayasu arteritis (TA), giant cell arteritis (GCA) and  SUVmax as well as DS were compared between (early and
and aortitis. The aim of this study is to investigate the usefulness of late) responders and non-responders defined according either bio-
FDG-PET/CT in the evaluation of therapy response with tocilizumab chemical (CPR-based) or clinical status (1 and 6 months after the end
(TCZ), a humanized anti-interleukin-6 receptor antibody, in patients of treatment). P \ 0.05 was regarded as significant.
affected by LVV. Results: PET and CPR levels were available at baseline and at
Methods: We retrospectively evaluated 11 patients (56 ± 19 years; 7 Interim evaluation in 58 patients while end of therapy evaluation was
female, 4 male) with LVV treated with TCZ. FDG-PET/CT were available in 31 patients. The mean CRP level was 54.4 ± 49 mg/L at
performed at baseline and with an interval of 3-26 months diagnosis. The mean SUVmax was 5.9 ± 2.2, 4.2 ± 1.7 and
(13.18 ± 7.69) after the initiation of TCZ therapy. PET images were 3.7 ± 1.7 (baseline, interim and end-of-therapy) while DS was scored
analysed visually and semi-quantitatively by measuring the maximum at baseline as: DS 5 n = :12 4 n = 34; 3 n = 12: 2 n = 1; at interim as
standardized uptake value (SUVmax) of the vascular wall of bilateral 5 n = 2: 4 n = 26; 3 n = 24; 2 n = 3, 1 n = 4 at end-of-therapy as 3
subclavian and common carotid arteries, ascending thoracic aorta, n = 22: 2 n = 4; 1 n = 5. No significant correlations were highlighted
abdominal aorta and bilateral iliac arteries. Moreover for each patient between PET-parameters and CRP at all time-points. As expected
we selected the vessel with most increased uptake and we calculated Interim-CRP, Interim-SUVmax, Interim-DS were significantly lower
the vessel-to-liver SUVmax ratios pre- and post-treatment. The  in early responders (p \ 0.001, p \ 0.005 and p \ 0.006, respec-
SUV ratio (pre-post treatment) was compared to changes in gluco- tively). However final-DS while not final-  SUVmax was
corticoid (GC) therapy, considered as an index of disease activity. significantly lower in clinical responders versus non responders at the
Results: Nine patients had a complete disease remission after TCZ, in end of therapy (p \ 0.05). Of note Interim-DS (while not interim-
one there was a reduction of vessels uptake and in one patient PET/  SUVmax) was significantly lower in patients characterized by
CT images highlighted new vessels inflammation. Vessel-to-liver normal Interim-CRP (p \ 0.006).
SUVmax ratio was significantly decreased in post-treatment PET/CT Conclusions: PET might be useful in the post-treatment evaluation of
(1.73 ± 0.82 vs. 0.82 ± 0.18; p = 0.002). Mean GC dose was tapered patients with spondylodiscitis. However while all PET-derived
from 28.86 ± 15.06 mg/d to 7.09 ± 4.66 mg/d (p \ 0.001). The 

123
S102 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

parameters were sensitive to early response only DS was able to tell Conclusions: In this case report 18F-FDG PET/CT identified
apart responders and non-responders in the end of therapy setting inflammatory pre-occlusive lesions, had a high sensitivity in the
possibly being able to decrease the false-positive results after therapy. evaluation of disease activity and managed medical team to establish
Finally Interim DS alone was more suitable to capture depth of early the best therapy avoiding an invasive exam.
biochemical response since the earliest stages thus possibly providing Although angiography remains the gold standard for the diagnosis of
information in patients not submitted to PET at baseline. TA, 18F-FDG PET/CT can be useful to detect early diagnosis and
consequently reduce vascular complications in patients with TA.

PO177
The role of 18F-FDG PET/CT for the assessment PO178
of Takayasu arteritis in a pediatric patient affected Role of 18FDG-PET/CT in infective endocarditis:
by complex congenital heart disease: a case report the experience in matera nuclear medicine department

E. Gay1, G.A.C. Pattarino3, L. Monaco2, M. Spallino1, C. Dolci1, S. Schiavariello2, M.A. Renna2, R. Armeno2, A. Linzalone1,
A.F. Scarale1, M. Cuzzocrea2, G. Cabrini1, C. Trabatti3, E. Preza1, G. De Stefano1
M. Milella1, B.L. Teruzzi3, R. Sara1, C. Rossetti1 1
Infectious Disease Department, Genoa, Italy. 2Nuclear Medicine
1
Nuclear Medicine Department, ASST Niguarda Hospital, Milan, Unit, Genoa, Italy
Italy. 2Nuclear Medicine Department, University Milan Bicocca, Background-aim: The aim of this study was to evaluate:
Milan, Italy. 3Pediatric Department, ASST Niguarda Hospital, Milan, - the diagnostic accuracy of 18FDG-PET for suspected infective
Italy endocarditis (IE)
Background-aim: Takayasu arteritis (TA) is an idiopathic granulo- - the sensitivity of 18FDG PET/TC to identify the site of infection
matous large-vessel vasculitis which predominantly involves the aorta - the accuracy of prolonged fasting acquisition protocol for sup-
and its main branches in their full thickness wall and it constitutes one pression of glucose metabolism.
of the more common vasculitides in children. The result is an Methods: We performed 18FDG-PET/CT in 10 high risk patients
endothelial damage, intimal proliferation and inflammation which (pts) with suspected IE (pts with prosthetic valve any type, pts with a
lead to segmental stenosis, occlusion, dilatation, and/or aneurysm previous episode of IE; pts with any type of congenital heart disease
formation. repaired with a prosthetic material).
Clinical manifestations of TA depend on the specific inflammatory All patients had fever [ 38 for at least 3 weeks and persistent ele-
phase, including systemic non-specific symptoms during the acute vation of erythrocytes sedimentation rate and Reaction C-Protein.
phase and symptoms due to ischaemia and arterial occlusion typical The protocol used for the suppression of glucose metabolism
of the chronic phase, respectively. included:
Although digital subtraction arteriography remains the diagnostic - prolonged fasting (for at least 12 h) and protein diet in the 36 h
gold standard, this case report wants to remark the role of 18F-FDG before the exam;
PET/CT as a non-invasive method in the management of a patient - evaluation of the cardiac blood pool score with a 3 cm ROI on
with TA. the left ventricle, related to a ROI on the liver by calculating the max
Methods: We report a 13-years old female carrier of complex con- and mean SUV.
genital heart disease, surgically corrected and ASA-treated. A score 2:1 between liver and left ventricle uptake was assessed as
After a first diagnosis of migraine with aura, an upper extremity appropriate for adequate suppression of glucose metabolism, without
Magnetic Resonance Angiography (MRA) done for radial artery pulse using heparin.
hyposphygmia revealed absent blood flow in the proximal right bra- The results were compared with conventional diagnostic tech-
chial artery compensated for valid collateral circulation. Inflammation niques and with clinical follow-up (FU) for 3–6 months.
parameters (CRP 4,1 mg/dl, ESR 89 mm/h, Serum Amyloid A Results: 18FDG-PET/CT did not detect focal pathological radio-
611 mg/L) were increased. pharmaceutical accumulation in the cardiac area:
Clinical examination confirmed hyposthenia in the upper - 5 patients had bilateral pulmonary thickening uptake; during the
extremity of the right arm without ischaemia signs. clinical-instrumental FU it was found that these patients were suf-
Ultrasound (US) and Computed Tomography (CT) neck confirmed fering from respiratory diseases;
a significant stenosis in the proximal right subclavian artery and a - 1 patient had diffuse accumulation at the level of a vascular
non-significant stenosis in the proximal right common carotid artery. prosthesis of the abdominal aorta up to the iliac bifurcations; during
MRA of the supra-aortic arteries defined multiple stenosis, in the FU it was found that he was affected by vascular prosthesis
particular a bilateral subocclusion in subclavian arteries with a greater infection;
extension in the right one, irregular lumen, without significant - 1 patient had accumulation at the level of the ascending aorta;
stenosis in the right vertebral and in the right common carotid artery, this patient was suffering from vasculitis in Behcet’s disease
and finally a low grade stenosis in both vertebral arteries origins. - 3 patients were negative: 2 of this pts had disease of the urinary
A18F-FDG PET/CT described high metabolic activity in right tract; in 1 patients the cause of the fever has not been recognized.
common carotid artery and right subclavian artery, while a less All patients was negative for infective endocarditis during hospi-
activity in left carotid and in left subclavian artery. talization and FU.
Results: 18FDG PET/CT circumscribed and identified active The negative predictive value (NPV) for IE = 100%.
inflammation, allowing to exclude the other arterial districts not The sensitivity for localizing the infection/inflammation’s
involved in the inflammatory phase. By the use of steroid and immune site = 70%.
system suppressant, biochemical inflammation parameters went to Conclusions: 18FDG-PET/CT negative predictive value is resulted
normal range, while persisted all the clinical signs due to stenosis. high in the diagnosis of IE and the sensitivity for localizing the
infection/inflammation’s sites is resulted 70% (also in relation to the
sample size of report). The patient preparation protocol is resulted

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S103

useful for the adequate suppression of cardiac glucose metabolism, PO180


also without using heparin. Clinical performance of human leukocytes labelled
with 99MTC-HMPAO using Leukokit with gelofusine
or HES as sedimentation agent
PO179
18
F-FDG PET/CT for lung invasive fungal infection D. Riolo1, S. Auletta1, P. Pizzichini1, D. Prosperi1, A. Signore1
(IFI) in acute myeloid leukemia (AML) patients
1
Nuclear Medicine Unit, Sant’Andrea Hospital, Department of
4 3 1 1 2
A. Franchini , F. Elisei , L. Verga , M. Fedele , E. De Ponti , Medical-Surgical Sciences and of Translational Medicine, University
C. Crivellaro4, C. Landoni4, L. Guerra3 of Rome ‘‘Sapienza’’, Rome, Italy
Background-aim: Radiolabelled autologous leukocytes (WBC) is
1
Hematology, ASST-Monza, San Gerardo Hospital, MB, Italy. considered the gold standard for imaging infections.
2
Medical Physics, ASST-Monza, San Gerardo Hospital, MB, Italy. Leukokit is a commercially available, disposable, sterile kit for
3
Nuclear Medicine Department ASST-Monza, San Gerardo Hospital, labelling WBC ex vivo. In this kit, WBC isolation from red blood
MB, Italy. 4Nuclear Medicine, University of Milano-Bicocca, Milan, cells (RBC) was performed using a sedimentation agent: poly (O-2-
Italy hydroxyethyl) starch (HES-steril 10%). Due to its poor availability,
Background-aim: Combined anatomic and functional imaging with HES has been recently replaced by Gelofusine in the Leukokit.
18F-FDG PET/CT is gaining foothold in the management of various Aim of this study was to compare the diagnostic accuracy of WBC
infective pathologic abnormalities. Aim of this study was to evaluate labelled with Leukokit with 10% HES vs Leukokit with Gelofu-
the role of FDG PET/CT in acute myeloid leukemia (AML) patients sine. In addition we also tested, in vitro, the suitability of Gelofusine
with lung invasive fungal infection (IFI). A comparison with con- as an alternative to 10% HES in terms of labelling efficiency, label-
ventional CT scan was also performed. ling yield and toxicity.
Methods: 20 patients with AML and suspected lung IFI performed a Methods: Clinical comparison was performed between 77 patients
chest CT scan (CT1) followed by a PET/CT (PET1) scan, before (33 males; age 67.5–14.2) injected with 99mTc-HMPAO-WBC, using
antimicotic treatment. CT and PET/CT were repeated 2 months after HES as sedimentation agent, and 92 patients (38 males; age
the beginning of treatment (n = 16 pts) and compared to basal eval- 68.2–12.8) injected with 99mTc-HMPAO-WBC using Gelofusine as
uations to assess treatment efficacy (CT2, PET2): lesions with the sedimentation agent, recruited for diagnostic WBC scan between
highest FDG uptake on PET was selected as ‘‘reference lesion’’ and 2014 and 2017. Patients had suspicion of prosthetic joint infections,
SUVmax was calculated for PET1 and PET2. Metabolic response peripheral bone osteomyelitis or vascular graft infection.
(MR) was measured as follows: complete MR (CMR, uptake B than As in vitro tests, cells from 50 ml of ACD-blood were sedimented
mediastinal blood-pool), partial MR (PMR, partial reduction of the with 7 ml HES or 7 ml Gelofusine for 45 min and then purified from
lesion uptake [ than mediastinal blood-pool), progressive disease platelets (PLT) and labelled with 1.1 GBq of freshly prepared 99mTc-
(PD, increase uptake and/or new lesions). HMPAO. After 15 min, cells were washed again and resuspended in
Results: In 20/20 cases (100%) PET1 and CT1 were positive for IFI. 10 ml PBS for assessing the following parameters: number and type
The mean SUV max was 6.4 ± 2.4 (range 2.2–11.8). PET2 (n = 16) of recovered WBC; RBC contamination; PLT contamination; via-
showed 8 CMR, 4 PMR, (with a mean reduction of SUVmax 53%), 2 bility of neutrophils; chemotactic properties of neutrophils. We also
PD and 2 with both PMR of reference lesion and concomitant new PD compared the radiolabelling efficiency (LE), final recovery yield (RY)
lung lesions with FDG uptake. In the same group of 16 patients, PET2 and diagnostic outcome (sensitivity, specificity and accuracy) based
was concordant with CT2 in 13/16 cases. Three of 16 patients were on microbiology or at least 1-year follow-up. Results were analyzed
discordant: in 2 cases CT2 showed partial reduction of lung lesions using t-test when normally distributed, or Mann–Whitney test.
with a CMR on PET2, while in the remaining patient PET2 showed Results: Results showed that Gelofusine was a better sedimentation
PD while CT2 was stable (patient died because of infection). Follow- agent as compared to HES as far as the number of WBC recovered
up was available for all patients (median follow-up 456 days): 8/16 after sedimentation and centrifugation. However, HES provided a
were alive (7 PET responders and 1 non responder) while 8/16 died (5 lower RBC and PLT contamination (all not significantly different).
PET responder and 3 non responders). Both HES and Gelofusine did not influence the chemotactic proper-
Conclusions: 18F-FDG PET/CT is a promising tool for detection and ties of isolated WBC.
monitoring treatment efficacy of IFI in AML patients. PET/CT and From clinical studies, no differences were found between the two
CT were concordant in 81% of cases (13/16). Further studies are methods in terms of LE and RY (LEHES = 74.5 ± 9.6 vs LEGel =
needed to better evaluate the effectiveness of the additional role of 71.4 ± 11.4; p = 0.06 and RYHES = 54.8 ± 10.4 vs RYGel =
PET/CT in this scenario. 55.6 ± 9.4; p = 0.57), sensitivity, specificity and accuracy were also
not significantly different for HES and Gelofusine, 66.7% (CI
22.3–95.7), 91.9% (CI 78.1–98.3), 88.4% (CI 74.9–96.1) and 91.7%
(61.5–99.8), 100% (CI 92.3–100), 98.3% (CI 90.8–100), respectively.

123
S104 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

Conclusions: In conclusion, Gelofusine can be considered a suit- PO182


able alternative of HES for WBC separation and labelling, yielding to Imaging joint inflammation in patients with rheumatoid
high WBC labelling efficiency, without cell damage and high diag-
nostic accuracy. arthritis: comparison between
18
F-FDG and 68Ga-DOTANOC

A. Saccomanno2, K.L. Anzola1, C. Lauri2, A. Signore2


PO181
The utility of 99mTc-HMPAO-labeled leukocyte SPECT 1
Nuclear Medicine Unit, Clinica Colsanitas Bogota, Bogota,
in assessing patients with suspected VAD infection Colombia. 2Nuclear Medicine Unit, Department of Medical-Surgical
Sciences and of Translational Medicine, Faculty of Medicine and
M. Siracusa4, N. Quartuccio4, R. Ricapito4, A. Arnone4, A. Vento1, Psychology, ‘‘Sapienza’’ University of Rome, Rome, Italy
R. Laudicella1, M. Pilato2, M. Morsolini2, M. Midiri3, S. Baldari1, Background-aim: PET with 18F-FDG has often been used to study
G. Arnone4 inflammatory processes being a pan-inflammatory marker. However,
FDG is uptaken by many different cell types participating in the
1
Department of Biomedical and Dental Sciences and inflammatory process, as well as by damaged tissues. In the attempt to
Morphofunctional Imaging, Nuclear Medicine Unit, University of find a more specific radiopharmaceutical, the use of radiolabeled
Messina, Messina, Italy. 2Department for the Treatment and Study of somatostatin analogues has been described, both in SPECT and PET,
Cardiothoracic Diseases and Cardiothoracic Transplantation, IRCCS- for the selective imaging of activated lymphocytes expressing SSTRs.
ISMETT, Palermo, Italy. 3Department of Radiology, DIBIMED, Although 111In- or 99mTc-octreotide scintigraphy has demonstrated its
University of Palermo, Palermo, Italy. 4Nuclear Medicine Unit, clinical role in the management of patients with rheumatoid arthritis
ARNAS PP.OO. ‘‘Civico, Di Cristina e Benfratelli’’, Palermo, Italy (RA), there is no study with 68Ga-DOTA-NOC in RA but only some
Background-aim: The cumulative incidence of infection in left- work with 18F-FDG.
ventricular assist device (LVAD) is over 50% within the first The aim of our work was, therefore, to compare, in a pilot study,
3 months after implantation. Infection of VAD is a serious adverse the articular and peri-articular distribution of the 18F-FDG and 68Ga-
event requiring rehospitalization and determines an increased direct DOTA-NOC.
cost for the health system. Any component of VAD can be subject to Methods: We selected 7 patients with newly diagnosed RA, ever
infection, including the pocket site, surgical site, driveline, preperi- treated, with an average age of 60, 5 women and 2 men. The disease
toneal device pocket site and the pump. Since the use of CT and MRI was diagnosed based on the presence of anti-citrulline antibodies and
are of debatable value, due to the presence of metallic artifacts and rheumatoid factor, as well as clinically and by ultrasound. All patients
MRI contraindications, there is an unmet need of a non-invasive performed two Total Body PET/CT scans within 1 week. First with
imaging tool to allow identification of site and extent of infection in 5–7 mCi (185–259 MBq) of 18F-FDG and then with 3–5 mCi
patients with VAD. Autologous leukocyte SPECT has proved useful (111–185 MBq) of 68Ga-DOTA-NOC. On the main joints (shoulders,
in the identification of infection in patients with implantable devices. hips, knees, ankles and carpus), thoracic aorta and gluteus muscle, the
However, particularly in VAD, data in literature are still limited. SUVmax and SUVmean were measured, and then we calculated the
Methods: In this retrospective study, six patients with suspected Targetmean/Aortamean (T/A), and Targetmean/Gluteusmean (T/M)
infection of VAD (based at least on clinical signs, elevated infectious for both radiopharmaceuticals in all joints.
markers or positive blood culture) underwent a total of 10 99mTc- Results: From the qualitative analysis of the images it emerged that
HMPAO-labeled leukocyte planar and SPECT scans at 4 h and 24 h the distribution of 68Ga-DOTA-NOC is mainly on the cartilage sur-
post-injection to evaluate suspected device-related infections (n = 6) face of the joint, while the uptake of 18F-FDG is predominantly
or to assess the efficiency of current antibiotic therapy (n = 4). The external to cartilages and associated with enthesitis and tendinitis.
scans were visually assessed and considered positive in case of Results of quantitative analysis showed that SUVmax of 18F-FDG is
detection of regions of increased radiotracer uptake compared with always higher than that of 68Ga-DOTA-NOC. The behaviour of T/A
adjacent background over time. Microbiological analysis on extracted and T/M ratios is similar, for both radiopharmaceuticals. With pre-
or in situ device or clinical evidence and findings in follow-up ferred to select T/M ratio to avoid possible interferences due to aortic
imaging were used as reference standard to confirm SPECT findings. wall uptake. Choosing an arbitrary threshold of 2 for T/M with 18F-
The mean duration of follow-up after imaging was 2 years. FDG and of 1.5 for T/M with 68Ga-DOTA-NOC, we found a posi-
Results: 99mTc-HMPAO-labeled leukocyte scans resulted positive for tivity in shoulders in 6 cases for 18F-FDG and in 5 cases for 68Ga-
infection in 5/10 cases (4 patients) providing the extent and exact DOTA-NOC, a positivity in knees in 7 cases with 18F-FDG and in 5
location of infection in all patients. Multiple sites of infection were cases with 68Ga-DOTA-NOC, a positivity in ankles in 8 cases with
18
demonstrated in 3/5 scans. Diagnostic accuracy of 99mTc-HMPAO- F-FDG and in 9 cases with 68Ga-DOTA-NOC, a positivity in carps
labeled leukocyte scan for VAD-related infections was 100%. in 10 cases with 18F-FDG and in 10 cases with 68Ga-DOTA-NOC. In
Scintigraphic findings contributed to change the clinical management particular, in 1 shoulder, 3 knees, 3 ankles and 4 carps 68Ga-DOTA-
in 3/4 patients, initially referred under clinical suspicion of VAD- NOC had T/M values higher than 18F-FDG.
related infection, allowing the inclusion in the transplant waiting list. Conclusions: In conclusion, the articular and peri-articular inflam-
Conclusions: In our single-centre experience autologous leukocyte mation in patients with newly diagnosed RA is extremely
scintigraphy demonstrated satisfactory accuracy in detecting VAD- heterogeneous, both for distribution of affected joints and for the
related infections highlighting the site and extent of septic processes degree of uptake of the two radiopharmaceuticals. The intra-articular
and helping patient management. Multicentre-centre studies are and peri-articular distribution of the two radiopharmaceuticals is
warranted to confirm these findings and validate the use of autologous different, expressing two different pathophysiological situations that
leukocyte scintigraphy as a potential guide for clinicians in the may require the use of different drugs.
management of patients with suspected VAD-related infections. Based on results of this pilot study we are now planning an inter-
ventional study in two groups of 23 patients treated with two different
drugs.

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S105

PO183 20 h with time-decay corrected protocol; SPECT/CT at 4 h). All


Sensitivity of the 18-FDG PET/CT for the search procedures were performed within 2-weeks. All pts showed no local
signs of infection, normal WBC counts, increased ESR and/or CRP. 8
of infectious foci in patients with sepsis pts were antimicrobial treatment naı̈ve. Final diagnosis was based on
arthrocentesis (3 pts), microbiological culture from sampling during
A. Farina1, C. Nanni1, A. Lambertini1, M. Maccagnani1, S. Fanti1 single stage prosthesis explantation/reimplantation (E/R) (7 pts) or by
clinical follow-up, at least 12 months (10 pts).
1
Nuclear Medicine Department, Sant’Orsola-Malpighi Hospital, Results: Vascular phase and late images of 3phase-BS were positive
University of Bologna, Bologna, Italy in all pts. WBC showed WBC accumulation stable/decreasing over
Background-aim: To evaluate the sensitività of 18F-fluo- time in 10 and 6 cases, respectively; therefore, all scans were con-
rodeoxyglucose (FDG) positron emission tomography (PET) for the sidered negative for infection. Microbiological cultures confirmed the
search of infectious foci in patients with sepsis. absence of micro-organism in 10 cases. No worsening of the clinical
Methods: This is a single centre retrospective review on patients condition/local signs of infection have been recorded in the remaining
selectect between subjects sent to our operating unit to be undergone 6 pts. WBC showed WBC accumulation increasing over time in 4
to FDG PET/CT between June 2016 and April 2018. Eligibility cri- cases, considered all positive for infection. Microbiological cultures
teria of this review was an already established diagnosis of sepsis. The confirmed the presence of micro-organism in all cases.
PET images were interpreted by a nuclear medicine physician. Conclusions: These small series of patients confirm the role of
Results: Thirty-nine patients were included in this analysis [M: 27%, 3phase-BS in low-risk patients with late hip/knee prosthesis mobi-
F: 12%, median age: 66 years (range 19–84)]. Two patients were lization as screening test to identify patients that will further benefit
subjected for 4 time for FDG-PET/CT; 1 patient was subjected to 3 from 99mTc-HMPAO WBC. A positive 3phase-BS alone is not
time for FDG-PET/CT; 6 patients were subjected twice for exami- sufficient to diagnose septic loosening and 99mTc-HMPAO WBC
nation. The total number of FDG-PET/CT was 53. The previous scintigraphy is mandatory to differentiate between mechanical loos-
bacteriological research showed: 48.8% staphylococcus aureus sepsis, ening associated with intense inflammation from infection.
17.9% methicillin-resistant staphylococcus aureus sepsis, 10.3%
klebsiella sepsis, 7.7% multiple bacterial strains sepsis, 5.1% ente-
rococcus sepsis, 5.1% candida sepsis, 5.1% escherichia coli sepsis. 7 PO185
patients could not undergone the examination for severe conditions
requiring their immediate first aid. The FDG-PET/CT’ reports were Added value of 99mTc-labeled antigranulocyte
35.5% negatives, 33.2% identified a specifics finds (lymphadenopa- monoclonal antibody scintigraphy in association
thy, pulmonary thickening, outcomes for previous known with three phase bone scintigraphy in the evaluation
pathologies), in 12.6% we found accessories (spondylodiscitis, Paget of prosthetic joint infection
disease, necrotic fasciitis), in 10.3% we found known findings, in
3.4% there was uptake in bone for surgery outcomes, 2.5% infection
of heart device, 2.5% uptake on heart valve. M.A. Renna1, R. Armeno1, A. Notaristefano1, G. Berloco2,
Conclusions: Our single-center, retrospective study showed that the A.M. Caponio2, R. Ricciardi1, S. Schiavariello1
18-FDG PET/CT had not a great sensitivity on the overall detection of 1
infectious foci in patients with sepsis. Nuclear Medicine Unit, Rome, Italy. 2Orthopaedics and
Traumatology Department, Rome, Italy
Background-aim: Suspect prosthetic joint infection (PJI) is based on
the presence of many signs and symptoms: acute onset of a painful
PO184 prosthesis, or any chronic painful prosthesis, a sinus tract or persistent
Comparison between three phase bone scan and 99mTc- wound drainage over a joint prosthesis, others.
HMPAO-labelled white blood cell scintigraphy Individuation of a possible PJI is often very difficult and should
in patients with suspicious of HIP or knee prosthetic include a thorough history and physical examination, laboratory tests
(SRE, CPR), diagnostic arthrocentesis, blood cultures, imaging
infected loosening studies.
The aim of this study was to evaluate the sensitivity, specificity,
R. Zanca1, A. Marciano1, F. Bartoli1, T. Depalo1, A.G. Cataldi1, negative predictive value (NPV) and positive predictive value (PPV)
P.A. Erba1, E. Lazzeri1 of 99mTc-labeled antigranulocyte monoclonal antibody scintigraphy
(AMAS) alone or in association with three phase bone scintigraphy
1
Regional Center of Nuclear Medicine, Department of Translational (TPBS).
Research and New Technology in Medicine, University of Pisa and Methods: We have retrospectively evaluated 44 patients (pts) with
AOUP, Pisa, Italy suspected PJI submitted to AMAS and 27 patients submitted to both
Background-aim: The incidence of prosthetic joint infection (PJI) of TPBS and AMAS.
primary implants is approximately 2% and significantly higher in case The sensitivity and specificity, PPV, NPV of each imaging technique
of revision. The differential diagnosis between septic or aseptic were determined and compared with the results of microbiologic and
loosening is very difficult in cases of low-grade nature of infection. histologic analyses, intraoperative findings or clinical follow up (FU)
Three-phase bone scan (3phase-BS) and 99mTc-HMPAO white blood of more than 6 months.
cell scintigraphy (WBC) are used to characterized patients (pts) with Results: Of the 44 pts submitted to AMAS, 26/44 had diffuse or focal
painful prosthesis. In this study, we assessed their respective role in a periprosthetic accumulation of medium–high intensity and these pts
consecutive series of pts with suspected late PJI. were considered positive for PJI at visual analysis. After FU [ 6
Methods: Twelve pts (15 women, 5 men; mean age 68 ± 20 years) months (included clinical FU, microbiologic-histologic analyses or
with suspicious late ([ 24 months) PJI (hip n = 10; knee n = 10) intraoperative findings) we found: 17/26 (66%) pts with mild-intense
were evaluated with 3phase-BS (dynamic and blood-pool images at periprosthetic accumulation had really PJI (very positive); 9/26 (34%)
5 min, late images at 3 h) and WBC (planar images at 30 min, 4 and pts did not have PJI (false positive).

123
S106 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

18/44 pts had insignificant uptake or absent accumulation and were were classified as Takayasu arteritis (TAK), while remaining 56%
considered negative for PJI at visual analysis: 15/18 pts with slight or (older than 50 years) as giant cell arteritis (GCA). Age- and sex-
absent accumulation did not have PJI (very negative); 3/18 pts was matched patients with lymphoma who underwent at least 2 PET/CT in
positive for infection (false negative). the same time interval, without evidence of aortic FDG uptake, were
Of the 27 pts submitted to both TPBS and AMAS: selected as controls (29 Patients). The first and last PET/CT study of
- 12/27 (44.5%): all three phases of bone scan were resulted each patient was independently evaluated by a radiologist (for aortic
positive and AMAS revealed diffuse or focal mild/high periprosthetic diameter measure) and by a nuclear medicine physician who graded
accumulation; these patients were considered positive for PJI at visual aortic FDG uptake using Meller four-points visual scale (0-3), and
analysis. reported scores ‘‘0’’ and ‘‘1’’ as ‘‘negative’’ for LVV, and scores ‘‘2’’
After FU [ 6 months, we found that 10/12 pts with periprosthetic and ‘‘3’’ as ‘‘positive’’ for LVV. Aortic diameter was measured at
accumulation at TPBS and AMAS had PJI (very positive); 2/12 pts ascending aorta, descending thoracic aorta, and abdominal infra-renal
did not have PJI (false positive). aorta. Diameter of [ 4 cm in the ascending aorta, C 4 cm in the
- 12/27 (44.5%) pts had the first 2 phases of TPBS always nega- descending thoracic aorta, and C 3 cm in the infrarenal aorta were
tive, the third phase of TPBS and AMAS revealed slight-mild or reported as vessel dilatation.
insignificant periprosthetic accumulation. After FU [ 6 months, we Results: 93 patients with LVV were included in the study. At first
have found 11/12 pts with slight or absent accumulation did not have PET/CT, the mean (SD) diameter of descending thoracic aorta was
PJI (very negative); 1/18 pts was positive for infection (false negative; significantly higher in LVV patients compared with controls [28.07
patient under antibiotic therapy). (4.40) vs 25.60 (3.59) mm, p = 0.012]. At last PET/CT, after a
- in 3/27 (11%) pts there was no agreement between TPBS and median time of 31 months, patients with LVV compared with con-
AMAS. After FU [ 6 months, 2 patient was resulted positive for PJI trols had higher diameter of ascending [35.41 (5.54) vs 32.97 (4.11)
and 1 pts negative. mm, p = 0.029] and descending thoracic aorta [28.42 (4.82) vs 25.72
Sensitivity of AMAS alone was resulted = 89% and speci- (3.55) mm, p = 0.007] and more frequently had aortic dilatation [19%
ficity = 55%; PPV of AMAS alone = 65% and NPV = 84%. vs 3%, p = 0.023]. Positive aortic FDG uptake (score ‘‘2’’ and ‘‘3’’),
Sensitivity of both TPBS and AMAS was resulted = 92% and disease activity, and elevated inflammatory markers at first PET/CT
specificity = 84%; PPV of both TPBS and AMAS was resulted = were not associated with an increased risk of aortic dilatation. Sig-
85% and NPV = 91%. nificant predictors of aortic dilatation were male sex [OR 7.27,
Conclusions: 99mTc-labeled antigranulocyte monoclonal antibody p = 0.001], and the diameter of ascending [OR 2.03, p \ 0.001],
scintigraphy can be used for imaging acute infections of peripheral descending thoracic [OR 1.57, p \ 0.001] and infrarenal [OR 1.25,
bones and soft tissues. However the association of three phase bone p = 0.005] aorta at first PET/CT study. The results remained
scintigraphy improve the diagnostic accuracy. The false positives of unchanged when the analysis were restricted to the 48 newly-diag-
99mTc-labeled antigranulocyte monoclonal antibody scintigraphy, on nosed LVV patients. Compared to TAK, GCA patients had higher
the other hand, seems to be correlated with the presence of chronic aortic diameter at all 3 levels evaluated in both first and last PET/CT
inflammation and with the expansion of the medullary tissue. study.
Conclusions: Positive aortic FDG uptake at first PET/CT is not
associated with increased risk of aortic dilatation. Patients with LVV
are at increased risk of aortic dilatation compared to age- and sex-
PO186 matched controls, but the most significant predictors of aortic
LVV patients with aortic dilatation: a longitudinal case dilatation are male sex and aortic diameter at first imaging study.
control study using 18F-FDG PET/CT

M. Casali3, F. Muratore5, F. Crescentini6, L. Spaggiari4, L. Boiardi6, PO187


G. Pazzola6, N. Pipitone6, S. Croci7, E. Galli8, R. Aldigeri2,
C. Salvarani1, A. Versari3
Added value of deep lymphatic circulation assessment
in lower limbs lymphoscintigraphy
1
(2) Rheumatology Unit, Azienda Unità Sanitaria Locale-Istituto di
ricovero e cura IRCCS-Reggio Emilia, University of Modena and C. Dolci1, R. Dentici2, A.F. Scarale1, M. Spallino1, C.E. Popescu1,
Reggio Emilia, Italy. 2Department of Medicine and Surgery, M. Cuzzocrea3, L. Monaco3, E. Preza3, M. Milella1, R. Sara1,
University of Parma, Parma, Italy. 3Nuclear Medicine Unit, Azienda E. Gay1, G. Cabrini1, C. Rossetti1
Unità Sanitaria Locale-Istituto di ricovero e cura IRCCS-Reggio
Emilia, Italy. 4Radiology Unit, Azienda Unità Sanitaria Locale- 1
Nuclear Medicine Department, ASST Niguarda Hospital, Milan,
Istituto di ricovero e cura IRCCS-Reggio Emilia, Italy. Italy. 2Nuclear Medicine Department, ASST Rhodense, Caduti
5
Rheumatology Unit, Azienda Unità Sanitaria Locale-Istituto di Bollatesi Hospital, Bollate, Italy. 3Nuclear Medicine Department,
ricovero e cura IRCCS-Reggio Emilia, University of Modena and University Milan Bicocca, Milan, Italy
Reggio Emilia, Italy. 6Rheumatology Unit, Azienda Unità Sanitaria
Background-aim: Lymphoscintigraphy (LSG) is currently used in
Locale-Istituto di ricovero e cura IRCCS-Reggio Emilia, Italy. 7Unit
the investigation of lymphedema but its execution protocol is not
of Clinical Immunology, Allergy and Advance Biotechnologies,
standardized and differs among diagnostic centers. Aim of the study
Azienda Unità Sanitaria Locale-Istituto di ricovero e cura IRCCS-
was to evaluate the value of deep lymphatic circulation assessment
Reggio Emilia, Italy. 8University of Modena and Reggio Emilia, Italy
together with superficial one in lower limbs (LL) LSG.
Background-aim: To evaluate 18F-FDG aortic uptake and aortic Methods: Seventy-eight LL LSGs performed in 78 patients (49
diameter as predictors of vessel dilatation in a longitudinally followed females, 29 males; mean age 38 years, range 10–77) at Caduti Bol-
cohort of patients with large vessel vasculitis (LVV) compared to latesi Hospital from 2016 to October 2018 were retrospectively
controls. analyzed. Clinical indications were suspect primary and secondary
Methods: We included all consecutive patients with LVV who lymphedema in 63 and 15 patients respectively. Deep lymphatic
underwent at least 2 PET/CT scans between January 2008 and May circulation was investigated first: a single deep injection of 2mCi
2015. 44% of Patients (younger than 50 years at symptoms’ onset) technetium-99m labeled albumin nanocolloids in the plantar arc of

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S107

each foot was performed and scintigraphic planar images were nodes were afterwards sent to pathologists for examination. Before
obtained at 5 and 25 min, after centripetal stimulation (prolonged the procedure, a written informed patient’s consent was obtained.
walking). Then superficial circulation was examined with the same Results: The OCC localizations were found to be the following:
protocol after multiple subcutaneous injections in the first and fourth tongue (11/19) retromandibular trigon (1/19), upper right dental arch
interdigital spaces and in the peroneal malleolus area (2 mCi overall (2/19), left dental arch (2/19), oral floor (1/19), palate (2/19). A
for each foot). Pathologic findings were abnormal transit time to standard lymphatic spreading, ipsilateral to the OCC (II–IV), was
regional nodes and dermal backflow. observed on LS in all but 8 cases (42.10%); patients who were found
Results: Eighteen out of 78 LSGs (23%) were negative, while 60/78 to present atypical lymphatic drainage showed involvement of the
(77%) were positive for alterations of LL lymphatic system. Among contralateral side (Ib, II (2), IIA, IV (2), III and V respectively) with
positive LSGs, only 3/60 (5%) showed alterations of superficial documented metastases in 3 cases (37.5%). Overall, lymph node
lymphatic circulation alone; 29/60 (48%) LSGs showed alterations of metastases were observed in 7 cases (34.84%): 4 in patients with
both deep and superficial circulation, while in 28/60 cases (47%) ipsilateral drainage (IIA, II, IV) and 3 (42.85%) in patients with
pathologic findings concerned only the draining capacity of deep contralateral drainage in an atypical lymph node compartment (II–III,
lymphatic system. In twenty-five out of 28 (89%) LSGs with deep V).
lymphatic system impairment alone, signs of superficial compensa- Conclusions: Although the results of our study are limited and pre-
tion were observed as early visualization of superficial lymphatic liminary, we found that the lymphatic drainage from OCC can be
channels and/or lymphnodes after radiotracer deep injection, with or abnormal, namely contralateral to tumor site in cervical region, in a
without superficial circulation iperplasia. non-negligible percentage of cases with possible cervical lymph
Conclusions: In Our series only few patients presented abnormal nodes metastatic involvement. LS should thus be taken into consid-
findings of superficial lymphatic circulation alone. Most patients eration as a useful tool to properly map the lymphatic drainage from
presented alterations of deep circulation, with or without concomitant OCC, allowing a selective and modified lymphadenectomy with
alterations of superficial one: in these cases assessment of superficial potential benefits both for patients in terms of more accurate staging
circulation alone could cause lack of relevant clinical information. and better disease management, and for health services in terms of
Therefore in LL LSG, despite a little more discomfort for patients, it’s costs. Our findings should be confirmed in a larger population.
preferable to investigate both deep and superficial circulation as fre-
quently alterations of deep circulation are totally offset by a
superficial one that functionally corrects a deficiency of primary or
secondary nature. PO189
Radio-guided lung lesion localization: introducing
a fluoroscopy system in a SPECT/CT scan
PO188
R. Durmo2, M. Lechiara4, D. Benetti5, C. Rodella1, L. Camoni2,
Lymphoscintigraphy (LS) in oral cavity cancer (OCC) D. Albano2, F. Bertagna3, R. Giubbini3
as a tool for a tailored surgical approach through
1
selective and modified lymphadenectomy: preliminary Department of Medical Physics, Spedali Civili di Brescia, Brescia,
results Italy. 2Nuclear Medicine Department, Spedali Civili Brescia, Brescia,
Italy. 3Nuclear Medicine Department, University of Brescia, Brescia,
Italy. 4Radiology Department, Spedali Civili Brescia, Italy. 5Thoracic
S. Panareo1, M. Nicola2, C. Cittanti1, I. Rambaldi1, I. Santi1,
Surgery Department, Spedali Civili Brescia, Brescia, Italy
S. Pelucchi2, M. Bartolomei1
Background-aim: Video-assisted thoracoscopic surgery (VATS) is
1
Nuclear Medicine Unit, Department of Oncology/Medicine- now the procedure of choice for surgical biopsy and removal of
Specialistic, University-Hospital of Ferrara, Ferrara, Italy. peripheral lung nodules. Nevertheless, the use of VATS can be dif-
2
Othorinolaryngoiatry Section, Department of Specialistic Surgery, ficult in the case of small, non solid, or deep lung nodules. The
University-Hospital of Ferrara, Ferrara, Italy purpose of this study was to report our experience in the use of
radiotracer localization and resection of small, indistinct, or non
Background-aim: The purpose of this study was to assess the role of
palpable pulmonary lesions. We developed an innovative technique
LS as a simple, accessible and cost effective technique for improving
installing a fluoroscopy system to a SPECT/CT scan that allowed to
OCC staging, surgical appropriateness and tailored approach to cer-
perform CT-guided injection of radiotracer in the nuclear medicine
vical lymph node dissection. We assessed the lymphatic drainage of
department.
selected OCC cases through LS, identifying patients with a lymphatic
Methods: Patients were selected for the radiotracer procedure when
drainage beyond the compartment classically included in tumor sur-
there was anticipated difficulty in VATS locating their nodules. Under
gery, extending lymphadenectomy to the side of abnormal drainage
CT-guide in or near the nodule 0.2 mL of 99TC-MAA (human serum
followed by evaluation of the metastatic status of excised lymph
albumin macroaggregates labelled with 15 MBq eluated 99TC) and
nodes.
0.3 mL nonionic iodinated contrast was injected. All CT-guided
Methods: From June 2015 to November 2018 we enrolled 19 patients
radiotracer injections were confirmed with SPECT/CT. During the
(7 female, 12 male, median age 63 ± 0.8 years) affected by OCC,
VATS procedure, an endoscopic gamma detecting probe was intro-
scheduled for elective surgery and without documented lymph node
duced to scan the lung surface. The area of major radioactivity, which
involvement (N0). The day before surgery all underwent LS with
matched with the area of the nodule, was resected.
acquisition of planar and SPECT/CT images of head and neck regions
Results: Between January 2016 and October 2018, 37 patients (22
after peritumoral administration of 99mTc-nanocoll (median
male and 15 females) with median age of 64 years (range
74 ± 1.2 MBq), documenting lymphatic drainage. Patients under-
27–83 years) underwent CT-guided radiotracer injection. The mean
went tumor excision and lymphadenectomy of affected laterocervical
nodule size was 11 mm (range 4–24 mm). The mean distance of the
compartment (depending on tumor localization) and radioguided
nodule to the nearest pleural surface, as measured in CT, was 18 mm
surgery of additional sites as indicated by LS. Tumor and lymph
(range 0–65 mm). On the CT the nodules morphology characteristics
presented were: 15 nodules ground glass, 12 solid and 10 partly solid.

123
S108 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

No significant adverse events occurred. Thirty-six patients had suc- the sensitivity of millimeter-sized tumour remnants. All the tumor
cessful localization of the nodules and one case presented a diffuse samples showed high counts of radioactivity, with difference from
extravasation of the tracer. In the patient with extravasation of the surrounding healthy tissues. The radioactivity in the tumour samples
tracer the surgeon decided to abandon the surgery. Thirty-five patients was between 4.5 and 17 9 greater than the background activity. In
underwent VATS and in one patient the surgeons decided for an open one patient, 11 surgical removed NET lesions identified on CT (8
thoracotomy after unsuccessfully VATS. Overall, lobectomy was lesions) or 68Ga-DOTATOC PET/CT (11 lesions) were found to have
performed in 2 patients, segmentectomy in 1, and wedge resection in foci of elevated activity at RGS. The abdomen CT missed 1 periph-
33 patients. No mortality occurred. The pathological diagnosis was 15 eral nodule and 2 nodules at the hepatic hilum but the complementary
(42%) primary lung cancer, 8 (22%) metastases and 13 (36%) benign evaluation of 68Ga-DOTATOC PET/CT increased the overall
lesions. accuracy.
Conclusions: Radiotracer localization of pulmonary lesions is a Conclusions: These first ex vivo RGS tests showed that through this
simple and feasible procedure with a high rate of success. In our probe we can discriminate very strongly between tumor and nearby
knowledge we are the first group who developed and successfully healthy tissues by the administration of low activities of 90Y-
used fluoroscopy system in a SPECT/CT scan. DOTATOC. We present the final results in NET and meningioma
patients, as it is well known that a complete surgery could better the
prognosis of this disease. Further developments of the probe could
increase its sensitivity, in order to reduce the dose for a given
PO190 administered activity. The association of CT and 68Ga-DOTATOC
Final results from ex-vivo experience in radioguided PET/CT in NET patients remain mandatory to obtain a correct min-
surgery technique with beta-radiation in meningioma imal invasive surgery.
and neuroendocrine patients

C.M. Grana7, M. Colandrea7, R. Faccini6, E. Solfaroli Camillocci6, PO191


E. Bertani10, F. Collamati5, E. Pisa8, L. Funicelli9, S.M. Baio7, The lymphoscintigraphic study of unpredictable head
S.L. Fracassi7, L. Gilardi7, P.A. Rocca7, L.L. Travaini7, M.E. Ferrari4,
S. Papi7, S. Morganiti5, M. Schiariti2, P. Ferroli2, M. Cremonesi4,
and neck cutaneous melanoma lymphatic drainage
C. Fodor1, G. Buonsanti7, M. Chinol7, N. Fazio3, B. Pollo2, R. Mei7
C. Altini1, A. Niccoli Asabella1, R. Ruta1, A. Branca1, G. Santo1,
1
Data Management, IRCCS European Institute of Oncology, Milan, G. Bianco1, G. Rubini1
Italy. 2Fondazione Istituto Neurologico Carlo Besta, Milan, Italy. 1
3
Gastrointestinal and NET Medical Oncology Division, IRCCS Nuclear Medicine Unit, Interdisciplinary Department of Medicine,
European Institute of Oncology, Milan, Italy. 4Health Physic, IRCCS University of Bari ‘‘Aldo Moro’’, Bari, Italy
European Institute of Oncology, Milan, Italy. 5Istituto Nazionale di Background-aim: Head and Neck Cutaneous Melanoma (HNCM)
Fisica Nucleare, Rome, Italy. 6Istituto Nazionale di Fisica Nucleare, does not always follow a standard lymphatic drainage; typical
Dip. Fisica, Univ. di Roma ‘‘La Sapienza’’, Rome, Italy. 7Nuclear expected lymphatic pathways are associated with unexpected ones.
Medicine Division, IRCCS European Institute of Oncology, Milan, The lymphatic drainage pathway of the head and neck is not pre-
Italy. 8Pathology Division, IRCCS European Institute of Oncology, dictable due to the high anatomical complexity of this region in which
Milan, Italy. 9Radiology Division, IRCCS European Institute of are present many organs and more than 300 lymphnodes. Furthermore
Oncology, Milan, Italy. 10Surgery Division, IRCCS European expected and unexpected lymphatic drainage pathways are different
Institute of Oncology, Milan, Italy according to the primary HNCM localization. The aim of this study
Background-aim: Introduction: Radioguided surgery (RGS) is a was to investigate by lymphoscintigraphy the relation between the
technique aimed at assisting the surgeon to reach a complete resection primary HNCM sites and all the possible lymphatic drainage path-
of the tumour, while minimizing the amount of healthy tissue ways with special focus on the unexpected sentinel lymphnodes
removed. RGS with beta-radioisotopes, as 90Y, is a novel approach (SLNs) detection.
focused on developing a new probe which, detecting electrons and Methods: 42 patients (29 M, 13 F; mean age 50 years) who under-
operating with low background, provides a clearer delineation of the went lymphoscintigraphy from January 2013 to November 2018 were
margins of lesions with low radiation exposition for surgeons. retrospectively analyzed. 99mTc-serum albumin was injected intra-
Aim: To validate this RGS procedure, tests on ex vivo specimens of dermal at the dose of 18–37 MBq in 0.2–0.4 ml; the dose was divided
tumors expressing somatostatin receptors as brain meningioma and in 2 to 4 visible wheal at the distance of 5 mm from the tumor margin
gastro-entero-pancreatic neuroendocrine tumors (GEP NET) were or scar. All patients underwent dynamic and static images acquisition
performed. in order to identify the SLNs. HNCMs were distributed in 18 different
Methods: We studied these tumors due to the high uptake of a beta- anatomical regions. For all patients the relation between the expected
emitting radiotracer already in use in clinical practice as 90Y- and unexpected SLNs was performed using the ‘‘Sidney Melanoma
DOTATOC. Patients were enrolled according to the tumour Standard Unit Database’’ (https://sites.bioeng.auckland.ac.nz/hrey004/head/
Uptake Value (SUV [ 2) and the expected Tumour to Non-tumour index.html) as reference. The relation was performed also according
Ratio (TNR [ 10) estimated from 68Ga-DOTATOC PET/CT images. to the primary HNCM localization.
So far, after giving written informed consent, 4 meningioma and 5 Results: In 24/42 (57%) patients SLNs were detected only in pre-
GEP NET patients, received 68Ga-DOTATOC/PET, and entero-CT dictable sites, while in 18/42 (43%) unexpected SLNs have been
scan, 2 weeks prior to surgery. Twenty-four hours before surgery, revealed; of these 18 patients, 7/18 (39%) showed both expected and
meningioma pts received a median activity of 4.5 mCi; NET pts unexpected SLNs, while the other 11/18 (61%) showed only unex-
received 5 mCi of 90Y-DOTATOC. pected SLNs.
Results: Surgery was performed as clinical and radiological indi- A total of 74 SLNs in the 42 patients have been detected: in 18/42
cated. Tumors and the around tissues were sectioned in different (43%) patients only one SLN has been detected, in 14/42 (33%) two
samples and were examined with the beta- detecting probe to assess SLNs and in 10/42 (24%) more than two SLNs were identified. The
74 SLNs belonged to 11 different drainage lymphatic sites. 50/74

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S109

(67.6%) SLNs have been found in the expected regions, 24/74 PO193
(32.4%) in unexpected regions. The role of intradermal-stress-lymphoscintigraphy
About the 24 unexpected SLNs, 12/24 (50%) SLNs have been
localized in the parotid region, 3/24 (12.5%) in retromandibular for differential diagnosis between lipedema
region, 3/24 (12.5%) in the submandibular region, 2/24 (8.3%) in and primary lymphedema
supraclavicular, 2/24 (8.3%) in the retroclavicular region and 2/24
(8.3%) in the retroangularmandibular region. G. Tartaglione1, F.P. Ieria1
The unexpected SLNs derived from HNCM localized in ear (3/24
1
SLNs, 12.5%), temporal region (2/24 SLNs, 8.3%), preauricular (4/24 Department of Nuclear Medicine, Cristo Re Hospital, Rome, Italy
SLNs, 16.8%), retroauricular (3/24 SLNs, 12.5%), cheek (2/24 SLNs,
Background-aim: Lipedema is a chronic fat disease characterized by
8.3%), laterocervical (2/24 SLNs, 8.3%), nose (2/24 SLNs, 8.3%),
a symmetric and bilateral enlargement of the lower limbs extending
jaw (2/24 SLNs, 8.3%), frontal region (2/24 SLNs, 8.3%), glabella (1/
from hips to ankles, classically sparing the dorsum of the feet.
24 SLNs, 4.2%) and parietal-occipital region (1/24 SLNs, 4.2%).
Lipedema is not caused by a disorder of the lymphatic system;
Conclusions: The HNMC lymphatic drainage is extremely variable
however, it is frequently misdiagnosed as bilateral primary lym-
as regards both sites and number of involved SLNs. The lym-
phedema. We propose the Intradermal-Stress-Lymphoscintigraphy for
phoscintigraphic study is mandatory to identify all the possible SLNs
differential diagnosis and for evaluation of lymphatic drainage dam-
in order to perform an accurate staging for all patients and to avoid
ages in advanced clinical stages of Lipedema (Lipo-Lymphedema).
missing the unexpected SLNs.
Methods: 36 women with a suspected lower limbs lipedema were
enrolled. Two doses of 50 MBq of 99mTc-HSA-nanocolloidal in
0.4 mL were injected intradermally at the first intermetatarsal space
PO192 and at the lateral malleolus. Two planar static scans at rest were
Cutaneous melanoma patients with unexpected sentinel acquired immediately after tracer injection. Stress scans were
acquired after stepping for 2 min. After that, the patients underwent
nodes: role of SPET/CT in radio-guided research prolonged muscular exercise (walking) limited by symptoms, and
later scans were acquired at 60 min to visualize regional lymph nodes
V. Lavelli1, A. Niccoli Asabella1, G. Bianco1, A. Ungaro1, and the effects of sustained muscular exercise. Body Mass Index and
A. Gaudiano1, A.R. Pisani1, N. Addante1, G. Rubini1 Transport Index were evaluated.
Results: The test showed: a normal visualisation of lymphatic path-
1
Nuclear Medicine Unit, Interdisciplinary Department of Medicine, ways at resting scan in 45% (32) limbs (a tortuous course of lymph
University of Bari ‘‘Aldo Moro’’, Bari, Italy pathway of legs was observed); the presence of collaterals in 19%
Background-aim: One of the main prognostic factor in Cutaneous (14) limbs; an unusual uptake of popliteal nodes in 25% (18) limbs;
Melanoma (CM) is the lymph nodal metastasis. Lymphoscintigraphy and a tracer stagnation area in 11% (8) limbs. The mean Body Mass
is the most important investigation allowing the study of lymphatic Index was 37.54 (nv \ 25). The mean Transport Index was 7
drainage pathways, not always predictable. It detects the sentinel (nv \ 10).
node, intended as the first lymph node (LN), located in a basin Conclusions: The Intradermal-Stress-Lymphoscintigraphy in lipe-
receiving lymphatic fluid from a specific cutaneous region. These dema patients showed a bilateral early and good visualisation of
basins can be in ‘‘classic’’ or in ‘‘unexpected’’ regions. Some authors lymphatic pathways and inguinal lymph nodes at resting scan, in
proposed the nomenclature of ‘‘interval’’ LN, intended as LNs iden- larger number of cases. A tortuous course of lymph pathway of legs
tified between the cutaneous region and the ‘‘classic’’ basin, and they was frequently observed, probably because the lymph path adapts its
have demonstrated that the ‘‘interval’’ LNs have the same chance of course to increasing presence of subcutaneous fat. At stress scan we
being the site of metastatic invasion as in classic basins. The aim of observed a frequent presence of collaterals, and/or unusual uptake of
this study is to evaluate the role of SPET/CT in identifying ‘‘unex- popliteal nodes, as minor signs of lymphatic disorder. Only in
pected’’ locations of sentinel nodes advanced clinical stages of Lipedema we visualized tracer stagnation
Methods: 128 patients (59 F and 69 M) underwent lymphoscintig- areas or lymphangiectasia at delayed scan, due to an abnormal lym-
raphy from April 2017 to April 2018. 99mTc-human serum albumin phatic drainage secondary to Lipedema (Lipo-Lymphedema).
(Nanocoll, GE Healthcare, USA) was injected intra-dermal at the
dose of 18–37 MBq in 0.2–0.4 ml. According to surgical time, 1 or
2 days protocol and site of injection, a dynamic acquisition followed PO194
by planar and SPET/CT was performed in all patients using Dis-
covery NM/CT 670 Pro (GE Healthcare, USA). All patients has a Added value of the double superficial and deep
confirmed histologic diagnosis of CM performed on the previous lymphoscintigraphy in patients with lymphedema
excision of suspected skin lesion
Results: A total of 128 lymphoscintigraphy were performed. The sites M. Povolato2, A. Onorato1, F. Giacomuzzi2, G. Ferretti2,
of the lesions were as follow: back in 39 pts (30%), chest in 12 pts D. Capobianco2, M. Rensi2, B. Crema2, F. Di Gregorio2
(9%), abdomen in 9 pts (7%), head and neck in 11 pts (9%), upper
1
limbs in 19 pts (15%) and lower limbs in 38 pts (30%). Unexpected Medicina Fisica e Riabilitazione-Associazione Lotta al Linfedema-
lymphatic drainage was detected in and 11 pts (9%) with final evidence Udine, Italy. 2Nuclear Medicine Unit, University/Hospital of Udine,
of interval LNs. SPET/CT detected the exact location of all interval Udine, Italy
LNs. 13 lymph node biopsies performed in the 11 pts with interval
Background-aim: Lymphedema is the abnormal accumulation of
LNs, resulted positive for metastatic nodal invasion in 3 of them
fluid within the soft tissue and is a chronic disease that affects over 2
Conclusions: SPET/CT is an important tool for anatomically accurate
million people in Italy. Lymphedema may be due to impaired lym-
detection of Sentinel Nodes in ‘‘unexpected’’ regions. SPET/CT
phatic drainage not only in the superficial system but also in the deep
images are better the planar ones, thank to the anatomic information,
district or both. Lymphoscintigraphy is a well tolerated imaging
that can affect positively the LN’s research and excision, improving at
the same time operators’ confidence. method to diagnose upper and lower extremity lymphedema, but

123
S110 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

usually only the superficial system is studied and the deep lymphatic metastatic nodes were found only in 4 out of 11 positive pts. At 5-year
system deficiency may be undiagnosed. follow-up we observed: Local recurrencies in 5 pts, Local and Neck
Aim of this study is to assess the diagnostic performance of double recurrencies in 1 pt, Local and distant recurrencies in 2 pts. In the
superficial and deep lymphoscintigraphy and its efficiency in the cohort of 29 out of 40 pts with SN negative only 1 pt had a recurrence
diagnosis of deep extremity lymphedema. on the contralateral neck. Outcomes in SN-were: alive no disease 85%
Methods: 32 Patients (22 Females and 10 Males) affected by lym- (24 pts), alive with disease 3.5% (1 pt), dead with disease 7% (2 pts),
phedema were analyzed. Deep and superficial lymphoscintigraphies dead no disease 3.5% (1 pt). Outcomes in SN ? were: alive no dis-
were performed in separate days using a simultaneous bilateral ease 73% (8 pts), dead with disease 18% (2 pts), dead no disease 9%
injection of 70 Tc-99 m-labelled albumin nanocolloid in each foot or (1 pt). One pt lost for follow up. At 5-year follow up SN demonstrated
hand. For the superficial lymphatic imaging the injection was sub- an Accuracy of 97.5%, and NPV 96.5%.
cutaneous in the first interdigital space; while for the deep lymphatic Conclusions: Our experience confirms the high accuracy of SN
system imaging the injection was sub-fascial in the proximal part of biopsy in predicting the presence of occult metastases in OSCC,
hand palm or the foot plant. Lymphoscintigraphy scan was started as allowing to spare unnecessary neck dissection in over 70% of cases.
static and whole body imaging at 10 min, 1 h and 2 h after injection. The dynamic and early scan and a same-day protocol are designed to
The patients stimulated lymphatic drainage after injection and waiting easy differentiate SNs (which are almost always on NLs I–III) from
for the scans by following a standardized protocol of active muscular second-tier lymph nodes. That allows to limit the number of nodes
exercise. The scans were analyzed for visualization of lymph vessels examined and the extension of the surgical approach, without
and lymph nodes, dilatation of lymphatic vessels and existence of reducing sensitivity.
collateral vessels. ROIs were drawn on injection sites and inguinal or
axillary nodes to quantify the lymphnode to injection site ratio at 1 h
by geometric mean method which was expressed as percentage
(normal value [ 14% of injected dose). PO196
Results: Double lymphoscintigraphy showed disease in only the Rationale for lymphoscintigraphic study of deep
superficial district in 6 patients, disease only in the deep district in 7 lymphatic vessels for the diagnosis and management
patients and both superficial and deep disease in 19 patients. Double
of peripheral lymphedema
lymphoscintigraphy demonstrated disease in the deep district in 26
out of 32 patients (81%) and was able to individual lymphatic disease
otherwise not diagnosed in 7 patients (21%). V. Ceriani2, C.C. Campisi1, M. Pennone2, S. Raffo2, F. Boccardo3,
Conclusions: Our data show that double superficial and deep lym- G. Sambuceti2, G. Villa2
phoscintigraphy is a a very useful diagnostic tool in patients with 1
lymphedema for diagnosis of deep lymphatic system. In this setting of Plastic, Reconstructive and Aesthetic Surgery, Lymphatic Surgery
patients double lymphoscintigraphy may provide reliable informa- and Microsurgery, Department of Surgery (DISC), Policnical
tions to modify prognosis and therapeutic approach. Hospital San Martino, Genoa, Italy. 2U.C. Nuclear Medicine,
DISSAL, Policlinical Hospital San Martino, Gena, Italy. 3Unit of
Lymphatic Surgery and Microsurgery, Department of Surgery
(DISC), Policnical Hospital San Martino, Genoa, Italy
PO195 Background-aim: Microsurgery for lymphedema is firmly estab-
Sentinel node in oral cancer, a 15-year single center lished as an effective long-term treatment for peripheral lymphedema.
experience It is important now to clarify which type of microsurgery is the most
appropriate for which patient. Aim of our study is the examination of
G. Tartaglione2, M.G. Vigili1 the lymphatic flows in affected limbs by lymphoscintigraphy in order
to develop a surgical treatment algorithm based on grade of lymphatic
1
Department of ENT, San Carlo GVM Hospital, Rome, Italy. impairment.
2
Department of Nuclear Medicine, Cristo Re Hospital, Rome, Italy Methods: We considered 450 subjects with clinical mono- or bilat-
eral lymphedema. All patient underwent a lymphoscintigraphy in
Background-aim: Data from literature show a significant incidence double day for the study of the superficial (subcutaneous injection of
of occult metastases in oral cancer. We report a single-centre usage of 99mTc-Nanocoll) and deep circuits (subfascial injection). The
Sentinel Node (SN) biopsy in cT1-T2N0 Oral Squamous Cell Car- transport index (TI) was calculated to categorize the flow of the
cinoma (OSCC) over a 15-year period. superficial and deep vessels as normal (\ 10) or pathological (greater
Methods: From July 2004 to December 2012, 40 pts (21 f, 19 m, or equal to 10). A total of 352 patients demonstrated a pathological
mean age 65.57 years) with cT1-T2N0, OSCC were enrolled. A dose segmental lymphoscintigraphy. The relationship between clinical
of 99mTc-nanocolloids, 70–100 mBq, 0.4 ml, was injected superfi- presentation and TI was also investigated.
cially in four points around cancer and dynamic, early and late scan Results: In general, the deep lymphatic pathways were more
were acquired immediately after tracer injection. A radio-guided SN adversely affected with worse TI for the upper and lower limbs. 86%
biopsy was performed during surgery, using a same-day protocol. The of patients with lymphedema had either deep lymphatic vessel
minimum follow-up was 5 years. Patients with negative SN were abnormalities or deep and superficial abnormalities and only 14% of
followed every 3 month by US. patients had superficial vessel injury alone. The patients demonstrated
Results: SNs were found in all pts. A total of 88 SNs (mean 2.2/pt) deep abnormality alone in 42%. This trend was even more evident for
were biopsied. The SNs were found at NL I 31.8% (28 SN), at NL II bilateral leg lymphedema with 96% with deep vessels affected (either
48.9% (43 SN), at NL III 17% (15 SN), and at NL IV–V 2.2% (2 SN). alone or also with superficial) and 4% with only superficial vessels
Metastases were found in 11 out of 40 pts (27.5%). The positive SN affected. Whereas 58% of patients with primary lymphedema had a
were localised on NL I in 3 cases, on NL II in 6 cases, on NL III in 1 match between clinical problem and the lymphoscintigraphic find-
case, and on NL IV-V in 1 case. All positive SNs were identified by ings, 42% had bilateral lymphoscintigraphic abnormalities but
step serial sectioning and routine H&E staining. An Elective Neck unilateral clinically-apparent swelling. Instead, for patients with
Dissection (END) was performed in 11 Pts with a positive SN, and secondary causes of lymphedema, 88% had a match between the
adjunctive 478 nodes of the neck were dissected. After END further

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S111

clinical swelling and the lymphoscintigraphy abnormalities but 12% a difficult anatomic district. Further larger studies are needed to
demonstrated bilateral problems on lymphoscintigraphy and unilateral confirm these results.
swelling.
Conclusions: Given that most patients have a pathological TI for the
deep lymphatic vessels, a surgical approach that anastomoses only the
superficial vessels is unlikely to be effective. These results suggest PO198
some percentage of patients with primary but also secondary lym- Preoperative lymphoscintigraphy: what is behind
phedema have an underlying vulnerability to the lymphatic vessels, imaging?
which predisposes them to lymphatic injury. We must consider the
possibility that a significant percentage of patients undergone a sur-
F. Mattana1, A. Paccagnella1, M. Levorato1, G.M. Lima1,
gical intervention and then developing a lymphedema were
R. Bonfiglioli1, S. Fanti1
inaccurately considered in the group of ‘secondary’ lymphedema,
instead in a primary, with a congenital lymphatic malformation. 1
S. Orsola Malpighi Hospital, Bologna, Italy
Background-aim: Breast cancer is the most common cancer affect-
ing woman worldwide. Axillary lymph node metastases (ALNM) are
PO197 the most important predictors of survival in these patients, therefore
99m
Tc-Tilmanocept (lymphoseek): a new receptor- the identification and analysis of the sentinel lymph node (SLN) are
targeted tracer in head and neck lymph nodes mapping essential to set up a correct therapeutic program. Preoperative lym-
phoscintigraphy (PLS) is a well-established imaging tool for lymph
in vertex melanoma nodes mapping. Different studies described the predictive value of
several tumor factors (TF: tumor size, tumor grade, proliferation
M. Maccauro1, G. Aliberti1, R. Patuzzo1, G. Agiroffi1, A. Lorenzoni1, index-Ki-67, estrogen receptors-ER, progesterone receptor-PR,
A. Maurichi1, G. Gallino1, M.R. Castellani1, M. Santinami1, human epidermal growth factor receptor 2-HER-2 expression and
E. Seregni1 lymph vascular invasion-LVI) for lymph nodes metastatic infiltration,
1
but these correlations are still discussed. Our aim was to study the
Fondazione IRCCS Istituto nazionale Tumori, Milan, Italy feasibility of preoperative lymphoscintigraphy (PLS) in detecting
Background-aim: In head and neck cases the albumin-based colloid positive uptake in axillary lymph nodes and its possible correlation
drainage is frequently unpredictable. The non-selective nature of with sentinel lymph node metastasis (SLNM). We also tried to
conventional sentinel lymph node (SLN) localization results in a high evaluate the correlation between metastatic lymph nodes seen in PLS
number of identified nodes with a long and complex surgical proce- and TF.
dure. Lymphoseek is a new promising option for elective neck Methods: We retrospectively reviewed the files of 51 breast cancer
dissection. The 99mTc-Tilmanocept confers an high affinity for the women who underwent PLS (with subcutaneous peritumoral injec-
CD-206 receptor protein, highly concentrated on macrophages and tion) for SLNM biopsy at our institution between January and May
dendritic cells’ surface. This radiotracer shows a rapid clearance and 2017. Oncology and surgical reports were used to collect PLS data
has the capability to selectively accumulate in few nodes, with limited and the TF. PLS was performed according to standard procedures
pass-through to second-echelon (station) nodes. The aim of this study using a SPECT/CT camera (Discovery 670, GE Healthcare) after
is to evaluate the drainage pattern detection using 99mTc-tilmanocept subcutaneous peritumoral injection of (99m)Tc-Nanocoll. Pearson
in head melanoma patients. correlation coefficient was used for statistics analysis.
Methods: Five patients with histologically proven head melanoma Results: In the cohort of 51 women, the mean age was 60 (range
underwent sentinel lymph node localization by 99mTc-tilmanocept 40–88). 11/51 were excluded because of previous therapeutic treat-
scintigraphy. The radiopharmaceutical was locally injected in four ments (surgical and neo-adjuvant chemo-therapy) to rule out possible
aliquots, administering either 74 MBq to patients who underwent interference in the lymphatic drainage. Out of 40, 15 patients (37.5%)
surgery the day after or 18.5 MBq the same day. Then LN were had only one lymph node visualized at PLS, 25 patients (62.5%) more
identified and localized by static planar scintigraphy and SPECT/CT than one, with the best sensitivity for all the patients in mapping
scan 20 min after the administration. Intraoperative localization of lymphatic drainage. In all the 40 patients examined, the ratio of
radioactive LN was performed by a hand-held gamma-probe set on SLNM was 30% (12/40). Out of 40, 34 (85%) were classified as T1, 6
99 mTc energy peak. Once localized radioactive lymph nodes were (15%) as T2, 15 (37.5%) as G1, 16 (40%) as G2 and 9 (22.5%) as G3.
excised and analyzed. Low positive correlation was found between the number of lymph
Results: All the patients showed bilateral cervical lymphatic drainage node seen at PLS (1 versus more than 1) and SLNM; in patients with
at planar and tomographic acquisitions. No radiopharmaceutical more than 1 lymph node the ratio of SLNM was 32%, in those with
spreading on the site of injection was detected. Number of detected only one 26%. Regarding to the correlation between the SLNM and
lymph node per patient was 2.9 (mean value, 1 node per anatomical TF, the most significant factor in influencing a positive histology
region) (range 1–4 nodes), localized in the following regions: lymph node appeared to be the tumor size, with an increasing rate
preauricular, submandibular and lateral cervical region. A good cor- from T1 (7/34 patients = 20.5%) to T2 (5/6 patients = 83%). This
respondence (90%) was found between scintigraphic LN mapping and correlation was weaker when considering tumor grade: G1 2/15
intraoperative nodal identification. The histological examination of (13%), G2 7/16 (44%), G3 3/9 (33%). The statistical analysis also
resected LN showed metastatic neoplastic cells in one patient (one out showed a low positive correlation between high Ki-67 index (8/20;
of two nodes detected, on third right lateral cervical region). 40%) and HER-2 expression (3/6; 50%) with SLNM.
Remaining findings were free from metastasis. Conclusions: The main role of PLS is still the anatomical mapping of
Conclusions: Compared to our routinary experience with albumin lymphatic drainage. Further studies are needed to better understand
colloids tracers, Lymphoseek showed a more rapid, uptake by LN, how PLS can predict SLNM, but according to our data there seems to
with high retention in first stations and fewer selective uptake in be a correlation between the number of lymph node visualized and the
second echelon nodes. Lymphoseek, allowing manageable surgical in risk of SLNM, although biased by short population. Regarding to
lymphatic drainage, some studies described the stimulation of neo-
lympho-vascular angiogenesis by tumor growing factors releasing,

123
S112 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

while others described the blockage of drainage related with tumor PO200
size. It should be useful to investigate which is the balance between A machine learning segmentation approach
these two mechanisms and how they may influence PLS.
for the extraction of radiomic features in PET studies

G. Russo3, A. Stefano3, A. Comelli2, S. Bignardi1, M.G. Sabini4,


PO199 P. Alongi6, A. Yezzi1, M. Ippolito5
Nuclear medicine technician external exposure
1
from patients undergoing PET/CT and whole body Department of Electrical and Computer Engineering, Georgia
Institute of Technology, Atlanta, USA. 2Department of Industrial and
bone scans Digital Innovation, University of Palermo AND Fondazione Ri.MED,
Palermo, Italy. 3Institute of Molecular Bioimaging and Physiology,
E. D’augello1, L. De Luca1, S.G. Modoni1 National Research Council (IBFM-CNR), Cefalù, Italy. 4Medical
Physics Unit, Cannizzaro Hospital, Catania, Italy. 5Nuclear Medicine
1
University Hospital Ospedali Riuniti, Foggia, Italy Department, Cannizzaro Hospital, Catania, Italy. 6Nuclear Medicine
Background-aim: In the diagnostic activity of a Nuclear Medicine Department, Giglio Hospital, Cefalù, Italy
Unit, the risk of external exposure from injected patients may vary Background-aim: Radiomics on PET, including semi-quantitative
significantly depending on the type of examination to which the (SUV, SUL, MTV, TLG, etc.), first-order intensity, shape and textural
patient undergoes. features extracted from the tumors, provides crucial information about
The aim of this study was to evaluate differences between dose rates tumor biology and behavior to get a better prognosis, and treatment
to which Technician is subjected, either in performing PET/CT scan response prediction in oncological patients. In this context, we present
and in performing WB bone scan (WBBS), and to check whether it is an innovative machine learning approach which purpose is to tackle
useful for Technician to use the leaded coat (Personal Protection the real-time, 3D tumor segmentation task in a nearly full automatized
Device = PPD), during these examinations. way.
Methods: Fifty patients underwent the measurement: twenty-five Methods: The proposed algorithm identifies a user-independent
were administered 18-FDG (207–404 MBq; mean ± SD region of interest (ROI) around the tumor in the PET slice containing
274.2 ± 53.6 MBq) and twenty-five were administered 99mTc-HDP the SUVmax. The volume is then reconstructed using a slice-by-slice
(696–788 MBq; mean ± SD 740.6 ± 26.8 MBq). marching approach until a suitable automatic stop condition is met.
PET/CT and WBBS patients, after bladder emptying, were measured, On each slice, the segmentation is performed using an enhanced local
respectively 50 min. and 120 min. after the radiopharmaceuticals active contour based on the minimization of a novel energy functional
administration. which integrates the information provided by a machine learning
Measurements were made by Victoreen 451P ionisation chamber, component based on k-nearest neighbor classification method. As a
at 20 cm and at 1 m from standing patient, with and without PPD result, the whole algorithm is automatic and the output segmentation
(0.35 mm Pb eq., 80 kV) is user independent. Five phantom experiments for a total of 30
Reception/leave, positioning and centering times were measured. radioactive spheres, and 41 clinical cases comprising 12 lung, and 29
Results: In PET/CT patients, 1 m and 20 cm Dose Rates without PPD head & neck cancers were used in our study. In particular, to train and
(mean ± SD) were, respectively, 14.27 ± 1.3 lSv/h and validate the machine learning component, fixed ROIs were placed by
82.32 ± 10.9 lSv/h, while those with PPD were 12.57 ± 1.5 lSv/h three expert physicians in a subset of 3 phantom spheres and 6 patient
and 69.76 ± 11.1 lSv/h; PPD use led to a reduction of about 12% of lesions from the initial PET dataset with the purpose of identifying 3
exposure at 1 m and 16% at 20 cm. different areas: tumor, background and border-line regions. The
In WBBS patients, 1 m and 20 cm Dose Rates without PPD remaining data were used to assess the performances of the seg-
(mean ± SD) were, respectively, 3.68 ± 0.7 lSv/h and mentation algorithm. The three physicians performed manual
18.12 ± 3.0 lSv/h, while those with PPD were 1.86 ± 0.4 lSv/h and segmentations around each lesion, and a ground truth estimation tool
9.05 ± 1.2 lSv/h; the use of the PPD led to a reduction of about 50% was employed to define a consolidated reference starting from dif-
of the exposure. ferent manual delineations.
The time during which the Technician was close to patient was Results: Phantom performance results were divided considering
about 170 s for PET/CT scan and about 220 s during the WB bone small spheres with diameters \ 22 mm and large spheres with
scan diameter [ 17 mm. In the smaller spheres, the mean dice similarity
PET/CT examination, in terms of total body dose, ‘‘weighs’’ on coefficient (DSC) was 78.84 ± 6.18%. In the larger spheres, mean
the Technician 0.66 lSv at 1 m, and 3.87 lSv at 20 cm (in the most DSC increased to 90.36 ± 2.75%. Clinical cases showed high
unfavourable situation). agreement with the gold standard (R2 = 0.98). In particular, the mean
WBBS, in terms of total body dose, ‘‘weighs’’ on the Technician DSC was 87.14 ± 3.31% and 87.88 ± 3.89%, in head and neck and
0.22 lSv at 1 m and 1.10 lSv at 20 cm. in lung cancers, respectively. In order to confirm that the proposed
Conclusions: The results showed that the operator who works in method was operator-independent, a sub-dataset of 5 head and neck,
PET/CT diagnostics receives a total body dose fivefold higher than and 5 lung cancers was segmented by the three physicians. The result
working in WBBS diagnostics, and that the use of PPD during the consisted of identical volumes.
WBBS test leads a significant whole body dose reduction (50%); the Conclusions: These results indicate that the proposed method can be
same concept cannot be applied to PET/CT (at most, 16% less). efficiently applied in the clinical routine for tumor segmentation, and
consequently, to extract radiomic features with potential benefit to
improve tumor phenotyping, prognosis, and treatment response pre-
diction, noninvasively.

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S113

PO201 PO202
Adjustment of a dose calibrator by a calibrated source Residual activity after transarterial radioembolization
of 177LU in a phase I/II study for treatment of non (TARE) with Y-90 glass microspheres
hodgkin lymphoma with 177LU-DOTA-HH1
(Betalutin) M. Lecchi2, G. Argiroffi3, A.M. Ierardi1, C. Scabbio2, R. Azzeroni2,
G. Carrafiello1, C. Floridi1, A. Del Sole3
S. Cardo3, P. Saletti1, S. Raspanti2, G. Belli3 1
Diagnostic and Interventional Radiology Unit, Department of Health
1 Sciences, ASST Santi Paolo e Carlo, University of Milan, Milan,
Health Physics Unit, Careggi University Hospital, Florence, Italy.
2 Italy. 2Health Physics Unit, ASST Santi Paolo e Carlo, Milan, Italy.
Nuclear Medicine Department, Careggi University Hospital, 3
Nuclear Medicine Unit, Department of Health Sciences, ASST Santi
Florence, Italy. 3University of Florence, Florence, Italy
Paolo e Carlo, University of Milan, Milan, Italy
Background-aim: The purpose of this study was to determine the
Background-aim: Glass microspheres impregnated with Y-90
calibration factor for the ‘‘non-standard’’ radioisotope Lutetium-177
(TheraSphere, BTG International Group) are indicated for inoperable
with a dose calibrator in use at Nuclear Medicine Department of
hepatocellular carcinoma (HCC) and HCC complicated by portal vein
Careggi University Hospital (Firenze); this radionuclide is present in
thrombosis. The aim of the present study was to investigate the
the new generation radiopharmaceutical called ‘‘Betalutin’’, pro-
residual Y-90 activity after TARE following the calculation proce-
duced by the pharmaceutical company ‘‘Nordic Nanovector’’ and
dure recommended by the medical-device manufacturer.
used in an experimental study for the treatment of relapsing Non-
Methods: Pretreatment procedure involved a liver angiography in
Hodgkin’s Lymphoma.
order to delineate the course of hepatic arteries and a [Tc-99m]MAA
’’Non-standard’’ radioisotopes aren’t set in the control units of dose
scan (after transarterial radiopharmaceutical injection) in order to
calibrators currently used, so that the determination of the appropriate
simulate the Y-90 microsphere distribution. Once the activity to reach
calibration factors for each radionuclide is an essential step for the
the prescribed tumour dose to the target was determined, the Y-90
correct quantification of the activity of a radiopharmaceutical to be
microspheres injection was performed with at least three washes with
administered to patients and to attend in the clinical trial.
sodium chloride solution after infusion. At the end of angiographic
In addition, the participation was also subject to the IFE’s
procedure, physicians put potentially radioactive waste into a 2L
acceptance of the ‘‘Dummy Shipment’’, that is a fictitious shipment
Nalgene cylindrical container (diameter: 14 cm, height: 28.6 cm and
without radioactive material in order to verify the integrity of the
thickness: 0.9 cm). Waste included the catheters, microsphere vial,
packaging and to check that the temperature had remained constant
forceps, gloves, towels used to wrap end of the catheters. Then, a
during transport.
PET/TC exam based on Y-90 emission was performed. Following the
Methods: Equipment involved in the calibration procedure were: a
manufacturer recommendation, percent residual activity was calcu-
dose calibrator Biodex model Atomlab 100 Plus, a 20 ml vial con-
lated using a series of dose-rate measurements (monitor AT6130(A),
taining Lutetium-177 chloride in hydrochloric acid at a concentration
ATOMTEX) at 30 cm from the 2L Nalgene cylindrical container.
of 0. 04 M, provided with a certificate of calibration, and a ‘‘BD
Before the Y-90 treatment, the microsphere vial shield (acrylic
PLASTIPAK’’ syringe, of the same type as the one that will be used
thickness: 1.2 cm) was placed in the container, while after TERA, the
for the administration of Betalutin to patients enrolled in the clinical
mean of 4 measurements performed rotating the waste cylinder in
trial. Various measurements were made with dose calibrator,
different positions was considered.
according to the procedures requested, in particular accuracy and
Results: Eight patients with advanced HCC were treated with Y-90
reproducibility of reading. The calibration value for 177Lu isotope
glass microspheres between April 2018 and October 2018 (mean age:
was first set as reported in the Atomlab 100 Plus manual. Then, two
66.8 ± 3.1 years; all males). The prescribed-activity mean was
specific calibration factors were identified, one for the vial and the
3.21 ± 0.4 GBq (range 1.59–4.91 GBq), while the dose-rate range
other one for the syringe, in order to ensure a deviation better than 1%
from the microsphere vial shield was 46–142 lSv/h. Angiographic
from reference value. Special ‘‘forms’’, sent by the sponsor, were
catheters were used for all the procedures (diameter: 1.67 mm and
filled into provide evidence of the operations carried out on the
length: 65 ? 20 cm or 100 cm), except for the last intervention where
Atomlab 100 Plus and certify its suitability for use with Betalutin.
a micro-catheter was used (diameter: 0.9 mm and length: 135 cm).
Results: Analysing the results of the calibration procedure, it can be
The percent residual activities after TARE were 2.12%, 41.59%. 3.40,
stated that the tolerances required by the sponsor are completely
0.70, 35.10, 4.07, 0.55 and 1.39%, respectively. Very large variability
satisfied; in particular, it results that both calibration factors set, one
was found and two very high unacceptable residual activities were
for the vial and the other for the syringe, differ by less than 1% from
deeply investigated (patients n. 2 and n. 5). In these cases, the max-
the factory value. This also shows that the calibrator does not require
imum dose rate measured from the waste (47 and 40 lSv/h,
any correction factors for the geometry of the source, since the factory
respectively) was found out of the microsphere vial shield, in prox-
calibration factor produces an error on the measurement of activity of
imity of the connector used to link the two catheters used for Y-90
a value slightly higher than 1%, considering vial and syringe.
infusion. In all the cases, good PET/TC exams were reported after the
Conclusions: The results obtained also confirm that Biodex Atomlab
Y-90 microspheres injection.
100 Plus dose calibrator is an excellent instrument for accurate and
Conclusions: The use of portal catheters and catheter connectors is
reproducible dose measurement and that important variations in the
contraindicated for Y-90 TARE. When the residual activity is not
geometry of the sample to be measured lead to contained errors;
contained in the microsphere vial shield, the methodology based on
moreover, the results have highlighted the possibility of how the
dose rate is not applicable and the residual activity could not be
calibrator can be used in the future with other ‘‘non-standard’’
established.
radioisotopes, given the presence of accurate calibration factors and
provided that a properly calibrated reference source is available.

123
S114 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

PO203 PO204
Voxel-based analysis of dynamic FET: a support tool I-131 activity calculation with thyroid mass reduction
for clinicians to characterize glioma in benign disease therapy following the EANM
guidelines
A. Fracchetti1, L. Lorenzon1, M. Farsad2, A. Golemi2, M. Haller1
1
P. Nocera1, M. Lecchi2, C. Romanò1, C. Scabbio2, R. Azzeroni2,
Department of Medical Physics, Hospital of Bolzano, Bolzano, Italy. A. Solop3, A. Del Sole3
2
Department of Nuclear Medicine, Hospital of Bolzano, Bolzano,
Italy 1
Department of Physics, University of Milan, Milan, Italy. 2Health
Background-aim: Dynamic 18F-FET PET seems to have a role in the Physics Unit, ASST Santi Paolo e Carlo, Milan, Italy. 3Nuclear
assessment of glioma grading, differentiating between histological Medicine Unit, Department of Health Sciences, ASST Santi Paolo e
low-grade gliomas (LGG) and high-grade gliomas (HGG). This Carlo, University of Milan, Milan, Italy
evaluation is typically performed by analyzing the kinetic behavior of Background-aim: In the radioiodine therapy of benign thyroid dis-
18F-FET uptake over a region of interest (ROI), which in literature is eases, EANM guidelines suggest the possibility of calculating the
defined in several different ways (for example using a threshold of activity to be administered to the patient taking into account the mass
1.6 9 background activity or an isocontour threshold of 90% or 70% reduction of the target volume. However, EANM does not report any
of the maximum SUV on standard 20-40 min time frames). This work formula to this scope. The aim of the present study was to include the
tried to overcome the limitation of a ROI-based analysis of dynamic thyroid mass reduction (TMR) in the compartment model proposed by
FET, by developing a voxel-based analysis, which generates para- EANM (EANM ? TMR). Moreover, the resulted I-131 activities
metric images that can be used by clinicians as a support visual tool were compared with those obtained without including mass reduction
for the glioma characterization. and with those computed using the biexponential model of the AIMN-
Methods: Dynamic studies were acquired up to 40 min after injection SIE-AIFM guidelines with thyroid mass reduction (AIFM ? TMR).
and included a total of 13 frames (4 9 30 s, 2 9 1 min, 7 9 5 min). Methods: A new formula considering the TMR hypothesis was
Dynamic 18F-FET PET and 20-40 min summed image were analyzed computed starting from the one proposed by EAMN guidelines. This
with Matlab and SPM8 software. Every time frame was first coreg- formula was exploited to calculate the required activity to administer
istered to the summed 20–40 image to correct for intra-acquisition in the treatment of benign thyroid diseases at Nuclear Medicine Unit
patient movement and then smoothed by means of an isotropic 3D of San Paolo Hospital of Milan. The therapy was always administered
Gaussian Kernel (FWHM: 10 mm). To determine the changes of SUV as an outpatient procedure with the maximum permitted activity equal
value, on a voxel level, in the different time frames (from 1 to 40 min to 600 MBq. Before the I-131 therapy, the thyroid mass was evalu-
post-injection), a weighted fit with a 2 degree-polynomial curve was ated measuring the thyroid volume with an ultrasounds examination
performed. The fit was weighted to account for the different frame and considering a density of 1 g/ml. For each patient, the I-131
duration and consequently for the nonconstant error variance in the kinetic was assessed by three uptake measurements with a NaI
data due to the low counting rates in the early perfusion phase. The counter after about 2–6, 24–48 and 120–192 h from the administra-
parameters of fit (in particular the first derivative calculated at half the tion. The radioiodine uptake curve was then obtained fitting the three
vertex of parabola, parameter m1) and the angular coefficient of a measures as a function of time. Given all the kinetic parameters from
linear trend (parameter m2), calculated on the last 4 frames, were used the curve fitting, it was possible to calculate the activity considering
to define three types of kinetic behavior: a monotonic decrease when the EANM, EANM ? TMR and AIFM ? TMR formulas. It is to be
m1 is negative and m2 positive, a steadily increase when both m1 and noted that for both EANM ? TMR and AIFM ? TMR formulas the
m2 are positive and an increase followed by a decrease when m1 is same dependence of the mass variation with the activity was
positive and m2 negative. For a visual representation, three color considered.
channel images were generated with a different color representing a Results: Eight patients affected by benign thyroid diseases were
different kinetic behavior: blue for monotonic decrease, red for treated with radioiodine from February 2018 to November 2018. The
monotonic growth (characteristic of LGG) and green for an increasing thyroid masses ranged from 14.2 to 64.8 g (mean and SD = 25.2 ±
followed by a decreasing dynamics (typical of HGG). The voxel value 16.4 g) and the prescribed doses from 90 to 300 Gy (mean value:
was defined as the parameter m2. 236 ± 82 Gy). The activities computed according to the EANM ?
Results: The voxel-based analysis was performed on several dynamic TMR formula resulted in the range of 182-532 MBq (mean and
18
F-FET PET scans and turned out to be feasible, allowing to char- SD = 381 ± 147 MBq), the EANM activities ranged from 211 to
acterize the lesion without defining the region of interest with some 595 MBq (mean and SD = 446 ± 164 MBq) and those of AIFM ?
advantages over the ROI-based analysis. Firstly the sub-volumes with TMR from 160 to 591 MBq (mean and SD = 401 ± 165 MBq). The
a kinetic behavior typical of HGG (green color) inside a lesion with relative difference between the activities computed with the two
an uptake pattern resembling PET characteristics of LGG (red color) EANM formulas was on average of about 15% (range - 22% to
could be identified. Secondly, unlike the ROI-based method, lesions - 8%). The same result of 15% (range - 26% to - 9%) was
near a vessel were characterized easily, since the vessel has a clearly obtained in the case of the activities from the two AIFM formulas.
decreasing dynamics, which was never observed in the lesion. Finally, the relative difference between the activities from the two
Conclusions: A new way to analyze the dynamic FET has been models implementing the TMR was on average of about 4% (range
developed. This voxel-based analysis is automatic, it does not require - 12% to 13%).
the definition of a ROI and allows the identification of pattern of sub- Conclusions: The inclusion of the reduction of the thyroid mass in
volumes inside the lesion with different kinetic behavior. The pro- the radioiodine activity calculation based on the compartment model
posed solution has potential for helping physicians during routine led to a decreasing of the required activity to reach the prescribed
visual/qualitative analysis by giving additional information. dose, as already known for the biexponential model. Moreover, the
decreasing is the same for the two models. Indeed, the relative dif-
ference of 4% between the EANM and the AIMN-SIE-AIFM
approaches showed that they are similar. However, it needs a bigger
sample of patients in order to increase the statistics. The next step will

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S115

be to implement the compartment model in the dependence of the settings should especially be considered when standardization and
mass variation from the activity. harmonization are necessary to obtain the best compromise between
lesion detectability, quantification and noise.

PO205
Clinical application of a BGO PET/CT scanner: effects PO206
of acquisition protocols, reconstruction parameters 41% of SUVmax threshold is highly reproducible even
on lesions quantification if obtained with different software for PET/CT
segmentation
E. De Ponti1, S. Morzenti1, C. Crivellaro3, R.V.A. Vicinelli3,
F. Elisei2, A. Crespi1, C. Landoni3, L. Guerra2 F. Bergesio1, A. De Maggi1, L. Guerra2, S. Chauvie1
1 1
Medical Physics, ASST-Monza, San Gerardo Hospital, Monza, Italy. Medical Physics Unit, Santa Croce e Carle Hospital, Cuneo, Italy.
2 2
Nuclear Medicine, ASST-Monza, San Gerardo Hospital, Monza, Nuclear Medicine Department, San Gerardo Hospital, Monza, Italy
MB, Italy. 3Nuclear Medicine, University Milano-Bicocca, Milan,
Background-aim: The aim of this work was to compare the vari-
Italy
ability in measuring the Metabolic Tumour Volume (MTV) of known
Background-aim: Tumor metabolism is a parameter of response to lesions obtained with 4 different software (SW) for PET
treatment in oncology measured as SUVmax and SUVpeak. However, segmentation.
SUV values can be strongly influenced by various factors as technical Methods: MTV of 24 known lesions of lymphoma were analysed by
features of the scanner, injected activity, acquisition time, recon- the same imaging expert with 4 SW: Rover (ABX GmbH), LifeX
struction parameters and lesion’s dimension. Aim of the study was to (Universite Paris-Saclay), Fiji (petctviewer.org) and MIM (MIM
investigate SUV variability respect to different size lesions, dose software Inc.) For each lesion three different segmentation algorithm
protocols and reconstruction algorithms when a 5-rings high sensi- were used: 41% of SUVmax (PER), 2.5 SUV (FIX) and the propri-
tivity BGO PET/CT scanner is used. The scanner is equipped with 2 etary segmentation algorithm (PSA). We hence calculate the ratio of
reconstruction algorithms: the standard OSEM plus the PSF option each MTV (RMTV) to the average of the four SW and report it hers
(OSEM ? PSF) and the regularized one (bayesian penalized likeli- as mean ± standard deviation and range.
hood algorithm-BPL). The last one incorporates a parameter, called Results: The mean, median, standard deviation e range of all MTV,
Beta factor, able to modulate the noise allowing the algorithm to expressed in cc, were (61.67 ± 82.64, median 20.26 range
reach the full convergence of the data without excessively increasing 4.76–291.61), (145.97 ± 174.26, median 72.12 range 6.24–719.10)
the image noise. and (73.10 ± 91.59, median 28.57 range 5.21–325.18) for PER, FIX
Methods: A 5 rings-BGO scanner (Discovery IQ from GE Health- and PSA respectively.
care) was used for List Mode acquisition of 25 patients, 12 injected RMTV for PER were: ROVER (0.99 ± 0.04, range 0.90–1.05);
with 3.7 MBq/kg (Standard Dose protocol) and 13 with 1.8 MBq/kg LifeX (0.99 ± 0.03, range 0.93–1.06); Fiji (1.02 ± 0.04, range
(Low Dose protocol). Each acquisition was reconstructed at different 0.93–1.14); MIM (1.00 ± 0.03, range 0.92–1.06).
time/FOV (from 45 s to 2 min/FOV for SD and from 2 min to 4 min/ RMTV for FIX were: ROVER (1.15 ± 0.38, range 0.66–2.30);
FOV for LD) with the standard OSEM ? PSF algorithm and with the LifeX (0.92 ± 0.21, range 0.35–1.40); Fiji (0.93 ± 0.27, range
regularized BPL (Q.clear) using seven different Beta factor (from 500 0.26–1.40); MIM (1.00 ± 0.33, range 0.22–2.23).
to 200 units, step 50). SUVmax and SUVpeak of all reconstructions RMTV for PSA were: ROVER (Adaptive Threshold)
were calculated and compared in 70 lesions stratified according to (0.74 ± 0.14, range 0.30–0.98); LifeX (NESTLE Algorithm)
injected activity and dimension (range 6–50 mm, cut-off 10 mm). (0.93 ± 0.21, range 0.34–1.30); MIM (Gradient Threshold):
SUVmax and SUVpeak variability was analyzed as a function of (1.33 ± 0.31, range 0.90–2.23).
time/FOV and Beta factor. The image quality was evaluated using the Conclusions: PER is a robust and reproducible procedure to evaluate
coefficient of variance (CV) of the liver. the MTV of PET-CT lesion even if using different software with
Results: SUVmax and SUVpeak showed a complete overlap between variability below 10%. The FIX showed a high variability related to
measurements changing time/FOV in both OSEM ? PSF and BPL the positioning and shape of the initial VOI used for segmentation.
reconstructions (maximum difference below 5% and linear regression The PSA showed a great variability related to the different segmen-
model p \ 0.0001). Quantification was not affected by time/FOV tation algorithm emphasising the fact that different PSA are not inter-
both in small and large lesions, whereas SUVmax and SUVpeak were changeable. MTV measured with PER are systematically lower than
significantly influenced by variation of Beta factor and differences with FIX.
were higher in small lesions (37% and 15% for SUVmax and SUV-
peak, respectively) with respect to larger ones (14% and 6%). A
maximum difference of 38.5% between OSEM ? PSF and BPL was
measured for SUVmax quantification in smaller lesions group. CV- PO207
liver ranged from 6% obtained for beta = 500 (LD and SD) to 13% SUV harmonization of different PET/CT scanners
for LD-beta 200. CV-liver of BPL reconstruction optimized for with and without PSF correction
clinical practice (beta = 350) in low-dose protocol was lower than
CV-liver of OSEM ? PSF standard dose.
A. Ferretti1, S. Chondrogiannis2, L. Rampin2, E. Bellan1, M.C.
Conclusions: When a BGO 5-rings PET/CT scanner is used, quan-
Marzola2, G. Grassetto2, M. Maffione2, M. Gava1, D. Rubello2
tification by means of SUVmax and SUVpeak is a robust standard
with respect to different dose protocols and scan durations, also if 1
Medical Physics Unit, Santa Maria della Misericordia Hospital,
SUVpeak is confirmed more stable respect to SUVmax, especially for
Rovigo, Italy. 2Nuclear Medicine Unit-PET/CT centre- Santa Maria
small lesions. However, both SUV values and CV are influenced by
della Misericordia Hospital, Rovigo, Italy
selected reconstruction algorithm and related parameters and these

123
S116 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

Background-aim: Last generation PET/CT scanners implemented receives the smallest possible amount of radiopharmaceutical that will
point-spread function (PSF) correction in reconstruction software. provide the appropriate diagnostic information. Appropriate selection
This novelty improved image quality but caused an increase of SUVs of the administered radiopharmaceutical activity depends on the
compared to conventional OSEM reconstruction of previous genera- patient population, choice of equipment, specific requirements of the
tion PET/CT scanners. The EANM identified the problem of SUV clinical protocols, radioprotection’s considerations and the physi-
harmonization since 2010 when the EARL FDG-PET/CT accredita- cian’s judgment. Therefore, deviation from the administered activities
tion programme was established: they suggested to produce two listed in the consensus guidelines should be considered appropriate
reconstructions, one optimised for maximum lesion detection and one when clinically indicated). On that basis, in our Department since
for semi-quantitative SUV analysis. In this work we investigated an 2013 we began a route of personalization of the injected activity,
alternative methodology, using a single reconstruction data set toge- taking into account age and physics parameters of patients, such as
ther with a post-reconstruction algorithm for SUV harmonization. weight, height and body surface area. In order to assess the efficacy of
Methods: Phantom measurements and subsequent patient data anal- this personalization in terms of reduction of radiation exposure, we
ysis were performed on a Siemens Biograph mCT system equipped perform a retrospective analysis (2015–2018) based on injected
with LSO crystals, PSF and TOF algorithms and on a previous-gen- activity of radiopharmaceutical (MBq) and estimation of the effective
eration General Electric Discovery STE system equipped with BGO imaging radiation dose (in mSv) and we compared these values with
crystals. Both EANM double reconstruction method and a dedicated corresponding LDR reported in Italian law (D.Lgs 187/00). We
intrinsic post-reconstruction algorithm (named EQ.filter) were tested evaluated the following of ALARA principle through the estimation
to harmonize quantitative values of the two PET/CT scanners. For of effective dose values to patients.
phantom measurements a NEMA IQ phantom and a Jaszczak cylin- Methods: First, we evaluated the injected activity prescribed for each
drical phantom equipped with small spheres (lesion to background diagnostic nuclear medicine procedure, following the prescriptions
ratios of 8:1 and 4:1) were used. Data obtained by phantom mea- reported in historical SOP (Standard Operating Procedure) of the
surements were validated on seven oncologic patients who accepted Department, and we compared these values with corresponding LDR
to perform a one-bed extra acquisition on a different scanner. The reported in Italian law (D.Lgs 187/00). Differences found into these
evaluation regarded 39 small lesions (diameters 0.3–2.6 cm) and was values suggested the idea of a personalization of the injected activity
performed by two experienced nuclear medicine physicians. and we decided to introduce a factor which took into account body
Results: The main benefit of PSF ? TOF PET/CT systems is the surface area, calculating with Mosteller standard formula. After a
increased percentage contrast of small lesions. On the other hand, the period of observation we further personalized the calculating taking
curves of recovery coefficients (RCs) measured according to NEMA into account theoretical estimates, clinical considerations and
standards exceeded those obtained by the OSEM reconstruction, with acquired experience and we introduced in clinical routine a factor of
discrepancies as high as 149%, while they drop below 10% applying activity for unit of body surface area (MBq/m2) for each diagnostic
the optimized value of EQ.filter, equal to 8 mm FWHM for the procedure and radiopharmaceutical. We implemented this calculation
reconstruction parameters used in our center. Patient data, analyzed by in the software in use in the Nuclear Medicine Department. Nowadays
Wilcoxon statistical test, confirmed phantom measurements. For each patient information (including weight and height) are automatically
scanner and reconstruction setting the optimal value of the EQ.filter collected from RIS and for each examinations and radiopharmaceu-
should be identified in order to minimize these discrepancies. ticals is calculated the value in MBq of personalized, optimized
Conclusions: Since we can not upgrade previous generation PET/CT activity that has to be injected to the patient.
scanners, for new generation scanners we should exploit the image Results: In the table we summarize the effective standard dose values
quality improvements but we should reduce their quantification obtained after the injection of different activity, after and before the
potential to make them fit the established (even if outdated) quan- optimization route.
tification specifications. This harmonization is particularly important Oncological PET F-18: 9856 patients; Eff.dose = 3.9 mSv (- 14%)
in clinical practice in each hospital provided with two or more PET/ Myocardic Gated REST: 1386 patients; Eff.dose = (5.9 ±
CT scanners of different manufacturers and technology, as well as 0.6) mSv (- 20%)
between neighboring hospitals to which a returning patient can refer. Myocardic Gated STRESS: 1521 patients: Eff. dose = (5.8 ±
EQ.filter can harmonize SUV values between different PET/CT 0.6) mSv (- 20%)
scanners using a single reconstruction optimized to maximum lesion Bone Scint.: 4603 patients; Eff. dose = (5.86 ? 0.77) mSv
detectability. In this way, the second reconstruction proposed by (- 3.5%).
EANM/EARL is avoided. The graph shows the injected activity/effective dose values after
the optimization process as function of body surface area (year
2015–2018).
Conclusions: Nowadays, in clinical routine, we personalize all the
PO208 administered radiopharmaceutical activities which have to be injected
Optimization and personalisation of injected activity into patients. We demonstrated the effectiveness of applying the
in diagnostic nuclear medicine: a retrospective analysis ALARA principle to individuals, especially to children and to adults
with a BSA lower than that of the standard person, maintaining the
(2015–2018)
diagnostic value of the examination.
R. Visentin2, S. Agostini1, E. Bagatin1, A. Palermo1, D. Donner1,
M. Erini1, G. Carbone1, L. Picori1, F. Chierichetti1, A. Valentini2
1
Nuclear Medicine Department, S Chiara Hospital, Azienda
Provinciale Servizi Sanitari (APSS) di Trento, Trento, Italy. 2Physics
Department, Azienda Provinciale Servizi Sanitari (APSS) di Trento,
Trento, Italy
Background-aim: Radiation dose for all nuclear medicine and
molecular imaging procedures should be optimized so that the patient

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S117

PO209 PO210
Reliability of Deauville scale in lymphoma PET Role of the nuclear physician in the management
assessment in multi-center clinical trials of nuclear and radiological maxi-emergencies

F. Bergesio1, L. Guerra13, F. Fallanca12, M. Gregianin9, A. Muni2, H. Rouhanifar2, L. Tommasi2, E. Pomposelli2, H. Belloni2,


S.D. Morbelli11, U. Ficola7, S. Peano8, G. Storto6, A. Franceschetto3, D. Maranzana2, O. Gandini2, D. Valentini1
L. Melis2, E. Borsatti4, G. Treglia5, A. Versari10, A. Biggi8,
S. Chauvie1 1
Health Physic Unit ‘‘SS. Antonio e Biagio e C. Arrigo’’ Alessandria
Hospital, Alessandria, Italy. 2Nuclear Medicine Unit ‘‘SS.Antonio e
1
Medical Physics Unit, Santa Croce e Carle Hospital, Cuneo, Italy. Biagio e C. Arrigo’’ Alessandria Hospital, Alessandria, Italy
2
Nuclear Medicine Department, A. Businco Hospital, Cagliari, Italy.
3 Background-aim: The Italian population is subject to the risk of a
Nuclear Medicine Department, Azienda Ospedaliera Universitaria,
nuclear accident due to the presence of nuclear sites inside and out-
Modena, Italy. 4Nuclear Medicine Department, CRO Hospital,
side the national territory and the possibility of terrorist acts resulting
Aviano, Italy. 5Nuclear Medicine Department, IOSI Hospital,
in the spread of radioactive contaminants in the environment. The
Bellinzona, Switzerland. 6Nuclear Medicine Department, IRCCS
terrorist threat can manifest itself either through radiological disper-
CROB, Rionero in Vulture, Italy. 7Nuclear Medicine Department, La
sion devices (dirty bombs) or the abandonment in a public place of
Maddalena Hospital, Palermo, Italy. 8Nuclear Medicine Department,
high activity radioactive sources (Radiation Exposure Device).
S. Croce e Carle, Cuneo, Italy. 9Nuclear Medicine Department, S.
In Italy there is in place a national intervention plan for these kinds of
Giacomo Apostolo Hospital, Castelfranco Veneto, Italy. 10Nuclear
events that must be supported by a local plan to deal with any possible
Medicine Department, S. Maria Nuova Hospital, Reggio Emilia, Italy.
11 emergency. Hospitals have an emergency plan in case of a mass-
Nuclear Medicine Department, S. Martino Hospital, Gena, Italy.
12 casualty influx, which must be periodically revised to be adapt to
Nuclear Medicine Department, S. Raffaele Hospital, Milan, Italy.
13 possible nuclear, biological, chemical, radiological events of an
Nuclear Medicine Department, San Gerardo Hospital, Monza, Italy
incidental or terroristic nature.
Background-aim: Positron Emission Tomography (PET/CT) is the Methods: Within this emergency plan the requirements and roles of
standard of care for response assessment in lymphoma. According to the members of the radiological emergency team are well defined. A
the Malignant Lymphomas Imaging Working Group, Deauville scale nuclear physician and a health physicist must be part of these teams
(DS) is recommended for PET/CT reporting. along with emergency doctors, DEA nurses and psychologists.
In this work we evaluated the reliability of the DS used in multi- If the emergency involves many people, it is difficult to identify the
center trials of Italian Foundation Lymphoma (FIL) to evaluate the absorbed dose of each individual. In this case triage must be based on
PET/CT during treatment (INT PET) or at the end of the treatment symptoms that allow rapid screening such as the presence/absence of
(EoT PET). gastrointestinal symptoms and the extent and severity of the symp-
Methods: Three multicenter study were included in this analysis: tomatology. Skin lesions caused by radiogenic damage must be
FIL-FOLL12 (Follicular Lymphoma, EoT PET reviewed), FIL- carefully evaluated as they can help in assessing the equivalent
DLCL10 (Diffuse Large B-Cell Lymphoma, EoT PET reviewed) and absorbed dose from the skin based on clinical evidence.
FIL-ROUGE (advanced-stage classical Hodgkin Lymphoma, INT Results: During the triage, the physicist and the nuclear doctor, after
PET and EoT PET reviewed). dressing in the personal protective equipment, control the external
PET/CT images were independently reviewed by a group of nuclear contamination of the patients, decontaminate the undamaged skin and
medicine physicians blinded to patient history, clinical data and wounds, send the patients presenting a generalized contamination of
treatment outcome. In each patient the location of the most active the whole body to the decontamination shower, collect the biological
residual lesion (reference lesion) was identified and visually scored material to be examined in cases of internal contamination and pro-
according to DS. vide for the decorporation of the internalized radionuclides with the
For each study we evaluated the reliability among all reviewers antidotes available in DEA. Retrospective dose assessment is
and for each couple of nuclear physicians using the Krippendorff important for fast screening in the case of a surgo of patients in order
Alpha Index (KA) and the Cohen Kappa Index (CK) respectively. to establish the priority of the interventions and estimate the dose
Results: 713 EoT PET included in the FIL-FOLL12 trial were distribution. The physicist and the nuclear physician have, at this
reviewed by 6 expert nuclear physicians. The KA value was 0.29, the point to determine the accidental dose through the monitoring of
mean CK was 0.58 (range 0.34–0.80). radioactive levels using the necessary instruments, symptom mani-
106 EoT PET included in the FIL-DLCL10 trial were reviewed by 5 festation time in prodromic phase, circulating lymphocytes count,
expert nuclear physicians. The KA value was 0.37, the mean CK was dicentrics and micronucleus examinations.
0.58 (range 0.43–0.69). Conclusions: In conclusion, the hospitals equipped with a 2nd level
98 INT PET and 48 EoT PET included in the FIL-ROUGE trial DEA and nuclear medicine unit must foresee in their emergency plan
were reviewed by 5 expert nuclear physicians. The KA values were an organization able to manage a nuclear/radiologic emergency and a
0.38 and 0.19 for INT PET and EoT PET respectively. The mean CK route through the hospital for the save movement of patients towards
were 0.73 (range 0.57–0.87) and 0.45 (range - 0.16 to 0.91) for INT the radiology department and/or the operation theatre should surgery
PET and EoT PET respectively. be unavoidable.
Conclusions: The results show that the Deauville Score is a repro-
ducible scale for multi-center clinical trials using FDG-PET/CT for
response assessment in several lymphomas diseases.

123
S118 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

PO211 PO212
Improving the quality of life in pediatric patients Comparison of 99mTc-MAA SPECT/CT predictive
submitted to radioiodine therapy: a return to daily life dosimetry and 90Y PET/CT posttreatment dosimetry
as fast as reasonably achievable in radioembolization of hepatic tumours

M. Pizzoferro3, C. Polito2, M. Longo2, M.F. Villani3, B. Cassano2, O. Ferrando1, E. Borso2, R. Leoncini2, M. Riondato2, F. Foppiano1,
E. Genovese2, A. Castellano4, A. Grossi1, M.C. Garganese3 A. Ciarmiello2
1 1
Endocrine Unit, IRCCS Bambino Gesù Children’s Hospital, Rome, Medical Physics Department, St Andrea Hospital, La Spezia, Italy.
Italy. 2Medical Physics Unit, IRCCS Bambino Gesù Children’s 2
Nuclear Medicine Department, St Andrea Hospital, La Spezia, Italy
Hospital, Rome, Italy. 3Nuclear Medicine Unit, IRCCS Bambino
Background-aim: The aim of this study was to evaluate the agree-
Gesù Children’s Hospital, Rome, Italy. 4Oncology Unit, IRCCS
ment between the predictive dosimetry based on 99mTc-MAA
Bambino Gesù Children’s Hospital, Rome, Italy
SPECT/CT and the post-treatment dosimetry based on 90Y PET/CT
Background-aim: Radioiodine (131I) therapies on younger children acquisitions
with differentiated thyroid cancer and neuroblastoma can be a dis- Methods: The study was applied to 15 patients with hepato-cellular
couraging experience as they are required to be isolated for a period carcinoma who underwent radioembolization with 90Y-resin spheres.
of time due to radiation safety concerns. Safety isolation period after We compared pre-treatment dosimetry based on 99mTc-MAA
radioiodine treatment depends on 1 m distance dose-rate value on the SPECT/CT and post-treatment dosimetry based on 90Y PET/CT. 3D
day of discharge (established by Radiation protection 97 and Italian dose maps and dose- volume histograms (DVH_spect, DVH_pet)
regulation). Pediatric patients usually have dose rate values on dis- were calculated using the methodology proposed in [1]. Mean
charge involving a month of school absence and no contacts with absorbed dose in tumour volumes (Dspect and Dpet) were calculated
other peers in order to avoid unduly irradiation. However, each using the MIRD method [2]. SPECT and PET volumes of interest
patient has an individual kinetic of radioactivity excretion depending (tumour volume) were delineated with a thresholding method using
on extension and uptake of disease, renal function, degree of hydra- the AMIDE software [3], lobar and whole liver volumes were
tion and other individual parameters. The aim of our study is to determined from CT images. Patient administered activity was cal-
improve the patient’s quality of life by reducing as much as possible culated using the Body Surface Area method as recommended by the
the isolation period after discharge by means of a patient-specific sphere manufacturer. Concordance between Dspect and Dpet,
radiometric protocol. DVH_spect and DVH_pet were evaluated with the Wilcoxon Signed
Methods: Children affected by thyroid cancer or neuroblastoma are Ranked test.
treated in our Institution in a child-friendly therapy room, accompa- Results: Patient administered activity ranged from 0.7 GBq to
nied by their parents, for a 3–4 days period. A well-established 2.2 GBq. Tumour volumes ranged from 75 mL to 1012 mL. The
dosimetric protocol is routinely applied including measurement of mean absorbed dose was 125 Gy for tumour volume and 45 Gy for
patient’s dose-rate at a distance of 1 m by dedicated instrumentation non-tumour volume. The comparison between Dspect and Dpet and
(Ludlum radiation detector) up to 7 days after radioiodine admin- the comparison between DVH_spect and DVH_pet evaluated with the
istration. All radiometric data are collected and analyzed to assess Wilcoxon Signed Ranked test were statistically significant with
individual radiotracer excretion/retention time. For each patient a = 0.01.
radiation isolation period is calculated according to Italian regulation Conclusions: Even if our results are limited to the restricted popu-
considering the dose rate on discharge. An update on 7th day after lation analysed in this study, we have found a quantitative agreement
therapy administration (when 131I Whole Body Scan is scheduled) is between predictive and post dosimetry of 90Y-radioembolization.
also performed on the basis of relative emission rate value. From our point of view predictive dosimetry with 99mTc-MAA
Results: 55 treatments were performed in our Institution from 2016 to SPECT/CT can provide valuable estimation of tumour and non-tu-
2018: 26 with high-administered activity of 131I-MIBG and 29 131I- mour tissues absorbed doses and these information can help in the
NaI administrations (12 thyroid remnant ablations, 17 metastatic decision of a more personalised activity administration.
treatments). The median age was 12 years (range 3–20 years); the References
median weight was 46 kg (range 12–123 kg). The median adminis- [1] A.C. Traino et all. Dosimetry for nonuniform activity distribu-
tered activities were: 9 GBq for 131I-MIBG (range 3.1–13.6 GBq), tions: A method for the calculation of 3D absorbed-dose distribution
1.6 GBq (range 1.11–1.85 GBq) of 131I-NaI for thyroid remnant without the use of voxel S-values, point kernels, or Monte Carlo
ablation, 5.8 GBq (range 3.7–10.8 GBq) of 131I-NaI for metastatic simulations. Med. Phys. 40 (4), April 2013
treatments. The relative difference between the dose rate measured on [2] M.G. Stabin et all. Recommendations of the American Asso-
discharge vs updated value on 7th day led to a reduction of isolation ciation of Physicists in Medicine on dosimetry, imaging, and quality
period of: 25 (range 6–34) days for 131I-MIBG treatments, 10 (range assurance procedures for 90Y microsphere brachytherapy in the
0–26) days for thyroid remnant ablations; 19 (range 6–32) days for treatment of hepatic malignancies. Med. Phys. 38 (8), August 2011
metastatic thyroid treatments. [3] AMIDE 1.0.4 open source software, http://amide.source
Conclusions: Our protocol, routinely applied in clinical practice, may forge.net
shorten the isolation period in both patients and their relatives, so
allowing a faster return to daily life. Radiometric data updated on 7th
day safely allow reducing radiation isolation period, improving life
quality in children submitted to radioiodine therapy.

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S119

PO213 PO214
Effectiveness of post therapy 90Y PET-CT dosimetry Full Monte Carlo internal dosimetry of TARE
in hepatic radioembolizations treatments of HCC: preliminary results

E. Richetta3, M. Poli3, M. Tabone2, B. Peiretti Paradisi1, M. Pacilio4, E. Amato5, L. Auditore4, A. Italiano1, P. Arce2, A. Campennı̀3,
N. Lanconelli6, R. Pellerito5, M. Stasi3 S. Baldari3
1 1
Energy Department, Politecnico di Torino, Turin, Italy. Istituto Nazionale di Fisica Nucleare, Sezione di Catania, Catania,
2
Gastroenterology Department, A.O. Ordine Mauriziano, Turin, Italy. Italy. 2Medical Applications Unit, Centro de Investigaciones
3
Medical Physics Department, A.O. Ordine Mauriziano, Turin, Italy. Energéticas, MedioAmbientales y Tecnológicas (CIEMAT), Madrid,
4
Medical Physics Department, A.O.U. Policlinico Umberto I, Rome, Spain. 3Nuclear Medicine Unit, Department of Biomedical and Dental
Italy. 5Nuclear Medicine Department, A.O. Ordine Mauriziano, Sciences and Morphofunctional Imaging, University of Messina and
Turin, Italy. 6Physics and Astronomy Department, Alma Mater University Hospital ‘‘G. Martino’’, Messina, Italy. 4Nuclear Medicine
Studiorum, University of Bologna, Bologna, Italy Unit, University Hospital ‘‘G. Martino’’, Messina, Italy. 5Section of
Radiological Sciences, Department of Biomedical and Dental
Background-aim: 90Y radioembolization is an effective treatment
Sciences and Morphofunctional Imaging, University of Messina,
for non resectable liver tumors. A preliminary simulation of the
Messina, Italy
treatment can be achieved on SPECT-TC 99mTc acquisition to esti-
mate the doses to target and healthy parenchyma. Post treatment Background-aim: Trans-Arterial Radio-Embolization (TARE) of
dosimetry is mandatory on 90Y PET-TC images to verify the effec- HepatoCellular Carcinoma (HCC) with yttrium-90 labeled glass or
tive uptake. Aim of this study was to compare simulation and resin microspheres is an effective therapy, increasingly employed,
verification dose results, to evaluate the dosimetric agreement demanding high dosimetric accuracy, due to the particular bio-dis-
between the two imaging modalities. tribution of the devices and the necessity to spare healthy liver.
Methods: 13 HCC patients underwent resin microspheres 90Y Three-dimensional internal dosimetry can give more information with
embolization. SPECT-TC 99mTc-MAA acquisition (Itera- respect to mean dose approaches and, among 3D methods, the full
tiveFlash3D, voxel4.8 mm, attenuation and scatter corrected) was Monte Carlo simulation is considered the gold standard, given its
performed within 10 days before therapy. 90Y PET-TC images were ability to account for both radionuclide distribution (from SPECT)
acquired 24 h after the treatment (TOF, OSEM3D, voxel 4 mm, and tissue inhomogeneities (from CT).
attenuation and scatter corrected, scan-time 20 min/bed). Mean dose Aim of this work was to develop a new approach to the dosimetry
to tumor T and whole normal liver NT were calculated both with of TARE patients, in order to produce 3D dose maps and dose-volume
MIRD and voxel method. Patients were divided into groups: similar histograms (DVHs) using SPECT-CT scans and a full Monte Carlo
uptake between SPECT-TC and PET-TC images for T and NL (group computation.
A) or completely different radiotracer distribution (group B). SPECT Methods: We exploited GAMOS (GEANT4-based Architecture for
and PET dose correlation for T and NL (group A and B) were Medicine-Oriented Simulations) Monte Carlo, together with ad-hoc
investigated with Pearson correlation coefficient (R) and Bland–Alt- ancillary codes managing data input/output, and we tested our method
man analysis. on clinical cases of TARE, comparing retrospectively the average
Results: 90Y resin microspheres were administered to 13 patients. absorbed doses to the liver and to the target lesions with those
For group A (10/13 patients) mean administered activity was obtained using the local energy deposition hypothesis.
1.73 ± 0.5 GBq, for group B (3/10 patients) 1.37 ± 0.5 GBq. For The imported CT image was converted in a 3D density map, and a
group A mean (± 1SD) tumor volumes were 213 ± 192 ml (range 20 segmentation in five tissue types was applied (air, inflated lungs,
7 647 ml) and 210 ± 187 ml (range 21 7 630 ml) on SPECT and adipose tissue, soft tissue, cortical bone), based on density intervals.
PET images respectively. MIRD and voxel mean doses (± 1SD) Voxelized geometry was modelled according to the above data. The
delivered to T were in SPECT-TC 201 ± 76 Gy and 203 ± 66 Gy radioactive source of yttrium-90 was spatially distributed according to
becoming 216 ± 100 Gy and 209 ± 86 Gy in PET-TC. MIRD and SPECT data, taking into account the physical decay time of the
voxel mean doses to NL were in SPECT-TC 28 ± 14 Gy and nuclide linked to the embolizing microspheres. Five VOIs were
30 ± 13 Gy becoming 29 ± 13 and 29 ± 12 in PET-TC. R coeffi- defined (Liver, Liver Perfused, Healthy Liver, Healthy Liver Per-
cients were 0.91 for T and 0.97 for NL; Bland–Altman 1.96SD were fused, Lesion) in order to compute average doses and DVHs in each
69 Gy and 6 Gy for T and NL respectively. For group B tumor vol- VOI.
umes were 342 ± 277 ml (range 34–572 ml) and 472 ± 47 ml Results: Looking at 3D dose maps, the uneven distribution of dose
(range 439–526 ml). MIRD and voxel mean doses (± 1SD) delivered within target volumes is apparent, as well as the absorbed dose to the
to T were in SPECT-TC 281 ± 262 Gy, 294 ± 253 Gy in SPECT- surrounding organs and tissues.
TC becoming 96 ± 65 Gy, 94 ± 53 Gy in PET-TC. In this group an Axial dose profiles, when compared with the corresponding density
higher variation between simulation and verification doses was profiles, reveal the influence of tissue inhomogeneity on absorbed
founded due to the different localization and volumes of the radio- dose. Particularly relevant are the absorbed doses to the proximal and
pharmaceutical into the liver. MIRD and voxel mean doses (± 1SD) distal lungs, despite their low tissue density. These local effects can
delivered to NL were 22 ± 17 Gy in SPECT-TC becoming be focused thanks to the complete computation of radiation interac-
23 ± 19 Gy in PET-TC. The small number of patients did not tions provided by Monte Carlo simulation.
allowed statistic tests. Calculations based on local energy deposition of beta energy,
Conclusions: When a good agreement in simulation and verification regardless of the VOI size, overestimate absorbed doses with respect
uptake localization is achieved, post-SIRT 90Y PET-CT dosimetry is to the Monte Carlo results. Deviations decreasing with the VOI mass
effective and well correlates with SPECT-CT99mTc-MAA pre-ther- were observed.
apy results. High dose discrepancies can be observed when tumor As a result of prescribing an average absorbed dose of 120 Gy to
90Y localization varies from 99mTc and the reasons must be further the perfused volume, which includes both lesions and the perfused
investigated. part of the healthy liver, an extended range of doses is recorded in that
volume.

123
S120 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

However, the justification on the basis of the risk–benefit ratio is Conclusions: The calibrations of the gamma camera represent the
found when comparing the Lesion with the Healthy Liver (full and first necessary and fundamental step for dosimetry. It is not con-
perfused) DVHs. In particular, the Lesion receives therapeutic doses ceivable to undertake this path without having performed the
with regions above 200 Gy. On the contrary, Healthy Liver exhibits a calibration measures of the gamma camera previously described. The
sharply decreasing DVH. nuclear medicine technician collaborates with the medical physicists
Conclusions: The Monte Carlo simulation of radiation transport and in the preparation of the sources, the setting of the image acquisition
interaction is the most accurate method for evaluating the radiation protocol and in the used methodology. Dosimetric studies require, in
absorbed dose distribution in internal radiotherapies with radionu- addition to a high level of expertise, long and complex procedures
clides, and can give a valuable contribution in the direction of there are expensive in terms of human and technical resources.
providing three-dimensional dosimetry in nuclear medicine treat-
ments. The produced dosimetric data demonstrate the value of such
approach, particularly when relevant tissue inhomogeneities are
present. PO216
Feasibility and prognostic impact of features analysis
on I-131 SPECT-CT images in metastatic thyroid
PO215 patients treated with radioiodine
Pediatric dosimetry practice: gamma camera
M. Poli1, C. Cutaia1, A. Pecora1, V. Garbaccio2, E. Richetta1,
calibration D. Deandreis3, R.E. Pellerito2, M. Stasi1

V. Nicoloso2, E. Villanucci2, B. Cassano1, P. Milena2, 1


Medical Physics Department, A.O. Ordine Mauriziano Umberto I,
L. Mariaconcetta1, S. Chiapparelli2, V. Maria Felicia2, Turin, Italy. 2Nuclear Medicine Department, A.O. Ordine Mauriziano
G. Maria Carmen2 Umberto I, Turin, Italy. 3University Nuclear Medicine, Department of
1
Medical Sciences, University of Turin, Città della Salute e della
2IRCCS Bambino Gesù Children’s Hospital, Medical Physics Unit, Scienza di Torino, Turin, Italy
Rome, Italy. 2IRCCS Bambino Gesù Children’s Hospital, Nuclear
Medicine Unit, Imaging Department, Rome, Italy Background-aim: In metastatic differentiated thyroid cancer
(MDTC) the radioiodine treatment is a consolidated approach. The
Background-aim: The objective of the dosimetric studies, adopted in effectiveness of the therapy can be verified on post administration
our center since 2016, is to determine the activity of the radiophar- imaging where tomography represents the most accurate option.
maceutical to be administered in order to obtain a high dose of Aim of this study is to evaluate the feasibility and prognostic impact
radiopharmaceutical to the target lesions without exceeding the of 131I SPECT-CT images features analysis (FA) performed on
maximum tolerable dose to the healthy tissues. The gamma camera metastatic lesion in MDTC patients.
used for dosimetry has been appropriately calibrated using different Methods: FA was performed on SPECT-CT images with a free
techniques through scintigraphic acquisitions of a source with known software (LIFEx, CEA 2017) taking into account texture features (TF)
activity. and first-order features (FF). TF include Gray-Level Occurrence
Methods: The gamma camera used for dosimetry is the double-head Matrix GLCM (e.g. homogeneity, contrast) and Gray-Level Zone
Siemens Symbia 1557. A set of measurements were performed for Length Matrix GLZLM (e.g. HGZE); FF include histograms indices
calibrating the gamma camera in order to obtain the sensitivity and (e.g. skewness, kurtosis and entropy).
the transmission curves. We used 99mTc, 123I and 131I sources for On a spheres phantom (NEMA PET IEC) filled with liquid 131I
LEHR, MEGP and HE collimators respectively. For sensitivity we (13 MBq/ml), 4 SPECT-CT images were acquired at 3,120,160 and
used a petri dish filled with a radioactive solution of known activity. 216 h after preparation. Five volume of interests (VOIs) were con-
We placed the petri dish on the bed and proceed with a static toured on phantom images, one for each sphere. VOIs were contoured
acquisition of 10 min, with both detectors at the same distances from with a 3D segmentation tool, choosing a threshold value to obtain a
the source, 128 9 128 matrix, zoom 1, acquisition window centered volume the most similar to the real one. Then, we performed TF and
on the photoelectric peak. This measure was then repeated for all the FF analysis using six different discretization levels (4, 8, 16, 32, 64,
used isotopes. 128) on every single VOI. As results, the best discretization level to
The transmission curve is measured by constructing the attenuation use and the minimum VOI volume that should be evaluated with this
curve in water with an open cylindrical phantom positioned on the method were defined.
bed with its axis perpendicular to the bed itself. Under the cylindrical For 6 MDTC patients (inclusion criteria: thyroidectomy, iodine
phantom we positioned the petri dish and proceeded with a series of remnant ablation) TF and FF analysis were computed on 4 SPECT-
static acquisitions where water thicknesses are progressively CT images (Siemens IntevoT2, 256 9 256, ITSCAC) acquired at 4,
increased from 0 at least up to 20 cm. The static images are acquired 24, 48, 96 h after administration. Mean doses to lesion (MIRD sphere
only with the upper detector, 128 9 128 matrix and zoom 1, while the model) were also evaluated. 22 lesions (14 bone, 8 visceral) were
acquisition time increases with the increase of the water volume. contoured by a nuclear medicine specialist using a 3D segmentation
Results: Sensitivity allows to transform the counts detected from the tool and TF and FF analysis were computed.
camera range into activity, dividing the geometric mean of the counts Treatment outcome was classified as responding (complete and
acquired by both detectors by the measured activity in the source. The partial response) or not responding (stable and progressive disease).
transmission curve will be used for attenuation correction allowing to FA was therefore correlated to 131I treatment response through ROC
determine the patient’s average thickness along the organ’s view. The analysis (AUC, sensitivity (SS) and specificity (SP)).
parameters obtained for sensitivity are 63,300 (cps/MBq) for 123I, Results: In phantom analysis the minimal assessable volume was
15,163 (cps/MBq) for 131I. Pseudo extrapolation number obtained found equal to 1.2 cc and the optimal discretization level was found
from transmission curve (n) are 1,093, 1,022, 1,050 for 99mTc, 123I equal to 64, as suggested by literature: those results were therefore
and 131I respectively. Linear attenuation coefficient obtained from applied in patients analysis.
transmission curve l (1/cm) are 0,145 for 99mTc, 0,147 for 123I and
0.106 for 131I.

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S121

In patients, mean dose ROC analysis showed an AUC equal to 0.62 Dead time in gamma-camera, due to effects of saturation induced by
(SS 75, SP 64). Similar results were found on GLCM features (ho- high activity, is corrected by method of monitor sources: to obtain
mogeneity AUC 0.62, SS 63, SP 71 and contrast AUC 0.61, SS 38, SP images corrected for dead time it is necessary to fix in a peripheral
93). Higher effectiveness to discriminate the patient treatment position of the collimator a monitor source of I131 and to acquire an
response was shown by some FF features (skewness and kurtosis image of the monitor source with and without the patient.
AUC 0.72, SS 50, SP 100, entropy AUC 72, SS 63, SP79) as well by For scatter correction it is necessary to perform acquisitions using
TF Gray-Level Zone Length Matrix (HGZE AUC 0.76, SS 75, SP three energy windows (364 keV, 637 keV and 723 keV). 637 keV
93). and 723 keV photons create scatter in the patient that falls on
Conclusions: In MDTC patients features analysis on 131I SPECT-CT 364 keV peak, which is immersed in a diffuse radiation that reduces
images is feasible. Phantom analysis points out methods limits, image contrast. Scatter-corrected image is obtained subtracting the
allowing a standardization. sum of the two scattered images from the emissive images.
Many features were evaluated in order to investigate their influence in Results: 13 patients (7 males, age range 3–17 years) affected by
the patient response discrimination. A positive prognostic capability relapsed/refractory NB, underwent tandem high dose 131I- MIBG
was shown. These results should be integrated with the standard between 2016 and 2018; each treatment included two administration
dose–response evaluation, giving to the physician a powerful tool in of 131I-mIBG, giving in total 24 administrations as two patients were
MDTC patients treatment management. treated once. The median administered activities were: 9 GBq for
However, the small sample involved does not allow clinical results 131I-MIBG (range 3.1–13.6 GBq).
yet: additional patients involved would consolidate the prognostic and Conclusions: Dosimetry represents a valuable tool to determine the
predictive role of FA on 131I treatment response. right amount of activity that makes treatment planning feasible for
each patient. Technologist role is important to maintain good quality
in patient dosimetry assessments in compliance to the elaborate
protocols set out by each discipline.
PO217
Pediatric dosimetry practice: technical approach

E. Villanucci2, V. Nicoloso2, B. Cassano1, P. Milena2,


PO218
L. Mariaconcetta1, S. Chiapparelli2, V. Maria Felicia2, Personalized radiometabolic therapy
G. Maria Carmen2 of hyperthyroidism: analysis of the clinical response
1
through a dosimetric evaluation
2IRCCS Bambino Gesù Children’s Hospital, Medical Physics Unit,
Rome, Italy. 2IRCCS Bambino Gesù Children’s Hospital, Nuclear
R. Posterli2, I. Martinelli2, M. Cacciatori1, A. Bresolin1,
Medicine Unit, Imaging Department, Rome, Italy
M. Andruccioli2, A. Corso2
Background-aim: A dosimetry-guided treatment planning can help
1
to deliver the appropriate dose, in order to achieve a patient-specific 2Medical Physics Department, ASST Lariana, Como, Italy. 2Nuclear
therapy. Medicine Department, ASST Lariana S.Anna Hospital, Como, Italy
Treatment planning following a prospective dosimetry has become a
Background-aim: The personalized radioiodine treatment of hyper-
legal obligation in all EU countries since the EU council directive
thyroidism, in accordance with the guidelines EANM (2010) and
2013/59/Euratom has been endorsed in each national legislation.
AIMN (2012), aims to achieve a high efficacy in the clinical response
Radionuclide therapy planning is complex and needs multidisci-
(restoration of euthyroidism or hypothyroidism) through a dosimetric
plinary approach. Pediatric patient management requires a well-
study of the effective dose to the thyroid, optimizing the activity of
coordinated and specialized trained staff to perform a safe procedure
radioiodine administered and reducing the exposure to a minimum.
obtaining patient cooperation.
Methods: The effectiveness of 420 personalized radioiodine outpa-
131I-meta-iodobenzylguanidine (131I-mIBG) combined with
tient treatments in patients with Graves’ disease and toxic thyroid
myeloablative chemotherapy is a modality of treatment in children
nodules was analyzed. The investigated sample consisted of 75%
affected by relapsed/refractory neuroblastoma (NB) used in our
females and 25% males, with mean age of 53 y.
Institution since 2016.
In the pre-treatment phase, a 131I sodium-iodide track activity (about
The highest activity of 131I-MIBG administrable in order to
2 MBq) was administered, in order to identify the uptake percentage
obtain myeloablation is determined using a dosimetric protocol rou-
maximum value Umax(%) and the radiopharmaceutical effective half
tinely performed in our Unit.
life T‘eff by thyroid uptake data (at 2, 6, 24, 96 h). The functional
Aim of our work is to describe this dosimetric protocol focusing
thyroid mass was evaluated by processing a tomographic 99mTc-
on technical aspect.
pertechnetate SPECT/CT image through a specific 3D reconstruction
Methods: Dosimetry for dose assessment of lesions requires scinti-
software.
graphic images. For acquisitions, we use a double-head gamma
The treatment consisted in a single outpatient intravenous
camera Siemens Symbia 1557. 7 whole-body and static acquisitions
administration of a customized 131I activity. For all patients, treat-
are performed at scheduled time-points (high-energy collimators,
ment efficacy was verified by a clinical follow-up of [ 12 months
matrix 128 9 128, zoom 1, 10 min acquisition time for static ima-
with periodic hormonal evaluation (TSH, FT3, FT4). The favorable
ges). One of the roles of the nuclear medicine technician is to pay
response was characterized by a stable condition of hypothyroidism or
particular attention to keep geometry and acquisition parameters
euthyroidism, while the unfavorable one by the persistence of
(energy window, scan speed, height of the table, position of detectors)
hyperthyroidism.
constant. Moreover, the technician collaborates with medical physi-
All treatments were grouped according to the administered dose
cist in correction for attenuation, dead time and scatter. For
(1st group \ 200 Gy; 2nd group between 200 and 400 Gy) and the
attenuation correction, it is necessary to acquire transmission and
corresponding dose–response data were obtained. Analyses of all
blank images before the administration. Transmission images are
favorable response treatments vs. unfavorable ones were also carried
acquired using a flood phantom positioned under the patient; acqui-
out.
sition of blank is identical, but without the patient.

123
S122 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

Descriptive statistics was adopted in order to characterize the 99mTc and a NEMA IMAGE QUALITY PET phantom with hot
sample under study. The t-Student, Mann–Whitney, ANOVA and spheres, filled with 177Lu.
Kruskal–Wallis tests were used to investigate both the dosimetric data In particular, in the case of Lutetium, a cylindrical phantom with
and the clinical response. The statistical analysis was performed with pockets filled with Lutetium was used in order to study volumes up to
the IBM SPSS Statistics 23.0 software (Armonk, NY: IBM Corp). 1000 ml to cover all the volumes of clinical interest. To obtain a
Results: Total remission was observed in 85.5% of treatments (359 complete study on RC and to understand which are the factors mainly
out of 420); no remission was obtained in 14.5%. The median influencing its evaluation, different contouring methods, time per
recovery time was 4.5 months. projection and number of iterations have been considered. The same
In the 1st group, 38 out of 66 treatments had a positive outcome procedure has been repeated with SIMIND.
(57.6%). In the 2nd group, the remission was observed in 90.7% of Results: The CF was 115.8 ± 6.3 cps/MBq for Technetium, and
treatments (321 out of 354). 17.2 ± 0.8 cps/MBq for Lutetium for both SPECT CT. These results
Conclusions: The study showed that radioiodine therapy of hyper- were confirmed by SIMIND. Moreover, a complete curve RCs vs
thyroidism with personalized dosimetry has a high clinical efficacy in Volume (ml) for Lutetium, with volumes up to 1000 ml, was deter-
the 2nd group with thyroid doses of between 200 and 400 Gy (un- mined to correct the PVE for all volumes of clinical interest.
favorable response of less than 10%). Conclusions: SIMIND Monte Carlo Code can be used for simulating
In the 1st group of patients with low thyroid dose (less than 200 Gy) different radionuclides and SPECT/CT camera. In none of the cases a
the clinical response was not good, despite maximal radioiodine RC factor equal to 100 was found emerges a large variability in
activity administered (600 MBq). contouring, which is hand-dependent. A good trade-off can be 20 s
The personalized radiometabolic therapy also allows a prediction with 16 iterations and a threshold of 25% 30% for volume contouring
of clinical effectiveness useful in the management of patient follow- through the isocontour technique.
up.

PO220
PO219 Tandem high-dose 131I-MIBG therapy for paediatric
Activity quantification for dosimetry of PRRT patients with relapsed-refractory high risk
in patients with neuroendocrine tumors neuroblastoma: a dosimetry based feasible and safe
treatment
S. Di Biaso2, G. Di Domenico1, E. Tonini2, A. Barboni2, L. Manco2,
C. Bertaggia2, A. Turra2, D. Farina3, M. Bartolomei3
M.F. Villani2, M. Longo1, B. Cassano1, M. Pizzoferro2, A. Serra3,
1 A. Castellano3, E. Genovese1, S. Donatiello1, V. Cannata’1,
Department of Physics and Earth Sciences, University of Ferrara,
M.C. Garganese2
Ferrara, Italy. 2Medical Physics Unit, Sant’Anna University Hospital,
Ferrara, Italy. 3Nuclear Medicine Unit, Sant’Anna University 1
IRCCS Bambino Gesù Children’s Hospital, Medical Physics Unit,
Hospital, Ferrara, Italy
Rome, Italy. 2IRCCS Bambino Gesù Children’s Hospital, Nuclear
Background-aim: The COUNCIL DIRECTIVE 2013/59/EURA- Medicine Unit, Imaging Department, Rome, Italy. 3IRCCS Bambino
TOM of the European Union fixes the need for individual and Gesù Children’s Hospital, Paediatric Haematology/Oncology
personalized dosimetry for patients treated with radionuclides. In Department, Rome, Italy
order to fulfil such directive, it is necessary an absolute quantification
Background-aim: 131I-meta-iodobenzylguanidine (131I-MIBG)
of the activity in the organs of interests and in the targets for each
combined with myeloablative chemotherapy represents an useful
patient.
modality of treatment in children affected by relapsed/refractory
Correct activity estimation is the base for correct dose evaluation.
neuroblastoma (NB) for increasing palliation and progression-free
The main factors that impact on the accuracy of the activity
survival, as demonstrated by previous studies. Aim of our study is to
quantification in SPECT imaging are the Collimator to Detector
evaluate the feasibility and safety of tandem high-dose therapy based
Response (CDR), the attenuation and the scattering in the volume
on two administrations of 131I-MIBG followed by Melphalan.
containing the activity.
Methods: 13 patients (7 males, age range 3–17 years) affected by
Therefore, firstly, the counts within volumes containing activity
relapsed/refractory NB, (all previously treated according to SIOPEN
need to be corrected for these effects. Then, the Calibration Factor
NBHR 01 protocol) who underwent high dose 131I-mIBG-Melphalan
(CF), which converts counts into activity, has to be evaluated. In our
between 2016 and 2018 were included, giving in total 14 treatments
case, the CF for both SPECT\CT Symbia Intevo Excel and Symbia T2
as two patients were treated once. Each treatment included two
and for Tc99m and Lu177 was estimated.
administration of 131I-mIBG (injected activity ranging from 6610 to
The last step was the computation of Recovery Coefficients (RC),
11100 MBq, median: 8963 MBq), following a dosimetry-based
which are correction factors for the partial volume effect (PVE). All
approach routinely performed in our Institution. Absorbed doses to
the results have been compared and validated through Monte Carlo
whole-body (WB) and red marrow (RM) were calculated according to
SIMIND. The aim of this study was to provide a correct activity
MIRD and EANM guidelines, collecting WB data and blood samples
estimation procedure, the RC values for all volumes of clinical
at 0.5-h, 6-h, 24-h, 30-h, 48-h, 72-h and 144-h after the administra-
interest, and, finally, a better image reconstruction.
tion. The WB absorbed dose resulting from the first administration
Methods: The Symbia NET is Siemens’ workstation to reconstruct
was used to determine the second activity to be administered to reach
and analyse SPECT/CT images; it corrects for attenuation, scatter and
a total WB absorbed dose of 4 Gy. According to MIRD approach,
CDR. Moreover, CF has to be computed for every radionuclide and
tumour absorbed doses were calculated individually for both thera-
collimator under usage and can be done by using a uniform Jaszczak
peutic administrations collecting five static images; tumour volumes
phantom. Then, the RC has to be evaluated; RC is the ratio between
were evaluated by means of SPECT, CT and MRI images.
measured activity and its true value, which can be evaluated con-
96 h after second 131I-MIBG administration, a single dose of Mel-
sidering different volumes. RC evaluation study has been performed
phalan (110 mg/m2) with peripheral blood stem cell (PBSC) rescue
with a Jaszczak phantom with hot different sizes spheres, filled with

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S123

was given. All patients received antifungal, antiviral and antibacterial Studying this graphic and using the effective half time of the radio-
prophylaxis. In all patients, a 123I-MIBG scintigraphy was performed pharmaceutical in the patient essay, the second radiopharmaceutical
before treatment and SIOPEN score was determined. administration was calculated by simply subtraction. So the activity of
Results: 123I-MIBG scan showed bone/bone marrow disease alone in this one is calculated measuring the absorbed dose in the first treat-
1/13 patient (7.7%), disease in both soft tissue and bone/bone marrow ment, subsequently subtracting to the 4 Gy, suggested by protocol,
in 12/13 patients (92.3%). In 13/13 patients, SIOPEN score was [ 3. those absorbed in the first cycle of 131I-mIBG.
WB absorbed doses ranged from 1.04 to 2.44 Gy (median 1.57 Gy) Then, a similar dosimetry measurement protocol followed, to
and in RM doses from 0.72 to 2.16 Gy (median 1.13 Gy). The WB verify real absorbed dose at the end of the whole VERITAS protocol.
and RM absorbed doses per unit activity lies between 0.11–0.36 Gy/ Results: The activity administered with the second infusion was 15%
GBq and 0.07–0.32 Gy/GBq respectively, varying to a factor of 3. greaten then calculated one; the absorbed dose resulted in ? 17% of
The cumulated activity in the blood contributes from approximately that specified in the protocol. This has involved a general dose equal
10 to 20% to the RM absorbed dose. The tumour absorbed doses show to 4.30 Gy.
a high variability (between 10 and 80 Gy) mostly depending on Conclusions: A simple dosimetry procedure can give the necessary
administered activities, tumor’s uptakes and biokinetics. data for an accurate total body dosimetry. In future, real amount
After treatment, all patients presented grade 3 haematological dosimetry could be performed beside organ dosimetry from 131I-
toxicity; no patients experienced grade 4 toxicity. No episode of mIBG post therapy acquisition.
febrile neutropenia was reported.
Conclusions: In our experience, high-dose 131I-MIBG therapy
combined with chemotherapy is a feasible and safe modality of
treatment in heavily pre-treated patients affected by relapsed/refrac- PO222
tory NB in order to achieve an effective myeloablation; dosimetric Effective dose in PET/CT: report on large dataset
approach allows to prescribe a tailored treatment, administering of patients imaged by different radiopharmaceuticals
activities as high as possible.
M. Sollini1, G. Tosi2, G. Matassa1, L. Leonardi2, K. Marzo2, A. Chiti1
1
PO221 Humanitas University, Pieve Emanuele (Milan), Italy. 2Humanitas
Clinical and Research Center-IRCCS, Rozzano (Milan), Italy
Total body dosimetry in treatments with 131I-MIBG
in pediatric patients affected by high-risk Background-aim: A reliable method of estimating patient dose is
crucial for any exam that involves ionizing radiation. This study
neuroblastoma aimed to measure the effective dose of diagnostic PET/CT scans in a
large dataset of patients imaged by different radiopharmaceuticals.
T. Marradini1, P. Saletti4, C. Olianti3, G. Belli2 Methods: The GE DoseWatchTM system (GE Healthcare) was used
1
for the study purpose. All PET/CT data from examinations acquired
Author. 2Department. 3Doctor. 4Professor according to standard institutional procedures, using the Discovery
Background-aim: The aim of the study was to verify the feasibility 690 PET/CT scanner (GE Healthcare) in the period 04/03/2018–04/
of a new Protocol of treatment with 131I-mIBG, called VERITAS, in 09/2018 were collected. Overall 1508 PET/CT data (1379 total-/
patient affected by High-risk Neuroblastoma and the relative total whole-body scans, and 129 dedicated brain imaging) were evaluated.
body dosimetry based on MIRD model, by means of dose rate mea- PET/CT scans acquired with other tracers than [18F]FDG, 11C-
surements in preset geometry and, from calculated dose, second Choline (11C-Cho), 11C-Methionine (11C-Met), and 68Ga-DOTA-
administration activity is then calculated. TOC were performed within clinical trials, and accordingly excluded
VERITAS is articulated in 2 arms, and Tandem, that we investigated, from the analysis. The effective dose was evaluated using standard
foresees 2 administrations of 131I-mIBG in 15–20 days for a total coefficients referring to a generic reference individual. The effective
dose absorbed of 4 Gy to whole body patient besides 2 cycles of dose from the CT component was calculated using the conversion
chemotherapy with Topotecan. factors k multiplied by the DLP (Dose Length Product) depending on
At Careggi hospital, 6 patients have been treated for High risk the scanned region. The PET effective dose was calculated by mul-
Neuroblastoma, being refractory or unsuitable to the therapy with tiplying the injected activity by the } dose coefficient for each
only 131I-mIBG. Among these, only one patient, that we will call radiopharmaceutical. The total PET/CT effective dose was calculated
A.A. (5 years and 24 kg), has followed the Protocol VERITAS and as the sum of the PET and CT effective dose values. Descriptive and
particularly the Tandem branch. summary statistics were performed.
Methods: The activity for the first administration of 131I-mIBG has Results: Twenty-two out of the 1508 exams, performed within clinical
been calculated as a function of patient weight (24 kg), on the base of trials, were excluded. Data from 1486 PET/CT ([18F]FDG 71%, 11C-
12–15 mCi/kg. The administration of the first cycle of radiopharma- Cho 14%, 11C-Met 9%-all dedicated brain imaging-, 68Ga-DOTATOC
ceutical starts with empty bladder for 60 min. During shielded 5%) were retrieved and calculated. The PET effective dose, the total
recovery, we measure the patient exposure rate with ionization DLP, the CT dose index, the CT effective dose, and the total PET/CT
chamber, a Victoreen 450P, at the distance of 1 m. The measure of effective dose were 6.8 ± 0.4 (4.3–10.5) mSv, 1037.4 ± 268.2
the background is followed by the first one AP-PA of the patient (LL (130.8–2114.2) mGy cm, 10.3 ± 2.4 (2.6–28.5) mGy, 15.3 ± 4.7
during the night) with full bladder. The second one is acquired with (0.9–36.9) mSv, and 22.1 ± 5.1 (5.2–47.4) mSv for [18F]FDG;
empty bladder and the following ones, every 2 h for the first 24, and 1.5 ± 0.1 (1.0–1.7) mSv, 1714.9 ± 337.8 (708.4–3085.5) mGy cm,
every 4–6 h for the followings, always with empty bladder. The 18.8 ± 3.6 (11.0–22.6) mGy, 27.4 ± 5.4 (15.9–33.8) mSv, and
recorded data produced an activity vs time graphic. Absorbed dose 28.9 ± 5.5 (12.3–51.0) mSv for 11C-Cho; 2.7 ± 0.3 (1.8–3.5) mSv,
was then calculated using the MIRD model, since, the area of the 521.0 ± 152.8 (92.1–897) mGy.cm, n.a. mGy, 1.2 ± 0.8
curve corresponds to the cumulative activity (Ã) that will be multi- (0.2–7.0) mSv, and 3.9 ± 1.1 (2.0–10.5) mSv for 11C-Met; and
plied then for a constant, where ‘‘S’’ = 1.9e-06 9 70 9 Wt - 0.918 3.7 ± 0.3 (2.5–4.4) mSv, 833.5 ± 125.9 (423.8–1160.2) mGy cm,
(Gy/MBq 9 h) and Wt is patient weight (kg). 8.4 ± 0.8 (5.1–10.3) mGy, 14.1 ± 2.5 (1.5–19.7) mSv, and
17.8 ± 2.8 (4.0–24.1) mSv for 68Ga-DOTATOC, respectively. PET

123
S124 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

contribution to the total PET/CT effective dose was 31, 5, 69, and 21% scintigraphies, the CT contribution on the total effective dose varies
for [18F]FDG, 11C-Cho, 11C-Met, and 68Ga-DOTATOC, respectively. from about 10% to 50%.
The lower dose from CT in 11C-Met brain imaging compared to other Comparisons with ‘‘pure’’ diagnostic CT scans show that a direct
examinations, is obviously related to the fact that CT scan is limited to polytrauma CT exam (that assimilates total body PET/CT scan)
the head. delivers an average 28.8 mSv of effective dose (3 times higher than a
Conclusions: The contribution of CT was higher than the PET one in PET/CT total body), whereas the polyphasic polytrauma protocol
determining the total effective dose in all the total-body examinations 76.8 mSv (8 times higher than PET/CT total body).
([18F]FDG, 11C-Cho and 68Ga-DOTATOC). Therefore, CT param- Conclusions: The concept of low-dose CT frequently used regarding
eters should be optimized in PET/CT scan in order to be compliant the hybrid CT scans is a concept confirmed by the present data. The
with the ALARA (As Low As Reasonably Achievable) principle. request for additional details after the standard PET/CT Total body
Nevertheless, the information derivable from the exam should exam leads to an increase in the average effective dose of about 25%,
empower the effectiveness of a hybrid technique; therefore, param- avoiding to the patient, in the case of total body images dubious,
eters optimization should not affect image quality. further investigations that can have greater dosimetric impact or be
more invasive.

PO223
Radiation exposure of patients undergoing PET/CT PO224
and SPECT/CT hybrid examinations Optimization of [18F]-FPSMA1007 synthesis HPLC
free on FASTLab platform
S. Chondrogiannis2, A. Ferretti1, S. Stanila2, A. Bassan2, M.C.
Marzola2, L. Rampin2, G. Grassetto2, A.M. Maffione2, D. Rubello2 E. Cazzola1, D. Peruzzi1, J. Amico1, A. D’angelo1, M. Malachini1,
A. Peroni1, A. Purgato1, G. Gorgoni1
1
Medical Physics Unit, Santa Maria della Misericordia Hospital,
Rovigo, Italy. 2Nuclear Medicine Unit-PET/CT Centre-Santa Maria 1
Cyclotron and Radiopharmacy Departmant, Sacro Cuore Hospital,
della Misericordia Hospital, Rovigo, Italy Negrar, Italy
Background-aim: The use of SPECT/CT and PET/CT hybrid sys- Background-aim: Over the past years, many different PET agents
tems allows: (1) the correlation between functional and have been developed to investigating on Prostate Cancer (PC) to
morphological imaging and (2) the attenuation correction necessary make the non invasive approach a reality, in order to replace the
for PET and SPECT data. The spread of these systems requires an biopsy and the related complications. The PC is the more common
analysis of the dose increase delivered to the patient. cancer that affect the male population. Due to the high incidence of
Methods: The hybrid equipment installed in the Nuclear Medicine this pathology are mandatory to investigate on a fluorine-18 tracer
center of the Rovigo hospital is: a PET/CT Discovery STE (General that give the possibility to overcame the gallium-68 tracers limitations
Electric), a PET/CT Biograph mCT (Siemens), a SPECT/CT Dis- [1].
covery NM/CT 670 (General Electric) which mount CT scanners of The aim of this study is to optimize an automatic synthesis for
different characteristics and performances. [18F]FPSMA1007 on Ge FASTLab module, in a stable high yield
In this work we performed phantom analysis and we collected dosi- with a wide range of inlet activity, and setting up a faster, efficient
metric reports of 90 patients undergoing hybrid imaging in our center. and EU Pharmacopoeia compliant quality control to shorten the time
The effective doses from CT scans were then calculated using the CT- of product realize [2].
Expo v.2.4 software, while doses from the radiopharmaceutical Methods: The synthesis method is based on one step synthesis using
administration were calculated according to the most recent ICRU/ a new precursor commercialized by ABX and is tuned on Ge FAS-
ICRP factors (from ICRP publications 107 and 103). Furthermore, the TLab synthesizer. All the reagents are included on a single use
collected data were compared with the dosimetric data of similar cassette. The [18F]Fluorine was trapped on QMA and eluted with a
‘‘pure’’ diagnostic radiological imaging. mixture of TBAHCO3/ACN or K222/ACN/K2CO3 and after drying
Results: The CT equipment has been characterized by the parameter at 125 C on synthesis reactor, the ABX precursor dissolved in
nCTDIw normalized on the mAs, parameter necessary for the dosi- DMSO was added to proceed with the nucleophilic [18F]-Fluorina-
metric calculations in the CT-Expo software. The average, minimum tion. The reaction mixture was heated up at 95 C for 10 min after the
and maximum effective doses were calculated, dividing the sample of reaction step the mixture was cooled at 35 C to starting the purifi-
90 patients between males and females, since there are different cation step followed by formulation. The total process takes place on
organs at risk. 37 min.
The total effective dose of a Total-Body PET/CT scan on average was HPLC analysis was performed on an Agilent 1260 Infinity HPLC
9.7 mSv for men and 9.8 mSv for women. To this is added the pos- equipped with an Agilent 1260 UV detector and a Raytest gamma-ray
sible CT scan of additional acquisitions (performed for doubtful detector, controlled with Gina Star software V.5.9. The analysis was
findings, movement artifacts, etc.) with an average increase of 13% in performed on a 4.6 9 100 Eclipse Plus C18 3.5 lm (Agilent) in
the case of PET/TC brain scan, 17% for the head-neck district and a isocratic conditions using CH3CN and 0.1% TFA (70/30, run time
28% for the scan of the abdomen. 15 min).
Regarding SPECT/CT, the myocardial perfusion scintigraphy, has TLC analysis was performed on Merk Silica Gel 60 on PET
the greatest dosimetric impact, since it requires two CT scans and two (10 9 5 cm, developed over 2/3 of the plate), mobile phase MeOH/
radiopharmaceutical administrations (mean total effective dose NaCl 0.9% a Perkin Elmer Cyclone.
9.6 mSv for males and 10 mSv for females); the contribution of the Other analysis were performed according to European Pharma-
CT component (essential to correct for the attenuation) is about 10%. copoeia ‘‘Radiopharmaceutical Preparations’’.
In our centre the most frequent SPECT/CTs are performed after Results: Two different elution solution was used to compare the final
whole body bone scan, and deliver a mean effective dose of 6.3 mSv process yields, at the same time, high activity runs were performed, in
for both sexes. Here the contribution of the CT component on the total different inlet activity range, to evaluating the yield and product
effective dose is about a half. For the remaining SPECT/CT stability in final formulation. For stability study a range of

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S125

1–2.5 GBq/ml radioactive concentration was evaluated at room and at PO226


40 C for up to 12 h. According to final product formula specification 68
Ga-Edotreotide: 10 years of experience of the IEO
the synthesis yield was stable on range 30–50% at the inlet activity
range (55–170 GBq) with a very high Am (800–3500 GBq/lmol) at radiopharmacy group
EOS.
The radiochemical purity for all the runs was [ 96% and chemical S. Papi2, A.S. Cascio2, S.M. Baio1, M. Colandrea1, S.L. Fracassi1, L.
impurities were \ 0.1 mg/V. The new HPLC/TLC method allow to Gilardi1, G. Manfrinato1, P.A. Rocca1, L.L. Travaini1, C.M. Grana1,
make the quality control in terms of general indications of European M. Chinol2
Pharmacopoeia Monographs.
1
Conclusions: All the synthesis performed by using the K222 elution Division of Nuclear Medicine, European Institute of Oncology,
solution shows slightly lower yield compared to TBA, at the same 20141, Milano, Italy. 2Radiopharmaceutical Production Unit,
time any difference, in quality control profile and stability were European Institute of Oncology, 20141 Milano, Italy
found, all the products collected were stable and in high chemical/ Background-aim: 68Ga-Edotreotide (68Ga-DOTA-Tyr-Octreotide) is
radiochemical purity. The HPLC and TLC methods setup allow to the gold standard for PET diagnosis of Neuroendocrine Tumours.
perform a complete purity evaluation on less than 15 min. Since the availability of 68Ge/68Ga generator, its production and
References quality control is carried out routinely throughout the radiopharma-
1. Giesel F.L., et al. [2017], EJNMMI 44:678–688. ceutical labs in the country. This report summarizes the decennal
2. Martin R., et al. [2017], J label comp radioph 60: 594. experience of 68Ga-Edotreotide production (synthesis, QC and
improvements) in the European Institute of Oncology Radiopharmacy
lab.
PO225 Methods: Since 2008, in our radiopharmacy lab an Eckert&Ziegler
Modular Lab synthesis module was installed along with several
[89ZR]Zirconium production and labeling Negrar EZAG 68Ge/68Ga generators (typically 1.85 GBq calibration). The
experience synthesis was initially performed by the ‘‘fractionated elution’’
method, to reduce 68Ge content in the eluate, well before the publi-
E. Cazzola1, J. Amico1, A. D’angelo1, A. Peroni1, M. Malachini1, cation of Pharmacopoeia Monograph of 68Ga-Chloride and 68Ga-
D. Peruzzi1, A. Purgato1, G. Gorgoni1 Edotreotide. In 2016 a substantial upgrade was performed, installing
the pre-purification of the eluate (with cation exchange Strata-XC
1 cartridge, HCl/Acetone method). Moreover, this improvement
Cyclotron and Radiopharmacy Department, Sacro Cuore Hospital,
Negrar, Italy allowed us to install two generators in series, pursuing an optimized
activity consumption (more patients with less syntheses). In the same
Background-aim: [89Zr]Zirconium is one of the emergent isotope in period, we switched from radiochemical grade to pharmaceutical
the last three years due to the favorable PET imaging characteristics grade (GalliaPharm) generators, to be compliant with current legis-
( ? max 0.9 MeV, 22.7%) and half life (T‘78.4 h) ideal to labeling lation. Synthesis of 68Ga-Edotreotide is currently performed on a
Antibodies. Monoclonal antibodies (MABs) are the most approved daily basis, carried out by two independent operators.
biopharmaceutical in the word with a multiple and selective targets. Results: Overall, elution yield was stably around 70% throughout the
Due of this needs a robust production, purification and labelling generator life. 68Ga-Edotreotide was routinely produced with repro-
procedure should be optimized and some new pathway need to be ducible yield. The overall radiochemical yield, considered from
investigated in order to obtain, a long terms stable tracer compatible elution of the generator to end of synthesis, was above 40% in most
with a biological half live of MABs. cases (\ 2% failure rate), as expected from manufacturer specifica-
This work want to present our experience in [89Zr]Zirconium pro- tions. The quality parameters controlled (radiochemical purity,
duction, purification and labelling using commercial equipment. chemical purity, radionuclidic purity, solvents, sterility, endotoxin
Methods: The Sputtered [89Y]Yttrium target was bombarded on TR- contamination) were all inside the specifications as stated in the
19 cyclotron at 12.5 MeV without degrader at different current Eu.Ph. Monograph. To guarantee the pharmaceutical grade of the
20–50 lA for a variable time 30–240 min. The coins was transferred product, bioburden tests and media fill tests were performed to vali-
on dedicated coated hot cell and transferred on a EZAG module in date the entire production sequence. In particular, the introduction of
order to dissolve and purify the [89Zr]/[89Y] material in a single use Pharmaceutical grade generator allowed us to obtain a 68Ga eluate
cassette. A 2 N HCl solution was used to dissolve the target material, with very low 68Ge breakthrough. The Pharmacopoeia limit for 68Ga
the solution was transfer to ZR resin from and recovered on oxalate or eluate radionuclidic purity is 0.001%, or 10 Bq/MBq. HPGe analyses
chloride form. The [89Zr]Zirconium solutions was used on different on our eluate showed a typical contamination of 10-5 %, or 0.1 Bq/
labelling procedure with DFOBzNCS. MBq, 102 fold below the limit. Moreover, with the introduction of
Results: For each test, the [89Zr]Zirconium recovery yield was on pre-purification method, we further reduced the 68Ge contamination
range 90–95% with a 99.998% radionuclidic purity and a production of another 102 factor, giving an almost 68Ge-free 68Ga solution after
yield of 7–10 MBq/lAh. The [89Zr]ZrOx2 and [89Zr]ZrCl4 solutions purification (final breakthrough typically 10-7 %, or 0.001 Bq/MBq).
obtained from the purification module were used to labeling the Conclusions: 68Ga-Edotreotide routinely produced in our radiophar-
DFOBzNCS with a high yield 100% in 15 min at room temperature macy lab showed to be safe, reproducible and compliant with national
starting from Oxalate formulation and 18% of yield by using requirements for radiopharmaceutical production.
[89Zr]ZrCl4 as starting material. The final product [89Zr]ZrDFO was
stable up to 72 h.
Conclusions: What we described on this work is one of the possible
way to optimize the [89Zr]Zr production starting to [89Y]Yttrium
sputtered target, with a simple and single use cassette recovery pro-
cess based on EZAG module to minimize the impurities. We also
summarize the results of DFO chelating reaction on EZAG module.

123
S126 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

PO227 PO228
Robustness and stability of single-dose 90Y-edotreotide Novel bisphosphonates, with antiresorptive effect
in-house preparation: radiopharmaceutical aspects in bone mineralization and osteoclastogenesis,
as moieties of RA 223-based radiotracers
S. Papi2, A.S. Cascio2, S.M. Baio1, M. Colandrea1, S.L. Fracassi1,
L. Gilardi1, G. Manfrinato1, P.A. Rocca1, L.L. Travaini1, A. Scilimati1, M.G. Perrone1, S. Ferorelli1, V. Dimiccoli2,
C.M. Grana1, M. Chinol2 A. Tolomeo2
1
Division of Nuclear Medicine, European Institute of Oncology, 1
Department of Pharmacy-Pharmaceutical Sciences, University of
20141, Milan, Italy. 2Radiopharmaceutical Production Unit, European Bari, Via E.Orabona 4-70125 Bari, Italy. 2ITEL Telecomunicazioni
Institute of Oncology, 20141, Milan, Italy Srl, via A.Labriola, 39, Ruvo di Puglia, Italy
Background-aim: Peptide Receptor Radionuclide Therapy (PRRT) Background-aim: Bisphosphonates such as zoledronic, alendronic
has shown its usefulness in the treatment of Neuroendocrine Tumours and risedronic acids are a class of drugs clinically used to prevent
since many decades. The widespread use of somatostatin analogs bone density loss and osteoporosis. Based on their structure a new set
radiolabeled with 90Y/177Lu is possible if the radiopharmaceutical is of P–C P bisphosphonates (BPs) was projected to be then transformed
widely available, its preparation is straightforward and the final sta- in radiotracers, as the anion of Ra 223, in place of the two chlorides of
bility meets logistic and distribution issues (especially for 90Y 223Radium chloride transformed into 223Ra-bisphosphate to be used
labelled compounds). In this study we analyze the in-house prepara- in the treatment of bone metastases derived from several types of
tion of a single-dose amount of 90Y-DOTATOC and its quality tumors, i.e., prostate cancer.
(including stability) over a large period of time, sufficient for Methods: Suitable methodologies to prepare C–P–C BPs were
preparation in advance and eventual distribution as needed. developed. Human farnesyl pyrophosphate synthase (hFPPS) and
Methods: 90Y-DOTATOC (90Y-Edotreotide) preparation was set up geranylgeranyl pyrophosphate synthase (hGGPPS) were obtained by
in our radiopharmacy thanks to our expertise in peptide radiolabeling gene expression and protein purification: expression vectors con-
with therapeutic emitters. The labelling was carried out and optimized taining cDNA sequences encoding for hFPPS or hGGPPS, pET-
for a single patient injection, following the requirements of a clinical 6xHis/hFPPS and pET-6xHis/hGGPPS, and were individually used to
protocol; moreover, due to the lack of a dedicated monograph, a full transform E. coli BL21 competent cells. The expression and the
Investigational Medicinal Product Dossier (IMPD) was prepared and purification methods were the same for both enzymes. IC50 values
filed to the competent authority. After receiving requirements from were determined using a colorimetric assay. Cytotoxic effect was
the authority to further characterize the active substance and the final evaluated by crystal violet assay and CCK-8 intracellular dehydro-
product, we finalized the preparation with full quality control line. genase assay [the activity of the intracellular dehydrogenases was
Typically 115 lg GMP grade DOTATOC were labelled with assessed by using the Cell Counting Kit-8]. Hydroxyapatite affinity
2.96 GBq pharmaceutical grade 90YCl3, incubating at 95 C for assay of BPs expressing affinity for bone mineral represents was
30 min in ascorbic buffer. After cooling, the mixture was transferred accomplished to predict the in vivo interaction with bone tissue and
to the final vial diluting to 10 mL with saline through an on-line eventually the possible clinical efficacy. Effects of novel BPs on
disposable 0.22 lm filtration, with no further purification. The com- mineralization of pre-osteblastic cell line: in the mineralization assay
pounded product was analyzed for: radiochemical purity (RCP), performed on pre-osteoblastic like cell line MC3T3-E1, the com-
chemical purity, radionuclidic purity, microbial count, endotoxin pounds under investigation were capable to induce osteoblastogenesis
count. Stability of the formulation was tested by Radio-HPLC up to and mineralization in the nanomolar concentration range
24 h at room temperature. (30e500 nM) after 10–15 days of incubation of the cells with the
Results: 90Y-Edotreotide preparations were found reproducible and mineralization medium (MM). Ex vivo investigation on the effects of
robust, with all parameters well inside specifications. The raw BPs on murine bone marrow cells: in the mineralization assay, per-
reagents and the final compounded product were found always sterile formed on bone marrow cells extracted from tibia and femur of the
and endotoxin free (\ LOD). In particular, RCP value ranged from mice, the compounds under investigation were capable to induce
(98.4 ± 1.0) % at end of synthesis to (97.0 ± 1.5) % at 24 h, safely osteoblasto genesis and mineralization in the nanomolar concentra-
higher than common 95% cutoff considered for therapeutic drugs. tion range (30e50 nM), after 10-15 days of incubation of the cells
Conclusions: The in-house preparation of 90Y-Edotreotide, following with the MM.
our internal procedure and competent authority suggestions, is safe Results: Novel P–C–P bisphosphonates were synthesized for target-
and reliable and can be transferred to clinical setting for therapeutic ing hFPPS and hGGPPS, key enzymes of the mevalonate pathway,
protocols. and capable of anti-proliferative action on a number of cell lines
(PC3, MG63, MC3T3, RAW 264.7, J774A.1, bone marrow cells and
their co-colture with PC3) involved in bone homeostasis, bone

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S127

formation and death. Among sixteen compounds, [1-hydroxy-2- ions treated cells, along with an increased uptake, a peak activity was
(pyrimidin-2 ylamino)ethane-1,1-diyl]bis(phosphonic acid) (10) was evident after 40 min, followed by a progressive decrease.
effective in reducing PC3 and RAW 264.7 cell number in crystal- Conclusions: As previously described in some studies 18F-FET (O-
violet and cell-dehydrogenase activity assays at 100 mM concentra- (2-[18F]fluoroethyl)-L-tyrosine) in T98G has increased uptake after
tion. 10 reduced differentiated osteoclasts number similarly with irradiation. Many factors could be involved in this paradox effect
zoledronic acid in osteoclastogenesis assay. At nanomolar concen- including p53mt expression and/or selection of more aggressive
trations, 10 was more effective than zoledronic acid in inducing radioresistant clones.
mineralization in MC3T3 and murine bone marrow cells. 10 signifi- 18F-FET and F-DOPA are accumulated via the LAT1 transporter:
cantly inhibited the activity of hFPPS showing an IC50 of 0.31 mM 18F-DOPA is incorporated into proteins while 18F-FET is not
and a remarkable hydroxyapatite binding of 90%. Docking calcula- metabolized. For that reason, time-activity curves (TAC) tend to
tions were performed identifying putative interactions between some plateau with 18F-DOPA and to present with rapid wash-up in case of
novel bisphosphonates and both hFPPS and hGGPPS. 18F-FET. After irradiation with photon ions 18F-DOPA TAC
Conclusions: The novel [1-hydroxy-2-(pyrimidin-2-ylamino)ethane- resembles the 18F-FET pattern. A possible explanation may be that
1,1-diyl]bis(phosphonic acid was found to behave similarly or even the effects of ionizing radiation uncouple the mechanism of uptake
better than zoledronic acid as a antiresorptive agent. Attempts of its (preserved and enhanced) and protein incorporation (impaired).
functionalization to subsequently complexation with stable divalent
ions, barium or strontium simulating Ra 223, were accomplished.
PO230
Therapeutic radiometals: global trends analysis
PO229
of scientific literature (2008–2018)
Effects of irradiation with photons and carbon ions
on the 18F-DOPA uptake by T98G glioblastoma cell L. Uccelli2, P. Martini2, C. Cittanti2, A. Carnevale2, L. Missiroli1,
line. Comparison with 18FET in vitro study M. Giganti2, M. Bartolomei3, A. Boschi2
1
F. Pasi5, M.G. Persico6, M. Vigorito2, M. Marenco4, A. Facoetti1, Bibliometric and Databases Unit, Research Office, University of
M. Hodolič3, R. Nano2, L. Lodola4, C. Aprile1 Ferrara, Ferrara, Italy. 2Department of Morphology, Surgery and
Experimental Medicine, University of Ferrara, Ferrara, Italy. 3Nuclear
1
CNAO Foundation, Pavia, Italy. 2Department of Biology and Medicine Unit, Sant’Anna University Hospital, Ferrara, Italy
Biotechnology ‘‘Lazzaro Spallanzani’’, University of Pavia, Pavia, Background-aim: Academic journals have published a large number
Italy. 3Nuclear Medicine Research Department, IASON, Graz, of papers in the therapeutic NM research field in the last 10 years.
Austria. 4Nuclear Medicine Unit, Fondazione IRCCS Policlinico San Despite this, a literature analysis has never been made before to point
Matteo, Pavia, Italy. 5Radiotherapy Unit, Fondazione IRCCS out the research interest in therapeutic radionuclides (RNs). For this
Policlinico San Matteo, Pavia, Italy. 6University School for Advanced reason, the present study has the aim to specifically analyze the
Study, IUSS Pavia, Pavia, Italy research output on therapeutic radiometals from 2008 (January) to
Background-aim: The differential diagnosis between brain tumors 2018 (October) with the aim to quantify and identify the global trend
recurrence and early neuroinflammation or late radionecrosis is still of scientific literature and emphasize the interdisciplinary nature of
an unsolved problem either with MRI or PET molecular imaging. this research field.
The aim of this study was to evaluate the effect of irradiation on the Methods: The data search has been targeted on conventional (I-131,
uptake of 18F-DOPA (3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine) Y-90, Lu-177, Re-188, Re-186, Sm-153, Sr-89, Er-186) and emergent
by the T98G glioblastoma cell line. (Cu-67, Sc-47, Ra-223, Ho-166, Tb-161, Tb-149, Pb-212/Bi-212, Ac-
Methods: Samples with 2 9 105 cells per flask were irradiated at 225, Bi-213, At-211, Sn-117) RNs. Authors, starting from this time
room temperature 20 h after seeding. The irradiation was performed frame data, have been quantitatively first, and qualitatively after,
with photon doses of 2, 10 and 20 Gy using 6 meV LINAC at a dose analyzed and interpreted the scientific trend of this topic. Bibliometric
rate of 3 Gy/min and with carbon ions (energy range 246–312 MeV/ data have been exported from Scopus database and elaborated with
u) using the synchrotron clinical beam at the National Centre for Excel. The number of article, article in press, note, short survey,
Oncological Hadrontherapy (CNAO), at a dose of 2 Gy (physical review and letter, have been divided per year and RN with the aim to
dose, dose rate of 0.7 Gy/min). make perceptible the trend of the last decade. Data have been cate-
Thirty-six hours post-irradiation, 18F-DOPA uptake was evaluated gorized also in terms of Journal Subject Areas in order to bring out the
after addition of 100 kBq of to each flask. Activity in the adherent multidisciplinary nature of the research in this field. Finally, for each
cells as well as the number of surviving cells and their viability at publication, authors country provenience have been extrapolated and
different incubation times (20, 40, 60, 80 and 120 min) were elaborated to map the global researcher interest and involvement of
measured. human and financial resources.
Results: Results were expressed as added dose (%) on 2 9 105 cells, Results: A total of 12.717 publications have been analyzed. 81.3% of
corrected for decay and for non-specific binding. Sham-irradiated the publications regards conventional RNs while 18.7% regards
cells (0 Gy) were considered as control. emergent RNs. The most investigated therapeutic RNs are I-131,
In basal conditions T98G cells reached a maximal uptake 40 min after Y-90, Lu-177 among conventional, Ra-223, followed by Sn-117, Bi-
18F-DOPA addition, afterwards reaching a plateau. In photon-irra- 213 and Ac-225 among emergent RNs. From the analysis, it is evident
diated cells the kinetic pattern changes dramatically: (a) absolute the multidisciplinary contribution to this field but in particular, as
uptake of 18F-DOPA increases more than two or three times after expected, in the case of conventional RN most publications comes
irradiation; (b) a peak activity was observable firstly at20 min) and from preclinical and clinical fields while for the emergents the con-
we cannot rule out earlier higher activity before 20 min, followed by tribution is unbalanced for Physics, Engineering, Material Science
a rapid wash-out and by a further re-uptake at 80 min; (c) in carbon- fields mainly focused on emergent RNs production studies. From the
geographical point of view we can see how almost half of the total
works have been published by European in both conventional and

123
S128 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

emergent RNs categories. It is also evident the high collaboration cartridge. After elution and azeotropic distillation, TET precursor
grade between countries characteristics in line with the multidisci- (10 mg in 3.5 ml ACN) was added to the activated fluoride and the
plinarity of this medical sector. Moreover, we extrapolated a countries mixture heated at 100 C for 500 s. Best hydrolysis condition was
top 20 for each category. On the podium for the conventional RNs are found with 1 N HCl (3.5 ml) at 100 C for 15 min. Diluted and
USA, Germany and China, while for emergent RNs are USA, Ger- cooled reaction mixture was transferred on a C18-Plus Long cartridge
many, United Kingdom. And much more. and washed with 17 mL ppi water. Cartridge containing the product
Conclusions: From this analysis arise that the success of NM has was then eluted with 9 ml of ethanol/water (5:95 v/v). First 2 ml
been intimately linked to the availability of new RNs and the radio- containing major impurities were discarted, while the rest collected
pharmaceuticals field is constantly evolving thanks to the contribution after purification on Alumina N cartridge. The product was refor-
of specialists coming from different disciplines and the collaboration mulated with saline to the standard final batch volume of 20 ml, and
between countries. In recent years the focus of the research shifted on finally delivered in the destination vial passing through a sterilizing
the field of emergent therapeutic radioisotope production and appli- filter. [18F]FET was obtained during validation syntheses in a non-
cation, such as Cu-67, Sc-47, for the interest in new treatment decay corrected yield of 23.2% ± 2.8% (n = 3).
strategies such as the theranostics personalized approach. Alpha After QCs all batches were respecting specifications reported in the
emitters, in particular Ra-223 and Ac-225 are also gaining attention in monograph. For the evaluation of enantiomeric purity, an easy, cheap
particular in USA and Germany. Instead, among conventional and fast thin layer chromatography (TLC) method was proposed and
radionuclides the research on Lu-177 is constantly growing. successfully carried out.
Conclusions: This work presents a feasibility study to perform
[18F]FET synthesis using an automated module, commonly applied
for 68Ga-tracers, in a radiopharmacy without cyclotron. Synthetic
PO231 strategy details and final purification without a HPLC are presented.
Feasibility study for the [18F]FET manufacturing Fully QCs are reported as well as an alternative method for the
with a gallium-68 automated synthesizer determination of enantiomeric purity.
in a radiopharmacy without cyclotron facility

M. Riondato2, S. Pastorino2, G. Giovacchini2, V. Duce2, PO232


O. Ferrando1, E. Cazzola3, G. Gorgoni3, A. Ciarmiello2 Identify and prevent risks in radiopharmacy:
1
Health Physics Department, S. Andrea Hospital, La Spezia, Italy.
implementation of a microbiological contamination
2
Nuclear Medicine Department, S. Andrea Hospital, La Spezia, Italy. control program based on a risk-assessment
3
Radiopharmacy and Cyclotron Department, IRCCS ‘‘Sacro Cuore-
Don Calabria’’, Negrar, Italy S. Pastorino2, M. Riondato2, F. Repetto1, F. Montagnani2,
M.T. Vannucci2, E. Giovannini2, A. Ciarmiello
Background-aim: Among PET imaging applications, O-(2-[18F]flu-
oroethyl)-L-tyrosine is gaining attention for the assessing brain 1
Department of Pharmacy, University of Genoa, Genoa, Italy. 2Unit
tumors. [18F]FET is an established radiopharmaceutical not com-
of Nuclear Medicine, S. Andrea Hospital, La Spezia, Italy
monly available in Italy, due to a unique foreign commercial
distributor or internal manufacturing and use by few hospital radio- Background-aim: One of the main risk in a radiopharmacy is the loss
pharmacies with a cyclotron facility. The aim of this study is to or reduction of sterility assurance and the subsequent microbiological
demonstrate that a radiopharmacy without a cyclotron facility, but contamination that might spread to injectable preparations. In Italy
implemented with an automated synthesizer typically dedicated for environmental parameters for pharma-grade A–B–C clean-rooms and
Gallium-68 chemistry and a fully equipped Quality Controls (QCs) hot-cells must be periodically monitored, in the respect of national
laboratory, can prepare [18F]FET according to the European Phar- legislation. However European Pharmacopoeia and Eu-GMP, which
macopoeia(PhE) monograph 2466. are the main guidelines in this context, have been recently imple-
Methods: Radiosynthesis was carried out using a standard Modular- mented towards the determination of the acceptable levels of risk to
Lab PharmTracer (Eckert and Ziegler, EZ) in the typical setting for ensure an appropriate radiopharmaceutical (RPh) quality. The extent
the production of gallium-68 peptides, implemented with a com- of the Quality System driven by the risks for the patients represents a
mercially available chemical vacuum pump and an external additional crucial advance in RPh-laws, now placing its emphasis on prevention
3-way valve (Burkert). EZ disposable cassettes were slightly modi- of incidents rather than cure.
fied, reactor vessel replaced with a glass MX-Tracerlab (GE), and The aim of the study is to develop an appropriated sampling layout for
finally adapted to the module. our radiopharmacy, related with the potential contamination of RPh-
[18F]FET was prepared by a two-step reaction: [18F]fluorine activa- manipulation, using risk analysis and experimental approaches.
tion using potassium carbonate and Kryptofix 222 (classic method) Results will be evaluated in order to implement the routinely
and fluorination of O-(2-tosyloxyethyl)-N-trityl-L-tyrosine tert-butyl inspections, to justify the microbiological monitoring frequencies and
ester (TET) first, followed by acid hydrolysis with 1 N hydrochloric to propose risk-reducing measures.
acid (all reagents were purchased by ABX). Final purification, Methods: The number of monitoring points for a pharma-grade area
reformulation and terminal sterilization were carried out before depends on the size of each isolated environment, while their posi-
determining the radiopharmaceutical product quality. All purifications tions are driven by the risk level of contamination for the product
were performed with on-line cartridges (QMA-Light, C18-Plus Long quality. Sampling point risk levels were assessed using the failure
and Alumina N cartridges, Waters). mode and effect analysis (FMEA) approach. Selected High risk points
[18F]fluorine for radiolabeling, respecting the PhE monograph were then experimentally tested. Room surfaces as well as gloved
2390, initially used to assess critical steps of radiosynthesis was fingertip and workbench sampling were monthly monitored with TSA
7.5–12 GBq. Labeling performances were then tested up to 28 GBq. Petri dishes, two times per day (begin and the end as the worst case).
Results: [18F]fluoride in enriched water was automatically transferred After sampling dishes were incubated at 25 C/35 C and the number
(pneumatic system) from the shipped vial to an anionic exchange of colony forming units (cfu) counted. Applied criteria for evaluation

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S129

of the results was based on UNI EN ISO 14644-1/Eu-GMP for clean- purity determination. The measurement (3–4 h lasting) is made using
rooms. For hot-cells [ 1 cfu for workbench and [ 3 cfu per hand a calibrated HPGe p-type detector coupled to a multichannel gamma-
indicated test failure. ray spectrometry analyzer with 29.1% relative efficiency(Co-
Results: The sampling point layout depends on the level of risk for [email protected] meV).Samples are placed into a calibrated measurement
the RPh quality, thus to patient health. Before sampling it’s critical to Marinelli beakers together with 450 ml rinsing water. The Ge-68
determine a selection of points based on the contamination risk level. activity of the sample is determined by quantification of the 511-keV
Kind of RPh-manipulation, infrastructure aspects, routinely practice photopeak and calibrated at the time point of Ga-68 activity mea-
and adequacy of cleaning specified in our procedures were considered surement. Samples of constant geometry (standard measurement
in the assessment, as well as 4 years historical data. Low, Mid and beaker of 450 ml) are counted with low dead time.
High risk level of contamination were addressed for 44 potential Results: All radionuclidic purity determinations, assessed on 113
sampling points. 17 spots with significant severity were identified and samples collected in our Department from 15/1/2018 until 30/11/
the microbiological contamination tested at rest and in operation, both 2018, comply with Pharmacopoeia limit of 0.001% of the total
for bacteria and fungi growth. Clean-rooms respected the environ- radioactivity for Ge-68 and other gamma-emitting impurities. In
mental requirements. Results for hot-cells were satisfactory, however detail, radionuclidic purity expressed as percentage of Ga-68 mea-
2 of the 4 isolators (for gamma emitters and 18F-FDG dedicated sured was: for eluate max 7.04E-05, mean 2.48E-05 standard
dispensing unit) showed a slight deviation from the imposed criteria, deviation 1.91E-05; for synthesis max 4.10E–05, mean 2.22E-05
probably due to the high frequency of entrance of disposable mate- standard deviation 1.32E-05.
rials, kits and syringe shields. Conclusions: This study suggests the possibility to avoid pre-purifi-
Conclusions: The radiopharmacy has achieved compliance to cation of the Ga-68 eluate and to use full generator eluate volume
guidelines implementing the microbiological contamination control directly for the labelling, considering that we have already evaluated
program using a risk-assessment approach. Due to experimental other factors like amount of the ligand and the selectivity of the
evidence, the cleaning and disinfecting procedures applied to isolators chelator. This approach could reduce synthesis time of 25%. Fur-
have been revised and are now in force. thermore, the solid-phase extraction step of the 68Ga-labelled peptide
at the end of the radiolabelling process also ensures also ensures an
almost complete removal of Ge-68. Before its introducing in clinical
routine, we would have to validate this new synthesis pathway, during
PO233 which we are planning to determinate metallic ion impurities(Al(III),
One year evaluation of radionuclidic purity In(III), Ti(IV), Zn(II), Ti(IV), Fe(III)),using ICP-MS, in samples of
of the 68GE/68GA eluate: a chance to avoid pre- eluate and synthesis.
purification?

S. Agostini2, R. Visentin3, A. Palermo2, D. Donner2, S. Pegoretti1, PO234


A. Fracchetti4, E. Bagatin2, S. Laner2, E. Pedrolli2, C. Ress2, Teceos quality control: does the stationary phase
D. Ravanelli3, F. Annese2, A. Valentini3, F. Chierichetti2
suffer cold temperature?
1
Laboratory Department, APPA Trento, Italy. 2Nuclear Medicine
Department, S Chiara Hospital, APSS Trento, Italy. 3Physics A. Iudicello1, A. Franceschetto1, N. Prandini1
Department-APSS Trento, Italy. 4Physics Department-ASDAA 1
Bolzano, Italy Unit Nuclear Medicine, University/Hospital Modena, Modena, Italy

Background-aim: The long half-life of Ge-68 links the radiotoxicity Background-aim: The analytical procedure for the determination of
of the radionuclide to a great extent to its long-term biodistribution radiochemical purity (PRC) of the kit based-radiopharmaceutical
and the biological fate of the daughter Ga-68 produced at the sites of preparations (RPs) required by the manufacturer sometimes
deposition of the Ge-68.The level of Ge-68 cannot be determined - can take too much time and create problems with QC execution
before injection of a Ga-68 radiopharmaceutical. The decay of Ge-68 before the clinical use
itself does not provide any detectable emissions and the amount of - needs equipments not always available in nuclear medicine
Ge-68 can be determined only after sufficient decay of Ga-68 gen- laboratories
erated by the decay of the residual Ge-68. Herein, we present - needs stationary phases (FS) not easily available in commerce.
radionuclidic purity data collected in 1 year use of 68Ge/68Ga phar- This is what happens with the 3,3-diphosphono-1,2-propanedi-
maceutical grade generator Galliapharm. Aim of the measurements carboxylic acid (DPD) (Teceos).
are: asses the stability of the TiO2 column and evaluate efficacy of the The manufacturer has prescribed two procedures to test the PRC
pre-purification of the eluate before radiolabelling and its impact on of the final RP.
radionuclidic purity of 68Ga-DOTATOC for clinical use. Method 1 Thin layer chromatography (TLC) using as FS two
Methods: Radionuclidic purity of the Ga-68 solution is determined ITLC-SG (2.5 9 20 cm), previously heated at 110 C for 10 min and
by measurements of Ge-68 activity (Ge-68 breakthrough) and coated to room temperature before use, and, as mobile phases (FM),
gamma-ray emitting impurities with a half-life longer than 1 h (our 1 M CH3COONa solution and MEK.
library: Co-57, Co-58, Ge-69, Y-88, Zn-88). We analyzed different Method 2 Ascending paper chromatography making use of two
Ga-68 solution samples: eluate after 4 days off, eluate after daily chromatographic systems: FS A = Whatman 31ET type
elution and solution of 68Ga-DOTATOC obtained with MiniAllinOne (2.5 9 20 cm), FM A = 1 M NaCl solution; FS B = Whatman 1 type
radiosynthesis module(TRASIS)and cationic pre-purification of the (2.5x20 cm), FM B = MEK.
eluate. For the detection and quantification of Ge-68 and gamma-ray- The aim of this study was to find out an alternative analytical
emitting impurities, Ga-68 samples with activity 10–15 MBq are procedure for the determination of PRC: it was to be quick and easy to
retained for at least 48 h to allow the Ga-68 to decay to a level that realize but absolutely reliable as a method.
permits the detection of impurities, according to European Pharma- Methods: As it was not available Whatman 31ET type, method 2 was
copoeia, test B.Gamma-ray spectrometry is applied for radionuclidic not taken into consideration.

123
S130 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

As an alternative to method 1 of the Summary of product charac- Methods: The subject of the study is the self-dispensing system
teristics (SmPC), four methods have been developed (A, B, C, D). called KARL100 (Tema Sinergie) recently acquired in our centre. Its
Method A FS = two ITLC-SG (2.5 9 20 cm), not previously shielding consists of lead panels with tungsten inserts, differentiated
heated at 110 C for 10 min, FM = 1 M CH3COONa solution and according to the working areas; the maximum shielding is equal to
MEK. 60 mm Lead, above the area of the mother vial. The system is
Method B FS = two Whatman 1 type (2.5 9 20 cm), not previ- associated with an automatic Rad-inject infuser, with 8.5 mm tung-
ously heated at 110 C for 10 min, FM = see method A. sten shielding, which is set to deliver the radiopharmaceutical in
Method C FS = two ITLC-SG (1 9 10 cm), not previously heated 1 min.
at 110 C for 10 min, FM = see method A. The system previously used, and to which these comparisons are
Method D FS = two Whatman 1 type (1 9 10 cm), not previously carried out, is a fixed isolator NMC 50 DSI (Tema Sinergie), with
heated at 110 C for 10 min, FM = see method A. front wall and glass equivalent to 50 mm Lead. Syringes already
The PRC of three RP has been determined both with the Method 1 inserted into the Tungsten shield are coupled to the dispensing system
and the four developed methods. before preparing the required activity.
The PRC has been determined three times with each method. The dosimetric evaluations were carried out through environ-
The limit of acceptability of PCR was the same indicated in mental measurements with Victoreen 450P ionization chamber and
SmPC. with the use of personal TLD dosimeters. Environmental measure-
The values of PRC obtained with A, B, C, D and values of method ments were performed during all phases of preparation, dispensing
1 have been compared trough test of Mann–Whitney (test without and administration of PET radiopharmaceuticals, measuring the
statistic parameters). instantaneous exposure rates and the duration of each operation.
It has been executed a specificity test to value the capacity of Results: The set-up operations of the two systems involve exposures
methods A, B, C, D to differentiate species: 99mTc-free, 99mTc- similar and low (0.4 lSv for the fixed insulator, 0.3 lSv for the
hydrolysed, 99mTc-DPD. Karl100). The operations of preparation and administration of 18F-
Finally it has been tested the stability of the final product after FDG dose to the patient, with the use of Karl100 ? RadInject,
eight hours from preparation, using both method 1 and methods A, B, involve exposures much lower than the previous obtained with the
C, D. fixed isolator. The average daily dosimetry obtained from environ-
Results: The four developed methods use FS usually available in mental measurements entails for the technician a reduction of
laboratories and do not require the heating of FS at 110 C for exposure to body of 51%, and to the physician of 74%. On the
10 min. extremities, the equivalent dose to the hands of the technician is
FS 1x10 cm have been tested in order to reduce the time of reduced by 77% and for the physician of 97%. The average monthly
chromatography. readings of the additional dosimeters worn by the technician from
In four developed methods, with 1 M CH3COONa solution Rf of February to September 2018 were unchanged for body simulation
99mTc-hydrolysed = 0, whereas Rf 99mTc-DPD ? 99mTc-free = (0.02 mSv equivalent to the minimum detectable dose) and reduced
0.8–1; with MEK Rf of 99mTc-hydrolysed ? Rf 99mTc-DPD = 0, by 72% for the hands (4.6 mSv vs 1.3 mSv), confirming the estimated
whereas Rf 99mTc-free = 1. From the comparison of the resulting environmental assessments.
p-values in the test of Mann–Whitney it is clear that there is not The monthly doses collected from the individual TLD dosimeters
significant statistic difference between method 1 and methods A, B, showed a reduction of 23% in the dose at the hands of technicians
C, D: p-value [ 0.05. The methods A, B, C, D can be considered (passing from 3.6 to 2.8 mSv a month) and on average of 42% to the
statistically equivalent at method 1 but method C was the quickest one physician’s body and hands. The body exposure of the technician is
(approx 2 min development time of chromatography), in addition the slightly increased (from 0.10 to 0.12 mSv a month), perhaps due to a
methods B and D were not reliable to differentiate 99mTc-free and slightly greater radiation background in the new working area.
99mTc-hydrolysed. Conclusions: The exposure of the operators, both for the technician
The stability of the final product was confirmed after 8 h from assigned to the 18F-FDG preparations, and for the nuclear physician
preparation using both method 1 and methods A, B, C, D. assigned to the administration, is significantly reduced with the
Conclusions: The method C can be used for determine the PRC% of introduction of the new Karl100 system.
DPD labeled with technetium-99m.

PO236
PO235 Targeting neurotensin receptor positive tumors:
A new mobile self-dispensing and administering system in vitro binding of malignant pleural mesothelioma
for 18F-FDG: evaluation of operator dose reduction with 68GA-DOTA-neurotensin engineered fragment
A. Ferretti1, A. Massaro2, M. Minerva2, S. Gusella1, A. Bassan2, M. Marenco2, V. Frangipane4, M.G. Persico5, M. Hodolic3,
S. Chondrogiannis2, M.C. Marzola2, A.M. Maffione2, L. Rampin2, F. Meloni4, C. Aprile1, G. Cavenaghi2, L. Lodola2
G. Grassetto2, D. Rubello2
1
1
Fondazione Centro Nazionale Adroterapia Oncologica (CNAO),
Medical Physics Unit, Santa Maria della Misericordia Hospital, Pavia, Italy. 2Nuclear Medicine Department IRCCS Policlinico San
Rovigo, Italy. 2Nuclear Medicine Unit-PET/CT centre- Santa Maria Matteo Foundation, Pavia, Italy. 3Nuclear Medicine Research
della Misericordia Hospital, Rovigo, Italy Department, IASON, Graz, Austria. 4Unit of Respiratory Diseases,
Background-aim: Recently, a new mobile fractionator/dispenser for IRCCS Policlinico San Matteo Foundation, Pavia, Italy. 5University
PET radiopharmaceuticals has been adopted in the Center of Nuclear School for Advanced Studies IUSS, Pavia, Italy
Medicine of Rovigo Hospital. It allows to automate and simplify the Background-aim: Malignant Pleural Mesothelioma (MPM) is an
process of FDG dose preparation. The aim of the present work is to aggressive tumor, with no effective therapy available, in fact MPM is
assess the advantage in radiation protection of operators. largely unresponsive to conventional chemo-radiotherapy. Many

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S131

patients do not experience symptoms until the late-stages of cancer, kinetic uptake assay of 68Ga-DOTA-NT-20.3 on PDAC cell line
since signs of disease are nonexistent or virtually undetectable in (AsPC-1).
earlier stages. To date, the diagnostic power of PET/CT imaging does Methods: 68Ge/68Ga generator was eluted with 8 mL 0.1 M HCl. A
not seem to significantly increase the accuracy of early diagnosis. cleaning elution was carried out to eliminate the 68Zn present in the
Neurotensin peptide fragment (6–13) DOTA-NT-20.3 labeled with generator, which can affect the synthesis yield. For the preparation of
68 68
Ga (engineered by IASON, Graz, Austria) is a new and promising Ga-DOTA-NT-20.3, 150-700 MBq of 68GaCl3 (app. 8.0 mL) and
imaging molecular probe. Due to the high neurotensin receptor-1 50 lg of precursor (provided by Iason, Graz, Austria), dissolved in
(NTR1) expression of MPM cells, we evaluated the diagnostic rele- 50 lL TraceSelect Water, were used in an automatic synthesis
vance of this drug in vitro on the mesothelioma cell line MSTO-211H, module. The 68Ga elution was pre-purified on SCX column. The
by cell kinetic uptake assay. We selected the human malignant purified 68Ga3? was obtained eluting the column with NaCl/HCl 3 M
mesothelioma cell line MSTO-211H because of its intense prolifer- solution (pH = 1). Two mL of 0.8 M sodium acetate buffer and 400
ative activity, its aggressive profile and its NT/NTR1 high expression lL EtOH/H2O at 50/50% (v/v) was added to 50 lg NT-20.3 and to
68
levels. Ga3? solution eluted from column. The reactor was heated to
Methods: For the preparation of 68Ga-DOTA-NT-20.3, 80 ± 2 C for 3 min and then to 110 ± 2 C for 7 min. The product
600–700 MBq of 68GaCl3 and 50 lg of precursor, dissolved in 50 lL was diluted to 8 mL with 0.9% saline solution. Final product pH
TraceSelect Water, were used in an automatic synthesis module. The ranged between 4.0 and 5.0. AsPC-1 were treated with 2.09 pmol of
68
product was diluted to 8 mL with 0.9% saline solution. Final product Ga-DOTA-NT-20.3 and uptake was measured at different time
pH ranged between 4.0 and 5.0. MSTO-211H cells were incubated points (60, 80, 100 and 120 min), with a 3’’x 3’’ NaI(Tl) pinhole
with 100 kBq of 68Ga-DOTA-NT-20.3 and uptake was measured at gamma counter (RaytestGita). In saturation binding experiments,
different time points (40, 60, 80, 100, 120 min), with a 300 9 300 AsPC-1 cells were incubated for 40 min with increasing amounts of
NaI(Tl) pinhole gamma counter. In saturation binding experiments, the radiotracer (0.58; 2.09; 5.64; 18.94; 31.33 pmol). Values of Kd
MSTO-211H cells were incubated for 40 min with increasing con- and Bmax were determined by nonlinear regression one-binding site
centrations of the radiotracer (0.224, 0.624, 1.05, 1.93 pmol), in order model, using GraphPad Prism 5.01 software.
to reach activities of about 50, 100, 300, 500 kBq. Results: The time activity curve showed a rapid 68Ga-NT-DOTA-
Results: Our findings showed that the radioligand uptake plateaued 20.3 uptake: it started at 40 min (2% of total activity), increased at
80 min after 68Ga-DOTA-NT-20.3 incubation. Moreover, the satu- 60 min (8% of total activity) and plateaued at 80 min (11% of total
ration binding experiments statistical analysis revealed a Hill slope activity). Results were expressed as activity (kBq) per 2 x 105 AsPC-1
value h between 0 and 1, thus indicating that the radiolabeled com- cells vs. added pmol of 68Ga-NT-DOTA-20.3. Kd (7.335 pmol) and
pound has multiple binding sites without a positive cooperation. Bmax (90.52 kBq) values were found. Bmax value was used to cal-
Conclusions: In conclusion, 68Ga-DOTA-NT-20.3 appears to be an culate AsPC-1 binding sites, resulting in 1.09 9 106 sites per cell.
innovative tool as an early diagnostic strategy, to improve preoper- Isotherm analysis for the determination of binding saturation showed
ative staging. Furthermore, the substitution of the 68Ga diagnostic a Hill slope (h) of 0.8301.
isotope with a therapeutic one (such as 223Ra, 90Y, 177Lu, 111In) could Conclusions: Results from our in vitro study showed that 68Ga-
lead to DOTA-NT-20.3 being used as a new specific treatment for DOTA-NT-20.3 is a promising candidate for future application in
MPM that can be delivered by local route. imaging of patients with PDAC. Clinical studies will help to deter-
mine the potential utility of this tracer in oncology.

PO237
Targeting neurotensin receptor positive tumors: PO238
in vitro binding of pancreatic ductal adenocarcinoma Optimized sodium iodide symporter (NIS) gene therapy
with 68GA-DOTA-neurotensin engineered fragment as a novel therapeutic approach in glioma cells:
a feasibility approach
L. Lodola2, M. Marenco2, M.G. Persico3, M. Hodolič4,
G. Cavenaghi2, A. Facoetti1, C. Aprile1 V. Turri3, A. Boschi5, G. Di Domenico8, P. Martini6, M. Parigi4,
F. Ruggeri1, G. Abbati1, A. Sarnelli2, G. Paganelli7, L. Uccelli5
1
National Center for Oncological Hadrontherapy (CNAO), Pavia,
Italy. 2Nuclear Medicine Department IRCCS Policlinico San Matteo 1
Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio
Foundation, Pavia (Italy). 3Nuclear Medicine Department IRCCS e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. 2Health Physics,
Policlinico San Matteo Foundation, Pavia (Italy); University School Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
for Advanced Studies IUSS, Pavia, Italy. 4Nuclear Medicine Research (IRST) IRCCS, Meldola, Italy. 3Healthcare Direction, Istituto
Department, IASON-Graz (Austria); Palacký University, Department Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)
of Nuclear Medicine, Faculty of Medicine and Dentistry, Olomouc, IRCCS, Meldola, Italy. 4Istituto Zooprofilattico Sperimentale della
Czech Republic Lombardia e dell’Emilia Romagna, Forlı̀ Section, Forlı̀, Italy.
5
Nuclear Medicine and Molecular Imaging Laboratory, Morphology,
Background-aim: Pancreatic Ductal Adenocarcinoma (PDAC) is the
Surgery and Experimental Medicine Department, University of
most common malignancy of pancreas. Due to the lack of specific
Ferrara, Ferrara, Italy. 6Nuclear Medicine and Molecular Imaging
signs and symptoms, as well as aggressive growth behavior, in
Laboratory, Morphology, Surgery and Experimental Medicine
majority of cases treatment is palliative achieving median overall
Department, University of Ferrara, Ferrara, Italy; Legnaro National
survival of only 8.5 months. To date, 18F-FDG PET/CT imaging did
Laboratories, Italian National Institute for Nuclear Physics (LNL-
not significantly increase the accuracy of PDAC diagnosis. Approx-
INFN), Legnaro (PD), Italy. 7Nuclear Medicine Unit, Istituto
imately 75% up to 88% of PDAC express neurotensin receptor 1
Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)
(NTR-1), the possible target for neurotensin (NT) fragment DOTA-
IRCCS, Meldola, Italy. 8Physics and Heart Science Department,
NT-20.3 labeled with 68Ga. The aim of our study was to evaluate the
University of Ferrara, Ferrara, Italy

123
S132 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

Background-aim: Sodium iodide symporter (NIS) is an intrinsic PO239


membrane glycoprotein responsible for iodide transport. In previous Cost-analysis of a new diagnostic strategy in patients
studies, NIS was effectively used as imaging reporter gene for the
uptake and accumulation of 125I and as therapeutic gene to enhance with solitary pulmonary nodule: the Italian tailored
the uptake of 131I in targeted tissue. Since radioiodine uptake is assessment of lung indeterminate accidental nodule
proportional to total NIS protein levels, enhancing NIS protein (Italian) multicenter trial
expression improves reporter sensitivity and the therapeutic efficacy
of radioiodine therapy. A highly efficient human NIS gene (opt-hNIS) L. Evangelista16, L. Pace13, L. Mansi2, E. Mazziotti12, S. Del
has been developed by codon optimization in order to improve the Vecchio12, G. Pepe4, L. Basso10, S. Annunziata15, A. Golemi7,
efficacy of iodine therapy. Our aim is to test opt-NIS gene therapy as A. Chiaravalloti14, R. Galicchio3, L. Guerra8, N. Frega5,
a novel therapeutic approach in cancer cells. M. Zuffante1, V. Rizzo9, A. Cuocolo12, A. Lambertini11,
Methods: NIS gene sequence (Genbank NM_000453) has been M. Spadafora6
codon optimized and cloned into vector pcDNA3.1 P2A EGFP.
Human Embryonic Kidney (HEK293T) cells and glioma U87MG 1
Azienda Universitaria Integrata di Verona, Verona, Italy. 2Centro
cells have been transiently transfected using Polyethylenimine (PEI) Universitario di Ricerca per lo Sviluppo Sostenibile, Napoles-Rome,
and Mirus TransIT, both 1:6 ratio with DNA, respectively. Italy. 3CROB-IRCCS; Rionero in Vulture, Potenza, Italy. 4Humanitas
Radioactivity uptake studies were performed in both cell lines in di Milano, Milan, Italy. 5Medicina Futura Acerra, Napoles, Italy.
order to test the function of human optimized NIS protein. Experi- 6
Ospedale del Mare, Naples, Italy. 7Ospedale di Bolzano, Bolzano,
mental conditions included: (1) cells transfected with pcDNA3.1 opt- Italy. 8Ospedale San Gerardo-AAST Monza, Italy. 9Ospedale san
NIS P2A EGFP; (2) cell transfected with pcDNA3.1 P2A EGFP as Giuseppe Moscati, Avellino, Italy. 10SDN-IRCCS, Naples, Italy.
negative control; (3) cells transfected with pcDNA 3.1 opt-NIS P2A 11
Università degli Studi di Bologna, Bologna, Italy. 12Università degli
eGFP and treated with perchlorate (100 lM for 30 min at 37 C) Studi di Napoli ‘‘Federico II’’, Naples, Italy. 13Università di Salerno,
which blocks radioactive uptake, as a functional negative control. Salerno, Italy. 14Università Tor Vergata di Roma, Rome, Italy.
150.000–200.000 cells have been plated for each well (6 well plates) 15
Universita’ Cattolica di Roma, Rome, Italy. 16Veneto Institute of
and experiments have been performed in triplicate for each condition. Oncology IOV-IRCCS, Padua, Italy
Cells were incubated with different activity of 99mTc-pertechnetate
(1.85–7.4 MBq) for 30 min at 37 C. After incubation, cells have Background-aim: The aim of the study was to estimate the impact of
been washed with HEPES and lysated with 1% SDS. Data were introducing a new diagnostic strategy by comparing the costs of
acquired with a Gamma counter Wallac Wizardone. standard FDG whole-body (wb)-PET/CT and the costs of s-PET/CT,
Results: Transfection efficiency at 48 h post transfection (EGFP in the context of the ITALIAN trial.
positive viable cells, flow cytometry analysis) was 90% and 30% in Methods: We estimated the differential costs of wb-PET/CT and
HEK 293T cells and U87MG cells, respectively. The presence of NIS s-PET/CT, based on the Italian costs for the FDG PET/CT procedures,
transcript in both the transfected cell lines was detected with Real by including the reimbursement of the scan and the price of FDG. The
Time PCR in both cell lines only in pcDNA3.1 opt-NIS P2A EGFP ITALIAN trial population (n = 502 patients) was considered for the
transfected cells. end-point of the present study. The costs were censored for study
The uptake percentage of 99mTc-pertechnetate in U87 MG cells purpose.
transfected with pcDNA 3.1 opt-NIS P2A eGFP (Lysates- NIS) Results: Based on the ITALIAN data, s-PET/CT compared to wb-
compared to internal controls (Lysates-CTRL and Lysates-NIS PET/CT could save more than 10 min per scan or it would need a
PERCL) is between 2.34 and 3.39% of the incubated radioactivity dose of 35% less than to obtain the same chest counts and the same
(1.85-7.4 MBq). Moreover, Lysates-NIS show an activity uptake scan-time of wb-PET/CT. Based in the first advantage, s-PET/CT can
between 10 and 40 times higher than the uptake in Lysates-CTRL and increase the earning of 358.644,00 Euro (the reduction of scan time,
Lysates- NIS PERCL. These results confirmed that U87 MG cells significantly increases the number of procedures from 502 to 803;
transfected with pcDNA opt-NIS 3.1 P2A eGFP are able to uptake which is equivalent to the ratio 10:16 for wb-PET/CT and s-PET/CT,
99mTc-pertechnetate significantly higher compared to both negative respectively), but it slightly increases the FDG cost (22.554,86 Euro
controls. vs. 36.078,79 Euro respectively for wb-PET/CT and s-PET/CT) (total
The percentage of 99mTc-pertechnetate in HEK293T cells trans- money saving: 60%).
fected with pcDNA 3.1 opt-NIS P2A eGFP (Lysates-NIS) results In accordance with the second supposition, the FDG costs can be
26.41 ± 1.37% of the incubated radioactivity (1.85–3.7 MBq). reduced from 22.554,86 with wb-PET/CT to 7.894,20 with s-PET/CT
Results show that the NIS uptake mechanism moves an average of (money saving: 65%), by considering a dose of 7 mCi per patient, that
1 on 4 atoms of 99mTc incubated. corresponds to the mean value for the ITALIAN trial.
Conclusions: Our data showed that opt-NIS protein is transcribed and Conclusions: Although present study estimates cannot easily be
functional in human transiently transfected cells, including a glioma generalized to any local setting, the model for cost calculation is easy
cell line. These experiments provide the rationale for in vitro clono- to be exported to another scenario by applying different local
genic assay with 131I in glioma cells. Opt-NIS gene therapy can be a parameters. The advantages to introduce s-PET/CT in SPN can be
novel therapeutic approach in cancer cells resistant to conventional found in a reduction of expenses for the hospital and the Italian
therapies and which do not express any receptor for other nuclear healthcare.
medicine treatments.

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S133

PO240 performed before imaging provides only a snapshot of the patients’


Dopamine transporter imaging with 123I-ioflupane current health condition. Relevant aspects of their overall clinical
history are not available also due to the fact that patients’ health data
SPECT: comparison between two different time are usually recorded in paper form and therefore, cannot be accessed
modality acquisitions by other health professionals. As a consequence, it is difficult for
physicians to receive a clear picture of the patients’ health situation,
S. D’onofrio1, S. Di Domenicoantonio1, G. Galli1, R. Lewandowski1, additionally the clinical request for imaging may only be understood
M. Massaccesi1, R. Morabito1, C. Ritelli1, S. Basili1, F. Palladino1, partially which altogether may reduce the quality of imaging reports
L. Burroni1 significantly.
To improve this situation, the EU-funded research project PICASO
1
Nuclear Medicine Unit, Ospedali Riuniti ‘‘Torrette’’, Ancona, Italy (Personalised Integrated Care Approach for Service Organisations
and Care Models for Patients with Multi-Morbidity and Chronic
Background-aim: Brain neurotransmission SPECT is currently
Conditions) focuses on building an ICT based integrated care plat-
devoted mostly to imaging of the dopaminergic system and tracers
form. It supports collaborative sharing of care plans and patient’s
used for studying presynaptic transporter binding or postsynaptic
health data across sectors in a cloud-based health platform ensuring
dopamine D2 receptor status are labeled with 123I. Common indi-
data privacy.
cations are early diagnosis of Parkinson’s disease and evaluation of
Methods: A field study is conducted to investigate suitable ap-
Parkinsonian syndromes. Although visual assessment of the images
proaches for information sharing among healthcare professionals and
can be considered sufficient in many diagnostic situations, semi-
the impact on patient’s health condition and clinical work force
quantitation is highly recommended in the measurement of striatal
optimization. Acceptability and usability by healthcare professionals
subregions. Aim of our study is to evaluate the degree of agreement in
are also in focus of the study. Two hospitals in Rome (IRCCS Santa
the semi-quantitative valuation of 123I-FP-CIT in basal ganglia
Lucia, SITE A and Policlinico Tor Vergata, SITE B) will participate
nuclei, comparing two different acquisition time.
in the field study, site A with its neurology and site B with its nuclear
Methods: Seven patients with clinical diagnosis of Parkinson’s syn-
medicine department. The study will include 30 patients with
drome were studied in single day using two different time protocols of
Parkinson disease and an associated cardiovascular comorbidity who
acquisition 3–4 h after ev injection of 185 MBq of 123I-Ioflupane.
will be allocated randomly to either a control group managed in
Selected matrix size (128 9 128) and zoom factors give a pixel of
current clinical practice or an experimental group involving IT based
3.5 mm. Step-and-shoot mode with angle improvement of 3 was
information sharing. Patient data will be made available to clinicians
performed acquiring 360 degree images for the same patients at 15
via a clinical dashboard displaying the most relevant patient infor-
and 40 s per position. Both acquisition were reconstructed, 6 ROIs mation extracted from different sources. By definition of care plans
(right striatum, left striatum, right putamen, left putamen, right cau-
addressing patients’ specific health concerns clinicians will be able to
date, left caudate) over basal ganglia nuclei were drawn and
specify individualized patient pathways for an optimal treatment that
compared with the GE commercially program of semi-quantitative
allows sharing and coordination of care across sectors. The PICASO
quantification, referencing a normal image template. 123I-FP-CIT
platform will also integrate risk prediction and decision support tools
studies were blindly reviewed by two independent observers. They
to provide personalized assessments.
classified every study as either ‘‘normal’’ or ‘‘abnormal’’ and assigned
Results: The trial is currently underway and preliminary data on
visual 123I-FP-CIT uptake scores (2: normal, 1: reduced and 0: no
home monitoring and data sharing are available on the PICASO
uptake) in basal ganglia nuclei. The inter-observer agreement for the
platform.
interpretation of studies and for visual score assignment was evalu-
Conclusions: We expect improvement in quality of medical care by
ated by means of | statistics.
enabling healthcare professionals to directly share information
Results: No statistical difference between the values calculated over
between site A and B leading to better quality of reports. Furthermore,
the basal ganglia was found (p = 0.00044; Wilcoxon Signed-Rank
we assume less stress for the patients who no longer are responsible to
test) in the different time acquisitions. There was excellent inter-
take all relevant documents from site A to B or vice versa.
observer agreement in classifying studies as ‘‘normal’’ or ‘‘abnormal’’
and fine agreement in assignment of visual scores (| [ 0.7).
Conclusions: Comparison between of 123I-FP-CIT different time
acquisition (15 vs 40 s/image) studies showed very good statistical PO242
agreement. Moreover, we found significant associations among Radiopharmaceuticals: clinical risk and quality
visual, semi-quantitative and clinical parameters.
assurance system

A. Di Lascio1
PO241
1
PICASO: a personalised integrated care platform AORN ‘‘A. Cardarelli’’, Naples, Italy
Background-aim: The safety of care is the ‘‘process that leads to
A. Chiaravalloti1, H. Gappa3, C. Schunck2, M. Talamo2, O. Schillaci1 avoiding, preventing and mitigating adverse effects or damage
deriving from the Healthcare process’’ and regards errors and devi-
1
Department of Biomedicine and Prevention, University Tor Vergata, ations from the rules that cause malpractice in the health sector, and is
Rome, Italy. 2Fondazione INUIT, Tor Vergata, Rome, Italy. carried out through prevention and risk management, with the purpose
3
Fraunhofer Institute for Applied Information Technology (FIT), of intercepting errors before they happen so that it is easier to do the
Sankt Augustin, Germany right things and more difficult to do the wrong ones
Background-aim: Most of nuclear medicine and radiological Methods: A slight deviation from the prefixed requirements may
examinations deal with patients in complex health conditions. They result in altered biodistribution of the Radiopharmaceutical and lead
are often affected by co-morbidities requiring treatment by specialists to unexpected situations or not easy interpretation of the functional
from different medical subjects. However, the medical examination data or reduction of treatment efficacy with negative outcomes for the
patient (repetition of the examination, undue exposure). The correct

123
S134 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

preparation of the Radiopharmaceutical represents, therefore, one of artificial and natural, of thermal, ultrasonic and magnetic resonance
the indispensable requisites to guarantee, following well defined rules, energies, as well as interventions for physical or dosimetric protec-
such as to reduce or cancel the onset of these phenomena. tion, together with other numerous related activities (registration,
Results: In the management of the Clinical Risk, it is important to iconography, archiving)
adopt systematic tools and processes of identification, detection, Results: In light of the professional context (which sees the TSRM
analysis, forecasting and treatment of current and potential risks responsible for the acts under its responsibility) and the revision of the
related to the use of Radiopharmaceuticals, as well as instruments legislative framework, it appeared necessary to equip the professional
monitoring over time and identifying suitable organizational and exercise with functional tools for the safety of care (such as the
management solutions. Management of Clinical Risk and the protection of Professional
To achieve what has been illustrated so far it is necessary: guarantee responsibility) and the structuring of a system of protection of the
the production and preparation of radiopharmaceuticals according to professional activity of the medical technician of medical radiology
the quality standards typical of ‘‘pharmaceutical’’ preparations; Conclusions: The new Responsibility paradigm requires that all
guarantee the traceability of production operations, preparation and professionals be strongly oriented towards improving safety by con-
results obtained; define the technical standards for production and tributing to the creation of a virtuous, proactive risk management
preparation (equipment, laboratories, personnel); define the manage- system that reduces risky events and actions for users’ health. In the
ment and documentation criteria for all production and preparation light of the new legislative provisions, a continuous review of the
stages of Radiopharmaceuticals (Quality Manual and Organization protection system of the professional exercise should be considered,
Charts). In this regard it is useful to note that the outcome of a quality which includes: (1) the observation of sentinel events and of the
control ‘‘not compliant’’ with the requirements requires that the accidents that occurred; (2) Technical and scientific associations
Radiopharmaceutical can not be used for clinical administration and present and operating; (3) evaluation, with respect to the typical and
therefore eliminated. Furthermore, any deviation from the established confidential activity of the TSRM, collection, cataloging and sharing
procedures must be recorded evaluating the impact on the quality of of Good Practices/Guidelines/Procedures; (4) their timely updating
the preparation, in order to make the necessary corrective actions. and the drafting of further documents (if necessary); (5) deepening
Conclusions: The application of the Standards of Good Preparation and updating of specific insurance aspects for the profession; (6)
of Radiopharmaceuticals for nuclear medicine represent the obliga- training and updating for members and managers on the aspects of
tory path in order to guarantee the quality of the radiopharmaceutical Responsibility and Management of Clinical Risk, the scope of legal
preparation. A Quality System is a ‘‘way of thinking’’ that must be protection. Law 3/2018 (the so-called Lorenzin Law) adds further
assimilated and experienced by all those who work in the department elements to guarantee treatment by setting up professional associa-
to determine correct attitudes and behaviors. Among these, the tions, non-economic public bodies that, acting as subsidiary bodies of
Medical Technician of Medical Radiology, which ‘‘carries out the the State, protect public interests guaranteed by law, connected with
operations necessary for the preparation of the radioactive doses to be professional practice
administered to the patients and to be manipulated in vitro and any
other operation concerning the work of the hot chamber’’. The
experience of these years confirms that the maintenance of high
quality and safety standards not only allows the patient to be protected PO244
from any type of undue exposure, linked to radiological risk, but also Tips and expedients for NEMA phantom preparation
to obtain, from the Radiopharmaceutical product, the maximum
diagnostic or therapeutic efficacy, minimizing risks and criticalities V. Carcereri2, F. Severi1, S. Pasetto1, M. Salgarello2
and guaranteeing the patient the best diagnostic and therapeutic
efficacy from performance 1
Medical Physics Unit, IRCSS Sacro Cuore Don Calabria, Negrar
(VR), Italy. 2Nuclear Medicine Department, IRCSS Sacro Cuore Don
Calabria, Negrar (VR), Italy
PO243 Background-aim: NEMA measurements are used as the reference
The protection of professional health responsibility: standard for acceptance tests and routine quality checks of PET
tomographs. These measures are articulated and human error can have
the technologist’s protection system in Italian health an important weight in the results, therefore we have looked for
legislation critical issues and identified solutions to improve the safety,
repeatability and accuracy of these procedures.
A. Di Lascio1 Methods: Two Siemens PET/CT systems with both TOF and PSF
capabilities were investigated using NEMA test: a 2010 3-rings mCT
1
AORN ‘‘A. Cardarelli’’, Naples, Italy and a 2015 4-rings mCT Flow.
To prepare the activity we used an automatic dose drawing station l-
Background-aim: Health activity is exposed to the risk of error
DDS-A with a Capintec CRC-25 Pet dose calibrator.
because it has a high degree of risk from which it can achieve a
We performed the test using NEMA phantoms filled by F18.
clinically significant adverse event. Throughout his entire profes-
Resolution: It consists of a point source made in sponge inside a
sional and professional activity, the Medical Radiology Technician
glass pile.
(TSRM), like any other health professional, is potentially exposed to
Scatter phantom: It’s a solid right circular cylinder made of
the risk of error and the possibility of an accident, which may result in
polyethylene with a F-18 fillable line source holder parallel to the
a professional liability.
center axis of the cylinder.
Methods: The technologist participates in the provision of nuclear
Sensitivity: It consists of 6 concentric 70 cm aluminum tubes, one
medicine, for diagnostic and/or therapeutic purposes, through a
of which is F-18 fillable.
coordinated, complex and complex set of consequential acts. The
Quality: It’s a body phantom containing six spheres (diameter 10,
TSRM, responsible for the acts of its competence, is authorized to
13, 17, 22, 28 and 37 mm) in a quasi-cylindrical cavity. All spheres
perform autonomously or in collaboration with other health figures,
and the background were filled with F-18 solution containing different
interventions that require the use of ionizing radiation sources, both
concentration, to obtain a sphere-to-background ratio of 4 or 8.

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S135

The resolution, scatter and sensitivity tests are performed by Results: In all patients, the mean values of DLP and scan length were
Siemens service software, while the quality test is done like a 60 min significantly higher for MB than FM modality of wb-PET/CT
list-mode patient acquisition and then we used reconstruction siemens (762.8 ? 381.8 vs 744.3 ? 376.0 mGy cm, p \ 0.001; 963.5 ? 78.0
software. vs 928.2 ? 75.2 mm, p \ 0.001, respectively). Similarly, mean ED
Results: The same mistake in different tests compromise the accuracy was significantly higher for MB than FM modality (13.7 ? 6.9 vs
differently. So for each test we focus on particular critical issues to 13.4 ? 6.8 mSv, p \ 0.001). The effective values of both DLP and
improve the overall accuracy. ED were slightly lower than the same parameters estimate before the
Before the first test with radioactivity we spent a few time to get used study (662.0 ? 342.8 mGy cm and 12.0 ? 6.2 mSv, respectively).
to the phantoms using coloured water. The lower DLP for FM than MB modality produces a lower relative
Resolution: During the capillary tube preparation, we need a very risk of cancer due to wb-PET/CT procedure (0.059 ? 0.05 vs
concentrated activity, and a small volume. Hereafter in the test exe- 0.058 ? 0.05%, p \ 0.001).
cution the spatial position is critical. Conclusions: The flexibility of FM significantly reduces the radiation
Scatter: the capillary tube preparation is trivial, but the activity is exposure and relative cancer-risk of wb-PET/CT, according to ICRP
very high so we need radioprotection precaution to reduce the dose. provisions, in comparison with the standard MB modality.
Sensitivity: the capillary tube preparation is similar to the scatter
one but the volume is reduced. In this case the activity is crucial and
usually below the dose calibrator accuracy.
Quality: Its the most complicated phantom to fill. It takes time, PO246
patient, handicraft work and a few radioprotection precautions. Clinical risk management with RCA method
Conclusions: Over the years in our nuclear medicine we have of the radiopharmacy activity in ‘‘SS. Antonio e Biagio
developed some tips, expedients and devices useful to ease the
e C.Arrigo’’ nuclear medicine unit
NEMA phantom preparation and the tests execution. So we have
improved the accuracy and the precision. We have decreased also the
preparation time and then the operator exposition. M. Muratori2, D. Maranzana2, O. Gandini2, M.L. Ferretti3,
H. Belloni2, G. Cuccu2, E. Pomposelli2, H. Rouhanifar2, R. Russo2,
L. Tommasi2, D. Valentini1, A. Muni2
1
PO245 Department of Physics, A.S.O. ‘‘SS. Antonio e Biagio e C.Arrigo’’,
Flow motion modality reduces the patient radiation Alessandria, Italy. 2Nuclear Medicine Unit, A.S.O. ‘‘SS. Antonio e
Biagio e C.Arrigo’’, Alessandria, Italy. 3Radiodiagnostic Unit, A.S.O.
exposure of whole-body PET/CT scan ‘‘SS. Antonio e Biagio e C.Arrigo’’, Alessandria, Italy

G. Pecchia1, E. Palladino1, S. Amabile1, G. Angeloni1, C. Lanotte1, Background-aim: The continuous adaptation to rules and the
U. Marra1, D. Palma1, V. Rizzo2, S. Imbimbo1, M. Spadafora1, increasing number of different Radiopharmacy activity has made the
A. D’acunzo1 process, already intrinsically thorny, more vulnerable and deserving
of an additional safeguard. A good Risk Management plan can reduce
Nuclear Medicine Unit, Ospedale del Mare, Naples, Italy. 2Nuclear
1 the incident connected to each activity. It is important to control the
Medicine Unit, Ospedale S.G. Moscati, Avellino, Italy different factors like human behaviors, procedures, warning, techno-
logical tools and protection devices. The risk management can have
Background-aim: The first priority of actual ICRP Strategic Plan, as two kind of approach: reactive and proactive. The reactive approach
well as the basic principle of radioprotection, is to reduce radiation involves the analysis of an incident (or near miss) starting from the
exposure maintaining diagnostic information. Continuous motion in reconstruction of the right sequence of events in order to identify the
flow modality (FM) of the patient table has recently been introduced factors that caused it or contributed to its occurrence. Some of the
in modern PET/CT scanners. This personalized acquisition, without most important reactive tools consist of ‘‘incident reporting’’ and
the limitations of multi-bed position-based planning (MB), increased ‘‘Root Cause Analysis’’ (RCA). The aim of this work is to collect all
the patient comfort and improve the image quality at least comparable information about the cause and the typology of incident that can
to that step-and-shoot acquisition. FM, avoiding additional CT range occurred during the radiopharmacy activity in order to find the best
scanning, can be conceptually advantageous from a dosimetric point strategies to reduce the risk.
of view. However, to our knowledge no studies have explored the Methods: 1. Data Collection of Radiopharmacy incidents, or near
effect of two modalities in reducing CT patient dose. The aim of this misses, through Incident Reporting and interviews
study was to compare the patient radiation exposure of FM and MB 2. Incident root cause identification. This step generally involves the
acquisition modality, relative to whole-body (wb) PET/CT scan. use of a cause-effect diagram (Ishikawa and fault tree)
Methods: Data from 40 patients who were referred for whole-body 3. Formulation and identification of possible improvement solu-
FDG-PET/CT in our Institute for different malignancies, were col- tions which can prevent or reduce the odds that the incident can occur
lected. PET/CT images were acquired using an integrated 3-D mode Results: The Radiopharmacy activity incidents and near misses
PET/CT systems, from the base or top of the skull to mid-thigh (wb- reported, mainly consist in radioactive contamination of the operator
PET/CT), starting 60 min after tracer administration. In each patient, and the environment contamination. The RCA tool used to analyzed
after the initial scout, two acquisition mode (FM and MB), were set in these events is explained below.
order to preliminarily obtain an estimation of dose-length product Incident: The contamination measurement carry out by the operator
(DLP) and scan length (in mm). At the end of PET/CT study, the after the radiopharmacy activity, results positive. The operator and the
effective values of both DLP and effective dose (ED) were recorded. working environment are contaminated.
DLP was calculated as CTDIvol * length of scan in mGy*cm. The After the mandatory decontamination procedure, the operator fill
transformation of DLP in ED (in mSv) was made accordingly ICRP up the Incident Reporting.
103. The relative risk of cancer was evaluated by the software X-ray Through the brainstorming of the team working in nuclear medi-
risk, based on the BEIR VII report. Differences between continuous cine the following contributing factors are identified:
data were assessed using paired Student’s t test. • Excessive workload of the operators

123
S136 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

• Prepare different radiopharmaceuticals type in a short period of Results: Post processing after List Mode modality can help the
time physician to read the exam on the right way, because useful to dis-
• Rare radiopharmaceuticals preparation cover the progression or the recurrence of brain tumor.
• Miscommunication between the operator who prepare the We studied 6 patient.
radiopharmaceutical and who administer the dose 4/6 with MRI doubtful were true positive.
• The Software doesn’t show error alarm 1/6 were doubtful for the low quantity of tracer in lesions.
• Defective or incorrectly used of consumables and equipment 1/6 had scan negative so was considered tumor free.
From the identification of these factors we have used both ‘‘fish- Conclusions: According to this study, the 18F-FET is useful when the
bone’’ diagram and fault tree diagram, to highlight the causal other type of examinations are inconcludent.
relationships that lead to the root causes of the problems: The List Mode modality, with an appropriate reconstruction, help the
• Interface problems between the manipulation cell and the ded- physician to obtain important diagnostic and biological informations.
icated software Unfortunately this modality is not suitable for all Tomographer and is
• Material manufacturing defect an implement only in new generation equipment.
• Incorrect use of the equipment/material
• Workload and organization of radiopharmaceutical activities
The improvement strategies are listed below:
• The operator involved in radiopharmaceuticals preparation must PO248
remain absolutely isolated in the laboratory Cost saving of PET/CT and contrast enhanced CT
• Further simulations should be done during the year to develop in lymphoma patients
dexterity of the operators
• Definition of ways to ensure optimization of preparations
R. Sanco1, C. Vazzana1, M. Trevisan1, F. Lincetto1, A. Biscotto1,
• An appropriate period of time between two different preparation
L. Evangelista1
activity should be taken into account
• Revision of workloads and distribution of resources. 1
Istituto oncologico Veneto IOV-IRCCS, Padua, Italy
Conclusions: RCA is a tool to identify critical issues during the
operator’s activity and the related improvement strategies to be taken. Background-aim: In modern oncology, combined imaging based on
The radiopharmaceutical activity will be monitored, in order to verify positron emission tomography/computed tomography (PET/CT) plays
the effectiveness of the improvement strategies implemented. a central role in the diagnosis, staging and post-treatment follow-up of
patients with neoplastic disease. The possibility of performing TNM
staging with a single examination PET/CT and contrast enhanced (ce)
CT, provides a full diagnosis immediately and reduces the time
PO247 required for the patient to undergo separate diagnostic examinations.
The standardization of execution 18F-fluoro-ethyl- Moreover, in a period of general economic difficulty, the evaluation
tyrosine (FET) for the detection of primary brain tumor of economic resources and their use is important for effective and
efficient healthcare management. The aim of our study was to analyse
the impact of medical and nonmedical costs of PET/CT with simul-
E. Canali1, M. Caternicchia1, M. Celli1, M. Detti1, F. Matteucci1,
taneous ceCT, in a cohort of patients with lymphoma.
V. Mautone1, A. Moretti2, M. Pancisi1
Methods: From October to November 2018, a total of 32 patients
1 with Hodgkin and non-Hodgkin lymphoma referred to our institute
Nuclear Medicine IRST, Meldola, Italy. 2Nuclear Medicine Unit
was administered a questionnaire to evaluate the nonmedical costs of
AUSL Romagna, Ravenna, Italy
fluorodeoxyglucose (FDG) PET/CT. The questions elicited current
Background-aim: 18F-FET is a experimental radiotracer used for the working status at the time of the questionnaire, the type of work done
detection of brain tumor after the MR imaging, in particular for (aimed at defining a mean value for each patient’s working day), the
primitive SNC tumor recurrence. distance from home to the institute, and the means of transport used
The standardization of this type of exam is important for diagnostical (public or private). In the case of private transport, they were asked to
and biological informations. provide the type of vehicle (model and cylinder size). Moreover, to
In this study we want to demonstrate the correct modality of the evaluate the costs of informal care, they were asked to indicate
execution for this type of imaging. whether someone accompanied them to the institute and the type of
Methods: After the diagnosis of suspect recurrence of cerebral work done by the person. In addition, the medical costs (equipment
primitive tumor by MRI the patient underwent to 18F-FET PET/CT. maintenance and depreciation, consumables and staff) related to PET/
We use a Siemens Biograph MCT Flow PET/CT, the modality of CT performed with ceCT, PET/CT with low-dose nonenhanced CT
exam is in List Mode, that provide the co-registration of a data set, in and separate ceCT were also recovered. The analysis of costs for PET/
Raw Data, during the exam so we can make dynamic and static CT, and ceCT separately, and the hypothetical PET/ceCT costs were
imaging at the same time. estimated.
Patient is positioned, whit radiological fixator, in PET/CT bed Results: The costs for ceCT, PET/CT, PET/ceCT in all patients, were
before the injection. Examination start with the Topogram and CT 7767.68 euro, 21,982.08 euro and 26,177.92 euro, respectively. The
part, than after 10 s from the start of PET part the patient is injected expense for all 32 patients was 2387.62 comprising the working day,
with 18F-FET (200–250 MBq). The duration of the exam is 40 min. transport, and caregiver. The medical costs were 929.68 euro for PET/
The FOV is 700 mm for the AC/CT image and 550 mm for the CT with separate ceCT, and 816.06 euro for PET/ceCT in a single
Reconstruct image. session. Therefore, the economic recovery for each patient was equal
The reconstruction of PET image is made both dynamic (5 to to 12%. However, in our study population, the cost saving was equal
10 min and 20 to 40 min) and static by Syngovia. to 17%, because the reduction of the number of hospital visits
The post processing is determined by the physician: SUV max and required by patients undergoing diagnostic imaging can improve the
mean (Standardized Uptake Value), TBR maximum and mean (Tu- global costs.
mor/Brain ratios), TTP (Time to Peak), different patterns of TAC
(Time activity curve).

123
Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138 S137

Conclusions: Our results show that FDG PET/CT performed with PO251
standard dose ceCT in a single session, in patients with lymphoma, Treatment of liver neoplastic lesions with 90Y radio-
provides benefits in terms of both medical and nonmedical costs.
embolization

C. Vazzana2, P. Reccia2, A.R. Cervino2, A. Di Lascio1,


PO249 L. Evangelista2
Preliminary low-dose ct protocol scan optimization
1
in SPECT/CT AORN A. Cardarelli Napoli, Naples, Italy. 2Istituto Oncologico
Veneto IOV-IRCCS, Padua, Italy
R. Rinaldi1, L. Camoni1, D. Albano1, M. Bonacina2, R. Durmo2, Background-aim: Malignant hepatic tumors, primary or metastatic,
F. Bertagna2, R. Giubbini2 involve a huge amount of people in Italy, as worldwide. Liver is the
most common metastatic site of different cancer types, among which
1 those of breast, gastro-intestinal and neuroendocrine origin.
Nuclear Medicine Unit, Spedali Civili di Brescia, Brescia, Italy.
2 The radioembolization (TARE) consists in a new mini-invasive
Nuclear Medicine Unit, Università di Brescia, Brescia, Italy
transcatheter endovascular therapy of the hepatic district, by which
Background-aim: The CT component of SPECT/CT is required for glass microparticles (TheraSphere) impregnated with the radionuclide
attenuation correction (AC) and anatomical localization (AL) in Yttrium-90 (90Y) are selectively injected in the hepatic artery. The
SPECT/CT imaging. 90Y-loaded microspheres (20-30 micron in diameter) remain trapped
The objective of this preliminary study is to evaluate quantitatively in the smallest branches of the hepatic artery supplying the neoplastic
the image quality of different low-dose CT protocols for AL-AC, in lesion and finally irradiate the tumor with a high beta energy-emission
order to reduce the patient radiation exposure maintaining an AL in a super-selective way.
image good quality. The radio-embolization (RE) can be performed in place of the
Methods: Using the 16-section CT component of a commercially trans-arterial chemoembolization (TACE) in those HCC patients
available SPECT/CT scanner, we compared the standard manufacture satisfying the criteria of Barcelona Clinic for Liver Cancer (BCLC)
protocol (main parameters: 120 kV, 80 mA,0.8 s, pitch 1.37) with staging classification.
different CT scans acquisitions with manually adjusted x-ray tube Absolute contraindications to RE are essentially limited to the
voltage (kV range 100–140), anode current (mA range 40–100), scan existence of an insufficient liver functional reserve and/or a severe
time (s range 0.5–1), and pitch (p range 0.938–1.75). pulmonary shunt.
The imaging performance of the CT system was evaluated using Methods: At the reference center of IOV-IRCCS (Padua), from
Cathpan 600 phantom (Phantom Laboratory, Salem, NY, USA). We January 2016 till today, a total of 42 patients (38 Males, 4 Females)
evaluated: uniformity (U), contrast-to-noise ratio for objects with have been subjected to RE.
nominal contrast of 1% and 0.5% (CNR1%–CNR0.5%), spatial res- The treatment process consists of three phases:
olution (SR) and CT linearity (L). The Volume Computed 1. Selection of the candidate: patient day-hospital recovery, where
Tomography Dose Index (CTDIvol) were registered by the scanner contrast-enhanced abdomen computed tomography (CT) scan and
software and compared between the different scanner acquisitions. liver angioscintigraphy with 99mTc-macroaggregated albumin
Results: The manufacturer protocol results were: U = 0.46 HU, (MAA) are performed for evaluating treatment eligibility.
CNR1% = 1.37, CNR0.5% = 0.98, SR = 7 line pair/cm, L = 0.998 2. Treatment: recovery in a single room, angiographic procedure,
and CTDIvol = 4.12 mGy cm. administration of 90Y-Therasphere, post-treatment monitoring of
The results of the manually adjusted acquisition protocols (24 environmental contamination of angiographic room, control PET-CT
acquisitions), expressed as mean, standard deviation and minimum– 3. Follow-up: CT-scan exams to be performed at 1, 3, 6 and
maximum, were: U = 0.48 ± 1.11 (0.02–2.51) HU, CNR1% = 1.28 12 months after the procedure for assessing the efficacy during time
± 0.4 (0.39–2.08), CNR0.5% = 0.8 ± 0.18 (0.42–1.19), SR = 7 line and for monitoring the global evolution of tumoral disease.
pair/cm, L = 0.998 ± 0.001 (0.993–0.998) and CTDIvol = 3.81 ± The indicators of treatment effectiveness (patient survival, disease
1.73 (1.29–7.44) mGy cm. down-staging) permit also to select the patients that could succes-
An image quality, with a CTDIvol decrease, comparable with the sively benefit of a curative liver resection or transplant.
manufacturer protocol for AL and AC, with loss in CNR0.5% Results: Observation of treatment response/efficacy is relative to a
between - 5.7% and - 36.8%, were obtained using the following 3–6 months period and results seem encouraging.
parameters: Conclusions: TARE represent a safe and reliable treatment for HCC.
(120 kV, 60 mA, 0.8 s, pitch 1.37) U = 0.39 HU, CNR1% = 1.25, Technologist is an essential professional figure for realizing the whole
CNR0.5% = 0.66, SR = 7 line pair/cm, L = 0.998 and procedure, having both Molecular Imaging and Interventional Radi-
CTDIvol = 3.09 mGy cm. ology competences.
(100 kV, 80 mA, 0.8 s, pitch 1.37)U = 0.02 HU, CNR1% = 1.25, Technologist takes care of radiopharmaceutical labeling (MAA-
CNR0.5% = 0.62, SR = 7 line pair/cm, L = 0.997 and 99mTc), quality control and scintigraphic exam in Nuclear Medicine,
CTDIvol = 2.56 mGy cm. with tasks linked to CT scan execution and angiographic room
(100 kV, 100 mA, 0.8 s, pitch 1.37)U = 0.86 HU, CNR1% = assistance (both in the simulation and procedure phase) in Radiology.
1.33, CNR0.5% = 0.85, SR = 7 line pair/cm, L = 0.996 and
CTDIvol = 3.19 mGy cm.
Conclusions: The different settings of tube voltage, anode current,
scan time, and pitch allow to reduce the CTDIvol up to - 37.9% for
AL and AC purposes, maintaining an image quality comparable to the
factory protocol. Further studies should be performed to verify the
effect on attenuation map of the reduced kV, using an anthropo-
morphic phantom.

123
S138 Clin Transl Imaging (2019) 7 (Suppl 1):S1–S138

PO252 any residual glandular tissue, in the presence of locoregional metas-


Diagnostic management of the patient with thyroid tases or in the presence of metastatic capturing lymph nodes. It is
important to collect an appropriate counting statistics. In any case at
cancer treated with 131I least 140,000 hits for each W.B. projection and at least 60,000 shots
for static images. Moreover, in order to complete the staging of dis-
C. Vazzana1, A. Zorzi1, M. Sperandio1, R. Sanco1, A.R. Cervino1, ease, a SPECT Imaging is performed in a specific body segment, by
P. Reccia1, L. Evangelista1 using the standard acquisition (3*, 20 min per step).
Results: The inclusion of ATA guidelines in 2015, has increased the
1
Istituto Oncologico Veneto IOV-IRCCS, Padua, Italy acquisition time for the post-therapy whole-body. Nowadays, the
Background-aim: The introduction of ATA guidelines has deeply majority of patients has the presence of metastasis, thus requiring
changed the indication for 131I therapy in patients with thyroid additional static and SPECT acquisition. The time has passed from
cancer. Nowadays, only patients with intermediate-high risk thyroid the conventional 30 min (WB and one static acquisition) to 45–60
cancer would be treated with radiometabolic treatment. These new min (WB, 2–3 static acquisition and SPECT). This clinical matter has
indications has had an effect also on the diagnostic applications. The an indirect effect on the gamma camera’s utilization and therefore a
aim of the study was to analyze the impact of ATA guidelines for the longer scan occupation.
management of thyroid. Conclusions: The effect of ATA guidelines was reported in the
Methods: Whole-body (WB) acquisition takes place at 48–72 h after therapeutic and diagnostic management of patients with thyroid
131I administration. It is performed both in anterior and posterior cancer. The prolong time for WB 131I scan should be considered
projection; ancillary static recordings for the study of particular body when we organized the gamma camera’s list.
segments are made with acquisitions of 5–10 min per image. A
special evaluation should be given to the anterior region of the neck Publisher’s Note Springer Nature remains neutral with regard to
through an image of this area in anterior projection, positioning the jurisdictional claims in published maps and institutional affiliations.
patient with the hyperextended head. This image is aimed at finding

123
European Journal of Nuclear Medicine and Molecular Imaging (2019) 46 (Suppl 1): S1–S952 S1
DOI: 10.1007/s00259-019-04486-2

EANM‘19

Annual Congress of the


European Association of Nuclear Medicine
October 12 – 16, 2019
Barcelona, Spain

Abstracts

European Journal of Nuclear Medicine and


Molecular Imaging (2019) 46 (Suppl 1): S1–S952
10.1007/s00259-019-04486-2

This supplement was not sponsored by outside commercial


interests. It was funded entirely by the association’s own resources.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S2

Welcome Message S3

Programme at a Glance S4

Oral Sessions S8

Scientific e-Poster Presentation Sessions S301

Scientific e-Posters S381

Technologists e-Poster Presentation Sessions S852

Authors Index S892

EANM Focus Meeting 3 S951

ESMIT Level 1: eLearning S952


S3 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

Dear colleagues, dear friends,

On behalf of the European Association of Nuclear Medicine, it is my great pleasure and honour to cordially invite you to the 32nd Annual
EANM Congress in October 2019. This year, our Congress will take place in Barcelona, Spain. The city is world famous for its hospitality, its
cultural attractions and its culinary highlights.
Molecular imaging is continuously expanding: it is increasingly being combined with advanced technologies such as artificial intelligence
and has become a principal component of medical imaging. In the therapy field, targeted radiopharmaceuticals have been demonstrated
to be effective and are increasingly used in a variety of clinical settings, often integrated with other therapeutic options. The ultimate goal
is to design personalised, super-selective therapies and to identify more precise means of monitoring response to treatment in routine
clinical practice.
In the last three years, the status of the EANM annual meeting as the world-reference congress in nuclear medicine has been confirmed.
In order to maintain the high level of excellence, the 2019 EANM Congress will build on the traditions that are highly appreciated by all
attendees, with the expansion of newer features. A specific educational track, implemented with the collaboration of the European School
of Multimodality Imaging and Therapy, will include up-to-date teaching sessions, enriched pitfalls seminars and Continuous Medical Edu-
cation interactive sessions. In all these active learning conferences, attendees will have the possibility to enhance their knowledge of mul-
timodality imaging. A careful evaluation procedure relating to the speakers will be implemented in order to gain feedback and ensure that
future interactive sessions continue to enjoy a positive response. With similar pedagogic intent, numerous multidisciplinary joint symposia,
organised by several EANM Committees in collaboration with our sister societies, will offer an integrative approach to various topics relevant
to the state of the art of our discipline.
All these learning sessions will not impact adversely on the predominant role of our Congress, which is to enable oral and electronic poster
presentations on the latest achievements in clinical nuclear medicine, science and technology. On the contrary, the oral sessions will be
enriched. Rapid Fire sessions will draw attention to the highly rated abstracts in specific fields, with a panel of top-level presentations fol-
lowed by extensive discussions; this will provide attendees with an integrated and coherent view on a wide variety of topics. Furthermore,
the concept of featured oral sessions in which an invited speaker places the presentations into a broader perspective will be generalised to
the other oral presentations. The now well-established tracks M2M – Molecule to Man (basic and translational science) and Do.MoRe (ra-
dionuclide therapy and dosimetry) promise to promote high-quality research through interaction between basic and translational clinical
scientists and to present the latest achievements and developments in the fields of clinical molecular imaging and nuclear medicine the-
rapy. During plenary lectures, distinguished speakers will address the state of the art and new developments in clinical and allied sciences,
covering a broad range of topics with the goal of fostering the provision of the best possible care for our patients.
I am particularly delighted that two young but very motivated and highly respected members of our European Nuclear Medicine commu-
nity, Dr. Valentina Garibotto from Geneva, Switzerland, and Dr. Sarah Schwarzenböck from Rostock, Germany, will provide the traditional
Highlights lecture.
For all these reasons, I cordially invite you to EANM’19 to actively participate in our 32nd Annual Congress, to meet and interact with friends
and colleagues from all over the world, to discuss science, to learn about the exciting developments in nuclear medicine, to break away
from the daily routine and to enjoy everything that the city of Barcelona has to offer.

Francesco Giammarile,
EANM Congress Chair 2017-2019
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S4

Saturday, October 12, 2019


Room 111 Room 113 Room 114 Room 115 Room 116
08:00 - 08:00 -
08:30 08:30

08:30 - 08:30 -
09:00 09:00

09:00 - 09:00 -
09:30 09:30
Pre- Pre- Pre- Pre- Pre-
09:30 - Symposium 1 Symposium 2 Symposium 3 Symposium 4 Symposium 5 09:30 -
10:00 Inflammation & Cardiovascular Radiopharmacy + Translational Molecular Dosimetry + Physics 10:00
Infection Committee Committee / EACVI Oncology & Imaging and Therapy Committee
10:00 - Systematic Reviews Quantification of Theranostics + + Drug Development Dosimetry from Image 10:00 -
10:30 and Meta-Analyses Myocardial Blood Dosimetry Committee + Radiopharmacy Reconstruction with 10:30
of Diagnostic Test Flow - Ready for Daily Alpha Therapy - Practical Committee Monte Carlo Modelling
10:30 - Accuracy (DTA) Practice? Aspects on Chemistry We can’t make it cool, 10:30 -
11:00 and Applications but we can make it 11:00
easier….
11:00 - 11:00 -
11:30 11:30
EANM
11:30 - Advisory 11:30 -
12:00 Council 12:00
Meeting
12:00 - 12:00 -
12:30 12:30

12:30 - 12:30 -
13:00 13:00

13:00 - 13:00 -
13:30 13:30
Pre- Pre- Pre- Pre- Pre-
13:30 - Symposium 6 Symposium 7 Symposium 8 Symposium 9 Symposium 10 13:30 -
14:00 Thyroid Committee Neuroimaging Oncology & Physics + Dosimetry Radiation Protection + 14:00
/ ESES Committee Theranostics Committee Dosimetry Committee
14:00 - EANM An Update on Reserve, Resilience and Committee / EAU Advances in Image European Projects for 14:00 -
14:30 Delegates‘ Differentiated Thyroid Protective Factors in PSMA Theranostics Processing Techniques Clinical Implementation 14:30
Assembly Cancer (DTC) - Overview AD - Contribution of and Beyond of Dosimetry in
14:30 - of Management Molecular Imaging Molecular 14:30 -
15:00 Radiotherapy 15:00

15:00 - 15:00 -
15:30 15:30

15:30 - 15:30 -
16:00 16:00

16:00 - 16:00 -
16:30 16:30

16:30 - 16:30 -
17:00 17:00
EANM
17:00 - Members‘ 17:00 -
17:30 Assembly 17:30

17:30 - 17:30 -
18:00 18:00

18:00 - 18:00 -
18:30 18:30

19:30 - Opening 19:30 -


20:30 20:30
Ceremony
S5 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

Sunday, October 13, 2019


Auditorium Room 311 Room 312 Room 117 Room 111 Room 112 Room 113 Room 114 Room 115 Room 116 Room 133/134
08:00 - 101 102 103 104 105 106 107 108 109 110 111 08:00 -
08:30 CME 1
CME
Joint Joint Symposium 2 Technologists‘ M2M - Do.MoRe - Pitfalls & Clinical Oncolo- Neuroimaging - Cardiovascular - e-Poster Presenta- 08:30
Dosimetry Symposium 1 Cardiovascular + Opening Parallel Session Rapid Fire Session Artefacts 1 - gy - Rapid Fire Rapid Fire Parallel Session tion Session 1
Committee Bone & Joint + Translational and Mole- (08:00-08:15) ICC* Session Session Oncology
08:30 - Inflammation & cular Imaging Therapy + Data Analysis Myocardial Blood 08:30 -
CTE 1 Paediatrics
09:00 An Educational Trip from Infection Committee
Inflammation & Infection
Improvement of PSMA Flow Quantification 09:00
Organ to Voxel-Based to Committee / ESMI Technologist Committee Kinetic Modeling Oncology - Greatest
/ EULAR Ligands Prostate - BCR with SPECT
Small Scale Dosimetry New Approaches for the Committee / Pitfalls and Artefacts and Computational Hits
and More
09:00 - Bone Imaging in More Specific Detection CAMRT / ANZSNM in Paediatric Ne- Approach in 09:00 -
09:30 Chronic Inflammatory of Inflammatory Cells Technologist Approach phro-Urology Neuroimaging 09:30
Joint Conditions than FDG
to Global Dose
Optimization
09:30 - 09:30 -
10:00 10:00

10:00 - 201 204 10:00 -


10:30 Plenary 1 Plenary 1 10:30
incl. Marie Curie incl. Marie Curie
Lecture Lecture
10:30 - 10:30 -
Radiomics and (in Auditorium)
11:00 11:00
Artificial Intelligence Radiomics and
Artificial Intelligence
11:00 - 11:00 -
11:30 11:30

11:30 - 301 302 303 304 305 306 307 308 309 311 11:30 -
CME
12:00 CME 2 Joint Joint CTE 2 M2M - Do.MoRe - Pitfalls & Clinical Oncolo- Thyroid - e-Poster Presenta- 12:00
Oncology & Symposium 3 Symposium 4 Technologist + Parallel Session Parallel Session Artefacts 2 - gy - Rapid Fire Rapid Fire Session tion Session 2
Theranostics Bone & Joint + Cardiovascular Radiation Protection ICC* Session Inflammation & Infection +
12:00 - Committee Paediatrics Committee / ASNC** Committee Diagnostic Dosimetry Translational and Molecu- 12:00 -
Dosimetry Thyroid and
12:30 Committee / EPOS Radionuclide Production lar Imaging Therapy 12:30
NET - PRRT and More New Development in Risk and Incidents Committee Parathyroid
Prostate - BCR only
Role of Bone SPECT/CT Nuclear Cardiology - From Imaging to
12:30 - in Paediatric Population Ready for Prime Time? Dosimetry - Step-by- Infection and 12:30 -
13:00 Step Patient Inflammation - Clinical 13:00
Dosimetry and Preclinical Studies

13:00 - Lunch Lunch EANM Young Lunch Lunch 13:00 -


14:30 Symposium Symposium Daily Forum Symposium Symposium 14:30

14:30 - 401
CME
402 403 404a 405 406 407 408 409 410 411 14:30 -
15:00 CME 3 Joint Joint Symposium 6 Mini Course 1 M2M - Do.MoRe - Teaching Clinical Oncolo- Thyroid - Clinical Oncology - e-Poster Presenta- 15:00
Radiation Protection + Symposium 5 Translational and Molecular (14:30-15:30) Parallel Session Parallel Session Session 1 - ICC* gy - Rapid Fire Parallel Session Parallel Session tion Session 3
Dosimetry Committee Imaging Therapy + Cardio-
Oncology & Technologist Paediatrics + Thyroid Session Neuroimaging
15:00 - Theranostics vascular + Inflammation &
Image Reconstruction + Translational and Thyroid Cancer 15:00 -
Metrological Aspects Committee Antibody-Based Lung, Head & Neck
15:30 Committee / EORTC
Infection Committee / AHA
Molecular Imaging 15:30
on the Implementation Research Methodology Radionuclide Therapy and More Neurodegenera-
Therapy Committee New Tracers and
of Dosimetry in The Future of Medical Imaging Inflammation as Major tion, Amyloidosis and
Machine Learning
15:30 - Radionuclide Therapy Imaging in Precision Determinant of Cardiovascular 404b Management of Neuroinflammation 15:30 -
Diseases - New Tracers and
16:00 Medicine Mini Course 2 Thyroid Cancer in 16:00
Clinical Applications
(15:45-16:45) Children

16:00 - Technologist 16:00 -


16:30 Committee 16:30
Stress Testing for
Technologists
16:30 - 501 CME 502 503 505 506 507 508 509 510 511 16:30 -
17:00 CME 4 Joint Joint 404c M2M - Do.MoRe - Teaching Clinical Oncolo- Neuroimaging - Cardiovascular - e-Poster Presenta- 17:00
Radiopharmacy + Drug Symposium 7 Symposium 8 Mini Course 3 Parallel Session Parallel Session Session 2 - ICC* gy - Rapid Fire Parallel Session Parallel Session tion Session 4
Development + Translational Physics + Dosimetry Cardiovascular (17:00 - 18:00) Radiopharmacy Session Paediatrics & Other
17:00 - and Molecular Committee / AAPM Committee / EACVI Lu PRRT and other + Inflammation & 17:00 -
Technologist Radiolabelled Peptides 177
Movement Disorders Cardiac Imaging - More Clinical Studies
17:30 Imaging Therapy + Oncology Preclinical & Clinical Infection + Oncology than Perfusion 17:30
Interventional Nuclear Which Strategy for Committee and Proteins and Neurotransmission
& Theranostics Dosimetry & Theranostics PRRT 4.0? Joint Paediatrics &
Committee Medicine the Evaluation of Theranostics -
17:30 - Patients at the Time of Fundamental Committee Other Clinical Studies 17:30 -
Role of Extracellular
18:00 Matrices in Cancer Multi-Modality Cardiac 18:00
and Other Diseases Imaging? Imaging Immune Cells

Monday, October 14, 2019


Auditorium Room 311 Room 312 Room 117 Room 111 Room 112 Room 113 Room 114 Room 115 Room 116 Room 133/134
08:00 - 601 602 603 604 605 606 607 608 609 610 611 08:00 -
CME
08:30 CME 5 Joint Joint Technologists M2M - Do.MoRe - Pitfalls & Clinical Oncology - Paediatrics - Endocrine - e-Poster Presenta- 08:30
Oncology & Symposium 9 Symposium 10 Parallel Session Parallel Session Artefacts 3 - Parallel Session Parallel Session Parallel Session tion Session 5
Theranostics + Bone & Neuroimaging Drug Development Oral ICC* Oncology
08:30 - Joint Committee Committee / ILAE / SRS Preclinical Dosimetry - 08:30 -
Presentations 1 Innovations in Bio- Cardiovascular + Paediatrics Neuroendocrine
09:00 What is the Future? Breast and 09:00
Radionuclide Molecular Clinical Use of Brain What is Molar Activity Nanotechnology Inflammation & Malignancies
Gynaecological Oncology - e-Poster
Imaging in Bone Imaging for Patients with and When does it Impact Infection Committee
Cancers All Stars
09:00 - Tumours and Multiple Epilepsy PET Imaging? Tips and Tricks in the 09:00 -
09:30 Myeloma - Pearls, Interpretation 09:30
Patterns & Pitfalls of Cardiac PET

09:30 - 09:30 -
10:00 10:00

10:00 - 701 704 10:00 -


10:30 Plenary 2 Plenary 2 10:30
Prostate (in Auditorium)

10:30 - Cancer-Reload Prostate 10:30 -


11:00 Cancer-Reload 11:00

11:00 - 11:00 -
11:30 11:30

11:30 - 801 CME 802 803 804 805 806 807 808 810 11:30 -
12:00 CME 6 Joint Symposium 12 Technologists M2M - Do.MoRe - Pitfalls & Clinical Oncology - Thyroid - Technologists 12:00
Inflammation & Symposium 11 Physics Committee Parallel Session Parallel Session Artefacts 4 - Featured Session Rapid Fire Session e-Poster Presentation
Infection + Translational Neuroimaging Technologist e-Poster ICC* Session Slot
12:00 - and Molecular Imaging Committee / ISCBFM** Clinical Dosimetry and Implementing 12:00 -
Digital Detection in Presentation Sessions 1-4 PET Radiosynthesis Oncology & Theranos- Prognostic Factors
12:30 Therapy + Radiophar- Modeling Radiomics into 12:30
New Applications for Clinical NM (PET/SPECT) tics Committee in DTC
macy Committee Hybrid Brain PET/MRI Technical Practice
12:30 - Molecular Imaging PSMA Imaging 12:30 -
13:00 Technologies for 13:00
Infectious Diseases

13:00 - Lunch Lunch EANM Young Lunch Lunch 13:00 -


14:30 14:30
Symposium Symposium Daily Forum Symposium Symposium

14:30 - 901 CME 902 903 904 905 906 907 908 909 910 911 14:30 -
15:00 CME 7 Joint Joint CTE 3 M2M - Do.MoRe - Teaching Clinical Oncology - Special - Inflammation & e-Poster Presenta- 15:00
Translational and Symposium 13 Symposium 14 Technologist Parallel Session Parallel Session Session 3 - Featured Session Parallel Session Infection - tion Session 6
Molecular Imaging Neuroimaging Dosimetry + Radiation Committee ICC* Evaluating Parallel Session Cardiovascular
15:00 - Therapy Committee Committee / EANO Protection Artificial Intelligence in Radiological Aspects of 15:00 -
Preclinical Studies, from Neurodegeneration and Immunotherapy - Tomorrow´s Experts
15:30 Committee / ICRP 15:30
Imaging Immune Low Grade Glioma Bench to Bedside Neuroinflammation Image Processing Thoracic Anatomy Where do we stand? Session - Best-Ranked Inflammation & Searching for
Therapy Radiological Protection Papers from the Infection - PET in Myocardial Ischemia
15:30 - in Therapy with Under-30s Vascular Infection 15:30 -
16:00 Radiopharmaceuticals and Myocardial 16:00
Inflammation

16:00 - 16:00 -
16:30 16:30

16:30 - 1001 1002 1003 1004 1005 1006 1007 1008 1009 1010 1011 16:30 -
CME
17:00 CME 8 Joint Joint Symposium 16 CTE 4 M2M - Do.MoRe - Teaching Clinical Oncology - Neuroimaging - Cardiovascular - e-Poster Presenta- 17:00
Thyroid Symposium 15 Dosimetry + Translational Technologist Parallel Session Parallel Session Session 4 - ICC* Featured Session Parallel Session Parallel Session tion Session 7
Committee Oncology & and Molecular Imaging Committee / SNMMI Translational and Mole- Do.MoRe
17:00 - Theranostics Therapy Committee Dosimetry for PSMA cular Imaging Therapy 17:00 -
Secondary Effects of Technologist Guide Tumour TAU Imaging Myocardial Blood
17:30 / ESTRO + Drug Development Hybrid PET/MRI - 17:30
Radioiodine Treatment Committee / ESMO Launch - Microenviroment & Radiopharmaceuticals Flow Quantification Image Reconstruction
Immunological Dosimetry in Preclinical Committee Quo Vadis? & Data Analysis
Radiopharmacy: Cancer Biomakers with PET
Landscape in Solid Setting to Determine Dose Chemical Entities that
17:30 - Tumours and its Limits and Extrapolation to An Update can Induce a Therapeutic 17:30 -
18:00 Implications in Response Clinical Dosimetry Response in Vivo - Light 18:00
to Immunotherapy vs Radioisotopes
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S6

Tuesday, October 15, 2019

Auditorium Room 311 Room 312 Room 117 Room 111 Room 112 Room 113 Room 114 Room 115 Room 116 Room 133/134
08:00 - 1101 CME
1102 1103 1104 1105 1106 1107 1108 1109 1110 1111 08:00 -
08:30 CME 9 Joint Joint Technologists M2M - Do.MoRe - Pitfalls & Clinical Oncology - Cardiovascular - Do.MoRe - e-Poster Presenta- 08:30
Cardiovascular Symposium 17 Symposium 18 Parallel Session Parallel Session Artefacts 5 - Parallel Session Parallel Session Parallel Session tion Session 8
Committee Oncology & Theranos- Thyroid + Inflammation Oral ICC* Bone & Joint
08:30 - tics Committee / AIO & Infection Commit- I-131 Dosimetry and 08:30 -
Non-Invasive Imaging Presentations 2 Immune Therapy Neuroimaging + Imaging the Vessel Wall Performance,
09:00 tee / ETA DNA Damage during Radioguided Surgery 09:00
Strategies in Heart Failure Challenge Technologists Standardisation &
Different Therapies Bone SPECT/
Pancreatic Cancer Imaging on Thyroiditis Committee Quality Control
CT - Clinical
09:00 - Brain PET and SPECT - Imaging Pattern and 09:00 -
09:30 Patients‘ Preparation Quantification Tools 09:30
and Acquisition

09:30 - 09:30 -
10:00 10:00

10:00 - 1201 1204 10:00 -


10:30 Plenary 3 Plenary 3 10:30
Next Generation (in Auditorium)

10:30 - PET Technology in Next Generation 10:30 -


11:00 the Clinical Setting PET Technology in 11:00
the Clinical Setting

11:00 - 11:00 -
11:30 11:30

11:30 - 1301 CME


1302 1303 1304 1305 1306 1307 1308 1311 11:30 -
12:00 CME 10 Joint Joint Technologists M2M - Do.MoRe - Pitfalls & Clinical Oncology - e-Poster Presenta- 12:00
Neuroimaging Symposium 19 Symposium 20 Parallel Session Parallel Session Artefacts 6 - Parallel Session tion Session 9
Committee / EAN Oncology & Theranos- Thyroid Committee / Oral ICC* Do.MoRe
12:00 - tics Committee / EHA ETA-CG / EFSUMB SPECT/CT Quantifica- 12:00 -
EANM-EAN Presentations 3 Preclinical Developments Cardiovascular
12:30 Recommendations for the tion & Data Analysis Therapy Response 12:30
PET/CT Guided Thyroid Cancer Imaging in Infectious Diseases Committee Dosimetry
Use of Brain 18 F-FDG-PET Assessment -
Treatment in Non- and Biomarkers Pitfalls & Artefacts in Conventional Criteria
in Neurodegenerative
12:30 - Cognitive Impairment and Hodgkin Lymphoma Cardiac Imaging and More 12:30 -
13:00 Dementia 13:00

13:00 - Lunch Lunch EANM Young Lunch Lunch 13:00 -


14:30 14:30
Symposium Symposium Daily Forum Symposium Symposium

14:30 - 1401 CME


1402 1403 1404 1405 1406 1407 1408 1409 1410 1411 14:30 -
15:00 CME 11 Joint Joint CTE 5 M2M - Do.MoRe - Teaching Clinical Oncology - Bone & Joint - General Nuclear e-Poster Presenta- 15:00
Physics + Symposium 21 Symposium 22 Technologist Parallel Session Parallel Session Session 5 - Parallel Session Featured Session Medicine - tion Session 10
Cardiovascular Oncology & Committee ICC* Bone SPECT/CT and Parallel Session Oncology
15:00 - Committee Theranostics Radiobiology and Dosi- PET/CT Quantification 15:00 -
TBA Patient Targeting the Brain Neuroimaging
15:30 Committee / ESGO** metry for Radioemboli- Therapy - PSMA - A Clinical Tool Oncology - Mixed 15:30
Advances in Communication Committee General Nuclear
sation Therapy and More for Diagnosis and Pickles
Quantitative Ovarian Cancer Neuroimaging - Before Medicine
15:30 - Cardiac Imaging Reading PET Scans Prognosis in Diffuse 15:30 -
16:00 and Localised Skeletal 16:00
Diseases

16:00 - 16:00 -
16:30 16:30

16:30 - 1501 1502 1503 1504 1505 1506 1507 1508 1509 1510 1511 16:30 -
CME
17:00 CME 12 Joint Joint CTE 6 M2M - Do.MoRe - Teaching Clinical Oncology - Neuroimaging - Clinical Oncology - e-Poster Presenta- 17:00
Paediatrics Symposium 23 Symposium 24 Technologist Parallel Session Parallel Session Session 6 - Parallel Session Parallel Session Parallel Session tion Session 11
Committee Oncology & Translational and Mole- Committee ICC* Cardiovascular
17:00 - Theranostics cular Imaging Therapy + New Concepts, 17:00 -
Response Evaluation of Parathyroid Imaging Preclinical Models in Radiological Aspects of Liver Selective Therapy Brain Tumours It‘s in the Blood!
17:30 Committee / ENETS Oncology & Theranos- Harmonisation and 17:30
Paediatric Sarcomas Translational Science Abdominal Anatomy - 90Y and Beyond Imaging Cardiomyo-
Theranostic in NEN - tics Committee / Standardisation in
EAU** / ERUS** Radiomics pathies
17:30 - What is New? 17:30 -
18:00 Image Guided Therapies 18:00
for Prostate Cancer
S7 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

Wednesday, October 16, 2019

Auditorium Room 311 Room 312 Room 117 Room 111 Room 112 Room 113 Room 114 Room 115 Room 116 Room 133/134
08:00 - 1601 1603 1605 1606 1607 1608 1609 08:00 -
CME
08:30 CME 13 Symposium 26 M2M - Do.MoRe - Pitfalls & Clinical Oncology - Radiation 08:30
Drug Develeopment + Implementation of the Parallel Session Parallel Session Artefacts 7 - Featured Session Protection -
Radiopharmacy new EANM Guideline ICC* Parallel Session
08:30 - Committee for Pulmonary PET/CT & SPECT/CT Prostate Translational 08:30 -
Radiolabelled Peptides Oncology &
09:00 Embolism and Beyond Instrumentation 09:00
Current and Future of Theranostics Radiation Protection
Radiopharmaceuticals Committee - Standards, Tools and
09:00 - NET Imaging - Multiple Model 09:00 -
09:30 Endocrine Neoplasias 09:30
(MEN)

09:30 - 09:30 -
10:00 10:00

10:00 - 1701 CME


1702 1703 1704 1705 1706 1707 1708 1709 10:00 -
10:30 CME 14 Joint Joint CTE 7 M2M - Do.MoRe - Teaching Clinical Oncology - Inflammation & 10:30
Bone & Joint Symposium 27 Symposium 28 Technologist Parallel Session Parallel Session Session 7 - Parallel Session Infection -
Committee/ IASP Radiation Protection Translational and Committee ICC* Parallel Session
10:30 - Committee / JSNM** Molecular Imaging PET/MR Physics Prostate - Primary 10:30 -
The Diagnosis is Updates in Lung Imaging Peptide-Based ESMIT
11:00 Therapy + Oncology & Staging and 11:00
Complex Regional Pain Lessons from Fukushima Radionuclide Therapy Reading with the Infection and
Syndrome I (CRPS-I a.k.a. - Low Dose Radiation Theranostics Commit- Experts - PET/CT Biochemical Inflammation (Beyond
11:00 - Reflex Sympathetic from Environment tee / WMIS** in Neuroendocrine Persistance Cardiovascular 11:00 -
11:30 Dystrophy). Or is it? Radioisotope Translational Aspects of Tumours System) 11:30
PSMA Targeting

11:30 - 11:30 -
12:00 12:00
1801 1804 - in Auditorium
Marie Curie Award Marie Curie Award
12:00 - (11:45 - 12:15) (11:45 - 12:15) 12:00 -
12:30 12:30
Plenary 4 - Highlights Plenary 4 - Highlights
Lecture Lecture
12:30 - (12:15 - 13:15) (12:15 - 13:15) 12:30 -
13:00 13:00
Closing Closing
(13:15 - 13:20) (13:15 - 13:20
13:00 - 13:00 -
13:30 13:30

Plenary Sessions CME Sessions Joint/Special Symposia Technologist Sessions Do.MoRe M2M Pitfalls & Artefacts / Teaching Sessions Clinical Oncology Sessions Further Parallel/Featured/Rapid Fire Sessions e-Poster Presentation Sessions
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S8

Oral Sessions PS2


PS1 Pre-Congress Symposium 2 - Cardiovascular
Committee / EACVI: Quantification of
Pre-Congress Symposium 1 - Inflammation & Myocardial Flow Reserve ? Ready for Daily
Infection Committee: Systematic Reviews and Practice?
Meta-Analyses of Diagnostic Test Accuracy
(DTA) Saturday, October 12, 2019, 9:00 - 12:00 Lecture Hall 113

Saturday, October 12, 2019, 9:00 - 12:00 Lecture Hall 111


PS-10
Pathophysiology of Coronary and Myocardial Flow
PS-01 Reserve
Introduction to Systematic Reviews and Meta-Analyses of T. van de Hoef; Department of Cardiology, Academic
Diagnostic Test Accuracy Medical Centre, Amsterdam, NETHERLANDS.
G. Treglia; Imaging Institute of Southern Switzerland
and Health Technology Assessment Unit, Ente PS-11
Ospedaliero Cantonale, Bellinzona, SWITZERLAND. How to Quantify MBF?
M. Lubberink; PET Centre, Uppsala University
PS-02 Hospital, Uppsala, SWEDEN.
Formulating the Review Question and Planning Eligibility
Criteria PS-12
G. Treglia; Imaging Institute of Southern Switzerland MBF Quantification Based on SPECT
and Health Technology Assessment Unit, Ente A. Manrique; Caen University Hospital, Department
Ospedaliero Cantonale, Bellinzona, SWITZERLAND. of Nuclear Medicine, Caen, FRANCE.

PS-03 PS-14
Systematic Search of Reports and Selection of Eligible MBF Quantification Based on PET
Studies A. Saraste; University of Turku, Heart and PET
B. Muoio; Oncology Institute of Southern Switzerland, Ente Centre Hospital/Institute, Turku, FINLAND.
Ospedaliero Cantonale, Bellinzona, SWITZERLAND.
PS-15
PS-04 MBF Quantification Based on CT
Discussion G. Pontone; Centro Cardiologico Monzino,
IRCCS, University of Milan, Milan, ITALY.
PS-06
Collecting Data and Performing the Quality Assessment PS-16
R. Sadeghi; Nuclear Medicine Research Center, How to Implement MBF in Clinical Practice?
Mashhad University of Medical Sciences, J. Knuuti; Heart and PET Centre, Turku, FINLAND.
Mashhad, IRAN, ISLAMIC REPUBLIC OF.
PS-17
PS-07 Discussion
Pooling Indices Across Studies (Meta-Analysis)
Y. Takwoingi; Institute of Applied Health Research, University
of Birmingham, Birmingham, UNITED KINGDOM.

PS-08
Analysis of Heterogeneity and Biases
Y. Takwoingi; Institute of Applied Health Research, University
of Birmingham, Birmingham, UNITED KINGDOM.

PS-09
Discussion
S9 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

PS3 PS4
Pre-Congress Symposium 3 - Radiopharmacy Pre-Congress Symposium 4 - Translational
+ Oncology & Theranostics + Dosimetry Molecular Imaging and Therapy + Drug
Committee: Alpha Therapy - Practical Aspects Development + Radiopharmacy Committee: We
on Chemistry and Applications can?t make it cool, but we can make it easier?.

Saturday, October 12, 2019, 9:00 - 12:00 Lecture Hall 114 Saturday, October 12, 2019, 9:00 - 12:00 Lecture Hall 115

PS-18 PS-26
An Overview of Production and Radiochemistry of Alpha- Too Many Regulations
Emitting Radionuclides O. Neels; German Cancer Research Center, Division of
A. Morgenstern; European Commission, DG Joint Radiopharmaceutical Chemistry, Heidelberg, GERMANY.
Research Centre-JRC, Karlsruhe, GERMANY.
PS-27
PS-19 Too Many “me too” Tracers
Safe Handling of Alpha-Emitting Radionuclides During A. Gee; St Thomas’ Hospital, Kings College London, Imaging
Preparation and Application of Radiopharmaceuticals Sciences Rayne Institute, London, UNITED KINGDOM.
S. Holm; Klinik for Klinisk Fysiologi, Nuklearmedicin
& PET, Copenhagen, DENMARK. PS-28
Too Expensive
PS-20 B. Cornelissen; RRI, Dept.of Oncology, univ. of
Stability of Alpha-Emitting Radiopharmaceuticals - Impact Oxford, Oxford, UNITED KINGDOM.
on TATs
M. Benesova; German Cancer Research PS-30
Center, Heidelberg, GERMANY. Too Much Bias in Animal Experiments
M. Schottelius; TU Munich, Pharmaceutical
PS-22 Radiochemistry, Garching, GERMANY.
Recoil Effect and its Impact on TATs Dosimetry
N. Chouin; French Institute of Health and PS-31
Medical Research, Nantes, FRANCE. Too Much Difficult Dosimetry
M. Konijnenberg; Erasmus MC, Radiology and
PS-23 Nuclear Medicine, Rotterdam, NETHERLANDS.
Antibody Derivatives as a Vehicle for TAT - Advantages,
Disadvantages, Future Prospects PS-32
S. Heskamp; Radboud Institute for Molecular Plenary Discussion with Focus on: How to Avoid
Life Sciences, Nijmegen, NETHERLANDS. Translational Hurdles

PS-24
Future Directions for Targeted Alpha Therapy Beyond PS5
Prostate Cancer
M. Miederer; Department of Nuclear Medicine,
Pre-Congress Symposium 5 - Dosimetry +
University Medical Center Mainz, Mainz, GERMANY.
Physics Committee: Dosimetry from Image
Reconstruction with Monte Carlo Modelling
PS-25
Discussion Saturday, October 12, 2019, 9:00 - 12:00 Lecture Hall 116

PS-33
Statistical Reconstruction Methods - Principles
J. Gustafsson; Department of Medical Radiation
Physics, Lund University, Lund, SWEDEN.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S10

PS-34 PS-44
An Introduction to Monte Carlo Calculations for Imaging Redifferentiation of Radioiodine Refractory DTC
and Dosimetry S. Leboulleux; Nuclear Medicine and Endocrine Oncology,
M. Ljungberg; Department of Medical Radiation Gustave Roussy and Paris Saclay, Villejuif, FRANCE.
Physics, Lund University, Lund, SWEDEN.
PS-45
PS-36 Discussion
Problems Related to Dosimetry for Therapy Based on
Quantitative SPECT Imaging
P. Minguez Gabina; Department of Medical PS7
Physics and Radiation Protection Gurutzeta/Cruces
University Hospital 48903, Barakaldo, SPAIN.
Pre-Congress Symposium 7 - Neuroimaging
Committee: Reserve, Resilience and Protective
PS-37
Factors in AD ? Contribution of Molecular
Examples of the Usefulness of Monte Carlo Modelling
Imaging
within a Reconstruction Process
H. de Jong; Department of Radiology, University Medical Saturday, October 12, 2019, 13:00 - 16:00 Lecture Hall 113
Center Utrecht, UMC, Utrecht, NETHERLANDS.

PS-38 PS-46
Discussion and Concluding Remarks Reserve and Resilience in AD - Evolution of the Concept
P. Vemuri; Department of Radiology, Mayo Clinic,
Rochester, MN, UNITED STATES OF AMERICA.
PS6
Pre-Congress Symposium 6 - Thyroid PS-47
Multimodal Interventions and Dementia Prevention
Committee / ESES: An Update on Differentiated S. Sindi; Karolinska Institutet, Department of
Thyroid Cancer (DTC) - Overview of Neurobiology, Stockholm, SWEDEN.
Management
PS-48
Saturday, October 12, 2019, 13:00 - 16:00 Lecture Hall 111 Functional Networks Underlying Cognitive Reserve
S. Morbelli; San Martino Hospital, Nuclear Medicine, Genoa, ITALY.

PS-39 PS-49
Surgical Strategy at Initial Diagnosis Discussion
F. Sebag; Assistance Publique Hôpitaux de Marseille,
Endocrine and Metabolic Surgery, Marseille, FRANCE. PS-51
Should we Considered Education as a Confounder on FDG-
PS-40 PET Diagnostic Accuracy in Alzheimer’s Disease?
Strategies and Concepts Regarding Post-Surgery V. Garibotto; Nuclear Medicine and Molecular Imaging
Radioiodine Treatment of DTC Division, Geneva University Hospitals, Geneva, SWITZERLAND.
E. Hindie; CHU hôpitaux de bordeaux Service
Médecine Nucléaire, Bordeaux, FRANCE. PS-52
Contribution of Amyloid and Tau PET to the
PS-41 Understanding of Cognitive Reserve
Multiscale Prognostic Factors for the Management of DTC M. Hönig; Department of Nuclear Medicine, University
L. Giovanella; Imaging Institute of Southern Switzerland, Hospital Cologne, Cologne, GERMANY.
Clinic for Nuclear Medicine, Bellinzona, SWITZERLAND.
PS-53
PS-43 Meditation in the Ageing Population to Foster Reserve and
Radioiodine Treatment for Metastatic DTC - How Much? Prevent Dementia
How Many? How Often? G. Chételat; Inserm UMR-S U1237, Normandie
M. Luster; University of Marburg, Department of Univ, UNICAEN, GIP Cyceron, Caen, FRANCE.
Nuclear Medicine, Marburg, GERMANY.
PS-54
Discussion
S11 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

PS8 PS-64
Whole Body Parametric PET/CT Imaging
Pre-Congress Symposium 8 - Oncology N. Karakatsanis; Mount Sinai Hospital, Cornell University,
& Theranostics Committee / EAU: PSMA New York, NY, UNITED STATES OF AMERICA.
Theranostics and Beyond
PS-66
Saturday, October 12, 2019, 13:00 - 16:00 Lecture Hall 114 Functional Volume Segmentation - State of the Art
M. Hatt; INSERM, LaTIM, University of
Western Britanny, Brest, FRANCE.
PS-55
Defining the Landscape of Potential Candidates for PSMA- PS-67
RLT Quantitative SPECT/CT Imaging
J. Walz; Institut Paoli-Calmettes Cancer Center, I. Armstrong; Nuclear Medicine Department, Manchester
Department of Urology, Marseille, FRANCE. University Hospital NHS Trust, Manchester, UNITED KINGDOM.

PS-56 PS-68
Overview of Clinical Data for 177Lu-PSMA MC vs Non-MC Dose Estimation for Radionuclide Therapy
B. Krause; University of Rostock, Department of M. Ljungberg; Department of Medical Radiation
Nuclear Medicine, Rostock, GERMANY. Physics, Lund University, Lund, SWEDEN.

PS-57
PSMA RLT beyond 177Lu-PSMA PS10
M. Eiber; Technische Universität München, Department
of Nuclear Medicine, Munich, GERMANY.
Pre-Congress Symposium 10 - Radiation
Protection + Dosimetry Committee: European
PS-58
Projects for Clinical Implementation of
Discussion
Dosimetry in Molecular Radiotherapy

PS-60 Saturday, October 12, 2019, 13:00 - 16:00 Lecture Hall 116
Overcoming Resistance to PSMA RLT
J. Czernin; University of California Los Angeles,
Molecular and Medical Pharmacology, Los PS-69
Angeles, CA, UNITED STATES OF AMERICA. Calibration protocols for quantitative imaging developed
within the MRTDosimetry project
PS-61 A. Robinson; National Physical Laboratory,
Targets Beyond PSMA Teddington, UNITED KINGDOM.
J. Babich; Weill Cornell Medical College, Department of
Radiology, New York, NY, UNITED STATES OF AMERICA. PS-70
Multicentre Quantitative Imaging Exercises and Dosimetry
PS-62 Tool Intercomparison in the MRTDosimetry Project
Discussion J. Tran-Gia; University of Würzburg, Department
of Nuclear Medicine, Würzburg, GERMANY.

PS9 PS-71
Multicentre Quantitative Imaging Exercises and Dosimetry
Pre-Congress Symposium 9 - Physics + Tool Intercomparison in the MRTDosimetry Project
Dosimetry Committee: Advances in Image N. Calvert; The Christie NHS Foundation Trust,
Processing Techniques Manchester, UNITED KINGDOM.

Saturday, October 12, 2019, 13:00 - 16:00 Lecture Hall 115 PS-72
Discussion

PS-63 PS-74
Principles and Developments of Deep Learning Intercomparison for Lu-177 Imaging in the Netherlands
Techniques in NM Image Processing S. Peters; Radboudumc, Radiologie & Nucleaire
A. McMillan; University of Wisconsin, Department of Geneeskunde, Nijmegen, NETHERLANDS.
Radiology, Madison, WI, UNITED STATES OF AMERICA.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S12

PS-75 OP-007
The Role of CT in Image-Based Dosimetry Impact of FDG-PET/CT in Patients with PMR
K. Sjögreen-Gleisner; Lund University, Medical O. Gheysens; Nuclear Medicine and Molecular
Radiation Physics, Lund, SWEDEN. Imaging, Department of Imaging and Pathology,
University Hospitals Leuven, Leuven, BELGIUM.
PS-76
Medirad I-131 Multicentre Trial Set-Up OP-008
F. Leek; Royal Marsden Hospital, Joint Department Imaging of Osteoblast-/OsteoclastActivity in New Bone
of Physics, Sutton, UNITED KINGDOM. Formation in Rheumatologic Patients
X. Baraliakos; Rheumazentrum Ruhrgebiet, Herne, GERMANY.
PS-77
Discussion 103
Joint Symposium 2 - Cardiovascular +
101 Translational and Molecular Imaging Therapy
+ Inflammation & Infection Committee /
CME 1 - Dosimetry Committee: An Educational ESMI: New Approaches for the More Specific
Trip from Organ to Voxel-Based to Small Scale Detection of Inflammatory Cells than FDG
Dosimetry
Sunday, October 13, 2019, 8:00 - 9:30 Lecture Hall 312
Sunday, October 13, 2019, 8:00 - 9:30 Auditorium

OP-009
OP-001 Device Infection
Organ Level Dosimetry F. Caobelli; Department of Nuclear Medicine,
J. Gear; Royal Marsden NHS Foundation Trust, Joint Universitätsspital Basel, Basel, SWITZERLAND.
Department of Physics, Sutton, UNITED KINGDOM.
OP-010
OP-002 Cardiac Remodeling
Voxel Level Dosimetry J. Thackeray; Department of Nuclear Medicine,
N. Chouin; French Institute of Health and Hannover Medical School, Hannover, GERMANY.
Medical Research, Nantes, FRANCE.
OP-011
OP-003 Atherosclerosis
Small Scale Dosimetry - Not so Appealing, but...It’s just J. Bucerius; Klinik für Nuklearmedizin, Universitätsmedizin
Dosimetry Göttingen, Georg-August-Universität, Göttingen, GERMANY.
P. Bernhardt; University of Gothenburg, Department
of Radiation Physics, Gothenburg, SWEDEN. OP-012
Myocarditis
C. Rischpler; University Hospital Essen, Essen, GERMANY.
102
Joint Symposium 1 - Bone & Joint + OP-013
Discussion
Inflammation & Infection Committee / EULAR:
Bone Imaging in Chronic Inflammatory Joint
Conditions

Sunday, October 13, 2019, 8:00 - 9:30 Lecture Hall 311

OP-006
Bone SPECT/CT Versus MRI in Rheumatologic Patients
H. Palmedo; Institute for Radiology and
Nuclear Medicine, Bonn, GERMANY.
S13 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

104 105
CTE 1 - Technologist Committee / ANZSNM / M2M - Parallel Session: Improvement of PSMA
CAMRT: Technologist Approach to Global Dose Ligands
Optimization
Sunday, October 13, 2019, 8:00 - 9:30 Lecture Hall 111
Sunday, October 13, 2019, 8:00 - 9:30 Lecture Hall 117

1OP-018
OP-014a
Opening Technologist’s Track Novel 177Lu-labeled albumin-binder-conjugated PSMA-
A. Santos; Hospital Cuf Descobertas, Nuclear targeting agents with extremely high tumor uptake and
Medicine Department, Lisbon, PORTUGAL. superior tumor-to-kidney therapeutic index
H. Kuo1, Z. Zhang1, C. Uribe1, H. Merkens1, C. Zhang1, F. Bénard1,2, K.
OP-014b Lin1,2;
Dose Optimization Principles 1
Department of Molecular Oncology, BC Cancer, Vancouver,
P. Fragoso-Costa; University Hospital Essen, Clinic BC, CANADA, 2Department of Radiology, University
for Nuclear Medicine, Essen, GERMANY. of British Columbia, Vancouver, BC, CANADA.

OP-015
Dose Reference Levels in Nuclear Medicine Aim/Introduction: The use of an albumin binder has
E. Bailey; Royal North Shore Hospital, Department been shown to improve tumor uptake of prostate specific
of Nuclear Medicine, Sidney, AUSTRALIA. membrane antigen (PSMA)-targeting radiopharmaceuticals.
We recently reported 177Lu-HTK01169[1], a 177Lu-PSMA-617
OP-016 derivative that delivered 8.3-fold higher absorbed dose to
PET/CT Dose Optimization and Occupational Exposure LNCaP tumor xenografts than 177Lu-PSMA-617, at the expense
T. Alden; BC Cancer Agency, Vancouver, CANADA. of a lower tumor-to-kidney therapeutic index. We systematically
investigated different linkers and albumin binders to maximize
the therapeutic index of PSMA-binding radiopharmaceuticals.
OP-017 We aimed to develop novel radiopharmaceuticals that
Cardiac Imaging Methods for Dose Reduction combine the effects of an improved linker with optimized
L. Camoni; Università & Spedali Civili di Brescia, Brescia, ITALY. albumin binders to maximize the tumor-to-kidney therapeutic
index. Materials and Methods: Two novel PSMA-binding
radiopharmaceuticals derived from the glutamate-ureido-
lysine backbone, HTK03121 and HTK03123, were synthesized
using a solid-phase approach. HTK03121 and HTK03123 were
synthesized with a linker containing the lipophilic 3-(9-anthryl)-
L-alanine and tranexamic acid, with the addition of albumin-
binding motifs 4-(p-chlorophenyl)butanoyl]-Gly (HTK03121)
and 4-(p-methoxyphenyl)butanoyl]-Gly (HTK03123). 177Lu
labeling was conducted in acetate buffer (pH 4.5). SPECT/CT
and biodistribution studies were performed in LNCaP tumor-
bearing mice. Radiation dosimetry in mice was calculated
using the OLINDA v.1.2. Results: SPECT/CT imaging showed
that both 177Lu-HTK03121 and 177Lu-HTK03123 had very high
and sustained tumor uptake and were excreted mainly via the
renal pathway. The blood retention values (%ID/g) at 1, 4, 24,
72 and 120h were 22.6±5.35, 15.3±2.07, 4.33±0.88, 0.75±0.19
and 0.23±0.05, respectively for 177Lu-HTK03121 and 14.1±1.01,
7.30±1.39, 0.71±0.29, 0.16±0.01 and 0.09±0.06, respectively for
177
Lu-HTK03123. Tumor uptake values of 177Lu-HTK03121 and
177
Lu-HTK03123 all peaked at 24h (104±20.3 and 70.8±23.7 %ID/g,
respectively), and remained stable up to 120h post-injection. For
a 350-mg lesion size, the dose delivered to tumors were 13,316
and 13,498 mGy/MBq for 177Lu-HTK03121 and 177Lu-HTK03123
compared to 846 mGy/MBq for 177Lu-PSMA-617. Kidney doses
were 15.8, 15.2 and 2.82 mGy/MBq for 177Lu-HTK03121, 177Lu-
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S14

HTK03123 and 177Lu-PSMA-617, for tumor-to-kidney absorbed the 177Lu-Ibu-PSMA and 177Lu-Ibu-Dα-PSMA (95%) followed by
dose ratios of 843, 888 and 300 respectively. Thus, compared 177
Lu-Ibu-N-PSMA (93%) and 177Lu-Ibu-DAB-PSMA (89%). Similar
to 177Lu-PSMA-617, 177Lu-HTK03121 delivered 15.7-fold higher observations were made in biodistribution studies where 177Lu-
absorbed dose to tumor and a 2.8-fold improvement in the Dα-PSMA showed the most pronounced blood retention and
tumor-to-kidney dose ratio. 177Lu-HTK03123 delivered 16.0-fold highest tumor uptake. 177Lu-Ibu-DAB-PSMA revealed the best
higher absorbed dose to tumor, a 2.96-fold improvement in tissue distribution profile with high tumor uptake (65% IA/g at
the tumor-to-kidney dose ratio. Conclusion: We report novel 4 h p.i. and 52% IA/g at 24 h p.i.) and most favorable tumor-to-
PSMA-targeting radiopharmaceuticals that showed, in a mouse blood dose ratios as compared to the other three candidates
model of prostate cancer, very high tumor uptake, 15.7- and and 177Lu-PSMA-ALB-56. Conclusion: 177Lu-Ibu-DAB-PSMA was
16.0-fold higher absorbed dose to tumors and superior tumor- identified as the most promising candidate of this new class of
to-kidney therapeutic ratios compared to 177Lu-PSMA-617. These albumin-binding radioligands. The favorable tissue distribution
compounds have the potential to improve treatment safety and profile warrants in-depth investigations of the therapeutic
efficacy using significantly lower quantities of 177Lu, and are potential of this new PSMA-targeting radioligand in tumor-
promising candidates for clinical translation. References: Kuo bearing mice, which will be decisive for a potential future
H-T, et al. Molecular Pharmaceutics 2018;15:5183-5191. clinical translation. References: [1] Lau et al. Bioconjug Chem
2019, 30:487 [2] Umbricht et al. Mol Pharm 2018; 15:2297

OP-019
Development of a new class of albumin-binding PSMA OP-020
radioligands A Sarcophagine Containing PSMA Ligand for Targeting
C. Mueller1, L. Deberle2, C. A. Umbricht1, M. Benesova2, F. Borgna1, V. Prostate Cancer with 64/67Cu
J. Tschan1, K. Zhernosekov3, R. Schibli2; J. M. Kelly1, S. Ponnala1, A. Nikolopoulou1, N. Zia2, C. Williams Jr.1, P.
1
Paul Scherrer Institute, Villigen-PSI, SWITZERLAND, 2ETH Zurich, S. Donnelly2, J. W. Babich1;
Zurich, SWITZERLAND, 3ITG GmbH, Garching, GERMANY. 1
Weill Cornell Medicine, New York, NY, UNITED STATES OF
AMERICA, 2University of Melbourne, Melbourne, AUSTRALIA.

Aim/Introduction: A number of albumin-binding radioligands,


targeting the prostate-specific membrane antigen (PSMA), Aim/Introduction: The use of PSMA-targeted small molecules
have been developed for radionuclide therapy of metastasized to image or treat late-stage prostate cancer is a clinically
prostate cancer [1]. 177Lu-PSMA-ALB-56 consists of a DOTA- validated concept. Although the tissue distribution of small
functionalized PSMA ligand with a p-tolyl-based albumin- molecule ligands is typically rapid, the longer half-life of 64Cu
binding entity which resulted in high tumor accumulation (t1/2=12.7 h) may offer logistical advantages over 68Ga or 18F
and, hence, improved therapeutic efficacy compared to 177Lu- without compromising image resolution1. An additional benefit
PSMA-617 [2]. High blood activity levels would be limiting for of 64Cu is that it forms a chemically identical theranostic pairing
therapy due to the risk of bone marrow toxicity. The aim of with 67Cu (t1/2=2.58 d, β-=100%), improving dosimetry and
this study was, therefore, the development of a new class of patient selection. Recently, we described novel trifunctional
PSMA ligands with a weak albumin binder and variable linker PSMA-targeting ligands with high tumor uptake and therapeutic
entities to enable fine-tuning of kinetic properties. Materials index2, but the complexation of copper by DOTA is suboptimal.
and Methods: Four glutamate-urea-lysine-based PSMA ligands Sarcophagine chelators such as MeCOSar complex copper
were synthesized using solid-phase chemistry in analogy to ions efficiently and with high stability3,4. We therefore aimed to
the previously described synthesis of PSMA-ALB-56 [1]. The develop a trifunctional sarcophagine ligand for PSMA-targeted
p-tolyl-entity was replaced with an isobutyl-phenyl-propanoic theranostics with 64/67Cu. Materials and Methods: RPS-085
acid-(Ibu)-based entity and connected either directly or via a was synthesized by conjugation of a PSMA-targeting moiety,
negatively (Dα), neutral (N) or positively (DAB) charged linker an Nε-(2-(4-iodophenyl)acetyl)lysine albumin binding group,
to the ɛ-amino group of the lysine residue. 177Lu-labeling was and a bifunctionalized MeCOSar chelator. The IC50 of metal-free
performed under standard conditions and the new PSMA RPS-085 was determined by competition binding in LNCaP
radioligands were tested using PSMA-positive PC-3 PIP and cells. Radiolabeling was performed at 25°C in 0.5 M NH4OAc,
PSMA-negative PC-3 flu tumor cells. Binding properties to pH 5-6. 64Cu-RPS-085 was administered intravenously to male
plasma proteins were determined using an ultrafiltration assay. BALB/c mice bearing LNCaP xenograft tumors. The mice (n=4/
Biodistribution and SPECT/CT imaging studies were performed time point) were sacrificed at 4, 24, and 96 h post injection (p.i.)
in PC-3 PIP/flu tumor-bearing Balb/c nude mice. Results: The for biodistribution. Results: 64Cu-RPS-085 was radiolabeled in
PSMA ligands were obtained in moderate yields of 3-15% at high nearly quantitative yield in 20 min. The metal-free complex was
purity (>99%). 177Lu-labeling was achieved at up to 100 MBq/ a potent inhibitor of PSMA (IC50 = 29±2 nM). Accumulation of
nmol with >96% radiochemical purity. PSMA-binding affinity the tracer was primarily evident in tumor and kidneys. Activity in
(KD: 18-38 nM) and internalization into PSMA-positive PC-3 PIP all other tissues, including blood, was less than 1 %ID/g. Tumor
tumor cells were in the same range for all radioligands, however, activity was 12.9±1.4 %ID/g at 4 h p.i., and remained at 9.8±1.3
binding to proteins of human plasma was most pronounced for %ID/g at 48 h p.i. By contrast, activity in the kidney peaked at
S15 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

4 h (13.7±2.3 %ID/g) and cleared to 1.6±0.05 %ID/g at 48 h p.i. the level below 100nM, what means ca. 8 times lower value than
At 24 h p.i., the tumor-to-kidney ratio was 3.4±0.7, the tumor- obtained for PSMA11. The biodistribution study of 99mTc-HYNIC-
to-blood ratio was 490±152, and the tumor-to-muscle ratio PSMA conjugates showed that 99mTc-PSMA-T4 was characterized
exceeded 10000. Conclusion: 64Cu-RPS-085 combines rapid by the fastest elimination with urine and the significantly lowest
tissue distribution with prolonged retention in LNCaP xenograft accumulation in kidneys (37%ID/g 4h piv) - the critical organ for
tumors. Good contrast to background is evident by 4 h p.i., the labelled HYNIC-PSMA. The pharmacokinetic study in tumour-
leading to an imaging window from 4-48 h p.i. Preliminary bearing mice showed very high accumulation of 99mTc-PSMA-T4
biodistribution studies indicate that tumor-to-background in tumors (20-30%ID/g), constant over 24h and impressive T/M
ratios increase with time, suggesting that the pharmacokinetic ratios (230 and 550, 2 and 6h piv, respectively). Conclusion:
profile of 64Cu-RPS-085 would be suitable for PSMA-targeted In the conducted studies the 99mTc-PSMA-T4 was pointed out
radioligand therapy with 67Cu. References: [1] Conti M, Eriksson as the most promising candidate for SPECT imaging of the
L. EJNMMI Phys. 2016;3:8. [2] Kelly J, et al. Eur J Nucl Med Mol prostate cancer. The in vitro and in vivo studies showed a very
Imaging. 2018;45:1841-1851. [3] Paterson BM, et al. Dalton Trans. high affinity of this tracer to PSMA, comparable to radiolabeled
2014;43:1386-1396. [4] Gourni E, et al. Mol Pharm. 2015;12:2781- PSMA-617 inhibitor and much better than PSMA-11 used for
2790. PET diagnostics of prostate cancer. References: None.

OP-021 OP-022
In vitro and in vivo evaluation of the new 99mTc labelled Sensitivity and specificity of 18F DCFPyL (PSMA agent)
PSMA tracers for prostate cancer diagnosis compared to MR in biochemically recurrent prostate
M. Maurin1, A. E. Sikora2, M. Orzełowska2, U. Karczmarczyk2, P. cancer patients
Garnuszek2; L. Lindenberg1,2, E. Mena Gonzalez1, B. Turkbey1, I. Lim1, Y.
1
National Centre for Nuclear Research Radioisotope Centre McKinney1, J. Weaver1, P. Eclarinal1, A. Forest1, A. Hankin3, A.
POLATOM, Otwock, POLAND, 2(1)National Centre for Nuclear Couvillon3, E. Schott4, W. Dahut3, D. Citrin4, S. Harmon5, E. Bergvall6,
Research Radioisotope Centre POLATOM, Otwock, POLAND. A. Lindenberg6, A. Ton1, S. Adler5, J. Eary7, P. Choyke1;
1
Molecular Imaging Program, National Cancer Institute, NIH,
Bethesda, MD, UNITED STATES OF AMERICA, 2F. Edward Hebert
Aim/Introduction: Prostate cancer is the second commonly School of Medicine, Uniformed Services University of the Health
occurring malignance in men. The selection of an effective Sciences, Bethesda, MD, UNITED STATES OF AMERICA, 3Center
therapy form depends on the proper assessment of the disease for Cancer Research, National Cancer Institute, NIH, Bethesda,
progression. The prostate-specific membrane antigen (PSMA) is MD, UNITED STATES OF AMERICA, 4Radiation Oncology Branch,
becoming increasingly recognized as a viable target for imaging National Cancer Institute, NIH, Bethesda, MD, UNITED STATES
and therapy of prostate and other types of cancer. In the present OF AMERICA, 5Clinical Research Directorate, Frederick National
work we synthesized and investigated the series of HYNIC- Laboratory for Cancer Research sponsored by the National
PSMA conjugates with differentiated construction of the linker Cancer Institute, Bethesda, MD, UNITED STATES OF AMERICA,
between the PSMA pharmacophore and HYNIC chelator. The 6
Ft Belvoir Community Hospital, Ft Belvoir, VA, UNITED STATES
aim of this study was to compare the biological properties in OF AMERICA, 7Cancer Imaging Program, National Cancer
vitro and in vivo of the developed PSMA tracers. Materials and Institute, NIH, Bethesda, MD, UNITED STATES OF AMERICA.
Methods: The HYNIC-PSMA conjugates (PSMA-T1,T2,T3 and
T4) were synthesised using standard fmoc based solid support
synthesis followed by HPLC purification. IC50 values of these Aim/Introduction: We prospectively studied prostate cancer
compounds were determined by competitive binding assay patients with biochemical recurrence and no evidence for
on LNCaP cell membranes using radio-iodinated (131I)MIP1095 disease on conventional imaging with 18F DCFPyL PET/CT and
radioligand with known high affinity to PSMA (IC50=0.3). As the multiparametric MRI of the pelvis. Materials and Methods:
reference substances, the PSMA11 and PSMA617 were used. The In this IRB approved trial, analysis was done on 30 prostate
HYNIC-PSMA inhibitors were labelled with 99mTc in the presence cancer patients with biochemical recurrence (average PSA
of tricine and EDDA co-ligands and SnCl2 as reducing agent. 3.56 ng/mL, range 0.44-9.97 ng/mL) who underwent whole-
The binding affinity of 99mTc-HYNIC-PSMA tracers was evaluated body 18F-DCFPyL-PET/CT at 2 h p.i (299.9±15.5 MBq), and
carrying out the studies on LNCaP cell membranes (PSMA multiparametric pelvic MRI, 2 weeks apart. PET/CT and MR
positive). The non-specific binding was determined using were independently read by nuclear medicine physicians and
PC3 membranes known not to express PSMA. The preliminary a radiologist, without knowledge of findings from either scan.
biodistribution of 99mTc-HYNIC-PSMA tracers (T1,T2,T3 and T4) Histologic biopsies were obtained from all. Results: Definitive
was conducted in normal Balb/c mice 4h piv. The selected prior therapy for the population included 14 who underwent
99m
Tc-PSMA-T4 tracer was further tested for pharmacokinetics in radiation therapy, 8 prostatectomies and 8 with a combination
normal Wistar rats and Balb/c Nude mice with subcutaneously of both. 18F DCFPyL detected a total of 91 lesions while MR
induced tumors using LNCaP cells. Results: The IC50 values of the detected 43. Only 6 lesions seen on 18F DCFPyL were outside the
three HYNIC-PSMA conjugates (T1,T3 and T4) were assessed at MRI field of view. In the prostate bed, 18F DCFPyL detected 21
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S16

lesions and MR detected 30, of which 12 were concordant. 18F uptake of up to 15 %ID/g at 1 h p.i. and low activity accumulation
DCFPyL detected 40 pelvic lymph nodes while MR reported 9 of in non-target tissues and bones. Based on the high binding
which 4 were concordant. 18F DCFPyL detected 30 metastatic affinity, convenient lipophilicity and excellent biodistribution,
lesions consisting of soft tissue, bone and lymph nodes above siPSMA-14 was found to be the most promising candidate for
the aortic bifurcation. MR detected 4 metastatic lesions in bone first clinical studies in patients. Conclusion: siPSMA inhibitors
and a lymph node above the aortic bifurcation. A pubic bone stand out for their simple and fast radiofluorination as well as for
lesion was concordant on both scans. Histologic validation their good in vitro properties. Furthermore, tracer lipophilicity
was available from 69 biopsy specimens. MR and 18F DCFPyL and thus excretion route and kinetics can easily be adjusted
were concordant with biopsy results in 42 sites. Histology was by the composition of the pharmacokinetic modifier leading
concordant only with MR in 8 lesions and with 18F DCFPyL alone to ligands with favorable in vivo distribution. The promising
in 17 lesions. One concordant MR and 18F DCFPyL lesion was preclinical assessment of 18F-siPSMA-14 was confirmed in
false positive. There were no concordant false negatives. MR was an encouraging proof-of-concept study in prostate cancer
false positive in 6 specimens while 18F DCFPyL was false positive patients. References: None
in 2 sites. MR was false negative in 9 lesions and 18F DCFPyL was
false negative in 8. 18F DCFPyL sensitivity 74%, specificity 92%,
with MR sensitivity 70%, specificity 81%. Concordant MR/18F OP-024
DCFPyL findings showed sensitivity 100% and specificity 97%. [111In]In-IRDye700DX-PSMA ligands for targeted
Conclusion: 18F DCFPyL and MR each had high sensitivity and photodynamic therapy of PSMA-expressing tumors
specificity in biochemically recurrent prostate cancer patients Y. H. W. Derks1, H. I. V. Amatdjais-Groenen2, A. Kip1, G. M. Franssen1,
with a slight advantage for 18F DCFPyL. Concordant findings J. K. van der Kamp1, D. W. P. M. Löwik2, O. C. Boerman1, M.
with both modalities significantly increased sensitivity and Rijpkema1, S. Lütje3, S. Heskamp1;
specificity suggesting combined use would enhance clinical 1
Radboud university medical center, Nijmegen, NETHERLANDS,
practice. References: None. 2
Radboud university, Nijmegen, NETHERLANDS,
3
University Hospital Bonn, Bonn, GERMANY.

OP-023
18
F-siPSMAs: A Novel Class of Radiofluorinated PSMA Aim/Introduction: Incomplete resection of prostate cancer
Inhibitors (PCa) and its metastases may lead to disease recurrence and
D. Di Carlo1, V. Prasad2, A. Beer2, H. Wester1; consequently poor patient outcome. To obtain complete
1
Technical University of Munich, Garching bei München, resection of tumor tissue, prostate specific membrane
GERMANY, 2Ulm University Medical Center, Ulm, GERMANY. antigen (PSMA) targeting multimodal ligands containing
both a radiolabel and a photosensitizer may be used for intra-
operative tumor detection, delineation, and tumor-targeted
Aim/Introduction: Inspired by the series of Radiohybrid PSMA photodynamic therapy (tPDT). Previously we produced a
inhibitors (rhPSMAs) recently developed in our group, we selection of 12 multimodal PSMA ligands which demonstrated
designed and evaluated another novel class of 18F-labeled PSMA both radionuclide and fluorescence imaging potential for
ligands (siPSMAs) comprised of a Silicon Fluoride Acceptor PCa. Here, we selected the multimodal ligand with the most
(SiFA) moiety and non-chelator based pharmacokinetic favorable tumor targeting properties and evaluated its potential
modifiers. While the SiFA-moiety provides very fast and efficient for PSMA tPDT. Materials and Methods: The multimodal PSMA
radiofluorination, the modifier composition is decisive for the ligand PSMA-N064 consists of a PSMA-binding motif, a linker,
pharmacokinetic performance in vivo. Here we present the the photosensitizer IRDye700DX and the chelator DOTAGA. In
preclinical results of some selected siPSMAs differing in the vitro, therapeutic efficacy of this ligand was evaluated using
modifier sequence with special regard to the most promising PSMA-transfected LS174T and PSMA-negative wild-type
inhibitor siPSMA-14. Materials and Methods: siPSMA ligands LS174T cells, which were incubated with PSMA-N064 followed
containing a urea-based binding motif linked by a spacer with by 100 J/cm2 NIR light irradiation (3-10 min). Additionally,
a pharmacokinetic modifier in close proximity to a SiFA-moiety PSMA-N064 (3 nmol/mouse) mediated tPDT, using 150 J/cm2
were synthesized via solid phase peptide synthesis. Direct NIR light irradiation, was tested in BALB/c nude mice bearing
radiofluorination of the SiFA-based PSMA inhibitors was achieved PSMA+ LS174T-PSMA xenografts >30 mm3. Tumor growth
by isotopic exchange within 5 min at room temperature followed and survival after tPDT (2h p.i.) was compared to control mice
by fast tracer purification via solid phase extraction. For in vitro that received NIR-light irradiation or tracer injection only (n=5
characterization, logP(o/w) values as well as binding affinities mice per group). Results: In vitro a dose-dependent PSMA-
(IC50) on PSMA-expressing LNCaP cells were determined. Small specific loss of cell viability was observed after 100 J/cm2 NIR
animal μPET imaging and biodistribution studies were carried irradiation, ranging from 29% ± 7.0% (3 nM) to 84% ± 2.6% (30
out on LNCaP tumor-bearing CB17-SCID mice. Results: Novel nM, P<0.001). Moreover, in a first in vivo feasibility study it was
siPSMA ligands exhibit suitable lipophilicities (logP(o/w): -3.0 to shown that PSMA-N064-mediated tPDT may lead to tumor
-4.0) as well as high binding affinities. Biodistribution studies of growth delay and a prolonged median survival. In mice treated
18
F-siPSMA-11 and 18F-siPSMA-14 in mice showed high tumor with tPDT the time interval until tumors reach a size of 500
S17 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

mm3 (12.8 ± 1.1 days) was longer compared to only NIR-light and 11.1±10.4 in 177Lu- PSMA-R2 and 177Lu-PSMA-617 groups,
irradiated (10 ± 4.9 days) or only tracer injected control mice respectively. No statistical differences were found in tumor
(6.4 ± 1.7 days, P<0.05). In addition, tPDT prolonged survival growth under 177Lu-PSMA-R2 or 177Lu-PSMA-617 treatment.
(defined as tumor growth >1000 mm3, humane endpoint) in SPECT/CT data acquired on 6 mice from each 177Lu-group
treated mice (16 days) compared to the two control groups (12 showed strong 177Lu- PSMA-R2 and 177Lu-PSMA-617 uptakes
and 10 days, respectively). Conclusion: Here, we demonstrated at tumor level 24h p.i. with very low uptake elsewhere. VOI
the feasibility of PSMA-targeted PDT using the newly developed quantification confirmed visual observation. Interestingly,
PSMA-N064 multimodal ligand. In the future, this ligand will be after 14 days of a single dose of 111 MBq of 177Lu-PSMA-R2 or
used for intra-operative tumor detection and PSMA-tPDT. Use 177Lu-PSMA-617, similar tumor growth was observed between
of tPDT during surgery can facilitate removal of unresectable 177Lu-PSMA-R2 and 177Lu-PSMA-617 treated mice despite this
tumor rest and positive surgical margins, potentially leading to different tumor uptake at 24h. Conclusion: 177Lu-PSMA-R2 and
improved surgical outcomes of PCa patients. References: This 177
Lu-PSMA-617 have a similar biodistribution in mice inoculated
work was supported by EKFS (2016-A64) and the Dutch Cancer with PSMA positive-PC3-PIP tumor grafts. Similar significant
Society (NKB-KWF 10443/2016-1). reduction of tumor size was observed, despite the difference in
clearance from tumor tissue. References: None.
OP-025
Assessment of in vivo biodistribution and treatment
efficacy of 177Lu PSMA-R2 and 177Lu-PSMA-617 on mice 106
bearing prostate cancer tumors
V. Muzio1, L. Ravasi1, L. Sacchetti1, L. Fugazza1, S. Bacot2, M.
Do.MoRe - Rapid Fire Session: Data Analysis
Debiossat2, M. Ahmadi2, C. Montemagno2, C. Ghezzi2, A. Broisat2;
1
Advanced Accelerator Applications, a Novartis Sunday, October 13, 2019, 8:00 - 9:30 Lecture Hall 112
company, Geneva, SWITZERLAND, 2Univ. Grenoble Alpes,
Inserm, CHU Grenoble Alpes, Grenoble, FRANCE.

OP-026
Aim/Introduction: Comparison of the in vivo biodistribution Standardized Radiomics of Clinical Myocardial Perfusion
and the treatment efficacy of 177Lu PSMA-R2 and 177Lu- Stress SPECT Images to Determine Coronary Artery
PSMA-617 in mice with prostate cancer grafts. Materials Calcification Score
and Methods: PSMA positive-PC3-PIP were subcutaneously S. Ashrafinia1, P. Dalaie1, M. Salehi Sadaghiani1, T. H. Schindler2, M.
implanted in athymic nude mice in the left flank. A single G. Pomper1, A. Rahmim3;
injection of 111MBq of 177Lu-PSMA-R2 or 177Lu-PSMA-617 1
Johns Hopkins University, Baltimore, MD, UNITED
or of saline was performed approximately two weeks later, STATES OF AMERICA, 2Washington University at St. Louis,
concomitantly to randomization into groups of similar average St. Louis, MO, UNITED STATES OF AMERICA, 3University
tumor volumes expressed in mm3 . SPECT/CT imaging was of British Columbia, Vancouver, BC, CANADA.
performed in a subset of 12 mice (6 from 177Lu-PSMA-R2
group and 6 from 177Lu-PSMA-617 group). Acquisitions were
performed 24h post injection of 177Lu-PSMA-R2 and 177Lu- Aim/Introduction: Myocardial perfusion stress SPECT(MPSS)
PSMA-617. Tumor volumes were monitored daily and expressed is an established diagnostic test for patients suspected with
either as absolute values in mm3 or as a volume relative to that coronary-artery-disease(CAD). Meanwhile, coronary-artery
measured the day of the 177Lu-PSMA- R2, 177Lu-PSMA-617 or calcification(CAC) scoring obtained from diagnostic CT is a
saline administration. Tumor growth curves were compared highly-specific test, offering incremental diagnosis information
using two-ways ANOVA from the day of first injection to day 14. in identifying patients with significant CAD yet normal
Results: Absolute tumor volumes were significantly reduced MPSS scan[1]. Nonetheless, CAC scoring is not commonly
in the 177Lu-PSMA-R2 and 177Lu-PSMA-617 groups vs control performed/reimbursed in a wide community setting. Our aim
group (p<0.001). Similarly, tumor volumes from 177Lu-PSMA-R2 is to quantify heterogeneity of uptake via radiomics of ‘normal’
and 177Lu-PSMA-617 groups were significantly reduced in MPSS scans to enable prediction of CAC scores, identifying
comparison to control group (p<0.001). No differences were subclinical CAD. Materials and Methods: 428 patients were
observed between the tumor volumes of the treated groups. At collected with normal (non-ischemic) MPSS (8-30mCi 99mTc-
later time points (14-36 days), the tumors of the control group Sestamibi) with consensus reading. NM physician verified
started to reach the 1500mm3-limit volume as opposed to those images (iteratively-reconstructed/attenuation-corrected) to
of the treated groups. Control mice were therefore euthanized. be free from fixed perfusion-defect/artifactual attenuation.
Although 177Lu-PSMA-R2 and 177Lu-PSMA-617 were no longer 3D images were automatically-segmented into 4 regions-
administered, a tumor regression was observed in both groups. of-interest(ROI), including myocardium+3vascular segments
By day 36th, tumors were no longer detectable in 5 out of 10 (LAD-LCX-RCA). We developed standardized environment for
tumors from 177Lu-PSMA-R2 group and 4 out of 10 tumors from radiomics analysis(SERA)[2] and calculated 215 3D radiomic
177Lu-PSMA- 617 group. Mean tumor volume was of 13.9±23.6 features in compliance with image-biomarker standardization
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S18

initiative (IBSI)[3], ensuring reproducibility of this study. disease and improve diagnostic accuracy in patients with
Isotropic-cubic-voxel-ROIs (no resampling/interpolation balanced ischemia. Emerging SPECT technology may enable
needed) were discretized using fixed-bin-number discretization quantitative evaluation as well, but proof hereof is still in its infancy.
into 8 grey-levels (GLs) (22,...,29). We first performed two-phase We aim to contribute to ‘ground truth’ validation of quantitative
blind-to-outcome feature-selection: A)Removing: A-1)three SPECT-MPI by evaluating the accuracy of flow quantification
smallest GLs (very-low dynamic-range), A-2)two highest-GLs using a novel myocardial perfusion phantom. Materials and
(causing highly-correlated features ρ>0.9), and A-3)GL=128 Methods: The in-house built perfusion phantom mimics the
(indifferent statistical properties), ultimately selecting GL=64, anatomy and (patho-) physiology of left ventricular first-pass
similar to findings from our previous study[4]. B)Post-feature perfusion. Pumped continuous flow is conducted through a 3D
calculation: removing features with B-1)identical values, B-2) printed left ventricle and aorta, which branches into coronary
very-low dynamic-range, B-3)varieties of higher-order feature- arteries that are connected to three myocardial modules. These
classes, B-4)redundant features(ρ=1), and B-5)highly-correlated represent the microcirculation of the main coronary territories.
features (Spearman ρ>0.95). Next, we ran multivariate analysis The modules are interchangeable and can consist of different
to predict CAC scores from i) radiomics, ii) clinical-features, iii) tissue fillings. Flow sensors are incorporated into the setup as
radiomics+clinical-features. We performed randomly-selected ‘ground truth’ flow measure. Flow distribution is controlled by
60%/25%/15% training/validation/testing. Training started adjustable end-resistances, which also enables simulation of
from a constant fit, following iteratively adding/removing local perfusion deficits. As with patients, a radioactive tracer is
features (stepwise-regression) based on sorted univariate- administered and a dynamic myocardial perfusion scan is started
Spearman-correlation with CAC-scores, invoking Akaike- simultaneously to monitor tracer distribution. The resulting time
information-criterion (AIC) to discourage overfitting. Validation activity curves (TACs) serve as input for myocardial blood flow
was run similarly, with the training output-model as initial fit. quantification. The absolute difference between measured and
We shuffled training-validation sets 20 times, then found the computed flow (in mL/min/g) is used as measure of accuracy. In
best model using log-likelihood to evaluate the test-set. The the phantom experiments, we used standard clinical protocols
sensitivity to test-set was further reduced by running the entire for SPECT-MPI (D-SPECT, Spectrum Dynamics) and subsequent
operation 50 times, then employing Fisher’s method to verify flow quantification (4DM Corridor software). We injected 500
significance of independent tests. Results: Feature-selection MBq 99mTc-tetrafosmin at an aorta flow of 2-5L/min. The flow
significantly reduced 8×215 features to 56. Median Absolute into the individual myocardial modules varied between 20-
Pearson’s-correlation coefficient|p-value for 3 feature-pools(ra 100mL/min and module fillings varied (e.g. different types
diomics,clinical,combined) were: (0.15±0.11,0.38±0.08,0.41±0 of sponge materials). Results: The obtained TACs inside the
.05)|(0.1,0.001,0.0006), (0.24±0.06,0.35±0.08,0.41±0.05)|(0.05,0. simulated left ventricle match physiological values. The area
004,0.0007), (0.07±0.05,0.24±0.1,0.28±0.09)|(0.4,0.06,0.02) (0.06 under the curve remains the same for the different aortic flow
±0.05,0.16±0.06,0.24±0.06)|(0.4,0.2,0.05) for Myocardium-LAD- rates, but the maximum of the curve goes down and smears
LCX-RCA, respectively. Results demonstrate combined features out over a longer period when lowering the flow. The TACs
enhance the significance of CAC score prediction across all corresponding to myocardial tissue segments have a relatively
segments. Conclusion: Our multivariate model enabled the fast washout of less than 20s. An aortic and myocardial flow
significant prediction of CAC scores at all cardiac segments of 2 and 100mL/min, respectively, resulted in the longest
when combining standardized-radiomics with clinical features, washout time. Conclusion: This study highlights the design
suggesting radiomics adds diagnostic/prognostic value to and realization of a novel myocardial perfusion phantom to
standard MPSS for wide clinical usage. References: [1] Shaw, contribute to ground truth validation of quantitative SPECT-MPI.
et-al, Radiology, vol.228, no.3, pp.826-833, 2003. [2] Ashrafinia, First testing showed promising results, as both geometry and
PhD Thesis, 2019. [3] Zwanenburg, et-al., arXiv:1612.0700s3. [4] tracer distribution resemble left ventricular microcirculation.
Ashrafinia, et al., Medical Physics. Vol.44. No.6, 2017. Subsequent evaluation of quantitative SPECT-MPI accuracy is in
progress. References: None.

OP-027
A novel myocardial perfusion phantom: performing OP-028
‘ground truth’ flow measurements to evaluate accuracy of Initial evaluation of an automated high temporal
flow quantification with SPECT resolution data-driven motion correction for rubidium
M. E. Kamphuis1, G. de Vries1, M. Saaltink2, J. Verschoor2, A. Agool2, cardiac relative perfusion PET
M. J. W. Greuter3,1, C. H. Slump1, R. H. J. A. Slart3,1; I. Armstrong1, C. Hayden2, P. Arumugam1;
1
University of Twente, Enschede, NETHERLANDS, 1
Manchester University NHS Foundation Trust, Manchester,
2
Ziekenhuisgroep Twente, Hengelo, NETHERLANDS, 3University UNITED KINGDOM, 2Siemens Medical Solutions USA,
Medical Center Groningen, Groningen, NETHERLANDS. Inc., Knoxville, TN, UNITED STATES OF AMERICA.

Aim/Introduction: Quantitative PET myocardial perfusion Aim/Introduction: Vasodilator stress, due to predominantly
imaging (MPI) can standardize detection of coronary artery respiratory side effects, can introduce varying degrees of patient
S19 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

motion during rubidium cardiac PET. The most commonly Aim/Introduction: The use of PET for myocardial perfusion
observed is periodic patient motion due to tidal breathing imaging (MPI) is increasing rapidly due to the increased
and non-periodic motion due to cardiac creep. Motion can availability of strontium-82/rubidium-82 (Rb-82) generators,
degrade perfusion images and is time dependant; in extreme high accuracy and the possibility of quantifying myocardial
cases rendering images non-diagnostic. In contrast to SPECT, blood flow (MBF). Recently, PET systems with digital photon
motion correction during PET imaging is challenging. It can counting technology have become available. These PET
be performed by aligning reconstructed dynamic images but systems have an increased temporal and spatial resolution but
is labour-intensive and requires frames to be sufficiently long the effect on image quality or visibility of perfusion defects in
to avoid noisy data but intra-frame motion can be a potential PET MPI is still unknown. Our aim was to determine the value of
problem. This work evaluates a prototype automated data- a digital PET system in comparison to a conventional PET system
driven high-temporal resolution motion correction strategy. in MPI using Rb-82. Materials and Methods: We prospectively
Materials and Methods: 10 rubidium stress and rest images included 30 patients who underwent rest and regadenoson-
(20 images total) from a Siemens Biograph Vision with evidence induced stress Rb-82 MPI using a conventional PET system
of motion blurring were included. Frame-by-frame motion (D690, GE Healthcare). In addition, patients underwent rest and
correction (FBFMC) was performed by manually aligning and stress Rb-82 PET within three weeks on a digital PET system
summing twelve 15-second dynamic frames from 120 to 300 (Vereos, Philips Healthcare). A nuclear medicine physician and
seconds post infusion of rubidium-82. Data-driven motion cardiologist scored the image quality on a 4-point grading
correction (DDMC) was performed by automatically locating scale and assessed the existence of possible defects in both the
and tracking the myocardium within a sub-volume of raw rest and stress scans. The images were presented in random
projection data with a temporal resolution of one second. The order and readers were blinded for the type of scanner used.
offset in the axial direction within each one second frame was The image quality, defect interpretation and the quantitative
determined with a precision of 1mm and shifted to a reference MBF and myocardial flow reserve (MFR) values were compared
position. Non-corrected (NC), FBFMC and DDMC data were between both PET systems. Results: Image quality was graded
reviewed by an experienced physician. Image quality was rated fair in 20% (6/30) of the conventional scans versus 10% (3/30) of
non-diagnostic, adequate or good while perceived motion was the digital PET scans. Moreover, 60% (18/30) of the conventional
rated as none, mild, moderate or severe. Intra-frame motion scans was graded good and 20% (6/30) excellent versus 50%
still present in the FBFMC 15-second frames was determined (15/30) good and 40% (12/30) excellent for the digital PET scans
from the DDMC position tracking. Results: For image quality, (p<0.03). In addition, the defect interpretation differed in 2 out
7/20 NC images were good, 5/20 adequate and 8/20 NC non- of the 30 scans (p=0.5). Whereas these two scans were scored
diagnostic; 8/20 FBFMC images were good, 7/20 adequate and as normal on the conventional PET, they were interpreted as
5/20 non-diagnostic; 19/20 DDMC images were good and 1/20 ischemic on the digital PET. There were no significant differences
was adequate. Of the 8 non-diagnostic NC images, 5 were still between both systems in rest MBF (p≥0.3), stress MBF (p≥0.11)
considered non-diagnostic with FBFMC and the other 3 were and MFR (p≥0.5). Conclusion: Digital PET provides better image
rated adequate whereas all 8 were rated good with DDMC. Intra- quality than conventional PET and flow measurements seem
frame motion of up to 42 mm was present in the FBFMC frames comparable between the two systems. Nevertheless, defect
highlighting the limitation of this technique. Conclusion: interpretation may still differ. Additional studies are required to
Effective motion correction requires high temporal resolution confirm this. References: None.
and is not possible by post-reconstruction image-based
methods. This new automated data-driven method is promising
from our preliminary data. While neither of these methods are OP-030
used in current clinical practice, further work on a larger cohort Cross validation of quantitative assessment of global
of patients and assessment of clinical impact is required to make cardiac function through hybrid PET/MR images
it routine. References: None. A. Villagran Asiares1, T. Vitadello2, J. Cabello3,4, T. Ibrahim5, S.
Nekolla1;
1
Nuclear Medicine Department, Klinikum rechts der Isar,
OP-029 School of Medicine, Technical University of Munich, München,
Value of Digital PET in Myocardial Perfusion Imaging GERMANY, 2Medizinische Klinik, Klinikum rechts der Isar,
Using Rubidium-82 PET School of Medicine, Technical University of Munich, München,
S. S. Koenders1,2, J. A. van Dalen3, P. L. Jager1, S. Knollema1, J. R. GERMANY, 3Ex-Nuclear Medicine Department, Klinikum rechts
Timmer4, C. H. Slump2, J. D. van Dijk1; der Isar, School of Medicine, Technical University of Munich,
1
Isala hospital, Department of Nuclear Medicine, Zwolle, München, GERMANY, 4Siemens, Nokxvill, TN, UNITED STATES
NETHERLANDS, 2Technical Medicine Centre, University of OF AMERICA, 5Kardiologie, Medizinische Klinik und Poliklinik,
Twente, Enschede, NETHERLANDS, 3Isala hospital, Department Klinikum rechts der Isar der TUM, München, GERMANY.
of Medical Physics, Zwolle, NETHERLANDS, 4Isala hospital,
Department of Cardiology, Zwolle, NETHERLANDS.
Aim/Introduction: The assessment of left ventricular (LV)
function via the ejection fraction (EF) is widely used with
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S20

almost all imaging modalities. So far, these techniques, acquired characteristics (1-2). The purpose of this study was to clarify the
separately, were correlated but inter-study variability was relationship between collimator characteristics and a calibration
significant. Therefore, more cross validation studies of EF obtained factor in a Monte Carlo simulation study using a dedicated
from a hybrid PET/MR images are needed to evaluate the effects phantom for cardiac 123I- MIBG imaging. Materials and
arising from separately scans. However, in MR modalities the ECG Methods: A digital phantom was created from the 123I-MIBG
signal used for EF calculation is distorted by the magnetic fields; phantom image acquired with X-ray computed tomography.
potentially causing the missing of some R-peaks detections. This The SIMIND Monte Carlo program was used to obtain 123I-MIBG
can produce a wrong delineation of the cardiac phases in the planar images, which were generated from various collimator
PET images, resulting in a motional blur. The aim of this work was specifications: collimator hole diameters were 1, 2, 3, 4, and
to compare different PET histogramming methods proposed 5 mm; septa thicknesses were 0.10, 0.45, 0.80, 1.15, and 1.50
to solve it. Materials and Methods: List-mode FDG PET and mm; and collimator lengths were 20, 30, 40, 50, and 60 mm.
cine MR images from cardiac PET/MR viability examination of Planar MIBG imaging was simulated with 256 × 256 matrix and
19 patients were used. Three methods of PET histogramming energy window of 123I was set to 159 keV ± 7.5 %. The calibration
were tested: 1) the standard approach (STD) defines relative bin factor was calculated from the planar image using a dedicated
widths dividing each RR interval in equal gates and include all of software program, and defined as a conversion coefficient. The
R-peaks detected, 2) relative bin width with beat-rejection (BR) conversion coefficient value shows an approximate range of
adds a beat rejection that allows the elimination of RR intervals 0.5 to 0.9, corresponding to low-energy (LE) to medium-energy
outside a user-defined window, 3) fixed bin width (FW) uses a (ME) collimators. The conversion coefficient was compared with
single width gate for each subject, obtained from an optimal that from a phantom image database, which consisted of 705
RR interval. For each method, the LV end-diastolic (EDV), end- image sets. Results: A total of 125 planar phantom images were
systolic volumes (ESV) and EF were obtained. Results: The generated with the digital phantom. When 123I-MIBG phantom
EF value, and the volumes obtained from both modalities imaging with the LE, extended LE (ELE), and ME collimators was
showed positive linear correlations. However, EF (STD:43+/- simulated, the conversion coefficients for LE, ELE, and ME were
11%, BR:48+/-12%, FW:46+/-11%) and EDV (STD:144+/-37 ml, 0.52, 0.75, and 0.85, respectively. The conversion coefficients
BR:148+/-36 ml, FW:148+/-38 ml) were underestimated and ESV derived from simulated MIBG planar images were equivalent to
(STD:80+/-29 ml, BR:78+/-30 ml, FW:81+/-32 ml) overestimated those from the phantom image database (mean LE, ELE, and ME
compared with MR (EF:52+/-13 %, EDV:156+/-43 ml, ESV:75+/- values were 0.54 ± 0.04, 0.75 ± 0.03, and 0.88 ± 0.04, respectively).
32 ml). Additionally, significant differences in EF were found with When the collimator hole diameter and length were set as
STD and FW compared with MR (p< 0.01). Bland-Altman analysis 1.0 mm and 30 mm, respectively, conversion coefficients for
for EF, EDV and ESV, between PET methods and MR reported the septa thicknesses of 0.10, 0.45, 0.80, 1.15, and 1.50 mm
biases below 9%, 12,5 ml and 6 ml, respectively; while the limits were 0.52, 0.67, 0.72, 0.74, and 0.77, respectively. Conclusion:
of agreements were lower than 36%, 159 ml and 78 ml, but The Monte Carlo program successfully simulated 123I-MIBG
still clinically not negligible. The BR method showed the best phantom imaging and conversion coefficients in the various
performance. Considering the linear regression between the collimator specifications. The collimator septal thickness was a
modalities, BR method provided the best overall correlation in EF prominent component in 123I-MIBG phantom simulation. When
(slope:0.68 and Pearson coefficient (r):0.74) and EDV (slope:0.52 the collimator specifications are determined, the conversion
and r:0.62), while in the case of ESV, FW performs best (slope:0.74 coefficients can be estimated without 123I-MIBG phantom scan.
and r:0.79). Conclusion: Ejection Fraction assessed with PET and References: (1) Verschure DO, et al. J Nucl Cardiol 2017:1-7. (2)
MR in simultaneously acquisitions have a positive association, Nakajima K, et al. J Nucl Cardiol 2014;21:970-8.
but there are still relevant differences depending on the PET
histograming method. References: None.
OP-032
Impact of deep learning artificial intelligence approaches
OP-031 on amyloid PET diagnosis
Effect of collimator characteristics on 123I-MIBG phantom M. Schürer1, K. T. Chen2, T. Jochimsen1, M. Rullmann1, M. Patt1, S.
imaging using Monte Carlo simulation Tiepolt1, M. Schroeter3, C. Weise4, D. Saur4, G. Zaharchuk2, O. Sabri1,
K. Okuda1, K. Nakajima2, C. Kitamura3, Y. Kirihara3, J. Taki2, M. H. Barthel1;
Hashimoto1, S. Kinuya2; 1
Department of Nuclear Medicine, University of Leipzig Medical
1
Kanazawa Medical University, Kahoku, JAPAN, Center, Leipzig, GERMANY, 2Radiology, Stanford University, Stanford,
2
Kanazawa University, Kanazawa, JAPAN, 3FUJIFILM CA, UNITED STATES OF AMERICA, 3Max Planck Institute for Human
Toyama Chemical Co., Ltd., Tokyo, JAPAN. Cognitive and Brain Sciences, Leipzig, GERMANY, 4Department of
Neurology, University of Leipzig Medical Center, Leipzig, GERMANY.

Aim/Introduction: We have proposed a standardization


method using a dedicated 123I-metaiodobenzylguanidine Aim/Introduction: Deep learning artificial intelligence
(MIBG) phantom for the determination of a heart-to- approaches have a great potential to simplify and improve
mediastinum count ratio for the calibration of the collimator medical imaging. This might, in case of PET imaging, also refer to
S21 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

shorten scan times/reducing tracer doses. In this present study Methods: Bone scintigraphies of 127 mCRPC patients treated
we evaluated whether this is the case for [18F]Florbetaben with 223Ra were collected before, during and after the therapy.
amyloid PET/MRI. Materials and Methods: We prospectively Follow-up images were taken after 3 months, 6 months and one
acquired list-mode [18F]Florbetaben brain PET/MRI scans year. DASciS software was used to process bone scans and BSI
(300MBq, scan start 90min p.i.) of 40 patients (“new data”, 21 was calculated. BSI values were analyzed alone and together
female, age=64±11yrs). The PET data were reconstructed for a with 3-PS (prognostic score based on basal values of Hb, PSA
(clinical standard) 20min scan duration as well as for 1min scan and ECOG-PS) in order to evaluate the OS predictive power of
duration. For the 1min scan duration data, different deep learning these parameters. Results: Employing DASciS software 546
approaches (a U-net was pre-trained with previous low-dose scintigraphies were analyzed, ( 127 basal, 211 intermediate,
PET/MRI data and was either (AI1) directly applied to new data 87 final, 60 after 3 months, 38 after 6 months and 23 after one
or (AI2) trained further with the new data, or trained from scratch year). Both the univariate (HR: 1,8, 1,61-2,02, p=0,001) and the
based on (AI3) new data only or (AI4) all existing data) were multivariate (HR: 1,82, 1,56-2,10, p=0,001) analysis -adjusted
applied. All PET data were analyzed visually (3 blinded experts, for BMI, age, Gleason Score, number of previous systemic
binary score for amyloid load and 5-point score for image quality treatments, basal PSA, tALP, Hb, PLT, ECOG-PS- confirm the OS
with 5 being the highest score for excellent image quality) and prediction power of basal BSI (Percentage of bone disease are:
semi-quantitatively (composite SUVRs, reference: cerebellar 0-3% = 28 months of median survival (MoMS), 3%-5% = 11
cortex, Hermes BRASS software). The 20min scan duration MoMS, more than 5% = 5 MoMS). The association of BSI with
majority visual read served as standard to truth (SoT). Results: 3-PS have however the best OS prediction power (AUC=91%).
According to the SoT, 19 and 21 patients were amyloid-positive Conclusion: Load of bone disease first of 223Ra treatment
and -negative, respectively. Mean sensitivity and specificity is an excellent predictor of OS and DASciS software is an
for the three blinded readers were 100% and 95%, 100% and accurate tool to calculate BSI. BSI and 3-PS together represent
78%, 100% and 100%, 100% and 100%, and 100% and 100% a unique multidimensional evaluation of mCRPC patients
for the 1min, 1min+AI1, 1min+AI2, 1min+AI3, and 1min+AI4 at basal conditions and are very useful for the stratification
data, respectively. Image quality in visual analysis was 2.5±0.3, of patients who are candidates to 223Ra treatment. Despite
3.0±0.3, 4.0±0.3, 3.9±0.1and 3.8±0.1. Cohen’s d effect sizes for EMA recommendation, the calculation of the bone disease
the composite SUVRs according to amyloid state in SoT were extension percentage instead of number of lesions appears to
significantly higher in the 1min+AI1/4 as compared to the 1min be a more reliable tool for patients recruitment. References: A
data (2.38/2.64/2.33/2.59 vs. 1.79). Conclusion: Using a trained 3-variable prognostic score (3-PS) for overall survival prediction
neural network, scan duration in [18F]Florbetaben amyloid PET/ in metastatic castration-resistant prostate cancer treated with
MRI can be reduced down to 1min without losing diagnostic 223Radium-dichloride. Ann Nucl Med. 2017 Dec 28; V 32 (2),
quality. This would alternatively translate to a reduction of 142-148, 1. DOI 10.1007/s12149-017-1228-6
tracer dose/radiation exposure by 95%. In conclusion, the deep
learning artificial intelligence approach developed has great
potential to improve patient convenience/throughput and/or OP-034
reduce tracer costs. References: None. Impact of PET/CT image reconstruction parameters
on patient dose distributions for quantitative 90Y liver
radioembolization
OP-033 X. Hou1, H. Ma2, P. Esquinas3, S. Tolhurst1, F. Benard4, D. Liu1, A.
DASciS software: a scintigraphic tool able to evaluate the Celler1;
scintigraphic load of bone disease as a survival predictor 1
Radiology Department, University of British Columbia, Vancouver,
in mCRPC Radium-223 patients BC, CANADA, 2Department of Physics and Astronomy, University
V. Frantellizzi, M. D. Ippoliti, M. Conte, G. De Vincentis; of British Columbia, Vancouver, BC, CANADA, 3IBM Watson
Sapienza University of Rome, Rome, ITALY. Health Imaging, Mississauga, ON, CANADA, 4Department of
Molecular Oncology, BC Cancer, Vancouver, BC, CANADA.

Aim/Introduction: Alpha-emitter 223Radium-dichloride is


associated to a clear survival benefit and significant bone pain Aim/Introduction: 90Y-radioembolization is a well-established
palliation in CRPC patients with symptomatic bone metastases. treatment option for nonsurgical patients with liver tumours.
Increase in Overall Survival (OS) is strictly associated to 6-cicles Measuring the dose distribution with 90Y PET/CT scans could be
therapy’s administration. Bone Scan Index (BSI) is defined as the useful for dose verification and to investigate tumour response
percentage of total amount of bone metastasis on whole-body to treatment. However, 90Y PET images are typically of very poor
scintigraphic images. To calculate BSI values we used DASciS quality due to the low intensity of positrons from 90Y. Regularized
software, developed by an engineering team of “Sapienza” reconstruction algorithms have recently been introduced in
University of Rome. Aim of our observational, prospective, non clinical scanners to iterative reconstruction algorithm to reach
randomized study was to assess the load of bone disease at convergence while minimizing image noise. The aim of this work
starting and in the time course of Ra-223 treatment, in mCRPC was: 1) to evaluate regularized image reconstruction parameters
patients, as an overall survival (OS) predictor. Materials and to optimize image quality and quantification accuracy using
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S22

phantom studies, and 2) to investigate their impact on the dose Materials and Methods: A series of phantom measurements
distributions in lesions and healthy livers in patient studies. with Sc-44 and F-18 at different activity concentrations were
Materials and Methods: The IEC-NEMA phantom (9.7L) and performed using Mediso nanoScan PET/MR. Raw data were
six spheres (0.5-26mL), filled with 90Y activities (0.325MBq/ analyzed with respect to different energy windows. After
mL and 2.45MBq/mL, respectively) were scanned using iterative 3D reconstruction, a quantitative image VOI analysis
GE-D690 PET/CT camera. Images were reconstructed with was performed by using PMOD. Results: In comparison to F-18,
OSEM (standard) and the Q.Clear regularized reconstruction Sc-44 showed a different energy spectrum of coincidences
method (β-parameter ranging 0-8000), both with the time- with a higher Compton peak, lower 511 keV peak and higher
of-flight option enabled. The reconstruction parameters were background due to its additional γ quanta. For Sc-44, 16.9-20.1
optimized for image quality by evaluating the background % of acquired coincidences were detected in an energy window
noise and contrast-to-noise ratios; while, the hot and cold of 400-600 keV in contrast to 19.3-23.7 % for F-18. On average,
contrast recovery coefficients were used for evaluating image the reconstructed activity of Sc-44 was 19.5% lower than that of
quantification accuracy. Then, the optimized reconstruction F-18. Conclusion: The co-emission of γ quanta of Sc-44 leads to
parameters were applied to PET/CT scans obtained from five a different energy spectrum in the raw data in comparison to
subjects following 90Y-radioembolization studies. Dose maps of F-18. As a consequence, lower activity was detected for Sc-44
healthy liver parenchyma and tumours were estimated using in the reconstructed images. Therefore, an additional correction
the MIM software. The variabilities (coefficients of variation factor should be applied in further studies, in particular for
(COV)) of dose volume histograms, Dmax, Dmean, D70, and V100Gy for quantification and dose calculations. References: None.
the entire range of investigated reconstructions were assessed.
Results: Generally, superior image quality was obtained from
Q.Clear compared to OSEM reconstructions. The β-parameter 107
optimized for best image quality was found to be in the range of
2000 - 2500 and equal to 300 for best quantification accuracy. In
Pitfalls & Artefacts 1 - Interactive Clinical Cases -
order to estimate how different reconstructions influence dose
Paediatrics Committee: Pitfalls and Artefacts in
distributions, β-parameter ranged from 300-8000 were applied
Paediatric Nephro-Urology
to patient studies. For Dmean, D70, and V100Gy, the COVs were <7%
for all five patients; whereas, the COVs for Dmax were >15%. Sunday, October 13, 2019, 8:00 - 9:30 Lecture Hall 113
Conclusion: There was a clear advantage of using regularized
(Q.Clear) over conventional OSEM reconstruction to maximize
image quality and quantitative accuracy for PET imaging
studies performed after 90Y-radioembolization studies. However, OP-036
the β-parameter used in Q.Clear reconstructions needs to be Dynamic Renal Scintigraphy
carefully selected based on the study objectives, since its value A. Santos;
will largely influence the visual quality of reconstructed images, Hospital Garcia de Orta,E.P.E., Nuclear Medicine
as well as quantification accuracy and dose distribution in Department, Almada, PORTUGAL.
tumours and healthy liver. References: None.

OP-037
OP-035 Static Cortical Scintigraphy
Impact of high energy co-emitted gamma quanta on Z. Bar-Sever;
quantification of Sc-44 Schneider Children´s Medical Center, Department
F. Rosar1,2, H. G. Buchholz2, M. Piel3, F. Rösch3, M. Schreckenberger2; of Nuclear Medicine, Petach Tikva, ISRAEL.
1
Department of Nuclear Medicine, Saarland University
Medical Center, Homburg, GERMANY, 2Department
of Nuclear Medicine, Johannes Gutenberg-University, OP-038
Mainz, GERMANY, 3Institute of Nuclear Chemistry, Radionuclide Cystography
Johannes Gutenberg-University, Mainz, GERMANY. L. Biassoni;
Great Ormond Street Hospital for Children NHS Foundation
Trust, Department of Radiology, London, UNITED KINGDOM.
Aim/Introduction: Scandium-44 is a promising PET nuclide with
a half-life of 3.97 h and a β+ fraction of 94.27 %. Several preclinical
and clinical trials have been performed using Sc-44 labeled
tracers e.g. Sc-44-PSMA-617 or Sc-44-DOTATOC. In contrast to the
F-18, Sc-44 emits additional γ quanta (E= 1157 keV), which may
influence the PET data acquisition. In this study we investigated
the differences in coincidence energy spectra of Sc-44
compared to F-18 and analyzed its influence on quantification.
S23 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

108 median SUVmax of the urinary bladder in 68Ga-PSMA-11 PET/


CT in comparison to patients receiving no preparation and
Clinical Oncology - Rapid Fire Session: Prostate - patients receiving only hydration with 500 ml sodium chloride.
BCR and More References: None.

Sunday, October 13, 2019, 8:00 - 9:30 Lecture Hall 114


OP-040
Next-generation PET is a sensitive and reproducible
biomarker of early CRPC
OP-039 M. M. Weber1, C. E. Kurek2, F. Barbato1, C. Rischpler1, M. Eiber3, T.
Impact of application of furosemide combined with Maurer4, B. Hadaschik5, K. G. Herrmann1, A. Wetter6, F. P. Wolfgang1;
hydration on the halo artefact and intensity of tracer 1
University Clinic Essen, Department of Nuclear medicine, Essen,
accumulation in the urinary bladder in 68Ga PSMA-11 PET/ GERMANY, 2University Clinic Essen, Deparment of Nuclear
CT medicine, Essen, GERMANY, 3Department of Nuclear Medicine,
C. Uprimny1, A. Kroiss2, B. Nilica2, H. Svirydenka2, E. Elmisgheri2, C. Klinikum Rechts der Isar, Technische Universität München,
Decristoforo2, E. Guggenberg2, G. di Santo2, I. Virgolini2; Munich, GERMANY, 4Martini-Clinic and Department of Urology,
1
Medical University of Innsbruck, Gaimberg, AUSTRIA, University Clinic Hamburg-Eppendorf (UKE), Hamburg, GERMANY,
2
Medical University of Innsbruck, Innsbruck, AUSTRIA. 5
Department of Urology; University Hospital Essen, Essen,
GERMANY, 6Institute of Diagnostic and Interventional Radiology
and Neuroradiology; University Hospital Essen, Essen, GERMANY.
Aim/Introduction: Comparative study to assess systematically
the influence of hydration and application of furosemide on
the occurence of the halo artefact, a photopenic artefact Aim/Introduction: At early diagnosis of castration-resistant
surrounding the urinary bladder, that might be present on prostate cancer (CRPC), PSA measurement is limited by
68
Ga-PSMA-11 PET/CT images. Materials and Methods: fluctuations and conventional imaging by low detection
200 consecutive prostate cancer patients referred for 68Ga- probability. We thus aim to assess the value of PSMA-PET/CT as
PSMA-11 PET/CT were included. Four groups receiving different biomarker at early CRPC. Materials and Methods: We screened
preparation prior to imaging, comprising 50 patients each, were our local database (n=1369) for patients with histopathologically
compared. Group one: no intervention. Group two: intravenous proven prostate cancer, rising PSA despite effective androgen-
hydration with 500 ml sodium chloride after tracer application. deprivation therapy and PSA ≤ 3. CT and PSMA-PET/CT scans
Group three: intravenous hydration with 500 ml sodium chloride of eligible patients (n=46) were anonymized and interpreted
and 20 mg furosemide injected after tracer application. Group independently by three blinded readers. Patients were stratified
four: intravenous hydration with 500 ml sodium chloride and by PSA (<1.0; 1-0-2.0; 2.0-3.0); primary endpoint was the per-
40 mg furosemide injected after tracer application. Images were patient detection rate. Secondary endpoints were the per-
analysed visually to judge whether halo artefact was present. region detection rate, interobserver agreement and risk factors
In addition intensity of tracer uptake in the urinary bladder was for PET positivity or M1-disease. Results: PSMA-PET/CT was
measured semiquantitatively with calculation of maximum positive in 74% of patients. 28% patients had local disease
standardised uptake value (SUVmax). Results: In group one (no only, 46% patients had M1-disease (26% bone, 4% visceral).
preparation) ten patients (20 %) demonstrated a halo artefact Interobserver agreement was substantial/almost perfect (Fleiss’
surrounding the urinary bladder with a median SUVmax of kappa 0.80, 95% confidence interval 0.63-0.97) for PET. Factors
66.9 (range: 9.3 - 349.9) of the urinary bladder. In group two typically associated with adverse outcome (e.g. Gleason Score
(intravenous hydration only) in seven patients (14 %) the halo ≥8, PSA doubling time≤6 months) were not associated with PET
artefact was present with a median SUVmax of 21.8 (range: 9.0 - positivity or M1-disease. Conclusion: PSMA-PET/CT localizes
170.6) in the urinary bladder. In group three (20 mg furosemide) prostate cancer in more than two thirds of patients with pre/
and group four (40 mg furosemide) no halo artefact could be early CRPC, even before PSA exceeds the 2 ng/mL threshold.
found. Median SUVmax of the urinary bladder in group three PSMA-PET/CT is a sensitive and reproducible biomarker of
and four was 8.9 (range: 2.3 - 32.1) and 9.7 (range: 2.3 - 26.8), disease that may allow earlier diagnosis and guided treatment
respectively. The difference in number of halo artefact and of CRPC. References: None.
median SUVmax of urinary bladder between group one and
group three and four was statistically significant (p <0.001).
Although median SUVmax was significantly reduced between OP-041
group one and two, number of halo artefact in these two groups Benefit of CT urography in 68Ga-PSMA-11 PET with low
did not differ significantly. No significant difference of results dose CT
could be observed in patients receiving 20 mg furosemide F. Rosar1, M. Hügle1, M. Ries1, S. Maus1, M. Bartholomä1, T. Stemler1,
and those injected with 40 mg furosemide. Conclusion: H. Bohnenberger1, P. Fries2, F. Khreish1, S. Ezziddin1;
Intravenous injection of 20 mg furosemide combined with 500 1
Department of Nuclear Medicine, Saarland University Medical
ml sodium chloride significantly reduces the halo artefact and Center, Homburg, GERMANY, 2Department of Radiology,
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S24

Saarland University Medical Center, Homburg, GERMANY. prostate cancer. To evaluate the advantages, disadvantages and
comparability of these PET tracers. Materials and Methods:
Prospective study of 58 patients with biochemical recurrence
Aim/Introduction: Accuracy of 68Ga-PSMA-11 PET/CT may be of prostate cancer after definitive primary therapy (radical
hampered by ureter accumulation. Depending on localization prostatectomy, radiation therapy). 18F-Fluciclovine and 68Ga-
and configuration it may mimic lymph node metastases. We PSMA-11 PET/CT were performed within a time window of
evaluated the benefit of intravenous CT contrast agent for median 9,4 days with standardized image acquisition protocols
urography in 68Ga-PSMA-11 PET with low dose CT to help to and interpretation criteria. The performance of both tracers were
differentiate between lymph node metastasis and urinary evaluated on a patient- and region-based analysis. Results: The
tract activity. Materials and Methods: Retrospective analysis patient-level detection rate for prostate cancer recurrence was
of n=247 PET/CT scans (Biograph 40 mCT, 124±17 MBq 68Ga- 79.3% in 18F-Fluciclovine and 82.8% in 68Ga-PSMA-11 (p=0.64).
PSMA-11, 60 min p.i. image-acquisition, iterative 3D OSEM Local recurrence was detected in 22/58 (37.9%) patients on
algorithm (3 iterations, 24 subsets), low dose CT (120 keV, max. 18
F-Fluciclovine PET/CT and only in 16/58 patients (27.6%) on
30 mAs)) for primary staging, biochemical recurrence or local 68
Ga-PSMA-11 PET/CT (p=0.03). In 6/58 patients (10.4%) local
therapy planning. For urography, a reduced amount of 30 ml recurrence could only be detected in 18F-Fluciclovine scans.
contrast agent (370-400 mg iodine/ml) was applied 10 minutes Local pelvic lymph node recurrence was detected in 27/58
prior to image acquisition. All foci of potential pathologic patients (46.6%) on 18F-Fluciclovine PET/CT and in 29/58
radiotracer accumulation were reviewed and analysed. The patients (50.0%) on 68Ga-PSMA-11 PET/CT (p=0.71). Local pelvic
success of achieving a contrasted ureter was verified by lymph node recurrence was only detected on 68Ga-PSMA-11
measuring Hounsfield units in the ureter. All foci were rated scan in 3/58 patients (5.2%), and on 18F-Fluciclovine scan in
and scored by at least three experienced physicians to assess 1/58 patients (1.7%). Extrapelvic lymph node metastases were
the provided benefit of urography. In addition, the imaging detected in 24/58 patients (41.4%) on 18F-Fluciclovine PET/CT
outcome for further decision making was evaluated. Results: and in 30/58 patients (51.7%) on 68Ga-PSMA-11 PET/CT (p=0.26).
By CT urography, it was possible to identify each ureter on In 6/58 patients (10.4%), distant lymph node metastases
low dose CT, with its major part contrasted. In 120/247 PET/ were only detected on 68Ga-PSMA-11. Bone metastases were
CT scans (48.6 %) with 189 sites of (peri)ureteral accumulation detected in 15/58 patients (25.9%) on 18F-Fluciclovine PET/CT
urography increased the diagnostic confidence. In 60 (24.3 %) and in 21/58 patients (36.2%) on 68Ga-PSMA-11 PET/CT (p=0.23).
scans, urography was rated important for decision making. In In 8/58 patients (13.8%), bone metastases were only detected
36 of 189 sites, the tracer accumulation would not have been on 68Ga-PSMA-11 scan, and on 18F-Fluciclovine scan in 2/58
attributable to lymph node metastases or ureter excretion patients (3.5%). Conclusion: The strength of 18F-Fluciclovine in
without urography. In 42 (17.0 %) scans, urography-enhanced comparison to 68Ga-PSMA-11 lies in detecting local recurrence
PET-CT reading was clinically relevant (up-/downstaging) with of prostate cancer especially when located in close anatomic
potential impact on subsequent patient care. In 30 of these 42 relation to the urinary bladder. In the detection of distant
cases (12.1 % of all), change in treatment would have resulted metastases 18F-Fluciclovine is almost comparable to 68Ga-
from misdiagnosed focus without urography. Conclusion: PSMA-11 PET/CT, with heterogeneity of tracer-avid disease
Additional administered contrast agent for CT-urography across both scans. References: None.
benefits the interpretation of 68Ga-PSMA-11 PET with low dose
CT by increasing diagnostic confidence in the differentiation of
lymph node metastases and urinary tract activity. A subsequent OP-043
change in patient management will result in a small but Impact of late pelvic acquisition on 68Ga-PSMA-11 PET/CT
significant subset (12% in our cohort). Reduced contrast amount positivity rate and inter-rater reliability analysis
of 30 ml (370-400 mg iodine/ml) applied 10 minutes prior to D. Nicolotti, F. Ceci, E. Pilati, B. Dionisi, I. Cerio, M. Finessi, V. Liberini,
image acquisition is adequate to identify the ureter on low dose R. Passera, G. Bisi, D. Deandreis;
CT. References: None. Nuclear Medicine Unit, Department of Medical
Sciences, University of Turin, AOU Città della Salute
e della Scienza di Torino, Turin, ITALY.
OP-042
Prospective intra-patient comparison of 18F-Fluciclovine
and 68Ga-PSMA-11 PET/CT in biochemical recurrence of Aim/Introduction: The primary aim of this study was to
prostate cancer after definitive therapy evaluate the impact of late-pelvic scan on 68Ga-PSMA-11-
B. Pernthaler, H. Kvaternik, R. Kulnik, C. Gstettner, R. M. Aigner; PET/CT accuracy in localizing recurrent prostate cancer (PCa).
Medical University Graz, Department of Radiology, Secondary objective was the comparison of inter-rater reliability
Division of Nuclear Medicine, Graz, AUSTRIA. between standard images and late acquisition, both in a per-
patient and per-region analysis. Materials and Methods:
68
Ga-PSMA-11-PET/CT is performed in our institution through a
Aim/Introduction: To compare 18F-Fluciclovine to 68Ga- prospective, single-centre, study (protocol P-5315) in hormone-
PSMA-11 PET/CT in patients with biochemical recurrence of naïve recurrent PCa. Data of the first 65 consecutive patients
S25 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

who performed late-pelvic acquisition were retrospectively Aim/Introduction: Limited data is available about the
analysed. Administered activity was 2.5 (±0.5) MBq/Kg. Vertex interobserver variability of PSMA PET/CT and intraobserver
to mid-thigh images were acquired at 60 (±10) minutes post- variability has not been published. We aimed to investigate
injection, 2.5 minutes per bed-position. Late-pelvic images intra- and interobserver agreement for 68Ga-PSMA PET/CT
were acquired at 120 (±15) minutes post-injection, 6 minutes interpretations according to miTNM and PSMA-RADS reporting
per bed-position, 2 beds centered on pelvis. All images were templates and identify PET/CT findings with high variability
acquired by the same scanner (Philips Gemini Dual-Slice EXP and investigate diagnostic confidence levels of readers at
PET/CT) and interpreted by three independent experienced specific PSMA PET/CT findings. We also investigated clinical
readers (R1=EP, R2=DN, R3=FC) using the same workstation outcome of interobserver variability. Materials and Methods:
(GE Advantage). Both acquisitions were interpreted in a per- Patients (n=136) were selected with simple randomization.
patient and per-region (prostate bed; pelvic lymph-nodes; pre- Anonymized images were evaluated by four experienced
sacral lymph-nodes; pelvic bones) analysis, using a 3-point scale readers independently according to miTNM and PSMA-RADS
(not suspected for PCa[0], undetermined[1] and suspected for templates. Diagnostic confidence levels of all findings also
PCa[2]). The impact of late-pelvic acquisition was evaluated as reported. Results evaluated with Feiss kappa test or intraclass
reader’s confidence (decreasing of undetermined findings rate) correlation coefficients test(ICC) using 2-way mixed model for
and number of lesions detected. The degrees of agreement absolute agreement. Results: Readers agreed substantially for
were assessed using intraclass correlation coefficients (ICC) and N and almost-perfectly for M categories (k=0.71 95%CI:0.67-0.79
their CI95%, using a 2-way mixed, single measure, consistency and 0.78 95%CI:0.74-0.82). Moderate agreement was observed
model. ICC was interpreted as follow: 0.0, poor; 0.0-0.20, slight; for initial T staging (k=0.63 95%CI:0.59-0.66). According to six-
0.21-0.40, fair; 0.41-0.60, moderate; 0.61-0.80, substantial; 0.81- quadrant prostate reporting template, moderate or substantial
1.00, almost-perfect reproducibility. Results: Overall 68Ga-PSMA- agreement were observed for intraprostatic lesion localization
11-PET/CT positivity rate increased from standard to late-pelvic (k=0.48 - 0.62). However, almost perfect interobserver
acquisition: R1=43.07% to 60%, R2=49.23% to 64.62%, R3=40% agreement was observed for number of intraprostatic sites (ICC:
to 55.38%, respectively. The reduction ratio of undetermined 0.90 - %95CI:0.86-0.93). In Gleason Group 1 (GS 3+3) moderate
scans was: R1=18.46% (21.54% to 3.08%), R2=15.39% (21.54% reproducibility was observed (κ=0.531 %95CI:0.34 - 0.722). In
to 6.15%), R3=15.38% (18.46% to 3.08%). All readers detected Gleason Group ≥2 substantial reproducibility was observed (κ=
additional findings in late-scan compared to standard: R1=66 0.655 %95CI 0.55-0.761). Substantial agreement was observed
to 68; R2=64 to 72; R3=61 to 68. In the per-patient analysis for vesicula seminalis invasion (k=0.622 - 95%CI:0.533-0.71). All
the inter-observer agreement resulted substantial in standard readers reported lower diagnostic confidence levels for «T3a»
scan (ICC=0.802, CI95%=0.733-0.834) and improved to almost- compared to other T stages (p<0.01). Three readers reported
perfect in late-pelvic acquisition (ICC=0.851, CI95%=0.785- lower diagnostic levels for «T0» compared to other T stages
0.900). In the per-region analysis the inter-observer agreement (p<0.001). Two readers reported lower diagnostic confidence
improved especially in the prostate bed (ICC-standard=0.531, levels in patients with N1 compared to N0&2. In 12% (n=16) of
CI95%=0.390-0.661; ICC-late=0.606, CI95%=0.476-0.721), which the patients, only one reviewer reported clinically significant
remains however the more difficult district to evaluate, with discordance (amendable errors with peer-review). In 9% (n=12)
moderate agreement. Despite high incidence of undetermined of the patient, the disagreement influences clinical management
findings, pelvic lymph-nodes reached almost-perfect agreement 3.8%(n=5). Almost-perfect intraobserver agreement was
both in standard (ICC=0.839, CI95%=0.770-0.892) and late-pelvic observed for 5-scale PSMA-RADS criteria (ICC=0.90 95%CI: 0.865-
acquisition (ICC=0.878, CI95%=0.824-0.920). Conclusion: Our 0.934). If lesions are grouped as benign (Score 1-2), suspicious (3)
results show that the late-pelvic scan increases the overall 68Ga- and malignant (4-5) moderate agreement was observed (k=0.5-
PSMA-11-PET/CT positivity rate and the number of detected 95%CI:0.434-0.564). Conclusion: PSMA PET has a substantial
lesions, improves reader’s confidence and allows better inter- interobserver agreement and an almost perfect intra-observer
observer reproducibility. References: None. agreement levels. Interobserver variance has a limited effect on
clinical decisions. PSMA PET/CT has the highest interobserver
agreement levels among the modalities used for imaging of
OP-044 prostate cancer. Lower (still moderate) interobserver agreement
Interobserver and intraobserver agreement of PSMA PET/ calculated for intraprostatic lesion localization due to limitation
CT according to miTNM and PSMA-RADS criteria of 6-quadrant template. Peer-review significantly increases
E. Demirci1, R. Akyel2, B. Caner1, N. Alan-Selçuk1, S. Güven Mese3, L. reproducibility and reliability of PSMA PET/CT. miTNM template
Kabasakal4; is better for standardization of PSMA-PET reporting, compared
1
Yeditepe University, Department of Nuclear Medicine, to PSMA-RADS template. References: None.
Istanbul, TURKEY, 2Sisli Etfal Training and Research Hospital,
Istanbul, TURKEY, 3Yeditepe University, Department of Medical
Oncology, Istanbul, TURKEY, 4Istanbul University-Cerrahpasa,
Department of Nuclear Medicine, Istanbul, TURKEY.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S26

OP-045 Aim/Introduction: A well-recognized barrier to therapy


Evaluation of [68Ga]Ga-PSMA-PET/CT in therapy response response assessment in castration-resistant prostate cancer
assessment of PSMA-targeted radionuclide therapy in (CRPC) is the lack of reliable surrogate markers of response to
patients with castration resistant prostate cancer treatment coupled with a potentially exaggerated reliance on
J. Kurth1, J. Kretzschmar1, M. Heuschkel1, G. Kundt2, O. W. changes in serum prostate-specific antigen (PSA) as an indicator
Hakenberg3, B. J. Krause1, S. M. Schwarzenboeck1; of treatment efficacy. Functional imaging modalities have been
1
Department of Nuclear Medicine, Rostock University Medical advocated as important markers of disease response and
Center, Rostock, GERMANY, 2Institute for Biostatistics and progression to different tumor entities.The aim of this study was
Informatics in Medicine and Ageing Research, Rostock University to investigate the role of 99mTc-HYNIC-PSMA SPECT/CT in the
Medical Center, Rostock, GERMANY, 3Department of Urology, early treatment evaluation and outcome prediction in patients
Rostock University Medical Center, Rostock, GERMANY. with CRPC treated with long-term abiraterone. Materials and
Methods: 99mTc-HYNIC-PSMA SPECT/CT was performed in 68
CRPC patients before and after 3-6 months treatment with
Aim/Introduction: Aim of this study was to retrospectively abiraterone. Treatment response was assessed according to
evaluate the value of [68Ga]Ga-PSMA-PET/CT in monitoring RECIST 1.1 and PERCIST 1.0 criteria, respectively. A decrease in
early and late response to PSMA-targeted radionuclide therapy serum PSA level of ≥50% was defined as biochemical response
(Lu-177/Y-90) in castration resistant prostate cancer patients. (BR). Univariate and multivariate Cox regression models
Materials and Methods: 38 patients were referred for [68Ga] addressed potential predictors of progression-free survival
Ga-PSMA-PET/CT before the first cycle (PET 1), after one/ (PFS) and overall survival (OS). Results: Declines in PSA level of
two cycles (PET 2) and after a mean of 3 cycles (range 3 to 5 ≥50% were seen in 21 of 68 (31%) patients. The concordance
cycles) (PET 3) of PSMA radioligand therapy (Lu-177/Y-90) for rate between SPECT and BR was 81% (Cohen κ = 0.60; 95% CI,
patient-based therapy response assessment. PET-based therapy 0.33-0.90;P ≤ 0.01), higher than for that between SPECT and CT
response was assessed according to EORTC and PERCIST with 55% (κ = 0.40; 95% CI, 0.23-0.68; P ≤ 0.01), as well as that
criteria, for PET 2 vs. 1 (early response assessment, ERA) as well between CT and BR with 40% (κ = 0.43; 95% CI,0.26-0.67, P ≤
as for PET 3 vs. 1 (late response assessment, LRA). PET-classified 0.05). In univariate analysis, PSA decline and PSMA SPECT/CT
response was compared to the results of ERA and LRA based on response predicted PFS and OS. In multivariate analysis, only
clinical criteria (best clinical response) and percentual change PSMA SPECT/CT (progression vs nonprogression) remained
in PSA. Additionally, relationship between change of SUVmax/ significant for PFS and OS (p = 0.013 and p = 0.022, respectively).
SUVmean and PSA (early and late, respectively) was evaluated. Conclusion: Early PSMA SPECT/CT can predict clinical outcome
Prognostic value of initial SUVmax and SUVmean was assessed. in CRPC beyond PSA response and conventional CT approach.
Results: About 76% of the patients were classified as SD or PR Our data support further studies on PSMA SPECT/CT for
(SD: 65.2%; PR: 10.9%) by clinical criteria and 77% by change in abiraterone monitoring and outcome prediction in patients
PSA as response criterion (SD: 46.7%; PR: 31.1%). However, by with CRPC. References: None.
PET-based response assessment approx. 95% were classified as
SD or PR (PERCIST: SD 23.9%; PR: 71.7%; EORTC: SD 23.9%; PR:
69.6%). Cohens kappa analysis showed no statistically significant OP-047
concordance between EORTC/PERCIST based and clinical Monocentric Intraindividual Comparison of 68Ga-RM2 and
criteria/PSA-based ERA and LRA; kappa < 0.2. No statistically 68
Ga-PSMA PET/CT in mCRPC
significant correlation was found between change in SUV and M. Heuschkel, J. Kurth, O. W. Hakenberg, S. Nitsch, S. M.
PSA in ERA and LRA; r < 0.1, for both ERA and LRA. No statistically Schwarzenböck, B. J. Krause;
significant prognostic value of initial SUVmax and SUVmean could Rostock University Medical Center, Rostock, GERMANY.
be shown. Conclusion: Pretherapeutic [68Ga]Ga-PSMA-PET/CT
is an essential prerequisite to detect sufficient expression of the
molecular target. However, a significant correlation between Aim/Introduction: 68Ga-PSMA PET/CT is the standard imaging
[68Ga]Ga-PSMA-PET/CT based and clinical criteria/PSA-based procedure in recurrent Prostate Cancer. Beyond PSMA, different
therapy response assessment during the early and late course agents addressing other targets in Prostate Cancer have been
of PSMA targeted therapy could not be shown. The role of [68Ga] developed, such as the GRPr-antagonist RM2. As well as PSMA
Ga-PSMA-PET/CT in this setting has to be evaluated in further it can equally be labeled with 68Ga and 177Lu in a theranostic
studies. References: None. approach. First evaluations in early stage recurrent Prostate Cancer
showed a high detection rate of 68Ga-RM2 PET/CT and overlap
with PSMA in this population (Minamimoto et al. JNM 2016).
OP-046 The aim of this retrospective study was an intraindividual
Preliminary results on response assessment using PSMA comparison of 68Ga-RM2 and 68Ga-PSMA PET/CT for lesion
molecular imaging in patients with metastatic prostate detection in patients with advanced metastatic castration
cancer undergoing abiraterone resistant Prostate Cancer (mCRPC). Materials and Methods: At
C. Liu, S. Hu, X. Xu, S. Song, Y. Zhang; the University Medical Center of Rostock we scanned 38 mCRPC
Fudan university cancer center, Shanghai, CHINA. patients with 68Ga-PSMA as well as 68Ga-RM2 to identify PSMA
S27 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

or RM2 positivity as prerequisite for radionuclide treatment with uptake on 68Ga-PSMA-11 PET/CT (SUVmax 23.4±24.1) compared
either 177Lu-PSMA or 177Lu-RM2.Visual uptake and semiquantitative to 11C-acetate PET/CT (6.7±3.9; p=0.001). 68Ga-PSMA-11 PET/
parameters (SUVmax and SUVpeak) were compared in 277 CT identified more lesions in 11 patients, less lesions in eight
metastatic reference lesions (5 local, 96 lymph nodes, 146 bone, patients, identical in seven patients, same number of lesions
18 liver, 5 lung, 7 others). Results: In the visual assessment 3/38 but at different regions in one patient. Significantly more lymph
patients showed neither PSMA- nor RM2-positive lesions. The node (n=107 vs n=80, McNemar test p=0.002) and bone lesions
remaining 35 patients showed a PSMA uptake of any grade, of (n=54 vs n=35, McNemar test p=0.0001) were detected on 68Ga-
whom only 3 showed a higher, 17 a much lower and 13 no RM2 PSMA-11 PET/CT. Nine patients (31%) with median PSA of 6.9 at
uptake. 2/38 patients showed complementary RM2-positive time of scan showed upgraded disease status on 68Ga-PSMA-11
/ PSMA-negative and RM2-negative / PSMA-positive lesions. PET/CT, whereas 17 patients (59%) showed no change and 3
SUVmax and SUVpeak were significantly higher for PSMA than patients (10%) had downgraded disease status, compared to
for RM2 subsuming all reference lesions (p < 0.001) as well 11
C-acetate PET/CT. Both scans were negative in two patients.
as in separate analysis of local recurrence (p = 0.043), lymph PSA at time of scan correlated better with 68Ga-PSMA-11 PET/CT
node (p < 0.001), bone (p < 0.001) and liver metastases (p = (spearman ρ >0.69, p<0.001) than 11C-acetate PET/CT (ρ>0.40,
0.022). Conclusion: Most of the included advanced mCRPC p<0.03). TLAmax had the highest correlation (ρ =0.80, p<0.0001)
patients showed a higher number of PSMA- than RM2-positive among the two modalities. Conclusion: 68Ga-PSMA-11 PET/CT
lesions and a higher uptake in 68Ga-PSMA compared to 68Ga- identified significantly more suspicious lymph node and bone
RM2 PET/CT. Nearly no tumor lesion showed a high PSMA and metastases compared to 11C-acetate PET/CT. PSA at time of scan
RM2 uptake at the same time, so there seems to be a different was well correlated with the findings on 68Ga-PSMA-11 PET/CT.
biological behavior of tumor cells. The small amount of patients References: None.
with missing or only faint PSMA but high RM2 uptake maybe
could benefit from the use of 68Ga-RM2 in restaging or in a
theranostic approach including 177Lu-RM2-therapy. References: OP-049
Minamimoto R et al., Pilot Comparison of ⁶⁸Ga-RM2 PET and Impact of 18F-PSMA-1007 Ligand PET/CT in Multimodal
⁶⁸Ga-PSMA-11 PET in Patients with Biochemically Recurrent Imaging of Recurrent Prostate Cancer
Prostate Cancer. J Nucl Med. 2016 Apr;57(4):557-62. L. Dronka1,2, M. Radziņa1,2, M. Tirāne1,2, L. Zemniece1, M. Kalniņa3,2,
L. Roznere3,2, V. Lietuvietis4, A. Freimanis4, E. Vjaters5;
1
Institute of Radiology, Pauls Stradins Clinical University
OP-048 Hospital, Riga, LATVIA, 2Riga Stradins University Radiology
Localizing biochemical recurrence of prostate cancer using Research Laboratory, Riga, LATVIA, 3Riga Stradins University
68
Ga-PSMA-11 PET/CT and 11C-acetate PET/CT Nuclear Medicine Clinic, Riga, LATVIA, 4Center of Urology,
N. Regula, V. Kostaras, S. Johansson, C. Pulido, E. Lindström, M. Riga East University Hospital, Riga, LATVIA, 5Center of Urology,
Lubberink, I. Velikyan, J. Sörensen; Pauls Stradins Clinical University Hospital, Riga, LATVIA.
Uppsala University Hospital, Uppsala, SWEDEN.

Aim/Introduction: Prostate cancer is generally a significant


Aim/Introduction: 68Ga-PSMA-11 PET/CT is increasingly used medical problem worldwide. Accurate localization of recurrent
for staging of prostate cancer (PCa), but no comparative studies prostate cancer at low PSA values is a major challenge.
with 11C-acetate are available. This study aims to compare Radiopharmaceutical 18F-PSMA-1007 has some advantageous
the performance of 68Ga-PSMA-11 PET/CT and 11C-acetate to characteristics in recurrent prostate cancer diagnostics. The
locate the PCa recurrence in patients with biochemical relapse. aim of this study was to evaluate the diagnostic performance
Materials and Methods: Twenty-nine PCa patients, with PSA of the 18F-PSMA-1007 in patients with recurrent PCa, correlating
relapse after primary curative therapy, recruited from 2017- with PSA levels, Gleason score(GS) and MRI Imaging results.
2018 were prospectively evaluated. PET/CT examination using Materials and Methods: This comparative prospective study
11
C-acetate and 68Ga-PSMA-11 was performed on a Discovery included 20 PCa patients with biochemical relapse (mean age
MI scanner (GE Healthcare, Waukesha, WI). All available clinical 64.15 ± 6.2 years) referred for 18F-PSMA PET/CT. Whole-body
data was recorded and evaluated. All highly suspicious lesions PET/CT imaging was performed in all patients 120 min. after
of local recurrence, regional or distal lymph node metastases injection of 376 ± 71,92 MBq 18F-PSMA-1007. Prostatectomy and
and bone metastases were counted and evaluated regarding radiation therapy has been performed in 90% (N=18) and 40%
uptake intensity (SUVmean, SUVmax) and tumor volume (TV) for (N=8) of the patients, respectively. PET/CT scans results were
both tracers. Total TV and total lesion activity (TLAmean: summed compared with GS, PSA level, doubling time and MRI Imaging
SUVmean*TV; TLAmax: summed SUVmax*TV) were calculated. PSA at results. Results: PET/CT confirmed pathological findings in
time of scan, the instrumental clinical finding at time of relapse, 16/20 patients, 80%, respectively. MRI data was available for
was correlated with findings of both scans. Results: Patients 13/20 patients and 76,9 % (N=10) showed local recurrence
with median PSA of 5 ng/mL at time of PET scan (range 0.36- findings also in MRI while regional lymph nodes were detected
240 ng/mL) were included in this study. Median Gleason sum at by PET/CT vs. MRI, 11 vs. 5 cases, respectively (p=0.001). The
time of diagnosis was 7. All pathological lesions showed higher higher SUVmax values were measured in pathological lymph
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S28

nodes (range 2.7-21.3), main reduced detection on MRI was seen findings were identified by 18F-rhPSMA-7 PET. 38.5% (15/39)
when SUVmax did not exceed value 10. The overall mean PSA patients with a PSA < 0.2 ng/mL presented with suspicious
level in study group was 1.62 ng/ml (range 0.38-21.6 ng/ml). The lesions. The detection rates were 63.8% (81/127), 86.5%
mean PSA doubling time - 2,63 months with high correlation to (90/104), 85.3% (87/102) and 93.8% (150/160) at PSA levels
Gleason score (rs=0.747; p=0.001). The mean PSA level in PET of 0.2-< 0.5, 0.5-< 1, 1-< 2 and ≥ 2 ng/mL, respectively. Local
positive finding group was 4,39 ng/ml, in PET negative finding recurrence was present in 42.1% (224) patients. Loco-regional,
group - 0,74 ng/ml. The median GS was 7 (range 5-9), and 75% retroperitoneal and supraphragmatic lymph node metastases
(N=12) had a score above 7 (with prevalence of 3+4), the rate were observed in 41.4% (220), in 16.6% (88) and in 6.8% (36) of
of pathological scans in these patients was 94% (N=11). In all the patients, respectively. Findings indicating bone and visceral
cases, when GS exceed value 7, local and nodal PET/CT finding metastases were presented in 21.1% (112) and 4.0% (21) of
was positive. Overall method sensitivity was for PET/CT and MRI patients. Higher detection rates were present in patients with
for local recurrence 83% vs 100% and for regional lymph nodes an initial Gleason score ≥ 8 compared with scores ≤ 7 (85.0
Se 100% vs. 62% with 37 % of false negative MRI nodes and vs. 77.2%, p<0.0001). Previous EBRT or ADT within 6 months
13% of false negative local recurrence results PET/CT (p=0.001). prior imaging did not influence the detection rate (82.2%
Conclusion: 18F-PSMA-1007 PET/CT is superior to MRI in vs. 77.5%, p=0.185; 84.6% vs. 78.0%, p=0.114), respectively.
detection of recurrent PCa in regional metastatic lymph Conclusion: 18F-rhPSMA-7 PET offer high detection rates in
nodes, with substantial false negative results for local patients with BCR after radical prostatectomy appear. These data
recurrence where MRI should be applied as confirmative indicate superiority to previous published data for 68Ga-PSMA-11.
method. Results are highly dependent on PSA level References: None.
increase and Gleason score, confirming result stability in
the groups with GS>7 and PSA doubling time>2.6 months.
References: None. 109
OP-050
Neuroimaging - Rapid Fire Session: Kinetic
Detection of biochemical recurrance of prostate cancer
Modeling and Computational Approach in
following radical prostatectomy through 18F-rhPSMA-7
Neuroimaging
positron emission tomography
L. Ulbrich1, M. Groenke2, A. Wurzer3, L. Jooss2, T. Maurer4, S. Kropf5, T. Sunday, October 13, 2019, 8:00 - 9:30 Lecture Hall 115
Horn6, H. Wester3, W. Weber2, M. Eiber2;
1
MRI/TUM, Munich, GERMANY, 2Department of nuclear
medicine, Klinikum rechts der Isar, TUM, Munich, GERMANY,
3
Chair of Pharmaceutical Radiopharmacy, TUM, Munich, OP-051
GERMANY, 4Martini-Klinik, UKE, Hamburg, GERMANY, Classification of [18F]Florbetapir brain PET studies in
5
Scintomics GmbH, Fuerstenfeldbruck, GERMANY, 6Department cognitively normal subjects using a Convolutional Neural
of Urology, Klinikum rechts der Isar, TUM, Munich, GERMANY. Network
R. Boellaard, B. de Vries, T. Timmers, J. Ebenau, S. Verfaillie, F.
Heeman, M. Cysouw, W. van der Flier, B. van Berckel, M. Yaqub, S.
Aim/Introduction: The new theranostic PSMA-targeting Golla;
agent 18F-rhPSMA-7 allows fast radiolabeling with 18F and Amsterdam University Medical Centers,
radiometals and shows only minimal renal excretion. Aim VUMC, Amsterdam, NETHERLANDS.
of this retrospective study was to evaluate the effficancy of
18F-rhPSMA-7PET in patients with biochemical recurrance
(BCR) of prostate cancer after radical prostatectomy. Materials Aim/Introduction: [18F]Florbetapir (AV45) positron emission
and Methods: The 18F-rhPSMA-7PET/CT or PET/MRI datasets tomography (PET) studies allow for in vivo assessment of
of patients with non-castrate BCR after radical prastatectomy amyloid deposition. Presence of amyloid deposition is usually
imaged between June 2017 and June 2018 were retrospectively assessed visually, which is highly dependent on observer
reviewed. One experienced nuclear medicine physician training and experience. These visual reads can be difficult
recorded all lesions suspicious for recurrent prostate cancer. in case of low amyloid depositions, e.g. in cognitively normal
Correlations between the detection rates and the patients’ individuals. The aim of this work was to develop, train and
PSA level, their primary Gleason score and previous therapy validate a Convolutional Neural Networks (CNN) able to
(androgen deprivation therapy [ADT] and external beam discriminate between amyloid negative and positive PET scans.
radiation therapy [EBRT]) were evaluated. Results: 532 patients Materials and Methods: 133 AV45-PET images (101 negative
were included. Their median PSA level was 0.97 ng/mL (range, and 32 positive) were acquired at 50-70 min post-injection on a
0.01-372 ng/mL). The median uptake time between injection Philips Gemini TF-64 PET/CT scanner and visually assessed by an
and start of the PET-scan was 76 min (range, 50-220 min). experienced nuclear medicine physician in the context of the
The median injected activity of 18F-rhPSMA-7 was 332 MBq SCIENCe project. AV45-PET SUVR images using cerebellum as
(range: 142-486 MBq).423 (79.5%) patients with pathological reference region were first spatially aligned (MNI). A 2D-CNN was
S29 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

developed consisting of 4 convolution layers, two max-pooling binding in striatum, caudate nucleus and putamen as well as
layers, batch-normalisation and one sigmoid output layer. Next, a putamen/caudate index for both left and right hemisphere.
106 (80%) scans were used to train a 2D-CNN. During training A stratified, 10-times repeated 10-fold cross-validation was
data balancing was achieved by oversampling the amyloid conducted to perform model optimization using mean accuracy
positive scans and data augmentation was achieved by rotating, and F1-score as evaluation measures. Subsequently, the derived
flipping, zooming and translating the images. Overfitting was SVM model was tested on the validation set. I-123-FP-CIT scans
avoided by applying dropouts. To study the impact of spatial and corresponding ratios of the validation set were scored as
resolution on the CNN model performance, PET images were either PD or non-PD by two expert nuclear medicine physicians
additionally smoothed with 5 and 10 mm FWHM Gaussian following European guidelines. Overread from a third expert
kernels. The 2D CNN model performance was tested using the 27 was performed in case of disagreement. Next, their prediction
(20%) unused scans, yielding accuracy, sensitivity and specificity. performance was compared to that of the SVM model. Results:
Results: The model classified amyloid negative and positive The highest mean prediction accuracy and F1-score as found by
scans with 100% accuracy. Applying 5 and 10 mm Gaussian cross-validation were 94.3% and 0.956, respectively. Testing the
smoothing to the 20% test scans resulted in an accuracy of derived SVM model on the validation set, an accuracy of 95.0%,
96.3% and 81.5%, respectively, and a specificity of 94.4% and sensitivity of 96.0% and specificity of 93.3% were obtained.
72.2%, respectively. Retraining the 2D CNN model using the Prediction performance did not differ from visual assessment of
lower but matched resolution images recovered the accuracy PD, obtaining an equivalent accuracy, sensitivity and specificity
to 100% and 92.6% and the specificity to 100% and 77.8% for of 95.0%, 96.0% and 93.3% (p > 0.99), respectively. Conclusion:
the 5 and 10 mm smoothed data, respectively. Conclusion: A ML-based interpretation of I-123-FP-CIT scans results in accurate
2D CNN was developed, trained and tested and showed very discrimination of PD from non-PD identical to standard visual
promising classification performance for amyloid PET scans in assessment, thereby encouraging implementation of this SVM
a SCD patient cohort. However, decreased image quality/image model as diagnostic aid in clinical practice. References: None.
resolution impacts the performance of the 2D-CNN, which can
partly be resolved by retraining the model using the lower and
matched resolution images. References: None. OP-053
Prognostic power of psoas muscles structure and
metabolism in amyotrophic lateral sclerosis
OP-052 A. Miceli1, M. Donegani1, R. Lai2, S. Morbelli1, V. Ceriani1, A. Borra1, S.
Machine-learning based interpretation of I-123 FP-CIT Raffa1, M. Bauckneht3, S. Capitanio3, C. Campi4, G. Sambuceti1, M.
scans allows high-accuracy detection of Parkinson’s Piana1, C. Marini5;
Disease 1
DISSAL University of Genoa, Genoa, ITALY, 2SPIN Institute, CNR,
M. Dotinga1,2, J. D. van Dijk1, B. N. Vendel1, C. H. Slump2, J. A. van Genoa, ITALY, 3IRCCS Policlinico San Martino, Genoa, ITALY,
Dalen1; 4
DIMED, Padova University Hospital, Padua, ITALY, 5CNR Institute
1
Isala, Zwolle, NETHERLANDS, 2University of of Molecular Bioimaging and Physiology (IBFM), Milan, ITALY.
Twente, Enschede, NETHERLANDS.

Aim/Introduction: Amyotrophic lateral sclerosis (ALS) is a


Aim/Introduction: Dopamine transporter SPECT imaging lethal degeneration of upper and lower motor neurons. Median
with I-123-FP-CIT allows for visualisation of dysfunction of the survival, from onset to death, is extremely variable and, to date, no
dopaminergic system, which is characteristic of Parkinson’s reliable prognostic factors have been validated. Recent literature
Disease (PD). Interpretation of scans based on visual assessment suggests a primary role of skeletal muscle and its derived signals
and semi-quantitative analysis imposes limitations as the latter in ALS progression. To verify this hypothesis, in the present study
requires a site-specific reference database that is often not we evaluated whether ALS is associated with alteration in FDG
available. Our aim was to develop a machine learning (ML)-based uptake and total volume of both psoas as a sample of skeletal
approach for interpretation of I-123-FP-CIT scans and determine muscles already used for prognostic stratification in different
its added value in clinical practice. Materials and Methods: We disorders. Materials and Methods: We analyzed 54 ALS patients
retrospectively included a consecutive cohort of 130 patients with spinal onset consecutively submitted to PET/CT imaging.
that underwent I-123-FP-CIT SPECT imaging (Discovery D670, These data were compared with the corresponding findings in
GE Healthcare) and had a clinically confirmed diagnosis. Patients an age-and sex-matched control population. A computational
were labelled as either having PD or a diagnosis other than PD 3D method was used to extract psoas muscle’s volumes from
(non-PD) and divided into a training set (58 PD, 32 non-PD) CT images and to evaluate total muscle volume and attenuation
and validation set (25 PD, 15 non-PD) using stratified random coefficient. In co-registered PET images, FDG accumulation was
sampling. The training set was used to build a linear support defined by average standardized uptake value (a-SUV) and the
vector machine (SVM) classifier to discriminate PD from non-PD heterogeneity of its distribution expressed by SUV standard
using I-123-FP-CIT striatal uptake ratios, age and gender as input deviation (SUV-SD). Psoas volume was normalized for the ideal
features. Ratios were obtained by means of semi-quantitative body weight. Results: Average psoas attenuation coefficient
analysis (Xeleris 4.0, GE Healthcare) and comprised specific was similar in patients and controls (39±9 vs 38±11 Housfield
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S30

units, respectively, ns). By contrast, ALS was associated with a curve was 0.97 (range 0.93-1.00), accuracy 0.91 (0.87-0.97), true
significant reduction in Psoas volume (221±74 mL vs 262±85 mL; positive rate 0.88 (0.80-0.97), and true negative rate 0.93 (0.90-
p<0.01). This difference persisted when normalization for ideal 0.97). Calculated HMR was 2.71&#177;0.70 in normal cases, and
body weight was considered (3.54±1.02 vs 4.12±1.33 mL/Kg; 1.78&#177;0.71 in abnormal cases (t ratio=9, p&lt0.001), and
p<0.05). Similarly, at PET imaging, a-SUV was significantly lower some overlap of ranges was observed for HMR. In additional
in patients than in controls (0.77±0.21 vs 0.90±0.18; p<0.01). patients for the validation, when thresholds of HMR=2.0 and
Finally, heterogeneity of psoas a-SUV, expressed by SUV-SD, probability of 0.5 were used for contingency analysis, 86%
predicted overall survival rate at Kaplan-Meyer analysis (p<0.05) of the data showed complete agreement (Pearson X2=23,
with a predictive power that was confirmed by univariate as p&lt0.0001). Conclusion: Machine learning with appropriately
well as by multivariate Cox analysis (p<0.02). Conclusion: trained neural network successfully classified mIBG images into
ALS is associated with a reduction in volume and FDG uptake normal and abnormal scans. Since anterior image was the only
of psoas muscles. The heterogeneity of glucose metabolism input without predefined ROI on the heart and mediastinum,
within this muscular district is related to disease aggressiveness. machine learning could be a novel approach to classify patients
References: None. with Lewy-body diseases. References: None.

OP-054 OP-055
Abnormal I-123 MIBG scan can be identified by artificial The impact of multi-center PET data harmonization on the
neural network: possible application to Lewy body classification performance of deep learning networks in
diseases neurological imaging
K. Nakajima1, S. Watanabe1, K. Maruyama2, A. Inaki1, H. R. Fahmi, L. Sibille;
Wakabayashi1, K. Okuda3, S. Kinuya1; Siemens Medical Solutions USA, Inc., Knoxville,
1
Kanazawa University, Kanazawa, JAPAN, 2Wolfram Research Inc., TN, UNITED STATES OF AMERICA.
Tokyo, JAPAN, 3Kanazawa Medical University, Kahoku, JAPAN.

Aim/Introduction: Comparison, longitudinal assessment, and


Aim/Introduction: 123I-meta-iodobenzylguanidine (mIBG) has quantification of multi-center PET data are challenging mainly
been used in neurology, and most of the studies have used a due to differences in scanner resolutions. Harmonization methods
heart-to-mediastinal average count ratio (HMR) for diagnosis of reduce inter-center variability and facilitate comparisons of such
Lewy-body diseases. This study aimed to determine abnormal PET data, typically by smoothing the data to match a lower target
mIBG scan with low cardiac uptake, which is typically observed resolution across used scanners. In this work, we investigated
in Lewy-body diseases, without specifying regions of interest the impact of harmonizing ADNI-PET data on the classification
(ROI), using machine learning algorithm. Materials and of FDG and amyloid images into Alzheimer’s (AD) and normal-
Methods: Anterior 123I-mIBG images with normal uptake (n=72, controls (NC) using a convolutional-neural-network (CNN).
148 scans) and low uptake (n=55, 110 scans) were used as the Materials and Methods: Longitudinal FDG and AV45 datasets
training database of machine learning including neural network corresponding to 479 subjects (222-AD, 257-NC) were obtained
(Mathematica, Wolfram Research). Anterior planar mIBG images from the ADNI database for a total of 801 FDG (343-AD, 458-NC)
(20 minutes and 3 hours) were directly input without any and 654 AV45 (168-AD, 486-NC) datasets. For each dataset, both
preparations, and the probability of abnormality was judged non-harmonized (summed image of co-registered dynamic
from 0 (abnormal uptake or absent uptake) to 1 (normal frames in native space) and harmonized (processed image that
uptake). In addition to visual interpretation of normal/abnormal, included smoothing with scanner-specific filter to achieve 8mm
conventional quantitation method of HMR was calculated using FWHM), registered to MNI space, were separately used to train
heart and mediastinum ROI. Accuracy of determining normal two identical CNNs designed to classify AD versus NC subjects.
or abnormal uptake was examined using receiver operating A 10-fold cross-validation scheme was used to evaluate
characteristic (ROC) analysis. The accuracy of the model was also classification performances. For each dataset, seven coronal
tested with additional consecutive patients with Lewy-body slices (7x91x91) sparsely covering the brain were selected as
diseases, amyloidosis, and other diseases (n=25, 50 scans; 15 CNN inputs, and went through four layers, each composed of
scans with HMR&lt2.0). Results: The best classifier among those a 2D convolution and a max-pooling operation. Outputs of
we studied was constructed by an artificial neural network these layers were aggregated and used for class prediction (AD
consisting of 10 layers (256x256-matrix grayscale images for or NC). Each CNN was trained to minimize the cross-entropy
encoder, two classes of normal and abnormal as output). error using Adam optimizer with leaky ReLu activation for each
Probability of abnormality was 0.997&#177;0.013 in patients layer, using a learning rate of 0.05 and dividing by 10 every 50
with abnormal or low uptake, and 0.003&#177;0.001 in patients epochs until convergence. The classification performance using
with normal uptake (t ratio=663, p&lt0.0001). A dataset of 196 harmonized and non-harmonized data from the same subjects
scans were randomly selected for the training, and 60 scans were compared and McNemar test was used to assess the
(abnormal/normal = 30/30) were used as the validation set. This effect of harmonization on classification performance. Results:
processing was repeated 10 times. Average ROC area under the Classification sensitivity, specificity, accuracy, and area-under-
S31 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

the-curve (AUC) were as follows: i) FDG (88.3%, 91.7%, 90.2%, respectively) with the SUVmax of the tumor on the VOI-based
and 0.956) for non-harmonized versus (87.1%, 90.8%, 89.3%, and analysis. Parametric images of Ki were obtained through a
0.955) for harmonized data; and ii) AV45 (76.7%, 93.5%, 89.2%, voxel-based Patlak analysis, and a good correlation was shown
and 0.921) for non-harmonized versus (78.2%, 89.9%, 87.0%, between these Ki parametric images and SUV images in each
and 0.919) for harmonized data, respectively. No significant patient (r2=0.95[median]; 0.62-0.99[range]). Following surgery, a
difference in class assignment consistency was found for FDG glioblastoma was confirmed in 16 patients, while the other two
(McNemar p=0.90) but this difference was significant for AV45 had a diagnosis of metastasis. Conclusion: FCho uptake kinetics
(p=0.027). Conclusion: We demonstrated that deep learning in HGG is best explained by an irreversible or near irreversible
potentially overcomes the variability in multi-center PET FDG 2-tissue-compartment model with blood volume fraction
and amyloid data for image-based classification of AD versus vB. The good linear relationship between the SUV and the K1
NC subjects using CNN. For both tracers accuracy was higher for rate constant suggests a strong influence of the perfusión/
non-harmonized data. We carefully suggest that harmonization BBB transport step on FCho tumor uptake. Clinical routine SUV
of multi-center brain PET data is not required for accurate images may serve as an adequate surrogate for the Ki influx rate
disease classification with deep learning. References: None. parametric images. References: None.

OP-056 OP-057
18
F-Choline PET Kinetic Modeling with Arterial Sampling in Quantification of aromatase binding in the human brain
Patients with High Grade Glioma using [11C]cetrozole PET
S. Rubí1, P. Bibiloni2, M. Valiente1, C. González2, M. Villar1, J. Molina1, M. Jonasson1, P. Nordeman2, H. Wilking1, G. Antoni1,2, I. Sundström
M. Brell1, J. Chinchilla1, M. López1, A. Mir2, M. González2, C. Peña1; Poromaa2, M. Lubberink1,2, E. Comasco2;
1
Hospital Universitari Son Espases / IdiSBa, Palma de 1
Uppsala University Hospital, Uppsala, SWEDEN,
Mallorca, SPAIN, 2Scopia Research Group, University 2
Uppsala University, Uppsala, SWEDEN.
of Balearic Islands, Palma de Mallorca, SPAIN.

Aim/Introduction: Aromatase is an enzyme that converts


Aim/Introduction: 18F-fluoromethylcholine (FCho) has gained androgens to estradiol and estrone in the brain and it is
interest as a PET radiotracer in the assessment of gliomas, but considered to play a role in different personality traits such as
full kinetic analysis has not yet been reported in this setting. aggression and sexual behaviour. The aim of this study was
Following its transport across the blood-brain-barrier (BBB), FCho to evaluate tracer kinetic models, as well as effect of scan
is intracellularly phosphorylated by choline-kinase. Our aim is to duration on outcome parameters, for quantitative analysis of
characterize the uptake kinetics of FCho in high-grade-gliomas the novel aromatase PET ligand [11C]cetrozole. Materials and
(HGG), as a required step for its rational use as a clinical diagnostic Methods: Data from ten subjects, with three 90 min dynamic
tool. Materials and Methods: Eighteen patients with suspected [11C]Cetrozole PET scans each at baseline and after two different
initial diagnosis of HGG underwent a 45min dynamic brain PET challenges, were included in this study. Arterial blood was
scan immediately after a FCho bolus injection, from which a VOI- sampled for measurement of blood radioactivity and metabolite
based tumoral time-activity-curve was extracted. Plasma input analysis, to obtain a plasma-input function, in eight of the scans.
functions were obtained using manual arterial blood sampling VOI-based analysis was performed using single-tissue (1TCM)
from a radial catheter, and parent fractions for metabolite and two-tissue (2TCM) reversible plasma-input compartment
correction were determined by thin-layer-chromatography. models and Logan graphical analysis, in the eight scans with
These data were fitted to several 1- and 2-tissue-compartment plasma data. In addition, simplified reference tissue models
models, the best of which was selected through the Akaike- (SRTM) and reference Logan analysis were performed for all
Information-Criteria (AIC). Parametric images of the main kinetic thirty scans with cerebellum as reference region. The optimal
rate constants were also generated for each patient. We finally reference model was used for evaluation of decreased scan
assessed the correlation between the kinetic parameters and duration of 60 min. Five VOIs were included in the evaluation;
the tumor SUV on static images, both for VOI-based and voxel- thalamus, hypothalamus, putamen and raphae, obtained from a
based approaches. Results: The 2-tissue-compartment model probabilistic VOI template on co-registered T1-MRI images, and
accounting for blood volume fraction (vB) yielded the lowest amygdala, obtained by manually drawing a 70% isocontour VOI
AIC score in all patients and was selected as the best model. on the uptake images. Correlation and agreement between the
The reversible step parameter k4 was either small compared to plasma-input and reference methods, as well as for the full and
the other exchange rate constants (in 12/18 patients) or even decreased scan duration, were assessed by linear regression.
fitted to zero (in 6/18 patients): K1 [median(range): 0.14 (0.06- Results: 2TCM performed better than 1TCM according to Akaike
0.30)ml·cm-3·min-1], k2 [0.11 (0.01-0.28)min-1], k3 [0.16 (0.00-0.46) criteria in all cases except one, but was not able to robustly
min-1 ], k4 [0.02 (0-0.03)min-1], vB [0.08 (0.04-0.15)]. The perfusion/ determine individual parameters. Plasma Logan distribution
BBB transport rate constant K1 and the influx macroparameter value ratio (DVR) agreed well with the 2TCM DVR and was
Ki =K1*k3 /(k2+k3) were clearly the most identifiable parameters used for validation of the reference models. Correlation and
and both showed a positive linear correlation (r2=0.66 and 0.69 agreement between plasma Logan DVR-1 and reference Logan
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S32

DVR-1 was very high (R2=1.00, slope=1.00) and slightly lower significant difference in semiovale VT between AD and healthy
for SRTM binding potential (BPND) values (R2=0.96, slope=0.86). subjects were observed (p>0.05). Preliminary analysis showed
Reference Logan was used for analysing the shortened data sets that the mean TRT for VT and SRTM BPND were -5.7 %±9.7 and
showing a high correlation and agreement for DVR-1 values -3.2%±14.5, respectively, for all subjects across all the different
between the full scan length and the 60 min data sets (R2=0.98, brain regions. Whole brain grey matter TRT for VT and SRTM BPND
slope=0.94). Conclusion: Reference Logan DVR-1 and SRTM were -3.4%±4.3 and -2.6%±6.0 respectively. Conclusion: [11C]
BPND values were highly correlated with plasma Logan DVR-1. UCB-J kinetics can be well described by a plasma input single
Reference Logan showed a higher agreement to the plasma- tissue compartment model and reliable fits can be obtained
input model and was chosen as the optimal reference model with a 60 min scan duration for both plasma input and reference
for VOI-based analysis. Reference Logan generated robust and tissue models, consistent with earlier reports (Finnema et al.,
quantitatively accurate results for a shortened scan, indicating JCBFM 2018). Our preliminary analysis shows TRT performance
that 60 min scan duration is sufficient for [11C]cetrozole PET. for VT and BPND of <10% and <15% (1 SD), respectively, across
References: None. brain regions and indicates adequate repeatability of [11C]UCB-J
PET for application in longitudinal clinical research. References:
None.
OP-058
Kinetics and 28 day test-retest repeatability and OP-059
reproducibility of [11C]UCB-J brain PET imaging ViQuant: an open-source PET/MRI pipeline for non-
H. Tuncel1, R. Boellaard1, E. F. J. De Vries2, P. Kopschina Feltes2, S. C. J. invasive determination of cerebral metabolic rate of
Verfaillie1, E. M. Coomans1, E. E. Wolters1, S. P. Sweeney3, J. M. Ryan3, glucose
M. Ivarsson3, B. A. Lynch3, P. Schober1, P. Scheltens4, R. C. Schuit1, A. L. Shiyam Sundar1, O. Muzik2, L. Rischka1, A. Hahn1, R.
D. Windhorst1, P. P. De Deyn2, B. N. M. van Berckel1, S. S. V. Golla1; Lanzenberger1, M. Hienert1, E. Klebermass1, M. Bauer1, I. Rausch1, E.
1
Amsterdam UMC, Amsterdam, NETHERLANDS, 2UMCG, Pataraia1, T. Traub-Weidinger1, T. Beyer1;
Groningen, NETHERLANDS, 3Rodin Therapeutics, 1
Medical University of Vienna, Vienna, AUSTRIA,
Cambridge, MA, UNITED STATES OF AMERICA, 4Alzheimer 2
Wayne State University School of Medicine,
Center Amsterdam, Amsterdam, NETHERLANDS. Detroit, MI, UNITED STATES OF AMERICA.

Aim/Introduction: [11C]UCB-J is a novel radioligand that binds Aim/Introduction: To introduce ViQuant, a fully-automated
to synaptic vesicle glycoprotein 2A (SV2A) which is present in MATLAB-based processing pipeline for PET/MRI to non-
neuronal presynaptic terminals. [11C]UCB-J Positron emission invasively determine the cerebral metabolic rate of glucose
tomography (PET) imaging enables quantification of brain (CMRGlc) images. Materials and Methods: The ViQuant
synaptic density in individual regions and may be used to study pipeline requires the following inputs: (1) PET list-mode data,
response to therapies in clinical trials. The main objective of this (2) attenuation correction (AC) map, (3) MR angiography (MRA)
study is to determine the 28-day test-retest repeatability (TRT) of images, (4) T1-w MRI and (5) MR navigators. No other user
quantitative [11C]UCB-J brain PET imaging in Alzheimer’s disease interaction is required. The processing pipeline includes three
(AD) patients and healthy controls. Materials and Methods: main components: (i) a component (IC) generating an image-
In this ongoing multicentre study 9 healthy and 5 AD subjects derived input function (IDIF) , (ii) a component that creates
have been included (age 64.2±5.9, 7 male - 7 female). Subjects MRGlc images(QC) and (iii) a report-generating component
underwent two 60 minutes dynamic [11C]UCB-J PET scans (RC). The IC component calculates an IDIF by first defining a
(radiotracer dose of 370±58 MBq) with an interval of 28 days. volume-of-interest through automated segmentation of the
Arterial blood sampling and metabolite analysis were performed MRA. This is followed by MR navigator-based motion correction
to generate a metabolite corrected plasma input function. (MC) and an MR-based partial volume correction (PVC). In
Various compartmental models +/- blood volume correction addition, AC maps are aligned with the PET emission data prior
(VB) have been evaluated and the optimal model(s) has been to reconstruction. Once an accurate IDIF is calculated, it is used
assessed using Akaike criterion. Volumes of distribution (VT) and to generate MRGlc images based on a voxel-wise Patlak analysis.
tracer delivery (K1) have been estimated using both 1T2k_VB Finally, a report is generated with a list of regional MRGlc values.
and 2T4k_VB models. Data were also analyzed using a simplified To validate the pipeline, 10 healthy volunteers underwent [18F]
reference tissue model (SRTM) with centrum semiovale (SO, FDG test-retest PET/MRI examinations in an integrated PET/MR
white matter) (Koole et al., EJNMMI 2019) as reference region, (Siemens Biograph mMR). The imaging protocol consisted of a
providing estimates of BPND. We also examined the effect of 60 min list-mode PET acquisition, with parallel MR acquisitions
plasma input model choice on model preferences, parameter consisting of MRA, MR navigators and T1-w MR. Arterial blood
estimation and TRT. Results: After intravenous injection, [11C] samples (AIF) were collected as reference standard. Pseudo-CT
UCB-J showed rapid kinetics. Based on AIC, both 1T2k_VB images derived from T1-w MR were used for AC. Quantification
and 2T4k_VB described the [11C]UCB-J kinetics equally well. VT accuracy of non-invasive determination of MRGlc was assessed
obtained from both models were similar, suggesting that a against the reference standard of MRGlc values derived using
1T2k_VB model can be used to assess the in vivo kinetics. No arterially sampled blood (AIF) based on the absolute percentage
S33 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

difference (APD) in regional MRGlc values determined in the PIB SUVrcentil. compared to the Klunk reported data (R2:
following 6 brain regions: corpus callosum (CC), brainstem (BS), 0.9988;Y=1.004X-0.06600), validating the PMOD3.9 workflow
cerebellum (CB), thalamus (TH), anterior cingulate cortex (ACC) based on the author criteria (R2 >0.98; slope/intercept between
and the superior frontal cortex (SFC). Results: The APD between 0.98;1.02/-2;2). For the step2 population, an excellent correlation
CMRGlc values obtained from AIF and IDIF were: (5.9 ±3.2%) for was found between the PMOD 3.9 and published SUVrcentil.
CC, (5.9 ±3.3%) for BS, (5.8 ±3.4%) for CB, (5.5 ±3.1%) for ACC, (5.8 for the n=74 pairs of F18-FLUT/C11-PIB (R2: 0.9945/0.9959). The
±3.14%) for TH and (5.9 ±3.3%) for the SFC. The total processing correlation between the F18-FLUT and C11-PIB SUVrcentil. was
time was ~6h on a dedicated high-end PC. Conclusion: We also very similar to those reported (R2:0.95 vs 0.96). The PMOD3.9
have developed a fully-automated open-source processing derived-equation to convert FLUT SUVrcentil. to centiloid
pipeline which allows non-invasive determination of absolute scale values was Centil.val=115.4xFLUTSUVr-113.2 (R2:0.9501)
MRGlc values in a clinical setting. The obtained CMRGlc values compared to Centil.val=116.5xFLUTSUVr-114.7 (R2:0.9617).
were validated to be within 6% of those determined using Conclusion: PNEURO 3.9 workflow seems a robust method
arterial sampling. At present, our processing pipeline is limited to reproduced GAAIN data and derived centiloid scale values
to data obtained from a Siemens PET/MR scanner due to its from Flutemetamol SUVrcentil. values. References: Klunk et al.
dependency on the e7 reconstruction tools. References: None. Alzheimers Dement, 2015. http://www.gaain.org/centiloid-
project
OP-060
How to convert F18-Flutemetamol centiloid SUVr to
Centiloid scale values ? A simple-method using PNEURO 110
3.9 software
R. Lhommel1, B. Hanseeuw1, V. Malotaux2, j. Cerman3, A. Ivanoiu1;
Cardiovascular - Parallel Session: Myocardial
1
Cliniques Universitaires Saint-Luc, UCLouvain, Brussels,
Blood Flow Quantification with SPECT
BELGIUM, 2Institute of Neuro-Science (IONS), UCLouvain,
Brussels, BELGIUM, 3Memory Disorder Clinic, Charles University Sunday, October 13, 2019, 8:00 - 9:30 Lecture Hall 116
and Motol University Hopsital, Praha, CZECH REPUBLIC.

Aim/Introduction: F18-Flutemetamol/Vizamyl PET is a OP-061


validated surrogate biomarker to reveal the amyloid brain The Clinical Value of Quantitative Myocardial Blood
status of patients presenting neurodegenerative disorders, Flow Derived by Dynamic 99mTc-sestamibi MPI Using A
either by visual or semi-quantitative analysis (SUVr). However, Cardiac-dedicated CZT Camera in Patients with Suspected
alternative tracers and quantification methods complicates Coronary Artery Disease
the possibility to compare clinical results between centers. In F. Liu1, S. Wang1,2, Y. Shiau1, Y. Wu1,2,3;
2015, Klunk proposed a methodological approach based on 1
Department of Nuclear Medicine, Far Eastern Memorial
C11-PIB PET to harmonize and reports semi-quantitative results Hospital, New Taipei City, TAIWAN, 2Department of Nuclear
on the same reference level scale (the so-called centiloid scale). Medicine, National Taiwan University Hospital and National
This approach was then endorsed by the Global Alzheimer’s Taiwan University College of Medicine, Taipei City, TAIWAN,
Association Interactive Network (GAAIN) to help centers to 3
Division of Cardiology, Cardiovascular Medical Center, Far
calibrate and report their data whatever the type of Amyloid Eastern Memorial Hospital, New Taipei City, TAIWAN.
PET tracer and quantification method used. We report here
the sequential calibration steps based on this approach to
convert Flutemetamol SUVr to the centiloid scale using the Aim/Introduction: SPECT myocardial perfusion imaging (MPI)
PNEURO3.9 software. Materials and Methods: The PNEURO is a clinical mainstay with static imaging protocol and semi-
3.9 (PMOD,Zurich) maximum_probability_workflow based on quantitatively assessed for perfusion abnormalities. Dynamic
3DT1 MRI segmentation was used to retreat C11-PIB/FLUT PET cardiac SPECT is a new quantitative index of stenosis severity and
scans and compute SUVrcentil. values (cortical centil.vois/whole ischemic burden by the assessment of myocardial flow reserve
cerebellum-reference). Two historical patients population (MFR) and myocardial blood flow (MBF). Our aim is to evaluate
were downloaded from the GAAIN website to qualify the the incremental value of dynamic SPECT in the detectability
PNEURO3.9 workflow. Step1:PMOD3.9 workflow validation for of multi-vessel coronary artery disease (CAD). Materials and
C11-PIB PET: n=79 (34 YHC-45 AD;C11-PIB/MRI; GAAIN, Klunk). Methods: Consecutive patients with suspected CAD, who
Step2:FLUT versus C11-PIB SUVrcentil. comparison and convertion underwent dynamic ECG-gated dipyridamole MPI using a
of SUVrcentil. to centiloid scale values; n=74 (24 YHC&50 AD; cardiac-dedicated CZT camera (D-SPECT) and invasive/or
F18-Flutemetamol/C11-PIB/MRI; GAAIN, GE Healthcare). computed tomography coronary angiography within 6 months
Statistical analysis and data plot fitting were computed using were retrospectively reviewed. Subjects with history of coronary
PRISM 8.0. Results: Step1 population analysis performed by interventions in the past 90 days were excluded. Dynamic
PNEURO3.9 demonstrated an excellent correlation between imaging data were analyzed using commercial Corridor 4DM
the PMOD3.9 Centiloid scale values derived from the C11- software package, and static perfusion and volumetric data
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S34

were analyzed utilizing QPS/QGS software, which provided the Carimas 2.4 software (Turku PET Centre, Turku, Finland).
automatically plots according to the 17-segment model, and Results: Rest and stress SPECT MBF values were similar with or
subsequently divided into three main vascular territories (LAD, without spline fitting (rest: 1.178 ± 0.385 vs 1.120 ± 0.457; and
LCX, RCA). Significant stenosis was defined as ≥ 50% luminal stress: 3.209 ± 0.880 vs 3.151 ± 0.758 for DY and SF respectively).
stenosis. The performance of static perfusion data, including At stress, both DY and SF MBF were increased compared to
summed stress, rest and difference scores (SSS, SRS and SDS), PET MBF (2.882 ± 0.967, p<0.05 vs SF, p<0.01 vs. DY). At rest, DY
and dynamic perfusion data, namely post-stress and resting but not SF MBF was significantly increased vs. PET MBF (1.027
MBF (MBFs, MBFr) and MFR were compared at the vessel-level. ± 0.237, p<0.05 vs DY). Correlations to PET MBF were similar
The statistical significance was p<0.05. Results: A total of 50 using DY (r= 0.90, p<0.0001) or SF (r= 0.88, p<0.0001) but the
patients with 139 stenotic vessels were included, 29 with multi- difference between SPECT and PET was optimized using SF
vessel disease (58%), and 11 patients (22%) with myocardial (0.18±0.58, p<0.05) compared to DY (0.24±0.51, p<0.001). The
infarction (MI). Both global and regional MBFs showed a differences observed in terms of MBF yielded no difference
significant correlation with global and regional SSS (r=-0.67 on the assessment of MFR (DY: 2.93 ±1.13, SF: 3.15±1.15, PET:
and -0.38~-0.68, p≤0.001, respectively). Globally increased SSS, 2.83±0.81, all p-values= ns). Conclusion: Spline fitting had only
SDS and impaired MBFs, MFR were significantly associated with a limited impact on the quantitative assessment of myocardial
significant CAD. In vessel-based analysis, SSS and SDS failed to blow flow and flow reserve using dynamic CZT SPECT.
detect LAD, LCX diseases, except SSS in RCA disease. Post-stress
MBF successfully detected LAD, LCX and RCA diseases, while References: [1] Agostini D et al. Eur J Nucl Med Mol Imaging.
MFR could only detect LAD disease. Using receiver operating 2018;45(7):1079-1090.
characteristic (ROC) curve analyses, the best cutoff value of
global MBFs to predict CAD was 2.4ml/g/min (area under the
curve: 0.569, p=0.005), but the best cut-off value of MFR was OP-063
not found. Conclusion: We validated a clinically available Evaluation of global and regional coronary flow reserve by
method for MFR quantification by dynamic 99mTc-perfusion routine perfusion SPECT, without first pass study
SPECT utilizing a CZT camera, which improves the detectability L. Philippe, C. Prunier-Aesch, Y. El Yaagoubi;
of multi-vessel CAD, and post-stress MBF is a better parameter Medecine Nucleaire Tourangelle, Chambray-les-Tours, FRANCE.
than MFR and static data. References: None.

Aim/Introduction: Multi-vessel disease is frequently a cause of


OP-062 false negative myocardial perfusion SPECT. The global reduction
Impact of spline fitting of dynamic CZT SPECT data on the of perfusion is difficult to see on the images. Scintigraphic
assessment of myocardial blow flow and flow reserve measurement of Coronary Flow Reserve (CFR), usually performed
N. Coudrais1, D. Agostini1,2, C. Nganoa1, M. Bouthiba3, P. Tager1, V. by dynamic SPECT or dynamic PET can decrease false negative
Roule1, N. Roth4, F. Beygui1,2, A. Manrique1,2,5; study. We developed an original method to evaluate the CFR,
1
CHU Côte de Nacre, Caen, FRANCE, 2Normandy University, Ea using routine SPECT 99mTc-tetrofosmin (1 day Stress-Rest
4650, FRANCE, 3EA 4650, Caen, FRANCE, 4Spectrum Dynamics protocol), without 1st pass acquisition. Materials and Methods:
Medical Ltd, Caesarea, ISRAEL, 5Cyceron PET Center, Caen, FRANCE. Myocardial uptake being related to myocardial perfusion, the
counts ratio stress/rest represents CFR. Successively, 5 corrective
factors are applied (completely automatic) at stress and rest , on
Aim/Introduction: Spline fitting allows to interpolate a myocardial short axis slices (Software Aladdin language - Xeleris
sequence of temporal data, generating temporal and spatial GE) 1. Subtraction of the stress residual activity in the rest images
smoothing of dynamic perfusion studies. We aimed to assess 2. Normalization of the injected tracer activity 3. Normalization
the impact of spline fitting on the assessment of myocardial of the time duration acquisition 4. Consideration of the flow
blood flow and flow reserve using dynamic CZT perfusion depending tetrofosmin myocardial extraction. 5. Normalization
SPECT. Materials and Methods: We retrospectively analyzed of the central ventricular pixel counts The 5 cumulative
CZT dynamic myocardial perfusion SPECT previously acquired applications produce global Coronary Reserve Index (CRI), and
in 28 consecutive patients in the framework of the Waterday [1] regional CRI (rCRI) corresponding to the 3 coronary territories
study (clinicaltrials.gov: NTC 02278497) using a DSPECT camera (LAD, LCx and RCA). These processings have been applied to
(Spectrum Dynamics, Caesarea, Israel). The CZT SPECT data were 32 patients addressed to our institution for routine myocardial
processed without (DY) and with (SF) applying a spline fitting stress (exercise, dipyridamole, or regadenoson) and rest SPECT;
function using a commercially available software (4DM, Invia, they underwent also Invasive Coronary Angiography (ICA).
Ann Arbor, MI). All reconstructed frames were automatically Results: The CRI evaluations were compared to ICA considered
segmented to extract the vascular input function and the as gold standard. ICA indicates 7 normal patients and 25
myocardial uptake curve, and a one-compartment model was Coronary Artery Disease (CAD) patients. CRI mean is 3.65 ± 2.10
used to estimate global uptake values. SPECT myocardial blood for normal patients, and 1.57 ± 0.56 for CAD patients. We found
flow (MBF) derived using Leppo correction and flow reserve 14 CAD patients with normal perfusion SPECT and low CRI. The
(MFR) were compared to 15O-water PET data quantified using optimal cut-off CRI to separate normal and CAD patients is 2.20.
S35 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

Considering this CRI value, we obtain: Sensitivity 92%, Specificity SSS (r=0.37; p=0.02), SDS(r=0.39; p=0.02). Based on univariate
86%, Positive Predictive Value 96%, and Negative Predictive logistic regression the following indexes allow to predict MVCAD
Value 75%. Among the 25 CAD patients, 8 present multi-vessel significantly: stress MBF per 0.1 unit increase (OR 0.75; CI 0.62-
epicardial disease with abnormal global CRI. Analysis of the 3 0.91; p=0.005); CFR (OR 0.12; CI 0.04-0.38; p=0.0003); FD per 0.1
regional CRI, shows that the difference between the maximal unit increase (OR 0.72; CI 0.57-0.91; p=0.0016 and SSS (OR 1.21;
and the minimal rCRI, normalized with the global CRI, is smaller CI 1.06-1.39; p=0.004); SDS (OR 1.19; CI 1.01-1.14; p=0.03). Based
for the multi-vessel disease (0.36 ± 0.45) than for the 17 others on the ROC analysis it was revealed that the areas under the
CAD patients (0.11 ± 0.08). A diffuse decrease of rCRI may ROC curves were higher for stress MBF (0.81;CI 0,71-0,9) CFR (0.8;
indicate multi-vessel epicardial disease and/or microvascular CI 0,68-0,88) and FD (0.78; CI 0,67-0,87) than for SSS (0.68; CI 0,55-
disease. Conclusion: Evaluation of global CRI and rCRI by routine 0,79) and SDS (0.64; CI 0,51-0,75). Conclusion: Our results found
99mTc-tetrofosmin SPECT is feasible. Using this evaluation after out that dynamic SPECT indexes reflect the severity of coronary
the routine SPECT reconstruction,with no additional time (fully artery lesion better than standard MPI. Absolute myocardial
automatic process) improves efficiency of perfusion SPECT blood flow indexes derived by CZT could be useful in clinical
analysis. Sensitivity and Positive Predictive Value are excellent. practice in the management of patients with multivessel CAD.
References: None. References: None.

OP-064 OP-065
Absolute myocardial blood flow and coronary flow Low-dose Dynamic Myocardial Perfusion Imaging by CZT-
reserve derived by dynamic single photon emission SPECT in the Identification of Obstructive Coronary Artery
computed tomography: correlation with invasive coronary Disease
angiography results in patients with multivessel coronary T. Mannarino1, W. Acampa1, A. Genova1, P. Buongiorno1, G.
artery disease De Simini1, A. D’Antonio1, L. Piscopo1, M. De Risi1, F. Volpe1, E.
K. Zavadovskiy, A. Mochula, A. Baev, A. Maltseva, S. Andreev; Zampella1, C. Nappi1, R. Assante1, V. Gaudieri1, M. Petretta2, A.
Cardiology Research Institute, Tomsk National Cuocolo1;
Research Medical Centre, Russian Academy of 1
Department of Advanced Biomedical Sciences, University
Sciences, Tomsk, RUSSIAN FEDERATION. Federico II, Naples, ITALY, 2Department of Translational
Medical Sciences, University Federico II, Naples, ITALY.

Aim/Introduction: To assess relative myocardial perfusion,


absolute myocardial blood flow (MBF) and coronary flow Aim/Introduction: Dynamic CZT-SPECT may be used to
(CFR) reserve by dynamic single photon emission computed measure myocardial blood flow (MBF) and myocardial perfusion
tomography on cadmium-zinc-telluride gamma camera in reserve (MPR). The aim of our study was to evaluate MBF
patients with multivessel coronary artery disease (MVCAD). and MPR using a low-dose CZT-SPECT protocol in patients
Materials and Methods: 38 patients with coronary artery with suspected or known coronary artery disease (CAD) and
disease (mean age 60±9,5 years; 52 men;) were enrolled. to investigate the accuracy of dynamic data in predicting
According to quantitative invasive coronary angiography results obstructive CAD. Materials and Methods: We analyzed 150
all the patients were divided into two groups: 1) multivessel patients (102 men, mean age 65±8 years) with suspected or
CAD: 12 patients with the two-vessel disease and 24 patients known CAD. All patients underwent dynamic CZT-SPECT after
with three-vessel disease; 2) non-multivessel CAD: consisted of the injection of 185 MBq and 555 MBq of 99mTc-sestamibi for
22 patients with nonobstructive disease and 12 patients with rest and stress imaging, respectively. Standard rest and stress
one vessel disease. Within one week all patients underwent the acquisition were performed at the end of each dynamic scan.
assessment of myocardial perfusion (SSS, SRS, SDS), stress and Summed stress score (SSS) >3 was considered as abnormal.
rest MBF (ml/min/g), CFR and flow difference (FD) by dynamic Obstructive CAD was defined as ≥75% stenosis at coronary
99mTc-Sestamibi CZT SPECT. Results: The mean SYNTAX score angiography. Results: In the overall population, global MPR was
was 16.5±11. The values of summed stress score were significantly significantly lower (P<0.05) in patients with abnormal (2.4±0.7)
(p< 0.01) different in patients with and without multivessel CAD: as compared to those with normal (2.7±0.8) myocardial
7.5 (IQR 5;10) and 4 (IQR 4;8), respectively. Summed rest score and perfusion imaging. Significant correlations between MPR and
difference score did not differ significantly in these two groups. SSS (r=-0.213, P<0.01) and between MPR and total perfusion
The values of global stress MBF, CFR and FD were significantly defect (TPD) (r=-0.217, P<0.01) were found. In a subgroup of
(p<0.01) lower in patients with multivessel disease than in non 60 patients with available coronary angiographic data, MPR
multivessel CAD group: 0.43 ml/g/min (IQR 0.29; 0.52) versus (2.11±0.56 vs. 2.72±0.65, P=0.001) and stress MBF (2.71±0.85
0.67 ml/g/min (IQR 0.53; 0.81); 1.38 (IQR 1.13; 1.64) versus 2.09 vs. 3.43±0.95 ml/min/g, P=0.009) were significantly lower
(IQR 1.59; 2.7); 0.1 ml/g/min (IQR 0.04; 0.19) versus 0.32 ml/g/min in patients with (n=17) compared to those without (n=43)
(IQR 0.19; 0.53), respectively. The correlations between SYNTAX obstructive CAD. At univariable logistic regression analysis,
and stress MBF (r=-0.6; p=0.00006), CFR (r=-0.58; p=0.0001), FD male gender, SSS, TPD, stress MBF, and MPR resulted significant
(r=-0.6; p=0.00009), were stronger than between SYNTAX and predictors of obstructive CAD. At multivariable regression
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S36

analysis only male gender (P<0.01) and MPR (P<0.005) were patients (50.0%) showed abnormal results on MBFQ, which was
significant predictors of obstructive CAD. Accordingly, in the significantly higher than the abnormal rate of MFR (58/126,
180 individual vessels analyzed, regional stress MBF (2.79±0.94 46.0%, p=0.000) and MPI (30/126, 23.8%, p-0.012). In patients
vs. 3.35±1.07 ml/min/g, P=0.015) and regional MPR (2.18±0.81 with multi-vessel intermediate disease, MBFQ also showed
vs. 2.74±0.81, P=0.002) were significantly lower in vessels with more abnormal results (40/71, 56.3%) than MFR (28/71, 39.4%,
(n=25) compared to those without (n=155) obstructive CAD. p=0.000) and MPI (33.3%, 14/71, p=0.013), suggesting more
Conclusion: MPR assessed by low-dose dynamic CZT-SPECT myocardial ischemia was found by MBFQ. In patients with one-
showed good correlation with myocardial perfusion imaging vessel disease, there was no significant difference in diagnosing
findings in patients with suspected or known CAD and it could myocardial ischemia of three methods. Conclusion: SPECT
be useful in predicting obstructive CAD. References: None. MBFQ detected more myocardial ischemia than MFR alone
and traditional MPI for patients with intermediate disease,
especially for patients with multi-vessel intermediate disease.
OP-066 References: [1] JACC Cardiovasc Imaging. 2012 Apr;5(4):430-40.
Comparison of SPECT Myocardial Blood Flow
Quantification and MPI for Detection of Myocardial
Ischemia in Patients with Intermediate Coronary Stenosis OP-067
Disease Diagnostic performance of myocardial perfusion imaging
L. Wang1, R. Ma1, M. Wang1, B. Hsu2, W. Fang1; with conventional and CZT single photon emission
1
Chinese Academy of Medical Sciences & Fuwai Hospital, computed tomography in detecting coronary artery
Beijing, CHINA, 2University of Missouri-Columbia, disease: a meta-analysis
Columbia, MO, UNITED STATES OF AMERICA. R. Green, V. Cantoni, T. Mannarino, A. Genova, R. Assante, V.
Gaudieri, C. Nappi, E. Zampella, P. Buongiorno, M. Petretta, W.
Acampa, A. Cuocolo;
Aim/Introduction: Evaluation of myocardial ischemia is crucial University Federico II, Naples, ITALY.
for patients with intermediate coronary stenosis disease.
Quantification myocardial blood flow (MBFQ) using technetium
labeled myocardial perfusion tracers and dedicated SPECT Aim/Introduction: Stress myocardial perfusion imaging
cameras has become clinically feasible. Comparison of SPECT (MPI) with SPECT accounts for the majority of tests currently
MBFQ, myocardial flow reserve (MFR) and myocardial perfusion performed for ischemia detection in patients with known or
imaging (MPI) has not been studied. Materials and Methods: suspected coronary artery disease (CAD). The novel gamma
Patients with suspected or known coronary artery disease who cameras with semiconductor cadmium-zinc-telluride (CZT)
were scheduled for SPECT MPI were consented to receive an detectors allowed an improvement in image accuracy and
adjunct dynamic SPECT (DySPECT) scan for MBFQ under the acquisition time. We performed a meta-analysis to compare the
same rest and stress test. Subjects with intermediate disease diagnostic performance of conventional SPECT (C-SPECT) and
defined as a coronary lesion with a visually estimated percentage CZT-SPECT systems in detecting angiographically proven CAD.
diameter stenosis ranging from between 50 and 80% were Materials and Methods: Studies published between January
included. Image processing of MBFQ employed full physical 2000 and February 2018 were identified by PubMed and Web
corrections for reconstruction of DySPECT images, one-tissue of Science databases search. We included studies assessing
compartment for kinetic modeling, and corrections for 99mTc- C-SPECT or CZT-SPECT as a diagnostic test to evaluate patients
Sestamibi extraction and rest rate-pressure-product to quantify for the presence of CAD, defined as at least 50% diameter
stress MBF, rest MBF and MFR using a dedicated SPECT MBFQ stenosis on invasive coronary angiography. A study was eligible
software. Flow values in myocardium were further converted regardless of whether patients were referred for suspected or
to corresponded flow statuses defined by the Gould’s flow known CAD. For each eligible study, data were extracted to
diagram[1] with slight modification. The patient-based positive estimate sensitivity, specificity, and diagnostic odds ratio (OR)
diagnosis of MBFQ met one of two independent criteria as 1) with 95% confidence interval (CI). The bivariate random-effects
≥3.01% extent of myocardium within ischemia-steal combined model was used to calculate the pooled summary estimates
flow status or 2) ≥20.3% extent of myocardium within moderate for sensitivities and specificities for both cameras. Results: We
abnormal and ischemia-steal combined status. MFR alone as identified 40 eligible articles (25 C-SPECT and 15 CZT-SPECT
criteria defined ischemia when MFR <1.74. Interpretation of studies) including 7334 patients (4997 in C-SPECT and 2337
MPI images were conducted by three experienced readers in in CZT-SPECT studies). The pooled sensitivity and specificity
a consented reading session. MPI was considered abnormal were 85% (95% CI 79-89) and 66% (95% CI 56-74) for C-SPECT
when SSS ≥4 or SDS ≥2 or index of transient ischemia dilation and 89% (95% CI 86-91) and 69% (95% CI 61-75) for CZT-SPECT
≥1.19. The patient-based diagnostic performance SPECT imaging studies. The area under the curve was slightly higher for
MBFQ, MFR and MPI for detecting myocardial ischemia were CZT-SPECT (0.89, 95% CI 0.86-0.92), compared to C-SPECT (0.83,
compared. Results: A total of 126 patients were included. 95% CI 0.80-0.86) (P=0.03); accordingly, the summary diagnostic
Among this population, 71 patients presented with multi- OR was 17 (95% CI 13-22) for CZT-SPECT and 11 (95% CI 7-15)
vessel disease and 55 patients showed one-vessel disease. 68 for C-SPECT (P=0.04). The accuracy of the two tests slightly
S37 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

differs between C-SPECT and CZT-SPECT (chi-square 11.28, 301


P=0.04). However, we were unable to demonstrate if the subtle
difference in global accuracy was due to sensitivity (chi-square
CME 2 - Oncology & Theranostics Committee:
2.13, P=0.14) or specificity (chi-square 0.21, P=0.65), also when
NET - PRRT and More
separate variances for each test were allowed in the models. At
meta-regression analysis, no significant association between Sunday, October 13, 2019, 11:30 - 13:00 Auditorium
both sensitivity and specificity and demographical and clinical
variables considered was found for C-SPECT and CZT-SPECT
studies. Conclusion: C-SPECT and CZT-SPECT have good
diagnostic performance in detecting angiographically proven OP-071
CAD, with a slightly higher accuracy for CZT-SPECT. This result PET/CT Imaging of PPGL in the Era of Genomic Disease
supports the use of the novel gamma cameras in clinical routine Characterization (EANM/SNMMI 2019 Guidelines)
practices also considering the improvements in acquisition time D. Taïeb;
and radiation exposure reduction. References: None. Department of Nuclear Medicine, La Timone University Hospital,
CERIMED, Aix-Marseille University, Marseille, FRANCE.

201/204
Plenary 1: Radiomics and Artificial Intelligence OP-072
Long-Term Outcome of PRRT and Predictors of Outcome
(incl. Marie Curie Lecture) M. Gabriel;
Allgemeines Krankenhaus Linz, Institut für
Sunday, October 13, 2019, 10:00 - 11:15 Auditorium Nuklearmedizin und Endokrinologie, Linz, AUSTRIA.
OP-073a
PRRT - Individualized Dosimetry vs. Fixed Dose Scheme
A. Haug;
OP-068 University Clinic of Nuclear Medicine, Medical
Radiomics - Predictive and Prognostic Modelling using University of Vienna, Vienna, AUSTRIA.
Multimodality Imaging
D. Visvikis;
INSERM UMR1101, LaTIM, CHRU Morvan, Bat 1, et 1, Brest, FRANCE. OP-073b
PRRT Treatment Sequencing and Combinations
R. Hicks;
OP-069 Department of Nuclear Medicine and PET, Peter
Artificial Intelligence in Nuclear Oncology MacCallum Cancer Institute, Melbourne, AUSTRALIA.
R. Hustinx;
Centre Hospitalier Universitaire, Service de
Médecine Nucléaire, Liège, BELGIUM. 302
Joint Symposium 3 - Bone & Joint + Paediatrics
OP-070
Committee / EPOS: Role of Bone SPECT/CT in
Marie Curie Lecture: Artificial Intelligence in Brain Imaging
the Paediatric Population
M. Forsting;
UK Essen, Institut für Diagnostische und Interventionelle Sunday, October 13, 2019, 11:30 - 13:00 Lecture Hall 311
Radiologie und Neuroradiologie, Essen, GERMANY.

OP-074
Bone Scan with SPECT/CT in the Assessment of Bone
Viability
I. Roca;
Vall d’Hebron University Hospital, Pediatric Nuclear Medicine
Unit, Nuclear Medicine Department, Barcelona, SPAIN.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S38

OP-075 OP-081
SPECT/CT of the Jaw in Condylar Hyperplasia Artificial Intelligence and Deep Learning
K. Strobel; P. Slomka;
Luzerner Kantonsspital (LUKS), Department of Radiology University of California Los Angeles, Department
and Nuclear Medicine, Lucerne, SWITZERLAND. of Imaging Cedars-Sinai Medical Center, Los
Angeles, CA, UNITED STATES OF AMERICA.

OP-076
Complex Adolescent Foot Pain - Clinical Scenarios and 304
Management
D. Eastwood;
CTE 2 - Interactive - Technologist + Radiation
Great Ormond Street Hospital for Children NHS Foundation Trust,
Protection Committee: Risk and Incidents
Department of Orthopaedics, London, UNITED KINGDOM.
Sunday, October 13, 2019, 11:30 - 13:00 Lecture Hall 117

OP-077
SPECT/CT in Complex Adolescent Foot Pain - Initial
Experience OP-082a
L. Biassoni; Risks and Incidents in Nuclear Medicine: A Medical Physics
Great Ormond Street Hospital for Children NHS Foundation Perspective
Trust, Department of Radiology, London, UNITED KINGDOM. K. Bacher;
Ghent University, Department of Medical Physics, Ghent, BELGIUM.
OP-082b
303 Discussion
Joint Symposium 4: Cardiovascular Committee / OP-083a
ASNC: New Development in Nuclear Cardiology Potential Risk and Incidents in HotLab
- Ready for Prime Time? A. Socan;
University Medical Centre, Department of
Sunday, October 13, 2019, 11:30 - 13:00 Lecture Hall 312 Nuclear Medicine, Ljubljana, SLOVENIA.

OP-083b
Discussion
OP-078
Whole-Body CZT Camera for Cardiac Imaging OP-084a
D. Agostini; Management of Risks and Incidents in Nuclear Medicine
Department of Nuclear Medicine, Caen G. Testanera;
University Hospital, Caen, FRANCE. St Bartholomew’s Hospital, Department of Nuclear
Medicine, London, UNITED KINGDOM.

OP-079 OP-084b
Quantification of Myocardial Blood Flow with SPECT Discussion
R. Nkoulou;
Department of Nuclear Medicine, University
Hospital Geneva, Geneva, SWITZERLAND. 305
M2M - Parallel Session: Radionuclide Production
OP-080
Measurement of Left Ventricular Dyssynchrony Sunday, October 13, 2019, 11:30 - 12:45 Lecture Hall 111
P. Soman;
University of Pittsburgh Medical Center, Division of
Cardiology and The Heart and Vascular Institute,
Pittsburgh, UNITED STATES OF AMERICA. OP-085
Cyclotron Production of 68Ga Using Enriched 68Zn Foils
J. Siikanen1, E. Jussing2,3, S. Milton2, C. Steiger2, J. Ulin3, T. Tran2,3, E.
Samén2,3;
1
Karolinska University Hospital, Department of Medical
S39 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

Radiation Physics and Nuclear Medicine, Stockholm, Aim/Introduction: With increasing clinical demand for
SWEDEN, 2Karolinska University Hospital, Department of gallium-68, the commercial 68Ge/68Ga generators fail to supply
Radiopharmacy, Stockholm, SWEDEN, 3Karolinska Institute, sufficient amounts of this short-lived isotope. In this study
Department of Clinical Neuroscience, Stockholm, SWEDEN. we develop and evaluate an automated method for multi-
Curie production of gallium-68 using solid targetry. Materials
and Methods: Gallium-68 was produced by irradiation of an
Aim/Introduction: Increased use of biomarkers for diagnostics enriched zinc-68 solid target (on silver backing) in an ARTMS
of neuroendocrine tumors and prostate cancer has amplified the QIS on a GE PETtrace cyclotron. Beam currents up to 80 µA were
clinical demand for 68Ga. For sites with access to a cyclotron, the applied for up to 120 min with a proton energy of 13 MeV. After
high price and limited availability/activity output of 68Ge/68Ga end-of-bombardment (EOB), the targets were automatically
generators are strong motivators for production of 68Ga (T1/2=68 transferred to a dissolution cell (ARTMS) in connection to a GE
min) via the 68Zn(p,n)68Ga-reaction. To expand production FASTlab 2 synthesizer unit. The targets were dissolved in hot,
capacity over generators and also over liquid cyclotron solution concentrated HCl followed by radiochemical separation of
targets the aim of this work is to optimize and automate solid gallium-68 from the target material on the FASTlab 2. Results:
target 68Ga production using enriched 68Zn-foils. Materials Irradiation was performed using up to 80 µA for 120 min,
and Methods: Enriched (98.80 % 68Zn, 0.46 % 64Zn, 0.43 % 66Zn, producing up to 194 GBq (5.24 Ci) of gallium-68 at the end of
0.29 % 67Zn, 0.02 % 70Zn) zinc foils (CMR, 15.5 mm diameter, separation from an expected >370 GBq (>10 Ci) gallium-68 at
0.10 mm thick) were pneumatically transferred to a solid target EOB. The fully automated dissolution/separation was performed
system (Comecer EDS/PTS) and irradiated with 25 µA protons in 35 min. Multiple productions were analyzed according to
(PETtrace, GE Healthcare). Proton energy was degraded to a Ph. Eur. Monograph draft1 and found to comply with all tests
nominal 12.6 MeV to minimize co-production of long lived 67Ga. completed to date. Analysis of metal impurities using ICP-OES is
Separation of 68Ga from zinc was programmed and automated in progress. Importantly, the radionuclidic purity (RNP) was high
with a separation module (I.e Comecer, Taddeo PRF). In these and allowed for a shelf-life of up to 7 h based on RNP alone.
initial trials foils were dissolved with 12 M HCl. The solution was In every instance the radiochemical purity was above 99.9%.
diluted to 6 M HCl and passed over a UTEVA resin (Triskem, Radiolabeling of DOTATATE and PSMA-HBED-11 were performed
100 mg) to trap gallium and to remove zinc and other metals. in high yields (>95%) and in clinically acceptable molar specific
Gallium was then eluted with 1.2 ml water. Radionuclidic purity radioactivity (≥ 24 MBq/nmol, non-optimized). This indicates a
(RNP) was determined with an energy and efficiency calibrated low amount of metallic impurities in the produced gallium-68,
HPGe-detector. Results: Irradiation of 136 min (i.e two half- i.e., similar to what is observed for the generator-produced
lives) yielded up to 48 GBq of 68Ga (saturation yield = 2.6 GBq/ isotope. Conclusion: We have developed and evaluated an
µA) in the foil at end of bombardment (EOB). Transfer (5 min) automated method for production of up to isolated 194 GBq
and gallium isolation (16 min) requires 21 min after EOB. Decay gallium-68 chloride in high radionuclidic and radiochemical
corrected trapping/elution on the UTEVA resin itself exceeds purity - expected to be suitable for compounding and
93 %. Up to 29 GBq of 68Ga was eluted with 1.2 ml of water at subsequent clinical use. References: 1 Gallium (68Ga) Chloride
end of separation. RNP in the eluate was 99.98 % at EOB. Other (Accelerator-Produced) Solution for Radiolabelling, Ph. Eur.
gamma lines corresponded to 66Ga (0.010 %) and 67Ga (0.015 Monograph draft 3109
%). This equates to an RNP above 98% out to 7.7 hrs post-EOB.
Conclusion: This setup produces approximately 20 times more
activity than eluates from new generators (1.5 GBq). Solid target OP-087
production using foils do not require any plating techniques. By Characterization of TrisKem Actinide resin for separation
using a 0.25 mm thick 68Zn foil, we estimate that production of of 51,52gMn from target material
approximately 140 GBq may be possible. Ongoing ICP-MS and K. Barrett1, E. Aluicio- Sarduy1, S. Happel2, C. Kutyreff1, A. Olson1, K.
titration studies are underway to assess alignment with current Seely1, P. Ellison1, T. Barnhart1, R. Nickles1, J. Engle1;
generator formulations. References: None. 1
University of Wisconsin- Madison, Madison, WI, UNITED
STATES OF AMERICA, 2TrisKem International, Bruz, FRANCE.

OP-086
Multi-Curie Production of Gallium-68 on a Biomedical Aim/Introduction: Radio-manganese shows promise for a
Cyclotron variety of nuclear medical applications including radiolabeling
J. Kumlin1, J. H. Dam2,3, C. J. Chua1, S. Borjian1, A. Kassaian1, B. antibodies, monitoring pancreatic beta cell viability [1], and as
Hook1, S. Zeisler1, P. Schaffer1, H. Thisgaard2,3; dual PET/MR imaging agents [2]. Cyclotron-produced 51Mn or
1
ARTMS, Vancouver, BC, CANADA, 2Department of 52g
Mn must be chemically separated from target materials to
Nuclear Medicine, Odense University Hospital, Odense, render the radiotracers suitable for in vivo use. This process has
DENMARK, 3Department of Clinical Research, University previously been accomplished only using multiple sequential
of Southern Denmark, Odense, DENMARK. columns, unwieldy liquid/liquid extractions, or complicated
precipitation methods. We studied the TrisKem Actinide (AC)
resin to investigate its potential to isolate 51,52gMn from bulk iron,
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S40

chromium, and common trace metal contaminants. Materials at the BR1 reactor to test the separation procedure using tracer
and Methods: Both batch and dynamic column experiments amounts. Following a 2 day cooling time, the ampoules were
were performed to characterize the AC resin’s affinity for transported to the lab for processing. High performance ion
representative masses of various metallic constituents. For chromatography (HPIC) was used to separate 161Tb from the
batch resin experiments, solutions containing Fe, Mn, Co, target matrix on a strong cation exchange resin by elution with
Zn, Cu and Cr were loaded onto columns containing 100 mg α-hydroxyisobutyric acid (α-HIBA). Gamma spectrometry and
resin equilibrated with varying concentrations of HNO3 and inductively coupled plasma mass spectrometry (ICP-MS) were
HCl. These columns were agitated for 30 min. Afterwards, the used for 161Tb characterization and quantification. To show that
solution was pushed through the resin, and concentrations the 161TbCl3 can be used for radiolabeling, we performed some
of each metal were assayed by Microwave Plasma - Atomic radiolabeling experiments with DOTA derivatives as a proof of
Emission Spectroscopy and HPGe (FWHM @ 1333 keV = 1.6 keV concept. Results: With the use of a step-wise gradient elution of
) to quantify the metal mass adhered to the resin and eluted in α-HIBA 161Tb was separated from the Gd target material. 50 kBq
solution. Affinity constants were calculated from these data for 161
Tb (specific activity of 49.2 GBq/mg 161Tb) was collected in one
Fe, Cr, and Mn. Batch experiment results were used to design fraction of circa 1 ml. Gamma spectrometry analysis pre- and
dynamic column experiments. A column containing 500 mg of post-purification showed successful separation of the 161Tb
resin was equilibrated with 5 mL of 0.05 M HNO3. A dissolved from the 159Gd (363.3 keV γ-emission). 161Tb was characterized
and reconstituted target solution was then loaded onto the and quantified by the analysis of the 25.5 (22%), 48.9 (16%), 57.2
column and washed with 46 mL of .05 M HNO3. In this wash, (2%) and 74.6 (10%) keV γ-emissions [2]. ICP-MS analysis of the
Cr, Fe, and other trace metals eluted from the column while Mn produced 161Tb is still ongoing. Initial radiolabeling experiments
was retained. The Mn was eluted in 2 mL of 5 M HNO3. Results: with DOTA derivatives however showed high radiolabeling
The results collected from both batch resin experiments and yields could be achieved with our 161TbCl3 solution. Conclusion:
preliminary dynamic column experiments show promising Preliminary results show that a fast and efficient method to
results for a quick and efficient separation chemistry of 51,52gMn purify MBq amounts of n.c.a. 161Tb has been developed. Further
from bulk target material. Conclusion: We hope to determine irradiations in the BR2 reactor are in progress to validate the
a quantified separation factor from multiple dynamic column procedure, analyse the radiochemical purity and yield by using
experiments, as well as binding efficiency with cheltors such higher activities and thus leading to regular production of 161Tb
as DOTA, EDTA, and PCTA. These final characterizations of the for in-house research at SCK•CEN. References: [1] Kostelnik, T.I.
separation method using TrisKem AC resin will provide insight and C. Orvig, Chemical Reviews, 2018. 119, 902-956.[2] Tuli, J.K.,
to the potential application of radio-manganese in nuclear Nuclear Data Sheets, 1974. 13, 493-547.2. Tuli, J.K., Nuclear Data
medicine. References: [1] Fonslet, J. et al. (2017). Optimized Sheets, 1974. 13, 493-547.
procedures for manganese-52: Production, separation and
radiolabeling. Applied Radiation and Isotopes. [2] GJ Topping
et al.,“Manganese-52 Positron Emission Tomagraphy Tracer OP-089
Characterization and Initial Results in Phantoms and In Vivo.”Med The development of 161Tb production and its
Phys (2013). characterization towards clinical application
N. van der Meulen1, N. Gracheva1, Z. Talip1, S. Heinitz1, J. Zeevaart2,
U. Koester3, P. V. Grundler1, C. Favaretto1, C. Bailat4, Y. Nedjadi4, T.
OP-088 Duran4, F. Juget4, R. Schibli1, C. Mueller1;
Tb Purification by High Performance Ion
161 1
Paul Scherrer Institut, Villigen, SWITZERLAND, 2Necsa, Brits,
Chromatography (HPIC) from Irradiated 160Gd SOUTH AFRICA, 3Institut Laue-Langevin, Grenoble, FRANCE,
M. Ooms1, A. R. Burgoyne1, B. Ponsard1, D. Elema1, T. Cardinaels1,2; 4
Institute of Radiation Physics (IRA), Lausanne, SWITZERLAND.
1
SCK-CEN, Institute for Nuclear Materials Science, Mol, BELGIUM,
2
KU Leuven, Department of Chemistry, Leuven, BELGIUM.
Aim/Introduction: 161Tb (T1/2 = 6.89 d) is a therapeutic
radiolanthanide which shows similar decay characteristics and
Aim/Introduction: 161Tb has many attractive properties (half- chemical behaviour to that of 177Lu. While 177Lu is currently
life of 6.9 d, β- decay energy of 593 keV, conversion and Auger regarded as the “gold standard” of radionuclide therapy, the
electron emission) for targeted radionuclide therapy with therapeutic effect of the former may be superior as a result
peptides and antibodies [1]. 161Tb can be produced via neutron of its co-emission of conversion and Auger electrons [1]. The
irradiation of 160Gd in a nuclear reactor, such as BR2 (flux of circa production of 161Tb was reported previously [2], however, further
1014 neutrons cm-2 s-1) at SCK•CEN. The aim of this project was development and improvement of the 161Tb purification process
to develop a fast and easy method to purify small amounts took place and will be presented. The product was characterized
(circa 250 MBq) of n.c.a. 161Tb with high specific activity, for and the 161Tb purity compared with that of 177Lu. Materials and
radiolabeling studies and in-house chelator design. Materials Methods: Enriched 160Gd oxide targets were irradiated at the
and Methods: 0.5 mg Enriched 160Gd (98.2%) was loaded in a SAFARI-1 (South Africa) reactor and the high flux reactor of
quartz ampoule under vacuum and irradiated at SCK•CEN. Initial ILL (France), as well as the spallation-induced neutron source
irradiations (ϕ0 = 3.67x1011 neutrons cm-2 s-1) were performed (SINQ) at PSI, Switzerland, using the 160Gd(n,γ)161Gd→161Tb
S41 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

nuclear reaction to produce a no-carrier-added (n.c.a.) product. liquid separation, cation exchange (AG 50W-8X), and extraction
161
Tb separation from the target material was performed using chromatography. Chelation reactions with trithiol chelator,
cation exchange chromatography, while the desired 161Tb was designed and synthesized by the Jurrisson Radiochemistry
concentrated using extraction chromatography before elution group at the University of Missouri [4], and Sb-chelate stability
of the final product in a small volume. The pH, radionuclidic in mouse serum were monitored using analytical HPLC. Results:
and radiochemical purity of 161TbCl3 was determined, with Various Sb radioisotopes were produced from natSn, with 120mSb
the radiolabeling capacity of 161Tb monitored over a two- (t1/2= 5.76 d), 122Sb (t1/2= 2.74 d), and co-produced 117mSn (t1/2=
week period post processing. The product was assessed 14.0 d) used as tracers for development and optimization of
metrologically towards future instrument calibration. The 161Tb chemical separation techniques. The cation exchange separation
was characterized and half-life measurements performed, method developed produces a separation factor between Sn
using various forms of detection, to ensure accuracy of activity and Sb of >104 and resulted in chemical purity and Sb speciation
measurements. Results: Irradiations of enriched 160Gd2O3 suitable for chelation. Reactions resulting in trithiol chelation of
targets, followed by chemical separation, resulted in yields of radioantimony isolated via cation exchange chromatography
8-20 GBq 161Tb. The final product was obtained with a >80% were fast (<30 min) and efficient (>95%). Recycling techniques
separation yield and activity concentration of 11-21 MBq/ that enable recovery of enriched 119Sn are being developed and
µL. The radionuclidic purity of 161TbCl3 was ≥99.9% at End of will be discussed. Conclusion: Radioisotopes of antimony were
Separation (EOS) with the 160Tb impurity, produced by the produced via proton irradiation of natSn, chemically separated,
159
Tb(n,γ) reaction, determined to be ≤0.007% of the total 161Tb and stably chelated, with ongoing studies into the recycling of
activity at EOS. DOTANOC was labelled with 161Tb at 180 MBq/ target material for future application of enriched 119Sn targets for
nmol specific activity at a labelling efficiency of ≥99%. The 119
Sb production. References: [1] H. Thisgaard and M. Jensen,
radiolabelling yield of DOTA with 161Tb was comparable to n.c.a. “Production of the Auger emitter 119Sb for targeted radionuclide
177
Lu over a two-week period. The half-life measurements of 161Tb therapy using a small PET-cyclotron,” Appl. Radiat. Isot., 2009.
are ongoing. Conclusion: High yields of 161TbCl3 in a quantity [2] H. Thisgaard, M. Jensen, and D. R. Elema, “Medium to large
and quality suitable for high-specific radiolabelling, useful for scale radioisotope production for targeted radiotherapy using a
preclinical and potential clinical application, was produced small PET cyclotron,” Appl. Radiat. Isot., 2011.[3] P. Møller and L.
using a variety of irradiation sources and an innovative chemical P. Nielsen, Advanced Surface Technology, 2nd ed. 2013.[4] A. J.
separation method. References: [1] Müller et al. Eur. J. Nucl. DeGraffenried, Y. Feng, C. L. Barnes, A. R. Ketring, C. S. Cutler, and
Med. Mol. Imaging 2014; 41: 476-85. [2] Lehenberger et al. Nucl. S. S. Jurrison, “Trithiols and their Arsenic Comounds for Potential
Med. Biol. 2011; 38: 917-24. Use in Diagnostic and Therapeutic Radiopharmaceuticals,” Nucl
Med Biol, vol. 43, no. 5, pp. 288-295, 2016.

OP-090
Target development and chemical separation for 306
radioantimony production
A. Olson1, P. A. Ellison1, E. Aluicio-Sarduy1, T. Kostelnik2,3, J.
Do.MoRe - Parallel Session: Diagnostic
Mynerich3, T. E. Barnhart1, R. J. Nickles1, V. Radchenko2,3, J. W. Engle1;
Dosimetry
1
Department of Medical Physics, University of Wisconsin
Madison, Madison, WI, UNITED STATES OF AMERICA, 2Medicinal Sunday, October 13, 2019, 11:30 - 12:45 Lecture Hall 112
Inorganic Chemistry Group, Department of Chemistry,
University of British Columbia, Vancouver, BC, CANADA,
3
Life Sciences Division, TRIUMF, Vancouver, BC, CANADA.
OP-091
Radiation Dosimetry of 18F - AzaFol as the the first Folate
Aim/Introduction: The Auger and conversion electron emitting Receptor-alpha (FRα) directed PET-Tracer
radionuclide 119Sb (t1/2 = 38.5 h) is a candidate for targeted S. Gnesin1, J. Mueller2, I. Burger3, A. Meisel4, M. Choschzick5, C.
radionuclide therapy (TRT) due to highly localized energy Mueller6, R. Schibli7, S. M. Amethamey7, J. O. Prior8, N. Schaefer8;
deposition of its emitted low energy electrons [1]. Antimony-119 1
Institute of Radiation Physics, Lausanne University Hospital
can be produced using 119Sn(p,n)119Sb reactions initiated by and University of Lausanne, Lausanne, SWITZERLAND,
proton irradiation on small cyclotrons, providing a scalable 2
Department of Radiology and Nuclear Medicine, Cantonal
production route [1]. Our efforts build upon previous work in Sn Hospital St Gallen, St. Gallen, SWITZERLAND, 3Department of
target development and chemical separation [2] with a focus on Nuclear Medicine, Kantonsspital Baden, Baden, SWITZERLAND,
producing radioantimony suitable for chelation-based labeling 4
Department of Internal Medicine - Hematology & Oncology,
of biological targeting vectors. Materials and Methods: At Stadtspital Waid, Zurich, SWITZERLAND, 5Institute for Pathology
the University of Wisconsin Madison, thick, electrodeposited and Molecular Pathology, University Hospital of Zurich, Zurich,
nat
Sn targets [3] were irradiated with 16 MeV protons using a GE SWITZERLAND, 6Center for Radiopharmaceutical Sciences ETH-
PETtrace, producing various radioisotopes of antimony. Chemical PSI, Paul Scherrer Institute, Villigen-PSI, Villigen, SWITZERLAND,
separation techniques explored and optimized included liquid- 7
Department of Chemistry and Applied Biosciences, ETH
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S42

Zurich, Zurich, SWITZERLAND, 8Department of Nuclear 2


Department of Molecular & Medical Pharmacology, UCLA,
Medicine and Molecular Imaging, Lausanne University Hospital Los Angeles, CA, UNITED STATES OF AMERICA, 3DOSIsoft
and University of Lausanne, Lausanne, SWITZERLAND. SA, Cachan, FRANCE, 4Department of Nuclear Medicine,
University Hospital Heidelberg, Heidelberg, GERMANY.

Aim/Introduction: The FRα has evolved to a valuable


diagnostic and therapeutic target in different cancer entities. Aim/Introduction: Targeting cancer-associated fibroblasts
Here we present the first in-human radiation dosimetry results (CAFs) has become an attractive goal in research and industry
of a prospective, multicentric trial (NCT03242993) evaluating the given that CAFs can constitute as much as 90% of tumor stroma.
18
F-AzaFol as the first clinically-assessed PET-tracer targeting the The serine protease, fibroblast activation protein (FAP), is highly
FRα. Materials and Methods: The prospective, multi-centric overexpressed in CAFs, suggesting FAP as a promising stromal
study was conducted in three Swiss academic hospitals. Eligible target(1). The recently developed quinolone-based FAP-inhibitor
patients (n=6) presented a histologically confirmed ovarian PET tracer, 68Ga-FAPI-46, has demonstrated encouraging results
cancer or adenocarcinoma of the lung with measurable lesions with high tumor-to-background ratios (TBR) in patients with
in the standard of care imaging modality with an indication for various cancers(2). Here we present a biodistribution and
systemic treatment. All patients had TOF-PET acquisitions at 5, radiation dosimetry study of 68Ga-FAPi-46 PET imaging in
10, 15, 30, 40, 50 and 60 minutes after the intravenous injection cancer patients. Materials and Methods: Radiotracer synthesis
of 327 MBq (SD=37, range: 299-399 MBq) of 18F-AzaFol. Source and image acquisition were conducted at the University of
organ segmentation for brain, thyroid, lungs, heart, liver, spleen, Heidelberg; image analysis and dosimetry were performed at
stomach, kidneys, prostate (in men), red marrow, intestines, UCLA. Six patients with different cancers underwent serial PET/
whole body, for the choroid plexuses and for tumors (primary CT 68Ga-FAPi-46 scans at three time points following radiotracer
carcinoma and metastases) was performed using the PMOD injection: 10 minutes, 1.2 hours, and 3.3 hours (injected activity
software based on sequential PET/CT data. Time integrated range 214-246 MBq). Source organ contouring and activity
activity coefficients (TIAC) were calculated by bi-exponential accumulation was calculated using PLANET®Dose (DOSIsoft SA,
analytical integration of the time activity curves for 0 ≤ t ≤ 60min Cachan, France). The source organs consisted of the kidneys,
then assuming mono-exponential physical decay to infinite. bladder, liver, heart, spleen, bone marrow, and uterus. OLINDA/
Organ absorbed doses (AD) and patient effective doses (ED) EXM was used to fit the organ activity kinetic data with a
where assessed using the OLINDA/EXM v.2.0 software using a monoexponential decay function and integrated according to
urinary voiding period of 1h. The OLINDA/EXM sphere model MIRD formalism to yield total body and organ absorbed doses.
was used to obtain AD in tumors. Dose estimates in patients Standardized uptake values (SUV) and TBR were generated from
were compared with those extrapolated from a previous study the contoured tumor and source organ volumes. Spherical
in mice [1]. Results: No patient had any serious adverse event volumes in muscle and blood pool were also obtained for TBR.
related to the experimental substance. The organs receiving Results: At all timepoints, the highest organ SUV was observed
the highest AD were the urinary bladder wall, the liver, the in the kidneys. Tumor and organs SUVs decreased with time
kidneys and the small intestine (51.3, 50.6, 44.9 and 26.2 μGy/ whereas TBRs increased with time. The highest TBRs at 3.3 hours
MBq respectively). Considering a 1h urinary voiding time, the ED were observed with the marrow (32.2), muscle (23.1), spleen
across our patient cohort and for the gender-averaged reference (19.6), and liver (17.3). The organs with the highest absorbed
person were of 18.3±2.7 and 20±1.4 μSv/MBq respectively. ED doses are the kidneys (1.66E-02 mGy/MBq), followed by the
in human exceeded the value of 13.2 μSv/MBq obtained from heart wall (1.11E-02 mGy/MBq) and liver (1.01E-02 mGy/MBq).
pre-clinical data. A specific biologic uptake and a significant The average total body effective dose is 7.84E-03 mSv/MBq -
AD (30 μGy/MBq) were reported for the choroid plexuses. similar to reported values for related FAP-inhibitors(3). Thus for
Average AD in tumors was 26.4 μGy/MBq (range: 9.6-47.1 μGy/ administration of 200 MBq 68Ga-FAPi-46 the total body effective
MBq). Conclusion: 18F-Azafol is a PET agent with favourable dose is 1.57 mSv ± 0.26 mSv, in addition to approximately 3.7
dosimetric properties and reasonable radiation dose burden mSv from one low-dose CT attenuation scan. Conclusion: 68Ga-
in patients (comparable to 18F-FDG), which merits further FAPi-46 PET/CT imaging is safe: for administration of 200 MBq(5.4
evaluation to assess its performance in patients with ovarian mCi) of 68Ga-FAPi-46 the whole body effective dose including
and lung adenocarcinoma. References: [1] T. Betzel et al, Chem. CT is 5.3 mSv. The biodistribution study showed high TBRs
2013 Feb 20;24(2):205-14. increasing over time, suggesting high diagnostic performance
and favorable tracer kinetics for potential therapeutic
applications. References: 1Hamson et al.(2014) Proteomics Clin.
OP-092 Appl., 8(5-6):454-463. 2Kratochwil et al.(2019) JNM, Epub ahead
Biodistribution and radiation dosimetry study of 68Ga- of print.3Giesel et al.(2018) JNM, 60(3):386-392.
FAPi-46 PET imaging in patients with various cancers
C. Meyer1,2, M. Dahlbom1,2, J. Czernin2, S. Vauclin3, T. Lindner4, U.
Haberkorn4, J. Calais2;
1
Physics & Biology in Medicine Interdepartmental Graduate
Program, UCLA, Los Angeles, CA, UNITED STATES OF AMERICA,
S43 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

OP-093 OP-094
Patient-Specific Estimates of Organ Dose in Paediatric Dosimetric Impact of Modeling the Epiphyseal Plates in
18
FDG PET/CT Imaging Studies Pediatric99mTc-MDP Studies
F. Fahey1,2, C. Kofler3, B. Sexton-Stallone1, R. Reddy1, R. J. L. B. Brown1, Y. Li2, B. Sexton-Stallone3, X. Cao3, D. Plyku2, E. C.
MacDougall1, W. Bolch3; Frey2, S. T. Treves3, F. H. Fahey3, G. Sgouros2, W. E. Bolch1;
1
Boston Children’s Hospital, Boston, MA, UNITED STATES OF 1
University of Florida, Gainesville, FL, UNITED STATES
AMERICA, 2Harvard Medical School, Boston, MA, UNITED STATES OF OF AMERICA, 2Johns Hopkins University, Baltimore,
AMERICA, 3Crayton Pruitt Family Dept. of Biomedical Engineering, MD, UNITED STATES OF AMERICA, 3Harvard Medical
University of Florida, Gainesville, FL, UNITED STATES OF AMERICA. School, Boston, MA, UNITED STATES OF AMERICA.

Aim/Introduction: Hybrid imaging using PET/CT provides Aim/Introduction: 99mTc labeled methylene diphosphonate
crucial clinical information for a variety of paediatric conditions. (MDP) is a commonly used radiopharmaceutical for imaging
Fahey et al. [1] noted that currently there are no standard skeletal regions of high bone turnover. These regions include
guidelines for the CT portion of a PET/CT in children. At fractures, infections, and tumors. In pediatric patients, 99mTc-MDP
Boston Children’s Hospital (BCH), a diagnostic-quality (Dx) CT is will also localize within the epiphyseal plates. Present biokinetic
acquired over essential portions of the field-of-view, with low- models given by the ICRP do not account for increased uptake.
dose attenuation correction (AC) CT applied to the remainder of The present study aims to quantify the dosimetric impact
the PET field-of-view. The objective of this study was to estimate of epiphyseal plate uptake through explicit modeling of the
CT and FDG organ and effective doses in a cohort of BCH epiphyseal plates within the femur of the reference 10-year-
patients undergoing FDG PET/CT. Materials and Methods: The old. The simulation study employs polygon mesh models
UF/NCI phantom library was used to estimate organ dosimetry of cortical bone, medullary marrow, distal and proximal
on 163 PET/CT scans performed on 100 children imaged at trabecular spongiosa, and epiphyseal plates. Polygon mesh
BCH (47 females, 53 males; 1 - 19 years, mean 11.4 years). For Monte Carlo (MC) radiation transport is a recent advancement
the PET component, organ dose coefficients from the UF/NCI that supersedes the implementation of memory intensive
reference phantom library were interpolated across patient voxel models. Materials and Methods: The UF/NCI reference
weight to determine patient-specific organ dose coefficients. 10-year-old phantom used in the study was modified to include
These coefficients were scaled by FDG administered activity epiphyseal plates in the long bones. To create the epiphyseal
recommendations from the North American Guidelines for plates, a Boolean splitting operation is performed at the location
children and adolescents [2]. For the CT component, patients of the epiphyseal plate and two planes that are separated 0.08
were matched by height/weight to individual phantoms within mm. This operation results in a 0.08-mm structure representing
the UF/NCI phantom library. CT parameters as well as scan the epiphyseal plate. Phantom triangle mesh structures are
length and body region imaged were taken into consideration. converted to a tetrahedral mesh using Tetgen. MC radiation
An attenuation-based algorithm was applied to account for tube transport was performed using PHITS to assess doses to all
current modulation (TCM). Patients in the cohort were scanned structures in the model. Results: Results were generated using
with specific BCH AC and Dx protocols. Results: Effective dose an isolated femur where the epiphyseal plates of the proximal
of the FDG PET component ranged from 4.1 to 9.2 mSv (average femoral head, greater trochanter and the distal femoral head
5.8 mSv). The effective doses of the CT component for AC and Dx were modeled. Cortical bone, spongiosa, and epiphyseal plates
scans ranged from 0.01 to 3.04 mSv (average 0.9 mSv) and 0.19 were then independently simulated as source regions using
to 11.2 mSv (average 4.1 mSv), respectively. For the combined the 99mTc decay scheme. This approach allows the assessment
PET/CT, effective doses for the AC and Dx scans ranged from of varying levels of activity for each source organ. Results for
4.8 to 9.6 mSv (average 6.9 mSv) and 5.3 to 17.7 mSv (average femur active marrow dose are shown to be highly dependent
10.1 mSv), respectively. The FDG, CT and total PET/CT effective on the percent of total femur activity localized in the epiphyseal
doses all varied with body weight. Conclusion: This work plate. For all structures, increasing the 99mTc-MDP activity
demonstrates the dependence of paediatric PET/CT effective concentration within the epiphyseal plates lowers the absorbed
dose (FDG, CT and total) on body weight. The CT effective dose to active bone marrow in the 10-year femur. Future efforts
dose also depends on scan type (AC or Dx) and CT acquisition will extend this modeling approach to all skeletal sites, and for
parameters (kVp, effective mAs, scan length and body region all reference patient ages. Conclusion: This work demonstrates
imaged) as well as the use of TCM. This work also highlights the the need for incorporating epiphyseal plates in long bones
range of effective dose typical in paediatric PET/CT imaging. for pediatric dosimetry. The assumption of a uniform uptake
References: 1. Fahey FH, et al. J Nucl Med. 2017;58:1360-1366. 2. across all bone surfaces leads to an overestimation of active
Treves ST, et al. J Nucl Med. 2016;57:15N-18N. marrow dose in comparison to that assuming some uptake
to the growth plates. Future work will incorporate epiphyseal
structures in all other regions of the pediatric skeleton.
References: Acknowledgements: Grant R01 EB013558
from the National Institute for Biomedical Engineering and
Bioengineering.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S44

OP-095 307
Radiation dosimetry of nasally administered PET agents
using computer simulations
Pitfalls & Artefacts 2 - Interactive Clinical Cases
J. O’ Doherty1,2, E. Hippelainen3,4, C. Mangini5, D. Hamby6, N.
- Dosimetry Committee: From Imaging to
Singh7;
Dosimetry ? Step-by-Step Patient Dosimetry
1
Sidra Medicine, Doha, QATAR, 2Weill Cornell Medicine Qatar,
Doha, QATAR, 3Helsinki University Hospital, Helsinki, FINLAND, Sunday, October 13, 2019, 11:30 - 13:00 Lecture Hall 113
4
University of Helsinki, Helsinki, FINLAND, 5Rennaisance Code
Development, Corvallis, OR, UNITED STATES OF AMERICA,
6
Renaissance Code Development, Corvallis, OR, UNITED STATES
OF AMERICA, 7Oxford University, Oxford, UNITED KINGDOM. OP-096
Dosimetry for Radioembolisation with 90Y Microspheres
C. Chiesa;
Aim/Introduction: The intranasal (IN) administration of Nuclear Medicine, Foundation IRCCS Istituto
radiopharmaceuticals is of interest in being a viable route for Nazionale Tumori, Milan, ITALY.
the delivery of radiopharmaceuticals that do not ordinarily cross
the blood brain barrier (BBB) [1]. For this imaging technique to
be viable in a patient population, certain conditions need to be OP-097
met for clinical use, for example good image quality and safety Dosimetry for 177Lu-PSMA Therapy
and efficacy of the administration. This work provides initial G. Böning;
dosimetry calculations related to the safety of performing such Ludwig-Maximilians-University of Munich - University Hospital,
experiments in patients. Materials and Methods: We utilized Department of Nuclear Medicine, Munich, GERMANY.
an analytical equation and VARSKIN software to estimate the
radiation dose to the skin tissue inside the nasal cavity assuming
a homogenous distribution of F-18 and C-11 radiotracers. OP-098
Furthermore, we performed a direct Monte Carlo simulation of Dosimetry for 177Lu-PSMA Therapy
radiation transport in tissue, and estimated radiation dosimetry H. Illhan;
to organs of interest such as the eyes, thyroid and brain by Ludwig-Maximilians-University of Munich - University Hospital,
way of calculation of dose factor (DF) values used in dosimetry Department of Nuclear Medicine, Munich, GERMANY.
calculations. Results: Analytical and VARSKIN calculation
methods estimated absorbed radiation doses to the skin of
the nasal cavity of approximately 11 mGy/MBq and 7 mGy/ OP-099
MBq per hour for 18F and 11C radiotracers administered via IN. Dosimetry for Alpha-Particle Emitters
Direct Monte Carlo simulations of radiation transport resulted C. Hindorf;
in DF values from nasal cavity to the thyroid, eyes and brain of Skåne University Hospital, Department of
1.72x10-6, 1.93x10-6 and 3.51x10-6 mGy/MBq·s respectively for Radiation Physics, Lund, SWEDEN.
F-18 radiotracers and 1.8x10-6, 1.95x10-5 and 3.54x10-6 mGy/
MBq·s for C-11 radiotracers respectively. Conclusion: Dosimetric
concerns about IN administrations of PET radiotracers should be OP-100
considered before human use. Depending on the administered Step by Step Estimation of Uncertainty on Absorbed Dose
amount of activity via the IN route, values presented in this J. Gear;
work can be used for assessment of dosimetric concerns. Royal Marsden NHS Foundation Trust, Joint Department
Based on these calculations, absorbed dose and thus safety of of Physics, Sutton, UNITED KINGDOM.
IN administration of future study protocols can be balanced
with requirements for good image quality. References: [1] N
Singh, M Veronese, J O’Doherty, T Sementa, S Bongarzone, D
Cash, C Simmons, M Arcolin, P K Marsden, A Gee, F ETurkheimer.
Assessing the feasibility of intranasal radiotracer administration
for in brain PET imaging. Nuc Med Biol, 66, 32-39, 2018
S45 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

308 recurrent PCa. No relevant difference of the accuracy was noted


among the participating countries, while the major clinical
Clinical Oncology - Rapid Fire Session: Prostate
role that PET may play in this setting was confirmed. Those
- BCR only
preliminary data from the first international multicentric trial
are supporting the benefits of the use of 68Ga-PSMA PET/CT.
Sunday, October 13, 2019, 11:30 - 13:00 Lecture Hall 114 References: None.

OP-102
OP-101 68
Ga-PSMA PET/CT in patients with recurrent prostate
68Ga-PSMA PET/CT in biochemical recurrent prostate cancer after radical treatment: prospective results in 1000
cancer: an international multi-institutional prospective patients
study promoted by the IAEA P. Caroli1, U. De Giorgi1, M. Celli1, L. Fantini1, A. Moretti2, R. Galassi2,
E. Estrada Lobato1, S. Fanti2, J. Cerci3; V. Di Iorio1, F. Ferroni1, A. Romeo1, M. Caracciolo3, G. Paganelli3, F.
1
International Atomic Energy Agency, Vienna, AUSTRIA, Matteucci1;
2
Universita di Bologna, Bologna, ITALY, 3Quanta 1
IRCCS IRST, Meldola, ITALY, 2Ospedale Morgagni-Pierantoni,
Diagnóstico e Terapia, Curitiba, BRAZIL. Forlì, ITALY, 3Ospedale S. Anna, Ferrara, ITALY.

Aim/Introduction: Biochemical recurrence is a major problem Aim/Introduction: We studied the usefulness of 68Ga-prostate-
in patients with Prostate Cancer(PCa), rising PSA occurs in 20- specific membrane antigen (PSMA) PET/CT for detecting relapse
30% of patients treated with radical prostatectomy and up to in a prospective series of patients with biochemical recurrence
60% in patients treated with external radiotherapy. Standard (BCR) of prostate cancer (PCa) after radical treatment. Materials
practice for suspected recurrence in PCa includes computed and Methods: Patients with BCR of PCa after radical surgery and/
tomography(CT), bone scintigraphy(BS); MR and PET have or radiotherapy with or without androgen-deprivation therapy
been suggested. The most accurate tracer used so far is were included in the study. 68Ga-HBED-CC-PSMA was prepared
Prostate Specific Antigen(PSMA), but there is lack of reliable according to national regulations, good radiopharmaceutical
data, as most of the published studies have been limited by practice (GRP) as outlined in EANM guidelines, using an Eazy®
retrospective design, single institution approach, small sample synthesis module (Eckert and Zieckert, Germany).68Ga-PSMA
size and lack of follow-up data/reference standard. Therefore, PET/CT scans performed from the top of the head to the mid-
this prospective, multicentric, international study was planned thigh 60 min after intravenous injection of 150 ± 50 MBq of 68Ga-
to evaluate the accuracy of 68GaPSMA-PET/CT in evaluating PSMA were interpreted by two nuclear medicine physicians.
patients with biochemical recurrent PCa; the study was 68Ga-PSMA PET/CT scans were performed on a Biograph mCT
promoted and supported by IAEA. We report the first interim Flow® (Siemens Healthineers, Erlangen Germany). Acquisition
analysis. Materials and Methods: Patients with PCa who have was made on Flow mode (0,7 mm/sec) in 3D mode. The results
undergone primary definitive treatment and with rising PSA were correlated with prostate-specific antigen (PSA) levels at
were recruited in the study from 17 centres in 15 countries the time of the scan (PSApet), Gleason score and patient age.
(Azerbaijan, Brazil, Colombia, India, Israel, Italy, Jordan, Lebanon, When available, 68Ga-PSMA PET/CT scans were compared with
Malaysia, Mexico, Pakistan, Poland, South Africa, Turkey, and 18F-choline PET/CT scans routinely performed within 1 month
Uruguay); all centres obtained ethical clearance for prospective previously. Results: From November 2015 to October 2018,
patient recruitment. Images and data were centrally reviewed; 1000 PCa patients with BCR were evaluated. Their median age
data were collected for positivity rate, detection rate, site of was 72.4 years (+/- 10.3 years) and their median PSApet was
findings, impact on patient management and clinical follow-up. 2 ng/ml (0,2 - 19 ng/ml). 68Ga-PSMA PET/CT localized one or
Results: 842 patients have been enrolled since 2017, while full more suspected PCa lesions detected in 653 patients (62.3%).
data are available for 704 cases. Overall 68GaPSMA-PET/CT was Lesions limited to the pelvis, i.e. the prostate/prostate bed and/
positive in 423 (60.1%); lesions were identified locally (prostate/ or pelvic lymph nodes (LNs), were detected in 415 patients
prostatic bed) in 169 cases; pelvic lymph nodes in 214 cases; (63%). At least one distant lesion (LNs, bone, other organs) was
bone in 137 cases and in other locations in 93 cases. There was detected in 238 patients (37%). For PSA categories 0.2-0,5, 0,51-
a clear relationship between PSMA positivity and Gleason score: 1, 1,01-2 and >2 ng/ml, 47,9%, 60,9%, 68,6%, and 87,3% of the
detection rate was 54.3% in patients with Gleason 7, 61.3% in scans were positive respectively. Conclusion: Our experience
Gleason 8, 76.0% in Gleason 9 and 76.9% in Gleason 10. Also, confirms 68Ga-PSMA PET/CT as a highly sensitive and accurate
there was a clear relationship between lesions identification restaging tool in biochemically-relapsing prostate cancer with
and PSA values: detection rate was 44.1% for PSA <1, 61,9% negative or equivocal conventional imaging also for PSA < 1.0
for PSA ≥1 and <2, 81.4% for PSA ≥2 and <4, and 87.1% in PSA ng/ml.These results support the use of 68Ga-PSMA PET/CT
>4. Conclusion: This is the largest multicenter trial on PSMA- in the clinical setting for an early localization of biochemical
PET reported so far; the data are in line with existing literature recurrence. References: None.
regarding diagnostic performances of PSMA PET in biochemical
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S46

OP-103 OP-104
The impact of clinical factors and inter-site variation on 68
Ga-PSMA-11 PET localizes residual prostate cancer
detection of recurrent prostate cancer with 18F-fluciclovine after salvage lymph node dissection in a multicenter
PET/CT and subsequent management decisions: data from retrospective study
the FALCON trial A. Farolfi1, M. Weber2, F. Barbato2, H. Ilhan3, A. Gafita4, M. Eiber4, J.
G. Cook, FALCON study group; Calais5, A. Afshar-Oromieh6, A. Wetter7, B. Hadaschik8, D. Pianori9, S.
King’s College London, London, UNITED KINGDOM. Fanti1, U. Haberkorn10, K. Herrmann2, W. P. Fendler2;
1
Nuclear Medicine Department, S.Orsola Hospital, University
of Bologna, Bologna, ITALY, 2Department of Nuclear Medicine,
Aim/Introduction:The FALCON study aimed to confirm the clinical University Hospital Essen, Essen, GERMANY, 3Department
benefit of PET radiotracer, 18F-fluciclovine, through its impact on of Nuclear Medicine, University Hospital Munich, Ludwig-
management decisions for men with recurrent prostate cancer. Maximilians-Universität (LMU), Munich, GERMANY,
Here, we explore the impact of clinical factors and variations 4
Department of Nuclear Medicine, Klinikum rechts der Isar,
between recruitment sites on the 18F-fluciclovine detection Technical University Munich, Munich, GERMANY, 5Ahmanson
rate (DR) and subsequent management decisions. Materials Translational Theranostics Division, Department of Molecular
and Methods: Data were collected at 6 UK sites from men and Medical Pharmacology, University of California Los
with a first episode of prostate cancer recurrence after curative- Angeles (UCLA), Los Angeles, CA, UNITED STATES OF AMERICA,
intent treatment who were now being considered for radical 6
Department of Nuclear Medicine, Bern University Hospital,
salvage treatment. Patients who received androgen-deprivation Bern, SWITZERLAND, 7Department of Radiology, University
therapy during the preceding 3 months were excluded. PSA Hospital Essen, Essen, GERMANY, 8Department of Urology,
and Gleason scores were recorded pre-scan.18F-Fluciclovine University Hospital Essen, Essen, GERMANY, 9Department
PET/CT was conducted and interpreted according to standard of Biomedical and Neuromotor Sciences, University of
protocols. The patients’ management plans were recorded Bologna, Bologna, ITALY, 10Department of Nuclear Medicine,
before and after scanning to document any post-scan Heidelberg University Hospital, Heidelberg, GERMANY.
amendments to plans. Results: In total, 104 patients (median
age, 67 years; median PSA, 0.79 ng/mL; 15.4% with Gleason
score ≥8) underwent 18F-fluciclovine PET/CT. Inter-site variation Aim/Introduction: In patients with prostate cancer (PCa)
was noted for the number of patients recruited per site (range: recurrence confined to the pelvic lymph nodes the main
3-37), the median PSA value (inter-site range: 0.25-5.00 ng/ aim of metastases-directed therapy is to delay androgen
mL), the proportion of patients with Gleason score ≥8 (inter- deprivation therapy and improve cancer-specific survival. The
site range: 0-33%), the scanning equipment used (5 PET/CT aim of this study was to identify regions at risk for residual
systems were used across the 6 sites), and the median activity disease in patients with PSA persistence after salvage lymph
of 18F-fluciclovine administered per site (inter-site range: 343.3- node dissection (SLND) using 68Ga-PSMA-11 PET (PSMA-PET).
373.0 MBq). The overall patient-level DR was 56%. Detection Materials and Methods: 21 patients were included in this
was broadly proportional to PSA and ranged from 33% (6/18) multicenter retrospective study with the following inclusion
at PSA ≤0.2 to 100% (8/8) at PSA >10.0 ng/mL. Inter-site criteria: a) SLND for PCa; b) persistently elevated post-operative
variation was also noted in DRs; across sites, the overall patient- PSA levels (≥0.1 ng/mL) ≥6 weeks after SLND; c) PSMA-PET
level DR ranged from 23% to 95%, while the patient-level DR performed within 12 months after SLND. Moreover, a subgroup
at PSA ≤1.0 ng/mL ranged from 13% to 50%. The site with the analysis was performed in 15 patients with both PSMA-PET
highest median PSA (5 ng/mL) reported the highest overall pre-SLND and PSMA-PET post-SLND. Images analysis was
DR (95%). Low patient numbers limited meaningful analysis, performed by three independent nuclear medicine physicians
however, Gleason scores ≤7 were associated with a lower DR applying the molecular imaging TNM system PROMISE.
(53%) compared with scores ≥8 (69%). Scores ≥9 showed the Lesions were confirmed by histopathology/biopsy, presence
highest extraprostatic detection (31% vs 19% for scores ≤6). In of lesion on correlative CT/MRI/bone scan or change in size/
total 66/104 (63%) of patients had a management change post- disappearance/appearance on follow-up CT/MRI/bone scan.
scan. Across sites, the proportion of patients with a post-scan Furthermore, management after PSMA-PET was documented
management change ranged from 15% to 100%. In general, when available. Results: PSMA-PET identified PCa-lesions in
the sites with the highest DRs showed the highest proportion 81% (17/21) of patients with PSA persistence after SLND at
of post-scan management changes. Conclusion: This UK-wide a median PSA level of 1.1 ng/mL (IQR, 0.2-12.0 ng/mL). The
study showed inter-site variation in patient characteristics, probability of detection of Tr, N1, M1 or multiple lesions was
18
F-fluciclovine DR and proportion of post-scan management positively associated with PSA PET (p=0.039). In the patient-
changes. 18F-Fluciclovine showed acceptable performance based analysis disease confined to the pelvis was detected in
at low PSA. Lesions, particularly in extraprostatic regions were 43% of patients (9/21), with predominant pelvic nodes disease
more common among patients with higher Gleason scores. (8/21, 38%). Most frequently affected pelvic nodal regions were
References: None. internal iliac (8/21, 38%). In the subgroup analysis (PSMA-PET
before and after SLND), 60% (9/15) of patients had at least one
lesion already detected at baseline (PET persistence) and 27%
S47 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

(4/15) had previously undetected lesions (PET recurrence). metastases (prostate-specific antigen doubling time [PSADT] ≤
Most frequently affected nodal regions with PET persistence 10 months, or Gleason score [GS] ≥ 8) who had no identifiable
were internal iliac (5/9), obturator (3/9) and external iliac (3/9). extrapelvic metastases on prior conventional imaging were
PSMA-PET was performed before SLND with a median time of assessed with PSMA-PET. Detection rate on PSMA-PET,
2 months (IQR, 1-2 months). Validation was available in 6/21 including local/pelvic and distant M1 disease, was determined.
patients (29%) and 9/9 validated regions were true positive. Association of baseline age ≥ 65 years, GS ≥ 8, PSA ≥ 5.5 ng/mL,
Management after PSMA-PET was recorded in 8/21 patients PSADT ≤ 6 months, pelvic nodes (N1 disease), and prior local
(38%). Conclusion: In this multicenter retrospective study, 68Ga- therapy with M1 disease in the PSMA-PET cohort was assessed
PSMA-11 PET detected disease in more than 80% of patients using univariate and multivariate analyses. SPARTAN patients
with PSA persistence after salvage lymph node dissection. Most were stratified by risk factors for PSMA-PET-detected M1 disease
common sites of persistent disease were within the internal iliac and analyzed using Cox proportional-hazards models. Results:
region. Our data suggests a role for PSMA-ligand PET for both Baseline characteristics of PSMA-PET and SPARTAN patients
staging before salvage surgery and early restaging after salvage were generally similar. PSMA-PET detected PC in 196/200 (98%)
surgery in case of PSA persistence. References: None. patients; 55% had local recurrence, 54% had N1 disease, 55%
had any extrapelvic distant metastatic disease despite being
negative on conventional imaging; 24% were diagnosed with
OP-105 local recurrence only, 29% with oligometastatic (1-3 lesions),
Prostate-Specific Membrane Antigen Positron-Emission and 46% with polymetastatic disease. PSA ≥ 5.5 ng/mL (OR, 2.0;
Tomography (PSMA-PET) in High-Risk Nonmetastatic 95% CI, 1.1-3.6; p = 0.03), pN1 disease (OR, 2.7; 95% CI, 1.2-6.0; p
Castration-Resistant Prostate Cancer (nmCRPC) SPARTAN- = 0.01), prior prostatectomy/salvage external radiation therapy
like Patients Negative by Conventional Imaging (OR, 4.6; 95% CI, 2.0-11.0; p < 0.01), and prior external radiation
W. Fendler1,2, M. Weber1, A. Iravani3, M. S. Hofman3, J. Calais2, J. therapy only (OR, 3.1; 95% CI, 1.5-6.2; p = 0.02) were significantly
Czernin2, H. Ilhan4, F. Saad5, E. J. Small6, M. R. Smith7, P. M. Perez6, T. associated with M1 disease detected by PSMA-PET. All clinically
A. Hope6, I. Rauscher8, A. Londhe9, A. Lopez-Gitlitz10, S. Cheng11, T. relevant subgroups of SPARTAN patients, including patients with
Maurer8, K. Herrmann1, B. Hadaschik12, M. Eiber8; independent predictors of PSMA-PET-M1 disease, significantly
1
Department of Nuclear Medicine, University of Duisburg-Essen benefited from apalutamide. Conclusion: PSMA-PET-positive
and German Cancer Consortium (DKTK), partner site University CRPC patients were similar to those at high-risk of developing
Hospital Essen, Essen, GERMANY, 2Department of Molecular and metastases from SPARTAN. Apalutamide added to ongoing ADT
Medical Pharmacology, University of California Los Angeles, showed significant benefit in all clinically relevant subgroups of
Los Angeles, CA, UNITED STATES OF AMERICA, 3Department of SPARTAN patients, including patients with risk factors for distant
Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, metastases detected by PSMA-PET but negative by conventional
AUSTRALIA, 4Department of Nuclear Medicine, Ludwig Maximilian imaging. Therefore, apalutamide plus ADT should be considered
University, Munich, GERMANY, 5Centre Hospitalier de l’Université for patients negative by conventional imaging but positive by
de Montréal, Université de Montréal, Montréal, QC, CANADA, PSMA-PET (stage migration). The added value of PSMA-PET over
6
Helen Diller Family Comprehensive Cancer Center, University PSADT in patients with high-risk nmCRPC should be explored
of California San Francisco, San Francisco, CA, UNITED STATES in prospective studies. References: 1. Smith et al. N Engl J Med.
OF AMERICA, 7Massachusetts General Hospital Cancer Center 2018;378:1408-1418.
and Harvard Medical School, Boston, MA, UNITED STATES OF
AMERICA, 8Department of Nuclear Medicine, Klinikum rechts
der Isar, Technical University of Munich, Munich, GERMANY, OP-106
9
Janssen Research & Development, Titusville, NJ, UNITED STATES Prognostic value of PSMA PET-derived skeleton tumor
OF AMERICA, 10Janssen Research & Development, Los Angeles, CA, burden parameters for overall survival in patients
UNITED STATES OF AMERICA, 11Janssen Research & Development, undergoing radium-223 treatment
Raritan, NJ, UNITED STATES OF AMERICA, 12Department of Urology, A. Gafita1, H. Wang1, M. Krönke1, W. Weber1, R. Tauber2, M. Eiber1;
University of Duisburg-Essen and German Cancer Consortium 1
Technical University Munich, School of Medicine,
(DKTK), partner site University Hospital Essen, Essen, GERMANY. Department of Nuclear Medicine, Munich, GERMANY,
2
Technical University Munich, School of Medicine,
Department of Urology, Munich, GERMANY.
Aim/Introduction: In SPARTAN, patients with nmCRPC
assessed by conventional imaging benefited from the addition
of apalutamide to ongoing androgen deprivation therapy Aim/Introduction: Prostate-specific membrane antigen
(ADT).1 PSMA-PET detects localized and metastatic PC with (PSMA)-targeted PET imaging showed enhanced accuracy
superior sensitivity to conventional imaging. We retrospectively in lesion detection compared to conventional imaging in
characterized disease extent using PSMA-PET in SPARTAN-like patients with prostate cancer. Radium-223 is a bone-targeted
patients and evaluated risk factors for distant metastases (M1 treatment for symptomatic metastatic castration-resistant
disease) detected by PSMA-PET. Materials and Methods: A prostate cancer (mCRPC) patients. Bone-scan-index (BSI)
total of 200 patients with nmCRPC at high risk of developing showed high predictive value for survival rate in patients
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S48

undergoing radium-223. The aim of this retrospective analysis improving the survival outcomes. Objective: to develop a
was to evaluate the prognostic value of baseline PSMA-PET clinical nomogram to predict 68Ga-PSMA-11-PET/CT positivity
derived skeleton tumor burden parameters for OS in patients in different clinical settings of PSA failure. Materials and
undergoing radium-223. Materials and Methods: Patients Methods: Design: seven-hundred-three (n=703) PCa patients
who underwent radium-223, received a PSMA PET/CT and had with confirmed PSA failure after radical therapy were enrolled.
available lab values prior to the treatment were considered. Each patient underwent 68Ga-PSMA-11-PET/CT to identify the
qPSMA was used for bone lesion segmentation using a fixed site of recurrence. Patients were stratified according to different
SUV-threshold of 3. Bone PSMA-avid tumor volume (bPSMA-TV) clinical settings of recurrence (first-time biochemical recurrence
and bone PSMA-total lesion (bPSMA-TL) were used as output [BCR]: group-1; BCR after salvage therapy: group-2; biochemical
parameters. Baseline alkaline phosphatase (ALP) values were persistence after radical prostatectomy [BCP]: group-3;
extracted from the database. Baseline tumor burden parameters advanced stage PCa before second-line systemic therapies:
were divided into two groups by medians and into tertile by group-4). All patients never received AR-targeted therapies
25th and 75thpercentiles. Kaplan-Meier curves and log-rank test and chemotherapy. Outcome measurements and statistical
were used to evaluate the association of bPSMA-TV, bPSMA-TL analysis: First, we assessed 68Ga-PSMA-11-PET/CT positivity rate.
and ALP with OS. Results: Fifty-four patients were included in Second, multivariable logistic regressions analyses were used to
the analysis. Median PSMA-TV, PSMA-TL and ALP were 502mL, determine which co-variates independently predicted positive
3255 and 191 U/L. Median OS was 17.5 (95%CI: 3.2-43.6) months scan. Third, regression-based coefficients were used to develop
and 6 patients were alive at the end of follow-up period. a nomogram predicting positive 68Ga-PSMA-11-PET/CT result
When divided by medians, a trend towards a higher median and 200 bootstrap resamples were used for internal validation.
survival for low vs. high tumor burden was noticed for bPSMA- Fourth, Receiver operating characteristic (ROC) analysis was
TV and bPSMA-TL and ALP (19.2 vs. 16.6 months, 19.5 vs. 16.6 used to identify the most informative nomogram’s derived cut-
months and 19.2 vs. 14.2 months; p=0.33, p=0.33 and p=0.26, off to predict the positive scan. Decision curve analysis (DCA)
respectively). When divided by percentiles, a longer survival rate were implemented to quantify nomogram’s clinical benefit in
was noticed among patients with low (<144mL) vs. moderate clinical practice. Results: 68Ga-PSMA-11-PET/CT positivity rate
vs. high (>1374mL) bPSMA-TV with a median OS of 24.4 vs. 14.2 was 51.2 % (CI95% 46.8%-71.3%), while was 40.3% in group-1,
vs. 6.8 months, respectively (p=0.003). No significant difference 54% in group-2, 60.5% in group-3, 86.9% in group-4 (p<0.001).
was noticed among patients with low (<1434) vs. moderate vs. Median PSA=0.7 ng/mL (IQR 0.4-1.3). At multivariable analyses
high (>10174) bPSMA-TL with a median OS of 19.5 vs. 17.2 vs. Gleason-grade, PSA, PSAdt and clinical setting were independent
11.5 months, respectively (p=0.22). For ALP a significantly longer predictors of a positive scan (all p≤0.04). A nomogram based
median survival was observed among patients with low (<121 on covariates included in the multivariate model demonstrated
U/L) vs. moderate vs. high (>393 U/L) levels: 21.4 vs. 19.5 vs. 6.8 a bootstrap-corrected accuracy of 82%. At ROC analysis, 40%
months, respectively (p=0.01). Conclusion: Baseline PSMA PET- resulted the best nomogram’s cut-off. Applying this cut-off,
derived skeleton tumor burden parameters showed promising 282/703 patients (40.1%) would be spared 68Ga-PSMA-11-PET/
results for OS prediction. Compared to ALP, PSMA-TV showed a CT and positive 68Ga-PSMA-11-PET/CT would be missed in 55
tendency to better differentiate survival rates in patients with patients (15.3%). The sensitivity, specificity and NPV associated
high vs. moderate tumor burden. Advanced analyses including with 40% as cut-off were 84.7%, 66.2%, and 80.5%, respectively.
larger patients cohort are warranted to establish the role of Finally, in DCA, the nomogram revealed clinical net benefit
PSMA-targeted PET imaging in the framework of radium-223. when the threshold probabilities of positive 68Ga-PSMA-11-PET/
References: None. CT is >10%. Conclusion: We developed and internally validated
the first nomogram aimed at predicting the likelihood of 68Ga-
PSMA-11-PET/CT positivity in different stages of PSA failure. This
OP-107 novel nomogram proved its good accuracy to predict a positive
Prediction Nomogram for 68Ga-PSMA-11 PET/CT in 68
Ga-PSMA-11-PET/CT results. The 40% cut off was the most
different clinical settings of PSA failure after radical informative threshold probability to predict positive 68Ga-PSMA-
treatment for prostate cancer 11-PET/CT. This tool might be markedly important as a guide to
F. Ceci1,2, L. Bianchi3, M. Borghesi3, G. Polverari2, A. Briganti4, A. clinicians in the best use of PSMA-based PET imaging, in order to
Farolfi2, R. Schiavina3, E. Brunocilla3, P. Castellucci2, S. Fanti2; select the best treatment option. References: None.
1
University of Turin, Turin, ITALY, 2Metropolitan Nuclear
Medicine, S.Orsola-Malpighi Hospital, University of Bologna,
Bologna, ITALY, 3Department of Urology, S.Orsola-Malpighi OP-108
Hospital, University of Bologna, Bologna, ITALY, 4Unit 68
Ga-PSMA-11 PET/CT in hormone-naïve recurrent
of Urology/Division of Oncology, Urological Research prostate cancer: a prospective, single-center study in
Institute, IRCCS San Raffaele Hospital, Milan, ITALY. patients eligible for salvage therapy
F. Ceci1, D. G. Nicolotti1, E. Pilati1, A. Guarneri2, B. Lillaz3, R. Passera1,
Aim/Introduction: The prompt identification of the site of V. Liberini1, M. Finessi1, M. Bellò1, P. Gontero3, U. Ricardi2, D.
prostate cancer (PCa) recurrence with 68Ga-PSMA-11- Deandreis1;
PET/CT may change the disease management, potentially 1
Nuclear Medicine, Department of Medical Sciences, University
S49 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

of Turin, Turin, ITALY, 2Radiation Oncology, Department OP-109


of Oncology, University of Turin, Turin, ITALY, 3Urology, 68Ga-PSMA-11 PET-CT study in prostate cancer patients
Department of Surgery, University of Turin, Turin, ITALY. with biochemical recurrence and non-contributive
18F-Choline PET-CT: impact on therapeutic decision-
making and biomarker changes
Aim/Introduction: Primary objective: to assess the efficacy C. Rousseau1,2, A. Michaud1, M. Barbaud1, C. Morvant1, B.
of 68Ga-PSMA-11-PET/CT to detect recurrent location(s) in Maucherat1, M. Le Thiec1, D. Rusu1, A. Morel1, V. Fleury1, M.
hormone-naïve prostate cancer (PCa) patients. Secondary Colombié1, A. Rauscher3, M. Frindel3, P. Baumgartner3, N. Fleury4, L.
objectives: 1) to evaluate changes in clinical management Campion5, F. Kraeber-Bodéré1,2;
occurred after 68Ga-PSMA-11-PET/CT; 2) to determine which 1
ICO Cancer Center, Nuclear Medicine Unit, St Herblain, FRANCE,
covariates independently predict positive scan; 3) to assess 68Ga- 2
CRCINA, University of Nantes, INSERM UMR1232, CNRS-ERL6001,
PSMA-11-PET/CT performance in different clinical setting of PSA Nantes, FRANCE, 3ICO Cancer Center, Pharmacy Unit, St Herblain,
relapse. Materials and Methods: This is a prospective, open- FRANCE, 4ICO Cancer Center, DRCI, St Herblain, FRANCE,
label, observational, single-centre study in hormone-naïve PCa 5
ICO Cancer Center, Biometrics Unit, St Herblain, FRANCE.
patients (protocol P-5315). All patients, were recruited at the uro-
oncological tumour board of University Hospital of Turin. Patients
were investigated with 68Ga-PSMA-11-PET/CT at single referral Aim/Introduction: The aim of this retrospective study was to
centre between November 2016 and January 2019. Inclusion investigate the impact of 68Ga-PSMA-11 PET/CT on current
criteria: 1) proven PCa; 2) radical therapy (radical prostatectomy management of recurrence prostate cancer patients with
[RP] or radiotherapy); 3) proven biochemical recurrence (BCR) negative PET/CT F-Choline. Materials and Methods: Eighty-
or biochemical persistence (BCP); 4) hormone-naïve patients; 5) nine patients with previously negative 18F-Choline (FCH)
PSA<1.5 ng/mL or any PSA in case of negative choline-PET/CT. were enrolled (PSA from 0.28 to 24.6 ng/mL). PET images were
Exclusion criteria: 1) not eligible for salvage therapy; 2) inability recorded 1 hour after injection of 150 MBq of 68Ga-PSMA.
to tolerate PET scan; 3) concurrent malignancy. Changes in Referring patient physician was asked about the care before
clinical management and definition of clinical settings of PSA and after PSMA PET imaging to determine the influence of
relapse were defined by a single-centre tumour board. Clinical PSMA results on therapeutic strategy. Six months after the end
settings: BCP after RP (group-1); first-time BCR (group-2); BCR of treatment, a PSA assay was requested to evaluate therapeutic
after salvage therapy (group-3). Multivariable logistic regressions efficacy. Results: Sixty-nine among the 89 patients (77,5%)
analyses were used to determine independent predictors of had a positive PSMA PET/CT. Detection rates were 85.6% and
positive 68Ga-PSMA-11-PET/CT. Results: Two-hundred twenty- 89.4% for serum PSA levels lower than 2 ng/ml, and > 2 ng/ml,
three (n=223) consecutive patients have been prospectively respectively. Three hundred and one lesions were detected:
enrolled: median PSA=0.65 ng/mL (0.2-8.9); median PSAdt=9.3 235/301 in lymph nodes (78.1%), 38/301 as metastatic sites
months (0.4-144.6). 96.9% received RP as primary therapy, (bone, mostly on axial skeleton, or lung) (12.6%) and 28/301 in
while 3.1% received radiotherapy. Overall positivity rate for the prostate bed (9.3%). The majority of lesions were detected
68
Ga-PSMA-11-PET/CT was 38.6% (CI95% 32.2%-45.3%). Disease in lymph nodes: in particular with 71.5% pelvic nodes, on
confined to pelvis (prostate bed and/or lymph-nodes) was the other hand with 17.9% of para-aortic nodes and 10.6%
detected in 19.3% of cases, while distant locations (extra-pelvic with sus diaphragmatic location. For the para-aortic and sub-
nodes, bone or visceral) were observed in 19.3%. Overall, 153 diaphragmatic node locations, initial surgical management
PSMA positive lesions were detected. Secondary objectives: 1) associated with pelvic salvage radiotherapy were the most
taking into consideration clinical, laboratory and imaging data common initial management which could explain the frequently
derived by 68Ga-PSMA-11-PET/CT, the multidisciplinary tumour supra-pelvic node recurrence. The median number of lesions
board changed in 35.4% of cases the treatment planned prior per patient was 2 [ranging from 0 to 67]. No particularity of the
to PET scan. 2) PSA, PSAdt and T stage≥3a were independent PSA serum level, doubling time or PSA velocity at the time of
predictors of a positive scan (all p<0.03). The same features PSMA PET-CT could explain why 68Ga-PSMA PET-CT was unable
resulted independent predictors of distant PCa locations. 3) to detect any suspicious tumor lesions in 20 patients. Thanks
68
Ga-PSMA-11-PET/CT positivity rate was 56% in group-1, 23.3% to PSMA PET/CT, therapeutic management changed in 59/69
in group-2, 47.2% in group-3. Positivity rate was significantly patients (84.9%). With a follow-up of 5.7 ± 1.8 months, 62/89
different among different clinical stages of PSA relapse (p=0.001). (69.6%) PSA assays after treatment guided by PSMA PET-CT were
Conclusion: This study attested the overall good performance collected. For 43.5% (27/62) of patients, the serum PSA level was
of 68Ga-PSMA-11-PET/CT to detect recurrent locations in lower than 0.2 ng/mL and a total PSA decrease of over 50% in 35
hormone-naïve PCa, influencing the subsequent therapy (56.5%) patients was obtained. Conclusion: Performing a PSMA
management. PSA, PSAdt, T stage and different clinical settings PET-CT when FCH PET-CT was negative allows the recurrence
should be taken into consideration by referent physicians, since localization in more 80% of patients and this had a major clinical
these parameters showed significant association with 68Ga- impact, as it resulted in treatment change in more than 80% of
PSMA-11-PET/CT positivity rate. References: None. patients as well as a significant decrease in PSA levels in more
than 55% of them. References: None.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S50

OP-110 309
Multi-phasic 68Ga-PSMA PET/CT in detection of early
recurrence in prostate cancer patients with PSA < 1 ng/ml:
Thyroid - Rapid Fire Session: Thyroid and
a prospective study of 105 cases
Parathyroid
M. Beheshti1,2, R. Manafi-Farid3, F. M. Mottaghy4, W. Loidl5, H.
Geinitz6, W. Langsteger7; Sunday, October 13, 2019, 11:30 - 12:45 Lecture Hall 115
1
Nuclear Medicine, University Hospital, RWTH University,
Aachen, GERMANY, 2Nuclear Medicine, Paracelsus Medical
University, Salzburg, AUSTRIA, 3Research Center for Nuclear
Medicine, Tehran University of Medical Sciences, Tehran, IRAN, OP-111
ISLAMIC REPUBLIC OF, 4University Hospital, RWTH University, The role of thyroid scintigraphy with Tc-99m in the era of
Aachen, GERMANY, 5Urology, Ordensklinikum, Linz, AUSTRIA, FNAC and molecular markers
6
Radiation Oncology, Ordensklinikum, Linz, AUSTRIA, 7PET-CT S. Sophocleous;
Center, St. Vincent’s Hospital, Ordensklinikum, Linz, AUSTRIA. Diagnostic center Agios Therissos, Strovolos, Nicosia, CYPRUS.

Aim/Introduction: The main objective of this prospective Aim/Introduction: In Cyprus with known iodine deficiency,
study was to determine the impact of multi-phasic acquisition thyroid nodules are found in ~15% of the adults. Recent
of 68Ga-PSMA PET/CT in the detection of local recurrence in investigations show that approximately 10% of them are
prostate cancer (PCa) patients in early stage of biochemical malignant, mainly diagnosed with FNAC. The use of thyroid
recurrence with PSA level < 1 ng/ml. In addition, 68Ga-PSMA scintigraphy in the work-up of thyroid nodules has been
PET/CT positivity were correlated with clinical parameters. dramatically decreased during last years. It is only used in cases
Materials and Methods: 105 patients (mean age 66.9±8.3) with low TSH level. Consequently autonomous functioning
with biochemical recurrence and PSA level < 1 ng/ml were thyroid nodules (AFNT) with normal TSH are rarely diagnosed
enrolled in this study. All patients have been subjected to and the number of unnecessary performed FNAC on these
initial prostatectomy with additional radiation therapy in 19.3% lesions is unknown. Materials and Methods: We investigate
(26/135) and anti-hormonal therapy in 7.4% (10/135) through the prevalence of AFTN with normal TSH level. Between
the disease course. A multi-phasic imaging including dynamic 01.01.2011 and 31.12.2018, 1505 nuclear scans were performed,
acquisition (1-8 min. p.i.) from prostate bed, standard whole- in two groups.In the first group we performed 1220 thyroid
body images (60 min. p.i.) and delayed studies (120-150 min. scan with Tc-99m to investigate the behavior of 2000 nodules
p.i.) from pelvis, were performed. 68Ga-PSMA PET/CT positivity found on ultrasound. In the second group, of 285 patients with
was also correlated with primary clinical findings (i.e. initial PSA, hyperparathyroidism a dual tracer scan with Sestamibi and
Gleason score, T-stage, positive surgical margin). Results: Overall, Tc-99m was performed. We used the Pertechnetate scan to
91 lesions were detected in 47.6% (50/105) of patients, of whom investigate the behavior of 90 incidentally found nodules on
18 were classified as local recurrence, 48 as malignant lymph ultrasound. Results: On the first group we demonstrated AFNT
node in pelvis, and 25 distant metastases. The detection rates in 30% of the cases. On the second group AFNT was found in
were 27.8% (5/18), 45.0% (27/60), and 66.7% (18/27) for PSA < 0.2 20/90 (22%). Conclusion: Thyroid scan using Tc-99m is able
ng/ml, 0.2 ≤ PSA < 0.5 and 0.5 ≤ PSA < 1, respectively. Standard to pick up the AFNT especially in multinodular goiters. The Tc-
whole-body images showed significantly higher detection 99m used in the dual tracer technique is a successful method to
rate in the pelvic region in comparison with dynamic phase evaluate the presence of AFNT. In patients with thyroid nodules
(p-value=0.039). However, there was no significant difference and normal TSH level to avoid unnecessary FNAC, a thyroid scan
in 68Ga-PSMA PET positivity between standard and delayed must be performed, especially in regions with iodine deficiency.
imaging (p-value=0.38). Nevertheless, reviewing the findings References: LITERATURESurvey on thyroid diseases in Cyprus
in all acquisition phases resulted in better determination of the 2005CANCER ARCHIVE(Urojod test 1997, thyrochem 2015).
equivocal lesions leading to higher diagnostic accuracy in 21.9% (ATA,ETA). guidelines
(23/105) of patients. Trigger PSA and history of antiandrogen
treatment were the significant predictor of 68Ga-PSMA PET/CT
positivity. Conclusion: 68Ga-PSMA PET/CT revealed promising OP-112
results for early detection of recurrent disease even in PCa Is there a role for semiquantitative parameters to
patients with PSA ≥0.5 - <1.0 ng/ml. However, it showed limited characterize incidental focal thyroid uptake on (18)F-FDG
value in cases with PSA level < 0.5 ng/ml.Stand-alone dynamic PET/CT study?
imaging seems to have no appreciable additive value in the R. Durmo1, D. Albano1, M. Bonacina1, M. Gazzilli1, E. Cerudelli1, F.
detection of local recurrences or pelvic lymph node metastases. Dondi2, A. Mazzoletti2, P. Bellini2, F. Bertagna2, R. Giubbini2;
However, performing multi-phasic 68Ga-PSMA PET/CT 1
Nuclear Medicine, Spedali Civili di Brescia, Brescia,
imaging may provide additional information leading to better ITALY, 2Nuclear Medicine, University of Brescia
determination of findings in about 20% of PCa patients with low and Spedali Civili di Brescia, Brescia, ITALY.
PSA of <1 ng/ml. References: None.
S51 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

Aim/Introduction: Thyroid incidental uptake (TIU) on Pierre and Marie Curie Center, Algiers, ALGERIA.
fluorine-18 fluorodeoxyglucose PET/CT (FDG PET/CT) is defined
as an uptake newly detected in patients who underwent
imaging for non thyroid diseases. The clinical significance of Aim/Introduction: Thyroïde nodules are common in endocrine
TIU in FDG PET/CT studies remains controversial. The aim of this pathology. Relatively, thyroid cancer is less frequent, but
large retrospective study was to (a) establish the prevalence affects the thyroid nodule management. The fine needle
and pathological nature of focal TIU, (b) to establish possible aspiration biopsy (FNAB) is the gold standard test. Nevertheless,
metabolic PET parameters cut-off over which a malignant lesion Technetium-99m-MIBI scintigraphy represents a supplementary
should be suspected and (c) to assess a gender correlation of alternative in difficult cases. Objectives of the study: Evauate the
PET/CT parameters and malignancy. Materials and Methods: diagnostic value of technetium-99m methoxyisobutylisonitrile
We retrospectively reviewed a total of 41169 patients who (99mTC-MIBI) scintigraphy in the assessment of cold thyroid
underwent a FDG PET/CT for non thyroid diseases between nodules. Materials and Methods: Prospective study of
January 2012 and December 2018. A TIU was diagnosed in 695 203 operated patients with nodular goiter (NG). The total
(1.6%) patients (159 male; 536 female; average age 64). Of 695 number of cold nodules on 99mTc-pertechnetate scans was
TIU, 184 (26.4%) underwent further investigation to determine 380, confirmed by ultrasonography and measured more than
the nature of the uptake. We measured the maximum 10mm or equal. The thyroid scan was performed 15 min and
standardized uptake value body weight (SUVmax), SUVmean, 120 min after i.v. injection of 555 MBq of 99mTc-MIBI. 99mTC-
lean body mass (SUVlbm), body surface area (SUVbsa), metabolic MIBI uptake in the nodule compared with that in surrounding
tumor volume (MTV), total lesion glycolysis (TLG) of TIU. normal thyroid tissue was scored for both early and delayed
Receiver operating curves (ROC) were calculated to determine images as follows: 0, cold; 1, decreased; 2, equal; 3, increased.
optimal cut-off values between malignant and benign lesions. Semi-quantitative analysis was performed using a lesion to non-
Moreover semiquantitative metabolic parameters between lesion ratio on early (ER) and delayed images (DR). Additionally,
benign and malignant TIU were compare using T-test. Results: a retention index (RI) was calculated using the formula RI= (DR-
Fifty-seven (22 male, 35 female) of the 184 patients who ER) x 100/ER. The malignancy criteria were a positive retention
underwent ultrasound guided fine-needle aspiration biopsy or and increased uptake in the nodule in the early and delayed
thyroidectomy had malignant disease (31%), 98/184 (29 male; images. And these data was compared to histopathological
63 female) were benign (53.3%) and 29/184 (8 male, 21 female) results. Results: Histopathologically, the nodules were found
were indeterminate (15.7%) at cytological examination in to be well-differentiated cancer in 29 cases, medullary cancer
absence of surgery. The ROC derived cut-off was SUVmax=7.27 in 3, poorly differentiated cancer in 5 and benign in 343 cases.
(sensitivity=78.6, specificity=56.1, AUC=0.713), SUVmean=3.84 None of the malignant nodules were cold on MIBI at the early
(sensitivity=74.5, specificity=54.4, AUC=0.663), SUVlbm=4.8 and delayed images. An increased uptake in both early and
(sensitivity=77.3, specificity=63.2, AUC=0.719), SUVbsa=2.14 delayed images was found in 24 malignant nodules (64.9%)
(sensitivity=82.3, specificity 56.1, AUC=0.79), MTV=1.5 from whom 18 (75%) with a positive retention index. A receiver
(sensitivity=80.6, specificity 41.8, AUC=0.592) and TLG=8.6 operating characteristic analysis was performed to determine
(sensitivity=71.4, specificity 45.5, AUC=0.509). A statistical threshold value for the RI as 1.95 with an area under the curve
significant difference at T-test was observed between benign (AUC) of 0.65. When nodules with increased uptake in both
and malignant SUVmax, SUVmean, SUVlbm, SUVbsa (p<0.05). the early and delayed images and a positive retention index
Metabolic tumor volume (MTV and TLG) were not significant were considered as malignant, sensitivity, specificity, positive
different between malignant and benign lesion. There were predictive value, negative predictive value and accuracy were
not significant statistical difference in the semiquantitative 0.49, 0.96, 0.56, 0.95 and 0.91. The highest sensitivity (0.95) was
parameters between female and male patients (p>0.05). obtained at multivariate analysis by logistic regression, when
Conclusion: There is a relatively high possibility of a malignant both score 2+3 at only delayed images with a positive retention
lesion in TIU. Semiquantitative parameters could be a useful index were considered as malignant Conclusion: 99mTC-MIBI
tool in the assessment of TIU, however there are no safe and scintigraphy could be helpful in the preoperative assessment
definitive cut-off values to discriminate between malignancy of thyroid nodules, particularly, those with non diagnostic or
and benign lesion. References: None. indeterminate cytology. References: None.

OP-113 OP-114
Technetium-99m MIBI Scintigraphy Contribution In The Diagnostic performance of technetium-99m (99m Tc)
Assessment Of Cold Thyroid Nodule methoxy-isobutyl-isonitrile (MIBI) for differentiation
A. Chehboun1, D. Foudil1, Q. Naili1, M. Serir2, L. Bougrina3, L. Griene4, of malignant from benign thyroid nodules with
S. E. Bendib2, S. Mimouni-Zerguini1; indeterminate or non-diagnostic fine needle aspiration
1
Endocrinology Unit-Pierre and Marie Curie Center, cytology (FNAC)
Algiers, ALGERIA, 2Radiology Unit-Pierre and Marie Curie I. Iakovou, E. Giannoula, A. Kalaitzoglou,
Center, Algiers, ALGERIA, 3Cytology Unit-Pierre and Marie V. Mpalaris, K. Michailo, G. Arsos;
Curie Center, Algiers, ALGERIA, 4Hormonology Unit-
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S52

Academic Dpt Of Nuclear Medicine, Aim/Introduction: To investigate the diagnostic performance


Papageorgiou Hsp, Thessaloniki, GREECE. of 18F-fluorocholine (FCH) PET/CT compared to 11C-methionine
(MET) PET/CT in the localisation of hyperfunctioning parathyroid
tissue in patients with primary hyperparathyroidism (pHTP) in
Aim/Introduction: Thyroid nodules are common, their case of negative or inconclusive 99mTc-sestaMIBI SPECT (MIBI)
prevalence being largely dependent on the identification findings. Materials and Methods: Fifty-eight patients with
method ranging from 4-7% when identified by palpation to 20- biochemical evidence of pHTP and negative or inconclusive
75% when detecting by ultrasound techniques. FNAC is a part of MIBI were referred for evaluation by MET and FCH-PET/CT for
the diagnostic algorithm to detect or exclude thyroid malignancy. pre-surgical localisation of hyperfunctioning parathyroid tissue.
However, there is a large range in the percentage of non- The PET/CT results were classified into 3 categories (positive,
diagnostic and indeterminate FNACs raising the need for new inconclusive or negative) based on the nodular aspect of tracer
molecular imaging techniques to further characterize thyroid uptake and the visualisation of corresponding nodules on the
nodules. Although, 99mTc-MIBI has been initially introduced for CT. The PET/CT results were confronted to the surgical and
myocardial perfusion and parathyroid scintigraphy, it has also histopathological findings used as gold standard. Results: Fifty-
a role as a non specific radiopharmaceutical for tumor imaging three patients with a median serum calcium level of 2.67+/-0.17
and in particular for diferentiating malignant from benign mmol/L and PTH level of 72+/-78 ng/L were included for analysis.
lesions in patients with non-diagnostic and indeterminate FCH PET/CT was positive in 39 patients (74%), inconclusive in 3
FNACs of thyroid nodules. The objective of the current work (6%) and negative in 11 (21%) compared to 30 (57%), 4 (7%) and
is to evaluate the utility of 99mTc-MIBI thyroid scintigraphy in 19 (36%) respectively for MET PET/CT. FCH localised 13 additional
differentiating malignant from benign thyroid nodules with foci (10 positive and 3 inconclusive) compared to MET. Twenty-
indeterminate or non-diagnostic cytology. Materials and six patients (sex F/M ratio16/10) underwent surgery and 31
Methods: We retrospectively evaluated 23 patients affected lesions were resected (22 adenomas, 6 hyperplasia, 2 cancers,
by thyroid nodules with either indeterminate (16, 69.5%), class and 1 normal gland). FCH PET/CT correctly localised 26 lesions
III or IV according to the Bethesda system or non-diagnostic (7, in 24/26 (92%) patients compared to 21 lesions in 20/26 (77%)
30.5%) cytology. Planar images of the thyroid were acquired 10 patients localised by MET PET/CT. Per patient-based sensitivity
and 60 minutes after 99mTc-MIBI administration, early and late and PPV were 96% and 96% for FCH vs. 87% and 95% for MET.
SPECT images were applied when needed and wash-out index Per lesion-based sensitivity and PPV were respectively 84% and
(WOI) was used as a quantitative method to evaluate thyroid 93% for FCH vs. 70% and 91% for MET (p=0,0010). At the follow-
nodules. All patients underwent total/near total thyroidectomy up, twenty-one (81%) patients were considered cured after the
and scintigraphic results were compared to histological surgery while 3 (12%) patients have a biological recurrence
findings. Results: Twelve out of 23 patients were diagnosed of hypercalcaemia. Conclusion: FCH was found significantly
with differentiated thyroid cancer (DTC) (7 papillary TC and more sensitive than MET for lesion detection and localisation
5 follicular TC) and the remaining with benign adenomas. of hyperfunctioning parathyroid tissue in case of negative or
Malignant nodules were detected by WOI with a threshold inconclusive MIBI scan. References: None.
of -19%. Therefore, overall sensitivity, specifcity, PPV and NPV
were 100%, 63.4%, 66.6% and 100%, respectively. Conclusion:
In conclusion, semiquantitative 99mTc-MIBI scintigraphy OP-116
imaging analysis is a useful tool in differential diagnosis of Added Value Of Fluorocholine (FCH) PET/CT To sestaMIBI
thyroid nodules with non-diagnostic and indeterminate FNAC. Scintigraphy/SPECT (Sc) And Ultrasonography (US) For
References: Thyroid nodules with indeterminate cytology: Preoperatory Detection Of Hyperfuntionning Parathyroid
molecular imaging with ⁹⁹mTc-methoxyisobutylisonitrile (MIBI) (PT) Glands In Patients With Hyperparathyroidism (HPT)
is more cost-effective than the Afirma gene expression classifier. And Chronic Kidney Disease (CKD)
Heinzel A, Müller D, Behrendt FF, Giovanella L, Mottaghy FM, J. Talbot1, J. Zhang-Yin2, T. Delbot3, M. Tassart4, I. Anton2, S.
Verburg FA.Eur J Nucl Med Mol Imaging. 2014 Aug;41(8): Select Balogova2, F. Montravers2, P. Haymann5, S. Périé6, M. Gauthé2, S.
item 23529672Diagnostic performance of (99m)Tc-MIBI scan in Gaujoux7;
predicting the malignancy of thyroid nodules: a meta-analysis. 1
Hopital Tenon, Paris, FRANCE, 2Hopital Tenon, Nuclear Medicine,
Treglia G, Caldarella C, Saggiorato E, Ceriani L, Orlandi F, Salvatori Paris, FRANCE, 3Hopital Cochin, Nuclear Medicine, Paris, FRANCE,
M, Giovanella L.Endocrine. 2013 Aug;44(1):70-8. 4
Hopital Tenon Radiology, Paris, FRANCE, 5Hopital Tenon,
Explorations fonctionnelles, Paris, FRANCE, 6Hopital Tenon, ORL,
Paris, FRANCE, 7Hopital Cochin, Endocrine Surgery, Paris, FRANCE.
OP-115
Comparison of 18F-fluorocholine PET-CT to 11C-methionine
PET-CT for the localisation of hyperfunctioning Aim/Introduction: Since the publication in 2014 of
parathyroid tissue in primary hyperparathyroidism our pilot study about 18F-fluorocholine (FCH)-PET/CT in
C. Mathey, C. Keyzer, G. Van Simaeys, N. Trotta, S. Lacroix, B. hyperparathyroidism (HPT), evidence have been widely
Corvilain, S. Goldman, R. Moreno-Reyes; provided on its ability to detect parathyroid (PT) adenomas in
Erasme hospital, Bruxelles, BELGIUM. case of primary HPT and non-conclusive sestaMIBI scintigraphy/
S53 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

SPECT (Sc) and ultrasonography (US). In contrast, there are available in HPT of HD. Brown tumours (BT) are rare skeletal
few data on FCH PET/CT performance when HPT is associated anomalies that occur in case of prolonged HPT. They result
with chronic kidney disease (CKD). Detection of PT hyperplasia from increased osteoclastic activity, often related to chronic
predominant in this setting is limited with Sc. We determined kidney failure. We also aimed to determine the ability of FCH
the added value of FCH PET/CT in this context. Materials and PET/CT to detect BT in HPT of HD. Materials and Methods:
Methods: HPT was diagnosed and parathyroidectomy planned We included in this retrospective study all HPT patients on
in 74 CKD patients. Based on the results of on-site reading (OR) of HD referred to our center between 2013 and 2018. FCH PET/
Sc and US performed by specialists of PT imaging, the surgeon CT was acquired on the neck and the thorax; if bone lesions
considered that the location of abnormal PTs was unclear and were visible on PET or on CT, a complementary whole-body
referred those patients to FCH PET/CT from 2012 until 2018. acquisition was performed. Results: In 41 patients on HD (13
Masked reading (MR) of Sc and FCH PET/CT was also performed. with kidney transplant), 50 FCH PET/CTs were performed (16
The equivocal results of readings were considered negative. The for recurrent HPT post-PTX). 36 patients were then (re)operated.
standard-of-truth was histology after parathyroidectomy and Initial PTX in 25 patients found 72 abnormal PT of which 62
follow-up to rule out recurrent HPT and consider non-resected were FCH-positive (detection-rate DR=86%); reoperation in 11
PT as normal. Results: According to the selection criteria, ORs of patients found 11 abnormal PT all FCH-positive (DR=100%).
Sc and US were both negative in 24 patients, discrepant in 17, In 6 patients, were also found multiple osteolytic lesions with
only US-positive in 28, only Sc-positive in 5. The overall patient- substantially increased FCH uptake, among them, 3 had more
based positivity-rate (PBPR) was 74% for FCH, 19% for Sc and than 5 osteolytic lesions. BT was diagnosed based on histology
55% for US.60 patients (80%) underwent parathyroidectomy; in 2 patients, in 1 patient on the post-PTX change of the bone
histology of 109 resected glands was hyperplasia in 61, adenoma lesions on CT from osteoclastic to osteoblastic scars, and on the
in 30 and normal in 18. According to OR, gland-based sensitivity typical aspect of BT on CT in the last 3 patients. Conclusion: In
was 71% for FCH, 20% for Sc, 44% for US and specificity 99%, patients on hemodialysis with hyperparathyroidism, FCH PET/
98% and 90%, respectively. Results of MR were sensitivity 77% for CT showed a high detection-rate for abnormal parathyroid
FCH, 16% for Sc; specificity 99% and 98%. When Sc and US were glands, particularly in case of post-PTX recurrence. This complete
both negative, FCH had a PBPR of 63% a gland-based sensitivity success in case of recurrent hyperparathyroidism may be
of 62% (OR) 76% (MR) and a 100% specificity. When US was explained by the increased metabolism of the gland which was
positive and Sc negative, gland-based sensitivity was 58% for left alone after initial PTX. Furthermore, brown tumours showed
US vs. 66% (OR) 79% (MR) for FCH. OR gland-based sensitivity a substantially increased uptake of FCH. In this context, brown
according to the KDIGO categories G2, G3, G4-5 respectively, tumours must be considered among the causes of osteolytic
was 67%, 79%, 90% for FCH; 15%, 29%, 40% for Sc and 43%, 50%, lesions with increased FCH uptake. Thus, FCH PET/CT represents
50% for US. Conclusion: FCH appeared effective for detecting a powerful “One-stop-shop” examination, since it appears to
abnormal PT in patients with HPT and CKD G2 to G5. When Sc be very sensitive for preoperatory detection of the abnormal
and US were non-contributive or discrepant to detect abnormal parathyroid glands, and since it can guide parathyroidectomy,
PTs, FCH PET/CT showed added value, improving the positivity the most effective option for correcting the metabolic trouble
rate and the gland-based sensitivity compared with both Sc and of the bone revealed by high FCH uptake and responsible for
US. References: None. brown tumours. References: None.
OP-117
Preoperatory 18F-fluorocholine PET/CT performed
in patients undergoing hemodialysis locates OP-118
hyperfunctioning parathyroid glands and may show Contribution of dual time point F-18 fluorocholine PET/
brown tumours CT for challenging pre-operative parathyroid imaging in
J. T. Zhang-Yin1, S. Perie2, M. Gauthe1, I. Anton1, H. Fessi3, J. primary hyperparathyroidism
Haymann4, P. Ronco3, F. Montravers1, S. Balogova1, J. Talbot1; L. M. Vija1, E. Gabiache2, P. Pascal1, S. Kanoun2, L. Dierickx2, C.
1
Service de Médecine Nucléaire, Hôpital Tenon, Paris, FRANCE, Renaud3, B. Jean3, B. Herbault-Barres4, S. Brillouet5, S. Grunenwald6,
2
Service d’ORL, Hôpital Tenon, Paris, FRANCE, 3Service de M. Vialon6, P. Caron6, F. Courbon2;
Néphrologie hémodialyse, Hôpital Tenon, Paris, FRANCE, 4Service 1
Nuclear Medicine,Institut Universitaire de Cancerologie
de l’Exploration rénale fonctionnelle, Hôpital Tenon, Paris, FRANCE. IUCTO, ICR, Toulouse, FRANCE, 2Nuclear Medicine, Institut
Universitaire de Cancerologie IUCTO, ICR, Toulouse, FRANCE,
3
Thoracic Surgery, University Hospital-CHU, Toulouse,
Aim/Introduction: In patients undergoing hemodialysis (HD), FRANCE, 4Pathology, Institut Universitaire de Cancerologie
nuclear functional imaging has the advantage to display and IUCTO, ICR, Toulouse, FRANCE, 5Institut Universitaire de
localize orthotopic and ectopic hyperfunctioning parathyroid Cancerologie IUCTO, ICR, Toulouse, FRANCE, 6Endocrinology,
glands (PT) prior to initial parathyroidectomy (PTX) and in case University Hospital-CHU, Toulouse, FRANCE.
of post-surgical recurrence. In primary hyperparathyroidism
(HPT), 18F-fluorocholine (FCH) PET/CT has shown superior
performance compared to sestaMIBI scintigraphy or SPECT/ Aim/Introduction: When cervical ultrasound and Tc-99m
CT. No data on its diagnostic performance are currently MIBI scans are not informative, second-line imaging should
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S54

be considered for preoperative localization of pathologic 401


parathyroid glands. Dual time point F-18 fluorocholine PET/CT
(FCH PET/CT) combines molecular (PET) and morphological
CME 3 - Radiation Protection + Dosimetry
(CT) information with uptake modifications within time,
Committee: Metrological Aspects on the
increasing sensitivity for parathyroid gland detection. However,
Implementation of Dosimetry in Radionuclide
the optimal time point for image acquisition for FCH PET/
Therapy
CT remains under debate. We evaluate image acquisition
time point for the localization of pathologic parathyroid Sunday, October 13, 2019, 14:30 - 16:00 Auditorium
glands on FCH PET/CT as well as detection rates and
sensitivities in patients with primary hyperparathyroidism
Materials and Methods: Patients with primary OP-119
hyperparathyroidism explored with a dual time point FCH PET/ Introduction
CT (at 10 and 60 minutes post injection) and with post-operative K. Sjögreen-Gleisner;
histological parathyroid analysis have been prospectively Lund University, Medical Radiation Physics, Lund, SWEDEN.
included in the study. Early versus late acquisitions have been
analyzed both on visual and semi-quantitative analysis. Results:
Thirty-seven patients (13 men, 24 women, mean age 51 years OP-120
(20-80) with primary hyperparathyroidism [serum calcium 2.79 Requirements for the Dosimetry-Guided, Multi-Center
mmol/l (2.4-2.91), PTH levels 108.6 ng/L (57-190)] had dual time Clinical Trial SELIMETRY
FCH PET/CT, 34 of them after a negative or discordant US/Tc- J. Wadsley;
99m-sestaMIBI scans. On visual analysis, uptake of pathologic Weston Park Cancer Centre, Sheffield, UNITED KINGDOM.
parathyroid glands was similar on early versus late FCH PET/
CT in 27 patients, in 1 patient early image acquisition was more
intense, whereas in 8 patients (22 %) uptake was better visible on OP-121
late acquisition. There was a tendency on FCH uptake increase Priorities of Dosimetry in Clinical Radionuclide Therapy -
in pathologic parathyroid glands on late images (p = 0.24), with The Italian Agreement Between National Nuclear Medicine
a significant increase of parathyroid to thyroid ratio on semi and Medical Physics Associations
quantitative analysis (SUVmax lesion/ thyroid; p = 0.01). On a C. Chiesa;
per-lesion analysis, FCH-PET/CT sensitivity, specificity, positive Nuclear Medicine, Foundation IRCCS Istituto
and negative predictive values were 86 %, 33 %, 96 % and 11 %
respectively. On a per-patient analysis, Se, Sp, PPV, NPV were 82 Nazionale Tumori, Milan, ITALY.
%, 14 %, 86 % and 11 %. FCH-PET/CT imaging made to remove OP-122
successfully pathologic glands in 34 patients (adenomas n = 31, European Initiatives to Ensure Traceable Dosimetry Across
hyperplasia n = 3), with a global cure rate of 92 % and cure rate Countries and Centers
related to FCH contribution of 65 %. Conclusion: With FCH-PET/ M. Lassmann;
CT in second line imaging of primary hyperparathyroid patients, Universitaetsklinikum Wuerzburg, Klinik fuer
most pathologic parathyroid glands are adequately visualized Nuklearmedizin, Würzburg, GERMANY.
on early imaging; for several patients, parathyroid adenomas are
better visualized on late time points. Therefore in pre-operative
parathyroid characterization, FCH-PET/CT with dual time 402
acquisition remains a useful option when first-line imaging and
Joint Symposium 5 - Oncology & Theranostics
early time FCH PET/CT are not informative. References: None.
Committee / EORTC: The Future of Medical
Imaging in Precision Medicine
YDF1
Sunday, October 13, 2019, 14:30 - 16:00 Lecture Hall 311
EANM Young Daily Forum

Sunday, October 13, 2019, 13:00 - 14:30 Lecture Hall 113 OP-123
The Future of Theranostic Radionuclide Approaches
U. Haberkorn;
YDF-1 Heidelberg University Hopsital, Department of
How to Meet More Great People at the EANM Congress Nuclear Medicine, Heidelberg, GERMANY.
R. Sheppard;
EANM Moderator, London, UNITED KINGDOM.
OP-124
Companion Diagnostics in Drug Development
S55 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

G. van Dongen; OP-131


Amsterdam University Medical Center, Department of A Clinical Perspective
Radiology & Nuclear Medicine, Amsterdam, NETHERLANDS. V. Taqueti;
Cardiac Stress Laboratory, Brigham and Women’s Hospital,
Harvard Medical School, Boston, MA, UNITED STATES OF AMERICA.
OP-125
Total Body PET-CT for Pharmacokinetic Analysis
S. Vandenberghe; OP-132
University of Ghent, Department of Electronics Discussion
and information systems, Gent, BELGIUM.

404a
OP-126 Mini Course 1 - Technologist Committee:
The Use of Artificial Intelligence in Precision Medicine
I. Buvat;
Research Methodology
Unité Imagerie Moléculaire In Vivo, CEA/DRF/Service,
Hospitalier Frédéric Joliot, Orsay, FRANCE. Sunday, October 13, 2019, 14:30 - 15:30 Lecture Hall 117

OP-127 OP-133
Panel Discussion Research Methodology for Technologists
C. Malamateniou;
Division of Midwifery and Radiography, City University
403 of London, London, UNITED KINGDOM.
Joint Symposium 6 - Translational and
Molecular Imaging Therapy + Cardiovascular 405
+ Inflammation & Infection Committee / AHA:
Imaging Inflammation as Major Determinant M2M - Parallel Session: Antibody-Based
of Cardiovascular Diseases ? New Tracers and Radionuclide Therapy
Clinical Applications
Sunday, October 13, 2019, 14:30 - 16:00 Lecture Hall 111
Sunday, October 13, 2019, 14:30 - 16:00 Lecture Hall 312

OP-134
OP-128 Targeted alpha therapy with 212Pb-NNV003 is efficient
New Concepts, New Targets in treatment of ibrutinib-resistant chronic lymphocytic
J. Thackeray; leukaemia in preclinical models
Department of Nuclear Medicine, Hannover A. Saidi1, H. Heyerdahl2, A. Maaland2, J. Torgue3, J. Dahle2;
Medical School, Hannover, GERMANY. 1
Orano Med SAS, Paris La Défense, FRANCE, 2Nordic
Nanovector ASA, Oslo, NORWAY, 3Orano Med LLC,
Plano, TX, UNITED STATES OF AMERICA.
OP-129
SPECT and PET in Cardiac Infection and Inflammation
C. Lauri; Aim/Introduction: Approximately 90,000 cases of chronic
Department of Nuclear Medicine and Molecular Imaging, lymphocytic leukaemia (CLL) and non-Hodkgin’s lymphoma
“Sapienza” University of Rome. -Sant’Andrea Hospital, Rome, ITALY. (NHL) are expected annually in the US. Standard of care includes
chemotherapy combined with anti-CD20 antibodies and
Bruton’s tyrosine kinase inhibitor ibrutinib. While these therapies
OP-130 are initially effective, most patients inevitably relapse. CD37
PET Imaging of Inflammatory Alterations in Ischaemic and is under clinical evaluation as a therapeutic target for B-cell
Non-Ischaemic Disease malignancies. Alpha-emitting radionuclides have demonstrated
F. Caobelli; potential for targeted therapies due to the short alpha
Department of Nuclear Medicine, Universitätsspital track, causing localized cytotoxicity. Orano Med and Nordic
Basel, Basel, SWITZERLAND. Nanovector developed a targeted alpha therapy combining
the CD37-specific antibody NNV003 with the alpha-particle-
emitting radioisotope 212Pb. We previously reported that 212Pb-
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S56

NNV003 is effective in disseminated animal models using CD37- Biodistribution of 203/212Pb-rituximab was evaluated in vivo by
expressing NHL and CLL cell lines (1). Here we compare the SPECT-CT imaging and post-mortem. Acute toxicity studies
efficacy of 212Pb-NNV003 with ibrutinib in a disseminated mouse (survey, hematological and renal parameters) were performed
model using the ibrutinib-resistant cell line MEC-2. Materials in order to determine the safety profile and safe administration
and Methods: The efficacy and tolerability of a single dose 212Pb- doses. To evaluate tumor biodistribution and in vivo efficacy of
NNV003 treatment were evaluated in disseminated models 212
Pb-rituximab, a mice lymphoma model was used: 8-week-
using human CLL (MEC-2) and Burkitt’s lymphoma (Daudi) cells. old C57BL/6JRj mice were injected intravenously with 25 x 103
Comparison to therapeutic doses of ibrutinib was investigated EL4-hCD20-Luc cells (mouse lymphoma cell line). Mice were
in the MEC-2 model. R2G2 or CB17-SCID mice were injected treated either 11 days or 20 to 30 days post-cell injection with
intravenously with 2.5×106 MEC-2 or 10×106 Daudi cells on day 277.5 kBq 212Pb-rituximab or controls (including 277.5 kBq 212Pb-
0, followed by intravenous injection of 212Pb-NNV003 (2.5, 5 or irrelevant mAb, cold rituximab and saline). Therapeutic efficacy
7.5 µCi in Daudi model and 5, 10, 15 or 20 µCi in MEC-2 model) or was monitored by bioluminescence imaging (BLI) and overall
daily oral administration of ibrutinib (12.5 or 25 mg/kg) starting survival. Results: 212Pb-rituximab biodistribution studies shows
on day 2 (n=10-12 per group). 212Pb-cetuximab (unspecific about 20% ID/g tumor uptake and that liver and spleen are the
isotype control), unlabelled NNV003 and NaCl were used as organs at risk. Acute toxicity was observed at 555 kBq with a
controls. Results: 212Pb-NNV003 treatments resulted in survival reduced mice survival. Transient and reversible hematological
of 67-91% of the mice 26 weeks after Daudi cell injection, and toxicity was observed from 277.5 kBq treatment dose. Mice
30-90% of the mice 27 weeks after MEC-2 cell injection. Control treated with 212Pb-rituximab 20 to 30 days post cell injection
mice presented a median survival of 7-8 weeks in the Daudi (BLI-detectable tumors) exhibited marked tumor growth
model and 4.9-9.3 weeks in the MEC-2 model. 212Pb-NNV003 inhibition compared to controls, with a median survival of 28
showed a significantly prolonged survival compared to ibrutinib days for 212Pb-rituximab-treated group instead of 9 to 13 days
and controls (p <0.0001). 15 and 20 µCi 212Pb-NNV003 resulted for control groups. Strongly improved median survival (above
in survival of 100% and 70% of mice 15 weeks after MEC-2 cell 105 days) was observed for mice treated with 212Pb-rituximab 11
injection. Ibrutinib treated animals presented a median survival days after cell injection, whereas median survival was reached
of 4.3-4.4 weeks, comparable to the NNV003 and saline groups 36.5 days post-treatment for 212Pb-irrelevant mAb, 64 days for
(4.1 and 4.4 weeks). Mice receiving 212Pb-cetuximab presented cold rituximab and 27 days for saline control. Conclusion: These
a median survival of 7 weeks. Conclusion: The study shows results show 212Pb-rituximab efficacy on a murine syngeneic
that a single injection 212Pb-NNV003 is safe and effective for the lymphoma model with significant tumoral regression and
treatment of CD37 positive CLL and NHL in preclinical models, increased survival. This study highlights alpha-RIT potency in
with promising efficacy in an ibrutinib-resistant CLL model. B-NHL treatment. References: (1) K. Yong and M.W. Brechbiel,
Further clinical testing is warranted. References: 1. Saidi et al., Dalton Trans. 2011
Blood, 2018, 132 Suppl1:4422

OP-136
OP-135 Preclinical evaluation of CEA-PRIT, a novel pretargeted
Preclinical study with212Pb-rituximab as an alpha- alpha therapy regimen for treatment of CEA-positive
radioimmunotherapy for Non-Hodgkin’s Lymphoma tumours with 212Pb
I. Quelven1,2, J. Monteil1,2, A. Saidi3, J. Torgue4, M. Cogne2, S. S. Frost1, A. Pichard1, A. Haas2, H. P. Grimm3, A. Mouchotte1, A.
Durand-Panteix2; Colmont1, O. Freytag1, J. Torgue4, S. Colombetti1, C. Klein1, P.
1
Limoges University Hospital, Limoges, FRANCE, 2CRIBL, CNRS UMR Umaña1;
7276, INSERM 1262, Limoges, FRANCE, 3Orano Med SAS, Paris, 1
Roche Pharma Research and Early Development, Zürich,
FRANCE, 4Orano Med LLC, Plano, TX, UNITED STATES OF AMERICA. SWITZERLAND, 2Roche Pharma Research and Early
Development, Penzberg, GERMANY, 3Roche Pharma
Research and Early Development, Basel, SWITZERLAND,
Aim/Introduction: Non-Hodgkin’s Lymphoma (NHL) is the 4
Orano Med LLC, Plano, TX, UNITED STATES OF AMERICA.
8thmost commonly diagnosed cancer in men and 11th in women.
Despite significantly improved response rate and survival, many
relapses are observed. Radioimmunotherapy (RIT) is an emerging Aim/Introduction: Pretargeted radioimmunotherapy (PRIT)
second line option for NHL. RIT with beta-emitters (Bexxar®, optimizes delivery of radioactivity to malignant cells, by allowing
Zevalin®) has been developed but presented hematological tumour-targeting bispecific antibodies (BsAb) to distribute
toxicity. The development of RIT with alpha-emitters is attractive within target tissue before administering a small radiolabelled
because of the high linear energy transfer (LET) and short path molecule that efficiently binds to pretargeted sites or is rapidly
length of alpha-radiation in tissues, resulting in higher tumor excreted. This dissociation of targeting and irradiation can
cell killing and lower toxicity to surrounding tissues. In this study, minimize the exposure of healthy tissues while increasing
we investigated the potential of alpha-RIT with 212Pb-rituximab. the tumour absorbed dose, especially using short-lived
212
Pb is used as an in vivo generator of the high-energy alpha- radionuclides such as 212Pb (t1/2 = 10.6 h), an in vivo generator of
particle emitting radionuclide 212Bi (1). Materials and Methods: the highly cytotoxic alpha emitter 212Bi (t1/2 = 60.6 min). Here we
S57 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

describe CEA-PRIT, a novel pretargeted alpha therapy regimen literature. The dose of bound and unbound radiopharmaceuticals
using a CEA-DOTAM bispecific antibody and 212Pb for PRIT of and free radionuclides in the tumour (0.02 l), kidneys and plasma
carcinoembryonic antigen (CEA)-positive tumours. Materials were calculated for various injected amounts and activities. The
and Methods: Mice with subcutaneous CEA-expressing contribution to dose and equivalent dose in the investigated
BxPC3 xenografts were injected with a pretargeting BsAb with organs were calculated for each radionuclide by using a
specificity for CEA and 1,4,7,10-Tetrakis(carbamoylmethyl)- weighting factor of 5 for alpha particles. The required activities
1,4,7,10-tetraazacyclododecane (DOTAM). Circulating BsAb was and amounts were estimated for a prescribed tumour absorbed
neutralized after 4-7 days using a dextran-based clearing agent; dose of 30 Gy for different molar activities. The excretion of free
2-24 h later, the radiolabelled effector molecule 212Pb-DOTAM 212
Bi after being released from the chelator due to a preceding
was injected. The three-step PRIT cycle was repeated twice with disintegration was studied by including a physiological kidney
2 weeks between radioactive injections for efficacy assessment. model1. Kidney parameter values were estimated in a separately
Tumour volumes were estimated through calipering, and developed excretion model for stable Bi (208.9 u). Results:
the biodistribution assessed 5 min-48 h after the radioactive The prescribed dose in tumour of 30 Gy was achieved by an
injection. Results: A pretargeting BsAb was generated that injection of 82 MBq 212Pb with a molar activity of 10.9 TBq/µmol;
binds bivalently with pM affinity to CEA and fM affinity to Pb- the corresponding dose to kidneys and plasma were 8 and 0.7
DOTAM. A single CEA-PRIT cycle of 0.37 or 1.11 MBq significantly Gy. The relative contributions of 212Pb_β, 212Bi_β, 212Bi_α, 208Tl_β
delayed tumour growth compared with control groups in an and 212Po_α to absorbed dose in the tumour were 8%, 14%, 21%,
activity-dependent manner in the BxPC3 model. Three cycles 3% and 54%, to the kidneys 8%, 13%, 21%, 6% and 52%, and
of 0.37 or 1.11 MBq prolonged tumour control further, with the to the plasma 8%, 13%, 20%, 7% and 52%, respectively. Alpha
strongest inhibition demonstrated after three cycles of 1.11 MBq. particle emissions contribute more than 88% to the equivalent
However, 1.11 MBq caused significant weight loss, whereas 0.37 doses in organs of investigation. For molar activities of 1.1 and
MBq was well tolerated. Subsequent studies using 0.74 MBq 0.1 TBq/µmol, the absorbed dose in both plasma and kidneys
demonstrated good multiple-cycle tolerability, and dosimetry of increased by 1% and 8% for the fixed prescribed tumour dose.
the optimized regimen confirmed the 212Pb-targeting specificity Conclusion: The developed basic 212Pb-labelled mAbs model
to tumour compared with normal tissues; the tumour uptake allows the simulation of the biokinetics of radiolabelled and
reached 43% of the injected activity per gram of tissue (IA/g) at unlabelled mAbs and released free radionuclides in the body.
6 h p.i., whereas kidneys had a maximum of 12% IA/g 5 min p.i., Thus, it holds promise to predict optimal dosing regimens
decreasing to 4% IA/g 2 h p.i. In vivo proof-of-concept was also (activity and amounts) for prescribed doses to tumours using
demonstrated using other targets, such as HER2. Conclusion: different radiopharmaceuticals. Ongoing improvements, e.g.,
The preclinical studies demonstrated therapeutic efficacy of inclusion of other organs, degradation, microdosimetry, will
the novel CEA-PRIT approach, combining the high cytotoxicity allow generating hypotheses for optimal treatment planning
and short half-life of 212Pb/212Bi with highly efficient and specific using 212Pb-labelled species. References: Kletting et al., J Nucl
tumour targeting for safe treatment of CEA-expressing tumours. Med 2016;57:503-508.
Translation of the described CEA-PRIT scheme to a phase I trial is
foreseen in the near future based on these encouraging results.
References: None. OP-138
In vitro and in vivo evaluation of bismuth-213 labeled
anti-HER2 nanobodies
OP-137 Y. Dekempeneer;
Pb-labelled monoclonal antibodies: A PBPK model for
212
Vrije Universiteit Brussel, Brussel, BELGIUM.
treatment planning in Targeted Alpha-particle Therapy
(TAT)
N. Zaid, N. Begum, P. Kletting, A. Beer, G. Glatting; Aim/Introduction: This study investigates a novel targeted
Department of Nuclear Medicine, Ulm Universiy, Ulm, GERMANY. therapy which combines the α-emitter bismuth-213 (213Bi) and
HER2-targeting nanobodies (Nbs) to selectively kill HER2pos
metastases in breast- and ovarian cancer. The use of nanobodies
Aim/Introduction: There is growing interest in 212Pb-labelled as vehicles in TAT is promising due to their excellent in vivo
monoclonal antibodies (mAbs) as promising targeted in properties, high target affinity and specificity, fast diffusion
vivo generators of alpha particles. A first physiologically- and clearance kinetics. Moreover, Nbs show good tumor
based pharmacokinetic (PBPK) model for describing the penetration due to their small size. The aim of this study is to
pharmacokinetics and dosimetry is presented as a step towards develop and evaluate the stability up to 105 min after labeling,
treatment planning in Targeted Alpha-particle Therapy (TAT). in vitro binding characteristics and cytotoxicity on HER+ SKOV-
Materials and Methods: A compartmental model for tumour 3 cells, and the in vivo biodistribution of [213Bi]DTPA HER2
and dose limiting organs, e.g. kidneys (0.33 l) and plasma (2.75 targeting Nb. Materials and Methods: First, a 213Bi-labeled-Nb
l) was developed and implemented in the modelling software was developed, using p-SCN-Bn-CHX-A′′-DTPA as bifunctional
SAAMII. The model was constructed based on physiological, chelator. Due to the 46 min half-life of 213Bi, the 213Bi labeling
chemical and physical properties with parameter values from the reaction and quality control of the resulting radioconjugate
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S58

was performed in a very short time frame to limit significant SUDHL-4, U2932 and WSU-DLCL2, and MCL cell lines Granta519
radioactivity losses. In vitro saturation binding assay, clonogenic and Rec-1 was evaluated by the Ray Design Methodology. Five
assay, IncuCyte® live cell imaging and double strand break ex rays per cell line were defined (two rays corresponding to the
vivo immunofluorescence staining were performed on HER2pos drugs alone and 3 rays with their combination). Cells were
cells to determine the affinity and cytotoxicity of [213Bi]DTPA-Nb. treated for 24 hours and their metabolic activity was measured
Its biodistribution and maximum tolerated dose was analyzed at days 3, 4 and 5 after seeding. The interaction index for each ray
in relevant mouse models. Results: Under optimized labeling (Ir) was calculated using the Loewe additivity model with 10%
conditions, the [213Bi]DTPA-Nb remained stable up to 100 min threshold, where Ir < 0.9 is synergistic, 0.9 < Ir < 1.1 is additive and
with a radiochemical purity ≥ 95%. In vitro, [213Bi]DTPA-Nb Ir > 1.1 is antagonistic interaction. In addition, RNA was extracted
bound HER2pos SKOV-3 cells in a HER2-specific way. [213Bi]DTPA- from all cell lines 24 hours after treatment with single treatments
anti-HER2Nb resulted in a high cytotoxic effect significantly or drug combinations and mRNA sequenced using an Illumina
different from the [213Bi]DTPA-controlNb. High tumor uptake TruSeq stranded mRNA kit. Results: Values of Ir varied between
was reached 15 min after injection. Extremely low uptake values 0.3 and 1.8 depending on cell line, ray and day of measurement.
were observed in normal tissues at all time points. [213Bi]DTPA-Nb Synergism was evident in all cell lines for at least one ray and
was excreted via the kidney into the urine, leading to a kidney one day of measurement, except for the combination of 177Lu-
retention of the radioconjugate of 59.9±5.1 %ID/g at 60 min NNV003 and venetoclax in U2932 and DOHH2 cells, where
post injection. Coinfusion of 150 mg/kg gelofusine resulted in additivity/antagonism was observed in all measurements. The
a 2-fold reduction of the kidney retention at all time points. The cell lines showing highest synergy were WSU-DLCL2 for both
injection of [213Bi]DTPA- control Nb resulted in 0.3±0.03 %ID/g combinations and U2932 for the combination of 177Lu-NNV003
tumor uptake 60 min post injection, which was confirmed by a with olaparib. Here, Ir < 0.9 was found for most rays and days
significant decrease in double strand DNA damage compared of measurement. Differences in sensitivity observed between
to the [213Bi]DTPA-anti-HER2Nb injected group. Conclusion: cell lines were not correlated to sensitivity to BH3 (DLBCL) or
Here we describe for the first time the successful labeling of ATM status (MCL) as described in the literature. Hence mRNA
an anti-HER2 Nb with the α-particle emitter 213Bi, using a DTPA sequencing data will be explored for potential differential gene
derivative, resulting in high yields with excellent preservation of expression (DGE) signatures. Conclusion: We have shown that
affinity for its HER2 target, high in vivo stability and high tumor- 177
Lu-NNV003 can act synergistically with venetoclax or olaparib
to-background ratios. This study shows that [213Bi]DTPA-Nb is a in DLBCL and MCL cell lines. DGE analysis may identify gene
promising new radioconjugate for targeted α-particle therapy expression signatures predictive of synergy. If these findings can
and supports its further development. References: None. be translated to the clinic, it will allow identification of patients
that could benefit from the combination of these drugs.
References: None.
OP-139
177
Lu-NNV003 Shows Potential Synergy with Venetoclax or
Olaparib In Diffuse Large B-cell Lymphoma (DLBCL) and OP-140
Mantle Cell Lymphoma (MCL) Cell Lines 90
Y-NM600 improves survival in a clinically relevant
A. H. Repetto-Llamazares1, A. F. Maaland1,2, M. M. Malenge1,2, H. immunologically cold melanoma model when combined
Heyerdahl1, S. Patzke1,3, T. Stokke3, A. Hansen Ree2, A. Kolstad4, J. with immunotherapies
Dahle1; J. Grudzinski, R. Patel, R. Hernandez, R. Brown, L. Zangl, P. Carlson,
1
Nordic Nanovector ASA, Oslo, NORWAY, 2Institute of P. Sondel, J. Weichert, Z. Morris;
Clinical Medicine, University of Oslo, Oslo, NORWAY, University of Wisconsin, Madison, WI, UNITED STATES OF AMERICA.
3
Institute for Cancer Research, Oslo University Hospital,
Oslo, NORWAY, 4Department of Oncology, Oslo University
Hospital, Radiumhospitalet, Oslo, NORWAY. Aim/Introduction: We have previously shown that 1.85 MBq of
90
Y-NM600, calculated to deliver 2.5 Gy to the tumor, enhances
tumor response to external beam radiotherapy (XRT) and both
Aim/Introduction: The next generation anti-CD37 immune checkpoint inhibition and in situ vaccine at both
radioimmunoconjugate 177Lu-NNV003 (Humalutin®) has irradiated and distant unirradiated B78 melanoma tumors.
previously shown therapeutic activity in preclinical models of The aim of this study is to investigate whether 90Y-NM600
non-Hodgkin lymphoma by inducing DNA damage, antibody can enhance efficacy in a more clinically relevant melanoma
dependent cellular cytotoxicity and apoptosis in the targeted cancer model consisting of a primary, an occult secondary, and
cells. In this study we have combined 177Lu-NNV003 with micrometastases. Materials and Methods: Mice with both
an inhibitor of DNA damage repair, the poly(ADP-ribose) large primary (200 mm3) and occult secondary (non-palpable
polymerase (PARP) inhibitor olaparib, or the anti-apoptotic on day of treatment) B78 heterotopic melanoma tumors were
protein BCL-2 inhibitor venetoclax to test for potentially injected IV with B16 melanoma cells on the day of treatment to
synergistic interactions in treatment of DLBCL and MCL cell lines. create micrometastases. The primary tumor was subsequently
Materials and Methods: The effect of the combination of 177Lu- irradiated with 12 Gy of XRT, which is required to establish an
NNV003 with venetoclax or olaparib in DLBCL cell lines DOHH2, in-situ vaccine (IS), and the mice were injected IV with enough
S59 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

90
Y-NM600 (TRT) to deliver 2.5 Gy of absorbed tumor dose. On tail vein) radiolabeled antibodies for biodistribution. Mice were
Days 4, 7, and 10, mice were injected IP with anti-CTLA4 and administered either 450 kBq 211At-farletuzumab (n=16); or with
PD1 (ICI). Day 6 through Day 10, the primary tumors were a combination of 150 kBq 125I-trastuzumab and 450 kBq 211At-
injected intratumorally with IL2 + anti-GD2 mAb (IS). Mice were MX35 (n=12). At 1, 3, 10 and 22 h, mice were sacrificed and
monitored out to Day 60 for survival and tumor volume. Mice tumors and organs weighted and measured for radioactivity in
who were complete responders (CRs) were re-challenged with a gamma-well counter. Therapeutic efficacy was investigated
B78 cells on the flank at Day 90. Treatment groups consisted of on 63 mice sorted into four groups. All mice were inoculated
TRT, ICI, or IS alone, or in combination with each other. Reason i.p. with 2×106 NIH:OVCAR-3 cells in a single-cell suspension.
for death was assessed at Day 90. Results: All the mice within Specific or control (sham) treatments, all in 0.7 mL, were
the control, TRT, IS, and TRT + ICI groups were dead by Day 90. delivered i.p. twelve days after cell inoculation. A specific group
Eighty-percent of the control group succumb to metastases and (A; n=22) received 0.7 MBq 211At-Farletuzumab together with
20% succumb to the primary; while, 100% of the mice within trace amounts (10 kBq) of 125I-Rituximab. One control group
the TRT only and TRT + ICI groups died from the primary. ICI was (B; n=22) received 0.7 MBq irrelevant 211At-Rituximab. Another
the only monotherapy that had survivors with 20% of the mice control (C; n=11) received unlabelled farletuzumab; and one
still alive at Day 90. In the ICI alone group, 60% died from the group (D; n=8) received PBS only. Results: The biodistribution
primary and 20% died from the metastases. However, 60% of the of 211At-farletuzumab was similar to that with 125I as radiolabel,
mice who received TRT + IS and 50% of the mice who received and also to that of 211At-labeled MX35 antibody. The tumor-free
ICI + IS were still alive. Surprisingly, the mice who received TRT fraction (TFF) of the three control groups of mice (PBS, unlabeled
+ ICI + IS all survived. Of these mice that survived, 83% were farletuzumab, and irrelevant 211At-rituximab) was 12%, 9% and
tumor free and rejected a re-challenge of B78 cells. Conclusion: 14%, respectively. TFF after treatment with 211At-farletuzumab
Low dose 90Y-NM600 can improve response to both local (IS) was 91%. Conclusion: The current pre-clinical work-up of
and systemic (ICI) immunotherapy treatments in “cold” tumors intraperitoneal therapy with 211At-farletuzumab, delivered at
that normally do not respond to immune checkpoint blockade clinically relevant 211At-mAb radioactivity concentrations and
alone. References: None. specific activities, warrant further clinical testing. References:
None.

OP-141
Biodistribution and Therapeutic Efficacy of 211At-labelled 406
Farletuzumab in a Disseminated Ovarian Cancer Mouse
Model
Do.MoRe - Parallel Session: Image
S. Palm1, E. Aneheim1, T. Bäck1, A. Hallqvist1, R. Hultborn1, L.
Reconstruction
Jacobsson1, H. Jensen2, S. Lindegren1, P. Albertsson1;
1
University of Gothenburg, Gothenburg, SWEDEN, Sunday, October 13, 2019, 14:30 - 16:00 Lecture Hall 112
2
Rigshospitalet, Copenhagen, DENMARK.

Aim/Introduction: Alpha-emitter astatine-211 (t½ = 7.2h), OP-142


labelled to high-affinity monoclonal antibody MX35, has Quantitative and Clinical Evaluation of a Block-Sequential
previously shown promise as an adjuvant treatment of ovarian Regularized Expectation Maximization Reconstruction
cancer, where any remaining microscopic tumors are typically Algorithm for 18F-FDG PET-CT in Oncology
contained within the peritoneal lining. Here we explore the use E. Tragardh1, D. Minarik1, H. Almquist2, U. Bitzén2, S. Garpered1, E.
of farletuzumab, a mAb with a more complex antigen targeting Hvittfelt1, B. Olsson2, J. Oddstig2;
and release pattern. The rationale was to see if a mAb with a 1
Skåne University Hospital, Malmö, SWEDEN,
seemingly multi-compartmental binding characteristics could 2
Skåne University Hospital, Lund, SWEDEN.
be beneficial for our presumed clinical setting, where both
cancer single cells and micrometastases up to ~1 mm need to
be eradicated. The aim was to evaluate the biodistribution and Aim/Introduction: Block-sequential regularization expectation
therapeutic effect of 211At-farletuzumab in in-vitro and pre-clinical maximization (BSREM), commercially Q.Clear (GE Healthcare,
experiments and, using our models for radiation dosimetry, to Milwaukee, WI, USA) is a reconstruction algorithm that allows
translate the findings to expected results in the clinical setting. for a fully convergent iterative reconstruction leading to higher
Materials and Methods: Anti-human FOLR1 farletuzumab was image contrast compared to conventional reconstruction
labelled with 211At and used for biodistribution and therapeutic algorithms, while also limiting noise. The noise penalization
efficacy studies. Control groups included 211At-labelled MX35 factor β controls the trade-off between noise level and resolution.
and rituximab. For biodistribution, mice (n=28) were inoculated The aim was to evaluate the influence of different β values for
subcutaneously with 1×107 NIH:OVCAR-3 cells in 0.1 mL, in the different activity time products (ATs = administered activity x
scapula region. Four weeks thereafter, the longest axes of the acquisition time) in whole-body 18F-fluorodeoxyglucose (FDG)
tumors were 5-7 mm, and mice were i.v. injected (0.1 mL in the positron emission tomography with computed tomography
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S60

(PET-CT) regarding quantitative data, interpretation, and quality additional update step using a weighted difference of the image
assessment of the images. Materials and Methods: Twenty- from the most recent update step with that from the last one (3, 6).
five patients with known or suspected malignancies, referred We utilize a novel step weighting and compare its performance
for clinical 18F-FDG PET-CT examinations acquired on a silicon by experiments using both simulated and clinical data. In our
photomultiplier (SiPM) PET-CT scanner, were included. The simulated experiments we use realistic patient derived images
data were reconstructed using BSREM with β values of 100 over a wide range of counts. Results: In both simulated and
- 700 (increments of 100) and ATs of 4 - 16 MBq/kg*min/bed clinical experiments we show that our momentum modification,
(acquisition times of 1, 1.5, 2, 3, and 4 min/bed). One nuclear with some parameter tuning, improves convergence as much
medicine physician identified two lesions per patient with slight as a factor of 2, while all other algorithm and regularization
to moderate hypermetabolism. Noise level in the liver, lesion parameters are fixed. Other momentum approaches, such
SUVmax, and lesion SUVpeak were calculated for ATs of 4-16. Image as Nesterov’s momentum, perform well with small subset
quality and lesion detectability were assessed by four nuclear sizes but fail to improve convergence for larger subsets and
medicine physicians for ATs of 4 and 6. Results: The noise level lower count data. We show similar improved convergence
decreased with increasing β values and ATs. Lesion SUVmax varied with un-regularized reconstruction as well. Conclusion: This
considerably between different β values and ATs. The highest modification, with minimal additional computational overhead,
median lesion SUVmax was found with an AT of 4 and a β of 100 can improve the convergence rate of the BSREM PET algorithm
(6.7, interquartile range 2.7) and the lowest with an AT of 16 and as implemented by GE in Q.Clear, as well as the un-regularized
a β of 700 (2.6, interquartile range 1.3). SUVpeak were stable over version of this algorithm. However, the optimal momentum
the range of ATs and decreased less than SUVmax with increasing step-size and subset relaxation parameters are data dependent
β values. For an AT of 6 (in our case 1.5 min/bed), the best complicating use and need further research. References: 1.
image quality was obtained with a β of 600 and the best lesion Ahn S, Fessler JA. Globally convergent image reconstruction
detectability with a β of 500. AT of 4 generated poor-quality for emission tomography using relaxed ordered subsets
images and false positive uptakes due to noise. Conclusion: For algorithms. Medical Imaging, IEEE Transactions on. 2003;22:613-
oncologic whole-body 18F-FDG examinations on a SiPM-based 626.2. 2. Nuyts J, Beque D, Dupont P, Mortelmans L. A concave
PET-CT, we propose using an AT of 6 (i.e. 4 MBq/kg and 1.5 min/ prior penalizing relative differences for maximum-a-posteriori
bed) reconstructed with BSREM using a β value of 500 - 600 in reconstruction in emission tomography. IEEE Transactions on
order to ensure image quality and lesion detection rate as well nuclear science. 2002;49:56-60.3. 3. Lin Y, Schmidtlein CR, Li Q,
as a high patient throughput. We do not recommend using AT Li S, Xu Y. A Krasnoselskii-Mann algorithm with an improved EM
< 6 since the risk of false positive uptakes due to noise increases. preconditioner for PET image reconstruction. IEEE transactions
References: None. on medical imaging. 2019.4. 4. Ross S. Q. Clear. GE Healthcare,
White Paper. 2014:1-9.5. 5. Ahn S, Ross SG, Asma E, Miao J, Jin
X, Cheng L, Wollenweber SD, Manjeshwar RM. Quantitative
OP-143 comparison of OSEM and penalized likelihood image
Momentum acceleration of the block sequential reconstruction using relative difference penalties for clinical
regularized expectation maximization algorithm PET. Physics in Medicine & Biology. 2015;60:5733. 6. Nesterov
as applied to General Electric’s Q.Clear PET image Y: A method of solving a convex programming problem with
reconstruction algorithm convergence rate O (1/k2). in Soviet Mathematics Doklady 1983.
C. Schmidtlein1, J. Guo2,3, Y. Lin3, A. Krol4, S. Li5, S. Ahn6, C. Stearns7, pp. 372-376.
Y. Xu2;
1
Memorial Sloan Kettering Cancer Center, New York, NY, UNITED
STATES OF AMERICA, 2Old Dominion University, Norfolk, OP-144
VA, UNITED STATES OF AMERICA, 3Sun Yat-sen University, Systematic inaccuracies in the timing offset calibration
Guangzhou, CHINA, 4State University of New York Upstate may lead to large reconstructed transaxial asymmetries in
Medical University, Syracuse, NY, UNITED STATES OF AMERICA, the GE SIGNA PET/MR MP24
5
Guangdong University of Technology, Guangzhou, CHINA, 6GE G. Schramm, A. Rezaei, J. van Aalst, D. Van Weehaeghe, M. Koole, J.
Global Research, Niskayuna, NY, UNITED STATES OF AMERICA, Nuyts, K. Van Laere;
7
GE Healthcare, Milwaukee, WI, UNITED STATES OF AMERICA. KU/UZ Leuven, Department of Imaging and Pathology,
Division of Nucelar Medicine, Leuven, BELGIUM.

Aim/Introduction: Regularized PET image reconstruction


can produce high quality PET images but is computationally Aim/Introduction: Recently we showed that systematic
expensive, requiring substantial computing resources. This study inaccuracies in crystal timing offset calibration procedures
presents a momentum modification to the block sequential can lead to substantial transaxial asymmetries in PET images
regularized expectation maximization (BSREM) algorithm as reconstructed with TOF OSEM. Moreover, we proposed a data-
implemented by General Electric known as Q.Clear with the driven method to compensate for those inaccuracies [1]. In this
purpose of accelerating the convergence of this algorithm (1- retrospective analysis, we investigate to what extent PET image
5). Materials and Methods: Momentum is implemented as an quantification in our GE SIGNA PET/MR (software version MP24)
S61 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

was affected by inaccuracies in the timing offset calibration. the volume of the phantom. The phantom was imaged on
Materials and Methods: First, we retrospectively analyzed TOF a digital photon counting PET/CT (Philips Vereos). Ten runs of
OSEM PET reconstructions of 20cm homogeneous cylindrical five minute acquisitions were repeated with the brain 256 mm
phantom acquisitions from 15 different calibration periods field of view (FOV) and the whole body 576 mm FOV. Each
between Sep 2015 and Dec 2018. Transaxial asymmetries in the acquisition was reconstructed using listmode data with high
reconstructed images were calculated in different directions definition (HD) 2x2x2 mm voxel volumes / 288x288 matrix with
(horizontal, vertical and oblique) by evaluating the relative 3 iterations and subsets ranging from: 23, 21, 19, 17, 15, 13, 11,
difference between 6 sectors of 2D annulus ROIs with inner 9, 7 and 5. Point spread function (PSF) only, Gaussian only, a
and outer radius of 68mm and 82mm, respectively. Second, combination of both or no filters were enabled. Sixteen regions
we retrospectively analyzed TOF OSEM reconstructions of 7 of interests (ROIs) were placed in background regions as well as
static [18F]FDG brain data sets of healthy controls (2F/5M, age over the spheres. Results: The most accurate quantitative results
56±12 years), where uptake is supposed to be essentially left- regarding hot spheres were determined when no filters were
right symmetric, all acquired in one timing offset calibration set for all subsets. The combination of both PSF and Gaussian
period in Jan 2017. Left-right asymmetries of ROI mean values filters was slightly less accurate, but better than Gaussian alone
in pairs of homologous ROIs of the AAL2 atlas were calculated which gave an underestimation of activity concentrations.
in MNI space. Moreover, the analysis was repeated with TOF There was little difference between the 256mm brain FOV and
OSEM reconstructions of the same data sets with corrected the 576 mm whole body FOV when no filter was applied. For
timing offsets using the method of [1]. Results: In the phantom the brain FOV, the average recovery coefficients (RCs) of the
measurements, we observed transaxial asymmetries of more hot spheres were similar within reconstructions with different
than 5% in 9 out of 15 calibration periods. The asymmetries subsets, ranging from 1.08, 1.04 and 1.00 for the 11, 7 and 5
were predominantly in the horizontal (left-right) direction and subset reconstructions, respectively. For the whole body FOV
varied strongly between calibrations. The biggest asymmetries with no filter the RCs were similar, averaging 1.09, 1.08 and 1.01
were up to 10%. In the brain data sets, the regionally averaged for the 11, 7 and 5 subsets, respectively. With the background
left-right asymmetries of ROI means were (mean ± std. dev.): ROIs, all reconstruction settings showed similar accuracy.
(7.0±5.4)% frontal, (6.9±5.6)% parietal, (8.8±4.6)% temporal, Conclusion: Next-generation digital photon counting PET/CT
(7.1±4.5)% occipital, (3±5.3)% cerebellum. After the data- allows for high definition imaging of the brain with accurate and
driven correction of the timing offset inaccuracies, those values robust quantification. Phantom analysis showed that excellent
decreased to: (1.5±4.0)% frontal, (-0.7±4.5)% parietal, (-0.2±5.3)% image quality can be achieved using both brain and whole
temporal, (-1.4±2.3)% occipital,(-2.2±5.3)% cerebellum. After an body field of view by adjusting reconstruction settings, such
update to software version MP26 in Jan 2019, the inaccuracies as the number of subsets per iteration. Quantitative accuracy
in the crystal timing offset calibration procedures were is maintained over the range of reconstruction settings, due
strongly reduced which was verified by an additional phantom in part to the quality of counts in the PET data resulting from
measurement. Conclusion: Inaccuracies in the timing offset digital photon counting. References: None.
calibration of the GE SIGNA PET/MR (MP 24) lead to substantial
time varying transaxial left-right asymmetries of up to 10%
in TOF OSEM reconstructions which can be corrected for by OP-146
applying the method of [1]. References: [1] Rezaei et al., “Data Clinical impact of Spatially Variant Positron Range
driven time alignment for TOF-PET”, 2017 IEEE Nuclear Science Correction for 68Ga-DOTATATE and 68Ga-PSMA PET/CT
Symposium and Medical Imaging Conference (NSS/MIC) A. Berger1, J. Cal-Gonzalez1, S. Rasul2, M. Hacker2, M. Grahovac2, R.
A Latiff3, G. Schembri4, I. Rausch1, T. Beyer1, P. Kench3;
1
QIMP Team, Center for Medical Physics and Biomedical
OP-145 Engineering, Medical University of Vienna, Vienna, AUSTRIA,
Quantitative Optimization of High Definition Neurologic 2
Division of Nuclear Medicine, Department of Biomedical Imaging
Imaging for Digital PET/CT and Image-guided Therapy, Medical University of Vienna, Vienna,
K. Binzel, A. Adelaja, J. Zhang, M. V. Knopp; AUSTRIA, 3Discipline of Medical Radiation Science and Brain
The Ohio State University Wexner Medical Center, and Mind Centre, Faculty of Health Sciences, The University of
Columbus, OH, UNITED STATES OF AMERICA. Sydney, NSW, AUSTRALIA, 4Department of Nuclear Medicine,
Royal North Shore Hospital, St Leonards, NSW, AUSTRALIA.

Aim/Introduction: To assess the accuracy of high definition


image reconstruction methodologies provided by digital Aim/Introduction: To evaluate the clinical impact of spatially
photon counting PET (dPET) for neurologic imaging applications. variant positron range correction (PRC) for 68Ga-DOTATATE and
Materials and Methods: A Hoffman brain phantom was filled 68
Ga-PSMA PET/CT. Materials and Methods: Five patients with
with 31 MBq 18F in the background volume and four spheres neuroendocrine tumor and 10 with prostate cancer underwent
with volumes ranging from 2ml to .125 ml were filled with 235.0 68
Ga-DOTATATE and 68GA-PSMA PET/CT examinations on a
kBq, 98.4 kBq, 47.0 kBq and 18.5 kBq of 18F as well as two spheres Siemens Biograph mCT system, respectively. The PET data was
filled with distilled water. The spheres were placed throughout reconstructed using standard clinical settings. In addition, a
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S62

post-reconstruction, tissue dependent PRC was performed has Ra-223 as a daughter and knowing the distribution of the
of all data-sets. A direct comparison of the PRC and non-PRC daughter can be important for accurate dosimetry. Materials
images was performed by two nuclear medicine specialists and Methods: We have developed a framework for comparing
independently. The image quality was classified on a 4-point the potential energy windows and collimators in terms of
scale considering noise, contrast, and spatial resolution. Absolute a signal-to-noise ratio criterion that considers unscattered
changes in scores of 1 and 2 points was classified as mild to photons passing through the collimator holes as the signal. The
moderate and high change, respectively. SUVmax of up to 3 quantum noise resulting from photons scattered in the body
noticeable lesions and SUVmean of the liver was measured for PRC and those penetrating through the septa, scattering in the
and non-PRC images. Results: PRC improvements in contrast septa, or backscattering in the compartment behind the crystal
were rated by reviewer1 / reviewer 2 as mild to moderate in is considered noise. Using this, we have selected the acquisition
73% / 87% of the patients. Improvements in spatial resolution energy windows and collimators for these radionuclides.
were denoted as mild to moderate in 60% / 80% and as high in We have also developed a general framework for modeling
27% / 13% of the patients. PRC-induced degradation of noise the image formation process of multiple radionuclides into
properties were denoted as mild to moderate in 53% / 60% and multiple energy windows and incorporated this into an iterative
as high in 13% / 27% of the patients. The PRC-induced change reconstruction code for estimating the activity distribution
of SUV (max) of all detected lesions was denoted by reviewer1 of one or more radionuclides. We have performed phantom
/ reviewer 2 as 35.8%±18.5% / 32.6%±19.7% and of SUV (mean) studies demonstrating the feasibility of quantitative SPECT
of liver as 1.0%±0.1% / 11.25%±7.8%. Note each reviewer may reconstruction of the activity distributions of radionuclides
have selected different lesions for analysis. After PRC mild to used in alpha therapy. This includes Pb-212, Ra-223, Th-227, and
moderate degradation in overall image quality was denoted in Ac-225. We have performed physical phantom experiments
20% / 86%, no change was denoted in 27% / 7% and mild to using simple geometries and Monte Carlo simulations of
moderate improvement of overall image quality was denoted anthropomorphic phantoms to evaluate the accuracy of this
in 53% / 7% of the patients. Conclusion: Images corrected method. Results: For Pb-212, the presences of a high energy
with PRC revealed in all reviewed cases a detectable change photon from Tl-208 results in substantial septal penetration
in the image quality. PRC can improve contrast and spatial and scatter and backscatter. While an HEGP collimator provided
resolution in 68Ga-DOTATATE and 68Ga-PSMA PET/CT. However, a higher signal-to-noise ratio, an MEGP collimator provided
how these changes are perceived are highly reader dependent. acceptable images. For Pb-212, Th-227, and Ra-223, we obtained
As expected, the deconvolution used in the PRC induces noise, accuracies of better than 10% in physical phantoms for spheres
leading to a mild to moderate degradation of the subjective ~5 cm in diameter. For Th-227 we obtained accuracies of better
scoring of overall image quality for one of the readers. Image than 10% for simultaneously estimating the activities of Ra-223
quality may be improved by different filtering/reconstruction and Th-227. For Ra-223, simulation studies indicate accuracies
of the PRC data. Acknowledgements: The financial support of on the order of 10% for organs. Conclusion: The results of this
Siemens Healthineers is gratefully acknowledged. References: work demonstrates the . References: None.
None.

OP-148
OP-147 Artefacts reduction in cardiac SPECT images by using a
Feasibility of Quantitative SPECT of Radionuclides used in novel reconstruction algorithm Maximum a Posteriori with
Targeted Alpha Therapy local regularization
M. Ghaly1,2, B. He2, Y. Du1, G. Sgouros1,2, E. C. Frey1,2; N. Denisova1, A. Ansheles2, V. Sergienko2, H. Kertész3, T. Beyer3, I.
1
Johns Hopkins University, Baltimore, MD, UNITED STATES OF Kolinko1,4;
AMERICA, 2Radiopharmaceutical Imaging and Dosimetry 1
Institute of Theoretical and Applied Mechanics, Novosibirsk,
(Rapid), LLC, Baltimore, MD, UNITED STATES OF AMERICA. RUSSIAN FEDERATION, 2National Medical Research Center
of Cardiology, Moscow, RUSSIAN FEDERATION, 3Medical
University of Vienna, Vienna, AUSTRIA, 4Novosibirsk State
Aim/Introduction: There is a great deal of current interest University, Novosibirsk, RUSSIAN FEDERATION.
in and high potential for radiopharmaceutical therapy using
alpha emitters. The most commonly used parent radionuclides
are Ra-223, Th-227, Ac-225, and Pb-212. Accurate dosimetry Aim/Introduction: Clinical methods are limited in studying
is important for these therapies in the regulatory process, for the causes of artefacts associated with mathematical aspects of
rational dose escalation and optimal therapy. Accurate dosimetry reconstruction algorithms and methods. In this work, a novel
requires a knowledge of the activity distribution. However, Maximum a Posteriori (MAP) reconstruction algorithm with
quantitative imaging of these radionuclides is challenging. local regularization is developed to increase the resolution
They all have multiple daughters and complex decay schemes and to improve the quality of reconstructed images. The aim
with overlapping x-ray and gamma emissions. For Pb-212, of this work is to evaluate the proposed algorithm in artefacts
there is a high abundance 2.6 MeV photon emitted by Tl-208 reduction in cardiac SPECT imaging. Materials and Methods:
that easily penetrates even high-energy collimators. Th-227 Joint clinical and simulation studies are performed. A special
S63 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

mathematical model of torso (MMT) was designed which plays (μ reduced by 15%) was introduced in order to understand the
the role of virtual patient and models spatial distribution of error propagation in terms of distance to the incorrect μ values.
99mTc-MIBI in thoracic organs. The MMT is easy transformed For the thorax phantom, both lungs were assigned μ values
to study patients with various constitutions and different 15% lower than the true values. TOF MLEM reconstructions
myocardial left ventricle (LV) forms. MMT was sampled on were performed over the range of TOF resolution values
grids 128*128*128 and 64*64*64. Computer simulations of using STIR, iterating until close to convergence. The influence
the SPECT/CT myocardial perfusion imaging (MPI) procedure of TOF resolution on the propagated errors was then studied
were performed. Projection (raw) data were calculated for 32 for regions drawn inside or outside the region of incorrect
and 64 angular views over an arc extending from the right μ values (lung versus heart). Results: For the cylinder, with
anterior oblique to the left posterior oblique in accordance low TOF resolution the errors are dominated by local effects;
with acquisition protocol of MPI SPECT. Standard OSEM and a however, as TOF resolution improves, the local error decreases
novel MAP reconstruction algorithm with local regularization linearly but the error in more distant parts of the image increase
were applied for images reconstruction. Two types of artefacts significantly (e.g. by a factor of 10 at 100ps compared to 400ps
were studied: false apical defects and artefacts of extra-cardiac at 2.1cm off-centre). The same trend is verified in the XCAT
activity. The simulation results were verified by comparing to the simulation. The errors within the lung decrease with improved
clinical data. Clinical MPI studies were performed in the National TOF resolution (from 13.11% to 4.63%), whereas bias in the left
Medical Research Center of Cardiology (Moscow) by using the ventricle increased by a factor of 3.2 at 70ps compared to 600ps
Philips Bright View XCT SPECT/CT hybrid system with low- (from 0.67% to 2.15%). Conclusion: Superior TOF resolution aids
energy high-resolution (LEHR) collimator. Results: The results of quantification in regions where the attenuation is not accurately
simulations have shown that the cause of false apical defects is known (e.g. effect of density changes in the lungs induced by
not associated with attenuation correction, as it was discussed motion). However, this is accompanied by significant increase
in some clinical studies, but it is related to the LV form and to in bias in areas remote from the incorrect attenuation. Future
the limitations of the standard OSEM reconstruction algorithm. improvement of TOF resolution could result in unforeseen bias
Severity of false apical defects was decreased by 10-15% using in PET quantification. References: [1] A. Mehranian and H. Zaidi,
the proposed MAP algorithm. It is shown that extra-cardiac 10.2967/jnumed.114.148817
activity artifacts are reduced by using the MAP algorithm with
local regularization. Conclusion: Joint clinical and simulation
studies in nuclear cardiology may be considered as a first- 407
line approach in analyzing sources of possible artifacts and
pitfalls. The proposed MAP algorithm with local regularization
Teaching Session 1 - Interactive Clinical
has shown as a promising approach to improve resolution of
Cases - Paediatrics + Thyroid + Translational
reconstructed images and to reduce artefacts in cardiac SPECT
and Molecular Imaging Therapy Committee:
images. References: None.
Management of Thyroid Cancer in Children

Sunday, October 13, 2019, 14:30 - 16:00 Lecture Hall 113


OP-149
Dependence Of Error Propagation Due To An Incorrect
Attenuation Map On PET Time-of-Flight Resolution OP-150
E. C. Emond1, A. Bousse2, A. M. Groves1, B. F. Hutton1, K. Paediatric DTC Management
Thielemans1; A. Piccardo;
1
University College London, London, UNITED KINGDOM, E.O. Ospedali Galliera, Dapartment of
2
Université de Bretagne Occidentale, Brest, FRANCE. Nuclear Medicine, Genoa, ITALY.

Aim/Introduction: In recent years, PET time-of-flight (TOF)


scanners have become available with improved timing OP-151
resolution, with many groups aiming towards a TOF FWHM of Molecular Imaging in Paediatric DTC
100ps or below. For TOF, in addition to the increase in SNR, it F. Van Leeuwen;
has been observed that the impact of inaccurate attenuation Leiden University Medical Center, Interventional Molecular
maps is reduced [1]. However, it is unclear whether a local Imaging Laboratory, Leiderdorp, NETHERLANDS.
error in attenuation values causes errors in distant parts of the
reconstructed image. The aim of this work is to investigate
the impact of incorrect attenuation (μ) maps in PET systems OP-152
with improved time resolution. Materials and Methods: Radioiodine Dosimetry and Therapy in Paediatric DTC
Simulations were performed for a uniform cylinder and XCAT Patients
phantom based on the geometry of the GE 690 discovery, M. Luster;
but with TOF resolution varying from 70ps to 1000ps. For the University of Marburg, Department of Nuclear
cylinder, a 12-mm diameter central area of incorrect attenuation Medicine, Marburg, GERMANY.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S64

408 T3 tumors, the best model had a mean AUC of 0.69±0.14 (COV
Clinical Oncology - Rapid Fire Session: New 20.5%) and a weighted accuracy of 0.65±0.10. Scores from
Tracers and Machine Learning 41%max delineation were higher than those of 50%peak,
but absolute differences in model performance were small.
Sunday, October 13, 2019, 14:30 - 16:00 Conclusion: Machine learning models using [18F]PSMA PET-
Lecture Hall 114
CT primary prostate tumor radiomics are robust and highly
accurate in predicting presence of metastatic disease. A lower
OP-153 classification accuracy was observed for post-surgery Gleason
Radiomics from [18F]PSMA PET-CT with machine learning score and tumor stage, indicating that the biological basis of
as a novel biomarker in primary prostate cancer radiomics features could be partly independent from these
M. Cysouw1, B. H. Jansen1, K. C. van der Zande1, B. M. de Vries1, R. histopathological tumor characteristics. The additive value of
J. van Moorselaar2, A. N. Vis2, O. S. Hoekstra1, T. van de Brug3, D. E. these radiomics features to clinical nomograms merits further
Oprea-Lager1, R. Boellaard1; investigation. References: None.
1
Amsterdam UMC, Vrije Universiteit Amsterdam, dept. of
Radiology and Nuclear Medicine, Amsterdam, NETHERLANDS,
2
Amsterdam UMC, Vrije Universiteit Amsterdam, dept. OP-154
of Urology, Amsterdam, NETHERLANDS, 3Amsterdam Comparison Of Ga-68 PSMA PET/MRI With Textural
UMC, Vrije Universiteit Amsterdam, dept. of Epidemiology Analysis Data In Transitional Zone Prostate Tumors:
and Biostatistics, Amsterdam, NETHERLANDS. Preliminary Results Of An On-Going Study
L. L. Uslu1, S. Tuncer2, B. Bakır2, S. Ozel Yildiz3, C. Demirdag4, E.
Güner5, S. Sager1, H. B. Sayman1, K. Sonmezoglu1;
Aim/Introduction: In primary prostate cancer (Pca) patients, 1
Istanbul University-Cerrahpasa, Cerrahpasa Medical
accurate staging and risk stratification is crucial to guide Faculty, Department of Nuclear Medicine, Istanbul, TURKEY,
treatment and optimize patient outcomes. Visual assessment 2
Istanbul University, Istanbul Medical Faculty, Department
of [18F]PSMA PET-CT has been demonstrated not to be suitable of Radiology, Istanbul, TURKEY, 3Istanbul University, Istanbul
for these purposes. However, high-throughput extraction of Medical Faculty, Department of Biostatistics, Istanbul, TURKEY,
quantitative features from these [18F]PSMA PET-CT images could 4
Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty,
improve sensitivity for metastatic deposits or yield additional Department of Urology, Istanbul, TURKEY, 5Health Sciences
data on unfavorable tumor characteristics. The aim of this University, Bakırköy Sadi Konuk Training and Research
study was to investigate the potential of [18F]PSMA PET-CT Hospital, Department of Urology, Istanbul, TURKEY.
radiomics and machine learning models as novel biomarkers
in primary Pca. Materials and Methods: 61 patients with
biopsy-proven Pca underwent whole body [18F]DCFPyL Aim/Introduction: Multiparametric prostate MRI (mp-MRI) is
(PSMA) PET-CT at 120min post-injection before planned radical an effective imaging modality for detection of primary prostate
prostatectomy with extended pelvic lymph node dissection. lesions. MRI textural analysis was introduced to improve the
Primary tumors were delineated using both a 50%peak and detection of primary prostate lesions, especially in the transitional
41%max background-adapted thresholds. Per primary tumor zone of the gland. Ga-68 PSMA PET on the other hand was
we extracted 480 radiomics features on morphology, intensity, shown to be superior to mp-MRI in detection of primary prostate
and grey-level co-occurrence. Random Forest, Support Vector lesions. The aim of our study is to compare textural analysis
Machine, Neural Network, and Logistic Regression with method and Ga-68 PSMA PET/MRI in transitional zone tumors.
optimized hyperparameters were combined with several data Materials and Methods: Data obtained from 21 patients who
normalization, feature selection, and (training) data balancing underwent hybrid Ga-68 PSMA PET/MRI for prostate cancer
methods. We assessed whether the models could discriminate between August 2017 and January 2019 for the on-going
between i) ≤7 vs >7 post-surgery Gleason score, ii) pathological prospective clinical study were retrospectively analyzed. All
T2 vs. T3 tumors, and iii) absence or presence of pathology- patients had radical prostatectomy operation following imaging.
proven lymph node and/or distant metastases. The models Sixty-two textural analysis were deduced from each manually
were trained and tested in a 10 times repeated 4-fold cross- contoured whole transitional zone on axial T2-weighted (T2W),
validation, each fold yielding test scores from unseen data. diffusion-weighted images (DWI) (b value=1400s/m2) and
Model performance was assessed using the mean receiver- apparent diffusion coeffient (ADC) map which was obtained
operator-curve integral (AUC) and mean weighted accuracy. from b value=0-50-800 s/mm2. Textural features of transitional
Model stability was assessed using the coefficient-of-variation zone were compared to PSMA expression on the corresponding
(COV%). Results: The highest performance was observed for PET images. T-test and Mann-Whitney U test were used for
prediction of presence of pathology-proven metastatic disease, comparison of textural features of transitional zone on three
with a mean AUC of 0.98±0.03 (COV 3.4%) and a weighted different sequences. Results: Twenty-one patients had mean
accuracy of 0.93±0.06. For discrimination between high vs. low 13.74 ng/ml (range=4.1-41) PSA value. Among 21 men, 9
Gleason score, the best model had a mean AUC of 0.83±0.12 patients had positive tumoral PSMA uptake on transitional zone
(COV 14.6%) and a weighted accuracy of 0.84±0.09. For T2 vs. whereas 12 patients had no PSMA uptake on the transitional
S65 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

zone. One patient had no DWI on b value=1400 s/m2 among classification of GS by groups (≤7, 8, ≥9). The average accuracy,
12 patients. Nine patients who had PSMA uptake on transitional specificities and sensitivities of the best classifiers on the
zone had statistically significantly higher mean signal intensity validation data is reported. Results: 130 patients were included
on DWI textural analysis compared to PSMA negative group in the analysis. 64% (83) of the patients exhibited a GS of 7, 21%
(p=0.024). There is no difference between skewness, kurtosis (27) a GS of 8 and 15% (20) a GS of 9. Slightly better results were
and standart deviation values on three different sequences on obtained with SMOTE oversampling compared to random and
transitional zone among PSMA positive and negative groups. no oversampling. The 10-fold averaged classification accuracy
Conclusion: Although T2W imaging is the dominant MRI of PET-MR radiomics (77%) as well as sensitivities (GS≤7: 78%,
sequence to evaluate transitional zone tumors, we could not GS=8: 83%, GS≥9: 80%) and specificities (GS≤7: 82%, GS=8:
find a significant difference in textural analysis parameters using 83%, GS≥9: 96%) were superior to PET-only radiomics (acc.:
T2W sequence. DWI (b=1400 s/m2) signal intensity on the other 73%; sens.: 83%, 50%, 60%; spec.: 73%, 87%, 92%) and T2-only
hand was shown to detect transitional zone tumors similar to radiomics (acc.: 67%; sens.: 89%, 33%, 40%; spec.: 69%, 86%,
Ga-68 PSMA PET/MRI. Therefore, combined usage of textural 79%). Conclusion: The strongly imbalanced dataset justifies
analysis with dominant T2W MRI sequence and Ga-68 PSMA the necessity of balancing strategies in training the model. The
PET/MRI may add up to each other to increase the diagnostic combined information gathered from PET and MR radiomic
accuracy in transitional zone tumors. References: 1. Bates A, et features improved performance compared to PET-only and
al. Eur Radiol. 2017;27:5290-8. 2. Patel N, et al. Clin Radiol. 2018, MR-only. Further analyses including a larger and more balanced
https://doi.org/10.1016/j.crad.2018.11.007; 3. Wang Y et al. Magn patient cohort and advanced radiomics are warranted. (This
Reson Imaging. 2019;60:76-84. project is funded by the European Union’s Horizon 2020 research
and innovation programme under the Marie Sklodowska-Curie
grant agreement No 764458) References: None.
OP-155
Preliminary evaluation of PSMA PET/MR radiomics for
primary staging in patients with prostate cancer OP-156
E. Solari1, A. Gafita2, B. Laurent3, T. Amiel4, R. Tauber4, D. Visvikis3, W. Machine Learning to Detect Prostate Cancer Recurrence
Weber2, M. Eiber2, M. Hatt3, S. G. Nekolla1; using 18F-Fluciclovine PET
1
Department of Nuclear Medicine, Klinikum rechts der Isar, G. A. Davidzon1, J. Lee2, H. Yang3, H. Song1, C. Harrison1, A. Iagaru1;
München, GERMANY, 2Department of Nuclear Medicine, 1
Stanford University, Stanford, CA, UNITED STATES OF
School of Medicine, Technical University Munich, München, AMERICA, 2Asan Medical Center University of Ulsan College
GERMANY, 3LaTIM, INSERM, UMR 1101, Univ. Brest, Brest, of Medicine, Seoul, KOREA, REPUBLIC OF, 3Dimensional
FRANCE, 4Department of Urology, School of Medicine, Mechanics, Seattle, WA, UNITED STATES OF AMERICA.
Technical University Munich, München, GERMANY.

Aim/Introduction: Development of machine learning


Aim/Introduction: Magnetic resonance imaging (MRI) (ML) classifiers for cancer detection in medical images has
radiomics have shown promising results in prostate cancer shown promise. Recent work using convolutional neural
(PC) staging. Prostate specific-membrane antigen (PSMA)- networks (CNN) has focused on the classification of positron
targeted PET/MR imaging showed enhanced accuracy in PC emission tomography (PET) using 18F-fluorodeoxyglucose
lesion detection compared to conventional imaging. Therefore, (FDG). 18F-Fluciclovine is a relatively newly FDA-approved
in the present analysis we aimed to evaluate the potential of radiopharmaceutical indicated when prostate cancer (PC)
applying handcrafted PSMA PET-MR radiomics for PC staging. biochemical recurrence (BCR) is suspected based on elevated
Materials and Methods: Patients with PC who underwent prostate specific antigen (PSA) levels following prior treatment.
PSMA PET/MR in a primary staging setting were included We evaluated the performance of a 3D-CNN to detect BCR PC
in the analysis. Histopathologic results (Gleason score (GS)) using 18F-Fluciclovine PET scans. Materials and Methods: 179
obtained during radical prostatectomy were collected. The consecutive 18F-Fluciclovine PET/CT scans were performed at
entire prostate organ was segmented in PET and T2 MR images. Stanford University between Dec 2017 and Feb 2019 in 163 PC
For PET, a semi-automatic FLAB segmentation (LaTIM, Brest) patients who had prior treatments and suspected recurrence.
was used, whereas a manual segmentation was carried out Patients’ age and serum PSA level at the time of PET were 71.8
on the MR images. Image biomarker standardization initiative +/- 9.1 years and 35.2 +/- 225.3 (range 0.05-2975.0 ng/mL). To
(IBSI)-compliant handcrafted features were extracted from augment the model’s accuracy and reduce computational
both PET and MR images. The cohort was split into training expense, the pelvis, which is the region most commonly affected
and validation using stratified K-fold cross-validation with 10 by early recurrence and metastases was included. Studies were
folds. The benefit of performing imbalance correction (random classified as normal (N), abnormal (A), and indeterminate (I) based
oversampling, SMOTE) was evaluated. Principal component on the clinical reports. N-scans were those with the expected
analysis (PCA) was performed for dimensionality reduction biodistribution of 18F-Fluciclovine and A-scans included those
(2 to 20 components). A radial-basis support vector machine with focal radiopharmaceutical uptake in the prostate gland or
(SVM) model with hyperparameter tuning was trained for the bed, in lymph nodes and/or the skeleton. A training set of 150
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S66

cases (A=106, N=38, and I=6) and a test set of 29 cases (A=24, standard showed a higher sensitivity of [68Ga]Ga-NODAGA-
N=4, and I=1) were randomly allocated. ResNet 3D model exendin-4 PET (100% (CI 60-100%)) than [18F]F-DOPA PET (57%
with 14 layers was built to classify the data into 3 classes. The (CI 18-90%)). SUVmax ratios between visually identified focal
model’s performance was calculated on a test set to assess for lesions and the area in the pancreas with the next highest tracer
sensitivity, specificity, and AUC by ROC curve analysis. Results: uptake are higher in GLP-1R PET than [18F]F-DOPA PET (1.83 ±
Sensitivity and specificity to determine the abnormality for the 0.75 and 1.47 ± 0.43 respectively). Conclusion: In this study we
test set were 91.7% and 75.0% in the ROC analysis (criterion of provide the first evidence of the possibility of diagnosis and
0.701) and area under the curve (AUC) was 0.896 (p<0.001). localization of focal CHI using [68Ga]Ga-NODAGA-exendin-4 PET.
Conclusion: 3D-CNN architecture showed good performance These first results show a better sensitivity and image quality of
for detection of BCR PC using 18F-Fluciclovine PET. Further work [68Ga]Ga-NODAGA-exendin-4 PET compared to [18F]F-DOPA PET,
is warranted to confirm results in larger and prospective cohorts demonstrating the potential of [68Ga]Ga-NODAGA-exendin-4
of patients. References: None. PET as a novel diagnostic tool for focal CHI. References: None.

OP-157 OP-158
68
Ga-NODAGA-exendin-4 PET/CT for the diagnosis and [68Ga]Ga-NODAGA-exendin-4 PET/CT for the localization of
localization of focal congenital hyperinsulinism insulinomas
M. Boss1, P. Shah2, W. Brenner3, O. Blankenstein3, C. Rottenburger4, M. Boss1, K. Mikkola2, M. Brom1, A. Eek1, M. Buitinga1, O. Eriksson3,
M. Brom1, A. Eek1, M. Buitinga1, M. Gotthardt1; D. Wild4, V. Prasad5, A. Brouwers6, F. Pattou7, H. Hofland8, P. Nuutila2,
1
Radboudumc, Nijmegen, NETHERLANDS, 2Great M. Gottthardt1;
Ormond Street Hospital, London, UNITED KINGDOM, 1
Radboudumc, Nijmegen, NETHERLANDS, 2University of Turku,
3
Charite University Hospital, Berlin, GERMANY, Turku, FINLAND, 3Uppsala University, Uppsala, SWEDEN, 4University
4
University of Basel Hospital, Basel, SWITZERLAND. Basel Hospital, Basel, SWITZERLAND, 5Charite University Hospital
of Berlin, Berlin, GERMANY, 6University Medical Center Groningen,
Groningen, NETHERLANDS, 7University Hospital Lille, Lille,
Aim/Introduction: Congenital hyperinsulinism (CHI) is the FRANCE, 8Erasmus Medical Center, Rotterdam, NETHERLANDS.
most common cause of persistent and recurrent hypoglycemia
in neonates. The focal subform of CHI, is caused by focal islet
cell hyperplasia. In contrast to the diffuse subform of CHI, it can Aim/Introduction: Insulinomas are usually small, single, benign
be cured with partial pancreatectomy or limited lesionectomy. pancreatic neuroendocrine tumors. Precise preoperative
For this, it is crucial to diagnose focal CHI and precisely localize localization of these tumors is essential for successful surgical
the lesion. With [18F]F-DOPA PET, the current standard technique treatment. The current standard imaging techniques CT, MRI
for non-invasive detection of focal CHI, about 15% of focal and somatostatin receptor (SSTR) PET have limited sensitivity.
lesions are missed. The stable glucagon-like peptide-1 analogue The stable glucagon like peptide-1 (GLP-1) analog exendin
exendin-4 specifically binds the glucagon-like peptide 1 specifically binds to the GLP-1 receptor (GLP-1R), which
receptor on pancreatic beta cells. 68Ga-labeled exendin has is markedly overexpressed in most insulinomas. [68Ga]Ga-
already been shown to detect insulinomas with high sensitivity. DOTA-exendin-4 PET/CT has been shown to be feasible for
In this multicenter trial we included prospective as well as detection of insulinomas with a higher sensitivity than MRI.
retrospective data of patients with CHI who underwent both Replacing the chelator DOTA by NODAGA in the labeling
[18F]F-DOPA PET and [68Ga]Ga-NODAGA-exendin-4 PET to process ensures higher specific activities, allowing imaging
compare the effectiveness of these two imaging techniques with sub-pharmacological peptide doses. We have performed a
for the diagnosis and localization of focal CHI. Materials and prospective multicenter imaging study in which we compared
Methods: We analyzed data of 14 CHI patients with a median the effectiveness of [68Ga]Ga-NODAGA-exendin-4 with all
age of 5 (2.2-9.4) months. All patients underwent [18F]F-DOPA current standard non-invasive imaging procedures for the
PET (according to standard procedure of each institute) and localization of insulinomas. Materials and Methods: 42 adults
[68Ga]Ga-NODAGA-exendin-4 PET with a median time of 4 (3 - 8) aged 24-62 with biochemically proven hyperinsulinemic
days between the procedures. For [68Ga]Ga-NODAGA-exendin-4 hypoglycemia were included. PET/CT images were obtained
PET, 1 hour dynamic acquisitions started at the time of injection, one and two hours after injection of 95-105 MBq 68Ga-NODAGA-
or 10 minute static acquisitions started 45 minutes post injection exendin-4 (5-7 µg). Current standard imaging, consisting of CT
were obtained after injection of 1.6 MBq/kg [68Ga]Ga-NODAGA- or MRI and SSTR PET, was performed within 8 weeks of 68Ga-
exendin-4 with a lower limit of 20 MBq (maximally 0.12 µg/kg). NODAGA-exendin-PET in all patients. A patient-based analysis
Quantitative analysis of all positive [18F]F-DOPA PET and GLP- was performed with histopathology as a reference standard.
1R PET/CT scans was performed by a non-blinded observer. Results: Suspicious lesions were identified in 33 patients. 31 of
Results: Suspicious lesions were detected in 7 patients. These these patients underwent surgery after which presence of an
patients underwent surgery and presence of a focal lesion was insulinoma was confirmed histopathologically. Plasma glucose
confirmed by histopathology in all these patients. Patients were values normalized after the procedure in all these patients
cured after surgery. Analysis using histopathology as a reference without further hypoglycemic episodes. Analysis showed that
S67 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

[68Ga]Ga-NODAGA-exendin-4 PET localized insulinomas with a a diagnostic CT of the chest, abdomen and pelvis, a whole-
higher accuracy and sensitivity (90.6% and 93.5% respectively) body [89Zr]Zr-DFO-girentuximab PET (37 MBq, 4 days p.i.), and
than conventional imaging (78.1% and 80.6% respectively) a whole-body [18F]FDG-PET according to EARL guidelines. The
and SSTR PET (59.4% and 61.3% respectively). In 12.5% of [89Zr]Zr-imaging procedures were harmonized. Scans were
patients, a correct diagnosis and decision to perform surgery independently reviewed and lesions of ≥10 mm and lymph
was only reached after [68Ga]Ga-NODAGA-exendin-4 PET. This nodes of ≥15 mm on CT were analyzed. For lesions with [89Zr]
novel technique therefore significantly influenced the clinical Zr-DFO-girentuximab or [18F]FDG-uptake visually exceeding
management of the patients in this population. The median size background, maximum standardized uptake values (SUVmax)
of the lesions identified by GLP-1R PET was 12 (10 - 18) mm, were measured. Results: In total 449 lesions were detected
including 5 lesions smaller than 10 mm, showing the excellent by ≥1 modality (median 7 per patient; inter quartile range
sensitivity of the technique. The lower peptide dose used in 4.25-12.75) of which 42% in lung, 22% in lymph nodes and
this study compared to previous studies with [68Ga]Ga-DOTA- 10% in bone. Combined [89Zr]Zr-DFO-girentuximab-PET and
exendin-4 (4-7 µg vs. 12-24 µg) resulted in fewer occurrences CT detected most lesions (91%, 95%CI:87-94) compared to CT
of nausea (5% vs. 27% of patients). Conclusion: This study alone (56%, 95%CI:50-62, p=0∙001) and combined CT and [18F]
demonstrates the superior performance of [68Ga]Ga-NODAGA- FDG-PET (84%, 95%CI:79-88, p<0∙005). Overall, the median
exendin-4 PET/CT compared to current standard imaging number of two involved organs per patient as determined by
modalities for pre-operative localization of benign insulinomas. CT alone increased to three per patient with the addition of
Because of its high sensitivity and excellent imaging quality, either [89Zr]Zr-DFO-girentuximab and [18F]FDG-PET (range: 1-7;
[68Ga]Ga-NODAGA-exendin-4 PET/CT could have the potential p<0.005), without adjusting for 9 lesions outside of the CT field-
to become the primary diagnostic imaging modality in patients of-view. The increase in the number of lesions was mainly due
with hyperinsulinemic hypoglycemia. References: None. to a better detection of bone and soft tissue lesions by PET
compared to CT alone. The [89Zr]Zr-DFO-girentuximab SUVmax
in metastatic lesions varied greatly (range, 3.8 to 230.8), and
OP-159 was highest in adrenal gland and metastatic kidney lesions
Lesion detection by [89Zr]Zr-DFO-girentuximab and [18F] and lowest in lung lesions (median SUVmax 69.9 and 61.1 vs.
FDG-PET in patients with newly diagnosed metastatic 9.4, respectively). Conclusion: In newly diagnosed good and
renal cell carcinoma intermediate prognosis metastatic ccRCC patients eligible for
S. Verhoeff1, S. C. van Es2, E. Boon1, E. van Helden3, L. Angus4, S. G. watchful waiting, the addition of [89Zr]Zr-DFO-girentuximab-
Elias5, S. F. Oosting6, E. H. Aarntzen1, A. H. Brouwers2, T. C. Kwee2, PET and [18F]FDG-PET to standard of care diagnostic CT leads to
S. Heskamp1, O. S. Hoekstra3, H. Verheul3, G. J. C. Zwezerijnen3, C. an increased lesion detection compared to standard diagnostic
Menke-van der Houven van Oordt3, A. A. M. van der Veldt4, E. G. E. CT only. The clinical and potential prognostic relevance of PET
de Vries2, O. C. Boerman1, W. T. A. van der Graaf7,1, W. J. G. Oyen8,9,1, using [89Zr]Zr-DFO-girentuximab and [18F]FDG in ccRCC patients
C. M. L. van Herpen1; warrants further investigation. References: None.
1
Radboud University Medical Center, Nijmegen, NETHERLANDS,
2
University Medical Center Groningen, Groningen,
NETHERLANDS, 3Amsterdam University Medical Center, OP-160
Amsterdam, NETHERLANDS, 4Erasmus University Medical Center, Theranostic [64/67Cu]SARTATE Clinical Trial - Uptake and
Rotterdam, NETHERLANDS, 5Julius Center for Health Sciences retention of [64/67Cu]SARTATE within meningioma
and Primary Care, Utrecht, NETHERLANDS, 6Univeristy Medical G. P. Schembri1, C. Yin1, K. Willowson1, A. Hedt2, E. Lengyelova2, M.
Center Groningen, Groningen, NETHERLANDS, 7Antoni van Parker2, C. Biggin2, M. Harris2;
leeuwenhoek, Amsterdam, NETHERLANDS, 8Rijnstate Arnhem, 1
Royal North Shore Hospital, St Leonards, AUSTRALIA,
Arnhem, NETHERLANDS, 9Humanitas University, Milan, ITALY. 2
Clarity Pharmaceuticals, Sydney, AUSTRALIA.

Aim/Introduction: The objective of this study is to evaluate Aim/Introduction: Somatostatin receptors (SSTR) are
the potential of contrast-enhanced CT, [89Zr]Zr-DFO- expressed in 60-100% of meningioma and peptide receptor
girentuximab-PET and [18F]FDG-PET for detection of clear cell radionuclide therapy (PRRT) utilising radiolabelled somatostatin
renal cell carcinoma (ccRCC) lesions in patients with a good analogues has been demonstrated used in the management
or intermediate prognosis metastatic ccRCC according to the of these tumours. SARTATE is a somatostatin peptide analogue
International Metastatic Database Consortium risk model, that can be labelled with 64Cu or 67Cu. We report preliminary
allowing to safely observe the course of disease in a period of findings in a first in human trial utilising [67Cu]SARTATE.
so-called watchful waiting. Materials and Methods: Between Materials and Methods: [67Cu]SARTATE is being evaluated in
February 2015 and March 2018, 42 patients with recently (<6 a Phase I-IIa multidose trial with recurrent or progressive grade
months) diagnosed mccRCC with a good or intermediate I-III meningioma (ACTRN12618000309280). Between July 2018
prognosis, were enrolled in the IMaging PAtients for Cancer drug and April 2019, 5 patients with histologically confirmed GRADE
selecTion (IMPACT)-renal cell cancer (RCC) study, conducted I to III meningioma underwent a baseline [64Cu]SARTATE PET/
at 4 Dutch academic medical centers. Patients underwent CT scan on a Siemens Biograph mCT. Three patients went on
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S68

to have therapy with [67Cu]SARTATE. Quantitative SPECT/CT was of tumours. Recently, a 68Ga-labelled antagonist to GRPRs,
performed on a Siemens Intevo camera and processed using NeoBOMB1, was developed for PET. We here report on the
in house quantification software. Lesion analysis was performed outcome of a Phase I/IIa clinical trial (EudraCT 2016-002053-38)
using MIM software. On the baseline 64Cu PET/CT studies, within the EU-FP7 project MITIGATE (grant 602306) in patients
SUVmax, SUVpeak and SUVmean were calculated at 1h, 4h and 24h with oligometastatic gastrointestinal stromal tumours (GIST).
time points. For the 67Cu SPECT/CT data, quantitative data was Materials and Methods: The main objectives were evaluation
assessed at 1h, 4h, 24h and 96h time points. Results: Five patients of safety, biodistribution, dosimetry and preliminary diagnostic
PET/CT studies were analysed. Three subjects proceeded to performance of 68Ga-NeoBOMB1 in patients with advanced
therapy with 11 treatments being completed. Average SUVmax TKI-treated GIST using PET/CT. Nine patients with histologically
at 1h was 15.8 (26.6 to 4.2), stable at 4h at 15.8 and reduced to confirmed GIST and unresectable primary or metastases were
7.7 by 24h. Retention compared to 1h values were similar across included. Eight patients had a documented first-line TKI-
SUV measures. Based on SUVpeak, [64Cu]SARTATE retention in resistance to imatinib. 68Ga- NeoBOMB1 was prepared using a kit
each patient’s intracranial lesion remained high for the first 4h procedure with a licensed 68Ge/68Ga generator. 3MBq/kg body
with average 97% retention at that time point. Between 4 and weight were injected intravenously and safety parameters were
24h, there is clearance, with 50% remaining at 24h. One patient assessed. PET/CT included dynamic and 1, 2 and 3-4h static
had increasing uptake with >100% retention at 24h. Serial 67Cu PET imaging for dosimetric calculations and pharmacokinetics
SPECT/CT demonstrated a similar pattern with slightly faster (including blood sampling and urine collection). Tumour
clearance rates. 88% retention was evident at 4h, 45% at 24h and targeting was assessed on a per-lesion and per-patient basis.
9% at 96h. Individual lesions demonstrated greater variation. At Results: 68Ga- NeoBOMB1 was prepared with high radiochemical
4h, the retention range was 75% to 100%, at 24h, 23% to 66%, purity (>97%). Patients received 176MBq (mean) corresponding
and at 96h 2% to 23%. Conclusion: There is excellent initial to 50µg of NeoBOMB1. Treatment was well tolerated with
uptake of [Cu]Sartate radiopharmaceuticals into meningioma only transient mild adverse events (maximum CTCAE grade
with high retention in the first 4h. Tumour clearance rates were 1) apparent within 4 weeks after application. Dosimetric
similar between 64Cu and 67Cu products on this initial data. At calculations (n=6 patients) revealed a mean adsorbed effective
24h, there was approximate 50% average retention for the 64Cu dose of 0.0287±0.06mSv/MBq with highest organ doses to
and 67Cu. The theranostic pair of 64Cu and 67Cu Sartate may have the pancreas (0.274 ± 0.099 mSv/MBq). Mean plasma half-life
a role in the management of these tumours. References: Hick was 27.3min with primarily renal clearance (mean 25.7±5.43%
RJ Et al: First-in-human trial of 64Cu-SARTATE PET imaging of of injected dose after 4h). Plasma metabolite analysis revealed
patients with neuroendocrine tumours ....J Nucl Med. 2018 Nov good stability, but only metabolites in urine. 5 patients showed
15 a significant tumour uptake with increasing SUV values
(SUVmax 2h p.i. between 4.3 and 25.9) and contrast over time.
4 patients had no tumour specific accumulation. A correlation
OP-161 between CT contrast-enhancement and 68Ga-NeoBOMB1 was
Results of a Phase I/IIa study using 68Ga-NeoBOMB1 in found. Conclusion: This Phase I/IIa provides human safety
oligometastatic GIST data for 68Ga-NeoBOMB1, a promising radiopharmaceutical
L. Gruber1, C. Decristoforo2, C. Uprimny2, P. Kaeopookum2, L. for targeting GRPR-expressing tumours. Pharmacokinetics are
Jimenez3, G. Glatting4, P. Hohenberger5, S. Schönberg6, F. Orlandi7, suitable for PET imaging and radiation dose is comparable
M. Mariani7, W. Jaschke1, I. Virgolini2; to other 68Ga-radiopharmaceuticals in clinical routine. In this
1
Department of Radiology, Medical University Innsbruck, preliminary evaluation of TKI-resistant GIST patients uptake
Innsbruck, AUSTRIA, 2Department of Nuclear Medicine, Medical of 68Ga-NeoBOMB1 was variable, potentially depending on
University Innsbruck, Innsbruck, AUSTRIA, 3Medical Radiation the degree of GRPR expression. PET imaging of other tumour
Physics/Radiation Protection, Universitätsmedizin Mannheim, entities expressing GRPR, such as breast, prostate or lung
Medical Faculty Mannheim, Heidelberg University, Mannheim, cancers is currently under investigation in a continuing Phase II
GERMANY, 4Medical Radiation Physics/Radiation Protection, study possibly also leading to a theragnostic pathway with the
Universitätsmedizin Mannheim, Medical Faculty Mannheim, corresponding Lu-177 counterpart. References: None.
Heidelberg University; Medical Radiation Physics, Department of
Nuclear Medicine, Ulm University, Mannheim, Ulm, GERMANY,
5
Division of Surgical Oncology and Thoracic Surgery, Medical OP-162
Faculty Mannheim, Heidelberg University, Mannheim, GERMANY, The role of FAPI-PET/CT for patients with lower
6
Institute of Clinical Radiology and Nuclear Medicine, University gastrointestinal malignancies - first clinical experience
Medical Center Mannheim, Medical Faculty Mannheim, S. A. Koerber1,2,3, F. Staudinger4, C. Kratochwil4, T. Lindner4, P.
Heidelberg University, Mannheim, GERMANY, 7Advanced Flechsig4, H. Rathke4, M. Roehrich4, K. Herfarth1,2,3, J. Debus1,2,5, U.
Accelerator Applications, Colleretto Giacosa TO, ITALY. Haberkorn4,6, F. L. Giesel4,6,7;
1
Department of Radiation Oncology, Heidelberg University
Hospital, Heidelberg, GERMANY, 2Heidelberg Institute of Radiation
Aim/Introduction: Gastrin releasing peptide receptors Oncology (HIRO), Heidelberg, GERMANY, 3National Center for
(GRPRs) are potential molecular imaging targets in a variety Tumor diseases (NCT), Heidelberg, GERMANY, 4Department of
S69 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

Nuclear Medicine, Heidelberg University Hospital, Heidelberg, OP-163


GERMANY, 5Clinical Cooperation Unit Radiation Oncology, Non-invasive imaging of tumor-associated fibroblasts
German Cancer Research Center (DKFZ), Heidelberg, GERMANY, by68Ga-FAPI-PET/CT - first experience in head and neck
6
Clinical Cooperation Unit Nuclear Medicine, German Cancer cancer
Research Center (DKFZ), Heidelberg, GERMANY, 7German S. Serfling1, Y. Zhi2, A. Schirbel1, T. Lindner3, A. Scherzad2, S.
Cancer Consortium (DKTK), Heidelberg, GERMANY. Hackenberg2, E. Gerhard-Hartmann4, U. Haberkron3, C. Lapa1, A.
Buck1;
1
Department of Nuclear Medicine, University Hospital Würzburg,
Aim/Introduction: For radiotherapy planning and oncological Würzburg, GERMANY, 2Department of ENT, University Hospital
management, reliable staging tools are essential. Recent Würzburg, Würzburg, GERMANY, 3Department of Nuclear Medicine,
development of positron-emission tomography (PET) - imaging University Hospital Heidelberg, Würzburg, GERMANY, 4Department
using tracers that act as fibroblast-activation-protein inhibitors of Pathology, University Würzburg, Germany, Würzburg, GERMANY.
(FAPI) demonstrated promising preclinical and clinical results
(Ref. 1,2). The current study aimed to evaluate the role of FAPI-
PET/computed tomography (CT) for primary malignancies Aim/Introduction: Positron emission tomography/computed
located within the lower gastrointestinal tract. Materials tomography (PET/CT) with radioactively labeled 2-deoxy-2-(18F)
and Methods: FAPI-PET/CT was performed in seven patients fluoro-D-glucose(18F-FDG) is the standard for nuclear medicine
with metastasized colon cancer and three patients with imaging of head and neck cancer (HNC). However, specificity of
metastasized rectal cancer; in addition two patients underwent this approach is hampered by reactive or inflammatory changes
FAPI-PET/CT for primary staging. All patients were referred for that require a number of various samples for histopathological
improved delineate target volume for planned external-beam examination during diagnostic endoscopy.The fibroblast
radiotherapy. A Biograph mCT Flow scanner (Siemens, Erlangen/ activation protein (FAP) is a transmembrane glycoprotein
Germany) was used for PET/CT, imaging was performed 10min overexpressed by so-called “cancer-activated fibroblasts” that
and 1h after injection of 122-312 MBq 68Ga-FAPI-04. We are present in over 90 % of epithelial carcinomas. Recently, a
quantified tumor uptake by standardized uptake value (SUV) radiolabeled diagnostic inhibitor for non-invasive visualization
max and SUVmean (60% isocontour). Results: PET/CT detected of FAP was developed (68Ga-FAPI). The aim of this study was
multiple FAPI-positive nodes, liver lesions as well as bone and to investigate the value of 68Ga-FAPI in patients with newly
pulmonary lesions for colon and rectal cancer patients. SUVmax diagnosed HNC. Materials and Methods: In this ongoing
values ranged from 5.5 to 16.5 for patients with colon cancer study, four patients with treatment-naïve primary tumors of
and 3.7 to 14.1 for patients with rectal cancer, respectively. The the tonsils were enrolled. 68Ga-FAPI-PET/CT was performed
highest SUVmax was observed for patients with anal cancer. 1h after i.v. injection of 136-156 MBq 68Ga-FAPI-04. Imaging
The cohort demonstrated a FAPI-uptake of 17.9/ 19.1 within results (including mean (SUVmean) and maximum (SUVmax)
the primary tumor, while no suspicious lesion was detected in standardized uptake values) were compared to 18F-FDG-PET/
nodes or organs outside the pelvis. Compared to conventional CT and histolopathologic work-up. For calculation of tumor-to-
imaging, we observed an excellent detection rate for FAPI-PET/ normal (T/N) ratios, tumor uptake was related to uptake in the
CT due to eminent tumor-to-background ratio. Conclusion: contralateral healthy tonsil. Results: All tonsil carcinomas were
For patients with lower gastrointestinal malignancies, FAPI-PET/ 18
F-FDG and 68Ga-FAPI positive. SUVmean and SUVmaxfor 18F-FDG
CT was able to demonstrate promising results with regard to and 68Ga-FAPI were 17.5±3.3 and 27.4±6.3 (18F-FDG) as well as
intense tumor uptake and image contrast. Considering some 12.5±5.5 and 18.0±5.9 (68Ga-FAPI), respectively. In contrast to
benefits when using FAPI imaging (no diet/ fasting, short interval 18
F-FDG, 68Ga-FAPI demonstrated higher Tmax/N ratios of 7.8±3.2
between injection of the tracer and start of the exam), FAPI-PET/ vs. 6.1±3.3. 68Ga-FAPI uptake in the tumors was confirmed
CT may open up new applications like staging or non-invasive by immuno-histochemical staining of the resected tissue.
tumor characterization for patients with malignant tumors of Conclusion: In comparison to 18F-FDG, 68Ga-FAPI could enable
the lower gastrointestinal tract. References: (1) Kratochwil C, a better differentiation between tumor tissue and inflammatory
Flechsig P, Lindner T, Abderrahim L, Altmann A, et al.: FAPI-PET/ changes. In the future, 68Ga-FAPI-PET/CT might serve as a useful
CT: Mean intensity of tracer-uptake (SUV) in 28 different kinds tool in the work-up of HNC. References: None.
of cancer. J Nucl Med. 2019 Apr 6. pii: jnumed.119.227967. doi:
10.2967/jnumed.119.227967. [Epub ahead of print] (2) Giesel
FL, Kratochwil C, Lindner T, Marschalek MM, Loktev A, et al.: OP-164
68Ga-FAPI PET/CT: Biodistribution and Preliminary Dosimetry A Pilot Study of Anti-HER2 Affibody Molecule 68Ga-
Estimate of 2 DOTA-Containing FAP-Targeting Agents in Patients MZHER2 in HER2-positive Gastric Cancer Patients
with Various Cancers. J Nucl Med. 2019 Mar;60(3):386-392. doi: X. Guo, N. Zhou, H. Zhu, Z. Yang;
10.2967/jnumed.118.215913. Epub 2018 Aug Peking University Cancer Hospital & Institute, Beijing, CHINA.
Aim/Introduction: The purpose of this study was to develop
a HER2-targeted affibody 68Ga-NOTA-MAL-MZHER2 and
confirmed the possibility of clinical transformation. We
measured the safety, bio-distribution of 68Ga-NOTA-MAL-
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S70

MZHER2, and determine its feasibility of detecting bone 409


metastases in HER2-positive noninvasively. Materials and Thyroid - Parallel Session: Thyroid Cancer
Methods: 68Ga-NOTA-MAL-MZHER2 successfully translated to
clinical PET imaging [ethical approval no. 2018KT61]. Four HER2- Sunday, October 13, 2019, 14:30 - 16:00
Lecture Hall 115
positive and two HER2-negative gastric cancer patients with
bone metastases by contrast enhanced MRI, CT or pathology
were included. Whole-body PET/CT were performed at 1, 2,
and 3 h after injection of approximately 185±18.5 MBq of the OP-165
probe 68Ga-NOTA-MAL-MZHER2. Volumes of interest were Thyroid Imaging Reporting And Data System (TIRADS)
drawn on all clearly identifiable source organs to evaluate the and Tc99m-MIBI-scintigraphy for the assessment of
bio-distribution of the probe. Each patient also underwent differentiated thyroid carcinomas and follicular neoplasms
standard 18F-FDG PET/CT for comparison analysis. Results: S. Schenke1,2, R. Klett3, P. Wagner4, M. Zimny5, M. C. Kreissl1;
NOTA-MAL-MZHER2 was efficiently radiolabeled with 68Ga over 1
Department of Radiology and Nuclearmedicine, University
a 99% radio-chemical purity and 1 GBq/µmol specific activities. Hospital Magdeburg A.ö.R., Magdeburg, GERMANY,
No adverse effects were noticed in all patients from 0 to 6 hour 2
ÜBAG Nuclearmedicine Hanau, Giessen, GERMANY,
after tracer’s injection. Regarding the bio-distribution of HER2- 3
ÜBAG Nuclear Medicine Hanau, Giessen, GERMANY,
targeted agents 68Ga-NOTA-MAL-MZHER2, predominant uptake 4
Department of Radiology and Nuclear Medicine, University
was in kidneys and liver at 1, 2 and 3 h. And uptake was also Hospital Magdeburg A.ö.R., Magdeburg, GERMANY,
noted in the lacrimal glands, salivary glands, spleen, and small 5
ÜBAG Nuclearmedicine Hanau, Hanau, GERMANY.
bowel. This was different from the 18F-FDG distribution. The
results of the study showed that the best time for assessment of
bone metastases was 2 h after the injection. Co-injection of 500 Aim/Introduction: Thyroid Imaging Reporting And Data
μg HER2-affibody was optimal to reduce the uptake in normal System (TIRADS) is helpful for sonographic risk stratification
hepatic tissue. In four HER2-positive cases, 13 metastatic bone of thyroid nodules (TN). However, there is a lack of data for
lesions could be clearly visualized by 68Ga-NOTA-MAL-MZHER2 the TIRADS classification of the follicular variant of papillary
PET/CT with the SUVmax of 26.01 ± 12.36 (range, 12.3~52.6), thyroid carcinoma (FVPTC), follicular carcinoma (FTC), and
which was significantly different from that of 18F-FDG (p < 0.001), follicular adenoma (FA) compared to the classical papillary
with the SUVmax of 6.51± 2.51 (range, 2.6~12). In two HER2- thyroid carcinoma (PTC). MIBI-Imaging has a high negative
negative cases, 18F-FDG showed obvious uptake (SUVmax 16.08 predictive value for the exclusion of thyroid malignancy in
± 8.67, range 7.3~28.1) of 13 metastatic bone lesions and low hypofunctioning TN. Aim of this analysis was to compare PTC,
uptake on 68Ga-NOTA-MAL-MZHER2 (SUVmax 4.0 ± 1.50, range FTC, FVPTC, and FA using three different variants of TIRADS and
2~6.3). There were obviously differences among metastatic MIBI-Imaging. Materials and Methods: We retrospectively
bone lesions uptake in HER2 positive and HER2 negative analyzed MIBI-Imaging studies performed between 2010 and
level in 68Ga-NOTA-MAL-MZHER2 at 2 h imaging (p< 0.0001). 2016. Inclusion criteria were a hypofunctioning TN, available
Conclusion: We produced clinical grade 68Ga-NOTA-MAL- B-mode ultrasound and histopathological diagnosis. All nodules
MZHER2 agent for HER2 targeting PET imaging. And a pilot PET/ were retrospectively classified according to Kwak-TIRADS, EU-
CT imaging demonstrated a favorable bio-distribution, safety TIRADS, and K-TIRADS. MIBI-imaging (planar/SPECT images 60
profile. Compared with 18F-FDG, it showed better detection minutes p.i.) was visual categorized as MIBI positive (hypointense
capability of bone metastases from HER2-positive gastric and isointense pattern of the TN compared to the paranodular
cancer. And 68Ga-NOTA-MAL-MZHER2 holds a great potential MIBI uptake) and MIBI negative (hypointense pattern of the
for noninvasive detection of metastatic bone lesions in patients TN). Results: We included 226 patients (177 female) with TN
with HER2-positive gastric cancer. References: None. (198 benign, 28 malignant TN). Among 28 malignant TN, we
found 17 (61%) PTC, 5 (18%) FVPTC, and 6 (21%) FTC. 42 (21%)
of the benign nodules were FA. When using Kwak-TIRADS > 4B
as as a marker for high risk nodules, we found 90.5% of the FA,
100% of the FTC, 80% of the FVPTC, and 47.1% of the PTC to be
below this cutoff. We found similar results for K-TIRADS. Using
EU-TIRADS 54.8% of the FA, 66,6% of the FTC, 60% of the FVPTC,
and 29.3% of the PTC were classified as EU-TIRADS 3 and 4. All
PTC and FVPTC were MIBI positive, and 83.3% of the FTC and
73.8 % of the FA were MIBI positive. Conclusion: Using TIRADS
for the risk stratification of thyroid nodules, FVPTC and FTC
may be missed. MIBI-imaging seems to detect FVPTC and FTC
better. However, neither TIRADS nor MIBI-scintigraphy is able to
differentiate between FA and FTC or FVPTC. References: None.

OP-166
S71 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

Variations in radioiodine ablation - decision making after RIA therapy [4] and results of ongoing prospective randomized
total thyroidectomy studies are likely to reduce uncertainty in approaching RAI
O. C. Maas1, M. Maas1, P. M. Putora2, C. M. Panje3, J. Blautzik4, M. treatment in DTC patients. References: 1. Haugen, B.R., 2015
Brühlmeier5, I. Engel-Bizik6, L. Giovanella7, A. Haldemann8, M. E. American Thyroid Association Management Guidelines for Adult
Kamel9, S. Kneifel10, C. Rottenburger11, N. Schäfer12, M. A. Walter13, S. Patients with Thyroid Nodules and Differentiated Thyroid Cancer:
Weidner14, F. Forrer1; What is new and what has changed? Cancer, 2017.123(3):p.372-
1
Cantonal Hospital St. Gallen, Dept. of Radiology and Nuclear 381. 2. Luster, M., et al., Guidelines for radioiodine therapy of
Medicine, St. Gallen, SWITZERLAND, 2Dept. of Radiation Oncology, differentiated thyroid cancer. European Journal of Nuclear
University of Bern, Bern, SWITZERLAND, 3Cantonal Hospital St. Medicine and Molecular Imaging, 2008. 35(10): p.1941. 3. Panje,
Gallen, Dept. of Radiation Oncology, St. Gallen, SWITZERLAND, C.M., et al., Applied Swarm-based medicine: collecting decision
4
Hirslanden Klinik St. Anna Luzern, Dept. of Radiology and trees for patterns of algorithms analysis. BMC Med Res Methodol,
Nuclear Medicine, Lucerne, SWITZERLAND, 5Cantonal Hospital 2017.17(1):p.123. 4. Tuttle, R.M., et al., Controversies, Consensus,
Aarau, Dept. of Radiology and Nuclear Medicine, Aarau, and Collaboration in the Use of I-131 Therapy in Differentiated
SWITZERLAND, 6University Hospital Zurich, Dept. of Radiology Thyroid Cancer: A Joint Statement from the ATA, the EANM, the
and Nuclear Medicine, Zurich, SWITZERLAND, 7Ospedale SNMMI, and the ETA. Thyroid, 2019.29(4):p.461-470.
Regionale di Lugano Civico, Medicina nucleare e Centro PET-CT,
Lugano, SWITZERLAND, 8Triemli Spital Zurich, Dept. of Nuclear
Medicine, Zurich, SWITZERLAND, 9Hôpital du Valais, Servie OP-167
Médince Nucléaire, Sion, SWITZERLAND, 10Cantonal Hospital Braf V600E mutation analysis in low and intermediate risk
Graubünden, Dept. of Radiology and Nuclear Medicine, Chur, papillary thyroid carcinoma
SWITZERLAND, 11University Hospital Basel, Dept. of Radiology and I. López Villar, T. Navarro Martínez, P. Jane Soler, J. Bonilla Plaza, A.
Nuclear Medicine, Basel, SWITZERLAND, 12CHUV Lausanne, Service Martínez Lorca, J. Pérez Iruela, M. Orduña Díez;
Médcine Nucléaire, Lausanne, SWITZERLAND, 13HUG, Service Ramón y Cajal University Hospital, Madrid, SPAIN.
Médcine Nucléaire, Geneva, SWITZERLAND, 14Inselpital Bern,
Dept. of Radiology and Nuclear Medicine, Bern, SWITZERLAND.
Aim/Introduction: B-Raf protein plays a role in regulating the
MAP Kinase/ERKs signaling pathway but its prognostic value in
Aim/Introduction: The role of radioiodine treatment papillary thyroid carcinoma (PTC) is still a matter of debate. This
following total thyroidectomy for differentiated thyroid cancer study aimed to evaluate BRAF V600E impact on the radioiodine
is changing. At the latest, the major revision of the American therapy decision in low and intermediate risk (PTC). Materials
Thyroid Assiciation (ATA) Management Guidelines for Patients and Methods: A retrospective observational study was
with Thyroid Nodules and Differentiated Thyroid Cancer in conducted from January 2014 to December 2016, at Universitary
2015 [1] changed treatment recommendations dramatically in Hospital, of 140 patients with PTC (T1-T3N0NxM0, T1-T3N1M0).
comparison to the European Association of Nuclear Medicine The patients were divided into two groups: The first group with
(EANM) 2008 guidelines [2]. We hypothesize that there is marked BRAF V600E mutation 53% (74/140): of them 41% age < 55 years
variability between the different treatment regimes used today. and 59% age > 55 years. The second group without BRAF V600E
Materials and Methods: We performed a decision-tree based mutation 47% (66/140): of them 39 % age < 55 years and 61%
analysis of management strategies from all Swiss hospitals age > 55 years. The association between clinicopathological
offering radioiodine treatment to map current practice within characteristics and BRAF mutation were evaluated and also
the community. Within this analysis [3], we collected data on compared based on the ongoing risk stratification (age,
treatment activities administered and treatment preparation as gender, histology and tumor staging). All patients underwent
well as decision criteria. Results: Our survey clearly points out a total thyroidectomy with or without lymphatic dissection. The
that for low risk DTC patients follow-up only after thyroidectomy response to treatment was evaluated one year after treatment
is recommended in some places while being offered RIA with with 131I (2,9-5,5 GBq), considering a complete response when
significant doses in other hospitals. E.g. for pT1b tumors without TG was less than 1 ng / ml (after stimulation with recombinant
evidence of metastases the level of agreement ranges from 50% TSHrh), antiTG antibody <20 IU and negative total body scan.
to 75% voting for RIT depending on histologic features; if treated Thyroid uptake of 131I was visually evaluated and graded with
administered activities of I-131 range from 1.1 GBq to 3.0 GBq. semiquantitative score. Results: We studied 140 PTC patients
For intermediate and high risk patients radioiodine treatment without distant metastases, with positive BRAF mutation in 53%
is recommended in general. However, dosing and treatment (74/140). 41 men (29%) and 99 women (71%), age range from 8
preparation (rTSH vs. THW) vary distinctly. Conclusion: to 77 years (mean 59). There was an excellent response in the first
Currently existing variety between treatment recommendation group with BRAF mutation (94% vs 90%) and also an excellent
after total thyroidectomy for DTC at Swiss Nuclear Medicine response in the second group without BRAF mutation (88%
facilities reflects differences in clinical guidelines as different vs 92%) p> 0.05 not significant, for the two groups. Significant
stimulation methods and activity ranges are suggested.The association was observed between BRAF mutation and gender,
recently proposed different approach on RIA therapy, based on proportion of male with positive mutation 60% (20/41), but not
integrated post-surgery assessment and clear defined aims of associate with a worse prognosis. In the 140 PTC the somatic
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S72

BRAF mutation does not associate with less radiodine uptake CT ameliorates the correct definition of the TNM stage,
according our semiquantitative score p> 0.05. Conclusion: improving detection rate and correct localization of both nodal
No significant difference in clinical outcome, was observed and metastatic lesions and reduces the number of equivocal
between these two groups (BRAF V600E mutation status), in findings on planar imaging. The changes in TNM scores may
patients with PDT free of metastasis. Significant association significantly influence the subsequent management of these
was observed between BRAF mutation and gender male. No patients. References: None.
correlation with loss of radioiodine uptake at the sodium/iodine
symporter (NIS) promoter in this retrospective study. Although
it requires long-term evolutionary studies. References: None. OP-169
Thirteen-year Outcome of a Prospective Randomized
Phase III study: 1.1 GBq and 3.7 GBq of Radioiodine Are
OP-168 Equally Effective in Ablation Therapy for Papillary and
Additional Value of 131I SPECT/CT in the Management of Follicular Thyroid Cancer
Patients with Differentiated Thyroid Carcinoma V. Ahtiainen, L. Vaalavirta, M. Tenhunen, H. Joensuu, H. Mäenpää;
I. Marini1,2, M. Maussier1,2, G. Perotti1, M. Salvatori1,2; Helsinki University Hospital, Comprehensive
1
Unità Operativa Complessa di Medicina Nucleare, Cancer Center, Helsinki, FINLAND.
Fondazione Policlinico Universitario A. Gemelli IRCCS,
Roma, ITALY, 2Istituto di Medicina Nucleare, Università
Cattolica del Sacro Cuore, Roma, ITALY. Aim/Introduction: The optimal activity of radioiodine (I-131)
administered for ablation therapy in papillary and follicular
thyroid cancer after thyroidectomy remains unknown in
Aim/Introduction: Differentiated thyroid carcinoma (DTC) is a long-term (>10 years) follow-up. Some, shorter follow-
the most common endocrine cancer in adult patients (1% of up studies suggest that activities 1.1 GBq and 3.7 GBq are
all malignant tumors). Patients undergoing 131I treatment or equally effective. We evaluated the long-term outcomes after
diagnostic examination are generally evaluated with planar radioiodine treatment to extend current knowledge about the
whole-body scans only. SPECT/CT has demonstrated to be optimal ablative dose of I-131. Materials and Methods: One
a promising tool in improving anatomical localization and hundred and sixty consecutive adult patients (129 females,
detection rate. The aim of our study was to determine the 31 males; mean age 46 ± 14y, range 18-89 y) diagnosed with
additional value of SPECT/CT imaging in the assessement and histologically confirmed papillary or follicular thyroid cancer,
in the management of patients affected by DTC. Materials and were randomized in a prospective, phase III, open-label, single-
Methods: we retrospectively enrolled 106 patients affected centre study during 2000-2004, to receive either 1.1 GBq or 3.7
by DTC (68 female, median age 45.7, range 10-86 years), who GBq of I-131 after thyroidectomy. At randomization, patients
underwent 131I post-therapeutic or diagnostic whole-body scan were stratified according to the histologically verified cervical
and a subsequent SPECT/CT, after total thyroidectomy, in our lymph node status and were prepared for ablation using thyroid
centre from June 2016 to December 2018. A total number of 121 hormone withdrawal. No uptake in the whole-body scan with
whole body scans (105 post-therapeutic and 16 diagnostic) and I-131 and serum thyroglobulin concentration less than one ng/
corresponding SPECT/CT has been considered. The images were mL at 4-8 months after treatment was considered successful
acquired within 2-3 days after oral radioiodine administration ablation. Results: Median follow-up time was 13.0 years (mean
(range 1-7.4 GBq, median 3.31 GBq, for post-therapeutic scans 11.0 ± 4.8 y; range 0.3-17.1 y). Altogether 81 patients received
and a median dose of 0.196 GBq for diagnostic scans). The TNM 1.1 GBq with successful ablation in 45 (56 %) patients. Thirty-
stage was determined according to the TNM classification 8th six patients (44%) needed one or more extra administrations
edition. Two experienced nuclear medicine physicians blindly to replete the ablation. Of these, 4 (8.9%) and 5 (14%) patients
reviewed both the planar and SPECT/CT images and separately relapsed, respectively. Of the 79 patients treated with 3.7 GBq,
evaluated the N and M stage, the number of metastatic lesions, 45 (57%) had successful ablation after one administration of
the anatomical localization of uptake and the management they radioiodine and 34 (43%) needed several treatments. Of these, 2
would have proposed for every case. Results: in comparison (4.4%) and 9 (26.5%) patients relapsed, respectively. The groups
with planar imaging only, SPECT/CT helped distinguish a total did not differ in the proportion of patients relapsing (p=0.591).
number of 138 more lesions (p 0.0012). It improved anatomical Three (1.9%) of the patients died from thyroid cancer during the
localization of 112 foci of uptake. The addictional use of SPECT/ follow-up, all in the higher activity group. Conclusion: During
CT changed the N stage in 11 cases (9.1 %) and the M stage follow-up of median 13 years, 1.1 GBq is as effective as 3.7 GBq
in 32 cases (26.4%), both reducing or upgrading the stage. in the radioiodine treatment after thyroidectomy in papillary
SPECT/CT also helped excluding a total number of 29 false and follicular thyroid cancer. References: Mäenpää HO, et al.,
positive findings. The proposed management (additional 131I Low vs. High Radioiodine Activity to Ablate the Thyroid after
therapy, surgery, RT) changed in 31 cases (25.6%). In 19 cases Thyroidectomy for Cancer: A Randomized Study, PLoS One.
(15.7%) the clarification of equivocal foci of uptake would have 2008 Apr 2;3(4):e1885. Schlumberger M, et al., Strategies of
avoided further unnecessary investigations or treatments. Radioiodine Ablation in Patients with Low-Risk Thyroid Cancer,
Conclusion: in patients with DTC the additional use of SPECT/ N Engl J Med. 2012 May 3;366(18):1663-73.
S73 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

OP-170 OP-171
Predictive factors of recurrence in patients with Prognosis estimation with the ratio of largest tumor
indeterminate or incomplete biochemical response diameter to total tumor diameter in multifocal T1
after radio-iodine therapy in patients followed for differentiated thyroid cancer
differentiated thyroid carcinoma M. Araz, P. Akkus, C. Soydal, E. Ozkan, M. K. Kir;
M. Chafai El Alaoui1, A. Kelly1, F. Kwiatkowski1, B. Barrès1,2, C. Ankara University, Ankara, TURKEY.
Valla1, B. Lardet1, M. Batisse-Lignier3, I. Tauveron3,4, F. Cachin1,2, S.
Maqdasy3,4;
1
Centre Jean Perrin, Clermont-Ferrand, FRANCE, 2UMR Aim/Introduction: To evaluate the prognostic importance of
INSERM 1240 IMOST UCA, Clermont-Ferrand, FRANCE, 3CHU the ratio of the largest tumor diameter to total tumor diameter in
Gabriel Montpied, Clermont-Ferrand, FRANCE, 4GReD UMR multifocal T1 papillary thyroid carcinoma following radioiodine
UCA - CNRS 6293 - INSERM U1103, Aubière, FRANCE. ablation (RAI). Materials and Methods: We retrospectively
reviewed 487 T1 differentiated thyroid cancer patients who
received RAI were reviewed. 176 patients with multifocal tumors
Aim/Introduction: The aim of this study was to identify were included in the analysis. Diameter ratio (DR) was defined
predictive factors of recurrence in patients presenting with as the largest tumor diameter divided by total tumor diameter
high stimulated serum-thyroglobulin (sTg) value on the in multifocal disease. Patients were divided into two groups
first evaluation of response 6 to 9 months after radioiodine according to a cutoff which was determined as the mean values
therapy (RAI), in differentiated thyroid carcinoma. Materials of total tumor diameter and DR. Relationship between DR and
and Methods: This is a retrospective study from our database the the largest tumor diameter with gender, histopathological
concerning 1688 patients followed in our center for differentiated subtypes, capsular or vascular invasion, extrathyroidal extension
thyroid carcinoma from 1990 to 2010. Complete response after were analyzed with Chi-Square test. Additionally to analyze the
surgery and RAI was considered for 923 patients according to prognostic importance of DR and the largest tumor diameter,
the European Recommendations. Metastatic patients, patients Kaplan Meier Test was used to predict the clinical outcome and
presenting with structural disease on iodine scintigraphy the disease progression. Results: Multicentricity was recorded
performed 6 to 9 months after RAI or neck ultrasonography, or in 176/478 patients (36.1%), among which the contralateral
with serum thyroglobulin antibodies were excluded. Finally, 145 lobe was involved in 112/478 patients (23%). Thus, a total of
patients (8.5%) with isolated high value of sTg were analyzed 176 patients aged >18y were involved (34M, 142F, mean age:
; mean follow-up was 8.7 years [0.6-19.7] in this population. 43.13 ±11.65 years min:20, max:83). Mean diameter of the
Recurrence rate (defined as structural local or metastatic largest tumor was 1.07±0.54cm (min:0.08cm,max:2cm) and
recurrence) was calculated and statistical analysis of recurrence- mean RAI ablation dose applied was 100.38±24.93mCi (min:75,
free survival was based on Kaplan Meier curves. Predictive factors max:200mCi). Capsular and vascular invasion was found in
of recurrence were identified using Log Rank tests on univariate 76/176 (43.2.%) and 10/176 (5.7%) patients respectively. Mean
analysis and Cox Model on multivariate analysis. Results: follow up was 103.55±42.49 months (min:20, max:228). 154/176
Recurrence rate was statistically different between the three (87.5%) of the patients were under remission with an excellent
groups individualized based on sTg value [sTg<1: 16/923 (1.7%); therapy response, but disease remained persistent in 18 (10.2%)
sTg 1-5µg/l: 12/111(10.8%); sTg>5: 10/34 (29.4%), p<10-21]. The patients and recurrence was observed in 4/176 (2.3%) patients.
Kaplan Meyer curves show a statistically significant difference Disease progression was found in 6/176 (3.4.%) patients. DR was
of recurrence-free survival between the three groups (Log-Rank significantly correlated with contralateral lobe involvement,
: Chi² = 57.594 / d.d.l. = 2 ; p < 10-7). Univariate analysis identified capsular invasion and male gender (p<0.001, p<0.05 and
tumor size (T), metastatic lymph nodes (N), male sex, initial p<0.05 respectively). No recurrence, persistant disease or
serum thyroglobulin (before RAI) and sTg as factors influencing progression was found in patients with a total tumor diameter
recurrence-free survival. On multivariate analysis, only the <1cm (p<0.05). On survival analysis, none of these factors were
tumor size appeared as a predictive factor of recurrence when found to be associated with clinical outcome and progression.
value of sTg exceeded 5µg/l . There was no significant difference Conclusion: The ratio of the largest tumor diameter to total
in terms of recurrence-free survival in the T1 subgroup whether tumor diameter calculated in patients with multifocal tumors
sTg<1 or sTg 1-5µg/l (p<10-7). A reduced recurrence-free survival was correlated with male gender, contralateral lobe involvement
is observed in other cases when sTg>1 (p<10-5). Conclusion: A and capsular invasion and can be a predictive parameter for
cutoff of sTg below 5 µg/l on the first evaluation of response aggressiveness. However, it does not seem to be a negative
to RAI for differentiated thyroid cancer can be considered as a prognostic factor in patients who receive radioiodine ablation
good factor of long recurrence-free survival when tumor size is treatment for multifocal papillary T1 tumors. Multifocality is not
less than 2 cm. A reduced recurrence-free survival was observed an important factor affecting clinical course of the disease in
in other cases when sTg>1. References: None. tumors with largest tumor diameter <1cm. References: None.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S74

OP-172 miRNAs 221,222 and 146b should be considered predictive of


Serum miRNAs measurements and diagnostic radioiodine persistent disease, thus suggesting a more aggressive follow-up.
whole body scintigraphy can be useful diagnostic tool in Dx-WBS allowed to identify all patients with persistent disease,
early identifying of persistent disease in differentiated confirming to be a useful tool in DTC follow-up. References:
thyroid cancer (DTC) patients with uninformative Tg values None.
A. Campenni’1, M. Aguennouz2, A. Vento1, F. Polito2, A. D. Comis1, R.
M. Di Giorgio2, F. Panasiti1, R. M. Ruggeri3, S. Baldari1;
1
Department of Biomedical and Dental Sciences and Morpho- 410
Functional Imaging, Nuclear Medicine Unit, University of Messina,
Messina, ITALY, 2Department of Clinical and Experimental
Clinical Oncology - Parallel Session: Lung, Head
Medicine, Unit of Neurology, University of Messina, Messina,
& Neck and More
ITALY, 3Department of Clinical and Experimental Medicine,
Unit of Endocrinology, University of Messina, Messina, ITALY. Sunday, October 13, 2019, 14:30 - 16:00 Lecture Hall 116

Aim/Introduction: Serum thyroid-tumor associated micro-


RNAs (miRNAs) have been recently evaluated as novel potential OP-173
biomarkers in the management of differentiated thyroid FLT-PET And FDG-PET/CT For The Detection Of Relapse
cancer(DTC), mainly in patients whose Tg is “uninformative” Following Definitive Radiotherapy In Non-small Cell Lung
(e.g positive Tg-antibodies/indeterminate biochemical Cancer. Preliminary Results
response). Aim of our study was to evaluate the role of miRNAs- T. Christensen1,2, S. W. Langer3, K. R. Larsen4, G. F. Persson5, A. G.
(221,222,375,155,146b) in early detection of persistent disease Amtoft1, H. H. Johannesen1, S. H. Keller1, A. Kjær1,2, B. M. B. Fischer1;
in radioiodine treated DTC patients. Materials and Methods: 1
Dept. of Clinical Physiology, Nuclear Medicine & PET,
We prospectively collected serum samples from 89 patients (65 Rigshospitalet, University of Copenhagen, Copenhagen, DENMARK,
F, 24 M) undergone (near)-total-thyroidectomy [(near)-TT] for 2
Cluster for Molecular Imaging, University of Copenhagen,
papillary thyroid cancer (PTC) (n= 49) or benign thyroid disease Copenhagen, DENMARK, 3Dept. of Oncology, Rigshospitalet,
(BTD) (n=49). miRNAs levels in bloodstream were evaluated at University of Copenhagen, Copenhagen, DENMARK, 4Dept.
131-radioiodine therapy (RaIT), 2 months after (near)-TT [basal of Pulmonary Medicine, Bispebjerg Hospital, University of
evaluation], six [i.e. eight months after (near)-TT] (first follow-up) Copenhagen, Copenhagen, DENMARK, 5Dept. of Oncology, Herlev
and twelve months later (second follow-up) in PTC patients and Hospital, University of Copenhagen, Copenhagen, DENMARK.
two and eight months after (near)-TT (basal evaluation and first
follow-up, respectively) in BTD patients. miRNAs levels were also
evaluated in twenty gender-age matched healthy-controls. The Aim/Introduction: Diagnosing relapsed lung cancer after
ratio between miRNAs levels of PTC/BTD patients and healthy- radiotherapy is challenging. CT and 18F-fluorodeoxyglucose
controls was reported as fold-change and considered significant (FDG)-PET/CT have a low specificity in this setting. Further,
if it was ≥2 and p-value ≤0.05. In PTC patients, the response to changes may evolve differently after normofractionated
RaIT was verified at second follow-up by means of basal and radiotherapy (nRT) and stereotactic body irradiation (SBRT).
rhTSH-stimulated Tg measurements, neck-ultrasonography, 18
F-fluorothymidine (FLT)-PET is considered a more cancer
diagnostic 123/131-radioiodione whole body scintigraphy (Dx- specific tracer compared to FDG-PET. Therefore, we investigated
WBS). Patients were classified in two categories: (I)Excellent if FLT-PET could improve diagnosis of relapse in patients
response; (II)indeterminate/incomplete bio-chemical and/ treated with nRT and SBRT. Materials and Methods: Lung
or structural response. Results: At basal evaluation, miRNAs cancer patients suspected for relapse after radiotherapy were
levels did not differ in DTC vs BTD patients (p>0.05), but they consecutively included in this prospective clinical study.
were significantly higher in both groups of patients than in Patients were stratified dependent on initial treatment: nRT or
healthy controls (p<0.05). At first follow-up, all BTD patients SBRT. FDG-PET/CT and FLT-PET/CT were conducted no more
and 41/49 DTC patients showed a reduction of miRNAs levels than three weeks apart. PET scans were evaluated visually,
≥50%. In eight DTC patients, the reduction of miRNAs (namely blinded for previous PET-scans. Lung lesions were evaluated
miR-221, miR-222 and miR-146b) levels was <50%. At second as malignant, benign or inconclusive. FDG- and FLT-PET from
follow-up, these 8 patients had persistent loco-regional disease, the same patient were evaluated at least three months apart.
as demonstrated at Dx-WBS; their miRNAs (miR-221, miR-222 Maximum standardized uptake value (SUVmax) was measured
and miR-146b) levels did not change compared to first follow- in the worst graded lesion in each patient. Differences in
up. In 3/8 patients, basal-Tg was less than 1 ng/ml while in 2 malignant vs benign lesions were tested with an independent
cases basal-Tg was ≥1 ng/ml. In 3 patients, TgAb levels did not t-test. Sensitivity and specificity were analysed for FDG-PET/CT
decrease. The remaining 41 DTC patients showed an excellent- and FLT-PET. The reference standard was based on histology
response to RaIT at second follow-up. Conclusion: In our PTC if available, otherwise on independent review of subsequent
patients, response to RaIT was early predicted by serum miRNAs imaging, conference decisions, and clinical course within 6
levels reduction six months after RaIT. A reduction rate <50% of months after FLT-PET. Results: We present the results from the
S75 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

first 40 patients. All patients had radiotherapy for non-small cell a key role in the characterisation of indeterminate solitary
lung cancer; nRT to 66 Gy (n=20) or SBRT to 45-66 Gy (n=20). pulmonary nodules (SNPs). Both qualitative scoring of the
Twenty-two patients received concurrent chemotherapy (19 nodule uptake in reference to the mediastinal blood pool and
nRT-patients; 3 SBRT-patients). FLT-PET was performed 35-581 quantitative scoring using SUVmax have been proposed. To
days after radiotherapy (median 225 days). FDG- and FLT-PET date these have been examined in single centre, single vendor
were conducted 1-17 days apart (median 6 days). During follow or retrospective multicentre descriptive studies. The objective of
up, 12/20 nRT-patients and 10/20 SBRT-patients had relapse. our study was to compare qualitative and quantitative criteria for
SUVmax was significantly higher in relapsed vs benign lesion the diagnosis of SNPs in a prospective multicentre multivendor
within the entire cohort (mean FDG-SUVmax: 10.9 (95 % CI: 8.5- environment. Materials and Methods: 380 (M 53%, F 47%)
13.3) vs. 5.1 (3.4-6.9); p<0.001; mean FLT-SUVmax: 4.3 (3.1-6.5) vs. patients were recruited to the SPUtNIk trial at 16 sites accredited
2.5 (1.8-3.3); p=0.007). The sensitivity of FDG-PET/CT was 100 by the UK PET Core Lab. The inclusion criteria were the presence
% (95 % CI: 85-100 %) within the entire cohort. The specificity of a dominant SPN on CT ≥8 and ≤30 mm on axial plane with no
of FDG-PET/CT was 61 % (36-83 %); lowest in nRT-patients ancillary evidence of malignancy. PET-CT scans were analysed
(50 % vs. 70 %). The sensitivity of FLT-PET was 64 % (41-83 %), and reported locally by PET physicians. Qualitative assessment
lowest in nRT-patients (58 vs. 70 %). The specificity of FLT-PET used a five-point scale compared to the mediastinal blood
was 100 % (81-100 %). Conclusion: FDG-SUVmax and FLT-SUVmax pool. Quantitative measures included SUVmax. The study’s end
were higher in lesions with relapse than benign lesions. The points were: the diagnosis of lung cancer via biopsy/histology
specificity of FLT-PET was 100 %, making FLT-PET promising for or a diagnosis of benign or non-lung cancer via either biopsy or
non-invasive diagnosis of relapse after RT with the potential radiological 2-year follow-up. Receiver Operating Characteristic
to obviate invasive procedures in some patients. References: (ROC) curve analysis was performed for the ordinal grading
None. and SUVmax, with sensitivity and specificity calculated at a
prespecified SUVmax cutoff of 2.5, and a visual score of uptake
equal to or greater than the mediastinum. Exploratory analysis
OP-174 of SUVmax as a continuous variable was also performed.
A comparison of quantitative and qualitative assessment Results: 311 (81.8%) participants with a baseline PET/CT
for the diagnosis of malignancy in solitary pulmonary completed follow-up with an outcome status at two years. The
nodules using 18Fluorine Fluorodeoxyglucose Positron overall incidence of lung cancer was 61% (189/311). Mean size
Emission Tomography/Computed Tomography (PET-CT) in diameter of SPN was 15.4±5.4mm at baseline CT. The area under
the multicentre SPUtNIk trial the ROC were 0.81 (95% CI 0.77; 0.86) for qualitative grading and
S. Dizdarevic1, J. R. Weir-McCall2, S. Harris3, L. A. Little4, J. Jones5, 0.85 (95% CI 0.81;0.90) for SUVmax. The sensitivity and specificity
K. A. Miles6, R. C. Rintoul7, N. R. Qureshi8, J. Madden4, K. Eichhorst4, were 77.8% (95% CI 71.3;83.1%) and 74.6% (66.2;81.5%) for
L. Durcan4, K. Cozens4, L. Pike9, D. Sinclair9, R. Eaton10, A. Shah10, qualitative uptake ≥ the mediastinal blood pool and 75.1% (95%
L. Brindle11, A. Cook4, S. George3, on behalf of the SPUTNIK CI 68.5;80.8%) and 80.8% (95% CI 72.9;86.9%) for pre-specified
investigators, F. Gilbert2; SUVmax cutoff of ≥2.5 The optimal SUVmax threshold with
1
Imaging and Nuclear Medicine Department, Brighton and Sussex the best balance between sensitivity and specificity was ≥1.95,
University Hospitals NHS Trust, Brighton, UNITED KINGDOM, which yielded a sensitivity, specificity and diagnostic accuracy
2
Department of Radiology, University of Cambridge School of of 87.3 (95% CI 81.8;91.3%), 70% (95% CI 61.3;77.5%), 80.1 (95
Clinical Medicine, Cambridge, UNITED KINGDOM, 3Public Health CI 75.3;84.1%), respectively. Conclusion: In this multicentre
Sciences and Medical Statistics, University of Southampton, multivendor prospective study, quantitative analysis was more
Southampton, UNITED KINGDOM, 4Southampton Clinical accurate than qualitative grading of the nodule uptake for the
Trials Unit, University of Southampton, Southampton, UNITED diagnosis of malignancy in solitary pulmonary nodules with the
KINGDOM, 5Centre for Innovation and Leadership in Health optimal SUVmax threshold of ≥1.95. References: None.
Sciences, University of Southampton, Southampton, UNITED
KINGDOM, 6Institute of Nuclear Medicine, University College
London, London, UNITED KINGDOM, 7Department of Thoracic OP-175
Oncology, Papworth Hospital, Cambridge, UNITED KINGDOM, Assessment of Pulmonary Lobar Perfusion Fraction and
8
Department of Radiology, Royal Papworth Hospital NHS Prediction of Postoperative Function in Lung Cancer
Foundation Trust, Cambridge, UNITED KINGDOM, 9Division of Patients
Imaging Sciences and Biomedical Engineering, King’s College C. von Nida1, L. Titze2, P. T. Meyer1, B. Passlick2, C. Goetz1;
London, London, UNITED KINGDOM, 10Radiation Protection 1
Department of Nuclear Medicine, Medical Center of the
Department, East and North Hertfordshire NHS Trust, Stevenage, University of Freiburg, Faculty of Medicine, University of
UNITED KINGDOM, 11Faculty of Health Sciences, University Freiburg, Freiburg, GERMANY, 2Department of Thoracic
of Southampton, Southampton, UNITED KINGDOM. Surgery, Medical Center of the University of Freiburg, Faculty
of Medicine, University of Freiburg, Freiburg, GERMANY.

Aim/Introduction: 18Fluorine-Fluorodeoxyglucose-Positron
Emission Tomography-Computed Tomography (PET-CT) plays Aim/Introduction: When planning surgical treatment of
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S76

lung cancer, preoperative assessment of the lung function is 4108 – FR CNRS 3638], Faculty of Medicine, University of Rouen,
an established tool to predict the expected residual function Rouen, FRANCE, 3Rouen University Hospital, Department of
after surgery in particular in patients with borderline function. Pathology and Normandie University, UNIROUEN, Inserm
Lung perfusion scans are recommended in clinical routine - U1245, Rouen University Hospital, Rouen, FRANCE, 4Clinic of
however multiple quantification methods are described and Cedre, Rouen, FRANCE, 5Unit of General and Thoracic Surgery,
used to predict the postoperative function. The aim was to Rouen University Hospital, Rouen, FRANCE, 6Department of
compare the prediction accuracy of planar and truly 3D-analysis Pathology, Henri Becquerel Cancer Center, Rouen, FRANCE.
methods based on CT-anatomy in a pre-operative pool of
patients. Materials and Methods: 100 patients (mean age
68+/-8 years, 63% male) bearing operable lung cancer with Aim/Introduction: Hypoxic areas are typically treatment
borderline lung function were referred to pre-operative lung resistant areas especially radiotherapy. For NSCLC, several
quantification and included. Perfusion planar- and SPECT-data studies have proposed to increase the dose of radiotherapy on
with subsequent low-dose CT were acquired after injection of these volumes defined by FMISO. In Head and Neck cancers, the
174+/-9 MBq Tc99m-MAA (Siemens Symbia Intevo 6, Siemens same approach was performed with FAZA or FMISO, but these
Healthcare GmbH, Erlangen, Germany) and reconstructed. two tracers have never been compared in NSCLC. Materials
Planar analysis was performed using the model-based (upper, and Methods: 20 patients were included before surgery for
median and lower vertical zone) Mende approach (T. Mende localized NSCLC cancer and benefited from three pre-surgical
et al., Nucl Med, 1990) for the calculation of the lobar fractions. PET scans: FDG-PET, FMISO-PET and FAZA-PET. For each patient,
3D-analysis used a CT-based segmentation and VOI transfer to the PET data of the three tracers were compared with each
the co-registered perfusion-SPECT (3D-Lung Quantification, other, and compared to immunohistochemical analysis (CD34,
HERMES Medical Solutions, Stockholm). All patients underwent GLUT-1, CAIX, LDH-5, MCT-4, HIF1-Alpha) after tumor removal.
pulmonary function tests (PFT) including FEV1 and DLCO prior Results: 19 patients were definitively included in this trial: 4
to surgery. This PFT-assessment was used in combination with women and 15 men, with a mean age of 67 ± 7.4 years. For
the scintigraphic planar and 3D lobar fractions to calculate FDG PET, the SUVmax was 12.3 (± 5.4) and the volume with a
the predicted FEV1 and DLCO according to the extent of the thresholding at 40% of SUVmax was 23.2 cc (± 19.2). 18 lesions
pulmonary resection. Comparison between the predicted had a significant uptake (SUV max greater than 1.4) for the F-Miso
values for each method (n=100) as well as a direct comparison and 17 for FAZA. The mean SUV max was respectively 3 (± 1.36)
to post-operative PFT-values (n=16, subgroup of operated with a mean volume of 25.8 cc (± 25.8) for FMISO and 2.16 (± 0.7)
patients) were performed using T-tests, Correlation tests and with a mean volume of 13.06 cc (± 13.76) for FAZA. The SUV max
Bland-Altman analyses. Results: In our population significant F-Miso was greater than SUV max FAZA (p= 0.0003).There was
differences (p<0.05) were found between the results from a good correlation between the SUV max F-Miso and SUV max
planar imaging and 3D-methods for the right upper lobe (23% FAZA at 0.88 (0.72 to 0.95) and a good correlation at 0.732 (0.42
of the tumors) and the left lower lobe (11% of the tumors). to 0.89) for the volume with a thresholding at 1.4 but there were
Correlation between predicted and measured PFT was also no correlation between SUV max FDG and SUV max F-Miso nor
higher for the 3D-analysis compared to the Mende approach FAZA. The immunohistochemical analysis was not correlated
(Spearman’s correlation coefficient 0.62 vs 0.45). Conclusion: to hypoxia PET whatever the staining. Conclusion: This study
The lobar perfusion values obtained by an anatomically driven confirms the very good correlation of the two tracers of hypoxia
3D-quantification differed significantly from the ones obtained and the superiority of FMISO over FAZA. Unfortunately, there is
from the traditional planar approach in 34% of the patients in no correlation with immunohistochemical analysis. References:
our group and showed the most accurate prediction of post- None.
operative PFTs - affecting potentially the operability of the
tumors in individual patients. Considering these preliminary
results, we recommend using 3D-anatomically driven methods OP-177
whenever available. References: None. Breath-Hold with High-Resolution, High-Sensitivity SiPM
PET/CT: Higher FDG Uptake Detected in Neoplastic Lung
Nodules
OP-176 M. Jreige, M. Meyer, G. Allenbach, M. Pappon, M. Nicod Lalonde, N.
First comparison of [18F]-FMISO and [18F]-FAZA for PET Schaefer, J. O. Prior;
imaging of hypoxia in lung cancer before surgery Lausanne University Hospital, Lausanne, SWITZERLAND.
S. Thureau1,2, N. Piton3, P. Gouel2, R. Modzelewski2, A. Dujon4, J.
Baste5, J. Melki5, P. Rinieri5, C. Peillon5, S. Hapdey2, J. Sabourin3, J.
Picquenot6, P. Bohn2, P. Vera2; Aim/Introduction: Accurate pulmonary nodules
1
Department of Radiation Oncology, Henri Becquerel Cancer characterization is highly important considering its impact on
Center and Rouen University Hospital, & QuantIF – LITIS [EA management and prognosis. The introduction of the latest PET/
(Equipe d’Accueil) 4108], Rouen, FRANCE, 2Department of CT scanners combing ultra-dynamic range, high-sensitivity
Nuclear Medicine, Henri Becquerel Cancer Center and Rouen detector technology (SiPM), faster time-of-flight and breath-
University Hospital, & QuantIF – LITIS [EA (Equipe d’Accueil) hold (BH) application may allow optimal visualization and
S77 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

uptake quantification in smaller lesions. Herein, we investigated FDG PET/CT therapeutic and prognostic impact in the initial
the outcome of a single 20-second-BH PET/CT acquisition as assessment of patients with HNSCC cancer. Materials and
compared to the standard free-breathing (FB) one and its effects Methods: From 2004 to 2014, 477 consecutive patients with
on metabolic lung nodule characterization. Materials and HNSCC were included (414M/63W; mean age 62). Conventional
Methods: We retrospectively analyzed all PET/CT examinations work-up (CWU) with clinical examination, endoscopy, cervical
from June 2018 to March 2019 acquired on a Siemens contrast-enhanced CT and/or contrast-enhanced MRI and
Biograph Vision 600 with a lung dedicated BH-acquisition in chest CT, was compared with 18-FDG PET/CT. A group of cancer
addition to standard FB-acquisition. Only nodules confirmed specialists met to determine if 18-FDG PET/CT had caused an
malignant on histopathological analysis or considered highly impact on the therapeutic decision, classifying changes as
suspicious for primary or secondary malignancy based on minor - type 1 (modification of NM staging and/or discovery
their radiologic progression on CT scan were included and of synchronous cancer), moderate - type 2 (modification of the
metabolic characteristics (SUVmax, SUVmean, MTV, TLG and surgical procedure or target volume in radiotherapy) or major
Signal-to-Background Ratio=SBR) were compared between - type 3 (change of treatment type). Three-year follow-up data
both acquisitions. Results: Forty nodules reported as highly were collected. Results: A total of 221 patients (46.3%) were
suspicious in 30 patients were included. The mean nodule affected by any therapeutic impact, and 94 of them (19.5%) had
size, SUVmax, SUVmean, MTV, TLG and SBR were 12.4±5.3mm, different treatment due to 18-FDG PET/CT (type 2 or 3). Type 2
9.3±7.4g/mL, 5.3±4.4g/mL, 1.4±2cm3and 10.2±23.9g and and 3 therapeutic impact was statistically equivalent between
23.9±22.2(1) in FB and 13.2±5.3mm, 14.4±10.7g/mL, 7±4.8g/ the stage I/II subgroup and the stage III/IV subgroup (p=0.02).
mL, 1.3±1.6cm3, 13.3±28.8g and 45.9±37.9(1) in BH, respectively. 3-year overall survival of patients with 18-FDG PET/CT upstaging
Both SUVmax and SBR were significantly higher in BH compared was significantly lower than patients with identical staging
to FB, p=0.016 and p=0.002, respectively. Concordance analysis (44.2% vs 59.8% respectively, p=0.002). In the CWU stage I/II
showed a statistically significant increase of 45%, 20% and 70% subgroup, 29 of them (22%) upstaged to stage III/IV following
of the SUVmax, TLG and SBR values in BH compared to FB. Using the 18-FDG PET/CT; their 3-year overall survival was significantly
BH, MTV was comparable and lung background was slightly, lower than that of concordant stage I/II patients (54.8% vs
but significantly lower (-4%, p=0.03). Conclusion: BH with 82.6%, p=0.001). CWU stage III/IV patients with 18-FDG PET/CT
high-resolution, high-sensitivity latest generation SiPM PET/ downstaging had better overall survival than others (64.8% vs
CT allowed to detect higher metabolic activity in lung nodules 44.4% p=0.01). Conclusion: Systematic 18-FDG PET/CT in the
categorized as highly suspicious with a better visualization due initial assessment of HNSCC should be discussed at any stage
to a higher SBR in comparison to FB. This increased detectability since it allows restaging with a significant impact on therapeutic
may help to increase the sensitivity and specificity of malignant management. References: None.
nodule PET/CT characterization. References: [1] Sonni I, Baratto
L, Park S, et al. Initial experience with a SiPM-based PET/CT
scanner: influence of acquisition time on image quality. EJNMMI OP-179
Phys. 2018 Apr 18;5(1):9. [2] Johnson GB, Peller PJ, Kemp BJ, et al. 18
F-FDG-PET/CT for the assessment and prognostication
Future of thoracic PET scanning. Chest. 2015 Jan;147(1):25-30. Cardiac Tumors
J. Meng1, X. Li2, H. Zhao3, M. Yun3, W. Dong3, M. Kreissl4, X. Zhang3;
1
Beijing Anzhen Hospital, Capital Medical University, BeiJing,
OP-178 CHINA, 2Medical University of Vienna, Vienna, AUSTRIA, 3Beijing
18 Fdg Pet Ct Therapeutic And Pronostic Impact In The Anzhen Hospital, Capital Medical University, BeiJing, CHINA,
Initial Assessment Of Head And Neck Squamous Cell 4
University Hospital Magdeburg, Magdeburg, GERMANY.
Carcinomas A Retrospective Study Of 477 Patients
J. Leclere1, O. Delcroix2, P. Robin2, S. Querellou2, P. Le Roux2, C.
Guezennec2, L. Ollivier3, U. Schick3, J. Rousset4, G. Valette1, R. Aim/Introduction: We sought to evaluate 18fluorine-
Abgral2; fluorodexoyglucose (18F-FDG) PET/CT in distinguishing benign
1
Department of Head and Neck Surgery, Brest University from malignant tumors, and for predicting all-cause mortality
Hospital, Brest, FRANCE, 2Department of Nuclear Medicine, in patients with cardiac neoplasias. Materials and Methods:
Brest University Hospital, Brest, FRANCE, 3Department of We retrospectively analyzed consecutive diagnosed patients
Radiotherapy, Brest University Hospital, Brest, FRANCE, with cardiac tumors (n = 58) undergoing 18F-FDG PET/CT for
4
Department of Radiology, Brest Military Hospital, Brest, FRANCE. staging. Thirty-three (“performance population”: 20 female, age
51 ± 13 years) had histopathological data, the gold standard
in assessing performance of the 18F-FDG variables, maximum
Aim/Introduction: Accurate initial staging of head and neck standardized uptake value (SUVmax) and maximum tumor to
squamous cell carcinoma (HNSCC) is essential for appropriate background ratio (TBRmax). Optimal SUVmax and TBRmax cut-offs
treatment planning and outcome prediction. 18-FDG PET-TDM identifying malignancy were derived by receiver-operating
performance to detect regional lymph node metastasis, distant characteristics analysis, then used to stratify 54 patients with
metastasis or synchronous primary cancer has already been follow-up data (“survival population”: 28 female, age 51 ± 14
demonstrated. The objective of this study was to evaluate 18- years) into “benign” or “malignant subgroups;” subgroups’ overall
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S78

survival, assessed by Kaplan-Meier methodology, was compared OS rates were 60% and 78%, while 3-year PFS and OS rates were
by log-rank testing. Prognostic power was evaluated by Cox 41% and 75% respectively. In multivariate analysis, only baseline
regression analysis. Results: In the performance population, MTV, TLG and positive PET/CT confirmed to be independent
13 patients had benign, 21 malignant cardiac lesions, by prognostic factors for PFS (p=0.032, p=0.046 and p=0.045). No
histopathology. Calculated optimal cut-offs indicating metabolic parameters were correlated with OS. Conclusion: In
malignancy were: SUVmax=4.22, with 100% sensitivity/91.7% conclusion, we have demonstrated that 18F-FDG pathological
specificity vs TBRmax=1.6, with 100% sensitivity/ 91.7% specificity. uptake in GIST occurred in 82% of the population evaluated,
Mean SUVmax and TBRmax were significantly lower in patients with being independently associated with mitotic index, stage
benign primary tumors (n=13) versus their counterparts with and tumor risk groups. Semiquantitative metabolic PET/CT
malignant primary tumors (n =9) or secondary tumors (n = 11) parameters (SUVbw, SUVlbm, SUVbsa, MTV and TLG) were
(SUVmax: 2.43 ± 1.56 versus 9.96 ± 4.02 versus 15.94 ± 7.69; TBRmax: not correlated with any histological, epidemiological and
1.09 ± 0.63 versus 4.12 ± 1.44 versus 6.83 ± 3.22; all p < 0.001). morphological features analyzed except of tumor risk group.
Lifespan was significantly shorter in malignant subgroups versus Moreover FDG-avidity and the metabolic tumour features (MTV
corresponding benign subgroups (p=0.001). SUVmax ≥4.22 and and TLG) were the only parameters significantly correlated with
TBRmax ≥1.59 independently predicted mortality (respective survival rates. References: None.
hazard ratios [95% CIs] 9.54, [2.18-41.84], p = 0.003, 47.434,
[1.399-1608], p = 0.032). Conclusion: In patients with cardiac
tumors, 18F-FDG uptake can be used to differentiate benign 404b
versus malignant lesions with high accuracy, and to foretell
mortality. References: None.
Mini Course 2 - Interactive - Technologist
Committee: Stress Testing for Technologists

OP-180 Sunday, October 13, 2019, 15:45 - 16:45 Lecture Hall 117
Metabolic Behavior And Prognostic Role Of Pretreatment
18
F-FDG PET/CT In GIST
D. Albano1,2, M. Bonacina1, R. Durmo1, E. Cerudelli1, M. Gazzilli1, F.
Dondi1, A. Mazzoletti1, P. Bellini1, F. Bertagna3, R. Giubbini3; OP-181
1
Spedali Civili Brescia, Brescia, ITALY, 2Univeristy of Brescia, Brescia, Stress Testing for Technologists
ITALY, 3Spedali Civili Brescia and University of Brescia, Brescia, ITALY. M. Attard;
Isala, Radiology and Nuclear Medicine
Department, Zwolle, NETHERLANDS.
Aim/Introduction: Our aim was to investigate the metabolic
features of GIST and whether the tumor stage, tumor risk group,
epidemiological (age, gender), histological (Ki-67 index, mitotic 501
index) and morphological (tumor size) variables might be
related to 18F-FDG-PET/CT results. Moreover, we investigated
CME 4 - Radiopharmacy + Drug Development
the prognostic impact of baseline PET/CT parameters on
+ Translational and Molecular Imaging Therapy
outcome survival. Materials and Methods: Thirty-five patients
+ Oncology & Theranostics Committee: Role
with histologically proven GIST were retrospectively enrolled;
of Extracellular Matrices in Cancer and Other
all patients underwent baseline 18F-FDG-PET/CT before any
Diseases
treatment. The PET images were analyzed visually and semi-
quantitatively by measuring the maximum SUVbody weight Sunday, October 13, 2019, 16:30 - 18:00 Auditorium
(SUVbw), SUVlean body mass (SUVlbm), SUVbody surface area
(SUVbsa), metabolic tumor volume (MTV) and total lesion
glycolysis (TLG). For the entire population, receiver operating
characteristic curve analysis was used to identify the optimal OP-182
cutoff point of semiquantitative parameters in the light of Extra Cellular Matrix - A Target in the Future?!
PFS and OS. Survival curves were plotted according to the M. Behe;
Kaplan-Meier method. Results: Twenty-nine (82%) patients Paul Scherrer Institut, Centre of Radiopharmaceutical
had positive 18F-FDG-PET/CT, while the remaining 6 had Sciences, Villigen, SWITZERLAND.
no increased FDG-uptake. 18F-FDG-avidity was significantly
associated with mitotic index, tumor stage and tumor risk group
and not correlated with other features. Semiquantitative PET/CT OP-183
parameters correlated only with tumor risk group. At a median Molecular Imaging of Collagen and Oxidized Collagen in
follow-up of 36 months, progression of disease occurred in 16 Fibrosis
patients with an average time of 21 months; death occurred in P. Caravan;
7 with an average of 36 months. The estimated 2-year PFS and Massachusetts General Hospital (MGH) & Harvard Medical
S79 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

School (HMS), Athinoula A. Martinos Center for Biomedical 503


Imaging, Charlestown, MA, UNITED STATES OF AMERICA.
Joint Symposium 8 - Cardiovascular Committee
/ EACVI: Which Strategy for the Evaluation of
OP-184
Patients at the Time of Multi-Modality Cardiac
Imaging of Activated Fibroblasts in ECM
Imaging?
U. Haberkorn;
Heidelberg University Hopsital, Department of Sunday, October 13, 2019, 16:30 - 18:00 Lecture Hall 312
Nuclear Medicine, Heidelberg, GERMANY.

502 OP-190
Which Role for Cardiac CT(A) in CAD?
Joint Symposium 7 - Physics + Dosimetry D. Andreini;
Committee / AAPM: Interventional Nuclear Centro Cardiologico Monzino, Milan, ITALY.
Medicine

Sunday, October 13, 2019, 16:30 - 18:00 Lecture Hall 311 OP-191
Which Role for MPI in CAD?
J. Knuuti;
OP-185 Heart and PET Centre, Turku, FINLAND.
Nuclear Medicine Approaches in Guiding Surgical
Procedures - Review and Current Status
F. Van Leeuwen; OP-192
Leiden University Medical Center, Interventional Molecular Which Role for Cardiac MRI in Infiltrative
Imaging Laboratory, Leiderdorp, NETHERLANDS. Cardiomyopathies?
M. Fontana;
Royal Free Hospital, UCL, London, UNITED KINGDOM.
OP-186
Methodological Aspects of PET/CT Guided Interventions OP-193
A. Kirov; Which Role for SPECT and PET in Infiltrative
Memorial Sloan-Kettering Cancer Center, Department of Cardiomyopathies?
Medical Physics, New York, NY, UNITED STATES OF AMERICA. O. Lairez;
University Hospital Toulouse, Toulouse, FRANCE.

OP-187
Future Perspectives of Radioembolization Interventional
Methods 505
M. Lam;
University Medical Center Utrecht, Department of Radiology
M2M - Parallel Session: Radiolabelled Peptides
and Nuclear Medicine, Utrecht, NETHERLANDS.
and Proteins

Sunday, October 13, 2019, 16:30 - 18:00 Lecture Hall 111


OP-188
NM Guided Focused Ultrasound - A Potential Future
Application
A. Melzer; OP-194
University of Leipzig, Innovation Centre for Computer Preclinical theranostic study of anti TEM-1 scFv-Fc fusion
Assisted Surgery, Leipzig, GERMANY. proteins
J. Delage1, A. Faivre-Chauvet2, J. Fierle3, N. Schaefer1, G. Coukos1, S.
Dunn3, J. Prior1, D. Viertl1;
OP-189 1
Lausanne University Hospital and University of Lausanne,
All Speakers: Panel Discussion, Questions Lausanne, SWITZERLAND, 2Nantes University Hospital and
University of Nantes, Nantes, FRANCE, 3Ludwig Center for Cancer
Research and University of Lausanne, Lausanne, SWITZERLAND.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S80

Aim/Introduction: TEM-1 (tumor endothelial marker-1) is University Medical Center, Nijmegen, NETHERLANDS.
a single pass transmembrane cell surface glycoprotein and
has been described as a suitable and safe candidate for
cancer therapy. Therefore, a panel of anti TEM-1 scFv-Fc fusion Aim/Introduction: Carbonic anhydrase IX (CAIX) is a molecular
antibody constructs isolated from naïve human antibody by target for several types of anti-cancer therapeutics. Hypoxia-
phage display has been developed in Lausanne. We decided independent overexpression of CAIX is frequent in renal cell
to radiolabel and study them in vitro in a novel theragnostic carcinomas (RCC) and might be used for targeted treatment
approach paradigm. Materials and Methods: Four scFv-Fc of disseminated tumors. However, CAIX can be expressed
fusion antibody constructs tested for purity (electrophoresis) heterogeneously, particularly in granular cell and mixed cell
and affinity to TEM-1 (flow cytometry) were used (2B11, 78Fc, RCC. Radionuclide molecular imaging of CAIX-expression
1C1, 1C1m). Each fragment was conjugated to p-SCN-Bn-DOTA could be a potential non-invasive tool to select patients who
using different excess molar ratio in buffer pH 9. After a 1-hour can benefit from CAIX-targeting therapy. Antibody-based and
coupling reaction time, the non-coupled ligand was eliminated small non-immunoglobulin scaffold protein-based radionuclide
by ultrafiltration on 50kD filters. The number of chelates grafted imaging are two possible approaches approaches. The aim
by antibody was evaluated both with a radiolabeling test and of this study was to compare the imaging properties of the
mass spectrometry analysis (MALDI). The immune fraction of new tracer [111In]In -DOTA-HE3-ZCAIX:2 with the currently
the modified antibody was measured by flow cytometry, using available tracers [99mTc]Tc(CO)3-HE3-ZCAIX:2 and [111In]In-
TEM-1 positive (SK-N-AS, neuroblastoma) and negative (HT- DTPA-G250(Fab’)2, Materials and Methods: Recombinantly
1080, fibrosarcoma) cells lines The purity and the stability of the produced ZCAIX:2 containing a unique C-terminal was site
native and of the conjugated antibodies were evaluated up to specifically conjugated with maleimido derivative of DOTA
one year by HPLC. Each fragment of antibody (500pmol) was chelator. DOTA-ZCAIX:2 was labeled with 111In. In vitro binding
labeled with 177Lu (non-carrier added, 20MBq) in ammonium specificity, cellular processing and affinity was measured using
acetate buffer (0,4M; pH 5,6). To determine radiolabeled SK-RC-52 (7× 105 binding sites/cell) renal cell carcinoma cell-
antibody immunoreactivity, Lindmo assays were performed line. The biodistribution of [111In]In-DOTA-ZCAIX:2 was directly
on SK-N-AS cell lines Results: Purity of scFv-fc fragments were compared with [99mTc]Tc(CO)3-HE3-ZCAIX:2 and [111In]In-DTPA-
confirmed by electrophoresis. MALDI analysis showed that the G250(Fab’)2 in female BALB/C nu/nu mice bearing SK-RC-52
concentration of 20 equivalents of DOTA (4 to 6 DOTA fixed per xenografts. Specificity of [111In]In-DOTA-ZCAIX:2 binding was
antibody) was the best for the radiolabeling. In flow cytometry, tested by saturation of CAIX in xenografts using 100-fold excess
the binding of conjugated fragments was similar to the native of non-labelled ZCAIX:2. Results: LC-MS data confirmed the
antibodies showing that the conjugation did not affect TEM- identity and purity of DOTA-HE3-ZCAIX:2. The radiochemical
1binding. HPLC profile of the native fragments and of the purity of all labelled conjugates was over 99%. In vitro, [111In]In-
conjugated antibodies was stable at one year. The labeling DOTA-ZCAIX:2 bound specifically to CAIX-expressing cells and
with 177Lu was successful with a radiochemical purity up to internalization was slow. The apparent dissociation constants
95%. Immunoreactivity of 2B11 and 78Fc was less than 20% were 1.2, 6 and 0.12 nM for [111In]In-DOTA-HE3-ZCAIX:2, [99mTc]
whereas immunoreactivity of 1C1m and 1C1 was respectively Tc(CO)3-HE3-ZCAIX:2 and [111In]In-DTPA-G250(Fab’)2, respectively.
80% and 90%. Conclusion: We could select 2 fusion antibodies In vivo, the tumor uptake of [111In]In-DOTA-ZCAIX:2 was highly
candidates (1C1 and 1C1m) with successful radiolabeling and specific. The tumor uptake at 4 h after injection was 15±3, 7±1,
radioimmunoreactivity properties. The next step will be to test and 6±1%ID/g for [111In]In-DOTA-HE3-ZCAIX:2, [99mTc]Tc(CO)3-
them in vivo in murine xenografts models with biodistribution HE3-ZCAIX:2 and [111In]In-DTPA-G250(Fab’)2, respectively. Tumor-
and therapeutic studies towards a future translation in patients. to-blood ratios were 63±11, 23±2, and 2.1±0.2 for these tracers.
References: None. At 24 h after injection, [111In]In-DTPA-G250(Fab’)2 demonstrated
tumor uptake of 5±1 %ID/g and tumor-to-blood ratio of 67±12.
111
In-DOTA-HE3-ZCAIX:2 provided significantly higher tumor-
OP-195 to-liver, tumor-to-lung and tumor-to-bone ratios compared to
Comparison Of Affibody- And Antibody Fragments-based both [99mTc]Tc(CO)3-HE3-ZCAIX:2 (parental variant) and [111In]
Caix Imaging Probes In Mice Bearing Renal Cell Carcinoma In-DTPA-G250(Fab’)2. These ratios are essential for imaging of
Xenografts CAIX expression in major metastatic sites of RCC. MicroSPECT/
J. Garousi1, F. Huizing2, A. Vorobyeva1, B. Mitran3, K. Andersson4, CT imaging confirmed the biodistribution data. Conclusion:
C. Dahlsson Leitao4, F. Frejd1, J. Löfblom4, J. Bussink2, A. Orlova3, S. [111In]In-DOTA-HE3-ZCAIX:2 provided the highest tumor-to-
Heskamp5, V. Tolmachev1; organ ratios and imaging contrast. Therefore, this probe can
1
Department of Immunology, Genetics and Pathology, Uppsala be considered as the most promising tracer to image CAIX-
University, Uppsala, SWEDEN, 2Department of Radiation expressing in RCC metastases. References: None.
Oncology, Radboud University Medical Center, Nijmegen,
NETHERLANDS, 3Department of Medicinal Chemistry, Uppsala
University, Uppsala, SWEDEN, 4Department of Protein Science,
KTH Royal Institute of technology, Stockholm, SWEDEN,
5
Department of Radiology and nuclear medicine, Radboud
S81 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

OP-196 OP-197
Pharmacodynamic changes of FAP-targeted IL2 variant [89Zr]-N-sucDf-Amc-2NaI -KuE (89Zr-DANKE) offers a
immunotherapy assessed with [68Ga]Ga-DOTA-Siglec-9 in prolonged time frame for prostate cancer imaging with
B16-FAP melanoma mice potentially improved tumor detection
R. Siitonen1, H. Virtanen1, H. Liljenbäck1,2, O. Moisio1, X. Li1, C. Klein3, S. Muñoz Vázquez1, H. Endepols1, T. Fischer1, B. Zimmermanns1, S.
T. Nayak3, S. Jalkanen4, A. Roivainen1,2; Tawadros2, V. Marmann1, A. Drzezga1, K. Schomäcker1;
1
Turku PET Centre, University of Turku, Turku, FINLAND, 2Turku 1
Clinic of Nuclear Medicine, Cologne, GERMANY,
Center for Disease Modeling, University of Turku, Turku, 2
Decentralized Animal Husbandry Network of the Faculty
FINLAND, 3Roche Pharma Research and Early Development, of Medicine University of Cologne, Cologne, GERMANY.
Roche Innovation Center Basel, Basel, SWITZERLAND, 4MediCity
Research Laboratory, University of Turku, Turku, FINLAND.
Aim/Introduction: The detection of prostate carcinoma lesions
by means of PSMA-PET is usually realized in within few hours
Aim/Introduction: Vascular adhesion protein 1 (VAP-1) is up- after injections with the available radiotracers such as e.g.
regulated at the sites of inflammation and supports contacts [68Ga]PSMA11 or [18F]JK-PSMA7. It cannot be expected that
between leukocytes and inflamed endothelium. Sialic acid the optimum contrast is achieved within such short time of
binding Ig-like lectin 9 (Siglec-9) is a leukocyte ligand for VAP- biodistribution. Therefore, in order to overcome this limitation,
1 and [68Ga]Ga-DOTA-Siglec-9 can be used for PET imaging we have proposed a new PSMA-binding compound that exploits
of inflammation and cancer (1). Interleukin-2 (IL-2) based the longer physical half-life (78h) of 89Zr: [89Zr]DANKE. Materials
immunotherapy is an efficient therapy against cancers but toxic. and Methods: EuK-2NaI-Amc-N-sucDf-Fe was provided by ABX
We evaluated B16-fibroblast activated protein (FAP)-transfected GmbH (Radeberg) and is formed by the pharmacophore EuK
melanoma tumors in mice with longitudinal [68Ga]Ga-DOTA- coupled to a naphthylic linker, and the chelator agent N-sucDf-
Siglec-9 PET/CT imaging during novel tumor stroma targeted Fe. The N-sucDF-Fe moiety functionalizes the molecule for
engineered immunocytokine FAP-IL2v immunotherapy. labeling with 89Zr. The [89Zr]DANKE was characterized in vitro
Materials and Methods: B16-FAP murine melanoma cells were by the calculation of the corresponding Kd value, the cellular
subcutaneously inoculated in immunocompetent C57BL/6J uptake and the internalization in LNCaP cells. Its biodistribution
mice and divided into anti-FAP-IL2v treatment and PBS groups. in vivo was studied with LNCaP prostate tumor xenograft in
The progression of tumor growth was monitored with external mice and PET-imaging experiments were conducted on a Focus
caliper. At 9 days after the inoculation of the cells, a 30-min 220 micro PET scanner. Analogue experiments and compound
dynamic [68Ga]Ga-DOTA-Siglec-9 PET/CT was performed as a characterization were carried out with [68Ga]PSMA11 and [18F]
baseline measurement. Thereafter, the mice were treated with JK-PSMA7. Results: [89Zr]DANKE was labeled in a radiochemical
intravenously injected anti-FAP-IL2v (n=12) or PBS (n=12) and purity ≥99.9%. [89Zr]DANKE, [68Ga]PSMA 11 and [18F]JK-PSMA7
the injections were repeated 3 days later. Subsequent PET/ showed high affinity for LNCaP cells of around 5 nM. The
CT imaging were performed 3, 5 and 7 days after the baseline internalization to cell-associated activity ratios of [89Zr]N-sucDf-
imaging. Mice were sacrificed 5 or 7 days after the baseline Amc-2NaI-KuE at 1 h, 2 h and 3 h was comparable to those of
imaging and tumors were cut into cryosections for ex vivo [68Ga]PSMA11 and [18F]JK-PSMA7. [89Zr]-DANKE showed very
autoradiography. Results: At the end of the study, the size of high stability in PBS and human serum until 7 d at 37 oC. At
the tumors were similar in anti-FAP-IL2v and PBS groups (P=0.73 2 h, all radiotracers showed a comparable tumor uptake of
at day 7). However, the tumor uptake of [68Ga]Ga-DOTA-Siglec-9 approximately 20% ID/g. The biodistribution profiles of [89Zr]
was significantly higher in anti-FAP-IL2v treated mice compared DANKE in normal tissues at 2 h and 4 h post injection were
to PBS group (day 7: tumor-to-muscle ratio 2.6 ± 0.091 vs. 2.1 ± found to be similar to those of [68Ga]PSMA11 (p<0.0001) and
0.17, P=0.026). This was confirmed by tumor autoradiography [18F]JK-PSMA7 (p<0.0001). [89Zr]DANKE allowed the acquisition
analyses (37 ± 2.6 vs. 29 ± 2.2 PSL/mm2, P=0.035). There were of small animal PET-images with demarcated tumor after 24 h
no differences between groups 3 or 5 days after the baseline and 52 h p.i., showing that over time the compound remains in
imaging. [68Ga]Ga-DOTA-siglec-9 PET uptake results correlated the tumor with very low activity in background except for the
well with tumor volume (r=0.48, P<0.0001). Conclusion: kidneys. The analysis of the PET-images also revealed that the
Although anti-FAP-IL2v treatment had no effect on tumor tumor-to-background ratio is increasing over time. Conclusion:
growth, the results suggest that it induced VAP-1 expression This study demonstrates that the tumor uptake and the
detected by [68Ga]Ga-DOTA-Siglec-9 in tumors and the [68Ga] biodistribution in normal tissues of [89Zr]DANKE is comparable
Ga-DOTA-Siglec-9 PET/CT imaging has potential as a useful to [68Ga]PSMA11 and [18F]JK-PSMA7. The small animal PET data
method for assessing pharmacodynamic changes during the suggest that [89Zr]DANKE remains in the tumor up to 52 h p.i.
anti-FAP-IL2v immunotherapy. References: (1) Aalto K. et al. with increasing tumor/background ratio. Together with the
Blood 2011;118(13):3725-33 long half-life of the [89Zr]-label, this novel tracer may therefore
allow late PET-acquisition with improved lesion detection.
References: None.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S82

OP-198 OP-199
Renal Radioactivity Accumulation In Mice Injected With EPI-PEG-DOTA: Novel androgen receptor ligand as an
Radiometal Labeled Affibody Molecules, Is Reduced By alternative to PSMA ligands
Maleate And Fructose F. Braun1, S. Muñoz1, V. Marmann1, T. Fischer1, H. Endepols1, M. von
M. Altai1, A. Vorobyeva1, A. Orlova2, V. Tolmachev1, J. Garousi1; Brandenstein2, M. Pietsch3, A. Drzezga1, K. Schomäcker1;
1
Immunology, Genetics and Pathology, Uppsala, SWEDEN, 1
University of Cologne, Clinic of Nuclear Medicine,
2
Department of Medicinal Chemistry, Uppsala, SWEDEN. Cologne, GERMANY, 2University of Cologne, Clinic of
Urology, Cologne, GERMANY, 3University of Cologne,
Institute of Pharmacology, Cologne, GERMANY.
Aim/Introduction: Advances in biotechnology have led to
the development of alternatives to monoclonal antibodies for
targeted radionuclide-based imaging and therapy. Affibody Aim/Introduction: Prostate carcinomas (PC) not only
molecules were successfully implemented for radionuclide overexpress PSMA but also different subtypes of the androgen
molecular imaging applications both in preclinical and clinical receptors (AR). Therefore, they can be used as an alternative target
settings. However, the high renal retention of radiometal- for radioactive vectors. In contrast to numerous ligands with high
labeled affibody molecules hampered their use in targeted AR affinity, the chlorohydrin-modified bisphenol-A based “EPI”
radionuclide therapy. Affibody molecules (7 kDa) are readily shows even irreversible AR binding, thus EPI-derivatives provide
filtered by glomeruli and subsequently reabsorbed. Like promising ligands for use in radionuclide based targeting of
many peptide-based agents, the reabsorption of radiolabeled PC. Here, we present a new radioactive vector, the EPI-PEG-
affibody molecules is mainly due to endocytosis in the DOTA, labeled with 68Ga and 177Lu and its accumulation rate in
proximal tubule cells. We have shown earlier that this process is PC cells in ovo. Materials and Methods: For the labeling with
independent on the nature of binding-site and is not mediated 68
Ga and 177Lu, EPI-064 ligand was modified with the linker PEG3
by the megalin-cubulin endocytic receptors complex. This and the chelator DOTA to generate the compound EPI-PEG-
study evaluates the effect of several drugs on the renal uptake, DOTA (EPD). EPD was synthesized and tested for radiochemical
processing and retention of the 99mTc radiolabeled anti-HER2 purity, cell binding, and in vitro stability. The pharmacodynamic
affibody molecule ZHER2:2395. For this we have tested the effect of properties of this compound were tested with the chicken egg
probenecid (organic anion transport inhibitor), furosemide (loop chorioallantoic membrane (CAM)-culture. LNCaP tumor cells
diuretic), mannitol (osmotic diuretic), colchicine (microtubule were CAM-xenotransplantated and cultured. Then the 68Ga-
inhibitor) as well as maleate and fructose (ATP depleting agents) labeled EPD, and for reason of comparison, [18F]FDG and [18F]
on renal activity post 99mTc-ZHER2:2395 injection. Materials and PSMA7 were injected into the bloodstream of chicken embryo.
Methods: Twenty eight NMRI normal mice were divided into 7 The uptake was monitored by a small animal positron emissions
groups (n=4). All groups were injected with 1 µg 99mTc-ZHER2:2395 tomography (PET)-scanner. Subsequently, the activity uptake
affibody molecule. In six of the groups mice were pre injected was monitored in the tumor tissue and blood and compared
with, probenecid (20 mg/kg, 1 h, i.p.), furosemide (2.5 mg/kg, 5 with the accumulation of the control tracers [18F]PSMA7 and
min, i.v.), mannitol (400 mg/kg, 5 min, i.v.), colchicine (1 mg/kg, 5 [18F]FDG. Results: The successful synthesis of the EPD-precursor
h, i.p.), maleate (400 mg/kg, 5 min., i.v.) and fructose (50 mmol/ was proven by 13C, 1H-NMR and mass spectrometry. The labeling
kg. 5 min, i.p.) prior to the injection of 99mTc-ZHER2:2395 affibody of EPD yielded a purity of >98% for 177Lu and >96% for 68Ga with
molecule. The last group was preinjected with PBS (control). a specific activity of 40 MBq/nmol with sufficient cell binding.
Mice were sacrificed 4 h post affibody injection and organs were In case of [177Lu]EPD, after 48h a value of 92% for the stability in
collected and measured for activity. Autoradiographic images human serum was found. Examination of the pharmacokinetic
of the kidneys from treated mice were acquired and compared properties observed in ovo showed significant accumulation
with controls. Results: Preinjection of probenecid, furosemide, of [68Ga]EPD in the tumor tissue. The tumor-to-blood ratio of
mannitol and colchicine did not influence renal-associated PET-derived uptake after 30 min was 1.82 in the case of [68Ga]
activity post 99mTc-ZHER2:2395 injection. Preinjection of the ATP EPD and 2.99 in the case of [18F]PSMA7. With [18F]FDG, only
depleting agents, fructose (50 mmol/kg. 5 min, i.p) and maleate tumor/blood ratios <1 were observed. Conclusion: The novel
(400 mg/kg, 5 min., i.v.) led to the reduction of renal associated compound EPD appears to be a promising candidate for the
radioactivity by 33 % and 51%, respectively, compared to the future use as PC targeting agent particularly in cases with low or
control group. Autoradiographic images showed that the lacking PSMA-expression. References: None.
accumulation of radioactivity post 99mTc-ZHER2:2395 injection was
in the renal cortex. Both fructose and maleate significantly
reduced this cortical accumulation of radioactivity, however at OP-200
different levels. Conclusion: A presumed mechanism of action Evaluation of Bivalent GRPR Radioligands for Targeting
for both fructose and maleate may be attributed to disruption Prostate Cancer
of ATP-mediated cellular uptake and endocytosis processes of N. Romantini1, S. Dobitz2, M. Alam1, M. Spillmann1, R. Schibli1, X.
99m
Tc-ZHER2:2395 in tubular cells. References: None. Deupi1, H. Wennemers2, P. Berger1, M. Behe1;
1
Paul Scherrer Institute, Villigen, SWITZERLAND, 2Federal
Institute of Technology (ETH), Zurich, SWITZERLAND.
S83 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

Aim/Introduction: Targeted radiotherapy (TRT) aims at the pilot studies. The aim of this phase I study was to assess the
destruction of tumor tissue by radioactivity specifically delivered safety and to validate 68Ga-SB3 PET-CT imaging of primary PCa
to neoplastic lesions. Since the gastrin-releasing peptide tumors in patients scheduled for prostatectomy. Secondary
receptor (GRPR) is overexpressed on prostate cancer cells, it aims included GRPr-expression levels, dosimetry and optimal
is an ideal target for TRT. In this project, 177Lu-labeled bivalent thresholding. After previously published primary data we
peptides are evaluated as high affinity ligands for GRPR. Two are now ready to present our complete dataset. Materials
agonistic recognition motifs are fused on a rigid oligoproline and Methods: We included ten therapy-naive PCa patients
backbone in different distances from each other (10, 20 or 30 scheduled for prostatectomy. 68Ga-SB3 (185±39MBq, 40±5μg)
Å), forming the three compounds BBN-10, BBN-20 and BBN- was administered, followed by an intensive PET-CT imaging
30. A monovalent oligoproline-backbone-based compound protocol. Surgically obtained prostate tissue was cut following a
(BBN-00) as well as the well-characterized agonist AMBA served template. Pathologists determined tumor localizations, Gleason
as references. Materials and Methods: We determined the Scores (GS), and in vitro autoradiography was performed. Time-
receptor-mediated cellular uptake of all compounds as well activity curves (TAC) were used to estimate residence times.
as the biodistribution of BBN-20, BBN-00 and AMBA in tumor- Recalculation to standard volumes, effective dose to the body,
bearing mice 4 h post-injection. Moreover, we established as well as absorbed doses to organs were calculated using
assays to explore the influence of bivalent ligands on G-protein IDAC dose 2.1 model. MRIs were matched to PET-CT by hand
and arrestin dependent receptor signaling using luciferase registration and trans-axial whole-prostate histopathological
complementation and BRET assays. Results: All bivalent overlays were created. ROC curves of PET thresholding and
compounds showed significantly higher cellular uptake (BBN- tumor positivity on histopathology were calculated. Results:
10: 29.2 ± 2.3%, BBN-20: 28.2 ± 2.5% and BBN-30: 20.2 ± 3.5%) Administration of 68Ga-SB3 proceeded without side effects. PET-
than the monovalent reference BBN-00 (7.0 ± 1.4%) but could CT imaging visualized lesions in 8 out of 10 patients. A total of
not outperform the literature reference AMBA (43.5 ± 3.5%) 15 lesions were found in pathological evaluation of 10 patients,
probably due to steric hindrance of the oligoproline backbone. 5x GS6, 9x GS7 and 1x GS8. PET-CT imaging had a sensitivity of
Moreover, the cellular uptake was clearly distance-dependent 82% in low Gleason disease (GS3+3 and GS3+4). PET showed
since BBN-30 showed significantly lower uptake than BBN-10 2 false positives and missed 2 tumor foci. Autoradiography of
and BBN-20. Signaling assays confirmed that all oligoproline- PCa tissue showed heterogeneous GRPr-expression and was
based ligands maintained their agonistic characteristics negative in 4 patients. The PET-negative patients had at least
and induced G-protein as well as arrestin recruitment. The one GRPr negative tumor. Of autoradiography-positive patients,
biodistribution study of BBN-20 resulted in a 1.5- to 2-fold SUVmax showed significant correlation to GRPr expression
increase in tumor uptake in comparison to the monovalent levels. Effective dose was 0.0144 mSv/MBq (1h voiding interval
BBN-00 and AMBA. Furthermore, both oligoproline-based ICRP103), similar to other 68Ga labeled compounds. Quick
compounds showed a decreased uptake in healthy receptor- renal excretion kinetics were observed. GRPr-rich pancreas
expressing organs such as the pancreas, leading to improved showed high physiological uptake, highest absorbed dose was
tumor-to-pancreas ratios (AMBA: 0.07 ± 0.02, BBN-00: 0.26 ± 0.05, therefore found in this organ (0.198 mGy/MBq), followed by
BBN-20: 0.26 ± 0.09). Conclusion: We show that bivalency is a bladder wall and kidneys. In the PET positive patients PET/CT-
promising strategy to increase the uptake into receptor-positive MRI-histopathology matching was performed. Optimal imaging
cells in vitro. This favorable effect depends on the distance time did not show significant differences between 60 or 150 min
between the recognition motifs. Furthermore, a biodistribution post injection. Optimal threshold was 35% SUVmax (range 35%-
study of the bivalent compound BBN-20 resulted in higher 75%). Conclusion: Based on this data we showed the potential
tumor accumulation compared to the literature reference. of 68Ga-SB3 PET-CT as a diagnostic tool in the imaging of early
References: None. PCa. References: None.

506
OP-201 Do.MoRe - Parallel Session: 177Lu PRRT and other
Imaging of Prostate Cancer in Therapy-Naive Patients
Using the GRPr Antagonist 68Ga-SB3
Preclinical & Clinical Dosimetry
I. L. Bakker1, A. C. Fröberg1, M. B. Busstra1, J. F. Verzijlbergen1, M.
Konijnenberg1, I. Schoots1, G. J. L. H. van Leenders1, E. de Blois1, J. Sunday, October 13, 2019, 16:30 - 18:00 Lecture Hall 112
Veenland1, W. M. van Weerden1, T. Maina2, B. A. Nock2, M. de Jong1;
1
Erasmus MC, Rotterdam, NETHERLANDS, 2INRASTES,
NCSR “Demokritos”, Athens, GREECE.
OP-202
In vitro dose-response comparison of [177Lu]Lu-labelled
Aim/Introduction: The prostate cancer (PCa) target gastrin somatostatin receptor agonist and antagonist
releasing peptide receptor (GRPr) shows overexpression in early G. Tamborino1,2, M. De Saint-Hubert1, L. Struelens1, S. Dalm2, E.
disease. The gallium-68-labelled GRPr-antagonist Sarabesin 3 Ruigrok2, M. De Jong2, J. Nonnekens2,3, M. W. Konijnenberg2;
(68Ga-SB3) was selected after excellent results in (pre)clinical 1
Research in Dosimetric Applications, Belgian Nuclear
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S84

Research Centre (SCK•CEN), Mol, BELGIUM, 2Department OP-203


of Radiology & Nuclear Medicine, Erasmus MC, University Absorbed doses to kidneys based on one or two SPECT
Medical Center Rotterdam, Rotterdam, NETHERLANDS, measurements versus three SPECT measurements in 777
3
Department of Molecular Genetics, Erasmus MC, University patients with neuroendocrine tumours receiving 177Lu-
Medical Center Rotterdam, Rotterdam, NETHERLANDS. DOTATATE therapy
M. Sandstrom1,2, D. Granberg1, A. Sundin1, M. Lubberink1,2;
1
Nuclear medicine & PET, Uppsala University, Uppsala, SWEDEN,
Aim/Introduction: Peptide receptor radionuclide therapy 2
Medical physics, Uppsala University Hospital, Uppsala, SWEDEN.
(PRRT) using radiolabeled somatostatin receptor (SST) is very
effective for treatment of neuroendocrine metastatic tumors.
Recent studies indicate that radiolabeled SST antagonists show Aim/Introduction: As in all therapies using ionizing radiation,
better tumor targeting during clinical imaging and preclinical a patient-specific optimization of the delivered radiation should
therapy, despite little to no internalization in the cancer cells. be performed in therapy with 177Lu-DOTATATE. At our centre, the
However, preclinical studies are often limited to activity uptake, number of treatments is based on the absorbed dose (AD) to
with no correlation between the delivered absorbed dose the kidneys. For logistical reasons, estimation of absorbed doses
and the biological end-point. This study aims to calculate the should be performed with as few measurements as possible. The
absorbed dose to the nucleus for [177Lu]Lu-DOTA-Tyr3,octreotate aim of the present work was to study how well kidney AD and
(177Lu-DOTA-TATE, SST agonist) and [177Lu]Lu-DOTA-JR11 (177Lu- effective half-life (teff) estimations using methods with one or
DOTA-JR11, SST antagonist), for comparison with DNA damage two measurement points agree with the method we use today
induction. Materials and Methods: Time-activity curves were that is based on three imaging points. Materials and Methods:
determined for 177Lu-DOTA-TATE and 177Lu-DOTA-JR11 uptake 777 patients (333 female and 444 male) with neuroendocrine
in medium, membrane-bound and internalized-fractions of tumors with high somatostatin receptor expression were
U2OS+SST2 cells during 4h incubation and 6 days follow-up. included. SPECT/CT over the abdomen were acquired at 24,
An upgraded version of our previously developed dosimetry 96 and 168 h after start of infusion of 177Lu-DOTATATE. AD
model[1], implementing polygonal mesh (PM) structures to and teff were calculated using single exponential fits to data
realistically represent the cells within Geant4, was used to from 3 measurements (24-96-168) or two measurements (24-
determine the absorbed dose-rate as function of time and 96 and 24-168). In addition, absorbed doses were calculated
absorbed dose to the nucleus at the end of the 4h-incubation, using a single measurement, assuming teff 50 h (96/50h). Bias
as well as cumulated over the 6 days follow-up. Visualization of AD and teff values relative to those based on the three-point
of p53 binding protein 1 (53BP1) foci was used to determine measurement were calculated. To test statistical significance
the number of DNA double-strand breaks (DSBs), after 4h a Wilcoxon matched-pairs signed rank test with a P-value of
incubation with 2.5 MBq/ml of [177Lu]Lu-diethylene-triamine- 0.05 for significance was used. Median, Min and Max of the
pentaacetic acid (177Lu-DTPA), 177Lu-DOTA-TATE and 177Lu- deviations were also calculated. Results: Bias versus AD(24-96-
DOTA-JR11. Results: After 4h-incubation, most of 177Lu-DOTA- 168) was -3%(-20-72) (Median (Min-Max)) for AD(24-96), 3%(-22-
JR11 uptake (80% ± 29%) was membrane bound, whereas most 30) for AD(24-168) and -7%(-51-27) for AD(96/50h). The bias for
of 177Lu-DOTA-TATE uptake (78% ± 31%) was internalized. The teff in the AD calculations versus AD(24-96-168) was -9% (-53-
total 177Lu-DOTA-JR11 uptake was 2.4 times higher than 177Lu- 63) for AD(24-96) and 0% (-9-4) for AD(24-168). In all tests there
DOTA-TATE, however, the SST antagonist uptake caused only 1.6 was a small but significant difference for the whole group. In
more DSBs compared to the SST agonist, demonstrating that about 15% of the patients the bias in teff was more than 20%
total uptake does not correlate well to the number of 53BP1 when ignoring the 168-h scan. In about 5-10% of the patients
foci. A good linear correlation (R2=0.95) between the absorbed AD differed more than 20% for all methods that excluded the
dose to the nucleus after 4h Lu-DTPA (0.34Gy±0.00), 177Lu-DOTA- 168-h measurement. Using a fixed limit of the absorbed dose
TATE (0.49Gy±0.03) and 177Lu-DOTA-JR11 (0.70Gy±0.07) and to the kidneys, this would mean that these patients would
the corresponding number of repair foci (3.63±0.58, 9.91±0.58, be given either too many or too few treatments. Conclusion:
15.28±0.77, 24.88±1.18, respectively) was found. Hence, the Although absorbed dose calculations based on only one or two
absorbed dose delivered by the antagonist after the first 4h measurement points may serve as a good approximation for
was 43±22% more than the agonist. Dose-response models the majority of patients, it leads to substantial errors affecting
for cell survival after 6 days need to be established but, from the number of given treatments in about 10% of patients. Since
preliminary calculations, 177Lu-DOTA-JR11 is expected to lead this is a radiation treatment a high precision for all patients is
to much lower survival than 177Lu-DOTA-TATE. Conclusion: Our warranted, and three measurements, or at least inclusion of a
cellular dosimetry model is currently successful in predicting the late 168-h measurement, are recommended. References: None.
number of DNA foci and we are eager to show it can predict cell
survival. This will lead to better understanding of dose-response
models and repair mechanisms at low dose-rate. References:
[1] G. Tamborino, et al. EANM Congress 2018
S85 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

OP-204 OP-205
Quantitative SPECT/CT voxel-based dosimetry in 177Lu- Personalized OAR dosimetry in patients with NET:
octreotate PRRT: the selection of the reference timepoint preliminary results of a Phase II study
for deformable CT registration impacts on the calculated E. Tonini1, M. Longo1,2, S. Di Biaso3, A. Barboni1, A. Turra1, L. Longo3,
absorbed dose to target tissues G. Di Domenico3, L. Uccelli4, S. Panareo4, C. Cittanti4, I. Santi4, I.
A. Desy1,2, G. F. Bouvet1,2, D. Mirando3, A. S. Nelson3, J. M. Rambaldi4, M. Bartolomei4;
Beauregard1,2; 1
Arcispedale Sant’Anna Hospital, Medical Physics Unit,
1
Department of Medical Imaging and Oncology Division Ferrara, ITALY, 2Sapienza University of Rome, Ph. D.
of Research Center, CHU de Québec - Université Laval, Program in Morphogenesis & Tissue Engineering, Rome,
Quebec City, QC, CANADA, 2Department of Radiology ITALY, 3Dipartimento di Fisica e Scienze della Terra,
and Nuclear Medicine and Cancer Research Center, Ferrara University, Ferrara, ITALY, 4Arcispedale Sant’Anna
Université Laval, Quebec City, QC, CANADA, 3MIM Software Hospital, Nuclear Medicine Unit, Ferrara, ITALY.
Inc., Cleveland, OH, UNITED STATES OF AMERICA.

Aim/Introduction: Peptide-receptor radionuclide-therapy


Aim/Introduction: Dosimetry based on serial quantitative (PRRT) represents the treatment of choice for patients affected
SPECT (QSPECT)/CT imaging allows personalizing 177Lu peptide by neuroendocrine-tumours (NET) and has been mostly
receptor radionuclide therapy. When performing voxel-based administered in subsequent induction-cycles. Kidneys and
dosimetry using deformable CT registration, the first timepoint bone-marrow (BM) toxicities are the dose limiting factor in
scan is typically set as the reference, to which other scan(s) PRRT, which has to be administered to not exceed cumulative
are registered1. Our aim was to investigate if selecting another absorbed-dose (AD) of 23 and 2 Gy to kidneys and BM
timepoint as the reference would impact on the calculated respectively. The present study aims to accurately perform
absorbed doses to target tissues. Materials and Methods: Data kidneys and BM dosimetry of patients treated with PRRT both at
from 22 consecutive patients with neuroendocrine tumours first- and last-administration cycle in order to use the dosimetric
enrolled in the P-PRRT trial (NCT02754297) were analysed using results to guide the administration of safe activities after the
a voxel-based dosimetry software package (MIM SurePlanTM first-cycle and to verify dosimetry at the last-cycle. Materials
MRT). Following the first injection of 177Lu-octreotate (8.9±2.0 and Methods: Forty-eight patients with NET have been treated
GBq), two QSPECT/CTs were acquired at 23.3±1.3 (Day-1) and at Arcispedale Sant’Anna (Ferrara, Italy) between 2018 and 2019
70.9±1.4 hours (Day-3) post-injection. A deformable registration according to the FENET-2016 protocol, which includes 5-cycles
of one CT to the other was performed and applied to the of 177Lu-DOTATOC administrations used alone or in combination
corresponding QSPECT, and the 3D dose map was calculated. with 90Y-DOTATOC on second and fourth cycle. SPECT/CT
This was repeated twice, with Day-1 and Day-3 CTs as the images were acquired on first- and fifth-cycle at 1, 24 and 48 h
reference, respectively. Resulting absorbed doses to target after the administration of the 177Lu- DOTATOC. For each patient,
tissues (kidney, spleen and tumour) were compared using (i) the kidneys and BM doses were calculated at first- and fifth-cycle.
maximum dose (Dosemax), and (ii) the isodose volume (Voliso). The activity concentration in kidneys was calculated according
For the kidney and the spleen, the latter was defined as the to MIRD scheme; the image-based method was applied for
volume of the lowest integer isodose allowing isolation of the calculating AD to BM (using L2-L4 activity concentration). The
tissue, while for the tumour, the 20 Gy field-of-view isodose was MIM software was used for contouring, image coregistration
used. Results: 53 of 60 (88%) evaluable target tissue samples and statistics while OLINDA for the AD calculation. For patients
had a higher Dosemax when Day-3 was the reference timepoint. treated in combination with the two radionuclides, dose
Selecting Day-1 as the reference resulted in a median (IQR) calculation was also performed for 90Y, scaling the activities
Dosemax that was lower by -8.4% (-13.4% to -5.6%), -8.9% (-11.0% in kidneys and BM to correct for the difference in half-life.
to -3.4%), and -11.4% (-18.5% to -2.8%) for the kidney, spleen and Dosimetric results between first- and fifth-cycle were compared
tumour, respectively. Similarly, 40 of 60 (67%) tissue samples had as well as those obtained with two radionuclides. Results: The
a larger Voliso with Day-3 as the reference. Fixing Day-1 lowered administered activities per cycle have been from 1.9 to 5.5 GBq.
Voliso by -4.3% (-14.3% to 1.5%), -7.2% (-21.1% to 3.2%), and -2.3% The kidneys AD per unit activity lie between 0.2÷1.2 Gy/GBq
(-15.4% to 4.9%), respectively. Our provisional hypothesis is that and 1.5÷4.0 Gy/GBq, while BM AD per unit activity are between
inconsistencies in the QSPECT vs. CT alignment, along with slight 0.01÷0.04 Gy/GBq and 0.07÷0.20 Gy/GBq for treatment with
redistribution of counts in the co-registered QSPECT matrix, 177
Lu and 90Y respectively. 90Y absorbed-doses are approximately
may translate into activity underestimations in the high-uptake a factor of five higher than those with 177Lu. The cumulative
regions. The impact of this on voxel dose calculations could be doses resulted from 5 to 27 Gy for kidneys and from 0.3 to 1.1 Gy
amplified when Day-3, the most contributory scan, is registered for BM, with differences between first- and fifth-cycle from 0 to
to Day-1. Conclusion: QSPECT/CT voxel-based 177Lu dosimetry 40%. Conclusion: Routine dosimetry for personalized treatment
is affected by the choice of the reference scan for deformable of patients underwent 177Lu- and 90Y-DOTATOC treatments also
registration. Using a later timepoint as the reference may be administered in combination has been successfully established
preferable for estimating absorbed doses to high-uptake tissues. in our institution. Comparing 177Lu and 90Y dosimetric results
References: 1. Jackson PA et al. Med Phys 2013;40(11):112503. has provided a useful method to guide the clinicians in using
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S86

combined treatment modality. References: None. References: 1Mora-Ramirez et al. Eur J Nucl Med Mol Imaging
45(Suppl 1), S180 (2018).2M. Stabin and A. Farmer, J. Nucl. Med.
53(Suppl 1), 585 (2012).
OP-206
Absorbed dose calculation considering organ mass
variation for patients treated with Luthatera OP-207
E. Mora Ramirez1,2, A. Vergara-Gil1, J. Ocampo-Ramos1, J. Pouget3, Cellular dose-response models for [177Lu]Lu-DOTA-
P. Kotzki3,4, L. Santoro4, E. Deshayes3,4, M. Bardies1; Tyr3,octreotate radionuclide therapy compared to
1
CRCT, UMR 1037, INSERM, Université Toulouse III Paul external beam radiotherapy
Sabatier, Toulouse, FRANCE, 2Universidad de Costa Rica, G. Tamborino1,2, M. De Saint-Hubert1, L. Struelens1, M. W.
Escuela de Fisica, CICANUM, San Jose, COSTA RICA, 3Institut Konijnenberg2, M. de Jong2, J. Nonnekens2,3;
de Recherche en Cancérologie de Montpellier, Montpellier, 1
Research in Dosimetric Applications, Belgian Nuclear
FRANCE, 4Nuclear Medicine Department, Institut Régional Research Centre (SCK•CEN), Mol, BELGIUM, 2Department
du Cancer de Montpellier, Montpellier, FRANCE. of Radiology & Nuclear Medicine, Erasmus MC, University
Medical Center Rotterdam, The Netherlands, Rotterdam,
NETHERLANDS, 3Department of Molecular Genetics, Erasmus
Aim/Introduction: Molecular Radiotherapy (MRT) dosimetry MC, Rotterdam, The Netherlands, Rotterdam, NETHERLANDS.
requires sequential quantitative SPECT/CT at different time
points to assess pharmacokinetics in order to compute the
absorbed dose delivered to the patient. Due to organ movements Aim/Introduction: To investigate the applicability of different
or wrong positioning of the patient, organ mass can vary at dose-response models for in vitro radiobiological experiments
each time point. Yet, most often clinical MRT dosimetry assumes with Peptide Receptor Radionuclide Therapy (PRRT) in
constant organ mass. The aim of this work is to integrate organ comparison to the well-established linear-quadratic (LQ)
mass variation in the case of peptide receptor radionuclide model. Materials and Methods: We upgraded our previously
therapy dosimetry. Materials and Methods: Two patients (1F, developed dosimetry model [1], implementing 9 polygonal
1M) treated with Lutathera® were previously reported1. The mesh structures (PM) to realistically represent the cell on
same patients were reprocessed using the Dosisoft workstation. Geant4 and assuming instant translocation of the radionuclide
Manual segmentation of liver, spleen and left/right kidneys was to the Golgi (G). After wash-out, we tested two hypotheses:
performed using the CT at each time point. The definition of the (1) re-localization in the cytoplasm (Cy) and (2) permanent
absorbed dose rate at each time point requires adjusting the incorporation in the G. This model was used to determine the
reference S-value by the organ mass ratio between reference absorbed dose to the nucleus for cells undergoing [177Lu]
model and patient: Spat(t) = Sref x [Mref/Mpat(t)]. The activity-mass Lu-DOTA-Tyr3,octreotate PRRT treatment. Clonogenic survival
concentration at each time point was integrated, considering assays were performed for [177Lu]Lu-DOTA-Tyr3,octreotate (0.1-
no activity at t=0 and a mono-exponential fit from the first 2.5 MBq/ml) and for an x-ray irradiation characterized by 86 keV
time point to infinity, and multiplied by the time-invariant of average energy (0.5-4 Gy). The LQ, repairable-conditionally
product (Sref x Mref). These results were then compared to repairable (RCR) and linear model (L) were used to fit the data.
previous calculations using OLINDA V22 where S-values were Results: Contrary to the results found with the truncated cone
adjusted from the model to the patient but assumed no time- representation of the cell [1], the absorbed dose per decay
related organ mass variation (one reference time was selected (S-value) for the PM structures is not increased if the radionuclide
to perform segmentation). Results: For liver, spleen and L/R is localized in Cy rather than cell membrane. However, if the
kidneys, the average organ mass and standard deviation were internalised fraction of activity is assumed to be translocated
1673.4±31.6g, 102.2±6.8g, 127.7±6.2g, 114.5±6.8; 1448±59.7g, into the G, the S-value increases on average +64% and up to
263.1±65.6g, 175.2±30.4g, 182.8±18.7g for the female and male +149%, depending on the cell morphology. The absorbed
patient respectively. Absorbed dose estimations for liver, spleen dose to the nucleus was 2.8-3 fold less, when modeling the
and L/R kidneys were 15.9Gy, 4.0Gy, 3.3Gy, 3.8Gy and 1.1Gy, cells realistically using PMs compared to MIRD-spheres. Testing
4.2Gy, 2.6Gy, 2.5Gy for the female and male patient respectively. hypothesis 2, the absorbed dose to the N (0.2-2.9 Gy) increases
In the case of OLINDA V2 the absorbed dose results were for on average with a factor of 1.38 compared to hypothesis 1
liver, spleen and kidneys 17.8Gy, 3.8Gy, 3.6Gy (for both kidneys) (0.1-2.1 Gy), corresponding to survival fractions 60%-40% for
and 1.1Gy, 4.5Gy, 2.7Gy (for both kidneys) for female and male the range of tested activities. The L-model, preferred by the
patient, respectively. The relative variation between results from Akaike Information Criterion, relies on the assumption of a high
the 2 approaches was between -10.6 and 4.8% among all organs α/β or a short sub-lethal damage repair half-life, which would
and for both patients. Conclusion: The proposed method lead to ignore the quadratic term of the LQ-model. The RCR
is indicated whenever important mass variations in time are model instead, favored by the F-test, assumes that the repair
observed. Further investigations will consider organ mass system can be triggered only by potentially repairable damage,
variation and integration of absorbed dose rates obtained using not detected at very low doses; this would explain the over-
the local energy deposition assumption, convolution or Monte response in the low-dose region and could be fostered by the
Carlo modelling of radiation transport and energy deposition. affinity with the so-called inverse dose-rate effect. Conclusion:
S87 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

Our cellular dosimetry model showed different dose-response registered in only one patient. Conclusion: Our preliminary
correlations for PRRT compared to EBRT. The flattening of the experience suggests that PPRT might be a safe and new
LQ-curve is representative of protracted exposures, whilst the valuable tool for palliative intent in pediatric patients affected
RCR model predicts the hypersensitivity in the low-dose region, by NETs. The main observed advantages are the improvement of
possibly explained by dose-rate dependent repair mechanisms. life quality with symptoms relief, the absence of kidney toxicity
References: [1] G. Tamborino, et al. EANM Congress 2018. and the short duration of hospitalization. Although the small
number of evaluated patients we observed that the absorbed
dose per administered activity was in line to the values reported
OP-208 in the literature for the adult patients and it is slightly constant
Preliminary dosimetric study with177-Lutetium Peptide for the duration of the treatment. Due to the lack of pediatric
Receptor Radionuclide Therapy for Pediatric Patients with standard dose limits for kidney further investigation are needed.
neuroendocrine tumors References: None.
B. Cassano1, E. Genovese1, C. Polito1,2, M. Longo3,4, S. Donatiello1,
A. Napolitano1, T. Insero1, S. Valeri5, M. Pizzoferro6, A. Serra7, M. C.
Garganese6, V. Cannatà1; OP-209
1
IRCCS Bambino Gesù Children’s Hospital, Medical Physics Unit, Biodistribution and dosimetry of a single dose of [177Lu]
Rome, ITALY, 2Sapienza University of Rome, Molecular Medicine Lu-DOTAZOL in patients with mCRPC
Department, Rome, ITALY, 3Arcispedale Sant’Anna Hospital, V. Kramer1,2, R. Fernandez1, W. Lehnert3, J. Flores1, C. Soza-Ried1, J.
Medical Physics Unit, Ferrara, ITALY, 4Sapienza University of Rome, Ribbeck2, M. Ceballos1, E. Eppard2, L. Jiménez-Franco3, A. Kluge3, M.
Ph. D. Program in Morphogenesis & Tissue Engineering, Rome, Meckel4, F. Roesch5, H. Amaral1,2;
ITALY, 5Tor Vergata Postgraduate School of Medical Physics, 1
Center for Nuclear Medicine & PET/CT Positronmed, Santiago
Rome, ITALY, 6IRCCS Bambino Gesù Children’s Hospital, Nuclear de Chile, CHILE, 2Positronpharma SA, Santiago, CHILE, 3ABX-
Medicine Unit/Imaging Department, Rome, ITALY, 7IRCCS Bambino CRO, Dresden, GERMANY, 4Isotope Technologies Garching,
Gesù Children’s Hospital, Oncoemathology Unit, Rome, ITALY. München, GERMANY, 5Institute of Nuclear Chemistry,
Johannes Gutenberg-University, Mainz, GERMANY.

Aim/Introduction: Peptide receptor radionuclide therapy


(PRRT) with 177Lu-labelled peptides is an effective strategy for Aim/Introduction: Palliative treatment of bone metastasis using
the treatment of metastatic/non-resectable neuroendocrine radiolabelled bisphosphonates is a well-known concept and
tumours (NETs) in adults, but its use is uncommon in pediatric proven to be safe and effective. A new, theranostic radiotracer
patients. The aim of this study is to report our initial experience for bone palliation, is [177Lu]LuDOTA-Zoledronic acid ([177Lu]
in 3 pediatric patients with evidence of cellular expression of Lu-DOTAZOL), which has improved pharmacokinetics when
somatostatin (SSTR) treated with 177Lu-DOTATATE. Materials compared to established radiopharmaceuticals. In this study,
and Methods: 2 patients (PAT-1 and PAT-2) affected by relapsed/ safety and dosimetry of therapeutic doses of [177Lu]Lu-DOTAZOL
refractory metastatic high-risk neuroblastoma (rrmHRNBL) and were evaluated based on a series of SPECT/CT images and
1 patient (PAT-3) with phaeochromocytoma were enrolled in blood samples. Materials and Methods: Eight patients with
this study. PAT-1 and PAT-2 were previously treated according to bone metastasis from mCRPC (71±8.6 y) and progression under
SIOPEN HRNB 01 protocol including 131I-MIBG as second-line conventional therapies were evaluated by laboratory tests and
treatment. PAT-1 and PAT-2 received 4 cycles of palliative PRRT PSMA-PET/CT to confirm absence of soft tissue lesions. After
(4.4 GBq in the 1st cycle in PAT-1, 7.4 GBq per administration receiving a single dose of 5778±328.2 MBq [177Lu]Lu-DOTAZOL,
in the other cycles) and PAT-3 is actually in treatment (he was patients underwent venous blood sampling (5, 15, 30 min and
administered twice). To reduce kidneys uptake, the patient 1.5, 6, 24 and 48 h p.i.) and 3D SPECT/CT imaging from top of the
received an intravenous infusion with bioarginine 20 g (body head to upper thigh using a pre-calibrated SPECT/CT camera
surface scaled) in 1200 ml of NaCl solution over 4 h starting 30 at 1.5, 6, 24, 48 h and 7 d p.i. Tumor lesions and volumes were
min before the administration. In a time-window ranging from defined by objective criteria on pre-therapeutic PSMA-PET/
0.5 to 144 h, 6 whole-body and static planar images, 11 blood CT scans and volumes of interest for organs and tumors were
samples and 9 acquisitions with a NaI external probe at 2 meters defined on SPECT/CT scans. Red bone marrow activity uptake
distance were collected. Red Marrow (RM) and renal dosimetry was conservatively estimated from venous blood samples
were performed according to the MIRD method and kidney (RMBLR = 1.00). QDOSE, OLINDA/EXM_v1.1 and IDAC-Dose_
toxicity was monitored assessing creatinine levels Results: PAT- v2.1 were used for dosimetric evaluations and calculation of
1, PAT-2, PAT-3, cumulative absorbed dose was 1.1, 0.6, 0.4 Gy for absorbed organ doses for red marrow, kidneys, skeleton without
RM and 26, 22, 11 Gy for kidney respectively. Kidney absorbed tumor and tumor lesions. Results: [177Lu]Lu-DOTAZOL showed
dose per activity administered was 0.98, 0.96, 0.91 Gy/GBq fast uptake and high retention in bone lesions and very fast
with a maximum intra-variability, measured as the maximum clearance from blood stream in all patients. Average retention
percentage difference, of 6.3%. The creatinine values show the in tumor lesions was 0.02 %ID/g at 6 h p.i. and approximately
absence of acute toxicity to kidneys. No disease regression was 0.01 %ID/g at 170 h p.i. with a high variability between patients,
observed but early symptoms improvement (mild flushing) was due to variations localization and size of lesions (mass range
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S88

from 0.63 g to 99.24 g). In this cohort, average doses in bone OP-214
tumor lesions, kidneys, red bone marrow and bone surface were Discussion/General Questions
4.21, 0.17, 0.36 and 1.19 mGy/MBq, respectively. Using the most
conservative estimation, red bone marrow was found to be the
dose limiting organ for all patients. A median injected activity 508
of 3.5 GBq will not exceed the defined threshold of 2 Gy for
the red bone marrow. Conclusion: The dosimetry calculations
Clinical Oncology - Rapid Fire Session: PRRT 4.0?
indicate that [177Lu]Lu-DOTAZOL has a very favourable therapeutic
index for the treatment of osteoblastic bone metastases Sunday, October 13, 2019, 16:30 - 18:00 Lecture Hall 114
caused by prostate cancer. The predicted therapeutic index
is superior, compared to other radiopharmaceuticals used in
the treatment of bone metastasis. Personalised dosimetry will,
however, be required to avoid hematotoxicity for individual OP-215
patients. References: Meckel et al;EJNMMI Radiopharmacy and LUTATHERA® in first line therapy of G2 and G3 GEP-NETs
Chemistry;2016,1-14. (the NETTER-2 study)
D. Ferone1, M. Pavel2, P. Kunz3, W. de Herder4, P. Santoro5, A.
Wegener5, P. Broberg5, L. Ravasi5, S. Singh6;
507 1
IRCCS AOU San Martino - IST, Genova, ITALY, 2FAU Erlangen-
Nurnberg, Erlangen, GERMANY, 3Stanford University
Teaching Session 2 - Interactive Clinical Cases School of Medicine, Stanford, ON, CANADA, 4Erasmus
- Radiopharmacy + Inflammation & Infection + MC Rotterdam, Rotterdam, NETHERLANDS, 5Advanced
Oncology & Theranostics Committee: Imaging Accelerator Applications, a Novartis company, Geneva,
of Immune Cells SWITZERLAND, 6University of Toronto, Toronto, ON, CANADA.

Sunday, October 13, 2019, 16:30 - 18:00 Lecture Hall 113


Aim/Introduction: The pivotal Phase III NETTER-1 study showed
that LUTATHERA® provided a significant increase in PFS to patients
with progressive midgut neuroendocrine tumors compared to
OP-210 those treated with 60 mg octreotide LAR. The NETTER-1 patient
Introduction population included 34.5% of patients with G2 and 65.5% with
P. Laverman; G1 NET while G3 were excluded. Only patients progressive on
Radboud University Nijmegen Medical Centre, Department of somatostatin analogs (SSAs) were eligible (2nd line), SSA-naïve
Radiology & Nuclear Medicine (757), Nijmegen, NETHERLANDS. patients were excluded. The aim of the NETTER-2 study is to
determine if LUTATHERA® in combination with octreotide LAR
prolongs PFS in patients (including adolescents ≥15 years of
OP-211 age and > 40 kg) with somatostatin receptor positive, high
Basics of Immune Cells - Expression, Role and Targeting proliferative rate (G2 with Ki67 index ≥10% and G3 with Ki67 ≤
Possibilities 55%) advanced GEP-NETs, when given as a first line treatment
E. Aarntzen; in comparison to treatment with high dose (60 mg) octreotide
Radboud Universtiy Medical Center, Department of Radiology LAR. Both SSA-naïve as well as patients previously treated
and Nuclear Medicine, Nijmegen, NETHERLANDS. with SSAs in the absence of progression are eligible. Patients
with high pace of disease progression, which would warrant
first-line chemotherapy in the opinion of the investigator,
OP-212 are excluded. Materials and Methods: In this multicenter,
Methods for Immune Cell Radiolabeling stratified, open-label, randomized, comparator-controlled Phase
R. Torres Martin de Rosales; III study, 222 patients will be randomized (2:1 randomization
St Thomas’ Hospital / King’s College London, School of Biomedical ratio) to receive treatment with LUTATHERA® (7.4GBq/200 mCi
Engineering & Imaging Sciences, London, UNITED KINGDOM. x 4 administrations every 8± 1 weeks; cumulative dose: 29.6
GBq/800mCi) plus octreotide LAR (30 mg every 8 weeks during
LUTATHERA® treatment and every 4 weeks after last LUTATHERA®
OP-213 treatment) or high dose octreotide LAR (60 mg every 4 weeks).
Imaging of Immune Cell - From Preclinical to Clinical Randomization will be stratified by Grade (G2 vs G3) and tumor
M. Kneilling; origin (pNET vs other origin). The primary end point is PFS
Eberhard Karls Universtiy, Werner Siemens Imaging Center, between the two treatment arms (centrally assessed according
Department of Preclinical Imaging and Radiopharmacy, to RECIST 1.1). Secondary endpoints include objective response
Department of dermatology, Tübingen, GERMANY. rate, quality of life, disease control rate, safety, side-effect profile,
and overall survival. In the control arm, any RECIST progressive
S89 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

patient (based on central assessment) has the option to enroll and a ratio of the SUVmax on 68Ga-SSTR PET to the SUVmax on
for post-progression cross-over, to receive maximum 4 cycles 18
F-FDG PET > 2, the median OS was 53.0 months, compared
of LUTATHERA® (7.4 GBq/200 mCi x 4 cycles; cumulative dose: toh 43.4 months in those patients with a ratio <2 (p =0.0296).
29.6 GBq / 800mCi) plus 30 mg octreotide LAR every 8 weeks. For those patients with no 18F-FDG uptake, the median OS were
Results: Not available yet Conclusion: An advanced GEP-NET 108.3 vs 76.9 months for a SUVmax >15.0 and a SUVmax ≤15.0
(G2 and G3) patient population including adolescents ≥15 years on 68Ga-SSTR PET, respectively. Conclusion: 18F-FDG PET/CT is
will be assessed in NETTER-2 to evaluate a potential new first line an independent prognostic factor in patients with NEN treated
radioligand therapy (RLT) option for these patients with high risk with PRRT. High uptake on 68Ga-SSTR PET/CT combined with
profile and high unmet medical need. References: None. negative 18F-FDG PET/CT is associated with a better long-term
prognosis. References: None.

OP-216
Prognostic value of 18F-FDG PETCT in a large cohort of 495 OP-217
patients with advanced neuroendocrine neoplasms (NENs) Influence of Pretreatment with Everolimus and/or
treated with peptide receptor radionuclide therapy (PRRT) Sunitinib on the Acute Hematotoxicity of 177Lu-DOTATATE
J. Zhang1, Q. Liu2,1, H. R. Kulkarni1, A. Singh1, C. Schuchardt1, K. PRRT
Niepsch1, R. P. Baum1; E. Medaer, C. Verslype, E. Van Cutsem, J. Dekervel, P. Clement, K.
1
THERANOSTICS Center for Molecular Radiotherapy & Precision Nackaerts, O. Gheysens, K. Goffin, S. Jentjens, K. Van Laere, C. M.
Oncology, ENETS Center of Excellence, Zentralklinik Bad Berka, Deroose;
Bad Berka, GERMANY, 2Department of Nuclear Medicine, UZ Leuven, Leuven, BELGIUM.
Peking Union Medical College (PUMC) Hospital, Chinese
Academy of Medical Science & PUMC, Beijing, CHINA.
Aim/Introduction: Peptide receptor radionuclide therapy is a
validated treatment for somatostatin receptor overexpressing
Aim/Introduction: To evaluate the role of 18F-FDG PET/CT in neuroendocrine tumors. The NETTER-1 trial has demonstrated
a large cohort of 495 patients with advanced neuroendocrine a pronounced positive effect on progression-free-survival
neoplasms (NENs) who were treated with peptide receptor compared to high dose somatostatin agonists, with a strong
radionuclide therapy (PRRT) and had long-term follow-up. tendency towards overall survival benefit. Our PRRT cohort
Materials and Methods: 495 patients (M 299; mean age consists of patients with heavy pretreatment with targeted
59.0±10.7 y; G1:G2:G3:NA=117:245:29:104; pancreatic NEN: agents, due to requirements for reimbursement within the
n=199, midgut: n=139, CUP: n=49, rectum: n=20, lung: n=38, Belgian healthcare system. Everolimus is approved for primary
stomach: n=8, thymus/mediastinum: n=4, other: n=38) received pancreatic, lung and non-functional intestinal NETs, sunitinib
PRRT with 177Lu and/or 90Y labeled somatostatin analogs for primary pancreatic NETs. Our aim was to determine the
(DOTATATE or DOTATOC), and were studied with both, 68Ga- influence of pretreatment with everolimus and/or sunitinib
SSTR and 18F-FDG PET/CT at baseline before PRRT. Kaplan-Meier on acute hematotoxicity of PRRT. Materials and Methods:
analysis, log-rank test (Mantel-Cox), and Cox regression analysis We analyzed the records of 90 consecutive patients treated
were performed for survival analysis. Results: 382 (77.2%) with 177Lu-DOTATATE PRRT (1 to 4 cycles of 7.4 GBq) at the
patients were classified as 18F-FDG-positive and 113 (22.8%) University Hospital Leuven, between November 2013 and July
as 18F-FDG-negative before PRRT. 3 (0.6%) patients were with 2018. Eight patients were excluded (incomplete data). All 82
tumors uptake on 68Ga-SSTR PET of grade 1 (SUVmax=liver), included patients were assigned to 2 groups according to their
whereas 161 (32.5%) patients of grade 2 (liver<SUVmax≤15), pretreatment: no targeted agents (naïve; N=41), or pretreated
106 (21.4%) of grade 3 (SUVmax≤20) and 225 (45.5%) of grade (with everolimus, sunitinib or both; N=41). The end point was
4 (SUVmax>20). The median follow-up was 94 months. For all the acute hematotoxicity, defined as the nadir value between
patients, the median PFS was 19.6 months and the median OS start of PRRT and the 3-months follow-up period after the last
was 59.4 months. The median OS of patients with pancreatic, PRRT administration, using the Common Terminology Criteria
midgut and bronchopulmonary NEN were 54.4 months, 77.8 for Adverse Events (CTCAE) 4.03 classification. Any grade and
months and 46.2 months, respectively. For patients with 18F-FDG grade 3/4 toxicity was examined. Fisher exact test was used for
PET- positive, the median PFS was 18.5 months and the median statistical analysis. Results: The primary tumor site was small
OS was 53.2 months. Patients with 18F-FDG PET-negative, had a intestine in 37 patients, pancreas in 25, unknown in 7, lung in
median PFS of 24.1 months and a median OS of 83.1 months. 5, colon in 4, paraganglioma in 2 patients and menigeoma and
A significant difference was found for both, PFS and OS, as p pheochromocytoma each in 1 patient. No statistically significant
= 0.0015 and p < 0.0001, respectively. In the pancreatic NENs differences in acute hematotoxicity were seen in the pretreated
subgroup, the median OS was 114.3 months in 18F-FDG-negative cohort vs. the naïve cohort for hemoglobin (any grade: 100% vs.
group and 52.8 months in 18F-FDG PET-positive group (p = 100%; grade 3/4: 12% vs. 22%), neither for leucocytes (any grade:
0.0006). In the midgut NENs subgroup, the median OS was 95.3 59% vs. 63%; grade 3/4: 10% vs. 7%), nor for neutrophils (any
months in 18F-FDG-negative group and 62.1 months in 18F-FDG grade: 56% vs. 59%; grade 3/4: 5% vs. 7%), lymphocytes (any
PET-positive group. For patients with positive 18F-FDG uptake, grade: 98% vs. 90%; grade 3/4: 49% vs. 37%) or platelets (any
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S90

grade: 61% vs. 61%; grade 3/4: 15% vs. 15%). Limitations of this of the antagonist DOTA-LM3 in metastases. Despite the also
study are its retrospective nature, potential bias in the lack of use high mean absorbed organ doses, PRRT using antagonist
of targeted agents in patients more susceptible to toxic effects, appears to be promising, as significantly high tumor doses are
and the limited number of patients and events. Conclusion: In achieved. These preliminary results have to be verified in further
a cohort of patients pretreated with everolimus and/or sunitinib, studies with a higher amount of patients and better statistics.
we could not demonstrate a significant influence of everolimus References: None.
or sunitinib on the acute hematotoxicity of 177Lu-DOTATATE
PRRT. References: None.
OP-219
Analysis of patient diaries in the NETTER-1 Study
OP-218 R. Srirajaskanthan1, J. Strosberg2, E. Wolin3, B. Chasen4, M. Kulke5,
Peptide Receptor Radionuclide Therapy using SSTR D. Bushnell6, M. Caplin7, R. P. Baum8, T. Hobday9, A. Hendifar10, P.
antagonists: biokinetics and dosimetry of Lu-177 DOTA- Santoro11, P. Broberg11, A. Demange11, K. Öberg12, P. Ruszniewski13,
LM3 L. Ravasi11, E. Krenning14;
C. Schuchardt, S. Wiessalla, A. Singh, J. Zhang, H. R. Kulkarni, D. 1
Kings College Hospital, London, UNITED KINGDOM, 2Moffitt
Mueller, R. P. Baum; Cancer Center, Tampa, FL, UNITED STATES OF AMERICA,
Theranostics Center for Molecular Radiotherapy and 3
Montefiore Einstein Center for Cancer Care, Bronx, NY, UNITED
Molecular Imaging, Bad Berka, GERMANY. STATES OF AMERICA, 4University of Texas MD Anderson Cancer
Center, Houston, TX, UNITED STATES OF AMERICA, 5Boston
Medical Center, Boston, MA, UNITED STATES OF AMERICA,
Aim/Introduction: Peptide Receptor Radionuclide Therapy 6
University of Iowa, Iowa City, IA, UNITED STATES OF AMERICA,
(PRRT) is used to treat patients with somatostatin receptor (SSTR) 7
Royal Free Hospital, London, UNITED KINGDOM, 8Zentralklinik,
positive tumors. Recent studies show a higher tumor detection Bad Berska, GERMANY, 9Mayo Clinic College of Medicine,
rate in PET/CT studies using SSTR antagonists compared Rochester, MN, UNITED STATES OF AMERICA, 10Cedars Sinai
to SSTR agonists. The aim of the present investigations was Medical Center, Los Angeles, CA, UNITED STATES OF AMERICA,
to determine the biokinetics and dosimetry of the Lu-177 11
Advanced Accelerator Applications, a Novartis company, Geneva,
labelled antagonist DOTA-LM3. Materials and Methods: SWITZERLAND, 12University Hospital, Uppsala University, Uppsala,
11 patients with neuroendocrine neoplasms (aged 64+/-12 SWEDEN, 13Hopital Beaujon and Paris Diderot University, Clichy,
years) were included in the analysis. High SSTR expression was FRANCE, 14Erasmus Medical Center, Rotterdam, SWEDEN.
verified before treatment by Ga-68 NODAGA-LM3 PET/CT. The
administered activity ranged from 2.8 to 7.3 GBq Lu-177 DOTA-
LM3. Biokinetics were determined based on planar whole body Aim/Introduction: The NETTER-1 trial primary statistical
scintigraphiy & SPECT/CT and dosimetry calculations were analysis showed a clinically and statistically significant PFS
performed (OLINDA 2.0). To analyze the kinetics, we used the benefit with 177Lu-DOTATATE vs. high-dose octreotide. 177Lu-
following parameters: effective half-life (HL in hours) and uptake DOTATATE treatment was also correlated with a significant delay
(%IA, fraction of injected activity), which were calculated using in time to deterioration in HRQoL. Patients were asked to record
the fit of the time-dependent activity curve to a mono- or bi- presence or absence of a range of symptoms in a daily diary.
exponential function. Results: Very intense uptake in the tumor Materials and Methods: A Mixed Model Repeated Measures
lesions as well as significant uptake in the kidneys, spleen and (MMRM) was used to analyze the change, compared to baseline.
liver was observed in all patients. There was rapid clearance of The symptoms considered to judge the overall disease status
tracer from whole body with a HL of 56-93 hours. The maximum were abdominal pain, diarrhea and cutaneous flushing. The
renal uptake at 20h p.i. was 15% IA (mean 7%IA) and showed a number of days with symptoms during the previous period
wash-out with HL of 47-159 hours. The highest uptake in the was calculated for each visit (week=0, 4, 8, etc.). At baseline, the
spleen was observed at 3h p.i. with 5%IA and an exponential number of days with symptoms was counted over the previous
decline with a HL of 74-156h. The liver also demonstrated 6 weeks, whereas the time frame between visits lasted 4 weeks.
moderate uptake at 20h p.i. up to 7% IA and a HL of 67-75 Results: The estimated number of days with symptoms declined
hours. Concerning malignant lesions we distinguished between significantly more in the 177Lu-DOTATATE arm compared to the
bone (8) and liver (9) metastases. The maximum uptake at 20h octreotide arm. Table 1 is showing the difference in change and
p.i. was 11.9% IA for liver and 1.3% IA for bone metastases. All the confidence intervals. Conclusion: Analysis of symptom
tumor lesions followed an exponential decline with a long diaries confirms that 177Lu-DOTATATE can palliate clinically
mean HL of 111 hours. The following organ- and tumor doses relevant symptoms when compared to high-dose octreotide.
were calculated: Whole body 0.12+/-0.03 Gy/GBq (0.07-0.18 Gy/ References: None.
GBq); kidneys 2.3+/-0.9 Gy/GBq (0.5-3.6 Gy/GBq); liver 0.39+/-
0.05 Gy/GBq (0.35-0.44Gy/GBq); spleen 3.4+/-1.6 Gy/GBq (1.2-
5.4Gy/GBq); bone lesions 1-57 Gy/GBq; liver lesions 15-81 Gy/
GBq. Conclusion: As already demonstrated in PET/CT studies
with antagonists, these first results show a high accumulation
S91 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

OP-220 in the Netherlands Cancer Institute between March 2016 and


First Results of Targeted Alpha Peptide Receptor February 2019, and from whom a pre-therapy 68Ga-DOTATATE
Radionuclide Therapy Using Ac-225 DOTATOC for PET/CT was available. Patients previously treated with PRRT
Progressive Metastatic Neuroendocrine Neoplasms were excluded. PRRT regimen comprised four administrations
H. R. Kulkarni, J. Zhang, A. Singh, C. Schuchardt, R. P. Baum; of ~7.4 GBq 177Lu-DOTATATE every 10 weeks. Haematological
Theranostics Center for Molecular Radiotherapy and Precision parameters were measured every 3, 6 and 8.5 weeks after
Oncology, Zentralklinik Bad Berka, Bad Berka, GERMANY. each administration or more frequent on clinical indication.
Haematotoxicity was classified if either Hb <5.5 mmol/L,
leukocytes <3.0×109/L, neutrophil granulocytes <1.0×109/L,
Aim/Introduction: Peptide receptor radionuclide therapy or thrombocytes <75×109/L between start of PRRT until 10
(PRRT) using beta emitters like Lu-177, is an established weeks after cycle four, comparable to Common Terminology
treatment option for somatostatin receptor positive Criteria for Adverse Events (CTCAE) grade ≥2. General patient
neuroendocrine neoplasms (NENs). Alpha-particles, due to and tumour characteristics, previous therapies, baseline
their much higher linear energy transfer, result in more double- laboratory values and the volume and number of bone
stranded DNA breaks. Therefore, alpha-particle emitters could metastases were evaluated. Bone metastases were segmented
have a higher therapeutic efficacy, when used for PRRT. We using 40% SUVpeak threshold on pre-therapy 68Ga-DOTATATE
present our first experience of targeted alpha PRRT (TA-PRRT) in PET/CT. Univariate logistic regression and correlation analysis
progressive metastatic NENs. Materials and Methods: Thirteen was performed to identify baseline variables associated with
NEN patients with widespread metastases, having progressed haematotoxicity. Results: In total 82 patients were included, of
after previous PRRT (2 - 9 cycles) using beta-emitters (Lu-177 / whom 60 (73.2%) completed four administrations and eleven
Y-90), received totally 23 cycles of Ac-225 DOTATOC. The primary (13.4%) are still continuing treatment. Eleven (13.4%) patients
tumors were pancreas (n=4), midgut (n=3), paraganglioma- had to discontinue therapy, of which three patients due to
pheochromocytoma (n=2), unknown (n=2), lung and kidney persistent haematotoxicity. Haematotoxicity in one of the four
(each n=1) TA-PRRT was performed using a mean administered blood parameters was observed in 29/82 (35.4%) patients.
activity of 9.7 MBq (5 - 19 MBq), including 5 intra-arterial A postponed next administration and reduced activity was
applications in 4 patients. All laboratory parameters (including used in 9/29 patients, while only postponement or reduced
complete blood picture 2-weekly, renal, hepatic function etc.) activity was used in 2/29 and 5/29 patients, respectively. No
were regularly monitored. The objective response was evaluated intervention was applied in 13/29 patients. Toxicity was most
by Ga-68 DOTATOC PET/CT. Results: The treatment (both intra- frequently observed in leukocytes (20/82, 24.4%), followed by
arterial and intravenous) was very well tolerated by all patients. thrombocytes (13/82, 15.9%), Hb (8/82, 9.8%) and the least in
There was no hematological toxicity; no worsening of counts neutrophil granulocytes (2/82, 2.4%). In univariate analyses,
even in patients with pre-existing anemia or pancytopenia. No baseline thrombocyte levels between 87-208×109/L [OR 3.8
evidence of hepatic or renal toxicity was noted. Ga-68 DOTATOC (95% CI 1.22-11.92)] were predictive for haematotoxicity (p-value
PET/CT at 3 months after therapy revealed an objective response = 0.015). In detail, baseline thrombocytes between 87-208×109/
in 85 % of the patients, including partial remission in 4 patients L were associated with leukopenia [OR 6.93 (95% CI 1.69-28.44)]
(31 %) and stable disease in 7 patients (54 %). Whereas, the and thrombocytopenia [OR 5.92 (95% CI 1.14-30.65)]. In addition,
disease continued to progress in 2 patients (15 %). Conclusion: a significant (p-value <0.001) but low correlation (Spearman’s
Targeted alpha PRRT administering Ac-225 DOTATOC appears to rho = 0.54) was observed between baseline and lowest
be feasible, safe and effective in progressive metastatic NENs, thrombocyte value. Conclusion: In roughly 20% of patients
refractory to beta emitters Lu-177 and Y-90. References: None. PRRT regime was modified due to haematotoxicity. Baseline
thrombocyte values ≤208×109/L were associated with increased
risk for haematotoxicity (CTCAE grade ≥2). No correlation with
OP-221 other parameters and between baseline thrombocyte values
Predictive factors for short-term haematotoxicity during and thrombocytopenia was observed. References: None.
peptide receptor radionuclide therapy
D. M. V. Huizing, M. W. J. Versleijen, I. Walraven, M. M. Geluk -
Jonker, M. E. T. Tesselaar, J. J. M. A. Hendrikx, B. J. de Wit - van der OP-222
Veen, M. P. M. Stokkel; Amino Acid Solutions in Premedication Peptide Receptor
Netherlands Cancer Institute, Amsterdam, NETHERLANDS. Radionuclide Therapy (PRRT) with Lutathera®: a Tolerance
Study
P. Courault1, V. Habouzit1, A. Deville1, L. Mele1, N. Bouzehouane1, F.
Aim/Introduction: The goal of this study was to identify pre- Bour1, E. Levigoureux1,2, C. Bolot1, C. Bournaud1;
treatment parameters associated with haematotoxicity during 1
Hospices Civils de Lyon, Groupement Hospitalier Est, Bron,
peptide receptor radionuclide therapy (PRRT), as moderate FRANCE, 2Université Lyon 1 Claude Bernard, Lyon, FRANCE.
haematotoxicity already affects therapy management.
Materials and Methods: A retrospective study was performed
in patients with a neuroendocrine tumour, treated with PRRT
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S92

Aim/Introduction: Co-infusion of amino-acid solutions Aim/Introduction: Peptide receptor radiotherapy (PRRT)


during PRRT reduces tubular reabsorption of Lutathera® with 177Lu-DOTATATE, has emerged as a promising therapy for
(177Lu-oxodotreotide), thus minimizing nephrotoxicity of the neuroendocrine tumors. PRRT has been used both as first-line
radiopeptide. In our nuclear medicine center, patients have and salvage treatment in small cohorts of patients, world-wide,
been treated with two different types of amino acid perfusions: diagnosed with pheochromocytoma (PCC) and paraganglioma
a commercial solution (CS) containing 10% of amino-acid and a (PGL). Materials and Methods: This was a retrospective cohort
2.5% Lysine-Arginine hospital preparation produced by a referral study including 22 patients with histopathologically confirmed
laboratory. The aim of this study was to analyze the tolerance of PCC and PGL, two were localized and 20 metastatic. 13/22
the two amino acid perfusions. Materials and Methods: Medical patients were tested for gene abnormalities,7 patients had
files of the patients have been analyzed with double checking. SDHx-related mutations, 2 patients with mutations in NF-1 gene
Data were gathered from paper or informatics folders and nurse and 4 patients were sporadic. Radiological response utilized
traceability sheets. Parameters recorded were: sex, age, primitive RECIST 1.1 and toxicity was graded according to CTCAE4 criteria.
site of the tumor, type of amino acid perfusion, adverse events Visually rated decrease (>50%) of tumor accumulation as
(AE) and their OMS grades, antiemetic premedication, clearance compared to scintigraphy during the first cycle was considered
of the creatinine and kalemia. Results: From February 2016 to as scintigraphic response. Reduction in plasma chromogranin
February 2019, 76 patients (male 55%, mean age = 63 years- A ≥50% was considered as biochemical response. Results:
old) were treated for a total of 235 cycles. Primitive tumor site 7.4 GBq per cycle of 177Lu-DOTATATE (median 4, range 3-11
was small intestine (73%), then pancreas (15%), bronchial (5%), cycles) was administered as first-line therapy in 13 patients or
rectum (5%) and other (2%). AE occurred in 69% (n=82/119) of because of progressive disease in 9 patients. Partial response
cycles with CS as compared to 18% (n=21/116) in the Lysine- (PR) was achieved in two and stable disease (SD) in 20 patients.
Arginine group (p<0.0001). One patient declined to continue The median overall survival (OS) in months was 49.6 (range
PRRT after the first cycle, because of grade 4 vomiting with 8.2-139) and median progression free survival (PFS) was 21.6
the CS. Most frequent AE consisted in nausea and vomiting (range 6.7-138). The median best response on CT according to
(n=83/103), flush (n=10/103), headache (n=6/103) or diarrhea RECIST 1.1, across the cohort was -10 % (range 0 to -65%). The
(n=6/103). In the CS group, AE were mostly graded 4 in the time to best response was median 14.4 months (range 4.7 to
OMS scale (n=24/82), whereas they were graded 1 in the 128 months). Scintigraphic response was seen in 9/19 (47%)
Lysine-Arginine group (n=13/21). Thanks to the reduction of patients. In 7 out of 15 evaluable patients (47%) biochemical
AE, patients received on average 3.2 and 1.4 lines of antiemetics response was achieved and 2 (13%) showed an increase in
before CS administration or Lysine-Arginine. Interestingly, 10 plasma chromogranin A. Subgroup analysis showed that low
patients (36 cycles) received both solutions. Sixty-four percent Ki-67 (<15%) was associated with longer OS (p=0.013) and PFS
(n=11/17) of these cycles with the CS were complicated by AE (p=0.005). PRRT as first-line therapy was found associated with
versus 15% (n=3/19) of cycles with Lysine-Arginine (p=0.005). increased OS (p=0.041).No hematological or kidney toxicity
Mean creatinine clearance was identical before and after grade 3-4 was registered. Conclusion: 177Lu-DOTATATE therapy
PRRT cycles, whatever the amino acid infusion. Three patients was associated with favorable outcome and low toxicity. High
underwent a temporary degradation of renal failure from stage Ki-67 (≥15%) and PRRT received because of progression on
2 to 3: one in CS group and two in Lysine-Arginine group. Four previous therapy, could constitute negative predictive factors
patients (6 cycles) were closely follow-up 1 or 2 days after PRRT for OS. References: None.
for the kaliemia and no significant variation was observed.
Conclusion: The Lysine-Arginine preparation offers a better
tolerance than the commercial solution. Short term follow-up OP-224
did not disclosed difference regarding nephroprotective effect A standardized and simplified dosimetric approach for
of both preparations. The change for Lysine-Arginine allowed a PRRT in patients with neuroendocrine tumor
reduction of the antiemetic premedication from 4 to 1 molecule. E. Tonini1, S. Di Biaso2, M. Longo1,3, A. Barboni1, A. Turra1, L. Uccelli4,
References: None. S. Panareo4, C. Cittanti4, M. Bartolomei4;
1
Arcispedale Sant’Anna Hospital, Medical Physics
Unit, Ferrara, ITALY, 2Dipartimento di Fisica e Scienze
OP-223 della Terra, Ferrara University, Ferrara, ITALY, 3Sapienza
Favourable outcome in patients with metastatic University of Rome, Ph. D. Program in Morphogenesis &
pheochromocytomas and paragangliomas treated with Tissue Engineering, Rome, ITALY, 4Arcispedale Sant’Anna
177
Lu-DOTATATE Hospital, Nuclear Medicine Unit, Ferrara, ITALY.
A. Vyakaranam1,2, J. Crona1, E. Thiis-Evensen3, P. Hellman1, O.
Norlén1, D. Granberg2, U. Garske-Román4, K. Fröss-Baron1, M.
Sandström1, A. Sundin1; Aim/Introduction: Since July 2018, Neuroendocrine Tumour
1
Uppsala University, Uppsala, SWEDEN, 2Akademiska (NET) patients are being treated with peptide-receptor
Sjukhuset, Uppsala, SWEDEN, 3Oslo Metropolitan University, radionuclide-therapy (PRRT) at Arcispedale Sant’Anna of Ferrara,
Oslo, NORWAY, 4Department of Nuclear Medicine, according to the FENET 2016 protocol, that includes the use
Sahlgrenska University Hospital, Gothenburg, SWEDEN. of both 177Lu-DOTATOC and combined 177Lu/90Y-DOTATOC. The
S93 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

aim of the study is to propose a shorter but patient-tailored Medicine HU Burgos, Burgos, SPAIN, 14Nuclear Medicine HU
dosimetric procedure to provide significant data for an accurate Sant Pau, Barcelona, SPAIN, 15Medical Oncology, Hospital
evaluation of each patient. Materials and Methods: Forty- Universitario Central de Asturias, Oviedo, SPAIN, 16Medical
eight patients are treated with systemic administration of a Oncology, Hospital Universitario Morales Meseguer de
cumulative activity between 11 and 28 GBq. The treatment is Murcia, Universidad de Murcia, UMU, IMIB, Murcia, SPAIN.
fractionated in 5-cycles, each ranging from 1.9 to 5.5 GBq (for
177
Lu-DOTATOC and 177Lu/90Y-DOTATOC). Dosimetric evaluation
is performed after the 1° cycle to modulate the activity of the Aim/Introduction: Radionuclide therapy is effective in
further 2°, 3° and 4° cycles and it is repeated after the 5° to assess advanced neuroendocrine tumors (NET), but we lack
the variation in term of uptake volume, absorbed dose and BED multicentre data from real word patients. The aim of this
on lesions and critical organs. A validated and simplified method paper has been to describe the caracteristics of patients with
based on 3 SPECT/CT at 1, 24, 48-hours after administration advanced NET´s and to show the results in efficacy, tolerance
was developed. The MIM® software was used by an automated and toxicity of treatment with 177Lu-DOTATATE (PRRT) in our
workflow that allows contouring the volume of interest (VOI) national experience. Materials and Methods: The data is taken
regarding lesions and kidneys on sequential fused images and from the national multicenter study SEPTRALU. Researchers
co-registered. Image counts were then corrected for scatter, from 18 centers (oncologists, endocrinologists, nuclear
attenuation and partial volume effects. The absorbed dose medicine physicians) recruited 177 patients. Toxicity was
have been computed through OLINDA2.0 and the BED in the registered according to CTCAE v3.0 criteria. The best response
selected VOI has been also obtained. Results: A high variability and maximum toxicity were reported. Survival was assessed
in tumor absorbed doses per unit activity was observed due according to Kaplan-Meier method and Cox model. Results:
to variability in target volume [16÷490 ml]; reported values are 177 patients were recruited (49.7% women) with median age
from 0.6 to 10.8 Gy/GBq and from 0.6 to 3.0 Gy/GBq at 1° and 5° of 58 years (18-89) and a good performance status (ECOG 1-2)
cycle respectively. 90Y kidney and lesions absorbed doses are a 89.3%. 61% were functioning NETs with Ki-67 <20% in 91%. The
factor of 4 and 5 higher than those with 177Lu; BED resulted in most common primary tumor location was gastrointestinal
a mean value of 42 Gy. For 177Lu-DOTATOC the mean absorbed 41%, followed by pancreatic 39%. The most common metastasis
dose in kidneys has been found of 3.1 Gy [1.0÷6.5 Gy], while location was the liver 83.6%, followed by lymph nodes 42.4%
the BED is 3.4±0.9 Gy, with an effective half-time of 42.0±5.4 h. and bone 27.1%. Prior to PRRT they had received a median of 4
For 90Y-DOTATOC the mean absorbed dose in kidneys is 7.8 Gy lines of treatment (1-7). 64.2% of the patients received 4 PRRT
[4.7÷12.1 Gy] with a BED of 9.3±3.2 Gy and an effective half-time cycles, and in 96% of them 7.4 GBq. Of 101 patients assessed
of 26.0±7.1 h. Conclusion: The final aim of this work is to ensure by RECIST 1.1 criteria, they reached partial response 25.7% (n
a dosimetric evaluation to all patients undergoing PRRT. MIM® = 26), complete response 3.9% (n = 4), stable disease 55.4% (n
software has allowed us to standardize the method by working = 56) and progression 14.8% (n = 15). The median progression
accurately and with a great saving of time. Our results suggest free survival and overall survival were 24.3 months (IC95% 21.3-
that a dosimetric evaluation at both 1° and 5° cycle is advisable NA) and 28.1 months (24.6-NA) respectively. Toxicity G3-G4 was
in order to provide a precision-treatment. References: None. registered in 9% (n = 16), the most common: haematologic
(4.1%, n = 7), asthenia (2.9%, n = 5), and nephrotoxicity (1.1%,
n = 2). In the multivariate analysis, the factors associated with
OP-225 overall survival were ECOG-PS (HR 1.16, p = 0.001), Ki-67%, HR
177Lu-DOTATATE in advanced neuroendocrine tumours: 1.02 (p = 0.026), extra-liver/extra-lymph nodes metastases (HR
real word data from SEPTRALU registry 2.63, p = 0.018). Conclusion: In our serie of patients from the
M. Mitjavila Casanovas1, C. Field2, P. Bello3, Z. Nogareda real world, meaning more heterogeneous than in clinical trials,
Seoane4, L. García-Cañamaque5, J. Arbizu6, A. Rotger7, P. Gajate8, we have confirmed that therapy with 177Lu-DOTATATE is safe
M. Castellón9, M. Muros10, A. Teulé11, A. Repetto12, M. Miguel and effective. It is necessary to understand the pattern of use
Martinez13, M. Estorch14, P. Jimenez Fonseca15, A. Carmona- of PRRT in daily practice to be able to understand the cost-
Bayona16; effectiveness of this therapy. References: None.
1
Nuclear Medicine HU Puerta de Hierro Majadahonda,
Madrid, SPAIN, 2Nuclear Medicine Hospitales Madrid, Madrid,
SPAIN, 3Nuclear Medicine, HU La Fe, Valencia, SPAIN, 4Nuclear
Medicine, HU Lucus Augusti, Lugo, SPAIN, 5Nuclear Medicine,
Hospitales Madrid, Madrid, SPAIN, 6Nuclear Medicine,
Clínica Universidad de Navarra, Pamplona, SPAIN, 7Nuclear
Medicine, Hospital Universitario Gregorio Marañón, Madrid,
SPAIN, 8Medical Oncology, HU Ramón y Cajal, Madrid, SPAIN,
9
Nuclear Medicine, HU Virgen de la Arrixaca, Murcia, SPAIN,
10
Nuclear Medicine,HU Virgen de Las Nieves, Granada, SPAIN,
11
Medical Oncology, ICO-Bellvitge, Barcelona, SPAIN, 12Nuclear
Medicine, HU Son Espases, Palma de Mallorca, SPAIN, 13Nuclear
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S94

509 p=0.032). The disease controls showed no significant differences


in the above target regions when compared to the HCs (p>0.9).
Neuroimaging - Parallel Session: Movement Even in PSP patients with low disease severity (PSP rating scale
Disorders and Neurotransmission ≤30; n=6), the globus pallidum DVRs were significantly higher
compared to the HCs (1.19±0.07 vs. 1.00±0.06; p=0.004). In vitro
Sunday, October 13, 2019, 16:30 - 18:00 Lecture Hall 115 autoradiography showed displaceable tracer binding in the
globus pallidus of PSP patients, but not in HCs. Conclusion:
This preliminary multi-centre data indicate a diagnostic value
of dynamic [18F]PI-2620 PET imaging in PSP, potentially both
OP-226 for early and differential diagnosis. More studies, in both PSP-RS
Multi-Centre Evaluation of the New-Generation Tau PET and non-PSP-RS patients and also with regard to the question
Tracer [18F]PI-2620 in Progressive Supranuclear Palsy of whether static PET imaging might suffice in establishing a
H. Barthel1, M. Brendel2, T. van Eimeren3, K. Marek4, L. Beyer2, binary diagnosis are thus warranted. References: None.
M. Song2, C. Palleis2, G. Respondek5, J. Sauerbeck2, J. Hammes3,
M. Barbe3, Ö. Onur3, F. Jessen3, J. Rumpf1, M. L. Schröter1, M.
Rullmann1, A. Schildan1, J. Classen1, G. Höglinger5, P. Bartenstein2, V. OP-227
Villemagne6, A. Drzezga3, J. Seibyl4, O. Sabri1, PI-2620 in PSP Study A Multiple-modality Pattern of Multiple System Atrophy
Group; Based on FDG PET/CT and MRI
1
Leipzig University, Leipzig, GERMANY, 2Ludwig-Maximilian L. Li1, S. Peng2, P. Wu1, J. Ge1, J. Lu1, J. Wang1, Y. Ma2;
University Munich, Munich, GERMANY, 3University of Cologne, 1
Huashan Hospital, Shanghai, CHINA, 2Feinstein Institute for
Cologne, GERMANY, 4Invicro, New Haven, CT, UNITED STATES Medical Research, New York, NY, UNITED STATES OF AMERICA.
OF AMERICA, 5Technical University Munich, Munich, GERMANY,
6
University of Melbourne, Melbourne, AUSTRALIA.
Aim/Introduction: This study established multiple system
atrophy related brain network (MSARP) based on multiple-
Aim/Introduction: Progressive supranuclear palsy (PSP) is a modality images and proved their comparable values in
4-repeat (4R) tauopathy for which post mortem histopathology diagnostic specificity Materials and Methods: We selected 20
of brain region-specific tau deposits is considered the diagnostic MSA (14M/6F, age: 57.6±7.7y, HY: 3.3±0.8, UPDRS: 30.5 ±18.6,
gold standard, and for which establishing a clinical diagnosis duration: 1.7±0.9y), 20 PD (12M/8F, age: 62.5±8.3y, HY: 2.0±0.7,
may be challenging. Respective in vivo PET imaging would UPDRS: 19.9±7.7, duration: 3.2±2.3y), 20 PSP (13M/7F, age:
potentially allow not only for improved early and differential 65.0±7.9y, HY: 3.1±1.1, UPDRS: 24.3±12.2, duration: 2.9±1.9y),
diagnosis, but also for more rationalized anti-tau drug trial and 20 healthy control subjects (5M/15F, age: 61.7±6.1y)
stratification/therapy monitoring. The available first-generation who underwent FDG PET and arterial spin labeling (ASL)
tau PET tracers have major limitations, especially in imaging and structural imaging (T1). We used multimodal images
PSP patients. [18F]PI-2620 is a second-generation tau tracer of patient and control groups separately to establish brain
which, due to its low non-specific binding and relative high network. Structural MRI data was segmented into maps of
affinity for 4R tau, might be a suitable alternative. Thus, a multi- gray matter and white matter using voxel-based morphometry
centre evaluation was conducted to investigate this question. to detect local changes in brain tissue volume. Maps of CBF
Materials and Methods: Twenty patients (71±6y, n=10 were extracted from ASL images. All PET/MRI images were
female) with probable or possible PSP-Richardson syndrome coregistered to the subject’s structural MRI scan and spatially
(RS) according to the MDS-PSP criteria (PSP rating scale: 38±17; normalized into the standard MNI brain space, then were
range 13-71) underwent [18F]PI-2620 PET at five different smoothed using a Gaussian filter with the width of 6-10 mm
centres, together with ten matched healthy controls (HCs) and (FWHM) depending on signal-to-noise ratio characteristics of a
ten disease controls (multi-system atrophy, Parkinson’s disease, particular imaging modality. Network analysis were performed
Alzheimer’s disease). Multilinear reference tissue modelling separately in each category of patients for FDG PET, ASL and T1
with cerebellar reference served for calculation of 0-60min p.i. MRI data using matlab 2013 by applying a voxel-based spatial
distribution volume ratios (DVRs). DVRs in PSP target regions covariance mapping algorithm known as Scaled Subprofile
(globus pallidus, substantia nigra, nucleus subthalamicus, Modeling based on principal component analysis (SSM/PCA),
nucleus dentatus) were compared between PSPs, HCs, and whose expression could best discriminate the patients from the
disease controls, and controlled for potential imaging centre, controls in a logistical regression model along with bootstrap
age and gender effects. In parallel, globus pallidum PSP and HC resampling. Network scores were z-transformed using the
slices were subjected to [18F]PI-2620 in vitro autoradiography mean and standard deviations of healthy control subjects in the
(with/without blocking with 10µM 19F-PI2620). Results: When original derivation cohort for each imaging modality. Results:
compared to the HCs, elevated [18F]PI-2620 DVRs were observed Three versions of MSARP were generated, which came from
in the PSP patients in the globus pallidus (1.17±0.09 vs. 1.00±0.06; 3~4 PCs accounting for 20~40% of subject × voxel variance.
p<0.001), the nucleus subthalamicus (1.20±0.08 vs. 1.05±0.09; There were similar effects of group in MSARP scores among
p=0.002), and the nucleus dentatus (1.13±0.05 vs. 1.07±0.04; all subjects with FDG/CBF/GM data (ANOVA: F[3,76] ≥30.4,
S95 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

p<0.0001) with differential elevation in MSA relative to NC/ the L-DOPA (t= 2.5, p = 0.02). Conclusion: MSA shows variable
PSP/PD. These scores correlated positively with duration in MSA dopamine degeneration patterns according to the FP-CIT PET.
(regression analysis: r=0.552, p=0.012; FDG only). MSARP scores The dopamine degeneration pattern identified by PET through
exhibited excellent accuracy in discriminating MSA from NC and a data-driven approach may contribute to the refining subtypes
PD (ROC analysis: AUC≥0.988±0.014 [SE], CI: 0.96-1.00) or the of MSA as well as to explain various clinical presentations.
three other groups (AUC≥0.943±0.025, CI: 0.90-1.00) with FDG/ References: None.
CBF/GM data. The discrimination of MSA vs PSP was greater
with FDG (AUC≥0.920±0.045, CI: 0.83-1.00) than with CBF/GM
data (AUC≥0.848±0.061, CI: 0.73-0.99) Conclusion: This study OP-229
produced highly robust MSARP across different modalities Differential Diagnosis of Parkinsonism using a 3D Deep
which may provide a reliable and objective marker of MSA in Residual Convolutional Neural Network based on 18F-FDG
clinical diagnosis References: None. PET Imaging
P. Wu1, Y. Zhao2, J. Wang3, N. Navab2, I. Yakushev4, W. Weber4, M.
Schwaiger4, S. Huang5, P. Cumming6, A. Rominger6, C. Zuo1, K. Shi6;
OP-228 1
PET Center, Huashan Hospital, Fudan University, Shanghai,
Variability of Dopaminergic Degeneration Patterns in CHINA, 2Department of Computer Science, Technische Universität
Multiple System Atrophy: Data-driven Approaches of München, Munich, GERMANY, 3Department of Neurology, Huashan
Dopamine Transporter PET Hospital, Fudan University, Shanghai, CHINA, 4Department
R. Lee, J. Shin, H. Choi, H. Kim; of Nuclear Medicine, Technical University of Munich, Munich,
Seoul National University Hospital, Seoul, KOREA, REPUBLIC OF. GERMANY, 5Department of Molecular and Medical Pharmacology,
UCLA, Los Angeles, CA, UNITED STATES OF AMERICA, 6Department
of Nuclear Medicine, University of Bern, Bern, SWITZERLAND.
Aim/Introduction: Multiple system atrophy (MSA) is a
progressive neurodegenerative disorder with highly variable
clinical presentations. Even though striatonigral dopaminergic Aim/Introduction: Idiopathic Parkinson’s disease (IPD) and
degeneration is a typical neuropathological feature, its spatial atypical parkinsonian syndromes (APS) have similar symptoms
pattern which can be evaluated by PET imaging in accordance at early disease stage, making the differential diagnosis difficult.
with the clinical presentation of MSA has not yet been clarified. 18F-FDG PET and machine learning can discriminate metabolic
Here, we identified variable dopamine degeneration patterns of patterns for the differential diagnosis of parkinsonism [1].
F-18 FP-CIT PET in MSA using a data-driven method. Materials We recently introduced deep learning to differentiate these
and Methods: Sixty-eight MSA patients who underwent F-18 syndromes based on projected 2D images of the 18F-FDG
FP-CIT PET/CT between 2009 and 2018 were retrospectively PET volumes [2], which may miss some characteristic features
enrolled. For quantitative analysis, the PET images were spatially due to dimension reduction. Therefore, we aimed to develop
normalized and transformed to binding-ratio (BR) maps an automated diagnosis framework operating directly on 3D
using occipital lobe as a reference region. As conventional image volumes based on a sufficient database. Furthermore,
quantification methods, the BR for putamen and caudate (BRput we depicted in salience maps the decision mechanism of the
and BRcau) were calculated. To identify voxel-wise patterns with deep learning method. Materials and Methods: 920 patients
a data-driven approach, principal component analysis (PCA) with evident parkinsonian features underwent 18F-FDG PET
was employed and correlated with the clinical presentation. The imaging and were subsequently diagnosed by movement
pattern of imaging data was also visualized by 2-dimensional disorders specialists as IPD (n=502), multiple system atrophy
projection using t-distributed stochastic neighborhood (MSA, n=239) and progressive supranuclear palsy (PSP, n=179),
embedding (t-SNE). Results: Of the 68 subjects, 42 presented respectively. We developed a 3D deep residual convolutional
with Parkinsonian subtype of MSA (MSA-P), 16 presented with neural network comprising a total of 18 layers. The residual
cerebellar subtype of MSA (MSA-C), and 10 presented with connections included in this network were helpful for
both features of MSA subtypes (MSA-PC) (mean age, 61.8 simplifying its optimization. We generated saliency maps
± 9.5 years; disease duration, 7.3 ± 3.4 years). The BRput was using the guided back-propagation method [3]. Five-fold cross
significantly lower in MSA-P patients than in MSA-C patients validation was applied to evaluate the proposed network, which
(2.6 ± 0.4 vs. 3.0 ± 0.5, p = 0.003). Each principal component was implemented in the TensorFlow platform and accelerated
(PC) represents a specific pattern of degeneration: PC1 and by a NVIDIA Titan-XP GPU. Results: We cross-validated the
PC2 was associated with the entire putamen and posterior diagnostic efficiency of the neural network in the 542 patients
putamen, respectively. PC3 was associated with caudate and with clinically definite diagnosis after pretraining in the 378
FP-CIT binding of dorsal raphe nuclei. PC1 and PC2 showed a patients with clinically probable diagnosis. The proposed
significant difference between MSA-P and MSA-C patients (-0.7 framework achieved 98.9% sensitivity, 90.0% specificity, 98.4%
± 3.0 vs. 1.2 ± 4.0, p = 0.023 and -0.4 ± 1.2 vs. 0.9 ± 1.1, p = 0.001). PPV and 95.0% NPV for the classification of IPD, versus 98.8,
PC2 and PC3 were associated with patients’ age (r= 0.42, p < 82.5, 96.1, and 96.0% for the classification of MSA, and 87.1,
0.001; r = -0.42, p <0.001, respectively). Moreover, MSA patients 97.8, 96.1, and 94.1% for the classification of PSP respectively.
with decreased PC2 were related to relatively good response to The figure demonstrates fused saliency maps of subjects (N=15)
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S96

with IPD, MSA, or PSA, showing main saliency in (A) the right binding-ratios (SBRs), caudate-to-putamen-ratios (C2PRs),
prefrontal cortex, (B) the bilateral thalamus and putamen, and asymmetries on predefined striatal volumes-of-interest.
and (C) the midbrain and left lingual gyrus. Conclusion: We We used linear-regression to correct for age-dependency of
successfully developed a 3D deep residual convolutional neural SBRs and to allow comparisons to age-matched references.
network for automated differential diagnosis of IPD and atypical Left and right SBRs were averaged to generate one reference
parkinsonism with excellent diagnostic accuracy. The greatest SBR per region. C2PRs and asymmetries were independent of
salience was in expected regions of the basal ganglia, but initial age. Women had higher SBRs than men but without statistical
findings also implicate high order visual cortex and prefrontal significance. We compared our results to ENCDAT-database[1].
cortex. The method is currently under detailed assessment in a Results: Overall average percent-decline of uptake per-
separate group of several hundred parkinsonian patients, and decade was 4.56%. Slope, intercept, and R2-value of linear-
with emphasis on the interpretation of the saliency maps in regression were, respectively: striatum (-0.016, 4.03, 0.27),
diagnosis. References: [1] Tang et al. Lancet Neurol 2010 [2] Wu caudate (-0.0145, 4.0, 0.22), and putamen (-0.018, 4.06, 0.32). In
et al. SNMMI 2018 [3] Springenberg, J.T., arXiv:1412.6806 comparison with uncalibrated ACSC-ENCDAT results, we found
comparable regression parameters according to gender (see
tables). Conclusion: Our 123I-FP-CIT reference values, generated
OP-230 from individuals with various neurological conditions without
123
I-FP-CIT reference values from subjects with non- dopaminergic degeneration scanned at a single center, have
degenerative Parkinsonism, comparable to values from similar distribution as a function of age as values from healthy-
healthy volunteers volunteers. Co-morbidities (e.g., diabetes, hypertension)
C. Scheiber1, G. Platsch2, S. Gouttard1, S. Thobois1,3, S. Zuehlsdorff4, didn’t seem to increase the variance when compared to
R. Fahmi4; healthy subjects, making it possible for clinicians to build their
1
HCL- Groupement Hospitalier Est, Lyon, FRANCE, own normal 123I-FP-CIT databases from day-to-day practice.
2
Siemens AG Healthcare, Erlangen, GERMANY, 3Hopital References: [1]Varrone et al.--EJNMMI’2013;40(2):213-27.
Neurologique, Lyon, FRANCE, 4Siemens Medical Solutions
USA, Inc., Knoxville, TN, UNITED STATES OF AMERICA.
OP-231
Neuroprogressive character of sigma-1 receptor
Aim/Introduction: The distinction between degenerative pathophysiology in unmedicated patients with acute
Parkinsonism and other entities without dopaminergic lesion major depressive disorder as investigated by (-)-[18F]
(e.g., atypical tremors and drug-induced-parkinsonism (DIP)) Fluspidine PET
are frequent indications of 123I-FP-CIT. In addition to visual P. Meyer1, M. Strauss2, G. Becker1, S. Hesse1, K. Bednasch2, B. Ettrich2,
interpretation of 123I-FP-CIT scans, semi-quantification and S. Wilke1, F. Zientek1, M. Rullmann1, J. Luthardt1, S. Fischer3, M. Patt1,
comparison to reference values are often needed, in particular B. Wünsch4, P. Brust3, O. Sabri1;
for equivocal cases. To overcome the challenges of multi-center 1
Department of Nuclear Medicine, University of Leipzig,
variability and the difficulty to recruit healthy volunteers, we Leipzig, GERMANY, 2Department of Psychiatry and
generated 123I-FP-CIT references from individuals with various Psychotherapy, University of Leipzig, Leipzig, GERMANY,
neurological diseases without dopaminergic-degeneration, 3
Department of Neuroradiopharmaceuticals, Institute
scanned at a single center following the same protocol, of Radiopharmaceutical Cancer Research, Helmholtz-
and compared them to references from healthy-volunteers. Zentrum Dresden-Rossendorf, Research Site Leipzig, Leipzig,
Materials and Methods: From a pool of 1,884 patients scanned GERMANY, 4Institute for Pharmaceutical and Medicinal
on a SymbiaT2 (Siemens Healthineers) with low-energy-high- Chemistry, University of Münster, Münster, GERMANY.
resolution collimators between Jan-2008 and Dec-2015, 256
subjects with normal 123I-FP-CIT imaging and a clinical diagnosis
follow-up of 4.8±1.3 years to ensure that they did not develop Aim/Introduction: We have previously shown that the sigma-1
degenerative-Parkinsonian-syndrome, were initially selected receptor (Sig-1R) availability is increased in unmedicated acute
based on visual (2 readers) and (in-house) semi-quantitative MDD (MDD) using (-)-[18F]Fluspidine PET. In order to assess
assessments (SC). Corresponding SPECT-projections and CT- whether this pathophysiology is progressive, we investigated
images were further assessed by a trained physician (GP) the relationship between Sig-1R availability and duration of
who kept 237 subjects (120 male, 117 female, age: 62.2±15.7 disease (DD), number of depressive episodes (DE) and severity of
[16-88]), the majority of which (49.8%) had either ET or DIP. A acute depressive symptoms (Hamilton Depression Rating Scale,
younger group (8.85%) had attention-deficit/hyperactivity HAMD) in this now completed first-in-human (-)-[18F]Fluspidine
disorder. Scans were acquired 3hrs post-injection of ~185MBq PET trial. Materials and Methods: Patients with moderate to
of 123I-FP-CIT with (rotational radius≤15cm, matrix: 128x128, severe MDD (n=18; 32±12 years; 9 females; DD 6±8 years; DE
120 projections over 360°, and zoom=1.23 x 1.23). Images were 3±1 years; HAMD: 20±4) were studied using (-)-[18F]Fluspidine
reconstructed with Flash3D (10-iterations, 8-subsets, CTAC, TEW PET (300 MBq, ECAT Exact HR+) and compared with sex-/age-
scatter-correction, and 8mm-Gauss post-filtering). Using syngo. matched healthy controls (HC; n=16; 32±13ys [n.s.]; 9 females
via® (Siemens Healthineers), we computed regional striatal- [n.s.]). VOI analyses were performed and regional distribution
S97 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

volumes (VT) were estimated by kinetic modeling (0-210 min p.i.; of action of pridopidine and the observed clinical outcomes
2TCM; metabolite correction). Results: In MDD, compared with in prior clinical trials, we quantitatively assessed, using S1R-
HC, VT was higher especially within the fronto-temporal, anterior specific (S)-(-)-[18F]Fluspidine and D2/3R-specific [18F]Fallypride
cingulate and insular cortices, amygdala, striatum, thalamus and PET, the S1R occupancy (S1RO) and D2/3R occupancy (D2/3RO)
ncl. raphe (P<0.005). Positive correlations were found between by pridopidine at previously used clinical doses in the brain of
HAMD and VT within the anterior and posterior cingulate and HVs and HD patients. Materials and Methods: Eleven male HVs
insular cortices, ncl. caudatus and thalamus (r=0.43 to 0.57, (27 ± 2yrs; pridopidine 90mg to 0.5mg in 6 dose groups) and 3
P<0.05, adjusted for DD, BMI).Negative correlations were male HD patients (43 ± 13yrs, pridopidine 90mg) were studied
found between DD and VT within the orbitofrontal cortex and twice before and 2hrs following single oral doses of pridopidine
hypothalamus (r=-0.40 to -0.47, P<0.05, adjusted for severity using (S)-(-)-[18F]Fluspidine PET (300 MBq, 0-90min p.i., Siemens
of MDD) and between DE and VT within the hypothalamus, PET/MRI). Distribution volume (VT) was quantified using kinetic
orbitofrontal, temporo-parietal and cingulate cortices, striatum, modeling (1TCM; metabolite correction). In addition, four male
thalamus and cerebellum (r=-0.42 to -0.60, P<0.05, adjusted HVs (29 ± 5yrs) were studied twice using [18F]Fallypride PET
for severity of MDD). Conclusion: Using (-)-[18F]Fluspidine PET, (200 MBq, 0-210min p.i.) before and 2hrs following a single
we showed for the first time increased cortico-(para-)limbic oral dose of pridopidine (90mg). Binding potential (BPND) was
Sig-1R availability during the DE of MDD, as compared with assessed using a simplified reference tissue model (cerebellum
HC, that was associated with the severity of acute depressive as reference region). VOI-analyses were performed. For each
symptoms (HAMD). Remarkably, in MDD, there is a negative subject/tracer, the receptor occupancy (RO) was calculated
correlation between DE or DD and Sig1-R availability, especially by Lassen plot analysis. Results: A typical non-linear sigmoid-
within orbitofrontal cortices and hypothalamus as well as shaped dose response relation for S1RO was established in
within various (sub)cortical-(para)limbic and cerebellar brain HVs for pridopidine doses ranging from 0.5mg to 90mg. In HVs,
regions. Although verification by longitudinal (-)-[18F]Fluspidine there was a high degree of S1RO (87 ± 3% to 91 ± 4%) across
PET studies is needed, our findings suggest a neuroprogressive all brain regions at pridopidine doses ranging from 22.5mg
character of Sig-1R pathophysiology in MDD. References: None. to 90mg. S1RO only dropped below 50% after reducing the
pridopidine dose to 1mg (43%). The lowest possible dose of
0.5mg pridopidine still achieved a blocking rate of 18%. In HD,
OP-232 very similar to HVs, there was a high degree of S1RO (87 ± 7%,
[18F]Fluspidine and [18F]Fallypride PET study to evaluate n.s.) for a pridopidine dose of 90mg. In contrast, in HVs there
sigma-1 receptor (S1R) and dopamine 2 / dopamine 3 was only negligible D2/3RO (3 ± 2%) for pridopidine 90mg.
receptor (D2/3R) occupancy by pridopidine in healthy Conclusion: Our PET findings indicate that after single dose of
volunteers (HV) and patients with Huntington disease 90mg (exposure correlates with 45mg bi-daily at steady state),
(HD) pridopidine shows full (approx. 90%) S1RO but only minimal
P. Meyer1, I. D. Grachev2,3, G. Becker1, M. Bronzel4, D. Marsteller5, (approx. 3%) D2/3RO. These data provide significant clarification
G. Pastino5, O. Voges4, L. Rabinovich5, H. Knebel5, F. Zientek1, M. about the mechanism of action/clinical effects of pridopidine.
Rullmann1, B. Sattler1, M. Patt1, E. Strauss6, A. Kluge4, J. Savola5, M. F. References: None.
Gordon5, M. Geva7, S. Hesse1,8, H. Barthel1, M. R. Hayden7, O. Sabri1;
1
Department of Nuclear Medicine, University of Leipzig,
Leipzig, GERMANY, 2Teva Branded Pharmaceutical Products OP-233
R&D, Inc, Malvern, PA, UNITED STATES OF AMERICA, 3Guide Simultaneous Sigma-1 Receptor PET/Multimodality MRI of
Pharmaceutical Consulting, LLC, Millstone Twp, NJ, UNITED the Effect of Pridopidine in Huntington Disease Patients
STATES OF AMERICA, 4ABX-CRO Advanced Pharmaceutical and Healthy Volunteers
Services Forschungsgesellschaft mbH, Dresden, GERMANY, 5Teva H. Barthel1, P. M. Meyer1, M. Rullmann1, G. Becker1, M. Bronzel2,
Branded Pharmaceutical Products R&D, Inc, Frazer, PA, UNITED D. Marsteller3, G. Pastino3, O. Voges2, L. Rabinovich3, H. Knebel3, F.
STATES OF AMERICA, 6AFL – Arzneimittelforschung Leipzig GmbH, Zientek1, B. Sattler1, M. Patt1, E. Strauss4, A. Kluge2, J. Savola3, M. F.
Leipzig, GERMANY, 7Prilenia Therapeutics Development Ltd., Gordon3, M. Geva5, S. Hesse1, M. Hayden5, I. D. Grachev3,6, O. Sabri1;
Herzliya, ISRAEL, 8Integrated Research and Treatment Centre (IFB) 1
University Hospital Leipzig, Leipzig, GERMANY, 2ABX-CRO,
Adiposity Diseases, University of Leipzig, Leipzig, GERMANY. Dresden, GERMANY, 3Teva Branded Pharmaceutical Products R&D,
Frazer, PA, UNITED STATES OF AMERICA, 4Arzneimittelforschung
Leipzig, Leipzig, GERMANY, 5Prilena Therapeutics Development,
Aim/Introduction: Pridopidine is an investigational drug which Herzliya, ISRAEL, 6Guide Pharmaceutical Consulting,
was initially designed as dopamine stabilizer to treat motor Millstone Twp, NJ, UNITED STATES OF AMERICA.
symptoms in HD. Interestingly, as shown previously in-vitro and
in rats, pridopidine has much higher affinity to S1Rs as compared
to D2/3Rs. S1R, located intracellularly at the endoplasmic Aim/Introduction: Pridopidine is currently under development
reticulum and mitochondria interface, may mediate as a drug to maintain functional capacity or to provide functional
neuroprotection and enhancement of mental dysfunction. Thus, benefit in Huntington disease (HD). Its pharmacological effect is
in order to improve the understanding about the mechanism mainly mediated via sigma-1 receptor (S1R) interaction. Little is
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S98

known so far about how this interaction exerts different brain V. Hugenberg1, W. Burchert1, R. Preuß1, N. Koglin2, M. Berndt2, A.
processes in vivo. It was, thus, the aim of this simultaneous Stephens2, C. Feldmann3, A. Kassner4, H. Milting4;
PET/MRI study to investigate the pridopidine effect on 1
Institute for Radiology, Nuclear Medicine and Molecular
neurotransmission, brain perfusion, metabolism, and functional Imaging, Heart and Diabetes Center North Rhine Westphalia,
connectivity. Materials and Methods: This is a sub-study of University Hospital, Ruhr University Bochum, Bad Oeynhausen,
a brain PET study which evaluated the S1R and dopamine-2 GERMANY, 2Life Molecular Imaging GmbH, Berlin, GERMANY,
receptor occupancy by pridopidine in healthy volunteers (HVs) 3
Department of Cardiothoracic, Transplantation and Vascular
and HD patients (abstract no. 2019-S-1338-EANM). Here, the Surgery (HTTG), Hannover Medical School, Hannover,
data of 3 HD patients (age 43±13yrs) and those of 7 HVs (age GERMANY, 4Clinic for Thoracic and Cardiovascular Surgery,
29±3yrs) are presented. All subjects underwent simultaneous Erich & Hanna Klessmann Institute, Heart and Diabetes
brain PET/multimodality MRI (up to 390min p.i., 3T Siemens Center North Rhine Westphalia, University Hospital, Ruhr
Biograph mMR) under baseline conditions and after a single University Bochum, Bad Oeynhausen, GERMANY.
oral dose of 90mg pridopidine. MRI included arterial spin
labelling (ASL, pulsed sequence, VOI and SPM analysis, global
normalisation, relative cerebral blood flow [rCBF]), resting-state Aim/Introduction: Left ventricular assist devices (LVADs)
fMRI (BOLD sequence, seed-based: basal ganglia, sensory- offer benefits for patients with severe congestive heart failure.
motor and default mode networks [DMN]), and proton MR Thromboembolic events like intra-pump thrombi, thrombi
spectroscopy (MRS, axial slice through striatum, 10 ROIs, each in inflow cannula or outflow graft are difficult to detect.
creatine [Cr]), choline [Cho], inositol [Ins], and glutamine/ Therefore, sensitive and specific diagnosis of pump thrombus
glutamate peaks, reference: N-acetylaspartate [NAA] peak). S1R remains a clinical dilemma. Currently, increased erythrocyte
occupancy was determined by (S)-(-)-[18F]Fluspidine PET and hemolysis, changes in LVAD power consumption and
VOI analysis, 1-tissue compartment modelling (metabolite- suggestive echocardiography are indirect evidences to suspect
corrected arterial input), and Lassen plot analysis. Results: In a pump thrombus. The LVAD titanium housing complicates the
HVs, 90mg pridopidine (i) occupied 91±4% of the S1Rs (n=4), application of noninvasive imaging techniques like MRI, CT or
(ii) decreased rCBF in temporal cortical (p=0.009) and cerebellar ultrasound. Therefore, a targeted nuclear medicine approach
(p=0.007) areas, (iii) decreased Ins/NAA in white matter using PET/CT would be of clinical impact for the direct detection
(p=0.037), and (iv) increased connectivity within the basal of a pump thrombus. 18F-GP1, a novel small-molecule PET tracer,
ganglia network (4/7 subjects) and DMN (6/7 subjects). In HD, targets the glycoprotein IIb/IIIa receptor on activated platelets
the drug effect was not different with regard to S1R occupancy. and was investigated for the imaging of thrombi in acute arterial
While no drug effects on rCBF were observed in HD, pridopidine and venous thrombosis. The objective of this work is to explore
increased Cr/NAA (p=0.050) and Cho/NAA (p=0.018) in the the feasibility of the direct imaging of a pump thrombus inside
putamina as well as functional connectivity within the default LVADs using 18F-GP1 PET/CT. Materials and Methods: The
mode (3/3 patients) network. Conclusion: Pridopidine in a radiosynthesis of 18F-GP1 was optimized for GMP-production.
clinically tested dose of 90mg intensively acts on S1Rs with 18
F-GP1 PET/CT was performed with adult patients who had
multiple associated (and at least in parts differential between symptoms of a pump thrombus. Explanted thrombi were
HD patients and HVs) effects on brain perfusion, metabolism, characterized by western blot using an HRP-labeled antibody
and functional connectivity. Especially the positive effect on against CD41. Results: GMP-compliant radiosynthesis of
the DMN network connectivity provides further support for 18
F-GP1 was realized via an automated two-step procedure
pridopidine improving functional impairment in HD. However, starting with the direct nucleophilic substitution of the Boc-
these data indicate that pharmacological PET/MRI is a useful protected tosylate precursor, followed by deprotection and
tool to improve understanding of drug effects in the brain on a HPLC purification. 18F-GP1 was obtained in radiochemical yields
multi-modality level in a one-stop shop approach. References: of 39±3% (decay corrected; rcp>98%) in 76-79 min (n=4) from
None. EOB. Preliminary preclinical studies revealed that 18F-attenuation
by LVAD titanium (1 mm) was 26-33%. Patients (n=5) suspected
of having an intra-pump thrombus or a thrombus in the outflow
510 graft were examined by 18F-GP1 PET/CT. Focal 18F-GP1 uptake
was observed in two patients inside the LVAD or in the outflow
Cardiovascular - Parallel Session: Cardiac graft, three patients were 18F-GP1-negative. After PET imaging
Imaging - More than Perfusion two patients (one 18F-GP1-positive, one 18F-GP1-negative)
underwent LVAD replacement. The clotted material derived
Sunday, October 13, 2019, 16:30 - 18:00 Lecture Hall 116 from the explanted LVADs confirmed the presence of GPIIb/IIIa
receptors on the 18F-GP1-positive thrombus, while no receptors
could be detected on fibrin material of the 18F-GP1-negative
case, confirming the imaging findings from the respective PET/
OP-234 CT scans. Symptoms of the other 18F-GP1-negative patients
Detection of Thrombi inside LVADs using 18F-GP1 PET/CT - were likely not caused by a pump thrombus. Conclusion: 18F-
Preliminary Results GP1 PET/CT is feasible for the specific detection of thrombi
S99 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

inside of LVADs. Furthermore, a differentiation between thrombi mouse? Journal of Nuclear Medicine, 2010. 51(8): p. 1269-1276.
and fibrin plaques might be of impact for therapy decision and Brodde, O.-E. and K. Leineweber, Autonomic receptor systems in
individualized patient management. References: Chae, EJNMMI the failing and aging human heart: similarities and differences.
Research (2019) 9:3. Kim, J Nucl Med (2019) 60:224. European journal of pharmacology, 2004. 500(1-3): p. 167-176.

OP-235 OP-236
Sex Hormones Preserve Cardiac Sympathetic Integrity Early inflammatory chances of myocardial ischemia-
Following Myocardial Injury reperfusion injury can be detected with vascular adhesion
A. Haider1,2, S. Bengs1,2, M. Maredziak1,2, A. Portmann1,2, G. protein-1-targeting PET imaging
Warnock1, F. Montecucco3, A. Akhmedov2, A. Müller Herde4, C. A. Autio1,2, S. Uotila1, V. Kytö3, M. Kiugel1, H. Liljenbäck1,4, T.
Keller4, S. D. Krämer4, R. Schibli4,1, L. Mu4,1, P. A. Kaufmann1, S. M. Saanijoki1, J. Knuuti1, S. Jalkanen2, A. Saraste1,3, A. Roivainen1,4;
Ametamey4, C. Gebhard1,2; 1
Turku PET Centre, Turku, FINLAND, 2University of Turku, Medicity
1
University Hospital Zurich, Zurich, SWITZERLAND, 2University Research Laboratory, Turku, FINLAND, 3Heart Center, Turku
of Zurich, Zurich, SWITZERLAND, 3University of Genoa, University Hospital and University of Turku, Turku, FINLAND, 4Turku
Genoa, ITALY, 4ETH Zurich, Zurich, SWITZERLAND. Center for Disease Modeling, University of Turku, Turku, FINLAND.

Aim/Introduction: Activation of the sympathetic nervous Aim/Introduction: Vascular adhesion protein-1 (VAP-1)
system is an initial physiological stress response facilitating mediates leukocyte trafficking into inflamed tissue (1). Sialic
inotropic and chronotropic adaptation of the heart. However, acid-binding Ig-like lectin 9 (Siglec-9) is a leukocyte ligand for
sympathetic overdrive following acute myocardial infarction VAP-1 and [68Ga]Ga-DOTA-Siglec-9 peptide can be used as a
(MI) - as observed predominantly in women - has been positron emission tomography (PET) tracer for in vivo imaging
linked to poor survival. Underlying mechanisms for the of inflammation (2). We hypothesized that [68Ga]Ga-DOTA-
female predisposition to persistent stress-induced adrenergic Siglec-9 would detect the inflammatory processes associated
activation remain elusive. The aim of this study was to assess with myocardial ischemia-reperfusion (I-R) injury. Materials and
the extent to which sex hormones regulate sympathetic activity Methods: The myocardial uptake of [68Ga]Ga-DOTA-Siglec-9
in the absence of myocardial injury as well as following acute was evaluated in rats subjected to temporary myocardial
myocardial infarction using small animal Positron-Emission- ischemia by transient surgical ligation of the left coronary artery
Tomography (PET). Materials and Methods: Gonodectomized (LCA). The LCA was ligated for 8-12 minutes (group 1, n=6) or 20
and sham-operated FVB/N mice of both sexes were scanned minutes (group 2, n=12) followed by a reperfusion of 24 hours.
following tail-vein injection of [11C]meta-hydroxynorephedrine In addition, group 3 consisted of rats with 8 minutes ligation and
([11C]mHED), a widely used PET probe in preclinical and clinical 4-6 hours reperfusion (n=3). Sham-operated rats (n=2-4) were
assessment of the cardiac sympathetic system. Subgroups of studied as controls. Animals were injected with [68Ga]Ga-DOTA-
each animal cohort were subjected to ischemia-reperfusion (I/R) Siglec-9 (27±13 MBq) and after 30 min, hearts were excised,
injury prior to in vivo cardiac imaging. [11C]mHED uptake was cut in short-axis slices and stained with triphenyltetrazolium
analysed in the myocardium and standardized uptake values chloride (TTC) for detection of myocardial injury. Dynamic
(SUVs) were used to compare sympathetic activity among PETand contrast-enhanced CT imaging were performed for a
different cohorts (n ≥ 5 for each cohort). Results: Female sham- subset of animals. [68Ga]Ga-DOTA-Siglec-9 uptake in the whole
operated mice generally exhibited higher myocardial [11C] heart was measured by ex vivo gamma counting. More detailed
mHED uptake compared to their male counterparts, however, radioactivity distribution in cryosections of the left ventricle was
these sex-differences vanished in gonodectomized animals. measured by autoradiography. Luminal VAP-1 induction was
In the absence of I/R injury, gonadal hormone deprivation evaluated by immunohistochemical staining of intravenously
resulted in significantly higher myocardial [11C]mHED uptake injected anti-VAP-1 antibody. Results: All animals in group
in both sexes. All mice exposed to sex hormones displayed 2 showed large TTC negative area of myocardial injury. PET
preserved [11C]mHED uptake following I/R injury. In contrast, imaging of this group showed significantly increased tracer
withdrawal of sex hormones resulted in cardiac sympathetic uptake in the injured myocardial area compared to remote
overdrive following I/R injury. Conclusion: Sex hormones myocardium (1.5-fold, p=0.014). Ex vivo gamma counting of
modulate baseline cardiac sympathetic tone and preserve excised hearts showed increased tracer accumulation in group
cardiac sympathetic integrity following I/R injury in mice. Given 2 (p=0.010) and group 3 (p=0.033) compared to sham-operated
(1) the detrimental role of sympathetic overactivation following controls. Autoradiography analysis showed significantly higher
myocardial injury in women, and (2) the potential role of sex [68Ga]Ga-DOTA-Siglec-9 uptake in the injured area compared
hormones in preventing sympathetic overdrive, assessment to non-ischemic myocardial area in group 2 (p=0.002) but
of cardiac sympathetic integrity may provide important differences in group 1 and group 3 were insignificant. The
prognostic information in postmenopausal women and elderly immunohistochemical staining showed VAP-1 positive vessels in
men. References: Law, M.P., et al., Molecular imaging of cardiac the ischemic left ventricle areas in groups 2 and 3. Conclusion:
sympathetic innervation by 11C mHED and PET: from man to The [68Ga]Ga-DOTA-Siglec-9 accumulates in the areas of
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S100

myocardial ischemia-reperfusion injury in rats and it reflects expression 15 days after myocardial infarction in mouse model
VAP-1 expression. References: 1. Salmi M, Jalkanen S. Trends assessed by 68Ga-sCD146 TEP imaging. We observed a higher
Immunol. 2001.2. Aalto K, Autio A, Kiss EA et al. Blood. 2011. TEP signal compared to 68Ga-PRGD2. Then, correlation study
showed that early post-ischemic 68Ga-sCD146 uptakes (Day
16) correlated with delayed later hearth perfusion allows us to
OP-237 postulate that 68Ga-sCD146 could represent a promising and
Comparison of a new68Ga-radiolabelled PET imaging innovative radiotracer to predict post-ischemic heart recovery.
agent sCD146 and RGD peptide forin vivoevaluation of References: None.
angiogenesis in mouse model of myocardial infarction
M. Anais, P. Garrigue, S. Fernandez, F. Hubert, L. Balasse, P. Brige, A.
Bouhlel, G. Hache, M. Blot Chabaud, F. Rochais, F. Dignat-George, OP-238
B. Guillet; Feasibility and potential time reduction of simultaneous
Aix marseille university, Marseille, FRANCE. 99mTc-tetrofosmin and 123I-BMIPP dual-tracer imaging
with cadmium-zinc-telluride detectors in patients with
acute myocardial infarction
Aim/Introduction: We recently reported that hindlimb S. Nakano1, Y. Yamada1, T. Muramatsu1, S. Nishimura1, N. Okano2, I.
ischemia induces an post-ischemic tissue increase of Matsunari2, K. Fukushima3;
angiomotin (AMOT) expression, which provides a promising 1
Department of Cardiology, International Medical Centre,
target for therapy and imaging. In this previous work, we Saitama Medical University, Hidaka, Saitama, JAPAN, 2Division
validated an AMOT-targeting 68Ga-radiolabled radiotracer of Nuclear Medicine, Department of Radiology, Saitama
(68Ga-sCD146) in peripheral ischemia. This present work aimed Medical University, Moro, Saitama, JAPAN, 3Department
to perform the first in vivo evaluation of 68Ga-sCD146 imaging of Nuclear Medicine, International Medical Centre,
compared to 68Ga-RGD2 and 18F-FDG imaging on a myocardial Saitama Medical University, Hidaka, Saitama, JAPAN.
infarction mice model. Materials and Methods: Myocardial
infarction was induced by permanent ligation of the left anterior
descending coronary artery and myocardial perfusion evaluated Aim/Introduction: Simultaneous perfusion-metabolism
by Doppler ultrasound imaging at Day 30 post-surgery and by dual imaging is clinically useful. However, use of Tc rather
18
F-FDG PET imaging at Days 16 and 30 post-surgery. NODAGA- than Tl as a perfusion tracer has been challenging due to its
conjugates of sCD146 were synthetized and radiolabeled with proximate photo-peak with BMIPP, resulting in poor resolution.
68
Ga. 68Ga-sCD146 and 68Ga-PRGD2 (5-10MBq) PET imaging This drawback could be overcome by improved properties
was performed on SHAM and myocardial infarction mice of cadmium-zinc-telluride (CZT)-based scanners. We aim to
respectively at 15-22 and 14-23 days post-surgery using µPET/ investigate feasibility and potential time reduction of 99mTc-
CT (nanoPET/CT®, Mediso). Results: On Day 16, 18F-FDG PET tetrofosmin and 123I-BMIPP dual-tracer imaging using a
imaging confirmed myocardial infarction, radiotracer uptake Discovery NM/CT 670 CZT. Materials and Methods: Thirty
infarct area (5.19±4.10%ID/g) was significantly decreased patients having undergone primary percutaneous coronary
compared to the viable heart (30.71±7.25%ID/g) (P<0.0001, intervention for acute myocardial infarction underwent single-
n= 7). 68Ga-sCD146radiochemical purity was 93.1%±2.0 (n=10) (Tc-tetrofosmin (TF) or I-BMIPP first) followed by simultaneous
and stability in serum evaluated up to 2 hours at 90±1.5%. Tc-TF/I-BMIPP dual-tracer imaging. To examine feasibility, QGS
In mice, 68Ga-sCD146 showed a rapid plasmatic clearance and QPS values of dual-imaging were compared with those of
(6.0±2.0min) and a pharmacokinetic profile compatible with single-imaging. To verify clinical utility, inter-rater concordance
PET imaging. In myocardial infarction model, heart to muscle between two radiologists was also assessed. Next, referenced
(H/M) ratio of 68Ga-sCD146 uptake 90min after injection showed images of dual-imaging with acquisition time of approximately
a radiotracer uptake in infarct area at Day 15 (H/M=3.23±0.82; 16 minutes were reframed to produce images with shortened
n=7) significantly higher than in sham (H/M=2.03±0.25; n=7), acquisition time, and the values were compared among
(P=0.02). 68Ga-PRGD2 didn’t show a significantly higher uptake various acquisition times. Results: The QGS/QPS values were
ratio in myocardial infarction model at Day 14 (H/M=2.67±1.36; comparable between the single- and dual-imaging (intra-class
n=6) compared to sham (H/M=1.64±0.81 n=6), (p=0.11). We correlation (ICC) coefficients for summed motion score: 0.95,
didn’t find any significant differences for both tracers between summed thickened score: 0.98, summed rest score (SRS) for Tc-
ischemic heart and sham heart at 22 and 23 days post-surgery TF: 0.97, SRS for I-BMIPP: 0.95). The inter-rater concordance for
(68Ga-sCD146: H/Mischemic=2.52±0.94, H/Msham=2.02±0.56);(68Ga- detection of infarction and perfusion-metabolism mismatch
PRGD2, H/Mischemic=0.95±0.19, H/Msham=0.65±0.12). Interestingly, was significant (P < 0.001). The QPS values with acquisition time
we also observed a significant correlation between H/M ratio of 8, 4 and 2 minutes showed good consistency with 16 minutes
assessed by 68Ga-sCD146 imaging on Day 15 and the latest (the lower 95% CI of ICC >= 0.8). The QPS values for Tc-TF with
perfusion of heart assessed by 18F-FDG on Day 30 (R2=0.58;n=7, shortened acquisition times (8, 4 , and 2 minutes) also showed
P=0.04). Conclusion: Based on the increased AMOT expression good consistency with those with 16 minutes. However, the
we recently reported in peripheral ischemia, this work QPS values for I-BMIPP with 2 minutes were not consistent with
demonstrated for the first time a transient increase of AMOT 16 minutes (the lower 95% CI of ICC < 0.8). Conclusion: The
S101 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

(semi-)quantitative values of myocardial function, perfusion, vs SUV mean septum:7.33±2.88, respectively, p=0.3). Similarly,
and fatty acid metabolism were closely comparable between absolute MBF was significantly different between the regions
the dual-tracer and single-tracer modes, suggesting clinical in the dyssynchrony group (lateral wall: 0.92±0.23 ml/g/min vs
feasibility of the novel CZT-based scanner for the simultaneous septum: 0.57±0.11 ml/g/min, p<0.0001), whereas in the non-
Tc-TF/I-BMIPP dual-tracer acquisitions. The QGS and QPS values dyssynchrony group absolute MBF was more homogeneous
obtained from images with shorter acquisition times (8, 4, and 2 (lateral wall: 0.77±0.21 ml/g/min vs septum: 0.61±0.23 ml/g/
minutes) correlated with the values obtained from images with min, p=0.16). Patients with mechanical dyssynchrony had
a reference acquisition time of 16 minutes. However, tracer- a significantly lower 18F-FDG SLR (0.50±0.13) compared to
specific predisposition should be considered, as the QPS values patients without dyssynchrony (0.86±0.23, p=0.02). However,
for I-BMIPP with acquisition time of 2 minutes were inconsistent no significant difference in MBF SLR was observed between
with those with 16 minute. In summary, simultaneous Tc-TF/I- both groups (dyssynchrony: 0.67±0.17 vs non-dyssynchrony:
BMIPP dual-tracer imaging with the novel CZT scanner may be 0.80±0.21, p=0.2). Moreover, ROC analyses showed that 18F-FDG
clinically feasible, and time reduction can be possible in view of SLR was highly predictive of the presence of mechanical
potential tracer-specific predisposition. References: None. dyssynchrony (area under the curve 0.91, p<0.0001) with
an optimal cut-off value of 18F-FDG SLR ≤0.74 (sensitivity
100%, specificity 83%). MBF SLR didn’t show any significance
OP-239 for predicting mechanical dyssynchrony. Conclusion: Non-
Low septal to lateral wall 18F-FDG ratio is a marker of ischemic heart failure patients with mechanical dyssynchrony
mechanical dyssynchrony in non-ischemic CRT candidates demonstrate heterogeneous regional metabolism and MBF
G. Degtiarova1,2, P. Claus3, J. Duchenne4,5, M. Cvijic4, H. J. Verberne6, compared to non-dyssynchrony group. However only 18F-FDG-
G. Schramm1, J. Nuyts1, J. Voigt4,5, O. Gheysens1,2; SLR is the significant predictor of the presence of mechanical
1
Nuclear Medicine and Molecular Imaging, Department dyssynchrony and might be associated with CRT response.
of Imaging and Pathology, KU Leuven, Leuven, BELGIUM, References: 1.Stankovic I, Prinz C, Ciarka A, Daraban AM,
2
Nuclear Medicine and Molecular Imaging, University Kotrc M et al. Relationship of visually assessed apical rocking
Hospitals Leuven, Leuven, BELGIUM, 3Cardiovascular Sciences, and septal flash to response and long-term survival following
Cardiovascular Imaging and Dynamics, KU Leuven, Leuven, cardiac resynchronization therapy (PREDICT-CRT). Eur Heart J
BELGIUM, 4Cardiovascular Diseases, University Hospitals Cardiovasc Imaging. 2016 Mar;17(3):262-9.
Leuven, Leuven, BELGIUM, 5Cardiovascular Sciences,
Cardiology, KU Leuven, Leuven, BELGIUM, 6Radiology
and Nuclear Medicine, Amsterdam UMC, location AMC, OP-240
University of Amsterdam, Amsterdam, NETHERLANDS. Cardiac 123I-mIBG scintigraphy as a tool to optimize CRT
patient selection
D. O. Verschure1, E. Poel1, V. Frantellizzi2, G. De Vincentis2, O.
Aim/Introduction: Presence of mechanical dyssynchrony is Gheysens3, J. R. de Groot1, H. J. Verberne1;
associated with favorable response to cardiac resynchronization 1
Amsterdam University Medical Center, Amsterdam,
therapy (CRT)1. Better understanding of the pathophysiological NETHERLANDS, 2Sapienza - University of Rome, Rome,
changes, induced by mechanical dyssynchrony, may improve ITALY, 3University Hospitals Leuven, Leueven, BELGIUM.
patient selection for CRT. In this study, we investigated the
effect of mechanical dyssynchrony on regional myocardial
metabolism and absolute perfusion assessed with 18F-FDG Aim/Introduction: Cardiac resynchronization therapy (CRT) is a
and 13N-NH3 PET/CT in non-ischemic patients selected for CRT. disease modifying therapy in patients with chronic heart failure
Materials and Methods: 30 consecutive patients underwent (CHF). Eligibility for CRT is based on QRS duration and NYHA
static 18F-FDG (using a hyperinsulinemic euglycemic clamping) functional capacity only. However, one-third of CHF patients
and resting dynamic 13N-NH3 PET/CT scans 1 week before CRT does not benefit from CRT. Moreover, CRT is associated with
implantation. Regional 18F-FDG uptake and absolute myocardial malfunction and high costs. In addition there is no consensus on
blood flow (MBF, kinetic modelling) were analyzed in the how to assess CRT response best. This study evaluated whether
septal and lateral wall and for both, septal-to-lateral wall ratios 123
I-mIBG assessed cardiac sympathetic activity could optimize
(SLR) were calculated. Based on the presence of mechanical CRT patient selection. Materials and Methods: 78 stable CHF
dyssynchrony (either septal flash or apical rocking or both) on subjects from Italy and the Netherlands (age 66.8 ± 9.6 years,
echocardiography, patients were divided into 2 groups - with 73% male, LVEF 25.2 ± 6.7%) referred for CRT-Defibrillator
(n=23) and without (n=7) mechanical dyssynchrony. Results: implantation were enrolled. All subjects underwent planar
A significantly higher mean 18F-FDG SUV in the lateral wall 123
I-mIBG scintigraphy prior to CRT implantation. Early and late
was observed compared to the septum in the group with heart-to-mediastinum (H/M) ratio and 123I-mIBG washout (WO)
mechanical dyssynchrony (SUVmean lateral wall: 11.19±4.10 were calculated. Improvement of LVEF (>35%), QRS duration
vs SUVmean septum: 5.58±2.65, p<0.0001), while in the (<150 msec) and NYHA functional class between baseline and
group without dyssynchrony 18F-FDG distribution was not 1 year follow-up were used as parameters of CRT response.
different between the walls (SUV mean lateral wall: 8.31±2.50 Results: Response to CRT using QRS duration occurred in 36
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S102

patients, NYHA functional class and LVEF identified 33 patients ArE was 10%, with sensitivity 90% and specificity 69% by the
each. Of all three response parameters only improvement ML model. Conclusion: The accuracy of the ML model with 14
of LVEF could be independently predicted by late H/M ratio variables and that of the four-variable statistical model were
(p=0.009). None of the other myocardial 123I-mIBG parameters comparable in predicting cardiac events. However, the ML
was associated with CRT response. Conclusion: In stable CHF model showed a better predictive accuracy for ArE and seems
myocardial late H/M ratio was associated with improvement of promising to predict serious arrhythmic events in patients with
LVEF as a measure of CRT response. Therefore cardiac 123I-mIBG CHF. References: Statistical model from European Heart Journal
could be seen as a tool to optimize the selection of CHF subjects - Cardiovascular Imaging 2018;19: 749-756.
who might benefit from CRT. References: None.

404c
OP-241 Mini Course 3 - Technologist Committee:
Prediction of cardiac death using 123I-MIBG: comparison
between statistical and machine learning models for
Theranostics - Fundamental
serious arrhythmic events and heart failure death
K. Nakajima1, T. Nakata2, T. Doi3, K. Maruyama4; Sunday, October 13, 2019, 17:00 - 18:00 Lecture Hall 117
1
Kanazawa University, Kanazawa, JAPAN, 2Hakodate
Goryoukaku Hospital, Hakodate, JAPAN, 3Teine Keijinkai Hospital,
Sapporo, JAPAN, 4Wolfram Research Inc, Tokyo, JAPAN.
OP-242
General Aspects of Theranostics in Nuclear Medicine
Aim/Introduction: Although we have been working on the S. Mirzaei;
prediction of sudden cardiac death (SCD) and heart failure Department of Nuclear Medicine with PET-Center,
death (HFD) using 123I-meta-iodobenzylguanidine (mIBG) Wilhelminenspital, Vienna, AUSTRIA.
in patients with chronic heart failure (CHF), an appropriate
classifier model to predict serious arrhythmic events (ArE) has
yet to be determined. The aim of this study is to establish the OP-243
model for predicting ArE using Japanese multicenter cohort Theranostics for Technologists in the Context of NET
database with machine learning (ML) method. Materials and N. Gulliver;
Methods: A total of 525 patients (66±14 years, male 72%) with Department of Nuclear Medicine & PET-CT | King’s College Hospital
CHF was used for creating the statistical and machine learning NHS Foundation Trust | Denmark Hill, London, UNITED KINGDOM.
(ML) models that are implemented on the Wolfram Language.
ArE comprised SCD, serious arrhythmic events and appropriate
therapy by implantable cardioverter defibrillator within a two- 601
year follow-up period. A multivariable statistical model used
four variables of age, left ventricular ejection fraction, NYHA
CME 5 - Oncology & Theranostics + Bone & Joint
functional class, and heart-to-mediastinum ratio (HMR) that was
Committee: Radionuclide Molecular Imaging in
calculated with an anterior planar mIBG image. To develop ML
Bone Tumours and Multiple Myeloma - Pearls,
models, in addition to 4 variables as above, a total of 14 variables
Patterns & Pitfalls
were used; sex, MIBG washout rate, estimated glomerular
filtration rate, ischemic etiology, b-type natriuretic peptide, Monday, October 14, 2019, 8:00 - 9:30 Auditorium
hemodialysis, diabetes, hypertension, dyslipidemia, and anemia.
The training of ML was performed with randomly selected 392
patients (75%), and the remaining patients (25%) were used for
validation. The accuracy of the models was compared using OP-244
receiver-operating characteristic (ROC) analysis with area under Radionuclide Molecular Imaging in Primary Bone Tumours
the curve (AUC) analysis and contingency table analysis. Results: T. Van den Wyngaert;
During the follow-up of 2 years, 7% and 20% of the patients Antwerp University Hospital, Nuclear Medicine, Edegem, BELGIUM.
experienced ArE and HFD, respectively. To predict cardiac events
including both HFD death and ArE, the four-variable logistic
model and ML-based classifier model showed ROC-AUC of OP-245
0.88 and 0.88, respectively (p=0.82). To predict ArE specifically, Radionuclide Molecular Imaging of Bone Metastases
the ML model showed better AUC of 0.83 compared with the G. Gnanasegaran;
statistical model AUC of 0.67 (p=0.049). The contingency table Royal Free Hospital, Nuclear Medicine, London, UNITED KINGDOM.
analysis for ArE events also showed a higher likelihood ratio
by the ML model than that by the statistical model (p=0.0002
and 0.04, respectively). The best cutoff probability to predict
S103 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

OP-246 OP-251
Radionuclide Molecular Imaging in Multiple Myeloma Optimal Molar Activity is a Precondition for a Sensitive
C. Nanni; and Specific Molecular Imaging in Oncology
S.Orsola-Malpighi Hospital, Policlinico S.Orsola Malpighi V. Tolmachev;
Bologna, Nuclear Medicine, Bologna, ITALY. Biomedical Radiation, Institute of Oncology, Radiology
and Clinical Immunology, Uppsala, SWEDEN.

602
Joint Symposium 9 - Neuroimaging Committee OP-252
Mass Effect of PET Radioligands for Neuroscience
/ ILAE: Clinical Use of Brain Imaging for Patients C. Halldin;
with Epilepsy Karolinska Institute, Department of Clinical
Neuroscience, Stockholm, SWEDEN.
Monday, October 14, 2019, 8:00 - 9:30 Lecture Hall 311

OP-247 604
The Use of MRI for Patients with Epilepsy and the Need of
Multimodal Imaging for the Clinician
Technologists: Oral Presentations 1
P. Federico;
Hotchkiss Brain Institute, Cumming School of Medicine, Monday, October 14, 2019, 8:00 - 9:30 Lecture Hall 117
University of Calgary, Calgary, CANADA.

OP-248 OP-253
FDG-PET for Partial Epilepsy Revisited Ability of artificial intelligence to diagnose coronary
F. Chassoux; artery stenosis using hybrid images of coronary computed
Sainte-Anne Hospital, Neurosurgery Department, Paris, FRANCE. tomography angiography and myocardial perfusion
SPECT
H. Yoneyama1, K. Nakajima1, J. Taki1, H. Wakabayashi1, T. Konishi1,
OP-249 K. Okuda2, T. Shiburani3, M. Onoguchi3, S. Kinuya1;
The Role of Ictal SPECT in the Presurgical Evaluation of 1
Kanazawa University Hospital, Kanazawa, JAPAN,
Patients with Drug-Resistant Epilepsy 2
Kanazawa Medical University, Kanazawa, JAPAN,
W. Van Paesschen; 3
Kanazawa University, Kanazawa, JAPAN.
UZ Leuven, Neurology Department, Leuven, BELGIUM.

Aim/Introduction: Detecting culprit coronary arteries in


patients with ischemia using only myocardial perfusion single-
photon emission computed tomography (SPECT) can be
603 challenging. This study aimed to improve the detection of culprit
regions using an artificial neural network (ANN) to analyze hybrid
Joint Symposium 10 - Drug Development images of coronary computed tomography angiography (CCTA)
Committee / SRS: What is Molar Activity and and myocardial perfusion SPECT. Materials and Methods: This
When does it Impact PET Imaging? study enrolled 59 patients with stable coronary artery disease
(CAD) who had been assessed by coronary angiography within
Monday, October 14, 2019, 8:00 - 9:30 Lecture Hall 312 60 days of myocardial perfusion SPECT. Two nuclear medicine
physicians interpreted the myocardial perfusion SPECT and
hybrid images with four grades of confidence, then drew
regions on polar maps to identify culprit coronary arteries. The
OP-250 gold standard was determined by the consensus of two other
What do I Need to Know? Basic Concepts of Mass in nuclear cardiology specialist based on coronary angiography
Radionuclide Imaging findings and clinical information. The ability to detect culprit
S. Bongarzone; coronary arteries was compared among experienced nuclear
King’s College London, Division of Imaging Sciences and cardiologists and the ANN. Receiver operating characteristics
Biomedical Engineering, London, UNITED KINGDOM. (ROC) curves were analyzed and areas under the ROC curves
(AUC) were determined. Results: Using hybrid images, observer
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S104

A detected CAD in the right (RCA), left anterior descending (p=0,03). The mean ± SD in the ischemic group was 1,31±0,27
(LAD), and left circumflex (LCX) coronary arteries with 83.6%, and in the non-ischemic group this was 1,44±0,30. The (positive)
89.3%, and 94.4% accuracy, respectively and observer B did so correlation between the RPP-ratio and the CFR is statistically
with 72.9%, 84.2%, and 89.3%, respectively. The ANN was 79.1%, significant (p=0.00) for both groups. However, the correlation
89.8%, and 89.3% accurate for each coronary artery. Diagnostic was shown to be negligible for the non-ischemic group (r2=0.09)
accuracy was comparable between the ANN and experienced and weak for the ischemic group (r2=0,25). Conclusion: RPP-
nuclear medicine physicians. The AUC was significantly improved ratios are significantly different for patients with and without
using hybrid images in the RCA region (observer A: from 0.715 myocardial ischemia. However, a correlation between the RPP-
to 0.835, p = 0.0031; observer B: from 0.771 to 0.843, p = 0.042). ratio and the CFR in the non-ischemic group is negligible and
To detect culprit coronary arteries in perfusion defects of the only weak in the ischemic group. References: None.
inferior wall without using hybrid images was problematic
because the perfused areas of the LCX and RCA varied among
individuals. Conclusion: Hybrid images of CCTA and myocardial OP-255
perfusion SPECT are useful for detecting culprit coronary Studies On Sterile Filters In The Preparation N-13
arteries. Diagnoses using artificial intelligence is comparable to Ammonia Injection
that by nuclear medicine physicians. References: 1) Nakajima K, C. Oh, S. Kim, J. Shin, M. Cha, Y. Ji, S. Choi;
Okuda K, Watanabe S, Matsuo S, Kinuya S, Toth K, et al. Artificial Samsung Medical Center, Seoul, KOREA, REPUBLIC OF.
neural network retrained to detect myocardial ischemia using a
Japanese multicenter database. Ann Nucl Med. 2018;32:303-10.
2) Nakajima K, Kudo T, Nakata T, Kiso K, Kasai T, Taniguchi Y, et Aim/Introduction: In the preparation process for N-13
al. Diagnostic accuracy of an artificial neural network compared ammonia injections, there were radioactive medicines adsorbed
with statistical quantitation of myocardial perfusion images: a on sterile filters remarkably. Hereby, we have compared the
Japanese multicenter study. Eur J Nucl Med. 2017;44:2280-3. adsorption rate and quality test on Millex GS filter and Satorious
Minisart filter, both representativly hydrophilic sterilizing filters,
also evaluated which filter is more accommodative for N-13
OP-254 ammonia injection production. Materials and Methods: The
The ratio between RPP in stress and rest in patients with filters used for sterilization of N-13 ammonia injections were
and without myocardial ischemia as assessed by 13NH3 Millex GS filter (pore size : 0.22 μm, Merk Millipore, Ireland) and
PET/CT Satorious Minisart filter (pore size : 0.2 μm, Satorious, Germany),
C. Bulder, S. V. Lazarenko, F. M. van der Zant, W. A. M. Broos, R. J. J. which are generally used to strain aqueous solutions. After
Knol; the N-13 ammonia passes through each sterilization filter, the
Noordwest Ziekenhuisgroep, Alkmaar, NETHERLANDS. adsorption rate of the filter (n = 10) is determined by measuring
not only the radioactivity through the filter but also the amount
of radioactivity remaining in it using a Dose calibrator. The
Aim/Introduction: The rate pressure product (RPP) is a widely N-13 ammonia injections after the each filter is tested by the
used hemodynamic parameter and a good predictor of quality control test to conform to the European Pharmacopoeia
myocardial oxygen consumption. In the present study, RPP- standard. Results: The ratio of radioactivity passed through Millex
ratios (ratio between RPPstress and RPPrest) were compared for GS indicated 29.0 ± 17.6 %, Satorious Minisart filters output was
groups of patients with proven myocardial ischemia as assessed 80.9 ± 3.2%, respectively. Each ratio of radioactivity adsorbed on
with 13NH3 myocardial perfusion PET/CT versus patients without the sterile filter was 71.0 ± 17.6% for Millex GS and 19.1 ± 3.2
ischemia. Also, the relation between the RPP-ratios and cardiac % for the Satorious Minisart filters, respectively. Furthermore, on
flow reserves (CFR) of both groups was investigated. Materials the ratio of filtered radioactivity, Using Satorious Minisart filter
and Methods: Data of 181 patients (90 M, 91 F) who underwent showed about 2.8 times higher than using Millex GS filter. The
an adenosine-induced pharmacologic stress 13NH3 PET/CT were quality testing of N-13 ammonia injections through each filter
analyzed. Of these, 66 patients showed evidence of myocardial met the European Pharmacopoeia standard. Conclusion: The
ischemia at myocardial perfusion PET/CT (ischemic group) Millex GS filter is composed of cellulose acetate and cellulose
whereas the other 115 patients had no signs of ischemia and nitrate, whereas the Satorious Minisart filter is composed only
normal myocardial blood flow (non-ischemic group). The RPP of cellulose acetate. Therefore, the presence of cellulose nitrate
was calculated using the following formula: heart rate (HR) on the membrane seems to have made differences. The quality
* systolic blood pressure. Subsequently, the RPP ratio was control test results of the radioactive medicines filtered using
calculated by using the following formula: RPP stress / RPP rest. both filters also met the European Pharmacopoeia standards
An independent t-test was used to evaluate the difference in without any net differences even after impurities concerns. In
RPP-ratio between both groups. Next, the correlation between this hospital, the loss of radioactive medicines caused by the
the RPP-ratio and the CFR (myocardial blood flow stress/ adsorption of filters was minimized by the use of Satorious
myocardial blood flow rest) was assessed using a Pearson’s Minisart filter in the preparation process of N-13 ammonia
correlation test for both groups. Results: The RPP ratio differs injection, thereby increasing the synthetic yield. References:
significantly between the ischemic and non-ischemic group None.
S105 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

OP-256 been radiolabelled with Tc-99m for various imaging studies;


The Importance of Timing of MRAC Acquisition on Co- however, its use for Red Cell Mass studies has not been fully
Registration in PET/MR Cardiac Stress Examinations explored; in particular whether it gives an accurate Red Cell
M. Thueringer, M. Hofbauer, S. Epp, E. von Felten, D. Patriki, T. Mass value and whether the label is stable. Using current
Fuchs, R. R. Buechel; methods for radiolabelling RBC with Tc-99m for imaging
University Hospital Zurich, Zurich, SWITZERLAND. studies, this study aims to establish whether labelling efficiency
is satisfactory, to assess the need for EDTA as a stabilising agent,
and to assess stability of radiolabelled RBC over the desired shelf
Aim/Introduction: Cardiac examinations with N13-ammonia life (up to 2 hours). Materials and Methods: Previous methods
are scanned in two PET parts, each lasting 18 minutes. Before of radiolabeling RBC have been evaluated and a proposed
starting the PET stress scan, adenosine is injected over two method established. The procedure is to be performed using
minutes. After starting the PET scan, the MR-attenuation venous blood samples from healthy volunteers. Dilute Stannous
correction (MRAC) is scanned first as default. Adenosine injection Chloride will be added to 10ml of blood, after incubation 4%
is stopped after six minutes at the latest. Due to the stress the Edetate solution is to be added before centrifuging the blood
adenosine creates, the diaphragm and therefore the heart are to obtain the packed RBC’s. To the RBC 10MBq of Tc-99m is
moving more at the beginning of the PET in comparison to added and incubated for 5 minutes. After which the sample is
the end. The aim of the study is to improve the accuracy of the washed with saline and the supernatant measured to calculate
co-registration of the MRAC to the PET images. Materials and the labelling efficiency (LE). A total of 4 samples have been
Methods: The standard workflow is as follows: 1.) Start of the processed using the Edetate solution and 4 samples without. At t
adenosine injection 2.) Start of the PET scan directly followed = 0, 1 and 2hrs the samples are centrifuged and the supernatant
by the acquisition of the MRAC 3.) N13-Ammonia injection 4.) measure to calculate the stability. Results: Total mean LE for
End of the adenosine injection. 30 patients were scanned using labelling method without using EDTA was 92%, with EDTA mean
the GE Signa PET/MR. In order to improve the co-registration LE was also 92%. Mean percentage loss after two hours without
of the MRAC to the PET images, we moved the MRAC to the EDTA was 3.9%, using EDTA was 3.1%. Conclusion: The use of
very end of the PET task, when the effects of the adenosine have Tc-99m to radiolabel RBC has been shown to give high labelling
subsided. The MRAC must be acquired within the 18-minute efficiency with acceptable in vitro stability, The use of EDTA
PET task, so it can be used for the reconstructions. Four patients to stabilise the product and bind any free stannous ions did
(ongoing) were scanned that way. Results: Performing the not impact the final labelling efficiency or the in vitro stability
standard workflow, MRACs had to be shifted manually (R/L, A/P, of the final labelled cells. Future work will look to confirm in
S/I) after every examination to gain a correct co-registration vivo stability of the label by assessing thyroid uptake, and by
in the dynamic PET reconstruction of the first seven minutes. measuring freeTc-99m in urine and blood plasma. References:
No manual shift of the MRACs was needed when it had been None.
acquired at the end of the PET task. Conclusion: The alternative
workflow reduces effort both on doctors’ side who provide the
shift values and on technologists’ side who set up the additional OP-258
PET reconstructions manually. Another advantage is the time Review of protocol change for SLN injections in patients
factor, because the gap between end of exam and start of with breast cancer
reading shortens significantly. Since the reconstructions with P. J. Campbell, H. Sharman, C. Caro;
shifted MRACs can only be set up, after all PET/MR examinations The Royal Marsden NHS FT, London, UNITED KINGDOM.
are finished and the reconstruction time itself is around 25
minutes. The alternative workflow is therefore more efficient
and saves time. The only action it requires is moving the MRAC Aim/Introduction: The purpose of the service review was
down to the end of the PET task, which can be set as default in to investigate the efficacy of the new standard of practice to
the scan protocol. References: None. reduce the presence of air artefacts on ultrasound for patients
undergoing sentinel lymph node injections and enhance
patient flow through departments. Previously there would
OP-257 be an air bubble behind the Tc99m Nanocolloid to “push” the
Investigation into Method for Radiolabelling Erythrocytes tracer out of the syringe due to the small volume (0.1mls). This
with Tc-99m for Use in Red Cell Volume technique was replaced by retrieving more tracer and purging
W. A. Sanders, J. Croasdale, A. Notghi; the air from the syringe. Materials and Methods: 142 patients
SWBH NHS Trust, Birmingham, UNITED KINGDOM. (49 2 day protocol and 93 same day protocol) using the new
technique were retrospectively investigated along with 92 of
the previous method. (63 same day and 29 2 day protocols).
Aim/Introduction: Use of Cr-51 Sodium Chromate for in-vitro Counts measured at the injection site, number of “hot” sentinel
labelling of RBC’s (Red Blood Cells) has been the gold standard lymph nodes detected and use of blue dye was documented.
for many years, and its withdrawal means a new radiolabelling Cases were excluded if the counts were omitted from the
method for Red Cell Mass studies is required. Red Cells have operation notes Results: The study showed some interesting
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S106

results. Previous studies using sulphur colloid have indicated 0.2%, but changed classification due to rounding; the second
that a one day protocol has marginally better axillary drainage changed from 7% to 2% (moderate to severe). Overall mean
whilst the two day protocol is still within limits. This single centre difference between the two methods was 0.8% retention. The
study showed that 14% of patients having SLNI using the old addition of 99mTc in the room caused an 18% increase in raw
technique required the addition of blue dye to identify the counts for DEW and 1.0% for HEW, when background corrected
sentinel lymph nodes compared to 20% of those requiring a this changed to DEW 0.7% and HEW 1.1%. 99mTc outside the
two day protocol. Comparing this to the new airless technique room increased raw counts in DEW by 0.6% and HEW by 0.7%.
we can see the one day protocol has a 24% requirement for the Conclusion: Results calculated with both methods were 99%
blue dye whereas the 2 day protocol has a 10% necessity for the comparable, with only 1 patient significantly changing - most
blue dye. This could be as a result of an increased activity injected likely due to a transient source adding counts to the lower
median 12.56MBq for the air push technique and 14.51MBq for energy window, demonstrating the potential risk of including
the airless technique. However this is contraindicated when the lower energy peak. External sources are only problematic
studying the median values for the 2 day protocol: 31.6MBq if they change during the procedure. The decision to include/
for the air push and 37.5MBq for airless. This could show that a exclude the lower energy peak will depend on local factors such
larger activity for a 2 day protocol than initially proposed could as department layout and session arrangements. Our working
result in better sentinel node detection and a value as close to conclusion is to continue with DEW but use the low and high
10MBq as practicable for the same day injections. Conclusion: windows separately as a QA step. Further measurements and
To conclude the 2 day protocol performs better than the same analysis are ongoing and will be presented at the conference.
day injections for sentinel node detection with the new airless References: None.
technique. This allows for a smother patient flow through the
department and minimal surgical delays arising from difficulties
obtaining ultrasound images due to the presence of air artefacts. OP-260
However careful consideration should be given to patient Establishing Local Dose Reference Levels for Low-dose
preference and convenience. References: None. CT Scans Associated with SPECT and PET Imaging
Examinations - Experience at Sultan Qaboos University,
Oman
OP-259 Y. Bouchareb1, N. Tag2, A. Al-Jabri2, N. Makhmari2, A. Al-Haji2, H.
Twin Peaks: Should we use Dual Energy Windows for [75Se] Al-Dhuhli2;
SeHCAT Studies? 1
Sultan Qaboos University, Muscat, OMAN, 2Sultan
A. List, B. Stiles, A. Paramithas; Qaboos University Hospital, Muscat, OMAN.
St George’s University Hospitals NHS Foundation
Trust, London, UNITED KINGDOM.
Aim/Introduction: The purpose of this study was to develop
effective local dose reference levels (LDRL) for use within
Aim/Introduction: Gamma emissions from 75Se occur at two SPECT-CT and PET-CT services in order to monitor and audit
principle energies, 136keV and 264keV. This presents a choice locally devised low-dose CT protocols associated with the
for the Nuclear Medicine department undertaking SeHCAT (GE most frequent SPECT/CT and PET/CT imaging examinations
healthcare) studies; collect data from both - maximising total performed at our institution. Materials and Methods: A
number of counts; or use only the higher energy emission - retrospective study included a total of 589 adult patients who
reducing the chance of interference from other sources. The have undergone SPECT/CT and PET/CT scanning over a period
former is our current clinical protocol. The aims of this study of 24 months was performed. Patients were scanned on the
were to; determine if using only the higher energy window Siemens Symbia SPECT/CT T16 and mCT 128 slices PET/CT
(HEW) gives equivalent results to using dual energy windows Siemens scanners. The 589 patients’ scans consisted of: 181
(DEW); and to assess whether interference from other sources whole body PET/CT scans, 140 SPECT/CT bone, 113 myocardial
are likely to have a clinically significant effect on the calculated perfusion imaging SPECT/CT, 87 thyroid post-ablation scans, 41
result. Materials and Methods: 141 SeHCAT patients were parathyroid and 27 octreotide SPECT/CT scans. Low-dose CT
reviewed retrospectively. Their 7-day retention was calculated scans, performed as part the PET/CT and SPECT/CT imaging
using both DEW and HEW and classified as: normal (≥15%), examinations, were only used for attenuation correction and
mild Bile Acid Malabsorption (BAM) (<15%), moderate BAM localisation at our institution. The CT dosimetry data (CTDIvol,
(<10%) or sever BAM (<5%). A phantom study was performed DLP and exposure settings) which was documented on RIS and
using a 370kBq 75Se-SeHCAT capsule taped to the back of a PACS, was collected for all patients scans. The mean, standard
water-filled phantom and imaged using the clinical protocol. deviation (SD) and third quartile were then calculated for CTDIvol
Imaging was repeated with 400MBq of 99mTc placed outside (mGy) and DLP (mGy.cm) for each SPECT/CT examination group
and then inside the room. Results: DEW classified 95 patients and whole body PET/CT examinations. The effective dose
as normal, 14 mild, 16 moderate, 16 severe BAM. HEW gave 94 range was calculated for each examination group using the
Normal, 15 mild, 15 moderate, 17 severe BAM. Of 141 patients k-factors devised by Shrimpton et al (2006) for effective dose
2 changed category; in one case the retention changed by per DLP (mSv/mGycm). Results: The calculated LDRLs are given
S107 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

as follows (third quartile DLP (mGy.cm), third quartile CTDIvol The low dose-CT is less than a tenth of the diagnostic-CT. The
(mGy)): PET whole body: 251, 2.3; SPECT bone: 246, 5.0; SPECT whole-body acquisition has the highest radiation dose to the
myocardial perfusion imaging: 191, 6.9; SPECT Parathyroid, 319, lens. The difference between the Head/Neck and the other
6.7; SPECT Octreotide: 183, 2.8 and SPECT thyroid post-ablation: protocols can be explained by the positioning of the arms. The
280, 5.5. The estimated effective dose range (min - max) was: arms are commonly positioned above the head to improve PET
(0.7 - 6.1), (0.4 - 1.1), (1.3 - 6.6), (1.3 - 8.7), (0.6 - 9.1), (1.05 - 10.3) imaging quality of the body. Considering the ALARA principle a
for PET whole body, SPECT myocardial perfusion imaging, change in positioning of the patient or scan range can be opted.
SPECT Octreotide, SPECT parathyroid, SPECT bone and SPECT References: 1 ICRP, 2012. ICRP Statement on Tissue Reactions /
thyroid post-ablation, respectively. The differences between Early and Late Effects of Radiation in Normal Tissues and Organs
these results and the published literature are believed to be - Threshold Doses for Tissue Reactions in a Radiation Protection
mainly due to differences in local practices. Conclusion: The Context. ICRP Publication 118. Ann. ICRP 41(1/2). 2 Januzis,
development of LDRLs has facilitated careful monitoring and Natalie Ann (2016). Radiation Dose to the Lens of the Eye from
could act as a trigger to investigate any reported CT dose that Computed Tomography Scans of the Head. Dissertation, Duke
exceeds the LDRL set. The on-going aim is to validate these University.
LDRLs with regular audit to provide a robust service provision
that is in-keeping with the ALARA principle. This will ensure that 605
LDRLs are not routinely exceeded, or prompt investigation if
otherwise. References: Shrimpton PC et al, BJR 2006.
M2M - Parallel Session: Innovations in Bio-
Nanotechnology

OP-261 Monday, October 14, 2019, 8:00 - 9:30 Lecture Hall 111
Estimation of radiation dose to the eye lens of patients
undergoing PET/CT scan with lowdose-CT compared to
diagnostic-CT head
E. C. Streefkerk, T. Young - Mylvaganan, J. olde Heuvel, D. Huizing, OP-262
B. de Wit - van der Veen; Ultrasound-Induced Mircobubble Cavitation For
Cancer institute, Amsterdam, NETHERLANDS. Optimisation Of Tumour Uptake Of Liposome-Based
Chemo-Radionuclide Therapy
K. A. Vallis, E. Thomas, J. Menon, J. Owen, S. Wallington, M. Gray, I.
Aim/Introduction: The eye lens is the most radiosensitive organ; Skaripa-Koukelli, R. Carlisle;
too much radiation exposure can lead to cataract formation. University of Oxford, Oxford, UNITED KINGDOM.
The International Commission on Radiological Protection (ICRP)
Publication 118 recommended a threshold for lens opacities of
0.5Gy1. Modern positron emission tomography (PET) imaging Aim/Introduction: Nanoparticles (NP) allow active targeting
includes a computed tomography (CT) scan for attenuation of cancer for diagnostic and therapeutic applications through
correction and anatomical reference. In this study we want incorporation of multiple functional components. However, the
to estimate the radiation dose to the eye lens of patients low penetration of NP into tumours sometimes hinders their
undergoing a low dose-CT compared to a standard diagnostic- efficacy. In this study, ultrasound plus microbubbles were used
CT, and between different PET/CT protocols. With these results to promote the intra-tumoural delivery of a novel liposome
we aim to optimize our acquisition protocols considering the (LP) for chemo-radionuclide therapy. The epidermal growth
ALARA principle. Materials and Methods: We retrospectively factor receptor (EGFR) is over-expressed by many types of
reviewed PET/CTs in three acquisition categories, Head/Neck cancer, making it an attractive molecular target. Materials and
(2mm), Whole-body (5mm) and PSMA (2mm) starting January Methods: Liposomes were loaded with doxorubicin (Dox) and
first 2018. These were compared to Diagnostic CT Brain (1mm) surface modified by addition of epidermal growth factor (EGF)
and Face (1mm). The PET/CT patients were scanned on the peptide conjugated to DTPA for radiolabelling with indium-111
GEMINI TF Big Bore (Philips, Netherlands). The diagnostic CTs (111In). Human breast cancer cell lines with high and low EGFR
were scanned on the Aquilion CX (Toshiba, Japan). The DICOM expression (MDA-MB-468 and MCF7 respectively) were used
information from all scans was analyzed using OSIRIX software. to study selectivity of liposomal uptake, subcellular localisation
The slice including the eye lens was used to extract the CTDIvol of drug payload, cytotoxicity (by clonogenic assay) and DNA
(mGy). A conversion factor for adults CFage was derived2. Using damage (by immunostaining for gamma-H2AX). Liposome
the following equation an estimation of the lens dose was made. extravasation following ultrasound-induced cavitation
Dlens = CFage x CTDIvol Results: A total of 60 scans were analyzed. of microbubbles (SonoVue) was studied using a tissue-
For the low dose-CT component the mean radiation dose to the mimicking phantom. In vivo stability, pharmacokinetic profile
lens was 3.4mGy (range 0.9-9.0mGy). The Head/Neck protocol and biodistribution were evaluated following intravenous
has a dose that is three times lower than the Whole-body or administration of 111In-EGF-LP to mice bearing subcutaneous
PSMA protocol. In comparison, the diagnostic-CT gave a mean MDA-MB-468 xenografts. The influence of ultrasound-mediated
dose of 43.0mGy (range 7.1-79.2mGy) to the lens. Conclusion: cavitation on the delivery of 111In-EGF-LP into tumours was
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S108

studied. Results: Liposomes were loaded efficiently with Dox, 29/ HCT116 and prostate cancer cells DU-145, expressing GRPRs.
surface decorated with 111In-EGF and showed selective uptake We investigated the specific binding of bombesin-like peptide
in MDA-MB-468 compared to MCF7 cells. Following EGF binding sequence PEG(4)-BBN(7-14) to GRP receptors by comparing
to EGFR, Dox was released in the intracellular space and 111In- the receptor interaction with radiolabeled 68Ga-DOTA-PEG(4)-
EGF shuttled to the cell nucleus. Radioactivity accumulated BBN(7-14) in the presence of an cold competitor antagonist
to a greater extent in the nuclei of MDA-MB-468 compared to ligand. Results: In vitro binding kinetics assessment showed over
MCF7 cells (16.8 +/- 0.9% vs. 2.2 +/- 0.7% of the internalized 60% radioisotope retention inside tumor cells in the presence
activity). DNA damage and cell kill were greater in MDA-MB-468 of AuNPs, higher than 68Ga-DOTA-PEG(4)-BBN(7-14) alone. This
than MCF7 cells. In addition, Dox and 111In were shown to have result is attributed to the possibility that AuNPs bind to several
an additive cytotoxic effect in MDA-MB-468 cells. Ultrasound- peptides on the cell surface and promote a higher internalization
mediated cavitation increased the extravasation of liposomes rate by receptor mediated endocytosis. Biodistribution studies
in an in vitro gel phantom model. In vivo, the application of were performed on tumor bearing nude mice, and the results
ultrasound plus microbubbles increased tumour uptake by 66% show high tumor uptake of the radiolabeled nanoconjugates.
p<0.05) despite poor vascularisation of MDA-MB-468 xenografts Conclusion: The combination of size-controlled distribution
(as shown by DCE-MRI). Conclusion: 111In-EGF-DOX-LPs are of nanoparticles, functionalization with bio-recognition
promising for targeted cellular uptake and drug delivery. In vivo, peptides and PET radioisotope labelling has resulted in highly
ultrasound plus microbubbles enhance delivery to tumour. The promising imaging probes. 68Ga-DOTA-PEG(4)-BBN(7-14) shows
extent of tumour vascularisation is likely a critical determinant very promising results regarding in vitro and in vivo behavior.
of success of this delivery strategy and will be further studied. Further investigations are to be performed to determine the
References: None. detailed dosimetry and pharmacokinetics and to extend the
potential use to targeted radionuclide therapy, by use of highly
cytotoxic potency of alpha radionuclides transported close to
OP-263 the cell nuclei. References: Livia E. Chilug et al., In vitro binding
Activated Gold Nanoparticles Conjugated with 68Ga- kinetics study of gold nanoparticles functionalized with 68Ga-
DOTA-PEG(4)-BBN(7-14) for Targeting Tumours Expressing DOTA conjugated peptides, J Radioanal Nucl Chem (2017)
GRP Receptors M. E. Panait et al., Biological Effects Induced by 68Ga-Conjugated
D. Niculae1, L. E. Chilug1,2, R. M. Serban1,3, A. J. Abrunhosa4, R. A. Peptides in Human and Rodent Tumor Cell Lines, Int J Peptide
Leonte1, R. Turcu5, A. Nan5, V. Lavric2; Res Therapeutics (2018)
1
Horia Hulubei National Institute for Physics and Nuclear
Engineering IFIN-HH, Bucharest (Magurele), ROMANIA,
2
University Politehnica of Bucharest, Faculty of Applied Chemistry OP-264
and Materials Science, Bucharest, ROMANIA, 3University of Direct radiolabeling of 89Zr-silica gadolinium nanoparticles
Bucharest, Faculty of Biology, Bucharest, ROMANIA, 4CIBIT/ICNAS (89Zr-AGuIX®) for tumor targeting via long term EPR effect
Institute for Nuclear Sciences Applied to Health, University of and in vivo clearance characterization in 9L brain tumor
Coimbra, Coimbra, PORTUGAL, 5National Institute for Isotopic model
and Molecular Technologies, Cluj-Napoca, ROMANIA. V. Tran1, B. Jego1, A. Winkeler1, A. Bouleau1, F. Lux2, O. Tillement2, B.
Kuhnast1, C. Truillet1;
1
Laboratoire Imagerie Moléculaire In Vivo (IMIV), Service
Aim/Introduction: Nanoparticles have recently emerged Hospitalier Frédéric Joliot, CEA, Inserm, Univsité Paris Sud,
as innovative tools for cancer diagnosis and therapy. Their CNRS, Université Paris-Saclay, Orsay, FRANCE, 2Institut
functionalization with biorecognition molecules (ligands), Lumière Matière, UMR 5306, Université Claude Bernard
forming targeted drug delivery systems, can make them Lyon 1, CNRS, Université de Lyon, Villeurbanne, FRANCE.
suitable for early detection of tumors, patient management and
therapy follow-up, using molecular imaging techniques. The
aim of this study was to investigate the potential as an imaging Aim/Introduction: High-Z nanoparticles (NP) are attracting
agent of activated N-Hydroxysuccinimide gold nanoparticles great attention as sensitizers for radiotherapy.1 A major challenge
functionalized with 68Ga-DOTA-PEG(4)-BBN(7-14) to target is to characterize and quantify intratumoral NP distribution
GRP (gastrine releasing peptide) receptors, overexpressed on spatially and temporally in order to optimize delivered dose in
colorectal cancer cells HT-29/HCT116 and prostate cancer cells the tumor area with minimal effect on normal tissues. Our aim
DU-145.Materials and Methods: The morphology and size is to assess the use of PET to quantitatively image ultrasmall
distribution of gold nanoparticles obtained were examined by silica gadolinium NP (AGuIX®), a promising nanosensitizer
TEM/SEM coupled with energy dispersion spectroscopy (EDS) currently under phase 2 clinical trial.2 We are interested in using
technique and, after functionalization, by UV-Vis spectroscopy 89
Zr, a long-lived positron emitter, which allows longitudinal
and DLS. The Gold NPs were functionalized with PEG(4)-BBN monitoring of tumor-specific accumulation of NP. Labeling
(7-14), previously radiolabelled with Ga-68 using DOTA as a 89
Zr on a nanostructure often requires introducing a chelator
chelating agent. The obtained radiolabeled nanoconjugate was such as DFO.3 This would probably affect its properties in vivo
incubated with neuroendocrine colorectal cancer cell line HT- and necessitates new approval application. In this study, we
S109 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

have shown that AGuIX® can be directly labeled with 89Zr. and Methods: Large amounts of MVs were generated from
Then labeled particles can be used to follow tumor uptake in primary cultures of HUVECs after TNFα stimulation. [99mTc]Tc-
a preclinical glioma model. Materials and Methods: AGuIX® AnnexinV radiolabeling (AnV-128, AAA) technically enabled
was labeled while taking advantage of free DOTA groups on to obtain radiolabeled MVs with a suitable yield for isotopic
the particle with 89Zr-oxalic acid in different conditions. Stability imaging. A purification-concentration method of these MVs
of the radiotracer has been tested in vitro with fetal bovine was then validated on specific size-exclusion columns, to
serum and mouse plasma. Transmetalation assays have been inject a purified and concentrated suspension of MVs to the
performed with different endogenous ions i.e. Fe3+, Zn2+, Ca2+, animal. Stability in serum at 37°C was assessed up to 2h after
Cu2+. Syngeneic tumor model was established by stereotactically labeling. MVs biodistribution was quantified on microSPECT/CT
implanting 9L gliosarcoma cells into the striatum of Fisher rats’ imaging data of healthy mice up to 3h after injection (n=6). MVs
brain. PET-CT images were acquired at different time points biodistribution was also quantified after i.v. injection in a mouse
after injection of labeled NP. Organs were collected for ex model of hindlimb ischemia (2-5.10^6 MVs/100µL, n=7 mice)
vivo analysis. Results: Complete labeling was achieved even while a control group (n=4 mice) was i.v. injected with 100µL
at mild condition. 89Zr- AGuIX® were stable in different in vitro PBS. Angiogenic activation and blood flow in the hindlimbs
conditions. 9L tumor growth was assessed by 18F-FDG PET and were respectively evaluated by [68Ga]Ga-RGD2 microPET/CT
histology. Expectedly, PET images post 89Zr-AGuIX injection (on days 3,4,7,10 post-ischemia) and by LASER-Doppler on
showed NP accumulation in the tumor. Long half-life of 89Zr days 1,3,7,14,21,28 days post-ischemia. Results: Labeling yield
allowed longitudinal follow-up of this accumulation, which didn’t exceed 5% but remained compatible with preclinical
lasted more than 24 h in accordance with previous studies. isotopic imaging. Radiolabeling stability as well as physical
NP accumulation was confirmed by autoradiograms of brain integrity of the MVs were confirmed up to 2h after labeling.
sections. In addition, ex vivo biodistribution indicated that Quantifications showed an accumulation of radiolabeled MVs
labeled NP were not retained in major organs and eliminated in the liver, intestines and kidneys of healthy mice. A significant
mainly via the kidneys. Conclusion: We have demonstrated that higher MVs SPECT signal was found in the ischemic hindlimb
AGuIX® can be directly labeled with 89Zr in simple conditions, compared to the contralateral 2h post-injection (*p=0.0467).
which can be readily applied for GMP manufacturing. Labeled On day 3, [68Ga]Ga-RGD2 microPET/CT quantifications showed
NP was stable and showed promising results for translational a significant higher ipsi- to contralateral signal ratio in the MVs
brain tumor imaging. References: 1. Rancoule, C. et al. Cancer group (**p=0.0082). We observed a better, earlier reperfusion
Lett. 375, 256-262 (2016).2. Lux, F. et al. Br. J. Radiol. 20180365 in the MVs group (***p<0.0001). We highlighted the intensity
(2018).3. Truillet, C. et al. Mol. Pharm. 13, 2596-2601 (2016). of the reperfusion was significantly, positively correlated with
the intensity of the number of MVs retained in the ischemic
hindlimb (r=0.9883, *p=0.0117). Conclusion: These preliminary
OP-265 data enabled to quantify endothelial MVs in vivo biodistribution,
Radiolabelling endothelial microvesicles and evaluating and for the first time the appreciation of a correlation between
their in vivo biodistribution in healthy and ischemic mice the intensity of the radiolabelled MVs SPECT signal and the
P. Garrigue1, R. Giraud1, A. Moyon1, V. Nail2, S. Simoncini3, L. therapeutic effect on revascularization. References: None.
Balasse4, S. Fernandez5, A. Bouhlel4, F. Dignat-George6, B. Guillet1, F.
Sabatier6;
1
C2VN INSERM 1263 INRA 1260 CERIMED Aix-Marseille Université OP-266
APHM, Marseille, FRANCE, 2CERIMED Aix-Marseille Université APHM, Novel radiolabeled silicon dyes for bimodal scintigraphic
Marseille, FRANCE, 3C2VN INSERM 1263 INRA 1260 Aix-Marseille and optical imaging
Université, Marseille, FRANCE, 4C2VN INSERM 1263 INRA 1260 T. Kanagasundaram1,2, M. Schäfer1, C. Kramer1, E. Boros3, K.
CERIMED Aix-Marseille Université, Marseille, FRANCE, 5CERIMED Kopka1;
Aix-Marseille Université, Marseille, FRANCE, 6C2VN INSERM 1263 1
German Cancer Research Center (DKFZ), Division of
INRA 1260 Aix-Marseille Université APHM, Marseille, FRANCE. Radiopharmaceutical Chemistry, Im Neuenheimer Feld 280,
Heidelberg, GERMANY, 2Institute of Inorganic Chemistry,
Heidelberg University, Im Neuenheimer Feld 270, Heidelberg,
Aim/Introduction: Microvesicles (MVs) are of great interest as GERMANY, 3Stony Brook University, Department of
biological markers in cardiovascular and oncologic diseases, Chemistry, New York, NY, UNITED STATES OF AMERICA.
but they are also currently evaluated as biotherapeutic agents.
However, although their characterization and their purification/
isolation method are now well established, to date there is Aim/Introduction: Radiolabeled fluorescent dyes are crucial
no published data about their systemic biodistribution after for bimodal imaging and currently in demand for scintigraphic
intravenous administration. The aims of this work were to and optical imaging. These dyes show unique optical properties
develop the radiolabeling of endothelial MVs to characterize such as high quantum yields and extinction coefficients (1).
their in vivo biodistribution in healthy mice by isotopic imaging, Organic fluorophores are well-known for fluorescent light-
and to evaluate their biodistribution in a mouse model of guided intraoperative surgery. The goal of this work was
ischemia and their impact on revascularization. Materials developing near-infrared (NIR) light-emitting Si-rhodamines
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S110

for scintigraphic and optical imaging. We have synthesized Aim/Introduction: Homogeneous Sn-117m colloid (HTC)
these first-in-class dyes for their subsequent conjugation to the is commercialized in the US as a treatment for osteoarthritis
SPECT-compatible radiometal technetium-99m with the aim (OA) in dogs using radiosynoviorthesis (RSO). Human clinical
to elucidate their potential as sentinel lymph node detecting trials using ascorbic homogeneous Sn-117m colloid (AHTC)
agents. Moreover, PET-compatible Si-rhodamine conjugation will commence in Canada in 2019. The outcome of safety and
to exemplary prominent tumor targeting binding vectors efficacy of repeat therapeutic RSO injections in canines may
such as the PSMA-binding motif has also been performed. be applicable to human subjects. Materials and Methods: 10
The introduced dyes are intended to be used for noninvasive dogs previously enrolled in a prospective trial to treat elbow
SPECT or PET imaging (prestaging) followed by light-guided R0- OA with one of three doses of HTC intra-articular injection
tumor-resection. Materials and Methods: The combination of were enrolled in a re-injection trial if their symptoms remained
scintigraphic and optical imaging leads to new approaches in unchanged or worsened by canine brief pain inventory (cBPI)
tumor imaging and resection. This powerful strategy enables the or force-plate analysis after 6-12 months. These dogs received
differentiation of healthy and affected tumor tissues. We have an additional RSO procedure with the commercial dose (1.7
developed dyes with absorption and emission properties in the mCi per elbow normalized for a 50 lb/22.7kg dog) in both
near-infrared region of ca. 660 nm. The synthesized dyes are elbows (n=20) and were followed for 12 months for safety and
belonging to the silicon (Si)-rhodamine family. We utilized the efficacy. Therapeutic success by cBPI was defined as either (1)
dyes for copper(I)-catalyzed alkyne-azide [3+2]-cycloaddition improvement of >1 for pain severity score (PSS) AND >2 for pain
with alkyne-functionalized biomolecules to receive respective interference score (PIS), or (2) improvement of >1 for PSS OR >2
1,2,3-triazoles for complexing the prominent SPECT-radiometal for PIS. Therapeutic success by clinician’s lameness examination
technetium-99m. Furthermore we have designed another was defined as significantly improved p values between the two
DOTA-functionalized 1,2,3-triazole for complexing the PET- assessment time points. Therapeutic success by force plate was
radiometal gallium-68. Finally, the dyes were characterized demonstrated by improvement of >5% at any time point in the
using NMR-, UV/VIS/NIR-spectroscopy and mass spectrometry. peak vertical force (PF) or the mean vertical impulse (IMP). Safety
Results: The conventional synthesis of novel Si-rhodamines was assessed by analysis of CBC and blood chemistry, joint
through xanthone building blocks provided novel amino- and fluid, UA, and by owner and clinician assessment. Results: The
azide-functionalized Si-rhodamines with overall yields of 60%. per protocol group of 9 dogs (18 elbows) showed therapeutic
The azide-functionalized Si-rhodamines were converted with improvement in three assessments. cBPI success using PSS AND
PSMA-inhibitor functionalized alkynes adapted from the PSMA- PIS demonstrated improvement over baseline of up to 37.5%
617 binding motif and L-propargylglycine to the corresponding during 12 months. cBPI success using PSS OR PIS demonstrated
1,2,3-triazoles (2). Already determined extinction coefficients improvement over baseline of up to 75.0% during 12 months.
up to 120.000 M-1cm-1 and quantum yields of 0.45 show Force plate evaluation demonstrated improvement in PF or IMP
promising results, making them potentially useful for optical in up to 66.7% of subjects over 180 days. Clinician’s lameness
imaging. Furthermore the dyes were prepared as precursors examination showed no statistical improvement. There were
for technetium-99m and gallium-68-labeling. For that purpose no safety issues noted associated with HTC. Conclusion: The
different chelators (e.g. DOTA) were used. Corresponding therapeutic success and demonstrated safety of reinjection
rhenium-Si-rhodamines [used as “cold” technetium-surrogate] using HTC for OA in dogs provides support for similar use in
were characterized as well. Conclusion: A variety of novel humans. References: None.
NIR fluorescent dyes based on the Si-rhodamine lead
structure were synthesized and chemically characterized. We
successfully developed non-radioactive analogues of putative OP-268
NIR dyes for bimodal scintigraphic and optical imaging and 68
Ga-labeled carbon nanoparticles for ventilation PET/
their radiolabeling precursors. Furthermore, our first-in-class CTimaging: physical properties study and comparison
radiolabeled silicon dyes are subject of current and future with Technegas®
biological evaluation. References: (1) T. Nagano et al., J. Am. F. Blanc-Béguin1, P. Eliès2, N. Kervarec3, P. Robin1, R. Tripier2, C.
Chem. Soc. 2012, 134, 5029-5031. (2) K. Kopka et al., J. Nucl. Med. Lemarié1, S. Hennebicq1, C. Tromeur1, P. Salaün1, P. Le Roux1;
2015, 56, 914-920. 1
Brest university hospital, Brest, FRANCE, 2Brest occidental university,
Brest, FRANCE, 3Brest occidental university, Brest, FRANCE.

OP-267
A Reinjection Study of Sn-117m Colloid to Treat Canine Aim/Introduction: For lung imaging, ventilation PET/CT is now
Osteoarthritis Shows Safety and Efficacy possible with 68Ga-labeled carbon nanoparticles. Radiolabeling
C. A. Doerr1, J. M. Donecker1, N. R. Stevenson1, G. R. Gonzales1, J. C. can be performed using the same synthesis device as Technegas®
Lattimer2; (Cyclopharm Ltd, Australia), by substituting 99mTc with 68Ga.
1
Serene, LLC, The Woodlands, TX, UNITED STATES OF AMERICA, Several studies showed promising results of ventilation PET
2
University of Missouri, Columbia, MO, UNITED STATES OF AMERICA. images for regional lung function assessment. However, no
study has assessed the physical properties of 68Ga-labeled
carbon nanoparticles. The aim of this study was to assess the
S111 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

size, shape, mass and particles composition of 68Ga-labeled nuclides experience a recoil energy of about 100-200 keV which
carbon nanoparticles, as compared with 99mTc-labeled carbon is much larger than the energy of any chemical bond, resulting
nanoparticles. Materials and Methods: 68Ga and 99mTclabeled in the daughter nuclide breaking free from any targeting agent.
carbon nanoparticles were produced using an unmodified These daughter can accumulate in healthy tissue as kidneys,
Technegas generator, following the usual technique proposed resulting in toxicity. Here, we evaluate the retention of the 225Ac
for Technegas production. Approximately 50 MBq of 68GaCl3 recoiling daughter 213Bi entrapped in poly-butadiene-poly-
and 700 MBq of 99mTcO4- Na+ were introduced in the carbon ethylene oxide (PBD-PEO) polymersomes in vivo, both upon
crucible, respectively. Nanoparticles were collected using an intravenous as well as intratumoral administration. Furthermore,
aerosol collector PA 2000 (Algade®) on a cellulose filter and on the suitability of 225Ac-containing polymersomes as therapeutic
a Transmission Electron Microscopy (TEM) grids coated with agents is assessed upon intratumoral injection. Materials and
a carbon film. The size and shape of particles were studied Methods: Polymersomes (100 nm) were labeled with 225Ac
by TEM (JEOL JEM 1400). The mass of carbon particles was through DTPA chelation or through co-precipitation within
studied by Time-Of-Flight Mass Spectroscopy (TOF-MS) InPO4 nanoparticles were injected intravenously in healthy
(spectrometer Bruker Autoflex III SmartBeam) from a solution mice, and intratumorally in MDA-MB-231 tumor-bearing BALB/c
obtained by infusing the cellulose filters in methanol. The nude mice, and the retention of the 213Bi daughter nuclide was
particles composition was assessed using scanning electron determined. Concentration of 213Bi in the blood, spleen, kidneys
microscopy (SEM) (HITACHI S-3200N) coupled with EDX and tumor was compared to that of 225Ac. The tumor retention
analysis. Results: On TEM, the mean diameter of 68Ga and and therapeutic effect of 225Ac-containing polymersomes upon
99m
Tc-labeled carbon nanoparticles was 22.6±17.3 nm and intratumoral injection was compared to 225Ac-DOTA, PBS or no
66.8±50.2 nm (p<0.05), respectively. The diameter of both treatment in MDA-MB-231 tumor-bearing BALB/c nude mice.
particles was consistent with previously published data for Results: 225Ac recoil daughter retention in InPO4 nanoparticles in
99m
Tc-labeled carbon nanoparticles, ranging from 5 to 400 nm polymersomes showed a significant (p<0.05) two-fold increased
(Lloyd et al. PMID: 7641756; Lemb et al. PMID: 8053994). Both retained fraction of 213Bi in the blood compared to 225Ac in
99m
Tc and 68Ga labeled carbon nanoparticles had similar shape DTPA-polymersomes (0.14 ± 0.07 vs. 0.06 ± 0.03) in healthy
with primary hexagonally structured particles. Mass spectra of mice. When injected intratumorally, polymersomes showed
68
Ga and 99mTc- labeled carbon nanoparticles showed the same good retention in tumor tissue (244 ± 74 %ID/g and 289 ± 130
326 and 327 daltons peaks, suggesting the presence of similar %ID/g at 1 and 7 days p.i, respectively), whereas 225Ac-DOTA was
particles in both aerosols. EDX spectra demonstrated higher rapidly cleared from the tumor (10 %ID/g and 5 %ID/g at 1 and
percentage of Sodium and Chlorine atoms in 99mTc labeled 7 days p.i, respectively). The two treatment groups showed a
carbon nanoparticles, consistent with the composition of 99mTc remarkable therapeutic efficacy (complete inhibition of tumor
eluate. However, the composition in Carbon and Oxygen of growth in 7/8 and 6/8 for 225Ac polymersome- and 225Ac-DOTA
both particles was similar. Conclusion: Using a Technegas treated tumors, respectively) with no tumor-related deaths
generator in the usual clinical way, 68Ga and 99mTc-labeled over the treatment period, while the survival of the PBS control
carbon nanoparticles demonstrated similar shape, mass and group was significantly (p<0.05) decreased over the course of
particles composition. 68Ga-labeled carbon nanoparticles were the experiment. Out of the PBS injected tumors and non-treated
significantly smaller than 99mTc labeled particles, but remained in tumors only 1/8 and 2/8 of the tumors showed inhibition of
the range of previously published data for 99mTc-labeled carbon growth, respectively. Conclusion: The observed polymersome
nanoparticles. This data support the use of 68Ga-labeled carbon retention in tumor tissue and tumor growth inhibition of
nanoparticles for the assessment of ventilation regional lung xenografts treated with 225Ac-labeled polymersomes indicate
function with PET imaging. References: None. that targeted alpha therapy with polymersomes has potential
for long-term irradiation of tumors upon intratumoral injection.
References: None.
OP-269
Recoil retention and therapeutic efficacy of 225Ac- 606
containing polymersomes
R. Raavé1, R. M. de Kruijff2, A. Kip1, J. Molkenboer-Kuenen1, A.
Do.MoRe - Parallel Session: Preclinical
Morgenstern3, F. Bruchertseifer3, S. Heskamp1, A. G. Denkova2;
Dosimetry - What is the Future?
1
Radboudumc, Nijmegen, NETHERLANDS, 2Delft
University of Technology, Delft, NETHERLANDS, 3European Monday, October 14, 2019, 8:00 - 9:30 Lecture Hall 112
Commission, Joint Research Centre, Directorate for
Nuclear Safety and Security, Karlsruhe, GERMANY.
OP-270
NM600, a theranostic alkylphosphocholine chelate, shows
Aim/Introduction: Alpha emitters can play an important role in promise as a universal tumor-targeting agent
cancer treatment. With their high linear energy transfer and short J. Grudzinski, R. Hernandez, I. R. Marsh, R. B. Patel, E. Aluicio-
range, alpha particles are ideal for localized cell killing. However, Sarduy, J. Engle, Z. Morris, B. Bednarz, J. Weichert;
upon emission of an alpha particle, the radioactive daughter University of Wisconsin, Madison, WI, UNITED STATES OF AMERICA.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S112

Aim/Introduction: We characterized the in vivo biodistribution Aim/Introduction: Actinium-225 has lately become a popular
and tumor selectivity of 86Y-NM600, a theranostic α-particle emitter and has been used both pre-clinically and
alkylphosphocholine radiometal chelate with broad tumor clinically against several types of cancers. Actinium-225 (T1/2=10
selectivity, in a variety of syngeneic and xenograft preclinical days) have in its decay chain a total net emission of four
cancer models (n=15) and estimated the tumor and normal α-particles and two β-particles. Actinium-225 is labeled to the
organ dosimetry of 90Y-NM600 in these models. We have targeting vector using a chelator. The chemical bond between
shown previously that precise tumor dosimetry of 90Y-NM600 is the chelator and the 225Ac-atom is weak (~10eV), and after the
important when combined with immunotherapies. Materials first α-particle is emitted the bond is broken due to the high
and Methods: Mice bearing heterotopic or orthotopic recoil energy (~100keV) of the atom. Consequently the 225Ac
tumors (breast, lymphoid, sarcoma, melanoma, oral, prostate, decay daughters (221Fr, 217At, 213Bi, 213Po, 209Tl and 209Pb) are no
pancreatic, lung and colon) were injected intravenously (IV) longer bound to the vector and are free to relocate within
with 9.25-9.75 MBq of 86Y-NM600 and imaged longitudinally the in vivo system. The α-particle emitting decay daughters
out to 72 hours using microPET/CT. Percent injected activity with the longest half-life are 221Fr (T1/2=4.9 minutes) and 213Bi
per gram (%IA/g) for each volume-of-interest (VOI) was (T1/2=45.6 minutes). These are decay daughters in the 225Ac
measured at each time point for the organs of interest. Mice decay chain that emit a gamma ray that can be either measured
were euthanized after the final time point and the tumor and or imaged. In this study we investigated the pharmacokinetics
organs of interest were counted with an automatic gamma in murine models of different 225Ac-labeled vectors (7.16.4
counter. Absorbed doses delivered by 90Y-NM600 per injected antibody against breast cancer; PSMA small molecule against
activity (Gy/MBq) were estimated using an inhouse Monte Carlo prostate cancer) and the in vivo generated unbound decay
platform. Mice bearing B78 flank tumors were injected with a daughters 221Fr and 213Bi. Materials and Methods: The mice
prescription of 90Y-NM600 that delivered 2.5 Gy of absorbed were injected i.v. with 225Ac-labeled vectors and sacrificed at
tumor dose and was compared to an equivalent absorbed dose specific time-points p.i. The organs/tissues were directly after
delivered via external beam radiotherapy (XRT) using tumor sacrifice harvested and measured in a gamma counter in 1
volume as a measure of response. Histology and complete minute intervals for a duration up to 5 hours. Bi-exponential
blood counts (CBC) were analyzed in naïve C57BL/6 mice who functions were fitted to the measured activity to determine
were injected with 9.25 MBq of 90Y-NM600 at 5, 10, and 28 days the amount of vector labeled 225Ac and unbound 221Fr and 213Bi
post injection (p.i.). Results: PET imaging showed consistent within the organs/tissues. Results: All murine models showed
tumor accumulation and retention across all tumor models accumulation of unbound 213Bi in the kidneys, accounting for
investigated with little off-target retention of NM600 except for ~60% of the absorbed dose. The main supplier of 213Bi to the
in the liver, which is characteristic of hepatobiliary metabolism. kidneys was the liver for the small molecule and the blood for
The tumor uptake was highest in the TC11 breast, MOC2 oral, the antibody. In addition, within the kidneys the vector labeled
and 4T07 breast cancer models, reaching peak concentrations 225
Ac was uniformly distributed for the antibody, and non-
of 11.68 ± 0.52%IA/g (n=2), 9.76 ± 1.02 %IA/g (n=3), and uniform for the small molecule and unbound 213Bi, suggesting
9.28 ± 0.55 %IA/g (n=3) respectively, at approximately 24-48 need for small scale dosimetry for more accurate calculations.
hr post injection. These corresponded to tumor dose estimates Conclusion: This study demonstrate that different targeting
of 3.97 ± 0.04 Gy/MBq, 3.13 ± 0.37 Gy/MBq, and 2.98 ± vectors for delivery of 225Ac alters the pharmacokinetics and
0.18 Gy/MBq, respectively. In the toxicity study, there were no suppliers of the unbound decay daughters. These properties are
visible signs of acute toxicity by histology, and perturbation important for translation to clinical studies as in vivo imaging
of hematological parameters was transient when observed, cannot distinguish between the vector labeled 225Ac and the
returning to pre-therapy levels after 28 days. Conclusion: unbound decay daughters 221Fr and 213Bi. This results in an
NM600 is a theranostic agent with a unique ability to selectively overestimation of the absorbed dose to the kidneys and an
target and safely deliver precise radiation to a variety of cancer underestimation of the absorbed dose to the supplying organ/
types, presenting a unique opportunity for PET image guided tissues. References: None.
TRT and combination with immunotherapies. References:
None.
OP-272
Organic melanin nanoparticles targeting prostate-specific
OP-271 membrane antigen (PSMA) and multimodality imaging for
Pharmacokinetic variability of vector labeled human prostatic cancer xenograft model
Actinium-225 and the in vivo generated decay daughters L. Xia1, Z. Cheng2, H. Zhu1, Z. Yang1;
Francium-221 and Bismuth-213 in murine models 1
Peking university cancer hospital, Beijing, CHINA, 2Stanford
A. Josefsson, J. R. Nedrow, S. R. Banerjee, M. G. Pomper, G. Sgouros, University, San Francisco, CA, UNITED STATES OF AMERICA.
R. F. Hobbs;
Johns Hopkins University School of Medicine,
Baltimore, MD, UNITED STATES OF AMERICA. Aim/Introduction: Prostate-specific membrane antigen is
widely used for the diagnosis and therapy of prostatic cancer. The
introduction of the nuclide-labelled PSMA targeted positron-
S113 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

emitting-tomography/computed-tomography (PET/CT) tracer more than 80 preclinical cancer models and has potentially
has proven highly sensitive for the detection of prostate cancer. broad applicability in pediatric oncology. The goal of this study
But radionuclide imaging still has the disadvantages of low was to compare subject-specific dosimetry for theranostic
resolution and difficult to detect microlymph node metastases. 131
I-NM404 and 131I-MIBG MTRT using PET/CT imaging of 124I-
Multimodal imaging has been an important research direction NM404 and 124I-MIBG in a murine xenograft model of MIBG-avid
and uses a versatile, integrated contrast agent to provide neuroblastoma. Materials and Methods: NSG mice bearing a
complementary imaging information for disease diagnosis and NB1691-hNET neuroblastoma flank tumor were administered
treatment evaluation. Nanoparticles are the most widely used with 9.2 MBq of 124I-NM404 or 9.7 MBq of 124I-MIBG via lateral tail
contrast agents or carriers for multimodal imaging due to their vein injection (n=4 each). Sequential microPET/CT scans were
excellent properties. Herein, we used safer organic melanin acquired at 1, 24, 48, 72, 96, and 120 h post-injection for 124I-
nanoparticles as a carrier and surface-loaded PSMA-11 to NM404 and at 1, 4, 24, 48, and 72 h post-injection for 124I-MIBG,
construct a prostatic cancer targeted nanoprobe (PSMA-PEG- to account for the relatively faster biological clearance. CT-
MNP). Materials and Methods: Organic melanin nanoparticles based contours of the flank tumor and contralateral muscle
are prepared from naturally produced biopolymers. The were overlaid on the PET volumes and in vivo pharmacokinetics
biocompatible PEG was modified on the surface and the PSMA- were reported in %ID/g. Using the PET image volumes and a
11 was bound by condensation reaction. MNPs have excellent Geant4 Monte Carlo based dosimetry platform, the integral
photoacoustic imaging (PAI) functions and can directly label prescription dose (Gy/MBq) delivered by 131I-NM404 and
metal nuclide 64Cu and magnetic resonance contrast agent Fe3+ 131
I-MIBG was estimated. The tumor-to-muscle ratio (TMR) of
without a coupling agent. Therefore, MNPs can be used not only integral prescription dose was used to compare the tumor-
for photoacoustic imaging, but also for PET and MRI. The LNCaP selectivity of the agents. Results: In vivo pharmacokinetic
prostatic tumor xenograft model with high PSMA expression analysis showed tumor-selective uptake of both 124I-NM404 (2.9
was constructed to evaluate the multimodal imaging ability %ID/g at 44 h) and 124I-MIBG (2.3 %ID/g at 4h). Subject-specific
of (64Cu, Fe3+) PSMA-PEG-MNP. Results: (64Cu, Fe3+) PSMA- tumor dosimetry predicted an integral prescription dose of 0.07
PEG-MNP showed good imaging abilities in PAI, MRI and PET Gy/MBq for 131I-MIBG which was significantly lower than the 0.64
imaging. The PA images showed that the photoacoustic signal Gy/MBq predicted for 131I-NM404. This discrepancy arose from
in the LNCaP tumor site gradually increased with time, and the the fundamental differences in uptake and biological clearance
LNCaP xenograft showed a clear increase in the T1-weighted such that MIBG was entirely excreted by 48 h whereas NM404
signal intensity after injection with Fe-PSMA-PEG-MNP at 24 exhibited prolonged uptake and retention beyond 120 h. The
h compared to that in the prescan. Micro-PET imaging and TMR of each MTRT agent’s prescription integral dose provides a
biodistribution showed that the uptake of LNCaP tumor (7.03 ± more apt comparison with 1.8 ± 0.6 for 131I-MIBG and 2.3 ± 1.0
0.45% ID/g) was significantly higher than that in the control PC-3 for 131I-NM404. Conclusion: Our results show that 124I-NM404
models (2.25 ± 0.41% ID/g) after injection with (64Cu, Fe3+) PSMA- and 124I-MIBG exhibit similar levels of tumor-specificity towards
PEG-MNP at 24 h. Conclusion: The (64Cu, Fe3+) PSMA-PEG-MNP neuroblastoma in an MIBG-avid murine model. This suggests
was successfully applied to multimodal imaging in prostatic that 131I-NM404 MTRT could potentially achieve therapeutic
cancer model with high PSMA expression. This nanoparticle may efficacy comparable to what has been established for 131I-MIBG.
be considered for clinical trials since it combines the numerous References: None.
advantages of organic nanoparticles. References: None.

OP-274
OP-273 Demonstration of significantly heterogeneous
Direct Comparison of Theranostic [124/131I]-NM404 and intratumoural [177Lu]Lu-PSMA-617 dose deposition in a
[124/131I]-MIBG Dosimetry in a Murine Xenograft Model of preclinical model of prostate cancer using ex vivo digital
Neuroblastoma autoradiography
I. R. Marsh, J. J. Grudzinski, R. Hernandez, J. P. Weichert, M. Otto, B. J. R. Crawford1, H. Kuo1, C. F. Uribe1, C. Zhang1, J. Rousseau1, Z.
P. Bednarz; Zhang1, K. Lin1, F. Benard1,2;
University of Wisconsin-Madison, Madison, 1
BC Cancer, Vancouver, BC, CANADA, 2University of
WI, UNITED STATES OF AMERICA. British Columbia, Vancouver, BC, CANADA.

Aim/Introduction: Neuroblastoma is the most common Aim/Introduction: For emerging targeted 177Lu therapies,
extracranial solid tumor in children. For patients with metastatic understanding the relationship between absorbed dose and
disease, 131I-meta-iodobenzylguanidine (131I-MIBG) molecularly therapeutic outcome provides a basis to optimize delivery
targeted radiotherapy (MTRT) is a standard treatment. However, parameters for maximum efficacy. Tumours are inherently
10% of neuroblastoma tumors are not MIBG-avid and patients heterogeneous with a complex microenvironment, which
are left with limited treatment options. 18-(p-iodophenyl) can lead to heterogeneity in deposited radiation dose.
octadecyl phosphocholine (NM404) is a radioiodinated The relationship between calculated dose and efficacy
alkylphospholipid ether analog with confirmed uptake in may be inaccurately described if non-uniform radiotracer
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S114

distributions are not considered in the model. We developed Imaging and Theranostics, National Institute for Quantum
a method for determining volumetric intratumoural activity and Radiological Sciences and Technology (QST), Chiba,
and corresponding dose rate distributions using an ex vivo JAPAN, 4Department of Radiology and Nuclear Medicine,
digital autoradiography system (BetaIMAGER DFine, Biospace Fukushima Medical University, Fukushima, JAPAN.
Lab) dedicated to beta-particle detection. Preclinical 177Lu
distributions were imaged in vivo with µSPECT (U-SPECT+/CT,
MILabs) and ex vivo by autoradiography. Dose rate distributions Aim/Introduction: The meta-[211At]astatobenzylguanidine
were interpreted using corresponding histological sections. (211At-MABG) has possibility for treatment of malignant
Materials and Methods: NRG mice bearing subcutaneous pheochromocytoma. In case of clinical application, 211At-
LNCap tumours were administered 37 MBq of [177Lu]Lu- MABG requires dosimetry. 211At-MABG needs a companion
PSMA-617 via tail-vein injection one day before µSPECT diagnostic imaging agent for dosimetry such as meta-[123I]
imaging. Tumours were then harvested and frozen with dry ice. iodobenzylguanidine (123I-MIBG). In this regard, the purpose
Tumour sections 16 µm in thickness were collected at intervals of the study was to evaluate the similarities and differences of
of 160 µm throughout each tumour and imaged using the dosimetry between 123I-MIBG and 211At-MABG in normal mice.
BetaIMAGER DFine. Three-dimensional activity distributions Materials and Methods: In this biodistribution study, male
were constructed in Matlab from high resolution planar normal mice (BALB/cCrSlc, 9 weeks old) received intravenously
images of the complete set of serial sections. Each image was either 997kBq of 123I-MIBG or 483kBq of 211At-MABG. The
aligned using intensity-based image registration followed by radioactivity levels (%ID/g) in the tissues were determined at 1
interpolation between adjacent sections to estimate activity min, 30 min, 1 h, 3 h, 6 h, 12 h and 24 h after injection (n = 5
distributions at 0.08x0.08x0.08 mm3 voxel size. Corresponding in each group) using a gamma counter. The absorbed radiation
dose rate distributions were calculated by convolving each dose for each compound was calculated by OLINDA EXM ver.
activity distribution with a dose kernel calculated with GATE 8.1 2.0. Results: 211At-MABG and 123I-MIBG showed very similar
simulating a 177Lu point-source in water. Results: Serial beta- biodistribution profiles in normal mice at every time point.
dedicated autoradiography with 3D analysis demonstrated Both drugs showed higher uptake in heart and adrenal glands.
significant intratumoural heterogeneity for [177Lu]Lu-PSMA-617 Specifically, at 6h, 123I-MIBG and 211At-MABG accumulation
dose rate distributions. The observed intratumoural distribution were similar in heart and adrenal gland, respectively. 123I-MIBG
was significantly more complex than a simple relationship showed lower uptake in lung and liver compared to 211At-MABG.
between a central void with radiotracer accumulation at the In contrast, 123I-MIBG showed higher uptake in thyroid than did
periphery. Histological sections (HE stain) confirmed a tight 211
At-MABG, suggesting that dehalogenation may occur more
spatial correlation between connective or necrotic tissue and easily in 123I-MIBG than in 211At-MABG. The absorbed dose of
voids in the activity distributions. Even after convolving with a 211
At-MABG showed a value close to 211At-MIBG (211At-MIBG
dose kernel, very significant intratumoral dose heterogeneity means estimated the extrapolated radiation dosimetry for
persisted, with higher dose delivered to clusters of tumour cells 211
At-MABG using 123I-MIBG-biodistribution.) because of similar
compared to necrotic areas or connective tissue. Conclusion: biodistribution in normal mice. However, the absorbed dose
These results confirm that intratumoural heterogeneity in of 211At-MABG was higher in the stomach wall (1.60 vs 0.98 Gy/
delivered radiation dose can be very significant in human MBq), lung (1.23 vs 0.78 Gy/MBq) and bladder (1.63 vs 1.04 Gy/
prostate cancer models following [177Lu]Lu-PSMA-617 MBq) than dose of 211At-MIBG. Moreover, the absorbed doses of
administration, even taking into account the path length 211
At-MIBG to thyroid gland was markedly higher (4.60 vs 1.79
of beta-particle emissions. This may significantly affect the Gy/MBq) than dose of 211At-MABG. Conclusion: At each time
accuracy of image-based dosimetry estimates performed using point, the trends for biodistribution of 211At-MABG and 123I-MIBG
low resolution imaging methods. Further research is needed were almost similar in normal mice. A certain level of difference
on how to best model this effect and establish an accurate was observed in heart and adrenal gland, in which have
dose-response relationship to take into account intratumoural higher density of noradrenalin transporter compared to other
heterogeneity. References: None. organs. Therefore, 123I-MIBG may be used for dosimetry and
imaging for treatment decisions for 211At-MABG radiotherapy
as a companion drug. However, it should be noted that thyroid
OP-275 grand of the absorbed dose of 211At-MABG has lower than the
Similarities and differences of dosimetry between meta- absorbed dose of 211At-MIBG. 123I-MIBG biodistribution data
[211At]astatobenzylguanidine (211At-MABG) and meta-[123I] needs certain adjustments to compensate for possible under-
iodobenzylguanidine (123I-MIBG) as companion diagnostic or over-estimation of 211At-MABG absorbed dose. References:
drug None.
N. Ukon1, S. Zhao1, K. Yoshinaga2, K. Washino2, M. Aoki1, K.
Nishijima1, S. Shimoyama1, C. Tan1, K. Washiyama1, N. Oriuchi1, K.
Takahashi1, T. Higashi3, H. Ito1,4;
1
Advanced Clinical Research Center, Fukushima Medical
University, Fukushima, JAPAN, 2National Institute of
Radiological Science, Chiba, JAPAN, 3Department of Molecular
S115 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

OP-276 607
Radiation doses from terbium-161 compared to
lutetium-177 in single tumor cells and micrometastases
Pitfalls & Artefacts 3 - Interactive Clinical Cases
E. Hindie1, M. E. Alcocer-Avila2, C. Morgat1, C. Champion2;
- Cardiovascular + Inflammation & Infection
1
Bordeaux University Hospital, Bordeaux, FRANCE, 2Centre Lasers
Committee: Tips and Tricks in the Interpretation
Intenses et Applications, Bordeaux University, Talence, FRANCE.
of Cardiac PET

Monday, October 14, 2019, 8:00 - 9:30 Lecture Hall 113


Aim/Introduction: Targeted radionuclide therapy is a very
promising modality for treating minimal residual disease,
occult micrometastases and single tumor cells. However, OP-277
the radionuclide needs to be appropriately selected. Indeed, Quantification of MBF
radiation doses delivered with traditional beta emitters decrease M. Lubberink;
as the size of tumors decreases (Hindié et al, 2016). Terbium-161 PET Centre, Uppsala University Hospital, Uppsala, SWEDEN.
is a medium-energy beta radionuclide like lutetium-177 and
with similar chemistry (Müller et al, 2018). However, terbium-161
abundantly emits conversion and Auger electrons which can OP-278
increase the dose to micrometastases. Materials and Methods: Viability
We used the Monte Carlo code CELLDOSE to compare the A. Saraste;
effectiveness of lutetium-177 and terbium-161 at irradiating University of Turku, Heart and PET Centre
single cells (14µm cell diameter with 10µm nucleus diameter) or Hospital/Institute, Turku, FINLAND.
small tumor clusters consisting in a central cell surrounded by 18
neighbouring cells. We here studied the dose to the nucleus of the
single cell according to various distributions of the radionuclides: OP-279
either at cell membrane, cytoplasmic, homogeneous in the Endocarditis
cell, or only intranuclear. For the tumor cluster we studied the F. Rouzet;
dose to the nucleus of the central cell considering the various Bichat Hospital, Paris, FRANCE.
distributions of the radionuclides. For both radionuclides, the
simulations were run assuming that 1 MeV was released per
μm3 (1436 MeV/cell). Results: For the single cell, the dose to the OP-280
nucleus was substantially higher with terbium-161 compared Sarcoidosis
to lutetium-177, whatever the radionuclide distribution: 5.0 Gy L. Leccisotti;
vs 1.9 Gy in case of cell membrane distribution; 8.3 Gy vs 3.0 Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, ITALY.
Gy for intracytoplasmic distribution; 19.5 Gy vs 5.8 Gy in case
of homogeneous distribution; and 38.6 Gy vs 10.7 Gy in case
of intranuclear location. The dose to the central cell increased 608
with the addition of the 18 neighbors, but remained higher for
terbium-161 compared to lutetium-177. For example, in the
Clinical Oncology - Parallel Session: Breast and
case of cell membrane distribution, the dose to the nucleus of
Gynaecological Cancers
the central cell was 15.1 Gy with terbium-161 and 7.2 Gy with
lutetium-177. Conclusion: Terbium-161 should be a better Monday, October 14, 2019, 8:00 - 9:30 Lecture Hall 114
candidate than lutetium-177 for irradiating single tumor cells
and micrometastases, whatever the radionuclide distribution
is. References: Hindié E, Zanotti-Fregonara P, Quinto MA, OP-281
Morgat C, Champion C. Dose Deposits from 90Y, 177Lu, 111In, 18
F-FDG PET/CT in Locally Advanced Cervical Cancer:
and 161Tb in Micrometastases of Various Sizes: Implications prognostic value of pre- and post-treatment examination
for Radiopharmaceutical Therapy. J Nucl Med. 2016; 57: 759- and the role of metabolic PET features in this setting
64. Müller C, Domnanich KA, Umbricht CA, van der Meulen G. M. Lima1, G. Dondi2, L. Muraglia3, A. Matti3, N. Naselli4, A. G.
NP. Scandium and terbium radionuclides for radiotheranostics: Morganti5, A. M. Perrone2, P. De Iaco2, M. Tredici1, P. Castellucci3, C.
current state of development towards clinical application. Br J Nanni3, M. Farsad1, S. Fanti3;
Radiol. 2018; 91: 20180074. 1
Nuclear Medicine Department, Bolzano Hospital, Bolzano, ITALY,
2
Department of Gynecology, S.Orsola-Malpighi Hospital, University
of Bologna, Bologna, ITALY, 3Nuclear Medicine Department,
S.Orsola-Malpighi Hospital, University of Bologna, Bologna, ITALY,
4
Radiology Department, S.Orsola-Malpighi Hospital, University
of Bologna, Bologna, ITALY, 5Radiation Oncology Department,
S.Orsola-Malpighi Hospital, University of Bologna, Bologna, ITALY.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S116

Aim/Introduction: Primary aim was to evaluate the prognostic were measured. And age, histology, FIGO stage, tumor grade
value of 18F-FDG PET/CT in locally advanced cervical cancer, by were recorded. We performed analysis of PET parameters for
investigating the association between both baseline and post- predicting the omental metastasis. Results: The patients with
treatment PET features and the Overall Survival (OS). Secondary omental metastasis showed higher VAT SUVmax(0.79 ± 0.14 vs.
aim was to investigate whether metabolic baseline PET and 0.69 ± 0.16, p=0.006) and tumor SUVmax(7.53 ± 2.53 vs. 5.99
clinical parameters may play a role as predictors of treatment ±3.87, p=0.042) than the patients without omental metastasis.
response. Materials and Methods: one hundred and seventeen In addition, VAT SUVmax was significantly associated with
patients were retrospectively enrolled. Each patient underwent distant metastasis. An optimal cut-off VAT SUVmax of 0.725 was
a 18F-FDG PET/CT both at baseline and after chemoradiation. proposed for predicting omental metastasis with a sensitivity
Post-treatment PET/CT were classified according to EORTC of 70.6% and specificity of 53.6% (area under the curve: 0.66;
criteria and then grouped as complete metabolic responders p=0.012) Conclusion: VAT SUVmax is significantly associated
(CMR) and non-complete metabolic responders (N-CMR). with omental metastasis in EOC patients. Furthermore, VAT
Baseline PET/CT parameters and post-treatment PET/CT results SUVmax can be useful as a complementary factor in predicting
were tested to investigate their possible correlation with omental metastasis. References: None.
prognosis, using Kaplan-Meier analysis and Cox’s proportional
hazard model. Baseline PET/CT parameters were also tested
to investigated their possible role as predictors of response to OP-283
therapy. Results: As regards the pre-treatment scan, the Cox Imaging in breast cancer staging: MRI of the breast versus
regression survival analysis showed a significant association dedicated breast PET and whole body PET/CT
between baseline MTV and OS (p=0.005). As regards the post- D. Grigolato1, A. Invento2, F. Pellini2, M. Zuffante1, M. Cucca1, E.
treatment scan, the Kaplan-Meier analysis showed a highly Biggi1, F. Padovano1, M. Naseri1, E. Fiorio3, Q. Piubello4, G. P. Pollini2,
significant difference in OS between the CMR and N-CMR M. Ferdeghini1;
groups (p<0.0001). As regard the prediction to metabolic 1
Nuclear Medicine Dept, Azienda Ospedaliera di Verona, Verona,
response to therapy, baseline MTV, TLG and Nodal PET-positivity ITALY, 2Oncologic Surgery Department, Complex Operative Unit
demonstrated to be independent predictors of response of Breast Surgery - Breast Unit, Azienda Ospedaliera di Verona,
(respectively, p=0.001, p=0.004, p =0.005). Conclusion: In our Verona, ITALY, 3Department of Oncology, Azienda Ospedaliera
cohort of patients, baseline MTV values and post-treatment PET di Verona, Verona, ITALY, 4Department of Diagnostic and
results are reliable prognostic tools. MTV, TLG and Nodal PET- Pathology, Azienda Ospedaliera di Verona, Verona, ITALY.
positivity are independent predictors of metabolic response
to chemoradiation therapy in locally advances cervical cancer.
References: None. Aim/Introduction: To assess the accuracy of two diagnostic
modalities, whole body PET/CT with dedicated breast
positron emission tomography and MRI of the breast and their
OP-282 retrospective fusion in patients with breast cancer. Materials
Predictive value of Visceral Fat Activity Assessed by and Methods: One hundred patients were retrospectively
Preoperative F-18 FDG PET/CT for omental Metastasis in analyzed, age ranged from 30 to 49 years with a clinical stadium
Patients with Epithelial Ovarian Cancer I-III at diagnosis. They where divided into five groups according
S. Choi1, J. Eo1, E. Lee1, S. Kim2; to the following characteristics: single cancer, multicentric/
1
Korea University Guro Hospital, Seoul, KOREA, REPUBLIC OF, multifocal lesions, pectoral invasion, prosthesis holders and
2
Korea University Anam Hospital, Seoul, KOREA, REPUBLIC OF. patients receiving preoperative chemotherapy. All patients
underwent 3T MRI of the breast and FDG PET/CT before surgery
or chemotherapy. A standard whole body PET/CT scan was
Aim/Introduction: Epithelial ovarian cancer(EOC) cells could immediately followed by a dedicated breast positron emission
directly spread from the primary tumor in to peritoneal cavity tomography with acquisition of two beds in high resolution in
and disseminate to organs in the abdomen. EOC preferentially prone position of the upper thorax including the axilla (dbPET).
metastasizes to the omentum. Dysregulated visceral adipose Biologic prognostic parameters obtained at diagnosis and, after
tissue(VAT) secretes various pro-inflammatory adipokines surgery, pathological results were correlated with metabolic
related to systemic inflammation which play key roles in features (SUVmax). Results: Primary multifocal/multicentric
metastasis. 18F-FDG PET/CT is a well-established imaging lesions were better identified by MRI in all groups, a good
method for evaluation of functional VAT activity. The aim of correlation in the detection of single lesions was noticed among
this study was to investigate the predictive role of functional the two methods. There was one false positive (FP) result at
VAT activity evaluated by preoperative F-18 FDG PET/CT for MRI and 5 false negative (FN) cases at dbPET, all patients with
omental metastasis in patients with EOC. Materials and infiltrating lobular cancer (ILC), low grade and low Ki-67, but
Methods: Ninety-patients(age 53.8 ±14.5) with EOC who fusion dbPET-MRI correctly changed the results in all these
underwent 18F-FDG PET/CT before the surgery were included patients. PET/CT identified 15 metastatic patients at diagnosis,
in this study. PET parameters (maximum SUV of the primary then confirmed at CT and/or MR. Bone metastases were
tumor, VAT SUVmax, and subcutaneous adipose tissue SUVmax) discovered in 13 patients, liver and lung lesions in 3 patients,
S117 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

and single cases with periocular soft tissue lesion, adrenal were performed to detect treatment response, particularly with
gland and brain metastasis, the latter identified by MRI. MRI a first FDG PET-CT at 6 weeks (18FDG-6W). Semi-quantitative
was more sensitive in defining pectoral invasion in 8 women, data were extracted from 18FES-BL, 18FDG-BL and 18FDG-6W, and
while dbPET showed high accuracy in detecting cutaneous compared to the progression free survival (PFS) during the 2nd-
infiltration, internal mammary chain involvement in 6 cases and HT treatment, among which SUVmax and adapted thresholded
macrometastatic axillary lymph nodes in 44 women, whereas Total Tumour Volume (TTV). Results: At breast cancer diagnosis,
partial, micrometastatic involvement of axillary lymph nodes was 6 patients (50%) had lymph node metastases and 5 (41,6%) had
only ruled out with sentinel lymph node biopsy (SLNB). MRI was visceral metastases. After first line hormonotherapy, only one
more precise in defining prosthesis state and their relationship patient had no positive FES (FES+) lesion while more than 40
with the pectoral muscle. Whole body PET/TC was useful in the FDG positive (FDG+) lesions were detected. Eleven patients
evaluation of chemotherapy response or disease progression (91,6%) had between 3 and more than 40 FES+ lesions. Three
and dbPET had great correlation with pathological response to patients (25%) had more FES+ lesions than FDG+ lesions, 4
neoadjuvant chemotherapy (p< 0.001). Conclusion: MRI alone patients (33,3%) had more FDG+ lesions than FES+ and 5 patients
or fusion dbPET-MR are among the best breast cancer diagnostic (41,7%) had as many FES+ lesions as FDG+. Despite the 2nd-HT
modalities allowing the more appropriate surgical approach started, no significant result was found for the semi-quantitative
or identifying patients for preoperative chemotherapy. Whole data outside a likely poor prognosis of 18FDG-BL TTV (p=0.079).
body PET/CT may become a part of the routine workup staging We noted a trend for a better PFS when the 18FES-BL TTV was
of high risk patients except for ILC. References: None. greater or equal to the 18FDG-BL TTV. Comparing 18FDG-BL and
18
FDG-6W, a 18FDG-BL TTV greater or equal to the 18FES-BL TTV
seemed predict the stability or progression of the 18FDG-6W
OP-284 TTV. Conclusion: 18FES PET-CT seemed to be interesting for the
First results of molecular imaging (FDG and FES) 2nd-HT response prediction. These results must be confirmed
in prospective study for selecting second line with the the following study patients. References: None.
hormonotherapy in estrogen receptors positive metastatic
breast cancer patients
B. Maucherat1, A. Leduc-Pennec2, N. Fleury3, L. Ferrer4,5, E. OP-285
Bourbouloux6, H. Simon7, M. Le Thiec1, D. Rusu1, V. Fleury1, M. Frequency Of Incidental Focal Breast Lesions Identified By
Colombie1, A. Morel1, F. Kraeber-Bodere1,5, L. Campion8,5, C. 18f-FDG PET/CT
Rousseau1,5; L. Petersen, J. D. Andersen, H. D. Zacho;
1
ICO Cancer Center, Nuclear Medicine Unit, Saint Herblain, Department of Nuclear Medicine, Aalborg
FRANCE, 2University Hospital, Nuclear Medicine Unit, Brest, University Hospital, DENMARK.
FRANCE, 3ICO Cancer Center, DRCI, Saint Herblain, FRANCE, 4ICO
Cancer Center, Physics Unit, Saint Herblain, FRANCE, 5CRCINA,
University of Nantes, INSERM UMR1232, CNRS-ERL6001, Nantes, Aim/Introduction: Incidental focal uptake of 18F-FDG in the
FRANCE, 6ICO Cancer Center, Oncology Unit, Saint Herblain, breast on PET/CT is rare. However, there is very few and often
FRANCE, 7University Hospital, Oncology Unit, Brest, FRANCE, quite small studies from Europe. Here we report data from
8
ICO Cancer Center, Biometrics, Saint Herblain, FRANCE. Denmark, a country with wide access to PET/CT as part of a free,
public health care system. Materials and Methods: All PET/CT
scans from a seven-year period (2010-2017) were electronically
Aim/Introduction: About 70% of primitive breast cancers searched for specific words and phrases indicative of breast
had positive estrogen receptors (ER) and may benefit from lesions. Potentially eligible PET/CT scans were manually reviewed
hormonotherapy. However, ER expression in breast cancer for incidental findings. All patients with known, suspected
metastases is heterogeneous and about 15% of metastases or previous cancer of the breast were excluded. Patients with
lost this expression over time. Biopsies were not possible diffuse FDG breast uptake were excluded. The extent of clinical,
systematically. 16α-18Fluoro-17β-Oestradiol (18FES) is a pathology, and imaging follow up were reviewed among
radiopharmaceutical which predict the response to the first patients with focal FDG uptake. Results: A total of 19.551 PET/
line hormonotherapy. The aim of this prospective study CT scans performed in the 7-year period of which 64 patients
(NCT03442504) was to determine the predictive value of PET at (0.3%) presented with an incidental, focal FDG-avid lesion of
the patient level, before a second line hormonotherapy (2nd- the breast. There were 63 women and 1 man with a mean age
HT) on the FDG response obtained at 6 weeks of treatment. of 67 ± 15 year. The main reasons for referral were staging of
Materials and Methods: We prospectively included 12 ER+ known cancer (45%) or suspected cancer (28%). Five percent of
metastatic breast cancer patients, HER2 negative, in progression the patients were referred with a non-cancer indication. Fifty-
despite first line hormonotherapy. For the complete study, two patients (81%) had a follow up, mostly with biopsy (n=39),
60 patients will be included. Due to 2nd-HT proposed by clinical evaluation (n=7), or imaging (n=6). Twelve patients had
oncologist, we performed 18FES PET-CT (18FES-BL) and 18FDG no follow up, mostly due to disseminated malignant disease.
PET-CT (18FDG-BL) at baseline in the month before the new Thirty-three patients had biopsy-verified cancer (33 primary
treatment introduction. Follow-up with 18FDG PET-CT and CT breast lesions, 2 metastases), i.e. 52% among the 64 patients
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S118

with a focal FDG breast uptake. However, the malignancy rate compared to other groups. 18F-FDG PET-CT can provide role
was 85% among patients with a biopsy (33 of 39 patients). The as prognostic marker in different molecular subtypes of breast
most frequently malignant lesion was ductal carcinoma (n=23). cancer. References: None.
Conclusion: We found a very low rate of incidental, focal
FDG uptake in the breast in patients evaluated on PET/CT in
Denmark. However, the malignancy rate was high among these OP-287
patients, in particular in patients who had a follow up biopsy. We Retrospective Analysis Of Baseline FDG PET/CT In
recommend biopsy in patients with focal uptake of FDG in the Prognostication Of Locally Advanced Breast Cancer
breast. References: None. Z. Nayeem, S. Shah, N. Purandare, A. Agrawal, A. Puranik, V.
Rangarajan;
Tata Memorial Centre, Mumbai, INDIA.
OP-286
To evaluate the role of F-18 FDG-PET/CT in different
molecular subtypes of breast cancer for prognostication Aim/Introduction: To correlate metabolic parameters on
R. Kumar, S. Arora, A. Passah, A. Prashanth, N. Mohan, A. R. baseline 18 F FDG PET/CT with outcomes i.e., disease free
Vuthaluru, C. Bal; survival (DFS) and progression free survival (PFS) in cases of
AIIMS, New Delhi, INDIA. locally advanced (LABC) and metastatic breast cancer (MBC)
respectively. Materials and Methods: This was a retrospective
observational study. Female patients with biopsy proven locally
Aim/Introduction: To find out whether, 18F-FDG PET/CT advanced breast cancer referred to our department for baseline
can be used as prognostic marker for survival outcome in 18 F FDG PET/CT scan during the period of Jan 2011 to June 2015
MBC, taking into consideration different molecular subtypes. with minimum follow up of 3 years were included in the study.
Materials and Methods: A total of 136 breast cancer patients Patients were segregated into LABC and MBC. Recurrence in
who underwent 18F-FDG PET/CT and having documented cases of LABC and progression in cases of MBC were confirmed
receptor status were included in this analysis. The patients were by clinical/ radiological follow up. Suitable cut-off points for SUV
divided into 3 subgroups, group 1 (ER+, PR+/-, Her 2neu-), group max, SUV mean, MTV and TLG for primary tumor and whole
2 (ER+/-, PR+/-, Her 2neu+) and group 3 (ER-, PR-, Her 2neu-)- body MTV were obtained using receiver operating characteristic
triple negative breast cancer (TNBC). Patients were followed till curve. Survival curves for DFS and PFS were constructed by
at least 1year after their last PET-CT study. Results: Among three using the Kaplan-Meier method. Results: 130 female patients
pathological groups, lymph nodal metastases was seen in 26/49 who met inclusion criteria were included in the study. 86
(53%) in group 1, 32/62 (51%) in group 2 and 19/25 (76%) in patients were LABC and 44 patients were MBC. On follow up,
group 3. There was significant difference between three groups 25 out of 86 patients of LABC developed recurrence (mean
regarding presence of lymph nodal metastases (p=0.09). Skeletal DFS -65 months). On analysis MTV of primary tumor showed
metastases was noted in 24/49 (49%), 21/62 (33%) and 12/25 significant correlation with DFS with cut-off value of 20.51 (53
(48%) in three groups respectively, with no significant difference months v/s 72 months) (p value- 0.036). While TLG of primary
in distribution (p=0.2). Liver metastases was noted in 8/49 (16%), tumor showed trend towards statistically significant value. 36
6/62 (9%) and 2/25 (8%) in three groups respectively, with no out of 44 patients of MBC developed progression (mean PFS -
significant difference in distribution (p=0.4). Lung metastases 23 months). On analysis whole body MTV showed statistically
was noted in 10/49 (20%), 21/62 (33%) and 8/25 (32%) in three significant correlation with progression free survival with cut-
groups respectively, with no significant difference in distribution off value of 83.24 (8 v/s 18 months) (p value-0.05). Rest of the
(p=0.2). Among Semiquantitative PET parameters, SUVmax metabolic parameters did not show any statistically significant
(mean, SD): 5.2(6.7) in Group 1, 4.8(3.6) in group 2 and 8.8 (5.08) correlation. Conclusion: MTV of primary tumor is a prognostic
in group 3), significant difference in SUVmax value of primary factor in determination of recurrence in case of LABC and whole
breast lesions was noted among three groups (p=0.04). Group body MTV is a prognostic factor in determination of MBC.
three (TNBC) lesions had highest SUVmax values, compared to Prospective multicenter studies in a larger homogenous patient
group 1 (p=0.03) and group 2 (p=0.01). Although within group cohort and longer follow up are required for the validation of
3, no significant difference between SUVmax values of primary these observations References: None.
lesions were noted among patients who expired or were alive
at last follow up. No significant difference in SUVmax value of
extra primary lesions, were noted among the three groups. On OP-288
follow up, significant difference regarding survival outcome Using 18F-FDG-PET/CT for Response Monitoring of
was noted among three groups (18/49 (36%) in group 1, Metastatic Breast Cancer: Interrater Agreement and
19/62(30%) in group 2 and 18/25 (72%) in group 3 ( p=0.001). Reliability of PERCIST and Visual Assessment
Also, on subgroup analysis, using age (younger patient group J. Sørensen1,2, M. H. Vilstrup2, J. Holm2, M. Vogsen1,2,3, J. Bülow2, L.
(<45year) showed increased mortality compared to age group Ljungstrøm2, M. G. Hildebrandt1,2,4, O. Gerke1,2;
(>45 years) (p=0.04). Conclusion: TNBC patients showed more 1
Department of Clinical Research, University of Southern
metabolic activity of primary lesion and worse survival outcome Denmark, Odense, DENMARK, 2Department of Nuclear
S119 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

Medicine, Odense University Hospital, Odense, DENMARK, 609


3
Department of Oncology, Odense University Hospital,
Odense, DENMARK, 4Center for Innovative Medical Technology,
Paediatrics - Parallel Session: Paediatrics
Odense University Hospital, Odense, DENMARK.
Monday, October 14, 2019, 8:00 - 9:30 Lecture Hall 115

Aim/Introduction: Palliative medical treatment is indicated


for metastatic breast cancer (MBC) along with response
evaluation at regular intervals[1]. Accurate response monitoring OP-289
is becoming increasingly important, and FDG-PET/CT may 18
F-FET PET/MRI for CNS-Tumors in Children and
have the potential to monitor treatment response accurately. Adolescents
The PERCIST criteria[2] may perform with better agreement L. Marner1,2, K. Nysom3, A. Sehested3, L. Borgwardt2, R. Mathiasen3,
between observers than qualitative assessment. The aim of this R. Mathiasen3, P. S. Wehner4, O. M. Henriksen2, M. Lundemann2,
study was to compare the interrater agreement and reliability C. Thomsen5, L. Bøgeskov6, J. Skjøth-Rasmussen6, H. Broholm7, D.
of the semi-quantitative PERCIST criteria to qualitative visual Scheie7, M. Juhler6, L. Højgaard2, I. Law2;
assessment in response evaluation of MBC. Furthermore, to 1
Department of Clinical Physiology and Nuclear Medicine,
investigate the intrarater agreement when comparing each University Hospital Bispebjerg, Copenhagen, DENMARK,
rater’s visual assessment to their own respective PERCIST 2
Department of Clinical Physiology, Nuclear Medicine and PET,
assessment. Materials and Methods: We performed a University Hospital Rigshospitalet, Copenhagen, DENMARK,
retrospective study on FDG-PET/CT in women with MBC who 3
Department of Pediatrics and Adolescent Medicine, University
received treatment at Odense University Hospital. Patients Hospital Rigshospitalet, Copenhagen, DENMARK, 4Hans
were recruited from September 2017 to December 2017, and Christian Andersen Children’s Hospital, University Hospital
data from medical files and scans were analysed retrospectively Odense, Odense, DENMARK, 5Department of Diagnostic
for consenting women. Three specialists in nuclear medicine Radiology, Zealand University Hospital, Roskilde, DENMARK,
categorized response evaluation by qualitative assessment 6
Department of Neurosurgery, University Hospital Rigshospitalet,
and standardized one-lesion PERCIST assessment based on Copenhagen, DENMARK, 7Department of Pathology, University
SULpeak measurements[2]. The scans were categorized into Hospital Rigshospitalet, Copenhagen, DENMARK.
complete metabolic response, partial metabolic response,
stable metabolic disease, and progressive metabolic disease.
Results: A total of 37 patients with 179 scans were included. Aim/Introduction: 18F-fluoro-ethyltyrosine (18F-FET) positron
Visual assessment categorization yielded moderate agreement emission tomography (PET) improves diagnostic accuracy in
with an overall proportion of agreement between raters of 0.52 adult patients with gliomas. We aimed to 1) determine accuracy
(95% CI 0.44-0.66) and a Fleiss kappa estimate of 0.54 (95% CI for detecting tumor using 18F-FET PET and MRI versus MRI alone
0.46-0.62). PERCIST response categorization yielded substantial in children and adolescents with CNS tumors and 2) test the
agreement with an overall proportion of agreement of 0.65 clinical impact of the scans. Materials and Methods: Ninety-
(95% CI 0.57-0.73) and a Fleiss kappa estimate of 0.68 (95% CI seven patients (57 males, 40 females, median age 10.1 years,
0.60-0.75). The difference in proportions of agreement between range 0-33 years) with primary pediatric CNS tumors were
overall estimates for PERCIST and visual assessment was 0.13 included consecutively and prospectively, and a total of 169
(95% CI 0.06-0.21; p=0.001), that of kappa was 0.14 (95% CI 0.06- hybrid 18F-FET PET/MRI (n=140) or PET/CT scans were performed
0.21; p<0.001). The overall intrarater proportion of agreement at time of diagnosis, recurrence, or before or after treatment. For
was 0.80 (95% CI 0.75-0.84) with substantial agreement by a Fleiss the estimation of a lesion-based accuracy for detection of tumor,
kappa of 0.74 (95% CI 0.69-0.79). Conclusion: Semi-quantitative the reference standard was operation, biopsy, or follow-up. The
PERCIST assessment achieved significantly higher level of overall accuracies between MRI, PET, and PET/MRI were compared using
agreement and reliability compared to qualitative assessment McNemar’s test, correcting for possible correlation between
among three raters. The achieved high levels of intrarater lesions belonging to the same patient. Clinical impact was
agreement indicated no obvious conflicting elements between assessed by sequential clinical decision making, first with only
the two methods. PERCIST assessment may therefore give more MRI and then with additional 18F-FET PET available. As scans were
consistent interpretations between raters as well as between performed consecutively for research purposes, the majority
institutions when using FDG-PET/CT for response evaluation in were not clinically indicated. The clinically indicated scans were
MBC. References: [1]Cardoso F et al. Ann Oncol. 2018;29:1634- identified before the 18F-FET PET scan was available, and were
57. doi:10.1093/annonc/mdy192. [2]Wahl RL et al. J Nucl Med. cases of anticipated impact of the PET scan due to important
2009;50 Suppl 1:122S-50S. doi:10.2967/jnumed.108.057307. clinical decisions combined with an equivocal MRI. Results: For
treated lesions, the sensitivity/specificity/accuracy for PET/MRI
was 0.88(0.82-0.94)/1.00(0.82-1.00)/0.91(0.87-0.96), as compared
to MRI alone 0.93(0.89-0.97)/0.48(0.30-0.70)/0.81(0.75-0.89),
p=0.31/p=0.0001/p=0.044. Of the 151 scans rated for clinical
impact, the addition of 18F-FET PET to MRI added extra relevant
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S120

information in 28% and influenced the clinical management in risk NB patients. On the PBA, the sensitivity of 123I-mIBG WBS
8%. Of the 30 18F-FET PET scans that were beforehand identified and 18F-DOPA PET/CT in detecting primary tumours, soft tissue
as clinically indicated (e.g. due to equivocal MRI), 40% added metastases and bone/bone marrow metastases was 83%, 50%,
new information and 33% influenced clinical management. 92% and 94%, 92% and 100% respectively. On the LBA, the
Conclusion: We collected a large dataset of 18F-FET PET scans sensitivity of 18F-DOPA PET/CT in detecting soft tissue and bone/
in a broad spectrum of pediatric tumor types. Interpretation of bone marrow metastases was 86% and 99%; significantly higher
MRI can be challenged by unspecific contrast enhancement than that 123I-mIBG WBS (41% and 93%). After chemotherapy, on
especially after treatment procedures. PET showed higher the PBA, the sensitivity of 123I-mIBG WBS and 18F-DOPA PET/CT
specificity (p=0.0001) and using the combined information in detecting primary tumours, soft tissue metastases and bone/
from PET and MRI showed a significantly higher accuracy for bone marrow metastases was 72%, 33%, 38% and 83%, 75% and
detecting pediatric tumors of 0.91 vs. 0.81 for treated lesions 54% respectively. On the LBA, the sensitivity of 18F-DOPA PET/CT
(p=0.04). Further, the addition of 18F-FET PET influenced clinical in detecting soft tissue and bone/bone marrow metastases was
management in 8% of all scans and in 33% of the clinically 77% and 86%; significantly higher than that 123I-mIBG WBS (28%
indicated scans. In conclusion, 18F-FET PET is useful in cases of and 69%). Over a median follow-up of 29.3 months, 8 cases of
pediatric brain tumors with difficult clinical decision making, disease progression and 5 deaths occurred. At multivariate level,
as 33% of scans influence clinical management in this group of the 18F-DOPA WBMB, evaluated after therapy, wasthe only factor
patients. References: None. independently associated to disease progression free survival.
Conclusion: 18F-DOPA PET/CT is more sensitive than 123I-mIBG
WBS to stage NB patients and to evaluate disease persistence
OP-290 after chemotherapy. In time-to-event analyses,18F-DOPA WBMB,
Diagnostic and Prognostic Role of 18F-DOPA PET/CT in evaluated after chemotherapy, remained the only risk factor
children affected by Neuroblastoma: Comparison with independently associated to disease progression. References:
123I-mIBG scan None.
G. Bottoni1, G. Ferrarazzo2, A. Cistaro3, M. Puntoni4, G. Morana5, S.
Sorrentino6, P. Zucchetta7, M. Ugolini8, M. Conte6, M. Pescetto9, M.
Lattuada9, A. Garaventa6, L. Giovanella10, E. Lopci11, A. Piccardo12; OP-291
1
Nuclear medicine unit Ospedali Galliera, Genova, ITALY, 2Nuclear Metastatic differentiated thyroid cancer in paediatric
medicine unit, Pavia, ITALY, 3Department of Nuclear Medicine, patients - radioiodine treatment after thyroid hormone
Galliera Hospital, Genoa, ITALY, 4Clinical Trial Research Unit, withdrawal or rhTSH stimulation
Galliera Hospital, Genoa, ITALY, 5Neuroradiology Unit, IRCCS D. Handkiewicz-Junak, A. Kropinska, A. Ledwon, J. Roskosz, D.
Istituto Giannina Gaslini, Genova, ITALY, 6Unit of Pediatric Kula, A. Kluczewska, T. Olczyk, E. Paliczka, Z. Puch, B. Jarzab;
Oncology, IRCCS G. Gaslini Genoa, ITALY, 7Department of M.Sklodowska Curie Memorial Institute – Cancer
Nuclear Medicine, University Hospital of Padova, Padova, ITALY, Center Gliwice Branch, Gliwice, POLAND.
8
Medical Physics Department, Galliera Hospital, Genoa, ITALY,
9
Anaesthesiology Department, Galliera Hospital, Genoa, ITALY,
10
Clinic of Nuclear Medicine and Molecular Imaging, Imaging Aim/Introduction: Distant metastases are diagnosed in about
Institute of Southern Switzerland, SWITZERLAND, 11Department 20% of children with DTC. Radioiodine is the treatment of
of Nuclear Medicine, Humanitas Research Hospital, Rozzano, choice, however, there are limited data on optional preparation
ITALY, 12Nuclear medicine unit, Galliera Hospital, Genoa, ITALY. for it. The aim of our retrospective study was to evaluate the
effectiveness of radioiodine treatment after thyroid hormone
withdrawal (THW) and rhTSH stimulation in metastatic
Aim/Introduction: We aim to validate the diagnostic role of paediatric DTC. Materials and Methods: From 501 children
18
F-DOPA PET/CT, at the time of first staging, in children affected diagnosed with DTC during the years 1988- 2018, 72 (14.4%) had
by Neuroblastoma (NB) and to investigate the ability of this distant metastases (lungs - 66, bones - 2, both- 4). All 72 children
technique in the assessment of treatment response. Lastly, we were treated with radioiodine after THW (group A:46 patients)
investigated the prognostic value of 18F-DOPA at onset and or combination of rhTSH and THW cycles (group B: 26 patients).
after chemotherapy. Materials and Methods: We included Median cumulated radioiodine activity was 16.8 GBq. Results:
children affected by NB at onset. All patients underwent, Median time of observation in the whole group of patients was
before and after chemotherapy, 18F-DOPA PET/CT and 123I-mIBG 11.5 years and was longer in group A (13 vs. 5 years, p < 0.05)
whole-body scan (WBS) with additional SPECT/CT.The18F-DOPA During the last radioiodine treatment complete scintigraphic
PET/CT results were compared with those of 123I-mIBG WBS. response was achieved in 63% and biochemical CR (Tg <2 ng/
For each modality, a patient-based (PBA) and lesion-based- ml) in 24% (p < 0.05). Complete scintigraphic and biochemical
analysis (LBA) was performed and sensitivity calculated. Specific response increased respectively to 86% and 40% during the
scoring systems applied to 123I-mIBG WBS and to 18F-DOPA PET/ last follow-up on TSH stimulation. During the last follow-up
CT were also calculated and the association between these suppressed Tg decreased below 1 ng/ml in 70% of children.
parameters, the principal NB risk-factors and outcome was When we compared last radioiodine treatment in group A and
evaluated. Results: We enrolled 16 high and 2 intermediate- B there was no statistically significant difference in scintigraphic
S121 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

(58% vs. 72%) or biochemical (25% vs. 18.5%) complete response. showed complete response, with event free survival of more
However, during last follow up on TSH suppression complete than 18 months, mostly in Hodgkin’s Lymphoma. Moreover
biochemical response was higher in group A (84% vs. 46%, p LC+ studies were independently and significantly associated
< 0.05). In 6 patients treated under rhTSH stimulation only (no with overall increased mortality and with more events in these
THW) complete biochemical and scintigraphic response was patients. Conclusion: Good response in interim PET/CT is strong
achieved respectively in 1/6 (17%) and 5/6 (83%) patients. No & independent predictor of prognosis with event free survival of
lung fibrosis nor secondary malignancies were diagnosed during more than 18 months without relapse in pediatric Lymphoma
follow-up Conclusion: Our study confirms that radioiodine and LC+ 18F FDG PET/CT in interim evaluation is significantly
treatment of disseminated DTC in children/adolescents is safe and independently associated with increased overall mortality
and effective. To confirm complete remission long follow-up is and more events. References: 1. Weiler-Sagie M,et all, 18F-FDG
necessary since the response is extended in time. rhTSH seem Avidity in Lymphamoa Readdressed, J Nucl Med 2010;51: 25-30.
not to decrease response rate to radioiodine treatment and the
observed difference between groups are probably related to
shorter follow-up time after rh-TSH. References: None. OP-293
Prognostic value of interim-PET in paediatric Hodgkin
lymphoma: the role of qPET
OP-292 S. Pacella1, C. Landoni1, M. Arosio2, E. De Ponti3, S. Morzenti3, C.
Significance Of Interim PET/CT And Lugano Criteria Crivellaro1, F. Elisei2, M. Spinelli4, A. Sala4, L. Guerra2;
For Early Response Evaluation With 18F-FDG-PET/ 1
University of Milano Bicocca, Milano, ITALY, 2Nuclear
CT In Pediatric Lymphoma--A Part Of Report On IAEA Medicine Department, ASST Monza San Gerardo Hospital,
Multicentric Prospective Study Monza, ITALY, 3Medical Physics Department, ASST Monza
K. Bashir Mir1, I. Iaea2, S. A. Bukhari1, S. Batool1, S. Fatima1; San Gerardo Hospital, Monza, ITALY, 4Fondazione MBBM
1
Nuclear Medicine And Oncology Institute, Islamabad, PAKISTAN, ASST Monza San Gerardo Hospital, Monza, ITALY.
2
International Atomic Energy Agency, Vienna, AUSTRIA.

Aim/Introduction: 18-Fluorodeoxyglucose (FDG) positron


Aim/Introduction: Pediatric lymphoma is third most common emission tomography/computed tomography (PET/CT) is
childhood malignancy with relapse rate of 5-20%. 18F-FDG PET/ an useful tool for staging and for the evaluation of response
CT is an excellent tool for staging and monitoring disease in to therapy in Hodgkin lymphoma (HL); interim-PET has also a
adult lymphoma but there is no validated standardized criteria prognostic role. Our study aimed to evaluate the prognostic role
for evaluation of treatment response by PET/CT in pediatric of r-PET in paediatric HL by calculating qPET , that is the ratio of
Lymphoma. Aims: To establish the significance of interim PET/ SUVpeak of a reference lesion to the liver SUVmean. Materials
CT (iPET/CT) in the treatment response evaluation of pediatrics and Methods: 63 children (32 males, mean age 13, range 5-17)
Lymphoma and to evaluate the prognostic impact of Lugano with newly diagnosed HL, stage I-IV disease (14 stage I- IIA,
criteria (LC) in the evaluation of pediatric 18F-FDG PET/CT 49 stage IIB-IVB) were retrospectively evaluated. All patients
in pediatric lymphoma. Materials and Methods: Between underwent a pre-treatment 18F-FDG PET/CT (baseline PET)
2013-2017 PET/CT studies performed for staging and interim and after 2, 3 o 4 cycles of chemotherapy (restaging-PET; r-PET)
response evaluation in 35 patients (n=35), <18 years of age according to the therapeutic group. r-PET scans were evaluated
of pediatric Lymphoma after taking informed consent. Whole according to Deauville Score (DS) criteria. DS 1-3 classified
body PET/CT (head to toe) was done. Staging PET/CT (sPET/CT) r-PET as negative, and DS 4-5 as positive. A qPET threshold ≥
and early response evaluation after 2 cycles of chemotherapy, 1.3 classified r-PET as positive for disease (Hasenclever et al.
iPET/CT was done. We prospectively reviewed results of sPET/CT 2014). Disease related major events (death and disease relapse)
and iPET/CT and in some patients with end of treatment (EOT) were correlated to r-PET results according both to DS and qPET
PET/CT, and their 18 months follow up after start of therapy to using the Fisher exact text, with a p value < 0.05 considered as
asses complete response (CR) and incomplete response (NCR) significant. Results: The median follow-up was 44 months for
of the treatment given. PET/CT findings were evaluated using DFS and 55 months for OS; at last follow-up, 53 children were in
visual and quantitative variables eg, Deauville criteria, Luganos complete remission , 2 had progression and died and 8 relapsed.
criteria, measurement of bulk of lesion in baseline and interim According to DS r-PET resulted negative in 53 patients (84%)
and differences in values of SUV Max and Mean in both s and i and positive in 10 (16%). There was no statistical difference
PET/CT . LC scores of 1-3 was considered negative, LC- ,4-5 was between r-PET results and the presence of relapse (p-value
taken as LC +. Results: n= 35, Age (Years) 7.8 +_ 3.7, Sex Ratio 0.19); conversely there was a statistical difference between r-PET
(M: F) (28 :07), Type (HL: NHL) 30:05). Comparison of baseline results and the number of exitus with a higher value in r-PET
and interim PET/CT scans were done on the basis of Deauville positive group (p-value 0.023). The positive predictive value
criteria, measurement of bulk of lesion in baseline and interim, (PPV) and negative predictive value (NPV) of r-PET to predict
difference in the values of SUV max and SUV mean and LC in both exitus were 100% and 87%. The mean values of qPET in relapsed
sPET/CT and iPET/CT. Long term follow up of patients showed and not relapsed patients were 1.32 (median 0.86, range 0.46-
that patients in which iPET/CT showed good response, (n=27) 3.93) and 0.91 (median 0.84, range 0.34-5.27) respectively,
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S122

without statistical difference between the two groups (p-value (interim) and at end of treatment. References: 1: Mueller WP,
0.07). Conversely qPET values in dead and alive patients were Melzer HI, Schmid I, Coppenrath E, Bartenstein P, Pfluger T.
0.91 (average value; median value 0.83; range 0.34-5.27) and 3.11 The diagnostic value of 18F-FDG PET and MRI in paediatric
(average value; median value 3.11; range 2.29-3.93) respectively histiocytosis. Eur J Nucl Med Mol Imaging. 2013 Feb;40(3):356-
with statistically significant difference (p-value 0.01); the PPV and 63.2: Lee HJ, Ahn BC, Lee SW, Lee J. The usefulness of F-18
NPV of qPET to predict exitus were 100 % and 92%. Conclusion: fluorodeoxyglucose positron emission tomography/computed
Our study suggests that DS and qPET are both strong predictors tomography in patients with Langerhans cell histiocytosis. Ann
of exitus with a slightly better performance of qPET in terms of Nucl Med. 2012 Nov;26(9):730-7.3: Phillips M, Allen C, Gerson
NPV. References: Hasenclever et al. 2014 P, McClain K. Comparison of FDG-PET scans to conventional
radiography and bone scans in management of Langerhans
cell histiocytosis. Pediatr Blood Cancer. 2009 Jan;52(1):97-101.4:
OP-294 Kaste SC, Rodriguez-Galindo C, McCarville ME, Shulkin BL. PET-
18
F-FDG-PET-CT in Paediatric Langerhans Cell Histiocytosis: CT in pediatric Langerhans cell histiocytosis. Pediatr Radiol. 2007
Extension, Diagnosis, Recurrence and Treatment Response Jul;37(7):615-22.
Evaluation
J. Alors-Ruiz1, C. Sábado-Álvarez2, A. A. Cardozo-Saavedra3, I.
Roca-Bielsa3, A. García-Burillo3, J. Castell-Conesa3; OP-295
1
Nuclear Medicine Department. Hospital Clínico Universitario Might STAGING 18FDG-PET stratify prognosis in
Virgen de la Victoria, Málaga, SPAIN, 2Paediatric Oncology Osteosarcoma and Ewing sarcoma?
and Haematology Department. Hospital Universitari Vall C. Olianti1, R. Di Dato1, M. Allocca1, A. Tamburini2, C. Caporalini2, R.
d’Hebrón, Barcelona, SPAIN, 3Nuclear Medicine Department. Sciagra’1;
Hospital Universitari Vall d’Hebrón, Barcelona, SPAIN. 1
University Hospital of Careggi, Florence, ITALY,
2
University Hospital Meyer, Florence, ITALY.

Aim/Introduction: At first clinical approach, Langerhans Cell


Histiocytosis (LCH) may be a systemic and severe disease or Aim/Introduction: To identify at staging18FDG-PET-CT the
just monosymptomatic. And the evolution of the disease may biological aspects of Osteosarcoma (OS) and Ewing’Sarcoma
be a spontaneous resolution or a rapid systemic progression, (ES) able to stratify the risk of poor response to therapy or
including death. PET-CT with 18F-FDG is used both for initial relapse, and correlate them with progression free survivor
diagnosis and for the treatment response assessment. Paediatric (PSF). Materials and Methods: SUVmax (Standardized Uptake
series published until now have a limited number of cases and Value) of lesion, MTV41% (Tumor Volume), TLG41% (Tumor
follow-up evaluations. Materials and Methods: From January Lesion Glycolysis), FDG%necrosis, cylindrical or ellipsoid
2010 till March 2019, 41 paediatric patients have been submitted morphology are evaluated in 48 patients with OS (26) and ES
to 18F-FDG-PET-CT under the clinical suspicion of LCH (later (22), age 4-29 years (mean 15.06+/-5.8) in staging18FDG-PET-
confirmed), for treatment response assessment of LCH during CT. Data-comparisons (t-student, test-U of Mann-Whitney) are
and after chemotherapy and in case of recurrence suspicion: performed with histological outcome (Huvos for OS, Picci for
mean age 5.3 ± 4.1 years; age range 6 months to 17.6 years. ES) and histological%necrosis, dividing the cohort in Poor/Good
A total number of 63 18F-FDG-PET-CT have been performed responders, Kaplan-Meier curves for 5years-PFR are builded,
corresponding to the 41 patients: 37 initial evaluation, 10 and ROC-analysis for cut-off evaluation performed. Results:
response assessment, 7 recurrence suspicion and 9 after Statistical-analysis shows a significant difference (p<0.05)
treatment. Results: Results in 18F-FDG-PET-CT have classified between OS and ES cohort for SUVmax (mean+/-SD: 7.06+/-3.82
the patients in single-system involvement in 26 patients (63.4%): OS vs 4.43+/-2.93 ES), MTV (mm3: 93.46+/-170.78 OS vs 39.87+/-
17 single site and 9 multiple sites. 15 patients (36.6%) were 23.18 ES) and TLG (355.75+/-128.81 OS 128.81+/-127.56 ES) and
assigned to multisystem group, 10 with risk organs involvement significant difference (p<0.05) of SUVmax and TLG41% between
(spleen, liver, bone marrow and central nervous system). At GoodES and PoorES (mean+/-SD: respectively 2.75+/-1.18 vs
diagnosis, bone system is the most frequently involved, with 6.78+/-3.75, p<0.02 and 59.5+/-33 vs 220.59+/-159.75, p<0.005).
bone lytic lesions (32 patients, 78%). Other initial presentations SUVmax cut-off of 3.4 and TLG41% cut-off of 136.13 correlate
includes: skin involvement (10 patients), diabetes insipidus with GoodES and PoorES stratification (AUC 0,83; p<0.05), not
(4 patients), haemophagocytic syndrome (3 patients), lung for OS; they also indicate a 86% risk of relapse (5y-PSF) if higher
involvement (1 patient) and soft tissue (1 patient).26 patients and 50% (5y-PSF) if lower (Kaplan-Meier). FDG%necrosis respect
received chemotherapy (based on prednisone/vinblastine tumor volume (mm3 : 253,86+/-273,57 OS vs 257.68 +/-276,21
protocols). Based on 18F-FDG-PET-CT results and clinical ES ) is 17% in OS and 13% in ES. Age at staging is 15.6+/-6 years
evaluation, complete resolution, stable lesions and progression for OS and 14.4+/-5.7 years for ES (p>0.05), otherwise a cut-off
were present in 27%, 46% and 27%, respectively. Conclusion: of 12.5y is found for GoodES and PoorES stratification (AUC
18
F-FDG-PET-CT is an all-in-one technique in LCH, with clinical 0,82, p<0.05), not for OS, and it indicates a 92% risk of relapse
usefulness for the initial extension diagnostic, in case of clinical (5y-PSF) if higher and a 20% of risk of relapse (5y-PSF) if lesser
suspicion of recurrence, for treatment response assessment (Kaplan-Meier). Cylindric morph. is found in 15.4% of OS, 25% of
S123 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

GoodOS and 75% of PoorOS, and in 50% of ES, 62.5% of GoodES after liver resection. Conclusion: Our results demonstrated that
and 37.5% of PoorES, (p < 0.05). Ellipsoid morph. is found 84.6% recent method of 99mTc-mebrofenin hepatobiliary scintigraphy
of OS, 52% of GoodOS and 48% of PoorOS, and in 50% of ES, for estimation of the FRL-F in adults can be successfully used
55% for GoodES and 45% for PoorES. Ellipsoid and cylindrical in children. In the most of the patients value of FRL-F was more
morphologies correlate respectively with a 14% and 50% risk than 2.7 %/min/m2 before surgery, which can be explained by
of relapse (5y-PSF Kaplan-Meier Curves) independently from lack of severe parenchymal diseases in children. FRL-F value
the tumor-site if arms, axial skeleton or pelvis. Conclusion: in pediatric patients increases after chemotherapy. To obtain
Preliminary data seem to assess prognostic value of SUVmax, reliable data it is necessary to continue the study with further
TLG, age at staging and morphology in ES only. A trend is recruitment and analysis. References: None.
suggested in OS to investigate with a larger cohort of patients.
References: None. 610
Endocrine - Parallel Session: Neuroendocrine
OP-296
Malignancies
Assessment of future remnant liver function in pediatric
patients with liver malignancies Monday, October 14, 2019, 8:00 - 9:30 Lecture Hall 116
Y. Likar, K. Chaurasiya, E. Kireeva, I. Vdovina, M. Chetchasova, D.
Akhaladze;
Dmitry Rogachev National Research Center of
Pediatric Hematology, Oncology and Immunology, OP-297
Moscow, RUSSIAN FEDERATION. [18F] DOPA PET/CT for the evaluation of primary or
recurrent medullary thyroid carcinoma
E. Rainer, S. Rasul, C. Scheuba, M. Mayerhöfer, P. Mazal, A. Haug, M.
Aim/Introduction: Liver malignancies are 3rdmost common Hacker, S. Li;
malignant tumors of the abdominal/retroperitoneal cavity in Medical university of Vienna, Vienna, AUSTRIA.
children. Surgery remains the most important treatment for liver
tumors. Post-resection liver failure remains a major problem,
which requires accurate preoperative assessment of future Aim/Introduction: Basal calcitonin (bCT) and carcinoembryonic
remnant liver function (FRL-F). Recently a novel method was antigen (CEA) can be used as tumor markers for diagnosis and
presented using 99mTc-mebrofenin hepatobiliary scintigraphy follow-up of MTC. [18F]DOPA-PET/CT has been reported to be
(HBS) for estimation of the FRL-F in adults. It has been shown useful for the detection of primary or recurrent MTC. However,
that the threshold value of FRL-F >2.7 %/min/m2minimizes the so far, no data have been published concerning the possible
postoperative liver failure. The aim of our study is to evaluate the relation between the sCT levels and the results of [18F]DOPA-
role of preoperative HBS for estimation of the FRL-F in pediatric PET/CT as well as possible gender differences in [18F]DOPA-PET
patients with liver malignancies. Materials and Methods: results. The aim of this study is to evaluate a possible correlation
Twenty-nine pediatric patients with liver malignancies (aged between bCT- or sCT levels and tracer uptake of [18F]DOPA.
from 27 days to 16.7 years) were included in this study. All Furthermore, we want to assess possible gender differences
patients underwent HBS for estimation of the FRL-F before in the results of [18F]DOPA-PET. Materials and Methods: 148
surgery. The study was performed immediately after intravenous [18F]DOPA-PET/CT examinations in 50 patients (26 female, 24
injection of 99mTc-mebrofenin using standard protocol with the male patients, mean age 59 ± 14 years, range 24 to 84) with
two dynamic phases and SPECT/CT of the liver. Venous phase histologically verified primary or recurrent MTC were included.
of CECT was used for more accurate segmentation of liver. 5 patients presented with hereditary MTC. Serum bCT and CEA
The boundary of future remnant liver was drawn manually. were measured in all patients. Calcium stimulation test was
Results: In 12 patients right side extended hemihepatectomy performed in 42 of the 50 patients. SUVmax was calculated for
was performed, the FRL-F was evaluated in S2, S3 segments each lesion. Correlation and cutoff values were determined with
and ranges from 1.2 to 11.7 %/min/m2. In 8 patients right SPSS Statistics using Pearson’s correlation, Chi square test and
hemihepatectomy was performed, the FRL-F was evaluated in ROC curves. Results: Positive [18F]DOPA-PET/CT results were
S2, S3, S4 segments and ranges from 2.8 to 19.3 %/min/m2. In shown in 127 examinations with a case-related sensitivity of
3 patients left hemihepatectomy was performed, the FRL-F was 86%. 43 patients had positive [18F]DOPA-PET/CT scans with a
evaluated in S5, S6, S7, S8 segments and ranges from 27.1 to sensitivity of 86%. 22 male patients (92%) had positive findings
29.5 %/min/m2. In 6 patient atypical resection was performed, in [18F]DOPA-PET/CT, whereas only 21 female patients (80%)
the FRL-F value was evaluated in S2, S3, S6 and S7 segments and were positive in the [18F]DOPA-PET/CT. However, we found no
ranges from 5.8 to 14.1 %/min/m2. At the initial diagnosis the significant difference in sensitivity between female and male
FRL-F value was less than 2.7 %/min/m2in 3 patients (1.2, 1.5, 2.4 patients. All 5 patients (100%) with hereditary MTC had positive
%/min/m2), after chemotherapy the FRL-F values was increased PET/CT scans. Significant correlations were found between
up to 9.0, 4.5 and 5.7 %/min/m2, respectively. No one has bCT and SUVmax (p<0,01) as well as between sCT and SUVmax
developed post-resection hepatic failure following one month (p<0,01). 119 examinations with positive [18F]DOPA-PET/CT had
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S124

bCT levels >82 pg/mL with a sensitivity of 90% and a specificity on 18F-FCH PET/CT had higher calcitonin (median 562.8 [IQR
of 67%. [18F]DOPA-PET/CT was positive in 53 examinations 243.9-2589.3] vs 35.8 [IQR 30.1-79.1] ng/l, Wilcoxon signed-rank
with sCT levels >1714 pg/mL with a sensitivity of 73% and a p = 0.01115) and CEA levels (median 9.7 [IQR 7.3-35.5] vs 4 [IQR
specificity of 63%. Cutoff value for CEA values >4 ng/L had a 2.7-6.2] µg/l, Wilcoxon signed-rank p = 0.1482) in comparison to
sensitivity of 80% and a specificity of 64%. Conclusion: Tracer- 18
F-FCH PET/CT negative patients. Conclusion: 18F-FCH appears
uptake of [18F]DOPA (SUVmax) correlates significantly with bCT to be a promising radiotracer for visualization of MTC recurrence
and sCT. We observed higher sensitivity of [18F]DOPA-PET/CT in with detection rates similar to 18F-FDOPA. Further evaluation of
male patients than in female patients, however no significant our data and comparison with other imaging modalities are
difference was shown. Higher sensitivity of [18F]DOPA-PET/CT needed to define the role of 18F-FCH PET/CT in the management
tends to be found in patients with hereditary MTC as compared of MTC recurrence. References: None.
to patients with sporadic MTC. [18F] DOPA-PET/CT may be
especially useful in patients with bCT levels >82 pg/mL or sCT
levels >1714 pg/mL or CEA >4ng/L. References: None. OP-299
Normal and Abnormal Adrenal glands’ Standard
Uptake Values in 123I mIBG scintigraphy for diagnosis of
OP-298 Pheochromocytoma and Paraganglioma
Diagnostic Value of 18F-Fluorocholine PET/CT for the R. Gregory1, E. Nowosinska1, Y. Bouchareb2, M. Burniston1;
Detection of Recurrent Medullary Thyroid Carcinoma 1
Barts Health NHS Trust, London, UNITED KINGDOM,
J. Jamsek1, M. Hocevar2, D. Bergant2, K. Zaletel1, S. Rep1, B. Peric2, L. 2
College of Medicine & Health Sciences Sultan
Lezaic1; Qaboos University Hospital, Muscat, OMAN.
1
University Medical Centre Ljubljana, Ljubljana, SLOVENIA,
2
Institute of Oncology Ljubljana, Ljubljana, SLOVENIA.
Aim/Introduction: Iodine-123 mIBG scintigraphy is the
standard imaging method for diagnosis of pheochromocytoma
Aim/Introduction: Medullary thyroid carcinoma (MTC) and paraganglioma. Pheochromocytoma develops in the
recurrence after primary surgery is found in 15-50% of patients. adrenal glands and it is challenging to distinguish abnormal
Our group recently reported the usefulness of 18F-Fluorocholine uptake from the physiological uptake in the adrenal medulla.
(18F-FCH) in primary MTC staging. Following those findings, we The aim of this work is to show whether quantitative imaging
wanted to assess the role of 18F-FCH PET/CT in biochemical can be used to aid distinction between normal and abnormal
recurrence of MTC. Preliminary results are presented. Materials (tumour) adrenal gland uptake. Materials and Methods:
and Methods: Twenty MTC patients (8 male, 12 female; aged Sixteen patients’ 123I mIBG SPECT/CT scans for suspected
33-74 years) with biochemical recurrence (calcitonin > 10 ng/L) pheochromocytoma or paraganglioma were analysed. These
after primary surgery performed an 18F-FCH PET/CT between scans were performed using medium-energy general purpose
May 2014 and March 2017 with a minimal follow-up of 2 years. collimators on SPECT/CT systems that had been calibrated for
18
F-FCH PET/CT examination included a three-phase scan of 123
I imaging. The injected activity and patient’s weight were
the head, neck and upper mediastinum (5 min, 45 min and used to calculate standard uptake values (SUVs). The maximum
90 min post application) and a whole-body scan (60 min post SUV in the adrenal glands were recorded. The mean SUV in a
application). Calcitonin and CEA levels before the PET/CT scan 3cm spherical VOI defined in the right liver lobe was used to
were measured. Suspicious lesions were either histologically calculate the adrenal glands-to-liver ratios (ALRs) [1]. The normal
analysed after surgery or evaluated based on FNAB or follow- and abnormal SUVs and ALRs were compared, using an unpaired
up imaging. Results with p < 0.05 were considered statistically two-tailed t-test assuming unequal variance. Results: Seven of
significant. Results: 18F-FCH PET/CT was positive in 16/20 the patients were diagnosed with pheochromocytoma, 5 with
patients (80%) with calcitonin > 10 ng/l, and in 13/14 patients paraganglioma and 4 were found to have no neuroendocrine
(93%) with calcitonin > 150 ng/l. Based on PET/CT, 8 patients disease. The average ±standard deviation(range) mean SUV
were reported as having only neck metastases (5 diagnosed in the liver was 2.14±0.93 (0.76-3.59). The average maximum
on follow-up imaging; 1 MTC and 2 benign on histology), while SUV in the normal adrenal glands in patients found to have no
12 were reported as having distant metastases (7 diagnosed disease was 5.83±2.25 (2.44-8.91) and the corresponding ALRs
on follow-up imaging; 2 MTCs and 2 benign on histology; 1 were 2.45±0.98 (1.23-4.39). The average maximum SUV in 7
lesion unconfirmed). Lesions defined as distant metastases abnormal adrenal glands of the pheochromocytoma patients
on PET/CT were visualized in the mediastinum (6/12), bones was 27.58±33.32 (7.00-102.22) with ALRs of 10.82±8.33 (4.40-
(5/12), liver (3/12), distant lymph nodes and soft tissues (2/12) 28.47). For the extra-adrenal masses of the paraganglioma
and lungs (1/12). One patient had diffuse sclerotic bone patients the average maximum SUV was 31.84±33.32(15.05-
lesions visible on CT that were not 18F-FCH avid (histologically 45.41) with ALRs of 20.22±12.16(7.13-33.52). These differences
unconfirmed finding). For neck metastases 18F-FCH PET/CT had between the normal and abnormal ALRs were statistically
100% sensitivity (95% CI 48-100%) and 65% specificity (95% CI significant with a p-value of 0.038; however the maximum SUVs
43-84%). The sensitivity of 18F-FCH PET/CT for the detection of were not statistically different (p-value 0.135). There were no
distant metastases was 83% (95% CI 36-100%). Patients positive statistical differences between the extra adrenal paraganglioma
S125 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

lesion and pheochromocytoma abnormal adrenal SUVs or SUVmax were 3 (2.3-3.4) and 8.6 (6.3-12.2); HU were 7.8 (-1.2-14.8)
ALRs (p-values 0.769 and 0.181 respectively). Conclusion: and 31.8 (26.9 and 36.9); TLG were 8 (4.4-14.3) and 27.9 (17-56.6)
The statistically significant difference between the ALRs for and T/LR 1 (0.8-1.3) and 3.4 (2.5-4.9) in benign and malignant
the normal and abnormal adrenal glands without overlap in adrenal lesions, respectively. Based on AUC, adrenal lesion
the range of values shows this semi-quantitative approach to ADMI, SUVmax and T/LR had the similar highest diagnostic
be useful in the pheochromocytoma diagnosis. However the performance for predicting malignant lesions (AUC:0.991, 0.992
maximum SUVs were not statistically different for this group of and 0.988 p=0.000), respectively. Multivariate logistic regression
patients and the range of SUVs did overlap. Therefore the ALR analysis revealed that adrenal lesion SUVmax and ADMI was an
effectively adjusts to the physiological uptake using the liver independent predictive factor for malignancy rather than TLG.
uptake, which was shown to vary widely for these patients. This Conclusion: Using a new parameter that consist of metabolic
investigation is to continue. References: 1. van Berkel A et al. J and morphologic feature of the adrenal lesions (ADMI) was
Nucl Med. 2015 Jun;56(6):839-46. statistically highly significant for differentiating benign from
malignant lesions, with high NPV. This analytic technique may
facilitate diagnosing of the adrenal lesions but needs further
OP-300 large series studies. References: None.
May It Be A New Parameter Of 18F-FDG PET/CT In
Differentiating Between Benign And Malignant Adrenal
Lesions: Adrenal Densitometabolic Index OP-301
E. Ciftci1, T. Y. Erdil2, Ü. Erkorkmaz3, H. T. İlçe1; Metabolic tumour volume on FDG PET predicts survival for
1
Sakarya University, School of Medicine, Research And Training patients with neuroendocrine tumours (NENs)
Hospital, Department of Nuclear Medicine, Sakarya, TURKEY, D. Chan1,2, G. Schembri2, P. J. Roach2, M. Johnson2, N. Pavlakis2, S.
2
Marmara University, School of Medicine, Research And Training Clarke2, D. L. Bailey2, E. Bernard2;
Hospital, Department of Nuclear Medicine, Istanbul, TURKEY, 1
University of Sydney, St Leonards, AUSTRALIA, 2Royal
3
Sakarya University, School of Medicine, Research And Training North Shore Hospital, St Leonards, AUSTRALIA.
Hospital, Department of Biostatistics, Sakarya, TURKEY.

Aim/Introduction: 18-Fluorodeoxyglucose (FDG) PET avidity


Aim/Introduction: Several reports have documented the ability in NENs has been associated with higher grade disease. FDG
of PET/CT to differentiate benign from malignant adrenal diseases avidity and high SUVmax have been demonstrated to predict
focusing on the ability of functional and metabolic advantages poor outcome. Quantitative metrics of FDG PET, specifically
of PET. This study evaluates the diagnostic importance of metabolic tumour volume (MTV) and total lesion glycolysis
a new parameter that consisting of the densitometric and (TLG), have been shown to be prognosticators in other
metabolic proporties of the lesion measured by 18F-FDG PET/ malignancies, but these have not been investigated to date in
CT in differentiating between benign and malignant adrenal NETs. Materials and Methods: Patients with NEN undergoing
lesions in cancer patients. Materials and Methods: In this 18
F-FDG at Royal North Shore Hospital were retrospectively
retrospective study, we evaluated 18F-FDG PET/CT parameters included (2012-18). Images were analysed using MIM software
of adrenal lesions of follow-up cancer patients referred to version 6.8.3, with automated segmentation (SUV cutoff of
our clinic between January 2017 and April 2019. Diagnosis 4) followed by contour verification by a nuclear medicine
of adrenal malignant lesions was based on interval growth, physician and manual segmentation where required. Variables
reduction after chemotherapy or MRI findings. For PET images, collected included patient age, histological grade, MTV, TLG, and
the ROI was placed within the adrenal mass while avoiding SUVmax/SUVmean. The primary outcome was overall survival (OS),
peripheral area. Also, ROIs were placed at the same level of an and the secondary outcome was progression-free survival (PFS).
adrenal mass on the unenhanced CT images. Based on these Univariate (UV) and multivariate (MV) analyses were performed
values, a new parameter “Adrenal Dansitometabolic index for OS and PFS for MTV and TLG separately. For univariate
(ADMI)” was calculated as the square root of the multiplication analysis, the median MTV and TLG were used to dichotomize
of SUVmax and HU values. Besides this, also analysis of mostly the cohort. MTV/TLG for NENs of different histological grade
used metabolic parameters such as SUVmax (maximum were compared using ANOVA. Results: 190 patients were
standard uptake value) and Tumor SUVmax/ Liver SUVmean included (median age 63.5, 49% female). Primary site: 42% small
ratio (T/LR), morphologic and metabolovolumetric parameters bowel, 32% pancreas, 15% other GI, 6% lung, 6% other. Grade
as Hounsfield Units (HU), metabolic tumor volume (MTV) and for GEPNENs: G1 37%, G2 40%, G3 15%, unknown 8%. Median
total lesion glycolysis (TLG) of adrenal lesions were calculated. MTV was 4.83mL and TLG was 29.22. Patients with high MTV had
PET/CT parameters were assessed using the Mann-Whitney U worse median OS compared to those with low MTV (29.7mo vs
test and receiving operating characteristic analysis. Results: 204 not reached, HR 4.1, 95% CI 2.25-7.49, p<0.00001). Considered
adrenal lesions in 181 cancer patients (121M/60F; mean±SD age as a continuous variable, MTV predicted for poorer OS on UV
65±10.6 years) underwent FDG PET/CT for tumor evaluation. Of (p<0.00001) and MV (p=0.003) analysis. Whilst histological grade
those 115 malign, 89 benign adrenal lesions were exist. ADMI was significant on both UV and MV, SUVmax was significant on
values (median (%25-75)) were 4.6 (1.7-6.5) and 16.9 (13.4-19.5); UV (p<0.00001) but not MV (p=0.76). Tumours of higher grade
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S126

had higher MTV (mean MTV - G1: 39.6mL, G2: 107mL, G3: 337mL; dimension (p=0.0002, p<0.0001 and p=0.0007, respectively),
p=0.0001 by ANOVA). Conclusion: Quantitative analysis of FDG remaining significant also when adjusting for multiple testing
PET in NEN is feasible. High MTV/TLG are predictors of poor (p=0.0023, p<0.0001 and p=0.0105, respectively). Entropy was
prognosis in NEN. Further analyses are underway to investigate significantly positively predictive for G (p=0.0236, but was
a larger cohort of NEN patients. References: 1. Binderup et al, not confirmed after p-value adjustment: p=0.3302). ZP was
Functional imaging of neuroendocrine tumors: a head-to-head predictive for the number of involved lymph nodes (p=0.0372,
comparison of somatostatin receptor scintigraphy, 123I-MIBG but not confirmed after p-value adjustment: p=0.5215). Co-V
scintigraphy, and 18F-FDG PET, J Nucl Med. 2010 May;51(5):704- was predictive for disease-free survival at 24 months (p=0.0055),
12. 2. Bahri et al, High prognostic value of 18F-FDG PET for not confirmed after p-value adjustment, probably due the low
metastatic gastroenteropancreatic neuroendocrine tumors: a number of events (n=6). 18F-FDG TA: IV, SZV and homogeneity
long-term evaluation. J Nucl Med. 2014 Nov;55(11):1786-90. doi: were significantly positively predictive for tumour dimension
10.2967/jnumed.114.144386. Epub 2014 Oct 6. (p<0.0001, p<0.0001 and p=0.0017, respectively) also when
adjusting for multiple testing (p= p<0.0001, p=0.0004 and
p=0.0231, respectively); IV and SZV were positively predictive
OP-302 for angioinvasion (p=0.0134 and p=0.0034, respectively) with
Texture analysis of dual tracer 68Ga-DOTATOC and only SZV confirmed after p-value adjustment (p= 0.0481).
18F-FDG PET/CT for preoperative risk assessment in Conclusion: Specific texture features derived from preoperative
pancreatic neuroendocrine neoplasms 68Ga-DOTATOC and 18F-FDG PET/CT could non-invasively
P. Mapelli1,2, M. Salgarello3, S. Pasetto3, S. Partelli1,4, P. Rancoita5, predict specific tumour characteristics. The retrospective nature
J. Doraku3, F. Muffatti4, V. Andreasi1,4, L. Gianolli2, M. Falconi1,4, M. of the study and its limitations (i.e. small sample, unbalance of G
Picchio1,2; categories) advocate the need of a further validation on larger
1
Vita-Salute San Raffaele University, Milan, ITALY, 2Nuclear prospective cohorts. References: None.
Medicine Department, IRCCS San Raffaele Scientific Institute,
Milan, ITALY, 3Department of Nuclear Medicine, Sacro
Cuore Don Calabria Hospital, Negrar, ITALY, 4Pancreatic OP-303
Surgery Unit, Pancreas Translational & Clinical Research Texture analysis of 68Ga-DOTATATE positron emission
Centre, IRCCS San Raffaele Scientific Institute, Milan, ITALY, tomography and computed tomography images as a
5
University Centre of Statistics in the Biomedical Sciences, prognostic biomarker in adults with neuro-endocrine
Vita-Salute San Raffaele University, Milan, ITALY. cancers treated with 177Lu-DOTATATE
C. Atkinson1, B. Ganeshan2, M. Gaze2, R. Endozo2, S. Wan2, M.
Aldridge2, A. Groves2, K. Miles2, J. Bomanji2;
Aim/Introduction: Aim of the present study is to carry on 1
Queens Hospital, Romford, UNITED KINGDOM, 2University
an explorative assessment of texture features, obtained from College London Hospitals, London, UNITED KINGDOM.
68Ga-DOTATOC and 18F-FDG PET/CT images that might define
a preoperative risk profile in patients affected by pancreatic
neuroendocrine neoplasms (PanNENs). Materials and Aim/Introduction: Neuroendocrine tumors (NETs) are a rare,
Methods: A retrospective analysis was performed including61 heterogeneous group of cancers whose behavior can be hard
patients (38 males, 23 females; mean age: 58.4 years, range 15- to predict. A better understanding of prognosis would aid
84) who underwent both a 68Ga-DOTATOC and a 18F-FDG PET/ individualized management decisions. We aim to demonstrate
CT before surgery for PanNEN between 2011 and 2017. For all the prognostic potential of tumor heterogeneity and avidity
patients histological and follow-up data were available. PET/ in NETs using PET and CT textural analysis (PTA & CTTA) and
CT scans were qualitatively interpreted. Texture analysis (TA) standardized uptake values (SUV). Materials and Methods: The
was applied to PET images of both scans; volumetric region of baseline 68Gallium-DOTATATE PET/CT scans of 49 prospectively
interests (VOIs) were drawn on positive findings and Chang-Gung recruited patients with NETs (carcinoid, pancreatic, thyroid,
Image Texture Analysis (CGITA) software package for statistical head and neck, catecholamine-secreting and unknown primary
radiomics metrics was used. Selected texture features from both tumours) treated with 177Lutetium-DOTATAE at a tertiary
scans (intensity variability-IV; size zone variability-SZV; Zone center were retrospectively analyzed. Non-contrast CT and PET
percentage-ZP; Entropy; Homogeneity, Dissimilarity; Coefficient heterogeneity was assessed using a commercially available
of Variation-CoV) were analysed with appropriate regression TexRAD texture analysis software (TexRAD Ltd www.texrad.
models to evaluate their possible role in predicting tumour com, part of Feedback Plc, Cambridge, UK) which employed a
characteristics (size, grade G2 vs G1, lymphnodal involvement, filtration-histogram technique. Regions of interest were drawn
angioinvasion). Bonferroni’s correction was applied to account around the most prominent metastases of each patient (up to 5
for multiple testing. P-values less than 0.05 were considered tumour foci) as seen on the 68Ga-DOTATATE PET scan. Gallium
significant. Results: According to the 2017 WHO classification, uptake on PET was quantified as SUVmax and SUVmean.
18 patients had G1, 39 G2 and 4 had G3 PanNEN. The mean Ki-67 Association between imaging and clinical markers with
index was 7.1% (range: 0.9-65). 68Ga-DOTATOC TA: SZV, Entropy progression-free (PFS) and overall survival (OS) were assessed
and IV were significantly positively predictive for tumour using univariate Kaplan-Meier and multivariate Cox regression
S127 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

analysis. Results: Amongst all available clinical factors, presence determined for the spheres. Patient images were assessed for
of lung metastases significantly predicted worse PFS (p=0.026) image quality by one expert reader. Scores were given by a five-
and having thyroid primary NET negatively impacted on OS grade scale (1=unacceptable to 5=very high image quality).
(p=0.012). Measures of texture heterogeneity (quantified as Results: Similar SNR were obtained in the truncated phantom
kurtosis, entropy and skewness) on filtered (coarse texture and patient images for a 2-minute acquisition time with beta-
scale) CT and unfiltered PET images predicted PFS (CT coarse value 700 and 1-minute acquisition time with beta-value 1100,
kurtosis: p=0.05, PET entropy: p=0.01, PET skewness: p=0.03) compared to the clinical protocol (3min;beta500). The recovery
and OS (CT coarse kurtosis: p=0.05, PET entropy: p=0.01, PET of the 2-minutes images and the 1-minute images was within
skewness p=0.02). Conventional PET parameters such as SUVmax +-10% for sphere sizes 10-37 mm and up to -30% for smaller
and SUVmean showed trends towards predicting outcome but spheres relative to the 3-minute images. The SNR was retained
did not reach statistical significance. Multivariate Cox analysis in liver and fat and the scored image quality was considered
identified that CTTA (coarse kurtosis: HR=2.57, 95%CI=1.22- equivalent for the three reconstructions: 2.1 (3min;beta500),
5.38, p=0.013) was an independent predictor of PFS and PTA 2.2 (2min;beta700) and 2.0 (1min;beta1100). Conclusion: Our
(unfiltered skewness: HR=9.05, 95%CI=1.19-68.91, p=0.033) study shows that it is possible to administer 0.8 MBq/kg with an
independently predicted OS. Conclusion: 68Ga-DOTATATE PET/ acquisition time of 3 minutes, with preserved assessed image
CT texture heterogeneity and SUV measurements could act as quality, constant SNR and a limited decrease in the recovery
prognostic biomarkers in NETs and potentially playing a key role when the beta-value is increased, i.e. a higher number of
in risk stratifying these patients. References: None. patients per batch can be examined. References: None.

612
OP-304 UEMS/EBNM Clinical Audit Session & New
Decreased administered activity for 68Ga-DOTATATE with
preserved assessed image quality
Fellows of EBNM
A. Stenvall1, L. Jönsson1,2, B. Olsson3, A. Svensson3, G. Brolin1, H.
Almquist3, C. Hindorf1; Monday, October 14, 2019, 8:00 - 9:30 Meeting Room
118/119
1
Radiation Physics, Skåne University Hospital, Lund, SWEDEN,
2
Department of Medical Radiation Physics, Lund University,
Lund, SWEDEN, 3Department of Clinical Physiology and OP-305
Nuclear Medicine, Skåne University Hospital, Lund, SWEDEN. Introduction & Welcome
J. O. Prior;
Médecine nucléaire, Centre Hospitalier Universitaire
Aim/Introduction: For PET/CT tumour imaging with 68Ga- Vaudois, Médecine nucléaire, Lausanne, SWITZERLAND.
DOTA-conjugated peptides, an injected activity of 100-200
MBq 68Ga-DOTATATE is recommended by guidelines. Due to
limited total activity of 68Ga-DOTATATE per batch produced, OP-306
the aim of this study was to evaluate if a lower activity could Quality in Nuclear Medicine
be administered with preserved image quality by optimization M. Hall;
of image reconstruction parameters. Materials and Methods: Royal Free Hospital, Nuclear Medicine, London, UNITED KINGDOM.
Ten patients were included and the NEMA-IQ-phantom with
spheres with diameter 37-10 mm and the Jaszczak-phantom
with spheres with diameters of 15.4-4 mm were filled with OP-307
activity concentrations of 68Ga corresponding to tumours in Implementation of Quality Systems in Nuclear Medicine
high activity background (e.g. liver) (41 kBq/ml, 10 kBq/ml, - Why It Matters. An Outcome Analysis of the IAEA’s
SBR4) and tumours in low activity areas (represented by fat) QUANUM
(12 kBq/ml, 0.3 kBq/ml, SBR40). In our clinical protocol patients D. Paez;
are administered 2.5 MBq/kg body weight and imaged 3 IAEA, Vienna, AUSTRIA.
minutes/bed position (Discovery MI), then reconstructed with
a block-sequential regularization expectation maximization
reconstruction with a beta-value of 500 (Q.Clear). The 3-minute OP-308
patient and phantom images were re-reconstructed to 1 and 2 Quality Improvement with Self-Assessments
minutes/bed position with beta-values from 100 to 1200 in steps J. T. Liukkonen;
of 100. Circular ROIs were drawn in liver and fat in the patient STUK - Radiation and Nuclear Safety Authority
images, and in spheres and background in the CT central slice in Finland, Helsinki, FINLAND.
of the phantoms. Max, mean and standard deviation (std) were
noted. Signal to noise ratios (SNR=mean/std) was calculated
in the phantom background and in liver and fat. Recovery
curves (ratio of measured and true activity concentration) were
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S128

OP-309a OP-312
Clinical Audits in Switzerland - Results of the Pilot Phase Ga-11PSMA
68

and Outlook M. Eiber;


R. Hesselmann; Technische Universität München, Department
Bundesamt für Gesundheit, Strahlenschutz, Bern, SWITZERLAND. of Nuclear Medicine, Munich, GERMANY.

OP-309b OP-313
Presentation of the Accredited Centers since last EANM 18
F-DCFPyL
2018 M. Pomper;
J. O. Prior; John Hopkins Hospital , Radiology, Nuclear Medicine and
Médecine nucléaire, Centre Hospitalier Universitaire Molecular Imaging, Baltimore, UNITED STATES OF AMERICA.
Vaudois, Médecine nucléaire, Lausanne, SWITZERLAND.

OP-314
OP-309c Others
Presentation of the Accredited Centers since last EANM K. Herrmann;
2018 Universitätsklinikum Essen, Nuclear Medicine, Essen, GERMANY.
S. Mirzaei;
Wilhelminenspital der Stadt Wien, Institute of Nuclear
Medicine with PET-Center, Vienna, AUSTRIA. OP-315
Is there Life Beyond PSMA Tracer?
C. Decristoforo;
OP-309d Medical University Innsbruck, Department of
FEBNM Examination - Certificate Handover to the New Nuclear Medicine, Innsbruck, AUSTRIA.
Fellows
A. Boubaker;
Service de Medecine Nucleaire, Clinique de La Source, OP-316
Institut de Radiologie, Lausanne, SWITZERLAND. PSMA Therapy - Where are we now?
R. Hicks;
Department of Nuclear Medicine and PET, Peter
OP-309e MacCallum Cancer Institute, Melbourne, AUSTRALIA.
Group Pictures for New Accredited Centers and New
FEBNM Members
801
701/704 CME 6 - Inflammation & Infection +
Translational and Molecular Imaging Therapy +
Plenary 2: Prostate Cancer ? Reload Radiopharmacy Committee: Molecular Imaging
Technologies for Infectious Diseases
Monday, October 14, 2019, 10:00 - 11:15 Auditorium
Monday, October 14, 2019, 11:30 - 13:00 Auditorium

OP-310
Introduction OP-317
S. Fanti; Imaging of Bacterial and Pathogen Infections, Infectious
Policlinico S.Orsola, University of Bologna, Radiological Disease Specialist’s Point of View
Sciences - Nuclear Medicine, Bologna, ITALY. M. Roestenberg;
Leiden University Medical Center, Department of Infectious
diseases and parasitology, Leiden, NETHERLANDS.
OP-311
18
F-1007PSMA
F. Giesel;
University of Heidelberg, Department of Nuclear
Medicine, Heidelberg, GERMANY.
S129 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

OP-318 803
Imaging of Bacterial and Pathogen Infections, Nuclear
Medicine’s Point of View
EANM Symposium 12 - Physics Committee:
M. Sathekge;
Digital Detection in Clinical NM (PET & SPECT)
Steve Biko Academic Hospital, University of Pretoria,
Department of Nuclear Medicine, Pretoria, SOUTH AFRICA. Monday, October 14, 2019, 11:30 - 13:00 Lecture Hall 312

OP-319
Novel Approaches to Image the Pathogen, OP-328
Radiopharmacy’s Point of View The Physics of SiPM PET Detection
C. Decristoforo; M. Lubberink;
Medical University Innsbruck, Department of PET centre, Department of Radiology, Oncology
Nuclear Medicine, Innsbruck, AUSTRIA. and Radiation Science, Uppsala, SWEDEN.

802 OP-329
The Clinical Aspects of SiPM PET
Joint Symposium 11 - Neuroimaging T. Mognetti;
Committee / ISCBFM: New Applications for Centre Léon Bérard, Département de Médecine
Hybrid Brain PET/MRI Nucléaire et de Radioprotection, Lyon, FRANCE.

Monday, October 14, 2019, 11:30 - 13:00 Lecture Hall 311


OP-330
The Physics of Large FOV CZT Detection
L. Imbert;
OP-323 Centre Hospitalier Universitaire de Nancy, service
Brain PET/MRI - Where Are We Now? de médecine nucléaire, Nancy, FRANCE.
H. Barthel;
University Hospital Leipzig, Nuclear Medicine, Leipzig, GERMANY.
OP-331
The Clinical Aspects of Large FOV CZT
OP-324 A. Verger;
Brain PET/MRI for Neuromodulation Centre Hospitalier Universitaire de Nancy, service
C. Sander; de médecine nucléaire, Nancy, FRANCE.
Harvard Medical School, A. A. Martinos Center for Biomedical
Imaging, Boston, MA, UNITED STATES OF AMERICA.
OP-332
The Clinical Aspects of Large FOV CZT
OP-325 P. Declerck;
Brain PET/MRI in Epilepsy Clinique Saint-Jean, service de médecine
M. Koepp; nucléaire, Brussels, BELGIUM.
University College London, Institute of
Neurology, London, UNITED KINGDOM.

OP-326
Quantification and Standardization in Brain PET/MRI
R. Boellaard;
Dept. of Radiology and Nuclear Medicine, Amsterdam University
Medical Centres, location VUMC, Amsterdam, NETHERLANDS.

OP-327
Summary and General Discussion
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S130

805 OP-334
Optimization of manufacturing process of [11C]-DMDPA for
M2M - Parallel Session: PET Radiosynthesis phase II clinical study
S. Krajewski1, L. Steczek1, J. Ambroziak1, J. Radłowska1, P.
Monday, October 14, 2019, 11:30 - 12:45 Lecture Hall 111 Kaźmierczak2, O. Shamni3, S. Cohen3, E. Mishani3, J. Włostowska1;
1
Research & Development Centre, Synektik S.A., Warszawa,
POLAND, 2Faculty of Pharmacy, Medical University of
Warsaw, Warszawa, POLAND, 3Cyclotron/Radiochemistry/
OP-333 MicroPET Unit, Hadassah Hebrew University Hospital,
Pd catalyzed cross coupling of [11C]MeLi and its application Hadassah Medical Organization, Jerusalem, ISRAEL.
in the synthesis and evaluation of a potential tracer for
vesicular acethylcholine transporter (VAChT)
H. Helbert1,2, B. Wenzel3, W. Deuther-Conrad3, G. Luurtsema1, W. Aim/Introduction: The potential of [11C]dimethyldiphenyl­
Szymanski1,2, P. Brust3, B. Feringa2, R. Dierckx1, P. Elsinga1; ammonium ([11C]-DMDPA) as a PET-myocardial perfusion
1
UMCG, Groningen, NETHERLANDS, 2RUG, imaging (MPI) agent has already been demonstrated [1]. Phase
Groningen, NETHERLANDS, 3Helmholtz-Zentrum I clinical study confirmed that single doses of [11C]-DMDPA
Dresden-Rossendorf, Leipzig, GERMANY. were safe and well tolerated by healthy male subjects when
administered as a single IV bolus injection. Furthermore, [11C]-
DMDPA showed a low radiation exposure in human subjects,
Aim/Introduction: The short half-life of 11C (t1/2 = 20.33 min) therefore it is a very good candidate for MPI. The aim of our
requires ultra-fast reactivity in order to perform efficient study was to optimize the API synthesis process together with
labelling of PET tracers. A recently discovered cross-coupling quality control methods for phase II clinical study. Materials
methodology[1] enables the coupling between aryl bromides and Methods: [11C]-DMDPA was synthetized as previously
and organolithium reagents within seconds and therefore can described [1] using Eckert&Ziegler Modular-Lab Standard: [11C]
be an attractive strategy to access 11C-labelled compounds. In CO2 was reduced to [11C]CH3I, activated to [11C]CH3OTf, reacted
this work several clinically relevant structures were labelled via with methyldiphenylamine (MDPA) to give [11C]-DMDPA and
this method. The scope of the reaction was further explored purified. The optimized synthesis parameters were: LiAlH4 and
and expanded, allowing radiolabelling of highly reactive MDPA concentration, reaction times, solvent and purification
compounds, such as aldehydes. Then we focused our attention cartridge used. The obtained API solution was transferred to the
on the development of a new potential tracer for vesicular Clio dispenser through initial sterilizing filter, where the product
acetylcholine transporter (VAChT) which was enabled by this was formulated by addition of saline solution. The product was
novel cross-coupling of [11C]MeLi. Materials and Methods: [11C] sterilized by a final filtration. The radiochemical and chemical
MeLi was prepared via lithium-halogen exchange by trapping purity were measured by HPLC using Waters XTerra Column. The
[11C]MeI in a solution of n-BuLi. The prepared [11C]MeLi was following method parameters were optimized: gradient, flow
further reacted in a Pd catalyzed cross-coupling reaction with and UV wave length to give reliable results in the shortest analysis
aryl bromides at r.t. for 4 minutes. After quench and evaporation time. The quality of manufactured [11C]-DMDPA was confirmed
of the solvent - or cartridge purification when the reaction was by PET acquisitions carried out on male Wistar rats. Results: The
done on a synthesis module - the mixture was directly purified most favorable synthesis conditions were: 0.1 M LiAlH4 in THF
by HPLC. A series of synthesized vesamicol derivatives were with distillation time of 170 s, [11C]CH3OTf and MDPA reaction
subjected to affinity studies. Results: Several clinically relevant conducted without solvent for 180 s, using for purification one
structures with application in breast cancer imaging and early Waters CM short cartridge. The total radiosynthesis time was
diagnosis of Alzheimer’s disease had been successfully labelled reduced to ≤ 25 min, [11C]-DMDPA was obtained in activities
and the procedure was later on automatized using a cassette up to 30 GBq, with radiochemical yield up to 63% (decay
based synthesis module. Employing this same methylation corrected). The product with highest radiochemical purity was
strategy, novel potential tracers for VAChT were synthesized and achieved when dichloromethane was used as a solvent, while
evaluated in vitro, identifying a compound with good selectivity reaction in pure MDPA gave the highest yield with the purity
for VAChT versus σ1 and σ2 receptors. Conclusion: A new not less than 95%. The most favorable HPLC analysis conditions
labelling methodology was successfully applied to the synthesis were: 14.9 min gradient time with flow of 1.3 ml/min, using 210
of clinically interesting radiotracers, providing the purified target nm for determination of DMDPA and MDPA concentrations. The
molecules in R.C.Y. ranging from 34% to 56% within 30 to 40 validation parameters were: accuracy, intermediate precision,
minutes (EOB). This procedure offers new opportunities in the repeatability and linearity, which met acceptance criteria. The
development of novel tracers, illustrated by the synthesis of a biodistribution results were in good agreement with those
novel VAChT tracer. References: [1]Heijnen D, Tosi F, Vila C, Stuart obtained by O. Jacobson et al. [1]. Conclusion: The synthesis
M, Elsinga P, Szymanski W, Feringa B. Angew. Chem. Int. Ed. parameters of [11C]-DMDPA and HPLC method were optimized
2017, 56 (12), 3354-3359. to ensure reproducible and convenient manufacturing process
for phase II clinical study.
References: [1] O. Jacobson et al. Nuc. Med. Biol. 2013, 40, 967-
973.
S131 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

OP-335 68
Ga-ADAPT6-NODAGA provided the highest tumour-to-organ
Selection Of The Optimal Macrocyclic Chelators For ratios for blood, muscles and major metastatic sites (lung,
Labelling With 111In And 68Ga Improves Contrast Of Her2 liver and bone). 111In-ADAPT6-DOTA provided the highest
Imaging Using Engineered Scaffold Protein Adapt6 tumour-to-organ ratios. This study provides evidences for
J. Garousi1, E. Witting2, S. Lindbo2, A. Vorobyeva1, M. Altai1, M. correlation between labelling chemistry and imaging sensitivity.
Oroujeni1, B. Mitran3, A. Orlova3, S. Hober4, V. Tolmachev1; References: None.
1
Department of Immunology, Genetics and Pathology,
Uppsala University, Uppsala, SWEDEN, 2Department of
Protein Science, KTH Royal Institute of technology, Stockholm, OP-336
SWEDEN, 3Department of Medicinal Chemistry, Uppsala Fluorescein-based 18F labeled probe for pre-targeted PET
University, Uppsala, SWEDEN, 4Department of Protein Science, imaging of cancer cells
KTH Royal Institute of technology, Uppsala, SWEDEN. H. Helbert1,2, D. Samplonius1, S. Blok1, V. Böhmer1,2, G. Luurtsema1,
R. Dierckx1, B. Feringa2, P. Elsinga1, W. Helfrich1, W. Szymanski1,2;
1
UMCG, Groningen, NETHERLANDS, 2RUG,
Aim/Introduction: Albumin-binding domain-derived affinity Groningen, NETHERLANDS.
proteins (ADAPTs) are one of the smallest (5 kDa) non-
immunoglobulin engineered scaffold proteins. These probes
have been designed for imaging of therapeutic targets Aim/Introduction: Bispecific antibodies (BsAb) that at the
expressed in disseminated cancers for personalizing medicine. same time contain binding sites for targets on cancer cells
Previous optimization studies demonstrated that positioning of and for specific small molecules[1] offer the possibility for smart
DOTA chelator at C-terminal of anti-HER2 (HE)3DANS-ADAPT6- pre-targeting approach. In this approach, the antibody is first
GSSC improves biodistribution properties for both 68Ga and 111In administered to the patient, and after some time (usually >24
labels. The available data for other scaffold proteins suggested h) the small molecules, modified with for example a short-
that selection of an optimal combination of radionuclide and lived radionuclide for PET imaging, is injected with the aim
chelator improves imaging sensitivity. The aim of this study was to visualize the tumor. The availability of BsAb with affinity for
to evaluate the influence of the commonly used macrocyclic different tumors, yet the same small molecule, lends versatility
chelators on tumour-to-organ ratios and select the best variant to this approach. Specifically, fluorescein has emerged as the
of ADAPT6 labeled with 68Ga and 111In for PET and SPECT, small molecule of choice[2] to bind to BsAb and therefore we
respectively Materials and Methods: Recombinantly produced aim for developing a tracer based on its core for imaging of
(HE)3DANS-ADAPT6-GSSC was site specifically conjugated with various tumors. Materials and Methods: The synthesis of the
maleimido derivatives of macrocyclic chelators DOTA, DOTAGA, precursor involves a modification of the fluorescein with the
NOTA and NODAGA. All labelled conjugates were purified using introducing an alkyne moiety. The [18F]fluoro-azide compound
size-exclusion Nap-5 columns. In vitro specificity and cellular was synthesized from its corresponding tosylate by [18F]F-. After
processing were studied using HER2-expressing SKOV-3 and HPLC-purification, the [18F]fluoro-azide was used in a copper(I)-
BT474 cell lines. Female BALB/C nu/nu mice bearing SKOV- catalyzed alkyne-azide cycloaddition “click” reaction[3],[4],[5] with
3 (1.6 × 106 receptors/cell) xenografts were used to evaluate the modified fluorescein to afford the final radiotracer [18F]
biodistribution of the radioconjugates with 68Ga at 3h and TPF. The binding of [18F]TPF to bispecific antibodies was then
with 111In at 3h and 24 h. Mice bearing HER2-negative Ramos evaluated in vitro. Results: [18F]TPF was synthesized in 2 steps
xenografts were used for in vivo specificity evaluation. Results: from [18F]F-, the whole labeling procedure takes 2h affording
LC-MS data confirmed the identity and purity of the constracts. [18F]TPF in 37% RCY (d.c.). The compound was then formulated
The radiochemical purity of all conjugates were over 98%. No and was found to be stable in its formulated form as well as
release of radioactivity was observed 3h after incubation with in human serum for several hours (>95% after 2h30). In vitro
500-molar excess of EDTA. In vitro, all probes bound specifically evaluation of the tracer shows significant specific binding
to HER2-expressing cells and internalization was slow. In vivo, all with bispecific antibodies PD-L1/FITC (2.9%) and MCSP/FITC
conjugates rapidly cleared from blood through the kidneys, but (3.3%) immobilized on agar beads. Conclusion: A novel tracer
renal reabsorption was high. Significantly higher uptake of all based on a fluorescein core was developed for pre-targeted
conjugates (p < 0.0005) in HER2-expressing compared to HER2- PET imaging. The radiotracer was stable and could be easily
negative xenografts demonstrated HER2-specificity. The analysis synthesized via copper(I)-catalyzed click reaction. From in vitro
revealed that there was no significant difference between assays, we obtained a proof of principle of its ability to bind to
tumor uptakes of all variants. In the case of 68Ga, NOTA and bispecific antibodies allowing specific imaging of various cancer
NODAGA conjugates cleared significantly (p<0.05) faster from cells with a single tracer. References: [1] R. E. Kontermann, U.
blood and normal tissues than DOTA and DOTAGA conjugates. Brinkmann Drug Discovery Today 2015, 20 (7), 838-847 [2] B.
On the opposite, DOTA and DOTAGA conjugates cleared faster Micheel, P. Jantscheff, V. Böttger, G. Scharte, G. Kaiser, P. Stolley
in the case of 111In. Accordingly, tumor-to-organ ratios for and L. Karawaje Journal of Immunological Methods 1988, 111,
conjugates with rapider clearance was higher. Conclusion: An 89-94 [3] Huisgen, R., Angew. Chem. Int. Ed. 1963, 75 (13), 565-
optimal combination of ADAPT6 targeting agent, radionuclide 598. [4] B. T. Worrell, J. A. Malik, V. V. Fokin Science, 2013, 340,
and macrocyclic chelator increased the sensitivity of imaging. 6131, 457-460. [5] L. Mirfeizi, L. Campbell-Verduyn, R. A. Dierckx,
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S132

B. L. Feringa and P. H. Elsinga, Curr. Org. Chem. 2013, 17, 2108- [3] H.R. Kulkarni, Br. J. Radiol. 2018, 91, 20180308. [4] Y. Tolkach,
2118. Breast Cancer Res.Treat. 2018, 169, 447. [5] M.C. Haffner, Hum.
Pathol. 2009, 40, 1754.

OP-337
Radiopharmacological Evaluation of Cyclohexanediamine- OP-338
Triazole-Peptide Conjugates Labeled via the Al18F- In vivo evaluation of [18F]-5-fluoroaminosuberic acid ([18F]
Approach FASu) isomers as PET imaging agents for different cancer
W. Sihver1, J. Böhme1,2, M. Walther1, R. Wodtke1, F. Reissig1,3, C. types
Mamat1, C. Neuber1, M. Ullrich1, J. Pietzsch1,3, H. Pietzsch1; M. Colovic1,2, H. Yang1, H. Merkens2, N. Colpo2, F. Benard2,3, P.
1
Helmholtz-Zentrum Dresden-Rossendorf, Dresden, GERMANY, Schaffer1,3,4;
2
Ernst-Abbe-Hochschule Jena, University of Applied Sciences, 1
TRIUMF, Vancouver, BC, CANADA, 2BC Cancer Research Centre,
Jena, GERMANY, 3Technische Universität Dresden, Faculty Vancouver, BC, CANADA, 3Department of Radiology, University
of Chemistry and Food Chemistry, Dresden, GERMANY. of British Columbia, Vancouver, BC, CANADA, 4Department of
Chemistry, Simon Fraser University, Burnaby, BC, CANADA.

Aim/Introduction: The Al18F-labeling method is as modern


technique an alternative to conventional 18F-labeling Aim/Introduction: 5-[18F]fluoroaminosuberic acid ([18F]
procedures that allows radiofluorination of biomolecules such FASu) is a novel positron emission tomography (PET) tracer,
as peptides and proteins in a one-step procedure in aqueous which exhibits uptake specific to system xC-, and has shown
solution [1]. In search for versatile applicable chelators, which favourable tumor uptake in lymphoma, ovarian and breast
allow stable binding of both 18F and radiometals such as 68Ga cancer xenografts in mice. With two optically active centres
or 111In, a cyclohexanediamine-triazole-chelator was designed. (positions 2- and 5-), [18F]FASu synthesis by the commonly used
This chelator was conjugated via copper-catalyzed azide- Kryptofix 2.2.2/K2CO3-facilitated fluorination method results in
alkyne cycloaddition (CuAAC) to the well-known binding motif four diastereomers. We recently reported the synthesis of the
(glutamate-urea-lysine) of the prostate-specific membrane optically pure 2S-[18F]FASu from chiral precursors and found
antigen (PSMA) [2-5] complemented by 2-azidoacetyl moiety as that this isomer is preferentially taken up by tumour cells, when
linker unit (ligand L1). Furthermore, ligand L2 was synthesized compared to 2R-[18F]FASu. The aim of this study was to compare
bearing a 6-azidohexanoyl moiety as linker to investigate the the 5-position diastereomers to the racemic (2S,5R/S-) mixture
influence of the linker on the stability of final 18F or radiometal as PET agents in three different tumour models. Materials and
complex. The aim of this study was to investigate the Methods: Cell uptake, biodistribution and PET imaging in mice
radiopharmacological potential of L1 and L2 after radiolabeling bearing glioblastoma (U-87), breast (MDA-MB-231) and prostate
regarding binding properties, cell internalization, and in vivo (PC-3) cancer xenografts were carried out using the 5-position
behavior in a murine prostate cancer model. Materials and diastereomers and the 2S,5R/S- racemic mixture. In vivo
Methods: For the in vitro assays PSMA-positive LNCaP cells were imaging studies were performed on a Siemens Inveon µPET/
used. The incubation with the respective radiolabeled ligand CT scanner at 2h post-injection (p.i.) on animals inoculated
(RCY>95%) was terminated via a cell harvester. Internalization with MDA-MB-231 tumours, and at 1h p.i. on U-87 and PC-3
experiments were carried out by the “acid wash” method. In vivo tumour-bearing mice. Results: We successfully visualised the
studies (biodistribution and small animal PET) were performed xenografts with all three tracer conformations. Quantitatively,
with mice bearing a prostate tumor. Results: In competition the 5-position racemic mixture (2S,5R/S-) displayed similar
assays versus [177Lu]Lu-PSMA-617 (“gold standard”), the affinity image contrast compared to the 5-position diastereomers. The
of non-labeled L1 and L2 was slightly lower than that of PSMA- 2S,5S-[18F]FASu conformation had clearer delineation of U-87
617. Saturation analysis of [68Ga]Ga-L1, [111In]In-L1, and [18F]F-L1 and PC-3 xenografts. Tumour uptake of the isomers was blocked
binding on LNCaP homogenate was comparable to [18F]F-L2 with coinjection of the cold standard, aminosuberic acid (ASu),
binding. The obtained Kd values were in a range of 20 to 30 nM. confirming target specificity. Biodistribution data indicated
Internalization experiments with LNCaP cells revealed a lower that PC-3 tumours had the highest tracer uptake and tumour-
uptake of the differently labeled L1 and L2 conjugates compared to-background ratios. Accumulation (%ID/g) of 2S,5R/S-, 2S,5S-
to [64Cu]Cu-PSMA-617. Furthermore, in vivo behavior of both and 2S,5R-isomers in the tumours were 9.19±1.14, 8.00±1.41,
[18F]F-L1 and [18F]F-L2 was investigated in prostate carcinoma and 7.16±2.13 at 1h p.i. Two-way ANOVA/Tukey’s multiple
bearing mice by biodistribution experiments and small animal comparisons test yielded adjusted p values of 0.8141 and 0.5459
PET imaging. Thereby, PSMA dependent tumor uptake could for 2S,5R/S- v. 2S,5S- and 2S,5R/S- v. 2S,5R- isomer comparisons
be observed. Conclusion: After successful radiolabeling, the respectively, and 0.8992 for the tumour uptake comparison
conjugates L1 and L2 showed promising binding properties between 2S,5S- and 2S,5R-enantiomers. The corresponding
towards PSMA. The chelator presented here offers a flexible tumour-to-muscle ratios were 33.68±9.52, 31.42±4.54, and
platform for radiolabeling of peptides or proteins for various PET 25.33±4.97, respectively. One-way ANOVA test showed no
and SPECT applications. References: [1] F. Cleeren, Bioconjugate statistically significant differences between the groups (p value
Chem. 2016, 27, 790. [2] K. Kopka, J. Nucl. Med. 2017, 58,17S. = 0.1701). MDA-MB-231 tumours had the lowest uptake, at
S133 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

1.13±0.12 %ID/g in the case of 2S,5S-[18F]FASu and 1.25±0.67 administered amount for therapy, relative to KD=10 nM, the
%ID/g in the case of 2S,5R-[18F]FASu, at 2h p.i. Conclusion: We absorbed doses increased by factors of 4±1, 7±5 and 10±8 for
found that in the case of [18F]FASu, chirality at the 5- position KD of 1, 0.1, and 0.01 nM, respectively. Favourable tumour-to-
does not greatly affect tracer biodistribution or tumour uptake kidney ratios could be obtained for all KD when choosing the
in all three tumour models studied. Furthermore, this work optimal amount. Conclusion: For imaging with the commonly
shows potential utility of [18F]FASu for detection of glioblastoma used amount of 1-10 nmol, a significant improvement in
and prostate cancer. References: None. tumour uptake is achieved with an increase in affinity only
with a KD 1-0.1 nM compared to KD=10 nM. A measurement
at 2 h p.i (18F-PSMA) is advantageous. For therapy, the increase
806 in affinity has a large influence on absorbed doses in tissues
with high perfusion. Therefore, especially for ligands with high
Do.MoRe - Parallel Session: Clinical Dosimetry
affinity, both, the given amount and activity must be optimized
and Modeling
to achieve the maximum tumour-to-kidney ratio References:
None.
Monday, October 14, 2019, 11:30 - 12:45 Lecture Hall 112

OP-340
Image quality of a 90Y pretreatment procedure for
OP-339 radioembolisation
Influence of affinity and total ligand amounts on B. Kunnen, M. M. A. Dietze, A. J. A. T. Braat, M. G. E. H. Lam, M. A.
pharmacokinetics and absorbed doses of PSMA-specific Viergever, H. W. A. M. de Jong;
ligands: A simulation study UMC Utrecht, Utrecht, NETHERLANDS.
N. Begum1, G. Glatting1, M. Eiber2, A. Beer1, P. Kletting1;
1
Ulm University, Ulm, GERMANY, 2Technical
University of Munich, Munich, GERMANY. Aim/Introduction: Prior to 90Y radioembolisation, 150 MBq
of 99mTc-magroaggregated albumin (MAA) is administered
to simulate the distribution of 90Y-loaded microspheres.
Aim/Introduction: For theranostic approaches ligands that This pretreatment procedure is performed to estimate the
can be used for both diagnostics and therapy are developed. lung shunt fraction (LSF), to detect potential extrahepatic
However, it is unclear whether ligands optimized for imaging depositions, and to quantify the liver parenchymal dose. The
are also ideal candidates for radionuclide therapy, because of accuracy of the pretreatment scan is currently limited, since
different target values (activity concentrations vs absorbed doses) the MAA particles and microspheres behave differently. Ideally,
and different administered ligand amounts. Therefore, the aim 90
Y microspheres would also be used for the pretreatment
was to investigate the effect of affinity and injected amount of procedure, but making such use inherently safe would limit
prostate-specific membrane antigen (PSMA)-specific ligands on activity to about 100 MBq1, which makes imaging challenging.
the activity concentrations for imaging and the absorbed doses Safe estimation of 90Y-based LSF has been suggested to be
for therapy. Materials and Methods: In this study, a recently feasible.1 This study investigates if it is also possible to accurately
published whole-body physiologically based pharmacokinetic detect extrahepatic depositions and quantify liver parenchymal
(PBPK) model for PSMA-specific ligands was implemented in dose for low activity 90Y pretreatment scans. Materials and
Simbiology/MATLAB and was used for simulations based on Methods: An anthropomorphic thorax phantom with three
13 virtual patients. The affinity is described by the dissociation extrahepatic depositions (2.0, 4.2 and 8.2 mL) was filled with
constant KD=koff/kon. Therefore, simulations with metastatic 90
Y chloride to acquire an LSF of 5.3% and a tumour to non-
castration-resistant prostate cancer (mCRPC) were conducted tumour ratio (T/N) of 7.9. PET/CT (Siemens Biograph mCT)
for KD of 0.01-10 nM and molar amounts of 1-1000 nmol. The and SPECT/CT (Siemens Symbia T16) images were acquired at
normalized activity concentration after injection (68Ga-PSMA at 2.0 GBq (typical treatment dosage) and 100 MBq (theoretically
1 h and 18F-PSMA at 2 h) for imaging and the absorbed doses safe pretreatment dosage). The LSF, T/N, and liver parenchymal
(177Lu-PSMA activity: (7.3±0.3) GBq) for therapy were calculated dose were measured. In addition, a radioembolisation
for tumour, background and organs at risk (OARs). Results: patient (3.1 GBq injected activity at time of imaging) received
Imaging shows similar concentrations in tumours for KD of 0.1- posttreatment PET/CT and SPECT/CT and was additionally
1 nM and for amounts of 1-32 nmol. A KD=0.01 nM only leads scanned with short acquisition times to simulate 100 MBq 90Y
to the highest uptake if the amount of substance is optimized. pretreatment scans. All SPECT scans were reconstructed with
The activity concentration 2 h after injection of the 18F-PSMA in-house Monte Carlo-based reconstruction software and PET
simulations results in significantly higher values compared to scans were reconstructed using clinical software. Results: At
68Ga-PSMA (e.g. by a factor of 1.3±0.1, using an amount of 10 a pretreatment activity of 100 MBq 90Y, PET/CT overestimated
nmol, a typically administered amount for imaging). In therapy, LSF (+10 pp), underestimated liver parenchymal dose (-3 Gy/
the reduction of KD led to a significant increase in the absorbed GBq), and could not detect extrahepatic depositions. SPECT/
dose in tumours. Using an amount of 100 nmol, a typically CT could detect all three extrahepatic depositions and was as
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S134

accurate for the low as the high activity scan in estimating LSF TOF-PET/CT based EUD formalism is the preferred dosimetric
(-0.7 pp at 100 MBq, -0.2 pp at 2.0 GBq), and liver parenchymal technique as it takes into account distribution heterogeneities
dose (-0.3 Gy/GBq at 100 MBq, +0.2 Gy/GBq at 2.0 GBq). The due to variable microspheres activities tuned by decay and
simulated pretreatment PET/CT patient scan was very noisy and to differences in tumor vascularization. References: (1) Tai
was not representative for the high activity posttreatment scan. A, Erickson B, Khater KA, Allen X. Estimate of radiobiologic
The simulated pretreatment SPECT/CT patient scan showed parameters fromclinical data for biologicallybased treatment
comparable activity distribution as compared to the high activity planning for liver irradiation. IntJRadiatOncol Biol Phys (2008)
posttreatment scan. Conclusion: The reconstructions of a 100 70:900-7. doi:10.1016/j.ijrobp.2007.10.037.
MBq 90Y pretreatment procedure are representative of a high
activity posttreatment 90Y scan when acquired with quantitative
SPECT/CT. References: 1.Kunnen et al. Radioembolization lung OP-342
shunt estimation based on a 90Y pretreatment procedure: a Personalized dosimetry for liver cancer radioembolization
phantom study Med Phys. 2018; 45(10):4744-4753. using computational fluid dynamics
E. Roncali, A. Taebi, M. Rusnak, B. Spencer, D. Caudle, C. Foster, C. T.
Vu;
OP-341 University of California, Davis, CA, UNITED STATES OF AMERICA.
TOF-PET/CT enables valuable EUD estimations in
heterogeneous 90Y distributions
M. Hesse, S. Walrand, F. Jamar, R. Lhommel; Aim/Introduction: Yttrium-90 (Y-90) transarterial
Cliniques Universitaires Saint-Luc, Brussels, BELGIUM. radioembolization (TARE) uses radioactive microspheres
injected into the hepatic artery to deliver internal radiation
therapy to liver tumors. One of the major challenges in making
Aim/Introduction: Several studies have shown the superior TARE more effective is the lack of reliable dosimetry methods
quality of TOF-PET/CT for 90Y imaging, providing better evaluation for dose prediction and dose verification. We present a patient-
of the absorbed dose distribution in the tissues and improving specific dosimetry approach for personalized treatment
dose-response analyses. We recently unified the patient dose- planning based on computational fluid dynamics (CFD)
response relationship for resin and glass 90Y microspheres by simulations of the microsphere transport combined with Y-90
using the Jones-Hoban equivalent uniform dose (EUD) derived physics. Materials and Methods: We developed a three-step
from the PET/CT imaging and assuming a radio-sensitivity α CFD dosimetry tool based on the individual patient Cone-
of 0.036 Gy-1. The aim of this study is to evaluate the accuracy beam CT (CBCT) angiograms performed in standard-of-care
of this PET based EUD estimation in known heterogeneous radioembolization planning: (1) segment the hepatic arterial
activity distributions. Materials and Methods: A hot rod insert tree from the patient CBCT, (2) predict the microsphere
(diameters: 4.8, 6.4, 7.9, 9.5, 11.1, 12.7 mm) placed at the bottom distribution using CFD with boundary conditions, (3) calculate
of a cylindrical Jaszczak phantom set in the vertical position was the absorbed dose based on the microsphere distribution with
imaged on a 590ps TOF-PET. A typical patient attenuation was Y-90 physics modeling. The hepatic arterial tree was segmented
reached by adding a 13cm-thick attenuating support under the for 2 patients from CBCT images acquired during treatment
phantom. A two bed 20min/position acquisition was performed planning with an Artis Zeego (Siemens Healthineers). The
after pouring a 3GBq 90Y - 300ml DTPA water solution into the microsphere transport was predicted using multiscale CFD
phantom, resulting in a 115 Gy mean absorbed dose in the 6 modeling [1]. The predicted microsphere distribution was
sectors. The acquisition was repeated after adding 300ml DTPA convolved with a Y-90 dose kernel computed with GATE [2] to
water solution reducing the mean absorbed dose to 57 Gy. calculate the dose distribution. These patients were enrolled
These doses are typical values used as response threshold for in pilot study for which they received an additional positron
glass and resin spheres, respectively. The PET spatial resolution emission tomography (PET) scan after radioembolization to
was modeled and the EUDs were computed using a 90Y dose image the Y-90 distribution. Results: The CBCT angiograms of
kernel. True EUDs were computed from the phantom drawing two subjects were used to segment the hepatic arterial tree.
using a radio-sensitivity extracted from EBRT in vivo studies (1). The segmented structures included one inlet at the CHA, and 23
Results: All rods larger than 7 and 6 mm were visible for the and 46 outlets for subject 1 and 2. The smallest detected outlet
57 and 115 Gy setups, respectively. Using the same 0.036 Gy-1 α diameter was ~0.5 mm, indicating the ability of our method
value, a good agreement (deviation < 8%) was found for both to segment small vessels. The vessels feeding the tumors,
setups between the PET based EUDs data and the true values for the liver Couinaud segments, and the injection points were
rod diameters larger than 9 mm. Such heterogeneity scales are identified using the CBCT images and the 2D digital subtraction
typically observed in biopsies post 90Y liver radio-embolization. angiograms (DSA) acquired during the planning. Here the
EUD overestimation of about 30% was observed for the smaller microsphere transport was assumed to follow that of the blood,
rod sectors. Conclusion: This study confirms the PET ability which allowed us to calculate a distribution of the spheres at
to image heterogeneous 90Y distribution allowing an accurate the outlets and calculate the subsequent dose distributions. We
EUD estimation. This explains the good patient dose-response qualitatively compared the predicted dose with the Y-90 PET
obtained previously for both microspheres types. Moreover images acquired 2h after the microsphere delivery. Conclusion:
S135 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

We demonstrate the feasibility of developing a complete enable characterisation of volumes beyond that practically
framework for personalized Y-90 microsphere simulation and measurable and enables scope to extend this work for different
dosimetry, using patient-specific input parameters. References: shaped inserts with varying lesion to background concentration
1. Westerhof, N., J.W. Lankhaar, and B.E. Westerhof, The arterial ratios. These phantoms have been used for quantification in the
Windkessel. Med Biol Eng Comput, 2009. 47(2): p. 131-41. 2. SOLLID and MEDIRAD clinical trials. References: None.
Jan, S., Ongoing developments in GATE and what to expect in
upcoming versions, in IEEE NSS/MIC, Gate User Meeting. 2015:
San Diego, USA. OP-344
Quantification of the Trabecular Bone Volume Fraction
with Dual Energy Quantitative CT to Calculate Patient-
OP-343 Specific Radionuclide S Values for Bone Marrow Dosimetry
Improving resolution recovery factors using 3D printed M. Salas Ramírez, J. Tran-Gia, U. Gbureck, A. Kosmala, M.
phantoms and Monte Carlo for quantitative imaging and Lassmann;
dosimetry University of Würzburg, Würzburg, GERMANY.
J. Gear, F. Leek, G. Flux;
Royal Marsden NHSFT, Sutton, UNITED KINGDOM.
Aim/Introduction: The correlation between bone marrow
toxicity and absorbed dose in radionuclide therapies is still
Aim/Introduction: Accurate absorbed dose calculations not well defined. Improvements of the techniques for patient-
require recovery factors applied post-reconstruction to correct specific skeletal dosimetry have led to the development of
for partial volume effects. The IEC PET phantom is widely increasingly realistic 3-dimensional geometry models for
available with insert diameters ranging from 10 to 37mm, which Monte-Carlo simulation of radiation transport. These models
whilst appropriate for PET are too small to fully characterise the require as inputs marrow cellularity (obtained by MR imaging)
recovery curve of SPECT isotopes such as Lu-177 or I-131. The and trabecular bone volume fraction (TBVF) in the patient bone
aim of the study was to improve characterisation of the recovery marrow to calculate patient-specific radionuclide S values for
curve and reduce standard uncertainty in recovery factors by bone marrow dosimetry. Therefore, the aim of this study was
complimenting the IEC phantom images with those using 3D to validate a phantomless post-reconstruction quantification
printed inserts and Monte Carlo derived images. Materials and method which enables the calculation of TBVF for bone marrow
Methods: Nine 3D-printed spheres with internal diameters of dosimetry in molecular radiotherapy based on dual energy
8 to 65mm where designed and manufactured using a Connex quantitative computed tomography (DEQCT). Materials and
photopolymer 3D printer. An adapted lid for the IEC phantom Methods: First, a phantomless post-reconstruction DEQCT
was manufactured to mount the spheres. Inserts were filled with method based on x-ray beam profile and detector sensitivity
Lu-177, I-131 and Tc-99m. Images were acquired on a Siemens function was implemented for a dual source computed
Symbia SPECT/CT system equipped with the appropriate tomography (DSCT) system and a SPECT/CT. The method was
collimator. A SIMIND Monte Carlo simulation was also performed validated in a homemade phantom composed of five 50-ml
of the SPECT/CT system with a cylindrical phantom containing vials; three of them contained hydroxyapatite (HA) in different
spherical inserts of diameter 10 - 80mm. All real and simulated concentration in a water equivalent medium, the last two
SPECT images were quantitatively reconstructed using an contained a mix of agar, paraffin (fat) and hydroxyapatite (HA).
OSEM algorithm using attenuation and scatter correction Additionally, the European Spine Phantom (ESP) was used to
but without collimator detector response. VOIs matching simulate the vertebral geometry. Bone mineral content (BMC)
the known insert volume were drawn over the reconstructed of each phantom vertebra and bone mineral density (BMD) in
images and the recovery coefficient taken as the ratio of the the spongiosa region of each phantom vertebra were measured
mean activity concentration measured in the VOI to the known with the DEQCT method and dual-energy x-ray absorptiometry
concentration. Results: With the additional images the recovery (DEXA). Furthermore, the BMC was measured in lumbar vertebrae
curve could be properly characterised up to volumes of 300ml, 1 (LV1) and 2 (LV2) of a patient using DEQCT and DEXA. Lastly, the
compared to only 26ml for the standard inserts. Recovery TBVF was quantified in the spongiosa region of each vertebra.
curves, fitting parameters and associated uncertainties for Results: Measured values of HA volume fraction and nominal
the different datasets were generated according to EANM values in the homemade phantom showed good correlation
guidelines. The standard uncertainty in fit parameters was (maximum error: 14.2%). Quantification of BMC (whole vertebra)
reduced by 15% and 20% when 3D printed and Monte Carlo and BMD (spongiosa) in the ESP showed a good agreement
derived datasets were included. For a Lu-177 lesion of volume between measured values and nominal values (relative error
of 150ml the calculated recovery factor varied from 0.81 to 0.74 [0.69%, 7.45%] for BMCSPECT/CT, [1.10%, 7.71%] for BMCDSCT, [5.44%,
when the additional datasets were included. Conclusion: The 31.96%] for BMDSPECT/CT, and [10.0%, 59.38%] for BMDDSCT).
ability to extend the recovery curve data beyond the insert Quantification of BMC in the patient vertebrae showed relative
volumes within the IEC phantom is essential for accurate image errors of 7.61% (LV1) and -8.39% (LV2) between DEXA and DSCT.
quantification and dosimetry. 3D printed inserts are a useful and The TBVF values were 0.071 (LV1) and 0.072 (LV2). Conclusion:
cost effective tool for achieving this. Monte Carlo simulations Our study shows that DEQCT using a commercial hybrid SPECT/
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S136

CT system enables the quantification of TBVF in a clinical setting. for prototyping nuclear medicine phantoms. This represents
However, this method is sensitive to the image reconstruction a major step towards a quantification of sub-organ activity
kernel and the chemical description of the reference material distributions which could, eventually, facilitate reliable absorbed
and requires a good characterization of the x-ray beam and dose calculations for radionuclide therapies. References: [1]
detector. References: None. Thomas;PhysMedBiol;2016;61(22).

807
OP-345 Pitfalls & Artefacts 4 - Interactive Clinical Cases
Towards a Patient-Specific Kidney Dosimetry in
Radionuclide Therapy
- Oncology & Theranostics Committee: PSMA
J. Tran-Gia, H. Neumayer, M. Lassmann;
Imaging
University of Würzburg, Würzburg, GERMANY.
Monday, October 14, 2019, 11:30 - 13:00 Lecture Hall 113

Aim/Introduction: SPECT/CT-based quantification of sub-


organ activities is one of the major challenges in radionuclide
therapies. The aim of this study was to fabricate a patient-specific OP-346
two-compartment kidney phantom (medulla and cortex) and Common Pitfalls of 68Ga-PSMA 11
validate it with a post-therapy SPECT/CT of the same patient C. Artigas;
(Lu-177-DOTATATE). Materials and Methods: To enable a good Ist Bordet, Nuclear Medicine, Brussels, BELGIUM.
differentiation of cortex and medulla, but also a validation
of the resulting activity distribution, a patient for whom a
venous-phase contrast-enhanced full-dose CT as well as a post- OP-347
therapy SPECT/CT acquisition were available, was selected. Un-usual Findings and Pitfalls of Different PSMA
Segmentation of the kidney was performed in 3D Slicer [1]: First, Compounds
a 3D volume around the right kidney was cropped out of both F. Ceci;
CTs, and the full-dose CT was co-registered to the low-dose CT University of Turin, Nuclear Medicine, Torino, ITALY.
(affine registration). Next, medulla and cortex were separately
segmentated based on the co-registered venous-phase CT and
exported as STL-files. Further modelling of the kidney phantom OP-348
was performed in Autodesk Netfabb 2019: After generating Pitfalls and Variants of 68Ga-PSMA 11 in CRPC -
shells from both segmentations (shell thickness: 1mm), filling Implications for RLT
tubes and attachment rods were inserted. The cortex was split W. Fendler;
into two separate shells for separate printing. A stereolithography University of Essen, Nuclear Medicine, Essen, GERMANY.
3D printer (Form 2, Formlabs) was used for manufacturing the
phantom. After 3D printing (resin: Clear V4), the three parts were
processed as suggested by the manufacturer. After agglutination 808
using a two-compoment adhesive, plastic threads were glued
into the filling tubes (M4) and the attachment rod (M6). Finally,
Clinical Oncology - Featured Session:
the entire phantom was clear coated. A Lu-177 SPECT/CT
Implementing Radiomics into Technical Practice
acquisition was performed (phantom mounted in Jaszczak
cylinder, activity concentration ratio of 5:1 [cortex:medulla]). Monday, October 14, 2019, 11:30 - 13:00 Lecture Hall 114
The total kidney activity of 62.6 MBq was based on the patient
data. Acquisition parameters were the same for patient and
phantom. Results: The venous-phase contrast-enhanced CT
image considerably facilitated the differentiation of cortex and OP-349
medulla. Although, in general, a good visual match between Scenarios and Challenges in Clinical Implementation of
the SPECT reconstructions of patient and re-printed kidney Radiomics
was achieved, minor differences were found in the cortex- D. Visvikis;
medulla border region. This could potentially be improved INSERM UMR1101, LaTIM, CHRU Morvan, Bat 1, et 1, Brest, FRANCE.
by varying the cortex-medulla activity concentration ratio. As
many Lu-177-labelled radiopharmaceuticals are accumulating OP-350
in large parts in the renal tubules in this border region, a three- Extraction of histogram and texture features from
compartment model (cortex, medulla, intermediate tubules parametric 18F-FET PET images for molecular-genetic and
region) would further improve the image quantification. histologic differentiation of gliomas
Conclusion: Additional imaging information such as contrast- L. Kaiser1, M. Grosch2, S. A. Ahmadi2, M. Unterrainer1, A. Holzgreve1,
enhanced CT or dedicated MRI techniques should be exploited E. Mille1, A. Gosewisch1, J. Brosch1, B. Suchorska3, N. Navab4, J. C.
S137 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

Tonn3, S. Ziegler1, P. Bartenstein1, N. L. Albert1, G. Böning1; OP-351


1
Department of Nuclear Medicine, University Hospital, LMU 18F-FDG PET/CT radiomic predictors of molecular markers
Munich, Munich, GERMANY, 2German Center for Vertigo and expression in oral cavity squamous cell carcinoma
Balance Disorders, University Hospital, LMU Munich, Munich, Y. G. Abdelhafez1,2, Y. Dou1, L. Nardo1, T. Yen3, C. Liao3, A. J.
GERMANY, 3Department of Neurosurgery, University Hospital, Chaudhari1;
LMU Munich, Munich, GERMANY, 4TUM Department of 1
University of California Davis, Sacramento, CA,
Informatics, Technical University of Munich, Munich, GERMANY. UNITED STATES OF AMERICA, 2South Egypt cancer
Institute, Assiut University, Assiut, EGYPT, 3Chang Gung
Memorial Hospital and Unviersity, Linkou, TAIWAN.
Aim/Introduction: Besides an improvement of PET
instrumentation or radiopharmaceutical properties, current
research is focussed on various methods aiming to enhance Aim/Introduction: To evaluate the association between
image read-out. For glioma classification, static and kinetic radiomic features extracted from pre-operative 18F-FDG PET/
parameters extracted from dynamic 18F-FET PET data have CT in patients with advanced stage oral cavity squamous
proven to be clinically relevant. In this study, histogram and cell carcinoma (OCSCC) and pathological molecular markers
texture radiomic features were derived from the respective expression. Materials and Methods: The study retrospectively
parametric images calculated on a voxel basis. Materials and included 99 patients with advanced stage OCSCC (pathologic
Methods: 322 patients with a newly diagnosed glioma were TNM stage III=26, IV=73; 93 males, 6 females; median age
included: 128 IDH-Mutant, 194 IDH-wildtype (IDHmut/wt); 91 49 years, range: 29-89). All patients had biopsy-proven SCC
low-, 231 high-grade gliomas (LGG/ HGG). Glioma volumes-of- of oral cavity, locally- or loco-regionally advanced disease
interest (VOI) were segmented with the clinically established with no distant metastasis (M0), and a staging 18F-FDG PET/
1.6 x background threshold, whereby a crescent shaped VOI on CT scan. Patients were treated with surgical resection of the
the contralateral side served as background VOI. Subsequent primary tumor followed by adjuvant chemo(radio)therapy.
histogram and texture analysis was performed using the The maximum pathologic axial tumor size was 33±17 mm.
following parametric images: tumour-to-background ratios Primary tumor from PET images was segmented using absolute
(TBR5-15, TBR5-20, TBR10-30, TBR20-40), late slope (Slope15-40), time-to- isocontour threshold of 40% of the maximum standard uptake
peak (TTP), distribution volume ratio (DVR) from Logan-reference value (SUV). Using TextIriX, a texture analysis plugin developed
tissue model, and net influx rate Ki/V’T from Patlak-reference for OsiriX by our group, a total of 78 radiomic features (including
tissue model. For each parametric image a total of 94 radiomic shape by graphics algorithms, first order, and texture features)
features was extracted. Univariate and multivariate ROC- were extracted. SUVs within the segmented volume were
analyses using logistic regression were performed with 5-fold normalized between the minimum and maximum values, then
cross-validation with stratified folds, aiming to identify IDHwt or discretized into 64-bins to construct the grey-level matrices. No
HGG gliomas. Results: The highest area-under the ROC curve spatial resampling was used. Receiver operating characteristics
(AUC) averaged over 5 folds was obtained for features derived (ROC) curves and area under the curve (AUC) of the extracted
from early static TBR5-15 images and the related parametric features were plotted against molecular markers status of the
images TTP, Slope15-40, and Ki/V’T (a). Parameters derived from primary tumor including TP53, EGFR, BRAF, PIK3CA, FGFR3
the highly correlated TBR20-40 and DVR images tended to yield and HRAS. Results: Small-area low gray-level emphasis was
lower AUC values (b). For the first parameter category (a) the associated with TP53 expression (n=63/99) with AUC of 0.63 (95%
highest univariate AUC values (>0.79) were obtained with confidence interval [95%CI] 0.52-0.74); p=0.03. The following
simple first order statistics such as mean, median, percentage radiomic features were significantly associated with EGFR
volume histograms (PVH), and percentiles. In contrast to this, expression (n=6/99): maximum 2D (AUC:0.78, 95%CI:0.66-0.90;
the features with the highest AUCs within the second parameter p=0.02) & 3D diameters, major & minor axis length, mesh & voxel
group (b) comprised more elaborate texture features, which still volumes, surface area, and run-length non-uniformity, size-zone
yielded only moderate AUCs (<0.77). Multivariate analysis based non-uniformity, and dependence non-uniformity. Axis length
on simple mean values from each parametric image yielded (AUC:0.72, 95%CI:0.57-0.87; p=0.03), gray-level non-uniformity
an AUC of 0.86 for the identification of IDHwt gliomas and dependence non-uniformity, size-zone non-uniformity, run-
0.80 for the identification of HGG. Inclusion of the remaining length non-uniformity, mesh & voxel volumes, and surface
features provided only a moderate improvement (IDHwt 0.87; area were significantly associated with BRAF expression
HGG 0.83). Conclusion: Although texture features allow for an (n=9/99). Both large-dependence (AUC:0.73, 95%CI:0.61-
improved classification of gliomas in case of TBR20-40 and DVR 0.85; p=0.002) and large-area low-gray-level emphasis were
as opposed to mean values, an incorporation of first order significantly associated with PIK3CA expression (n=80/99).
parameters describing 18F-FET kinetics is highly recommended. Kurtosis was marginally associated with FGFR3 expression.
Besides multi-parametric information, a further incorporation of No features were predictive of HRAS status. Conclusion:
information from other imaging modalities might be of interest Radiomic features, extracted from pre-operative 18F-FDG PET/
for future studies aiming to provide an elaborate description of CT images of the primary tumor of advanced stage OCSCC
the tumour microenvironment. References: None. patients, are associated with the expression of some important
molecular markers including TP53, EGFR, BRAF and PIK3CA.
References: None.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S138

OP-352 OP-353
Baseline FDG-PET/CT Radiomics to Predict Outcome in Baseline Radiomic CT Features Differentiate Mediastinal
Lung Cancer Patients Treated with Surgery Masses As Thymic Neoplasms Or Lymphomas
M. Kirienko1, L. Cozzi1, L. Antunovic2, E. Voulaz3, A. Chiti3, M. Sollini1; G. Ninatti1, M. Kirienko1, L. Cozzi1,2, E. Voulaz2, F. Ricci2, C. Carlo-
1
Humanitas University, Milan, ITALY, 2Humanitas Stella1,2, P. Zucali2, A. Chiti1,2, M. Sollini1;
Clinical and Research Center - IRCCS, Rozzano (Milan), 1
Humanitas University, Pieve Emanuele (MI), ITALY, 2Humanitas
ITALY, 3Humanitas University, Humanitas Clinical Clinical and Research Center, Rozzano (MI), ITALY.
and Research Center - IRCCS, Milan, ITALY.

Aim/Introduction: To evaluate the ability of computed


Aim/Introduction: The study aimed to identify a radiomic tomography (CT) radiomic features to classify prevascular
signature (from FDG-PET and/or CT) capable of predicting mediastinal masses as thymic neoplasms or lymphomas.
disease-free and overall survival (DFS and OS) in non-small cell Materials and Methods: This is a retrospective single-center
lung cancer (NSCLC) patients undergoing surgery. Materials study. Inclusion criteria: pathologically assessed either thymic
and Methods: This was an update of a retrospective single- neoplasia or lymphoma with at least one mediastinal localization,
center study. Inclusion criteria: patients with a pathological and availability of baseline non-contrast enhanced CT. Exclusion
diagnosis of NSCLC, surgically treated between 01/01/2011 criteria: age <16 years; mediastinal lymphoma lesion <4 cm. We
and 30/11/2016 in our institution, and availability of baseline selected 108 patients (M:F=47:61, median age 48, range 17-
FDG-PET/CT. Exclusion criteria: age <18 years. A cohort of 259 79) and divided them into a training and a validation group.
patients (M:F=177:82, mean age 70±8.4 years) was selected. Mediastinal masses were manually delineated using LIFEx and
Then, we randomly assigned the patients to a training and Eclipse software. Two different resampling settings (1x1x4 and
a validation group. Lung lesions were semi-automatically 2x2x2) were used. Radiomic features (n=41) were extracted using
segmented on PET images applying a 40% of SUVmax threshold the LIFEx software and used as predictors in linear discriminant
using a commercial software (PET VCAR, General Electric). analysis (LDA) with backward stepwise variable insertion to
Textural features from both CT and PET were calculated using classify the lesions. Different radiomic models considering
LifeX (www.lifexsoft.org, [1]) and used as predictors. R platform segmentation software and resampling setting were built.
was used for statistical analysis. Kaplan-Meier analysis was Additionally, a clinical model was built considering age, sex, B
used to test the ability of the models to stratify patients with symptoms, lymphadenopathies, autoimmune disorders, and
different outcomes. Covariables significant at univariate analysis white blood cell count. Scoring metrics included sensitivity,
were fed into a multivariate Cox proportional hazard regression specificity, accuracy and analysis of the receiver operating
model that was used to predict DFS and OS. Cox-Snell residuals characteristic curves in terms of area under the curve (AUC).
were used to verify the goodness of the Cox model. Results: Wilcoxon paired test was used to compare the AUCs of the
One hundred thirty patients experienced relapse, 69 died; 40 validation models. A p value <0.05 was considered significant.
patients were lost at follow-up and excluded from the DFS R platform and SPSS were used for statistical analysis. Results:
prediction analysis. For the whole cohort, median DFS and OS Fifty-five patients (27 males, 28 females) were affected by thymic
were 17 (range 1-89) and 28 (range 1-89) months, respectively. neoplasia (52 thymoma, 3 thymic carcinoma) and 53 (20 males,
In the training dataset, the radiomic CT, PET and PET+CT-based 33 females) by lymphoma (39 Hodgkin, 12 Non-Hodgkin, and
models were able to identify low-risk and high-risk patients 2 Grey-zone Lymphoma); median age of 62 (range 26-79)
with respect to DFS (p=0.021, and p=0.007). In the validation and 36 (range 17-79) years, respectively. The radiomic model
dataset the CT, PET and PET+CT-based models confirmed to be that resulted to have the highest performance selected 13 CT
able to predict low vs high-risk disease (p=0.025, p=0.0009, and radiomic features. In the training group, sensitivity, specificity,
p=0.025). Within the OS analysis, in the training dataset radiomic accuracy and AUC resulted 88.2±5.5, 94.3±3.9, 91.3±4.4 and
CT, PET and PET+CT-based models provided the following 0.93±0.05, respectively; in the validation group, the same metrics
performance in differentiating low-risk from high-risk patients: resulted 76.2±7.0, 77.8±5.5, 76.9±6.0 and 0.84±0.06, respectively.
p=0.60, p=0.08, and p=0.035, while in the validation dataset the The clinical model included 4 clinical variables selected by LDA.
CT, PET and PET+CT-based models showed stratification ability In this model, the training group values for sensitivity, specificity,
with the following significance: p=0.05, p=0.08, and p=0.05. accuracy and AUC resulted 88.2±5.5, 82.9±6.4, 85.5±;6.3 and
Conclusion: A radiomic signature, for either CT, PET or PET/CT 0.95±0.05, respectively; while the same metrics in the validation
images, has been identified and validated for the prediction of group resulted 95.2±7.0, 88.9±8.9, 92.3±8.5 and 0.98±0.07,
disease-free survival in NSCLC patients treated with surgery. The respectively. No statistically significant difference was found
combination of PET and CT features was able to stratify lung between the AUC of the best radiomic and the clinical model.
cancer patients with respect to overall survival. These findings Conclusion: CT radiomic model had similar performances to
confirmed our previous results, supporting the prognostic role the clinical one, proving the potential to play a crucial role in
of radiomics. References: 1.Cancer Research 2018;78(16):4786- asymptomatic patients differentiating thymic masses from
4789. lymphomas and, in a selected clinical setting, avoiding invasive
diagnostic procedures. References: None.
S139 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

OP-354 OP-355
Contribution of tumour blood-flow for prediction of Radiomic features of glucose metabolism enable
response to neoadjuvant chemotherapy in breast cancer prediction of bone marrow involvement in mantle cell
using 18F-FDG PET/CT lymphoma
N. Payan1, B. Presles1, J. M. Vrigneaud1,2, A. Cochet1,2; M. Mayerhoefer, C. Riedl, H. Schöder;
1
ImViA laboratory, EA 7535, University of Burgundy, Dijon, Memorial Sloan Kettering Cancer Center, New
FRANCE, 2Department of Nuclear Medicine, Georges- York, NY, UNITED STATES OF AMERICA.
François Leclerc Cancer Centre, Dijon, FRANCE.

Aim/Introduction: Mantle cell lymphoma (MCL) is a rare


Aim/Introduction: The aim of this prospective study is to subtype of B-cell Non-Hodgkin lymphoma, and can be
assess the contribution of tumour blood flow (BF) and tumour associated with an aggressive or, less frequently, an indolent
metabolism heterogeneity in the prediction of pathological course. Bone marrow infiltration, which is routinely assessed
complete response (pCR) to neoadjuvant chemotherapy by bone marrow biopsy (BMB) is present in about 60% of the
(NAC) in patients with newly diagnosed breast cancer (BC). cases at the time of diagnosis. It was therefore the aim of this
Materials and Methods: One hundred and ninety-seven study to determine whether [18F]FDG-PET/CT-derived radiomic
newly diagnosed BC patients underwent a 18F-FDG PET/CT features are predictive of bone marrow infiltration in MCL,
exam before any treatment. Tumour BF and tumour metabolism alone or in combination with laboratory findings. Materials
were extracted from dynamic first-pass and delayed PET images and Methods: Ninety-seven treatment-naïve MCL patients
respectively. Standard PET parameters and texture features (TF) who had undergone [18F]FDG-PET/CT as well as iliac crest
were computed from BF and metabolic parametric PET images. bone marrow biopsy (BMB) were retrospectively included.
The pCR was defined as the absence of residual invasive cancer Standardized uptake values (SUVmax, SUVmean, and SUVpeak)
after NAC in primary tumour and lymph nodes. Multivariate and 16 co-occurrence matrix radiomic features were extracted
logistic regressions were performed to predict pCR using (a) from metabolic tumor volumes of the bony pelvis on pre-
only clinical characteristics such as tumour histological type, therapeutic [18F]FDG-PET/CT. Kendall’s correlation coefficients
hormonal receptors, (b) using clinical and metabolic tumour in combination with Lasso regression analyses was used to
features and (c) using clinical, metabolic and perfusion tumour determine the three best radiomic features for prediction of
parameters. Five stratified k-fold cross-validation experiments, bone marrow involvement. This step was repeated for different
with 80% of the population selected for the training set and absolute and relative thresholds of bone marrow involvement
20% for the testing set, were performed. After univariate feature according to histology: Abs10% (absolute involvement >10% of
selections performed on the training sets, hyperparameter the total analyzed bone marrow); Abs20%; Rel10% (involvement
optimization, done via inner cross validations, were then carried >10% of the cellular/red bone marrow); and Rel20%. A multi-
out to maximise the f1 score as recommended for unbalanced layer perceptron neural network was then used for prediction of
classes (pCR: ~25%). Generalisation errors were evaluated on bone marrow involvement, with training-to-validation dataset
the independent test sets through three metrics, the f1 score, ratios of 70% to 30% percent, using only radiomic features, and
the area under the receiver operating characteristics curve then, separately, also including LDA (lactate dehydrogenase)
(AUC) and the accuracy. Results: Models including clinical, and white blood count (WBC). Median areas under the receiver
metabolic and perfusion tumour features yielded to the best operating characteristic curve (AUC) based on five repetitions
test prediction results, with f1 values ranging from 0.44 to 0.67, of the classification step, respectively, were used as main
AUC values from 0.64 to 0.85 and accuracy values from 0.70 to outcome measures. Results: In total, 67/97 patients (69.1%)
0.87. In comparison, the f1 score, the AUC and the accuracy of of the patients showed bone marrow involvement at BMB,
the models using clinical and metabolic features ranged from whereas involvement rates were 35/97 (36.1%) for Abs10%,
0.40 to 0.63, from 0.61 to 0.75 and from 0.73 to 0.82, respectively. 31/97 (32.0%) for Abs20%, 41/97 (42.3%) for Rel10%, and 34/97
For the predictions based on clinical features only, results varied (35.1%) for Rel20%. Based solely on [18F]FDG-PET/CT-derived
from 0.30 to 0.71 for the f1 score, from 0.53 to 0.78 for the AUC radiomic features, median AUC values were 0.77 for Abs10%,
and from 0.63 to 0.87 for the accuracy. For all models including 0.73 for Abs20%, 0.70 for Rel10%, and 0.72 for Rel20%. Based on
clinical, metabolic and perfusion tumour features, various the combination of radiomic features and laboratory features,
TFs, such as correlation or entropy, were selected during the median AUC values were 0.81 for Abs10%, 0.79 for Abs20%, 0.73
univariate selection process which highlights the prognostic for Rel10%, and 0.76 for Rel20%. Conclusion: In MCL, radiomic
value of these parameters. Conclusion: This study showed that features of glucose metabolism may be useful for prediction of
the association of tumour BF with tumour metabolism and bone marrow involvement. Results may be further improved by
clinical parameters enables to improve the pCR prediction and a combination of [18F]FDG-PET/CT-derived radiomic features
highlighted TFs as significant prognostic variables. References: with laboratory parameters. References: None.
None.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S140

810 opposite 19 of 31 (61%) pN1 patients without additional lymph


node metastases on TxWBS (p=0.009). Conclusion: Pre-ablation
Thyroid - Rapid Fire Session: Prognostic Factors
DxWBS could optimize DTC risk stratification and patient-
in DTC
tailored I-131 administration. Selective application of DxWBS
is recommended in patients with pN1 stage or patients at risk
Monday, October 14, 2019, 11:30 - 12:45 Lecture Hall 116 for in situ lymph node metastases, in whom DxWBS results
could change the course of treatment and potentially improve
treatment outcome. Although it enables fitted I-131 dosimetry
and accurate Tg-based follow-up, DxWBS is not recommended
OP-356 to determine thyroid remnant size: it is unrelated to treatment
Radioiodine In Differentiated Thyroid Carcinoma: Can success. References: None.
Diagnostic Pre-Ablation Scintigraphy Optimize Treatment?
E. J. de Koster1, T. Sulaiman2, J. F. Hamming2, A. Schepers2, M. Snel2,
F. H. P. van Velden2, L. de Geus-Oei2, D. Vriens2; OP-357
1
Radboud University Medical Centre, Nijmegen, NETHERLANDS, Clinical implications of radioactive iodine - avid metastatic
2
Leiden University Medical Centre, Leiden, NETHERLANDS. lymph nodes on post-ablation whole body scans in 1-4cm
differentiated thyroid cancer
R. Gao, X. Jia, Y. Wang, L. Yang, G. Zhang, A. Yang;
Aim/Introduction: Changing insights and ongoing The First Affiliated Hospital of Xian Jiaotong Universit, Xi’an, CHINA.
global debate regarding postoperative radioiodine (I-131)
administration in differentiated thyroid carcinoma (DTC) also
stir up the discussion on whether pre-ablation diagnostic Aim/Introduction: Controversy exists in surveillance of low-risk
scintigraphy (DxWBS) could optimize treatment. Materials and differentiated thyroid cancer (DTC), especially in cases with 1-4
Methods: Post-therapy I-131 whole-body scintigraphy (TxWBS) cm tumors. The risk of recurrence/metastasis was suggested
data were retrospectively qualitatively and semi-quantitatively to be estimated based on their response to initial therapy.
assessed in a blinded manner for clinically relevant findings that However, the specific value of radioactive iodine (RAI) -avid
would have influenced the course of treatment, had they been lymph node metastasis (mLN) revealed in whole body scans
detected on pre-ablation scintigraphy. This included a thyroid (RxWBS) as a predictor of recurrent or progressive structural
remnant, lymph node metastasis and distant metastasis. Uptake disease was not clear till now. Materials and Methods: We
counts in the thyroid bed were measured using an isocontour- performed a retrospective review of patients with 1-4 cm DTC
based volume-of-interest on SPECT/CT images. Thyroid remnant who were treated from January 2015 to January 2018. Enrolled
size was semi-quantitatively assessed through a background- patients received total thyroidectomy and RAI, followed by
and volume-corrected value for the relative additional iodine a radioiodine whole body scan. Patients revealed distant
uptake in the thyroid bed above background (remnant- metastasis or lost of follow-up were excluded for further
to-background ratio), to correct for inter-patient and time- analysis. The clinical, pathologic, and incidence of RAI-avid
specific variability. Next, clinical, histopathological and surgical mLN on RxWBS were reviewed, and the risk factors related to
parameters were evaluated for their association with thyroid recurrence and/or metastasis were analyzed. Results: In total,
remnant size and treatment success. Successful treatment was 401 patients with 1-4 cm tumors were enrolled. The median
defined as no clinical, biochemical (i.e. serum thyroglobulin age was 45 years (range, 14-88 years) with 289 women. More
(Tg) <0.5 ng/mL in absence of Tg-antibodies) or structural (i.e. than half tumors manifested capsule invasion (82.54%) and
on imaging) evidence of disease at nine months. Results: 19.20% demonstrated gross extra thyroidal extension. 89.53%
97 consecutive DTC patients were included. TxWBS findings (359/401) cases received lymph node dissection and metastatic
included a thyroid remnant in 89 (92%) patients, suspicion of disease was found in 76.88% (276/359). The median RAI dose
lymph node metastasis in 26 (27%) and unexpected distant administered was 4.44 GBq (range, 2.96-47.63 GBq) and RAI-avid
metastasis in 6 (6%). Pre-ablative knowledge of these findings mLN was found in 28.43% (114/401) on RxWBS. After a median
could have influenced management in 48 (50%) patients. On follow-up of 28 months (range, 11-91 months), recurrent/
multivariable linear regression analysis, surgery with oncological metastatic disease was detected in 17.52% (65/371) of the
intent and surgery performed by two dedicated thyroid surgeons patients. Significantly higher incidence of recurrence was found
were independently associated with a smaller thyroid remnant. in patients who demonstrated RAI-avid mLN after initial therapy
Multivariable logistic regression analysis demonstrated that as compared with those who did not (p < 0.001).The univariate
one or more surgeries at a referring hospital, aggressive tumour analysis identified gross extrathyroidal extension, more than
histopathology, histopathological lymph node metastasis and 5 lymph node metastasis, and RAI-avid mLN as significant
new lymph node metastasis on TxWBS were independently and independent risk factors for recurrence or metastasis (p <
associated with an unsuccessful treatment. Thyroid remnant size 0.005). In a multivariate analysis, RAI-avid mLN appeared to be
was not associated with treatment success. All 13 (100%) TNM- the only significant risk factor for recurrent /metastatic disease
stage pN1 patients in whom additional lymph node metastases after initial therapy (HR, 17.457; 95% CI, 8.760 - 34.788; p < 0.001).
were detected on TxWBS had an unsuccessful treatment, Conclusion: RAI-avid mLN is a significant risk factor for disease
S141 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

were equally effective in low-risk to intermediate-risk DTC,


recurrence/metastasis in 1-4 cm DTC. More careful surveillance
according to the American Thyroid Association. However, a
is suggested in patients demonstrated RAI-avid mLN after initial
few studies reported differences in the intermediate- to high-
treatment. References: None.
risk DTC. This study aimed to compare the clinical outcome
between the methods. Materials and Methods: Between
May 2012 and October 2018, 136 patients who underwent
OP-358
ablation with high dose (3,700 MBq) RAI for DTC, without any
Prognosis of high-risk papillary thyroid cancer patients
macroscopic residual lesions or metastatic lesions after surgical
with pre-ablation stimulated Tg <1 ng/mL
resection, were retrospectively evaluated. Patients were exclu-
T. Tian, Y. Kou, R. Huang, B. Liu;
ded if distant metastasis was confirmed during RAI ablation or
West China Hospital, Sichuan University, Chengdu, CHINA.
if the outcome could not be confirmed; thus, 112 patients were
evaluated. Patients either underwent a 3-week I restriction with
thyroxine withdrawal or a 2-week I restriction with rhTSH admi-
Aim/Introduction: The prevalence of undetectable pre-
nistration. We measured the thyroglobulin (Tg) concentration
ablation stimulated thyroglobulin (s-Tg) and its clinical
and performed 131I scintigraphy (370 MBq) 3 to 12 months after
implications in high-risk papillary thyroid cancer (PTC) patients
RAI ablation. The initial success of RAI ablation was defined as
have been less described. We attempted to investigate the
the disappearance of the uptake of 131I at the thyroid bed and
rate of tumor recurrence in PTC patients initially classified as
Tg concentration <2.0 ng/mL. Patients who did not undergo
high risk but with pre-ablation s-Tg< 1 ng/mL and negative 131
I scintigraphy were evaluated based on the Tg value, and
anti-Tg antibody (TgAb). Materials and Methods: In order
those who had anti-Tg antibodies were evaluated based on 131I
to have follow-up period of at least 5 years for each patient,
scintigraphy. The results of ablation were compared between
PTC patients consecutively seen at our department from May
the groups using the Fisher’s exact test, and the TSH levels and
2008 to June 2013 with the following characteristics were
estimated glomerular filtration rate (eGFR) using the Welch’s
selected: (i) classified as ATA high risk on the basis of the tumor
t-test. Results: The THW and rhTSH groups included 47 and 65
histopathological features; (ii) submitted to adjuvant 131I therapy
patients, respectively, and the intermediate-risk and high-risk
after total thyroidectomy; (iii) a postoperative pre-ablation
groups included 63 and 49 patients, respectively. There was
s-Tg<1 ng/mL and negative TgAb. Results: Among 767 high risk
no patient classified into the low-risk group. In the THW and
PTC patients submitted to adjuvant 131I therapy, 69 patients met
rhTSH groups, the initial RAI ablation goal was achieved in
inclusion criteria. Sixty seven patients (97.1%) were diagnosed as
30/47 (63.8%) and 46/65 patients (70.8%), respectively (p=0.54);
classical PTC, the remaining 2 patients (2.9%) as follicular variant
mean±standard deviation of the TSH levels was 120.9±49.7
PTC. When evaluated 9-12 months after 131I therapy, 67 patients
µIU/mL and 272.1±102.4 7 µIU/mL, respectively (p<0.01); and
(97.1%) were classified as excellent response. Two (2.9%)
eGFR (treatment/pre-treatment) was 0.81 and 0.98, respectively
patients had a s-Tg >1 ng/mL (<3 ng/mL) in the absence of
(p<0.01). In the intermediate-risk and high-risk groups, the
apparent disease detected by imaging methods (indeterminate
initial RAI ablation goal was achieved in 43/63 patients (68.3%)
response). During a median follow-up duration of 5.6 years,
and 33/49 (67.3%), respectively (p=1.0). Conclusion: There
recurrence was observed in only 2 (2.9%) patients. The 67
were no significant differences in initial success of RAI ablation
(97.1%) patients without tumor recurrence were not submitted
between the preparation methods. However, patients in the
to any additional therapy, and all had a suppressed Tg <1 ng/mL
rhTSH group showed higher TSH levels and retained eGFR.
in the last assessment. Conclusion: High-risk PTC patients with
References: None.
pre-ablation s-Tg < 1 ng/mL and negative TgAb had a favorable
prognosis. References: None.
OP-360
Interleukin-6 is over-expressed in Differentiated thyroid
OP-359 cancer and could act as the prognostic factor for disease
Comparisons between Thyroid Hormone Withdrawal persistence or recurrence
and Recombinant Human Thyroid-stimulating Hormone Z. Guo-Qiang;
Administration for Radioiodine Ablation in Patients with Department of Nuclear Medicine, Shanghai Jiao Tong
Intermediate-risk to High-risk Differentiated Thyroid University Affiliated Sixth People’s Hospital, Shanghai, CHINA.
Cancer
Y. Iizuka, T. Katagiri, K. Ogura, M. Inoue, K. Nakamura, T. Mizowaki;
Kyoto University, Kyoto, JAPAN. Aim/Introduction: It has been repeatedly reported that
Aim/Introduction: Radioactive iodine (RAI) ablation is perfor- Differentiated thyroid cancer (DTC) was associated with
med to destroy residual normal thyroid tissue after the surgical inflammatory microenvironment, evidenced by a mixture of
resection of differentiated thyroid cancer (DTC). Two methods immune cells and cytokines within or surrounding primary
are used to prepare the subjects for RAI ablation: thyroid hor- thyroid cancer. Interleukin-6 (IL-6) acts as the pro-inflammatory
mone withdrawal (THW) and administration of recombinant cytokine to maintain the chronic inflammatory environment
human thyroid-stimulating hormone (rhTSH). The methods in the microenvironment and has been reported to be an
independent prognostic factor in melanoma patients. This study
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S142

was to evaluate the relationship between the IL-6 expression = 3, p-value = 0.007791), Tg basal values (W = 67.5, p-value =
in DTC and clinicopathologic factors and Disease-free survival 0.0005168) and stimulated Tg (W = 100, p-value = 0.0006464),
(DFS). Materials and Methods: Immunohistochemistry with a strong association. Therefore these values should be
staining was conducted to evaluate the expression level of IL-6 taken into account in patients with suspected dedifferetiated
in a total of 108 DTC tumor and corresponding para-carcinoma thyroid tumors. 5 of these patients were submitted to surgery,
tissues. Results: IL-6 expression was positive in 72.2% (78/108) 6 are in treatment with Sorafenib/Levantinib and the rest are
of DTC tumor tissues, which was significantly higher than in in close surveillance. Conclusion: PET/CT 18F-FDG is a very
corresponding non-tumor tissue (p=0.002). The expression sensitive diagnostic technique for radioiodine-refractory thyroid
level of IL-6 was associated with tumor pathological type cancer patients. Basal and stimulated Tg, age at the moment of
(p=0.021), lymph node metastasis (p=0.021), distant metastasis diagnosis and tumor staging are predictive factors that need
(p=0.036) and disease persistence or recurrence (p=0.032). to be taken into account for an early diagnosis and better
Univariate analysis of factors influencing DFS shows that DFS management; they demonstrate a significant correlation with
was associated with the IL-6 expression level (p=0.028), tumor the risk of tumoral dedifferentiation. References: None.
size (p=0.005) and TNM stage (p=0.010). In multivariate Cox
regression analysis, positive IL-6 expression in tumor tissue was
significantly associated with worse DFS (Hazard Ratio 5.813 OP-362
[confidence interval 1.471-22.727], p=0.013). Conclusion: IL-6 Contrast-Enhanced 18F-FDG PET/CT in Detection of
is overexpressed in differentiated thyroid cancer and associated Recurrent/Metastatic Radioiodine Negative Differentiated
with the aggressiveness of the disease and could act as a factor Thyroid Carcinomas
to predict the prognosis of DTC patients. References: None. P. Koranda1, H. Polzerová1, L. Quinn1, E. Buriánková1, R. Formánek1,
M. Halenka2, M. Mocňáková3, M. Kamínek1;
1
Dept. of Nuclear Medicine, Univ. Hosp. and Palacký
OP-361 University, Olomouc, CZECH REPUBLIC, 2Dept. of Internal
Radioiodine-refractory thyroid cancer, looking for Medicine III, Univ Hosp., Olomouc, CZECH REPUBLIC, 3Dept.
predictive factors of Surgery II, Univ Hosp., Olomouc, CZECH REPUBLIC.
M. Guiote Moreno1,2, A. M. Santos Bueno1,2, J. Márquez Fernandez1,
J. C. Prieto Prieto1, M. Albalá González1, E. Rodriguez Cáceres1, R.
Carlos Zamora1, J. A. Vallejo Casas1,2; Aim/Introduction: Localization of radioiodine-negative
1
Hospital Universitario Reina Sofía, Cordoba, SPAIN, 2Instituto remnants or recurrences of differentiated thyroid carcinomas
Maimonides de Investigación Biomédica, Cordoba, SPAIN. (DTCs) is mandatory because only it allows to effectively
cure the patients using a locoregional treatment. The aim of
this study was to assess the diagnostic value of 18F-FDG PET/
Aim/Introduction: To analyze the data of radioiodine-refractory CT in this indication. Materials and Methods: A total of 160
thyroid cancer patients diagnosed with PET/CT 18F-FDG; and its patients (pts) with suspicion of recurrent DTC and negative 131I
correlation with dedifferentiated tumor with possible predictive scans in the period 2009-2018 underwent contrast-enhanced
factors. Materials and Methods: We recruited 61 patients 18
F-FDG PET/CT. Examination was performed in 150 pts due to
with differentiated thyroid cancer who underwent surgical a positivity of TSH-stimulated thyroglobulin (TSH-Tg) (in case
and ablative treatment with 131I that presented an incomplete of TSH-Tg < 2 µg/l suspicious sonography or high-risk disease
response. A PET-CT with 18F-FDG was performed between the was also a condition of PET/CT indication) and in 10 cases due
years 2015-2019 to patients, after stimulation with rTSH and a to persistent elevation of anti-Tg. Only the first 18F-FDG PET/CT
negative 131I wholebody scan. Refractory and dedifferentiated examinations were evaluated, all subsequent examinations of
tumors were considered in patients that had positive results in the same patient were excluded. Results: Contrast-enhanced
PET/CT scans. Age, sex, histology, tumoral staging, treatment 18
F-FDG PET/CT was true positive in 76/160 (48%) cases - false
131
I dosage, biochemical levels of thyroglobulin and antibody positive in 4/160 (3%). Subgroup of 26 patients with TSH-Tg 0
anti-thyroglobulin were taken into account in these patients. A < 2 µg/l and suspicious sonography or high-risk patients: true
hypothesis contrast was obtained for each one of these variables positive 7 (27%), false positive 1 (4%). Subgroup of 46 patients
and the dedifferentiated variable to calculate if they correlate with TSH-Tg 2 < 10 µg/l: true positive 20 (43%), false positive
using the chi square for the qualitive variables and the U Mann- 2 (4%). Subgroup of 78 patients TSH-Tg >10 µg/l: true positive
Whitney-Wilcoxon for the cuantitative variables. Results: 28 43 (55 %), false positive 1 (1%). Subgroup of 10 patients with
patients were suggestive of dedifferentiated tumor on PET/CT; anti-TG pathology: true positive 6 (60%). Incidentally 2 other
18 were women and 10 were men with a mean age of 57 (SD ± malignancies and 1 interstitial lung disease were detected. The
16,7 years). Total thyroidectomy and 131I ablation was performed surgery or external beam radiotherapy or targeted imunotherapy
predominantly on stage III (47%) papillary thyroid cancer (89%) was subsequently performed in 56, 19 and 2 cases, respectively.
with a mean dose of 5,1 Gbq (SD ± 2,8 Gbq). Statistical significance Treatment management plan was changed in 61/160 patients
was seen only with age and tumor diagnosis after analyzing (38%). Conclusion: Contrast-enhanced 18F-FDG PET/CT is able
the variables with the dedifferentiated tumor (W = 123.5, to identify recurrent/metastatic radioiodine-negative DTCs
p-value = 0.00005323), tumoral staging (X-squared = 11.884, df in an important part of patients with elevation of TSH-Tg or
S143 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

with another suspicion of metastases. The detection rate of show uptake almost exclusively in FDG-PET/CT with only a small
recurrences increases with increase of TSH-Tg. Nevertheless the fraction demonstrating positive iodine uptake. Thus, rendering
number of positive findings in patients with low positive level of FDG-PET/CT the imaging method of choice for these patients
TSH-Tg represent a significant part of examinations. Therefore, it during follow-up. References: None.
is not possible to set a TSH-Tg limit for 18F-FDG PET/CT indication.
TSH-stimulated 18F-FDG PET/CT is an efficient diagnostic tool
with a significant impact on therapy. References: None. OP-364
A Prospective Study of the Effect of Radioiodine
Therapy on Ovarian Reserve Function in Patients with
OP-363 Differentiated Thyroid Carcinoma
Course of disease and outcome in patients with poorly W. Miao, R. Lin;
differentiated thyroid cancer: a single center study The First Affiliated Hospital of Fujian Medical
F. Ahmaddy, V. Wenter, P. Bartenstein, S. Lehner, H. Ilhan, A. Todica; University, Fuzhou, CHINA.
Department of Nuclear Medicine, University
Hospital, LMU Munich, Munich, GERMANY.
Aim/Introduction: The aim of this study was to prospectively
assess the effect of radioiodine therapy (RAIT) on ovarian
Aim/Introduction: Poorly differentiated thyroid cancer (PDTC) reserve function for the patients with DTC. Materials and
is a rare but very aggressive variant of thyroid carcinoma. Due Methods: Seventy-six pre-menopausal women (34.1±6.8years)
to the relative rarity of the disease, studies on diagnostic and pathologically diagnosed with DTC planning to receive RAIT
treatment findings are limited. Therefore, we investigated the after surgery were recruited for this study, of which 8 subjects
clinical course of these patients. Materials and Methods: underwent the twice RAIT. Serum FSH, LH, estradiol(E2),
A retrospective analysis was conducted in 47 patients with progesterone(P), TSH and anti-Müllerian hormone (AMH) levels
histologically proven PDTC, who were treated between 2005 during the early follicular phase were measured before and 1,
and 2019 at the Department of Nuclear Medicine of the 2, 3, 6, 9 and 12 months after RAIT (M0, M1, M2, M3, M6, M9,
University Hospital of Munich. All patients underwent total M12). Results: ① The mean AMH levels were 2.15(0.92-3.74),
thyroidectomy, followed by adjuvant radioiodine ablation 1.21(0.52-2.82), 1.19(0.28-2.22), 1.20(0.38-3.28), 2.10(0.65-3.59),
(RAI). Clinico-pathological features, Tg levels, 131-I Uptake in 1.95(0.44-3.45) and 1.59(0.44-4.55) ng/mL respectively at M0,
whole body scan and FDG-Uptake in PET/CT were analyzed. M1, M2, M3, M6, M9, M12. The AMH level at M2 was significantly
A stimulated Tg level below 0.5 ng/ml was defined as lower than that at M0 (P=0.021), while no significant difference
undetectable. Results: The mean age at diagnosis was 57±18 was found among other time points (P > 0.05).② The
years (55% females) and mean follow-up was 7 years. According descent rates of AMH level based on M0 were(49.0%±23.4%),
to the 7th TNM classification, 22% of patients had pT1b/pT2- (46.1%±25.5%), (42.0%±23.7%), (33.1%±20.5%), (36.0%±22.9%)
stage disease, 70% pT3, 8% pT4a/b. At initial presentation, and(25.4%±17.6%) at M1, M2, M3, M6, M9, M12, respectively. The
28% of patients had regional lymph node metastases and 19% number at M1 was significantly higher than that at M6, M9 and
extrathyroidal extension and 4% showed R1 resection. A mean M12 (P=0.003, P=0.038 and P=0.002) and the number at M12
I-131 activity dose of 5.8±2.0 GBq was applied at initial RAI. 68% was significantly lower than that at M1, M2 and M3 (P=0.002,
patients underwent further RAI therapy treatment cycles. At P=0.008 and P=0.034).③ The AMH levels after the second RAIT
initial presentation 72% of patients (N=34) showed no distant were lower than that after the first RAIT, the descent rates
metastases. 28% of the patients (N=13) already showed distant showed the opposite trend, but no statistically significant
metastases at initial presentation. During follow-up, 32% (N=15) relation was found between the two therapy (P> 0.05).④ At M1,
showed no evidence of disease (NED), 34% (N=16) showed AMH descent rate was positively correlated with age (r=0.381,
persistent disease, out of which in 12 patients structural disease P=0.000) and negatively correlated with basic AMH level (r=-
was diagnosed during follow-up. Recurrence occurred in 6% 0.358, P=0.002). The descent rate of AMH had no correlation
(1 patient biochemical, 2 patients structural). During follow-up with the age at menarche, BMI, 131I dose, Hashimoto’s thyroiditis
FDG-PET was available in 96% of patients with distant metastases and the interval time between surgery and RAIT(P>0.05). ⑤ The
(22/23) of whom all patients showed a pathological uptake. Out difference in FSH, LH, E2 and P levels among all time points were
of these patients with distant metastases only 5 patients were found to be insignificant (P> 0.05). ⑥50.7% (38/75) patients had
radioiodine positive. At the time of last follow-up 36% (N=17) menstrual disorders after RAIT. But there was no significant
showed NED, 9% (N=4) persistent biochemical disease and 47 difference in AMH decent rates and age between patients
% (N=22) structural disease. 3 patients (6%) were lost to follow- with menstrual disorder and those with normal menstruation
up. Disease related death was reported in 5 patients until last (P>0.05). Conclusion: This study prospectively showed that
follow-up. Conclusion: Poorly differentiated thyroid cancer ovarian reserve declined rapidly after RAIT, with a partial
is acting more aggressively than well differentiated forms of recovery in the subsequent follow-up. References: None.
thyroid cancer, with a high number of patients with distant
metastases at initial presentation and an increasing number of
patients with structural disease during follow-up. These patients
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S144

OP-365 901
Clinical study on the effect of TSH suppression on left
ventricular systolic synchrony in patients with DTC
CME 7 - Translational and Molecular Imaging
R. Wang1, l. Yang1, S. Jin2, B. Wu1, X. Han1, Y. Liu1, B. Liu1;
Therapy Committee: Imaging Immune Therapy
1
Nuclear Medicine Department, the First Affiliated Hospital of
Zhengzhou University, Zhengzhou, CHINA, 2Nuclear Medicine Monday, October 14, 2019, 14:30 - 16:00 Auditorium
Department, Zhe Jiang Cancer Hospital, Hangzhou, CHINA.

Aim/Introduction: To investigate the effect of TSH suppression OP-366


therapy on left ventricular systolic synchrony in patients with Imaging of Immunological Targets
DTC. Materials and Methods: Patients with differentiated W. Weber;
thyroid cancer who underwent TSH suppression were treated Nuclear Medicine Department, Klinikum rechts der Isar,
with gating myocardial perfusion imaging before suppression, Technische Universität München (TUM), Munich, GERMANY.
6 months, 12 months, and 24 months after suppression. The
left ventricular systolic synchrony parameter was obtained
including phase angle, phase standard deviation, and entropy. OP-367
Patients with differentiated thyroid cancer who do not require Current State of Imaging in Assessment of Immunotherapy
TSH suppression therapy in the same age group are normal C. Bodet-Milin;
controls. Data were tested for covariance by SPSS 19.0 with age Nuclear Medicine Department, University Hospital,
as a covariate to analyze the effect of TSH suppression on left CRCINA, INSERM, CNRS, Université d’Angers,
ventricular systolic synchrony. Results: After TSH suppression Université de Nantes, Nantes, FRANCE.
treatment, the phase angle, phase standard deviation, and
entropy of the experimental group gradually increased with time.
However, at 6 months and 12 months of suppression, there was OP-368
no statistical difference compared with the control group. There Emerging Imaging Concepts in Immuno-Oncology
were statistical differences in phase angle, phase difference, and M. Schottelius;
entropy at 24 months, with p values of 0.006, 0.007, and 0.001, TU Munich, Pharmaceutical Radiochemistry, Garching, GERMANY.
respectively. Conclusion: This study used GMPI to evaluate the
left ventricular systolic synchrony in patients with PTC after TSH
suppression. Long-term TSH suppression led to left ventricular 902
systolic synchrony, suggesting early intervention. References:
None.
Joint Symposium 13 - Neuroimaging
Committee / EANO: Low Grade Glioma

YDF2 Monday, October 14, 2019, 14:30 - 16:00 Lecture Hall 311

EANM Young Daily Forum

Monday, October 14, 2019, 13:00 - 14:30 Lecture Hall 113 OP-369
Imaging Low Grade Glioma
N. Albert;
Ludwig-Maximilians-Universität, Dept of
YDF-2 Nuclear Medicine, Munich, GERMANY.
Presentation Skills for Medical Professionals
R. Sheppard;
EANM Moderator, London, UNITED KINGDOM. OP-370
State of the Art Neurosurgical Management in Low Grade
Glioma
J. Tonn;
Ludwig-Maximilians-Universität, Dept.
Neurosurgery, Munich, GERMANY.
S145 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

OP-371 OP-376
Non-Surgical Management of Low Grade Glioma Preclinical PET Imaging and Quantification
M. van den Bent; M. Koole;
Erasmus MC Cancer Center, Brain Tumor UZ Gasthuisberg, Nuclear Medicine and
Center, Rotterdam, NETHERLANDS. Molecular Imaging, Leuven, BELGIUM.

903 OP-377
Nanobody Applications for Radionuclide Imaging and
Joint Symposium 14 - Dosimetry + Therapy - Process from Camel to Patient
Radiation Protection Committee / ICRP: M. Keyaerts;
Radiological Protection in Therapy with UZ Brussels, Nuclear Medicine, Brussels, BELGIUM.
Radiopharmaceuticals

Monday, October 14, 2019, 14:30 - 16:00 Lecture Hall 312 905
M2M - Parallel Session: Neurodegeneration and
Neuroinflammation
OP-372
ICRP framework for Individual Absorbed Dose Estimation Monday, October 14, 2019, 14:30 - 16:00 Lecture Hall 111
W. Bolch;
University of Florida, Biomedical Engineering,
Gainesville, FL, UNITED STATES OF AMERICA.
OP-378
First-in-human investigating and translational study of
OP-373 18
FS3-1 a novel alpha-synuclein PET tracer
Justification and Optimisation of Protection in B. Hooshyar Yousefi1, K. Shi2, T. Grimmer3, R. Arakawa4, H. Wester3,
Radiopharmaceutical Therapy Patients C. Halldin4, M. Schwaiger3, W. Weber3, I. Yakushev3, T. Arzberger5;
G. Flux; 1
Phillips University of Marburg, Marburg, GERMANY, 2University
Royal Marsden NHS Trust & Institute of Cancer Research, of Bern, Bern, SWITZERLAND, 3Technical university of Munich,
Joint Department of Physics, Sutton, UNITED KINGDOM. Munich, GERMANY, 4Karolinska Institutet, Stockholm, SWEDEN,
5
Ludwig-Maximilians University of Munich, Munich, GERMANY.

OP-374
EANM Framework for Individualized Treatment Planning Aim/Introduction: α-Synuclein aggregates (α-syn) imaging in
and Dose Verification the living brain would enable to diagnose and track the degree
C. Stokke; and location of α-synucleinopathies over time. We have been
Oslo University Hospital, Rikshospitalet, developing several small molecule diagnostic probes based
Intervention Centre, Oslo, NORWAY. on 4,4’-diaryl-2,2’-bithiazole suitable for quantification of α-syn
by nuclear medicine imaging. Recently, we studied 18FS3-1 as a
promising lead compound for noninvasive, specific imaging of
904 a-syn as opposed to other proteopathies (e.g. Aβ and tau). Here,
we report the results of studies aimed at the clinical translation
CTE 3 - Technologist Committee: Preclinical of FS3-1 lead by PET using α-syn E46K mutant rat model
Studies, from Bench to Bedside as well as in nonhuman primates (NHP) and first-in-human
investigation. Materials and Methods: The 18FS3-1 shows 3nM
Monday, October 14, 2019, 14:30 - 16:00 Lecture Hall 117 affinity for α-syn and high selectivity (120 fold) for Aβ and tau
was labeled with the Neptis module. The brain-specific binding
kinetics were investigated in 12 month-old rats with E46K
α-syn mutation and controls using dynamic PET coregistered
OP-375 to a 7T-MRI. Furthermore, in collaboration with Karolinska
How to Develop the Ideal Radiopharmaceutical Institute, we studied its brain uptake kinetics and plasma
G. Bormans; stability in NHP. Preliminary toxicology studies carried out in
Ku Leuven, Radiopharmacy Department, Leuven, BELGIUM. mice. Patients with α-synucleinopathy underwent dynamic PET
imaging for 120 min in Siemens mMR. The image data were
spatially normalized based on MRI using PMOD. Images were
analyzed by comparing binding potentials (BP) obtained using
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S146

a reference tissue model, and distribution volume (DV). Results: The majority of compounds showed no binding to MAO-A or B
The comparisons of distribution volume showed statistically and 8/10 regioisomers showed no measurable binding to beta-
significant differences between a-syn E46K rats and controls amyloid. 8/10 compounds were successfully radiolabeled with
for the substantia nigra, cerebellum, thalamus, and brainstem. 18
F and brain-uptake was evaluated by PET imaging in NMRI-
In NHP FS3-1 showed initial brain uptake of up to 1.4% ID (1.3 mice. The brain-uptake ranged from 2.1-8.2 % ID/g for those
SUV) and a rapid washout with marginally increases in later time compounds. Five compounds showed defluorination in mice.
points (up to 0.4SUV at 120min). FS3-1 showed no toxic effect Three compounds showed excellent wash-out properties in mice
at 154nmol/Kg dose in mice and higher than 55% 120 min p.i. with peak brain-uptake-to-60 min ratios > 20. Two compounds
in vivo stability in monkey plasma. The specific binding of FS3-1 showed a comparable preclinical profile based on their affinity
was detected in the cases with underlying α-synucleinopathies. and PK-properties and were further characterized in NHPs and
Conclusion: The suitable uptake kinetics in rats and NHP and for binding to Tau-aggregates in PSP. Conclusion: Preclinical
target affinity suggests that FS3-1 is promising selective α-syn characterization of the ten fluoropyridine regioisomers showed
tracer that may allow for the first non-invasive imaging of that small changes of the same general scaffold can surprisingly
αsynuclein aggregates in patients with dementia with Lewy result in significantly changed properties with respect to tau-
bodies or Parkinson’s disease. Further human investigation and binding, off-target binding and PK properties of the different
new candidates optimization and their translation study are compounds. Based on these results, PI-2620 was selected as
in progress. References: Wester HJ, Yousefi BH Compounds candidate for clinical validation. This compound displayed high
binding to neuropathological aggregates US20170157274A12. affinity for tau-aggregates in AD and PSP brain-homogenate
competition-assays. Specific binding to aggregated tau was
demonstrated by ARG and micro-ARG on AD and PSP brain
OP-379 sections, whereas no specific binding was observed on brain
Discovery and preclinical characterization of [18F]PI-2620, sections from non-demented donors. PI-2620 showed excellent
a next generation tau PET tracer for the assessment of tau selectivity with no off-target binding to beta-amyloid or MAO-
pathology in Alzheimer’s disease and other tauopathies A/B. Good brain-uptake and fast wash-out were observed in
A. Mueller1, H. Kroth2, F. Oden1, F. Capotosti2, M. Berndt1, J. Molette2, mice and NHPs. References: None.
H. Schieferstein1, V. Darmency2, J. Castillo-Melean1, E. Vokali2, H.
Schmitt-Willich1, D. Hickman2, A. Pfeifer2, S. Poli2, L. Dinkelborg1, A.
Stephens1; OP-380
1
Life Molecular Imaging, Berlin, GERMANY, 2AC Characterization of the Serotonin 2A receptor selective
Immune SA, Lausanne, SWITZERLAND. PET tracer (R)-[18F]MH.MZ in the human brain
V. Kramer1,2, A. Dyssegaard3, J. Flores2, C. Soza-Ried2, F. Roesch4, G.
Moos Knudsen3, H. Amaral1,2, M. Herth5,6;
Aim/Introduction: Tau deposition in the brain is a key 1
Positronpharma SA, Santiago de Chile, CHILE, 2Center for
pathologic feature of Alzheimer’s disease (AD) and other Nuclear Medicine & PET/CT Positronmed, Santiago, CHILE,
neurodegenerative disorders. PET is currently explored for 3
Center for Integrated Molecular Brain Imaging, Rigshospitalet,
detection of aggregated tau in these diseases. Several PET tracers Copenhagen, DENMARK, 4Institute of Nuclear Chemistry,
targeting tau-aggregates have been described and tested in Johannes Gutenberg-University, Mainz, GERMANY, 5Department
humans. Limitations have been reported for first-generation Tau of Drug Design and Pharmacology, University of Copenhagen,
tracers regarding their selectivity. In our screening campaign we Copenhagen, DENMARK, 6Department of Clinical Physiology,
utilized the MorphomerTM library to identify pyrrolo[2,3-b:4,5-c’] Nuclear Medicine & PET, Rigshospitalet, Copenhagen, DENMARK.
dipyridine core structures with high affinity for aggregated Tau.
Further characterization showed compounds containing this
moiety had significantly reduced MAO-A binding compared Aim/Introduction: The serotonin receptor subtype 2A is of
to pyrido[4,3-b]indole-derivatives like AV1451. Here we present significant clinical interest due to its relevance in diseases such
preclinical data of ten fluoropyridine regioisomers attached as depression, Alzheimer’s disease, or schizophrenia and as
to the pyrrolo[2,3-b:4,5-c’]dipyridine scaffold, leading to target for hallucinogenic drugs and atypical antipsychotics. The
compounds with superior properties. Materials and Methods: radiolabelled antagonist (R)-[18F]MH.MZ has been identified as
Tau binding of fluoropyridine regioisomers and AV1451 was a promising PET imaging agent for quantification of 5-HT2ARs,
evaluated in competition binding-assays using AD brain- combining an excellent selectivity profile (as for [11C]MDL
homogenate. Off-target binding of the ten compounds and 100907) with the favorable isotopic properties of fluorine-18. In
AV1451 was evaluated using radiolabeled MAO-A/B and beta- this study, we aimed to evaluate the potential of (R)-[18F]MH.MZ
amyloid binders. Compounds were radiolabeled with 18F and in the human brain by PET. Materials and Methods: Nine
brain-PK properties were evaluated in NMRI-mice by Micro- healthy volunteers (HCs) underwent (R)-[18F]MH.MZ PET imaging
PET imaging. The most promising compounds were further at baseline for 180 min. 5/9 HCs participated in additional arterial
characterized by (micro)ARG and PET imaging in NHPs. Results: blood sampling and metabolite analysis during PET imaging. 4/9
Using human AD brain-homogenates, pIC50 values ranging from participated in a second PET scan after ketanserin pretreatment
7.35 to 8.42 were measured for the fluoropyridine regioisomers. to determine specificity of (R)-[18F]MH.MZ. Regional time-activity
S147 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

curves of 17 brain regions were analyzed comparing different occupancy was estimated using a Lassen plot (PMOD,v4.0). These
kinetic modeling approaches (1TCM, 2TCM, Logan, SRTM, ...) values were considered as gold standard. First, baseline blood-
and stability of outcome measures was evaluated. Results: to-plasma ratios and metabolite fractions were combined with
Highest uptake was determined in 5-HT2AR rich cortical regions sampled, post-dose arterial blood IF for calculating post-dose
with distribution volumes (VTs) of approximately 4.5-5.0 and VT and occupancy. Second, baseline blood-to-plasma ratios
BPNDs of 1.5. No radiometabolism was observed. 1- and 2-TCM and metabolite fractions were combined with post-dose IDIF
resulted in similar outcome measure, whereas reference tissue as arterial blood IF. IDIF was extracted by defining carotids and
models resulted in a stable and predictable overestimation. (R)- background volume-of-interest (VOI) guided by time-of-flight
[18F]MH.MZ displayed specific binding and could be blocked by MRA (TOF-MRA), acquired simultaneously at the beginning of
pretreatment with ketanserin. Moreover, outcomes measures the dynamic PET. Correction for partial volume effects between
were stable after 100-110 minutes allowing a 5% deviation arterial blood and background was optimized by comparing
to the control. Conclusion: (R)-[18F]MH.MZ is a suitable PET baseline IDIF with sampled baseline blood IF. Results of both
tracer to image and quantify the 5-HT2AR system in humans. approaches were compared with the gold standard by a Bland-
In comparison to [11C]MDL 100907, faster and more precise Altman analysis. Results: Similar post-dose VT were found
outcome measure could be obtained using (R)-[18F]MH.MZ. for all regions by using baseline blood-to-plasma ratio and
We believe that (R)-[18F]MH.MZ has the potential to become metabolisation information (4.1% bias,95%CI[-3.4%;11.5%] for
the antagonist radiotracer of choice to investigate the human cortex). For the IDIF-approach, similar results were found with
5-HT2AR system. References: Herth MM, Kramer V, Piel M, Palner a slightly higher bias (7.4%,95%CI[-8.2%;23.0%]). Occupancy
M, Riss PJ, Knudsen GM, et al. Synthesis and in vitro affinities of was observed with -1.8% bias (95%CI[-9.0%;5.3]) for the first
various MDL 100907 derivatives as potential 18F-radioligands approach, while for the IDIF-approach the bias increased to
for 5-HT2A receptor imaging with PET. Bioorg Med Chem. -5.8% (95%CI[-19.2%;7.5%]). Conclusion: A post-dose IDIF,
2009;17(8):2989-3002. guided by TOF-MRA, can be used as arterial blood IF and can be
combined with baseline blood-to-plasma ratios and metabolite
fractions for accurate post-dose P2X7-quantification, thus
OP-381 avoiding the need for repeated invasive arterial blood sampling
A minimally-invasive approach to quantify P2X7 receptor in pharmaceutical dosing studies, thereby increasing flexibility
occupancy using 18F-JNJ-64413739 dynamic PETMR and in study design. References: None.
MRA-driven image-derived input function
N. Mertens1, M. Schmidt2, A. Hijzen2, P. Ravenstijn2, K. Van Laere1,
M. Koole1; OP-382
1
University Hospital and KU Leuven, Leuven, BELGIUM, The influence of high-fat diet on neuroinflammation
2
Janssen Research & Development, Beerse, BELGIUM. and D2 receptor availability in a rat model of Parkinson`s
disease
L. Reali Nazario1,2, A. Dellink3, R. Moraga-Amaro1, B. Lima
Aim/Introduction: 18F-JNJ-64413739, a selective P2X7- Giacobbo1, A. Schildt1, R. A. J. O. Dierckx1, C. Maria Moriguchi
inhibitor, has been extensively evaluated as a candidate PET- Jeckel2, R. Souza da Silva2, J. Doorduin1, E. F. J. de Vries1;
ligand. A 2-tissue compartment model (2TCM) with arterial 1
University Medical Center Groningen, Groningen,
blood sampling was identified as the most suitable kinetic NETHERLANDS, 2Pontifícia Universidade Católica do
model for 18F-JNJ-64413739 brain PET quantification in humans, Rio Grande do Sul, Porto Alegre, BRAZIL, 3University
since no reference region could be identified. In the context of of Groningen, Groningen, NETHERLANDS.
a P2X7-PET dose occupancy study, we evaluated a minimally-
invasive approach by limiting arterial blood sampling to
baseline conditions and combine baseline blood-to-plasma Aim/Introduction: Lifestyle can influence on the incidence
ratios and metabolite fractions with an image-derived input and progression of Parkinson’s disease (PD) (Paul et al., 2019).
function (IDIF) using MR-angiography (MRA) on a simultaneous However, the underlying molecular mechanisms in the brain
PETMR-system, to calculate post-dose distribution volumes (VT). are still unknown. The objective of this study is to evaluate the
This non-invasive approach to estimate post-dose regional VT effect of a high-fat diet (HFD) on neuroinflammation (11C-PBR28)
was validated by comparing post-dose MRA-IDIF based VT and and the D2-receptor (11C-Raclopride) availability in the brain of a
corresponding occupancy with full arterial blood sampling. rat model of PD. Materials and Methods: Nine weeks old male
Materials and Methods: 4 healthy volunteers (M;30.8±13.7yrs) Wistar rats were fed with either a HFD (60% fat) or a standard
underwent a 90-min dynamic 18F-JNJ-64413739 PET scan (84- diet (STD; 10% fat) for three months. The bodyweight and food
155 MBq, GE Signa PETMR) with arterial blood sampling under intake were measured twice a week and a glucose tolerance test
baseline and P2X7-antagonist dosing conditions at antagonist (GTT) was performed every month. After two months of diet the
Tmax. Two subjects received a second post-dose scan (later animals were submitted to stereotactic surgery injecting a low
timepoint), resulting in 6 pairs of baseline and post-dose scans. dose of 6-OHDA (2x 3µg) in the right striatum. Static 11C-PBR28
VT was calculated using 2TCM with sampled arterial blood and 11C-Raclopride PET scans were performed two days before
and metabolite-corrected plasma input function (IF), while and one month after the surgery. Tracer uptake in the striatum
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S148

was measured and expressed as SUV. GraphPad Prism 7.02 and (anteroposterior, +1.8; mediolateral, +2.0; dorsoventral,-3.0)
IBM SPSS 23 were used for statistical analysis. Results: After using a Hamilton syringe (Stoelting, IL, USA). Splenocytes (2 x
three months, animals on HFD had 8.9% higher bodyweight 107) were isolated from luciferase expressing transgenic mice
than those on STD (p<0.038). The surgery caused a temporary (B6.LucTg), and adoptively transferred to recipient B6 (C57BL/6)
small decrease in bodyweight in both groups. No difference in mouse by intravenously injection for visualizing immune cell
the glucose tolerance test between the STD and HFD groups localization with bioluminescence imaging. Simultaneous PET/
were found in the first two months, but in the third month MR scans were acquired using 18F-CB251 activity at a dose
the HFD group did show a slower recovery of glucose levels, ranging from 9.25 to 11.1 MBq per mouse. To monitor the effect
suggesting a pre-diabetic state. In the HFD group, 11C-PBR28 of anti-inflammatory drug with our multimodal imaging, mice
uptake in the 6-OHDA-injected caudate putamen significantly were also treated with an inflammatory cytokine inhibitor,
increased (33%; p=0.0193) between both PET scans. This effect CDDO-methyl ester (200 nM, 3 times). Results: 18F-CB251
was not observed in the contralateral striatum, nor in the STD was specific to the cells with the different TSPO expression,
group. 11C-Raclopride PET showed significantly lower uptake and activated immune cells. Simultaneous 18F-CB251 PET/MR
in all regions of the striatum in the HFD group than in the STD showed that 18F-CB251 radioactivity was co-registered with the
group (p<0.05). After the surgery this effect disappeared, except MR signals in the same region of LPS-injected mouse. Luciferase-
for the right accumbens core (p<0.05). 11C-Raclopride PET did expressing splenocytes were clearly localized at the LPS-injected
not reveal any effect of 6-OHDA injection. Conclusion: HFD site of the right striatum, indicating that peripheral immune
significantly reduced D2 receptor availability in rat striatum, cells were infiltrated in the LPS-induced inflammatory region of
but this effect was no longer present one month after 6-OHDA brain. Though BLI signals from peripheral immune cells in the
injection. Moreover, the HFD aggravated 6-OHDA-induced inflamed region of mouse brain were very sensitive to measure
neuroinflammation in the Parkinson model. Both observations the degree of inflammation, they were only detectable in the
suggest a detrimental role of the HFD-induced pre-diabetic state mouse brain under the skin. On the other hand, 18F-CB251-PET
on the onset or progression of Parkinson’s disease. References: radioactivity targeting TSPO successfully reflected the anti-
Paul KC, et al. The association between lifestyle factors and inflammatory effect of CDDO-Me by quantitatively assessing
Parkinson’s disease progression and mortality. Disord. 2019 the degree of neuro-inflammation without invasive methods.
Jan;34(1):58-66. Conclusion: Our multi-modal imaging modalities with
18
F-CB251-PET/MR and BLI have great potential to detect neuro-
inflammation and to evaluate the efficacy of anti-inflammatory
OP-383 drugs for pre-clinical studies, and 18F-CB251-PET targeting
TSPO-targeting 18F-CB251 PET/MR in an intracranial LPS TSPO can be suggested as an effective method to investigate
induced neuro-inflammation model: comparative analysis severity of neuro-inflammatory diseases for clinical applications.
with bioluminescence imaging of peripheral immune cells References: None.
K. Kim1,2, H. Kim1, S. Bae1,2, Y. Kim1,2, J. Na1, C. Lee1, M. Lee3, G. Ko2,
K. Kim2, J. Paeng2, G. Cheon2, K. Kang2, S. Kim4, J. Chung3, E. Kim3, J.
Lee2, B. Lee4, H. Youn3; OP-384
1
Samsung cancer institute, Seoul, KOREA, REPUBLIC OF, 2Seoul Synthesis Of A Potential Cannabinoid Receptor Subtype
National University, Seoul, KOREA, REPUBLIC OF, 3Seoul National 2 (CB2) Receptor Binding Ligand, Nucleophilic [18F]
University Hospital, Seoul, KOREA, REPUBLIC OF, 4Seoul National Fluorination and First Preclinical Results
University Bundang Hospital, Seoul, KOREA, REPUBLIC OF. D. Modemann, C. Bouter, A. Kreyenschmidt, C. Breunig, D. Stalke, J.
Wiltfang, C. Sahlmann, Y. Bouter, B. Meller;
Georg-August University Göttingen, Göttingen, GERMANY.
Aim/Introduction: Imaging the inflamed region and the
interaction of immune cells in the brain is important because
neuro-inflammation is a primary defence mechanism and Aim/Introduction: There is evidence that cerebral
closely related to neurodegenerative disease. Here, we inflammatory processes play a central role in the development of
established multi-modalities imaging using PET/MR imaging neurodegenerative diseases. These processes are characterized
with a recently developed TSPO-targeting radionuclide by the activation of microglia which is associated with the
PET probe, 18F-CB251, for detecting neuro-inflammation expression of CB2 in this cell type. Therefore the visualization of
in a mouse harbouring intracranial lipopolysaccharide CB2 is of major interst. 3-acylindoles shows high affinities to CB1
(LPS)-induced regional inflammation. In addition, since the and CB2.1 Depending on substitution, the selectivity towards
infiltration of peripheral immune cells exacerbated neuro- one receptor subtype could be achieved. The substitution with
inflammation to greater neuro-toxic levels, we monitored tetramethylcyclopropyl group lead to receptor ligands with
peripheral immune cells infiltration in neuro-inflammation with high selectivity for CB2. Based on this, (1-(3-[18F]fluoropropyl)-
bioluminescence imaging by adoptive transfer of luciferase 1H-indol-3-yl)(2,2,3,3-tetramethylcyclopropyl)methanone
expressing splenocytes into the inflamed mouse. Materials was chosen as a potential tracer for the nuclear imaging
and Methods: Lipopolysaccharide (LPS) was used to induce of CB2 receptors. Materials and Methods: A [19F]fluorine-
regional inflammation in the right striatum of a mouse brain substituted reference compound and a tosylated precursor
S149 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

were synthesized and characterized (1H, 13C, 19F NMR). In both for noise reduction of short time DIBH PET scans and validate
cases indole was first acylated followed by N-alkylation. [18F] the accuracy using standard clinical metrics. Materials and
Fluoride was dried by azeotrope distillation using MeCN and Methods: 62 patients injected with 4 MBq/kg 18F-FDG was
TBAHCO3. The precursor (40 µmol) was substituted in MeCN imaged on a Siemens mCT. Six PET repetitions of 20 sec over
(5 min, 85 °C) and isolated by SPE- and HPLC-purification. Log the lung were acquired in DIBH followed by CT. Images was
P was determined by measurement of activity distribution reconstructed using PSF modeling 3i21s, fully anonymized and
between n-octanol and aqueous phosphate buffer (pH 7.4). cropped to 256x256 voxels. The first DIBH scan were used as
Protein plasma binding was measured after incubation of input to the DL network along with the CT and the average of
the tracer in fresh human blood plasma, followed by protein the 6 scans (in total 120 seconds scanning time) representing
precipitation and activity measurement. Additionally the tracer ground truth. We used 3D U-net with four blocks in the encoding
was incubated with CB2-expressing cell lines (HEK 293), the part, each consisting of strided convolution, dropout and ReLU
blocking of the receptor was performed by coincubation with activation function. 8 adjacent image residuals (full time - short
HU308, a high affine CB2 Agonist. Results: The non-radioactive time) were used as input along with the CT. We used MAE as loss
reference compound was obtained in 66% total yield and the function, learning rate of 10-4 and trained for 2000 epochs. We
corresponding tosylate-precursor was synthesized with 73% used a 2-fold setup each using 48 patients for training. During
total yield, both in a four-step synthesis. The radioactive tracer validation, we predicted the residual noise, which was added
was synthesized on a commercially available module (Neptis to the single short-time DIBH images to obtain a denoised PET
Perform, Ora) in up to 38% RCY and molar activities of up to 67 image. Metabolic tumor volumes were delineated on the 28
GBq/µmol (6-16 nmol carrier per Batch). The log P of the tracer validation images by a nuclear medicine specialist. SUV mean
was 3,83±0,04 (shake-flask method). Furthermore, protein- and standard deviation are reported. Results: Visual inspection
plasma binding was 81%. In blocking experiments using HU308 showed high resemblance of the denoised images compared to
in CB2-expressing HEK cultures the cell-bound tracer fraction full time PET images. Tumor outline showed no visible change.
could be significantly reduced time-dependently (40−50%, SUV mean was reproduced in all tumors with a mean error of
p<0.05). Conclusion: A new potential tracer for nuclear imaging -4.0% [-17% - 13%]. Relative change in noise level (SD) in the
of CB2 in CNS was synthesized. The automated radio synthesis tumors was -7% [-29% - 11%]. Outliers were located in the noisy
can be performed on a commercially available module and images at the ends of the scanning field. Conclusion: We have
delivered the tracer in good yield and high molar activity. First demonstrated that by using residual training a DL network can
preclinical evaluations were performed and present results are be used to reduce the scanning protocol from 6 repetitions
quite promising. References: 1 J. M. Frost et al. J. Med. Chem. to just a single breath-hold PET without loss of clinical quality.
2010, 53, 295-315. References: None.

906
Do.MoRe - Parallel Session: Artificial Intelligence OP-386
Deep Learning segmentation of planar thyroid
in Image Processing scintigraphy: application of U-net for cold nodules
detection
Monday, October 14, 2019, 14:30 - 16:00 Lecture Hall 112 F. Hanin1, M. Destiné1, J. Marques-Trindade2, I. Mathieu1, B.
Willemart1;
1
CHU UCLouvain Namur, Namur, BELGIUM,
OP-385 2
Neuralys Diagnostics, Brussels, BELGIUM.
Low-count PET reconstruction using deep learning:
application to FDG imaging of Hodgkin lymphoma during
deep inspiration breath hold Aim/Introduction: Deep Learning covers the use of neural
M. Gæde, C. N. Ladefoged, A. K. Berthelsen, A. Loft, F. L. Andersen; networks build with several layers of artificial neurons (or
Rigshospitalet, Copenhagen University, Copemhagen, DENMARK. perceptrons). A specific network design called U-net allows to
segment images. This network was trained and tested on 99mTc
- thyroid planar scintigraphies for segmentation and test if such
Aim/Introduction: Deep inspiration breath-hold (DIBH) can network can detect cold nodules. Materials and Methods:
reduce radiation doses to the lungs, heart, and cardiac structures The same operator retrospectively manually segmented 1135
without compromising target dose in Hodgkin Lymphoma thyroid scintigraphies. Consecutive masks were generated
(HL) during radiation therapy. 18F-FDG PET/CT is the choice for from ROIs and used as ground truth. Data augmentation was
diagnostic and planning of HL and thus needs to be acquired performed on the data by horizontal flip to reach a total of 2270
in DIBH. Today, this is performed in a series of self-monitored images and corresponding masks. Dice loss function was used
breath-hold scans producing an averaged fulltime PET scan. for training on an 1800 images batch, and testing was applied
Recently, methods utilizing deep learning (DL) for denoising on 470 remaining images. The training was performed using
have been proposed, but the impact on clinical accuracy has keras 2.2.0 and Tensorflow-GPU 1.8 as backend installed on
yet to be established. In this study we aim to use a DL network ubuntu 17.10 running CUDA 9.2 for two NVIDIA GTX 1070 GPUs.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S150

Training of the network was performed with various batch sizes architecture, the training procedure and the data augmentation
(from 1 to 20) and epochs (40 to 200). Dice value was computed strategy) that can be successfully applied for tumor
for each test image, except for thyroids with no uptake (mask segmentation on PET images and that is nearly indifferent to
entirely negative, dice coefficient is not computable). Results: image properties specific for a particular center. We used a
Best network performance was obtained by training with 3D-version of the popular U-Net model as a benchmark and
batches size of 2 and 150 epochs. Dice values on 427 test presented its modified version that demonstrated significantly
segmentations were: mean 0,98 ± 0,01; maximal value 0,992; better results on our dataset. To estimate the performance
minimal value 0,78; median value 0,983. Visual assessment of of the model, we used cross-validation where each fold was
each of the 470 test images showed 29 wrong segmentations comprised of only samples from a particular institute. A number
(6,1 %). Cold nodules were correctly included inside of the of metrics including Dice similarity coefficient (DSC), sensitivity
thyroid even when the uptake was visually similar to the and positive predictive value were used for evaluation. Results:
background. Conclusion: Deep Learning shows interesting The designed CNN obtained good average accuracy for all
promises for diagnostic assistance. The training process is long, considered institutes (DSC of 0.82 ±0.03) without requiring
requires massive computing power and is subject to flaws as any change in the whole pipeline. Most importantly, it was
overfitting; however, these results show that specific tasks can able to learn in most cases not to include the nearby bladder
be learned by artificial neural networks and even recognize cold in the resulting segmentation mask, hence allowing for a fully
nodules as part of the thyroid. Further research and data pooling automated primary tumor functional volume delineation.
are required to develop clinically valuable tools. References: Conclusion: We showed that CNNs can be successfully
U-Net keras code implementation used, https://github.com/ implemented for fully automatic tumor delineation on PET
petrosgk/Kaggle-Carvana-Image-Masking-Challenge. images without the need for user input, even in a multicentric
context. The described general pipeline can be implemented
with minimal modifications to solve a variety of segmentation
OP-387 tasks for PET images. References: None.
Automated Cervical Primary Tumor Functional Volume
Segmentation in PET Images
A. Iantsen1, F. Lucia2, M. Ferreira3, P. Bonaffini4, I. Masson5, A. OP-388
Mervoyer5, C. Reinhold4, P. Lovinfosse3, R. Hustinx3, M. De Cuypere3, Fully automated computations of putamen and caudate-
F. Kridelka3, U. Schick2, D. Visvikis1, M. Hatt1; based clinical measures in 18F-FE-PE2I-PET/CT dopamine
1
LaTIM, INSERM, UMR 1101, University Brest, Brest, FRANCE, transport imaging using deep learning segmentation
2
Radiation Oncology Department, University Hospital, Brest, L. Anderberg1, C. N. Ladefoged1, K. Korsholm2, L. Friberg2, M.
FRANCE, 3Centre Hospitalier Universitaire de Liège, Liège, BELGIUM, Lonsdale2, I. Law1, F. L. Andersen1;
4
Department of Radiology, McGill University Health Centre 1
Department of Clinical Physiology, Nuclear Medicine and
(MUHC), Montreal, QC, CANADA, 5Department of Radiation PET, Rigshospitalet, Copenhagen, DENMARK, 2Department of
Oncology, Institut de Cancérologie de l’Ouest, Nantes, FRANCE. Clinical Physiology and Nuclear Medicine, University Hospital
of Bispebjerg and Frederiksberg, Copenhagen, DENMARK.

Aim/Introduction: Radiomics studies, radiotherapy treatment


planning and response assessment mostly rely on manual or Aim/Introduction: The aim of this project was to develop a
semi-automatic tumor segmentation in medical images such as fully automated and practically useful method of delineating
MRI, CT and PET. The use of convolutional neural networks (CNNs) putamen and caudate for the newly introduced PET-tracer,
is relevant for fully automatic tumor delineation. However, this 18
F-FE-PE2I, in the context of diagnosing Parkinsonism, and
approach is challenging, especially in a multicentric context thus removing a time-consuming step required in computing
with images having different properties. Currently, most of clinically relevant measures. Materials and Methods: 170
the published studies have been devoted to the use of CNNs patients 18F-FE-PE2I PET/CT scanned for clinically uncertain
for automatic tumor segmentation in MRI and CT, whereas Parkinsonism over a continuous eight month period were
considerably less attention have been paid to PET images. selected and divided for training/validation sets (80/20). The
Moreover, the majority of studies on applying CNNs for PET have validation set had 24 abnormal and 10 normal PET scans. A
used only datasets with small cohorts of patients from one or 10-minute static PET-acquisition was performed 30-minutes
two centers. Our goal was to investigate the use of CNNs for fully after an i.v. injection of 200 MBq 18F-FE-PE2I. Preprocessing of
automatic tumor delineation on PET images in a multicentric the data consisted in intensity normalization, skull stripping
context and the challenging case of cervical cancer, where the and spatial normalization to MNI space. A 3D U-net CNN was
primary tumor functional volume is often close to the bladder. trained on ground-truth segmentations of putamen and
Materials and Methods: We collected FDG PET images of 252 caudate derived semi-manually on both CT and 18F-FE-PE2I PET
cervical cancer patients from five different institutions located in data. Patch shape was 80x48x48, stride one, sigmoid activation
Europe and Canada. All ground-truth labels were determined by function on final layer, batch size 10, learning rate 5x10-5,
clinical experts that followed the same annotation procedure. generalized Dice loss, max pooling with pool size 23 and image
We developed a versatile pipeline (data preprocessing, CNN augmentation was used. In validation, VOI-specific Dice-scores
S151 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

were computed, as well as specific binding ratios (SBR’s) relative tissue if necessary.The segmentation results were processed
to cerebellar gray matter and putamen-caudate activity ratios by the AI algorithm and classified into physiological or non-
as the clinically relevant semi-quantitative metrics. Results: For physiological. Two experienced nuclear medicine physicians
normal and abnormal scans the Dice-scores for putamen mean (CvG,DT) reviewed the results independently and corrected
(SD; range) were 97.6 (0.3; 97.2 - 97.9) and 89.3 (4.9; 79.1 - 96.9), the proposed classification if necessary. Both physicians were
respectively, and for caudate 96.3 (0.8; 95 - 97.5) and 83.7 (8.8; blinded to the disease type and patients’history and only findings
72 - 98.1), respectively. The mean difference in putamen-SBR with agreement between the two physicians were considered
given the two segmentations (neural network minus ground- Results: The performance of the algorithm for 5744 findings
truth) for normal and abnormal scans were mean (SD; range) with reader agreement was [sensitivity/specificity/accuracy/
0.03 (0.02; 0.01 - 0.05) and 0.62 (0.12; -0.10 - 0.38), respectively. precision]: Overall [0.97/0.99/0.99/0.97]; Disease type: Lung
For both methods, separation between normal and abnormal cancer [0.99/1.00/1.00/0.99]; Lymphoma [0.98/0.99/0.99/0.98];
patients was perfect in the validation set, leading to an AUC of Melanoma [0.84/01.00/0.99/0.97]; Colorectal cancer
1.0 in both cases. Similar results were observed for the putamen- [0.93/1.00/0.99/1.00]; Other cancer types [0.93/0.99/0.98/0.92];
caudate activity ratios. Inference time was approximately 5 Scanner type: TruePoint [0.98/1.00/0.93/1.00]; Horizon
seconds/scan. Conclusion: Using a 3D U-net CNN is a viable [0.97/0.99/0.98/0.95]; mCT [0.95/1.00/0.99/0.98]; Vision
and computationally efficient method for delineating putamen [0.99/0.99/0.99/0.96]. Conclusion: These results demonstrate
and caudate and thus computing clinically relevant measures robustness of the AI algorithm to disease type, scanner model
used in diagnosing Parkinsonism using 18F-FE-PE2I PET/CT. and reconstruction parameters. This suggests that this approach
Main obstacles are associated with abnormal scans for which may be suitable for routine clinical work. References: [1] Sibille
activity in both structures is reduced. Yet in terms of clinical et al. PET Uptake Classification in Lymphoma and Lung Cancer
measures, separability between abnormal and normal patients using Deep Learning, Proc. SNMMI, Philadelphia, (2018) [2] Wahl,
remained intact. References: None. R. et al, From RECIST to PERCIST: Evolving Considerations for PET
Response Criteria in Solid Tumors. J Nucl Med 50, 122S-150S
(2009).
OP-389
Performance assessment of Artificial Intelligence-
supported lesion classification in a heterogenous 18F-FDG OP-390
PET/CT population Consensus of machine learning pipelines for outcome
C. Von Gall, D. Thomas, V. Shah, L. Sibille, B. Spottiswoode; prediction relying on clinical and radiomics features from
Siemens Medical Solutions USA, Inc., Knoxville, 18
F-FDG PET/CT images in non-small cell lung cancer
TN, UNITED STATES OF AMERICA. M. Hatt1, S. Sepehri1, T. Upadhaya2, D. Visvikis1, C. Cheze Le Rest2;
1
INSERM, Brest, FRANCE, 2CHU Milétrie, Poitiers, FRANCE.

Aim/Introduction: Artificial intelligence (AI) in PET/CT reading


could support routine tasks, such as the identification of Aim/Introduction: Radiomics consists in extracting a large
physiological uptake. As a prerequisite, the technology should number of quantitative features from medical images and
perform robustly in a heterogeneous patient cohort. The aim combining these features with clinical variables in order to
of this work is to assess the performance of a deep learning predict patients outcome, tumor sub-type or gene expression.
algorithm that classifies 18F-FDG uptake in a such a population. Given the potentially very large number of features compared to
Materials and Methods: 181 PET/CT scans were evaluated the usually limited number of patients, machine (deep) learning
using a convolutional neural network [CNN], that was trained (ML) is today a crucial part of the methodological toolbox used
previously with 18F-FDG scans of lung cancer and lymphoma for radiomics analyses. In this work we evaluated the interest
cases from two scanner types [1].The evaluation data consisted of combining several classifiers to improve the prediction
of lung cancer, lymphoma, melanoma, colorectal and other performance. Materials and Methods: We implemented and
cancer types [27.1%,26%,9.4%,4%, and 24.3%, respectively]. optimized three popular ML methods: random forest (RF),
In 9.4% the underlying disease was not available. Data was support vector machines (SVM), -both with embedded features
acquired on TruePoint, mCT, Horizon and Vision Biograph PET/ selection- and logistic regression (LR) -with stepwise feature
CT scanner generations (4%,19%,57% and 20%,respectively) selection- for predicting overall survival (OS) relying on clinical
(Siemens Medical Solutions USA, Inc.).Acquisition and variables and 18F-FDG PET/CT radiomics features in a cohort
reconstruction methods consisted of OSEM and OSEM3D PSF- of 145 non-small cell lung cancer patients with stage 2 and 3,
ToF (214ps to 540ps), with Gaussian post filter FWHM’s varying which was split into a training set (67%, n=97) and a testing set
from 0 to 5 mm. None of the data used for this evaluation (33%, n=48) using stratified sampling, ensuring similar outcome,
was part of the initial development, training or testing of the number of events and clinical characteristics in both sets. The set
AI algorithm. Automated segmentation was performed by endpoint for this study was to identify patients with OS below
identifying significant uptake using PERCIST recommendations the median (15 months). The outputs of the three ML pipelines
(SUVpeak,Liver VOI) and segmenting using 42% of max[2]. The were then aggregated through majority voting in order to
liver VOI was manually re positioned to cover normal hepatic derive a consensus classification. The classification accuracy was
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S152

used to evaluate the performance in the testing set. Results: (SUV), shape, GLCM, GLSZM, GLRLM, NGTDM and GLDM.
In the training set, the 3 different ML pipelines selected slightly Following feature extraction, we apply a union on embedded
different sets of features (25, 27 and 37 variables for RF, SVM and feature selection with different methods to get a set of useful
LR) and reached similar although slightly different accuracy features. After getting the union, we investigated correlations
(90%, 95% and 74% for RF, SVM and LR respectively). In the between features to eliminate high correlate features. The
testing set the accuracy was 68%, 67% and 65% for RF, SVM and selected features were fed into different classifiers including
LR respectively. The majority voting of their outputs reached a decision tree(DT), bagging, gradient boosting (GB), random
higher performance (accuracy of 100% in the training set and forest (RF), ada-boost (AB), logistic regression (LR), support
75% in the testing set). Conclusion: Different ML pipelines vector machine (SVM), naïve Bayesian (NB), LASSO, multi-layer
reached similar accuracy in predicting the notoriously difficult perceptron (MLP), and an ensemble of the above methods.
endpoint of survival in NSCLC. Implementing simple majority By comparison, our deep learning framework included a 3D
voting of these outputs allowed to increase the accuracy. Even deep convolution neural network (CNN) composed of 3×3×3
though the level of accuracy reached can seem relatively low convolutions, batch norm, LeakyReLU, and 2×2×2 max pooling
(~75%), the resulting prognostic stratification is higher than blocks followed by fully connected layers. The final layer is a soft-
when relying on clinical stage (58%), and of interest for clinical max for binary classification. We evaluated the performance of
practice as it could help identifying patients with higher risk classifiers using receiver operating characteristic (ROC) area
amongst stage II and III patients, that could benefit from under the curve (AUC) analysis with 10-fold cross validation.
intensified treatment and/or more frequent follow-up after Results: NB and RF with AUCs of 75.04 and 72.02 had the
treatment. References: None. highest performance in predicting EGFR and KRAS mutations,
respectively. Ensemble methods hadAUCs of 86.98 and
77.05 for predicting EGFR and KRAS, respectively. Finally, CNN
OP-391 had AUCs of 89.95 and 79.02 in predicting EGFR and KRAS
Radiogenomics analysis of PET/CT images in lung cancer mutations,respectively. Conclusion: Radiogenomics analysis
patients: Conventional radiomics versus deep learning of PET images in NSCLC patients was undertaken to link
I. Shiri1, G. Hajianfar1, S. Ashrafinia2,3, E. Jenabi4, M. Oveisi1,5, A. PET uptake and heterogeneity quantitation with genomics.
Rahmim6,7; Ensemble learning in the context of radiomics analysis can result
1
Department of Biomedical and Health Informatics, Rajaie in significantly higher performance compared to individual
Cardiovascular Medical and Research Center, Iran University learning models, while deep learning (CNN; implicit feature
of Medical Science, Tehran, IRAN, ISLAMIC REPUBLIC OF, extraction) showed the highest performance in prediction of
2
Department of Radiology and Radiological Science, Johns EGFR and KRAS status. The results of the current study indicate
Hopkins University, Baltimore, MD, UNITED STATES OF AMERICA, the potential of advanced machine learning methods within
3
Department of Electrical and Computer Engineering, Johns radiogenomics analysis towards non-invasive prediction of
Hopkins University, Baltimore, MD, UNITED STATES OF AMERICA, mutation status in patients with NSCLC. References: None.
4
Research Center for Nuclear Medicine, Shariati Hospital,
Tehran University of Medical Sciences, Tehran, IRAN, ISLAMIC
REPUBLIC OF, 5Department of Computer Science, University OP-392
of British Columbia, Vancouver, BC, CANADA, 6Departments Towards fully automated image processing in the clinic
of Radiology and Physics & Astronomy, University of British J. Taylor, P. Metherall;
Columbia, Vancouver, BC, CANADA, 7Department of Integrative Sheffield Teaching Hospitals, Sheffield, UNITED KINGDOM.
Oncology, BC Cancer Research Centrer, Vancouver, BC, CANADA.

Aim/Introduction: Machine learning has huge potential in


Aim/Introduction: Analysis of the mutation status of epidermal Nuclear Medicine for increasing efficiency and improving
growth factor receptor (EGFR) and Kirsten rat sarcoma viral accuracy. In particular, numerous authors have demonstrated
oncogene (KRAS) mutations arefrequently used as treatment high performance in segmentation, classification and regression
management tools in non-small cell lung cancer (NSCLC). The tasks. However, many studies are based on assumptions which
objective of this study was to investigate and compare EGFR may not be reflective of the clinic, for instance using research
andKRAS mutation status in PET images using conventional rather than clinical data. Implementation for routine patient
radiomics (explicit-feature-extraction) versus deep learning care has so far been limited. This study aims to demonstrate the
(implicit-feature-extraction). Materials and Methods: 147 performance of established machine learning methods for two
NSCLC patients were included in the study, where 32 had routine nuclear medicine processing tasks, currently performed
effective EGFR mutations, 37 had KRAS mutations, and 110 and manually in clinic: 1) segmentation of the myocardium in MPS
115 had no EGFR or KRASmutations, respectively. Tumors were stress-rest scans (the segmentation mask being used to guide
segmented by semiautomatic method from the PET images a rigid registration, to quantify differences in patient position)
(expert radiologist). For conventional radiomics analysis,images and 2) segmentation of the left ventricle blood pool for ejection
were first discretized into 64 bin levels. 105 features were fraction estimation on MUGA scans. Automating either of
subsequently extracted from the lesions, including statistical these tasks would achieve significant reductions in workload.
S153 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

Materials and Methods: A large set of historical clinical data 908


was used for both applications: 9604 MPS studies (stress and
rest), acquired from a GE Discovery 530nm camera and 4092
Clinical Oncology - Featured Session: Evaluating
MUGA scans acquired from a range of different gamma cameras,
Immunotherapy - Where do we stand?
all with manually drawn segmentation masks, were extracted
from the archives at Sheffield Teaching Hospitals. In each case Monday, October 14, 2019, 14:30 - 16:00 Lecture Hall 114
a convolutional neural network was trained on 80% of the data
using niftynet software (www.niftynet.io). For segmentation of
the myocardium on MPS data the highres3dnet architecture OP-396
was used. For the MUGA ejection fraction task, an architecture Scientific Programme
based on U-net was adopted. 10% of the data was set aside TBA;
for validation and 10% for testing. Automatically generated TBA.
segmentation masks were compared to those generated
manually in terms of Dice scores. Output quantities from both OP-397
processing tasks were also compared between automated and Total Metabolic Tumor Volume (TMTV) correlates with
manual methods. Results: For task 1) a mean Dice of 0.85 was treatment failure after CD19 CAR T-cell therapy in patients
achieved on test data. Patient offset measurements gave a mean with relapsed/refractory diffuse large B-cell lymphoma
difference of -0.006mm when using the automatically generated (DLBCL)
segmentation, rather than the manual one (far smaller than the L. S. Vercellino1, J. Paillassa1, A. Martineau1, S. Chevret1, R. Di Blasi1,
reconstructed pixel size). For task 2) automatic segmentations S. Bernard1, E. De Kerviler1, V. Meignin1, M. Meignan2, P. Merlet1, C.
have so far been compared to manual across the whole cardiac Thieblemont1;
cycle (i.e. treating the MUGA scan as a 3D dataset, with each 1
Hôpital Saint Louis, Paris, FRANCE, 2LYSA Imaging Henri
slice representing a single cardiac phase). Preliminary results Mondor University Hospitals, Créteil, FRANCE.
have demonstrated a mean Dice of 0.75. Conclusion: Existing
machine learning technology can achieve high performance
for routine nuclear medicine processing tasks. Fully automated Aim/Introduction: Despite significant clinical benefit in
patient positioning checks have now been implemented in the relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL),
local department based on these results References: None. patients treated with autologous anti-CD19 chimeric antigen
receptor (CD19 CAR) T-cells may experience early relapse/
907 progression within the first 90 days after infusion. High total
metabolic tumor volume (TMTV) measured with 18F-FDG PET/
Teaching Session 3 - Interactive Clinical Cases: CT before R-CHOP is significantly associated with the outcome
Radiological Aspects of Thoracic Anatomy of patients with DLBCL. The aim of our study was to evaluate
if high TMTV measured immediately before infusion was
Monday, October 14, 2019, 14:30 - 16:00 Lecture Hall 113 associated with early relapse in patients with R/R DLBCL treated
with CAR T-cells. Materials and Methods: We performed a
retrospective cohort analysis including consecutive patients
OP-393 treated with CAR T-cells for R/R DLBCL between June 2018 and
Radiological Aspects of Thoracic Anatomy February 2019. Median follow-up was 86 days (range: 15-198).
T. Lynch; TMTV was measured on pre-infusion PET/CT with either the
Belfast, UNITED KINGDOM. 41% SUVmax threshold method (TMTV41%), or a fixed threshold
of SUV>4 (TMTV4), using the free semiautomatic software Fiji.
Total Lesion Glycolysis (TLG) was calculated for each method.
OP-394 Relapse and progression were determined based on the
Radiological Aspects of Thoracic Anatomy Lugano criteria. Predictive factors associated with relapse
N. Magee; were assessed using univariate (10% level) then multivariate
Belfast City Hospital, Belfast, UNITED KINGDOM. Cox models. To measure the predictive accuracy of TMVT for
relapse, cumulative / dynamic ROC curves were used. Results:
31 patients received CD19 CAR T-cells. The median age was 48
OP-395 years (range: 23-77), with 20, 5 and 6 patients having R/R DLBCL,
Radiological Aspects of Thoracic Anatomy primary mediastinal B-cell lymphoma and transformed follicular
K. McManus; lymphoma, respectively. Tumor bulk >5 and>10 cm was
Belfast, UNITED KINGDOM. reported in 12 (39%) and 7 (23%), respectively. Median TMTV41%
was 37.9 cm3 (range: 1.44-630.9) and median TMTV4 was 48
cm3 (range: 0-940). Median TLG41% was 294.3 g (range: 2.43-
6685.2) and median TLGSUV4 was 379.5 g (range: 0-781.839).
Treatment failure occurred in 11 patients, with a median time of
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S154

18 days (range: 4-119). IPI (p=0.045) and aaPI (p=0.09), number was 32±10 and 37±14 years in the training and validation sets,
of previous lines (p=0.01), C-reactive protein (p=0.002), Albumin respectively. Fourteen patients had bone disease (14/36) in the
(p=0.005), Ferritin (p=0.001), lactate dehydrogenase (p=0.0006), training set, and 9/21 in the validation set. Eleven and 10 patients
most intense SUVmax (p=0.09), TMTV41%(p=0.003) and TMTVSUV4 were classified as responders in the training and validation sets,
(p=0.006), TLG41% ((p=0.003), TLGSUV4 (p=0.010) were significantly respectively. Six radiomics features (SUVmean, TLG, NGLDM_
associated with relapse by univariate analyses. After multivariate Coarseness, GLRLM_LRLGE, GLZLM_GLNU, GLZLM_ZP) were
analysis and model selection, only the number of previous fed into the model. The radiomics model correctly predicted
lines (HR 1.66, CI95% [1.10;2.52], p 0.016), and TLG41% (HR 4.46, all patients as responders and non-responders in both the
CI95% [1.58-12.6], p 0.005) were predictive of relapse. Similar training and validation cohorts. The clinical model correctly
results were reached with TMTVSUV4 (HR 4.91, CI95% [1.47-16.5], identified 11/11 patients as responders and 22/25 patients as
p 0.010). Conclusion: In our cohort, TMVT and TLG at baseline non-responders in the training set. The clinical model correctly
were correlated to relapse in patients with R/R DLBCL treated predicted all patients as responders and non-responders in the
with CAR T-cells. References: None. validation cohort. Conclusion: Radiomics features performed
slightly better than clinical parameters in predicting checkpoint
inhibitor treatment outcome. Patients who benefit from
OP-398 checkpoint inhibitor treatment can be successfully selected by
Value of FDG-PET/CT radiomic features in predicting pre-treatment PET/CT textural features. References: 1. Cancer
response to anti-programmed death 1 (PD-1) antibodies Research 2018;78(16):4786-4789.
treatment in refractory Hodgkin Lymphoma patients
M. Sollini1, M. Kirienko1, L. Cozzi2, C. Torrisi2, L. Antunovic2, E.
Tabacchi3, L. Calderoni3, C. Nanni3, A. Alessi4, E. Seregni4, S. Fanti3, OP-399
A. Guidetti4, F. Ricci2, P. Corradini4,5, P. Zinzani3, C. Carlo Stella1,2, A. FDG PET/CT in the early assessment of NSCLC response
18

Chiti1,2; to immunotherapy: results from a prospective study


1
Humanitas University, Pieve Emanuele, ITALY, 2Humanitas O. Humbert, N. Cadour, M. Paquet, D. Chardin, J. Otto, J. Darcourt;
Clinical and Research Center, IRCCS, Rozzano, ITALY, Centre Antoine-Lacassagne, Nice, FRANCE.
3
Policlinico S.Orsola – University of Bologna, Bologna,
ITALY, 4Fondazione IRCCS Istituto Nazionale dei Tumori,
Milan, ITALY, 5University of Milan, Milan, ITALY. Aim/Introduction: Few data are available regarding the role
of 18FDG-PET to monitor non-small cell lung cancer (NSCLC)
response to immunotherapy. This prospective study aimed to
Aim/Introduction: To assess the predictive role of positron describe the PET response patterns to immunotherapy and their
emission tomography (PET)-derived radiomic features in patients association with clinical outcome. Materials and Methods: Fifty
affected by refractory Hodgkin Lymphoma (HL) undergoing patients with metastatic NSCLC were prospectively included
checkpoint inhibitor treatment. Materials and Methods: This before pembrolizumab or nivolumab initiation. FDG-PET scan
retrospective multicenter study evaluated HL patients who was performed at baseline and after 7 weeks of treatment
performed a PET/CT before the initiation of anti-programmed (PETInterim1). On PETInterim1, different criteria/parameters of tumor
death 1 (anti-PD-1) monoclonal antibodies. The volume of response were assessed (PERCIST; ΔSUV; new lymph nodes
interest (VOI) of the target lymph node (the largest in transverse or visceral lesion(s)). If a first PERCIST progressive disease (PD)
diameter and/or with the highest maximum standardized without clinical worsening was observed, the treatment was
uptake value (SUVmax)) - was semi-automatically defined on continued and a subsequent FDG-PET scan (PETinterim2) was
PET images with a threshold of 40% of the SUVmax using a performed at 3 months of treatment. If a second PERCIST
commercial software (PET VCAR, GE Healthcare, Waukesha, WI, PD was assessed, a homogeneous progression of lesions
USA). The features were extracted using LifeX software (http:// (termed immune progressive disease: iPDhomogeneous) was
www.lifexsoft.org, [1]). The dataset was geographically split distinguished from a heterogeneous one (termed immune
into training (center 1) and validation (centers 2 and 3) sets. dissociated response: iDR). Pseudo-progression (PsPD) was
Combinations of imaging features were used as predictors defined as a delayed PERCIST response or stability after a first
in k-nearest neighbors after principal component analysis PD. PETinterim2 was confronted to patients’ clinical status for
reduction. Moreover, clinical parameters (age, sex, bone therapeutic management. A durable clinical benefit (DCB) of
disease) were tested as predictors. Treatment response was immunotherapy was defined as treatment continuation over a
assessed according to Lyric criteria. Patients were classified as 6-month period. The association between PETinterim1 parameters,
responders (stable disease, partial or complete response) and PETinterim2 evolutive profiles and DCB were assessed. Results:
non-responders (progressive disease).The discriminative ability Using PERCIST on PETinterim1, 42% (21/50) of patients showed
of the models to identify responders and non-responderswas a response or stable disease, most of them (18/21) reached a
calculated as true positive, true negative, false positive, and false DCB. In contrast, 58% (29/50) showed a PD, but more than one
negative. Statistical analysis was performed using STATA. Results: third (11/29) were misclassified as they finally reached a durable
Fifty-seven HL patients, 36 in the training set (M:F=21:15) and clinical benefit of immunotherapy. None of the standard
21in the validation cohort (M:F=15:6)were analyzed. Mean age PETinterim1 parameters could accurately identify non-responding
S155 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

patients with early treatment failure. Treatment was continued (95%CI 0.8-2.0) months (both p<0.001). The score also correlated
in 19/29 of patients despite a first PD. The subsequent PETinterim2 with response. The good prognosis group was associated with
demonstrated iPDhomogeneous, iDR and PsPD in 47%(9/19), DCR, with an OR of 8.5 (95%CI, 2.3-31.5, p=0.001), which was
26%(5/19) and 25%(5/19), respectively. Whereas no patients even higher than those determined with MTB or dNLR alone
with iPDhomogeneous experienced a DCB, all patients with iDR and (OR 3.5, p=0.01 and 3.6, p=0.008, respectively). Results were
PsPD reached a clinical benefit to immunotherapy. Conclusion: reproducible in the validation cohort for OS, PFS, and DCR.
In patients with a PERCIST progressive disease on a first interim Conclusion: Pretreatment score, combining MTB and dNLR,
FDG-PET, a subsequent exam will identify more than half of them was correlated with worse outcomes for ICI. This innovative
with iDR and PsPD, both patterns being strongly associated with scoring approach could improve the selection of appropriate
a favorable clinical outcome. References: None. candidates and might be useful for identifying NSCLC patients
unlikely to benefit from treatment with an ICI. References:
None.
OP-400
Combined Pre-Treatment Metabolic Tumor Burden on
18F-FDG PET/CT and Derived Neutrophils to Lymphocytes OP-401
Ratio as Prognostic and Predictive Biomarkers in FDG-PET/CT Imaging Of Immune-related Adverse Effects
Advanced Non-Small Cell Lung Cancer Patients Treated In Patients With Cutaneous Melanoma Treated With
with Immune Checkpoint Inhibitors Pembrolizumab
R. Seban1,2, L. Mezquita2, L. Champion1, A. Berenbaum2, A. A. Sabaté-Llobera1, P. C. Notta2, M. Martínez de Bourio2, L.
Botticella2, C. Le Péchoux2, C. Caramella2, L. Cabel1, M. Massiani1, Jiménez-Colomo3, J. Martín-Liberal3, M. Cortés-Romera2, J.
L. Dercle2, S. Grimaldi2, S. Leboulleux2, D. Planchard2, N. Girard3, B. Marcoval4, J. L. Vercher-Conejero2, C. Gámez-Cenzano2;
Besse2; 1
PET Unit, Department of Nuclear Medicine-IDI. Skin Cancer
1
Institut Curie - René Huguenin, Saint-Cloud, Multidisciplinary Team. Hospital Universitari de Bellvitge-IDIBELL,
FRANCE, 2Gustave Roussy, Villejuif, FRANCE, 3Institut L’Hospitalet de Llobregat (Barcelona), SPAIN, 2PET Unit, Department
du Thorax Curie-Montsouris, Paris, FRANCE. of Nuclear Medicine-IDI. Hospital Universitari de Bellvitge-IDIBELL,
L’Hospitalet de Llobregat (Barcelona), SPAIN, 3Department of
Medical Oncology-ICO. Skin Cancer Multidisciplinary Team.
Aim/Introduction: We aimed to evaluate if a score combining Hospital Universitari de Bellvitge-IDIBELL, L’Hospitalet de
Metabolic Tumor Burden (MTB) on pretreatment 18F-FDG PET/ Llobregat (Barcelona), SPAIN, 4Department of Dermatology.
CT and derived Neutrophils to Lymphocytes Ratio (dNLR) could Skin Cancer Multidisciplinary Team. Hospital Universitari de
predict clinical outcomes in patients with advanced non-small Bellvitge-IDIBELL, L’Hospitalet de Llobregat (Barcelona), SPAIN.
cell lung cancer (NSCLC) treated with immune checkpoint
inhibitors (ICIs). Materials and Methods: In this retrospective
bicentric study, we enrolled 105 patients (80 for training and 25 Aim/Introduction: Pembrolizumab is a PD-1 inhibitor that
for validation) with advanced NSCLC who underwent baseline has demonstrated to improve progression-free survival
18F-FDG PET/CT before ICI initiation between July 2013 and and overall survival in patients with advanced melanoma*.
October 2018. Clinical, biological (including dNLR=neutrophils/ However, it is not exempt of secondary effects, mostly due to
[leukocytes minus neutrophils]), pathological and PET blocking the inhibitory pathways of T-cell activation, which
parameters (including MTB) were evaluated. MTB was defined as can cause autoimmune-like pathology. We describe different
the sum of the Metabolic Tumor Volume of all hypermetabolic immune-related adverse effects (IRAE) detected on FDG-PET/
lesions, measured with setting a margin threshold as 42% of CT in patients treated with this immune checkpoint inhibitor.
SUVmax. A score based on MTB (high if > to the median value Materials and Methods: Retrospective review of prospectively
and dNLR (high if >3), was developed, characterizing 3 groups collected data of 13 patients (8 women) with cutaneous
(good, 0 factors; intermediate, 1 factor; poor, 2 factors). A melanoma treated with pembrolizumab due to systemic disease
multivariate prediction model was developed using Cox models relapse. All of them had FDG-PET/CT scans performed before
for progression-free survival (PFS) and overall survival (OS) and a initiating systemic therapy and at different time-points during
logistic regression for disease control rate (DCR). Results: In the treatment. FDG-PET/CT detection of possible IRAE was reported
training cohort, median follow-up was 11.6 months (95%CI 7.7- and evaluated, both clinically and/or in subsequent FDG-PET/
15.5). Sixty-four and 52 patients experienced progression and CT studies. Results: Seven patients (53.8%) presented findings
death, respectively. DCB was 40%. Median PFS and OS were 2.5 suggestive of IRAE at follow-up FDG-PET/CT; six of them (87.5%)
(95%CI 1.6-3.3) and 9.2 (95%CI 6.2-12.2) months, respectively. were women. The most common adverse effect was thyroiditis
In multivariate analyses, MTB>median (75cm3) and dNLR>3 (3 patients), followed by sarcoid-like reactions (2 patients),
were associated with shorter OS (HR 2.5, 95%CI 1.3-4.7, p=0.004 aortitis (1 patient), and arthritis/synovitis (1 patient). In 6 cases,
and HR 3.3, 95%CI 1.6-6.4, p=0.001, respectively). Median OS these effects appeared after 2-8 cycles of pembrolizumab,
for good, intermediate, and poor score was 35.0 (95%CI 14.6- while one of the sarcoid-like reactions appeared 2 months after
55.4), 12.5 (95%CI 6.6-18.5) and 2.4 (95%CI 1.9-2.9) months and finishing the treatment (36 cycles). All thyroiditis presented with
median PFS was 9.8 (95%CI 5.2-14.4), 2.7 (95%CI 1.7-5.8) and 1.4 hypothiroidism parameters at blood tests and were treated
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S156

with levothyroxine. Both cases with sarcoid-like reactions increasing concentrations of unlabeled tracers to determine
were histologically confirmed, one through an endobronchial the relative binding affinities. To assess tumor-specific binding,
ultrasound bronchoscopy and the other one with a cutaneous autoradiography assays were performed on cryosections of
biopsy. The patient with arthritis/synovitis complained of human salivary- and renal tissue incubated with the [177Lu]
articular pain, while the one with aortitis was asymptomatic; no Lu-labeled PSMA-tracers with or without an excess of the
blood tests with inflammatory parameters were performed in same unlabeled tracer. The in vivo biodistribution patterns of
this patient, and vascular wall activity persisted in subsequent [177Lu]Lu-DOTA-PSMA-617 and [177Lu]Lu-DOTA-PSMA-I&T were
FDG-PET/CT. Among patients with IRAE, four reached a determined in athymic nude mice bearing PC295 PDXs. Mice
metabolic complete response (57.1%), one a partial response, were intravenously injected with the [177Lu]Lu-labeled tracers
and two progressed (28.6%). Of those who had not IRAE, five (30MBq/0.3nmol) and sacrificed 4h, 8h, or 24h post injection (p.i.)
were progressing (83.3%), and one had stable disease after (n=4 per group). Organs and blood were collected and tracer
having progressed at 2 cycles of pembrolizumab. Conclusion: uptake was measured. Results: In vitro displacement studies
IRAE are frequently evidenced in FDG-PET/CT of patients revealed high and PSMA-specific binding affinity for all three
treated with pembrolizumab for cutaneous melanoma, being tracers with IC50 values in the nanomolar range. [177Lu]Lu-DOTA-
thyroiditis the most common in our series. Despite the little JVZ-007 could not be displaced by DOTA-PSMA-617 and DOTA-
number of patients analysed, those with IRAE seem to have a PSMA-I&T, suggesting this tracer to target an alternative PSMA
better response to treatment. References: Robert C, Schachter binding site. Autoradiography assays showed a ±90% lower
J, Long GV, et al. Pembrolizumab versus Ipilimumab in Advanced tumor binding of [177Lu]Lu-DOTA-JVZ-007 and interestingly, a
Melanoma. N Engl J Med 2015; 372:2521-32. 4-times lower tumor-to-kidney and tumor-to-salivary gland ratio
as compared to [177Lu]Lu-DOTA-PSMA-617 and [177Lu]Lu-DOTA-
909 PSMA-I&T. In vivo biodistribution assays revealed a comparable
average tumor uptake of [177Lu]Lu-DOTA-PSMA-617 and [177Lu]
Special - Parallel Session: Tomorrow?s Experts Lu-DOTA-PSMA-I&T of ±5% at all time points. However, [177Lu]Lu-
Session - Best-Ranked Papers from the Under- DOTA-PSMA-I&T showed a ±40x higher uptake in the kidneys at
30s 4h and 8h p.i. resulting in an unfavorable tumor-to-kidney ratio.
Conclusion: While in vitro binding characteristics for [177Lu]
Monday, October 14, 2019, 14:30 - 16:00 Lecture Hall 115 Lu-DOTA-PSMA-617 and [177Lu]Lu-DOTA-PSMA-I&T are highly
comparable, [177Lu]Lu-DOTA-PSMA-617 has a more favorable
biodistribution in mice with a higher tumor-to-kidney ratio
compared to [177Lu]Lu-DOTA-PSMA-I&T. Concerning [177Lu]Lu-
OP-402 JVZ-007, the significantly lower in vitro binding of this tracer to
First extensive preclinical evaluation of PSMA-specific the salivary and renal tissue is very favorable and underlying
tracers for prostate cancer radioligand therapy reasons are being explored further. References: None.
E. Ruigrok, S. U. Dalm, E. de Blois, N. van Vliet, D. C. van Gent, J.
Haeck, C. de Ridder, D. Stuurman, M. W. Konijnenberg, W. M. van
Weerden, M. de Jong, J. Nonnekens; OP-403
Erasmus MC, Rotterdam, NETHERLANDS. Synthesis and Preclinical Evaluation of GRPR/PSMA
Bispecific Heterodimers for the Theranostics Application in
Prostate Cancer
Aim/Introduction: Prostate specific membrane antigen A. Abouzayed, C. Yim, B. Mitran, S. Rinne, V. Tolmachev, M. Larhed,
(PSMA) is overexpressed in >90% of prostate cancer (PCa) cases. U. Rosenström, A. Orlova;
Therefore, various radiolabeled PSMA-targeting tracers are Uppsala University, Uppsala, SWEDEN.
clinically applied for PCa imaging and radioligand therapy (RLT).
The PSMA binding affinities and biodistribution of these tracers
however, have not yet been compared. Furthermore these PSMA- Aim/Introduction: Prostate cancer is one of the most prevalent
targeting radiotracers show toxicity in other PSMA-expressing and deadliest cancers in men worldwide. Several prostate
organs, such as the salivary glands. A proper evaluation cancer cell markers have been identified, including gastrin-
therefore is essential to determine the best performing tracer, releasing peptide receptors (GRPR) and prostate-specific
however, such evaluation is currently missing. This study is the membrane antigens (PSMA). GRPR and PSMA are overexpressed
first extensive preclinical evaluation of the clinically relevant in the majority of prostate cancer samples with GRPR expression
PSMA targeting tracers DOTA-PSMA-617, DOTA-PSMA-I&T being higher in earlier stages and PSMA expression increasing
together with nanobody DOTA-JVZ-007 using PSMA expressing with the disease progression. The aim of this study was to
cell lines and PCa patient-derived xenografts (PDXs). Materials develop and evaluate GRPR/PSMA bispecific heterodimers for
and Methods: In vitro displacement assays were performed the management of prostate cancer. The heterodimers consist
on PSMA-expressing cells (LNCaP, DU145-PSMA, U2OS-PSMA) of urea derivative PSMA-617 and bombesin-based antagonistic
and cryosections of PSMA-positive PDXs (PC295), which were analogue RM26 (D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH2)
incubated with the 3 [177Lu]Lu-labeled tracers together with linked via X-triazolyl-Tyr-PEG2 (X= PEG2 (BO530), (CH2)8 (BO535),
S157 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

or none (BO536)). The heterodimers can be radioiodinated the main PET system axis (z-axis). The distribution of positron
with I-123 for SPECT imaging, I-124 for PET imaging, or annihilation points was modelled as a direct product of (i) the
I-131 for therapeutic purposes. Materials and Methods: radial distribution of annihilation events and (ii) a 1D height-
The heterodimers were synthesized by solid phase peptide distribution that intrinsically models the impact of B0 according
synthesis, radiolabeled with I-125, and evaluated in vitro for to the performed simulations [3]. Mean positron range (Rmean)
their binding specificity, cellular retention, and affinity towards was calculated from the simulation output. Results: Elongated
GRPR and PSMA. In vivo specificity was studied on mice bearing annihilation point distributions were observed for high B0 for
PC-3 (GRPR+) or LNCaP (PSMA+) xenografts for all heterodimers. all simulated isotopes. The line profiles of positron annihilation
[125I]I-BO530 was further evaluated in PC-3pip (GRPR+/PSMA+) points of 124I/68Ga show a relative reduction of 2D positron range
xenografted mice 1, 3, 24 and 72 h pi. MicroSPECT/CT scans of up to 53%/62%, measured perpendicular to the B0 axis for a
were acquired 3, 24 and 72 h pi. Results: The heterodimers field of 9.4T respectively. Absolute reduction of mean positron
were radiolabeled with I-125 with high radiochemical yields. range (Rmean) for 18F/68Ga in water (0.32/1.94 mm), bone
After HPLC purification radioiodinated heterodimers bound (0.09/0.34 mm) and lung (1.58/6.89 mm) was seen for increasing
specifically to GRPR and PSMA in vitro. The half-maximal B0 from 0.0T to 9.4T. General agreement of simulated PR with
inhibitory concentrations were 8-25 nM for GRPR and 95-127 measured values was 3.0% / 9.1% for 18F / 68Ga respectively
nM for PSMA. The heterodimers demonstrated high degree of [4]. Conclusion: A parameterized mathematical model to
activity retention in PC-3pip cells (after 24 h incubation 65% of calculate PR in magnetic field was established based on Monte
initially bound activity were cell associated). In vivo, only [125I] Carlo simulations that correctly estimates PR for various B0
I-BO530 demonstrated in vivo specificity to both GRPR and field strengths. The inclusion of this model into PR correction
PSMA receptors. The biodistribution study of [125I]I-BO530 in algorithms is work in progress and it will be presented at the
mice bearing GRPR+/PSMA+ xenografts showed relatively slow conference. References: [1] Kolb A. et. al. Shine-Through in PET/
for small peptides blood clearance that resulted in high tumor MR Imaging: Effects of the Magnetic Field on Positron Range
activity uptake (21±3%ID/g at 1 h pi). While activity uptake in and Subsequent Image Artifacts. JNM 2015 [2] Stute et al.,
normal organs rapidly decreased, activity uptake in tumors was Monte Carlo simulations of clinical PET and SPECT scans: impact
stable between 3 and 24 h pi (30-35%ID/g). Already 24 h pi of the input data on the simulated images. Phys Med Biol 2011
activity uptake in tumors exceeded all other organs, including [3] Blanco A. Positron range effects on the spatial resolution of
excretory organs. At 72 h pi activity uptake decreased only 2-fold. RPC-PET. IEEE Nucl Sci Symp Conf Rec 2006 [4] J Cal-González
The SPECT/CT images confirmed ex vivo results. Conclusion: et. al. Positron range estimations with PeneloPET. Phys Med Biol
The radioiodinated PSMA-617/RM26 heterodimer [125I]I-BO530 2013.
is a promising agent for the theranostics application in prostate
cancer. References: None.
OP-405
CTCA based assessment of endothelial shear stress and
OP-404 functional significance of coronary lesions: relationship
Parameterized Mathematical Modelling of Positron Range and comparative performance in predicting impaired
Effects in PET/MRI vasodilating capability by PET myocardial perfusion
A. Berger1, J. Cal-Gonzalez1, I. Rausch1, H. Kertesz1, J. Herraiz2, A. imaging
López-Montes2, M. Conti3, T. Beyer1; G. E. Kalykakis1,2, A. Antonopoulos3, T. Pitsargiotis1,4, P. Kafouris5,1,
1
QIMP Team, Center for Medical Physics and Biomedical P. Siogkas6, A. Giannopoulos7, R. Liga8, P. Kaufmann7, A. Scolte9,
Engineering, Medical University of Vienna, Vienna, AUSTRIA, G. Pelosi8, O. Parodi8, J. Knuuti10, D. Neglia8, D. Fotiadis11, C.
2
Grupo de Física Nuclear and UPARCOS, Universidad Anagnostopoulos1;
Complutense de Madrid, Madrid, SPAIN, 3Siemens Medical 1
Biomedical Research Foundation Academy Of Athens, Athens,
Solutions, Knoxville, TN, UNITED STATES OF AMERICA. GREECE, 2Ionian University-Department of Informatics, Kerkyra,
GREECE, 3General Hospital of Athens Hippocrates, Athens, GREECE,
4
University of Patras-Department of mechanical engineering and
Aim/Introduction: Positron range (PR) limits the spatial aeronautics, Patra, GREECE, 5National & Kapodistrian University
resolution of PET imaging and it is affected by magnetic fields of Athens-Department of informatics and communication,
in PET/MR systems, causing an axial elongation of the PR that Athens, GREECE, 6Biomedical Research Institute - FORTH, Ioannina,
degrades image quality and introduces artefacts [1]. Here, GREECE, 7University Hospital Zurich, Zurich, SWITZERLAND,
we present a mathematical modelling approach of PR in the 8
Institute of Clinical Physiology, Pisa, ITALY, 9Leiden University
presence of external magnetic fields that can be used for PR Medical Center, Leiden, NETHERLANDS, 10Turku PET Centre,
correction. Materials and Methods: GATE (GEANT4 Application Turku, FINLAND, 11University of Ioannina, Ioannina, GREECE.
for Tomographic Emission) simulations [2] of point sources of
various radionuclides with significant positron emission energies
(18F, 68Ga, 82Rb and 124I) were performed in three different tissues Aim/Introduction: Interrogation of functional significance of
(water, lung and bone). Simulations were performed for static coronary lesions and shear stress forces acting on atherosclerotic
magnetic fields (B0) of 0T, 1.5T, 3T, 5T, 7T and 9.4T set along plaques detected by CCTA has become feasible through
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S158

application of computational fluid dynamics in CTCA datasets. are much sought-after. Voxel-wise analysis of dynamic 18FFET PET
Οur aim was to investigate a) the relationship of local endothelial has recently been introduced as a reader-independent tool for
shear stress (ESS) with anatomic, morphologic and functional in vivo characterisation of glioma. However, the value of voxel-
characteristics of coronary stenoses and b) the comparative wise analysis of dynamic 18FFET PET for non-invasive prediction
performance of ESS and virtual functional assessment index of IDH genotype is hitherto unknown. Materials and Methods:
(vFAI), a validated surrogate of FFRCT, in predicting impaired 322 patients with a newly diagnosed FETpositive glioma were
coronary vasodilating capability assessed by PET perfusion included (194 IDH wildtype, 128 IDH mutant). All patients
imaging in patients with stenoses of intermediate severity underwent dynamic 18FFET PET imaging and contrast-enhanced
in CTCA. Materials and Methods: Thirty-two patients (21 MRI prior to surgery. The biological tumor volume in PET was
male, mean age 65.6 ± 7.2 years) with intermediate pre-test defined by the established threshold of 1.6 × background
likelihood of coronary artery disease (CAD), who were enrolled activity (2040 min p. i.). Voxel-wise analysis of static and dynamic
in the EVINCI and SMARTool projects and had undergone CTCA PET parameters was performed, e. g. tumortobackground ratios
and PET myocardial perfusion imaging using 15O-water or (TBR) or the percentage of tumor voxels with a time-to-peak
13
N-ammonia, were included in the study. PET was considered lower than 12.5 min (%TTP≤12.5). Optimal cutoffs to predict an
positive for abnormal vasodilating capability when >1 IDH wildtype status were chosen according to Youden’s index
contiguous segments showed both stress MBF ≤2.3 mL/g/min following ROC analysis and the positive and negative predictive
and MFR ≤ 2.5 for15O-water or <1.79 mL/g/min and ≤ 2.0, for values were calculated. Results: IDH wildtype gliomas showed
13
N-ammonia respectively. A previously validated vFAI threshold generally a higher uptake intensity than IDH mutant gliomas (e.g.
of 0.85 was used as predictor of impaired vasodilating capability. TBRmax 3.32 vs. 2.79; p=0.01) and a higher percentage of voxels
ESS computation was based on a mean aortic pressure of 100 with a short TTP (%TTP≤12.5 34% vs. 7%; p<0.01). TBR analyses did
mmHg for the inlet and a mean mass resting blood flow rate not reveal reliable cutoff values for the discrimination between
0.00105 kg/s for the outlet. ESS was calculated in the full length IDH wildtype and IDH mutant gliomas. Conversely, voxel-wise
of the stenosis and the mean value was obtained. High-risk TTP analysis was able to discriminate between IDH wildtype
atherosclerotic plaque characteristics, (calcified-non calcified and IDH mutant gliomas: In the overall group, %TTP≤12.5 (cutoff
volume, thickness, eccentricity, plaque burden), were extracted >22%) predicted an IDH wildtype status with a PPV of 89%
in the lesions using image analysis techniques in the CTCA (NPV 69%). 113 gliomas did not show contrast-enhancement
datasets. Results: Sixty-two coronary segments were evaluated. in MRI (40 IDH wildtype, 73 IDH mutant). In this subgroup,
Forty-one lesions with stenosis 31-50% and 21 lesions with %TTP≤12.5 with a cutoff of >24% predicted an IDH wildtype
stenosis 51-70% were identified. ESS was higher in the latter status with a PPV of 75% (NPV 83%). By adding a subsequent
(3.0, IQ: 1.85 to 5.24 vs. 1.8, IQ: 1.39 to 3.6, p=0.04). There was a TBRmax analysis (cutoff >2.06) PPV could be increased to 100%
moderate positive correlation between ESS and plaque burden (n=32 IDH wildtype gliomas). Conclusion: Voxelwise analysis of
(r=0.675, p<0.0001) and a weak negative correlation (r=-0.3, dynamic 18FFET PET enables the non-invasive prediction of the
p=0.017) between the former and vFAI. ESS was not different in prognostically pivotal IDH mutation status in gliomas at initial
stenoses with impaired vasodilating capacity compared to those diagnosis. Especially in the critical subgroup of non-contrast
without (2.5, IQ: 1.70-6.92 vs. 1.85, IQ: 1.32-3.84, p=0.25), but vFAI enhancing gliomas, the combination of static and dynamic
was (0.75, IQ:0.65-0.79 vs 0.87, IQ:0.82-0.93,p=0.002).The latter voxel-wise 18FFET PET analyses further increases the diagnostic
was also a good predictor of impaired coronary vasodilating accuracy. References: None.
capability (AUC=0.840, CI:0.69-0.93, p<0.0001). Conclusion:
ESS is related with stenosis severity and atherosclerosis plaque
burden. It is weakly associated with vFAI, but in contrast to the OP-407
latter does not appear to be a predictor of impaired coronary Histologically-confirmed diagnostic efficacy of
vasodilating capability. References: None. 18
F-rhPSMA-7 positron emission tomography for lymph
node staging of patients with high risk primary prostate
cancer
OP-406 L. Jooss1, M. Kroenke1, A. Wurzer2, K. Schwamborn3, L. Ulbrich1,
VoxelWise Analysis of Dynamic18FFET PET Enables T. Maurer4, S. Kropf5, T. Horn6, B. Haller7, H. Wester2, W. Weber1, M.
NonInvasive Prediction of IDH Genotype in Newly Eiber1;
Diagnosed Glioma 1
Department of Nuclear Medicine, Klinikum rechts der Isar, TUM,
A. Holzgreve1, M. Unterrainer1, L. Kaiser1, F. Vettermann1, B. Munich, GERMANY, 2Chair of Pharmaceutical Radiopharmacy,
Suchorska2, J. Tonn2, P. Bartenstein1, N. Albert1; TUM, Munich, GERMANY, 3Institute of Pathology, TUM,
1
LMU Munich University Hospital, Dept. of Nuclear Munich, GERMANY, 4Martini-Klinik, UKE, Hamburg Eppendorf,
Medicine, Munich, GERMANY, 2LMU Munich University GERMANY, 5Scintomics GmbH, Fuerstenfeldbruck, GERMANY,
Hospital, Dept. of Neurosurgery, Munich, GERMANY.

Aim/Introduction: Prognosis of glioma patients notably relies 6


Department of Urology, Klinikum rechts der Isar, TUM, Munich,
on mutation of the isocitrate dehydrogenase (IDH) gene and GERMANY, 7Institute of Medical Statistics and Epidemiology,
non-invasive methods for the prediction of the IDH genotype Klinikum rechts der Isar, TUM, Munich, GERMANY.
S159 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

Aim/Introduction: 18F-rhPSMA7 is a new PSMA (prostate specific 374 patients who received primary treatment with ABVD or
membrane antigen)-targeting agent with the advantage of both BEACOPP therapy were retrospectively analyzed. All patients
efficient labeling with 18F and radiometals and a minimal renal underwent FDG-PET/CT at baseline and end-of-treatment
excretion. This retrospective analysis investigates the diagnostic (PETeot) and 348 during treatment after 2 (PET2) or 4 (PET4)
efficacy of 18F-rhPSMA7 PET for lymph node staging compared courses of chemotherapy. The receiver operating characteristic
to morphological imaging (CT and MRI) for patients with primary (ROC) curves were used to determined optimal cut-offs of TLr
high-risk prostate cancer, validated by histopathology. Materials (SUVmax target residual lesion/SUVmax liver) at PET2, PET4 and
and Methods: Data from 58 patients with high risk prostate PETeot. ΔSUVmax optimal cut-offs were also determined with
cancer (defined by D’Amico) who were staged with 18F-rhPSMA7 ROC curves at PET2 and PET4. Positive and negative predictive
PET/CT or PET/MRI between July 2017 and June 2018 was values were calculated and compared to Deauville score for
analysed. Median pre-scan PSA was 12.4 ng/mL (range, 1.2-81.6 predicting progression free survival (PFS). Cox proportional-
ng/mL). Median injected activity of 18F-rhPSMA-7 was 327 MBq hazards model was performed to test the relationship between
(range, 132-410 MBq), with a median uptake time of 79.5 min the study variables and survival rates. Survival curves were
(range, 60-153 min). All patients underwent subsequent radical estimated using Kaplan-Meier analysis. Results: Median follow-
prostatectomy and extended pelvic lymph node dissection. PET up was 56.6 months. TLr optimal cut-offs were 1.66 at PET2,
and morphological datasets were rated independently by an 1.35 at PET4 and 1.29 at PETeot. ΔSUVmax optimal cut-off were
experienced reader for the presence of lymph node metastases. -73% at PET2 and -69% at PET4. TLr, ΔSUVmax and Deauville
Results were compared to histopathological findings on a Score were strong predictors of clinical outcome with a better
patient and templated based manner. Results: Lymph node positive predictive values (PPV) for TLr and ΔSUVmax and similar
metastases were present in 18 patients (31.0%) located in 52 of negative predictive values (PPV were 33%, 40% and 58% at
375 templates (13.9%). On patient-based analyses 18F-rhPSMA-7 PET2 and 53%, 67% and 70% at PET4 for DS, deltaSUVmax and
PET showed a sensitivity of 72.2%, a specificity of 92.5% and an TLr respectively). In univariate analysis, the three interpretation
accuracy of 86.2%. Morphological imaging resulted in 50.0%, methods were statistically significant (p<0.001 for PFS and OS).
72.5% and 65.5%, respectively. On template-based analyses In multivariate analysis, only TLr was an independent prognostic
the sensitivity, specificity and accuracy of 18F-rhPSMA-7 PET factor for PFS at PET2, PET4 and PETeot and ΔSUvmax was an
were 53.8%, 96.9% and 90.9%, and those of morphological independent prognostic factor at PET4. BEACOPP treatment
imaging were 9.6%, 95.0% and 83.2%, respectively. ROC was also statistically significant for survival rates. Chemotherapy
analyses showed 18F-rhPSMA-7 PET to perform significantly regimen combined with PET results according to TLr identified
better than morphological imaging on both patient (AUCs of 4 groups with very different outcome: i) patients treated with
0.858 vs. 0.649, p=0.012) and template-based analyses (AUCs BEACOPP and a negative PET, ii) patients treated with ABVD and
of 0.765 vs. 0.589, p<0.001). Median histopathological size of a negative PET, iii) patients treated with BEACOPP and a positive
lymph node metastases missed in 18F-rhPSMA-7 was 3.5 mm PET, iiii) patients treated with ABVD with a positive PET. These 4
(range: 0.3-15 mm). Conclusion: 18F-rhPSMA-7 PET is superior groups had a 89.1%, 84.8%, 64.8% and 25.4% 2y-PFS (p<0.0001)
to morphological imaging for lymph node staging of high respectively at PET4. Conclusion: TLr is a strong predictor of
risk primary prostate cancer. Its diagnostic efficacy is similar to therapeutic response during interimPET whether it is used
published data for other PSMA-ligands. References: D’Amico after two or four courses of chemotherapy and at the end of
AV, Whittington R, Malkowicz SB, et al. Biochemical outcome treatment and can outperform Deauville Score. DeltaSUVmax is
after radical prostatectomy, external beam radiation therapy, an independent prognostic factor at PET4. Larger prospective
or interstitial radiation therapy for clinically localized prostate studies should be done to validate these cut-offs. References:
cancer. JAMA 1998;280:969-974. None.

OP-408 OP-409
SUV-based interpretation is better for prognosting Integrating radioguidance during robot-assisted
response than Deauville Score in Hodgkin Lymhpoma laparoscopic surgery - In-human evaluation of a DROP-IN
patients gamma probe
E. Texte1, J. Lequesne2, P. Vera1, A. Stamatoullas-Bastard3, S. Becker1; M. N. van Oosterom1,2, P. Dell’Oglio1,3, P. Meershoek1,2, T. Maurer4,
1
Centre Henri Becquerel, Nuclear Medicine Dpt, Rouen, FRANCE, P. J. van Leeuwen2, E. M. K. Wit2, H. G. van der Poel2, F. W. B. van
2
Centre Henri Becquerel, Statistical analysis Dpt, Rouen, FRANCE, Leeuwen1,2,3;
3
Centre Henri Becquerel, Haematology Dpt, Rouen, FRANCE. 1
Interventional Molecular Imaging Laboratory, Department of
Radiology, Leiden University Medical Center, Leiden, NETHERLANDS,
2
Department of Urology, Netherlands Cancer Institute-Antoni
Aim/Introduction: To evaluate the prognostic role of Tumor/ van Leeuwenhoek Hospital, Amsterdam, NETHERLANDS,
Liver ratio (TLr) and SUVmax reduction (ΔSUVmax) in patients 3
ORSI Academy, Melle, BELGIUM, 4Martini-Clinic, University
with Hodgkin Lymphoma (HL) at interim and end-of-treatment Medical Center Hamburg-Eppendrof, Hamburg, GERMANY.
FDG PET-CT and to compare these methods with visual
interpretation (Deauville-Score). Materials and Methods:
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S160

Aim/Introduction: In the surgical management of prostate 910


cancer, robot-assisted laparoscopic surgery has rapidly
evolved into a routine procedure. While the robot offers many
Inflammation & Infection - Parallel Session:
advantages, it can also create challenges e.g. when attempting
PET in Vascular Infection and Myocardial
to apply radioguided surgery using a rigid laparoscopic gamma
Inflammation
probe. The limited maneuverability of such a probe restricts
lesion identification when low-activity lesions are situated in Monday, October 14, 2019, 14:30 - 16:00 Lecture Hall 116
close proximity to a high-activity background. Furthermore,
in the robot-assisted setup, the surgeon relies on the bedside
assistant for probe positioning. To regain autonomy and to
increase maneuverability during radioguidance, by allowing OP-410
the (wristed) robotic tools to position the probe, we created a 18F-FDG-PET accuracy for diagnosis of Infective
tethered DROP-IN gamma probe in 2014 and translated it into Endocarditis compared to Duke echocardiographic criteria
humans in 2018 [1-4]. We have successfully demonstrated in M. Gazzilli1, R. Durmo1, D. Albano1, E. Cerudelli1, M. Bonacina1, F.
vivo use of this technology during the SN procedure and PSMA- Dondi1,2, A. Mazzoletti1,2, P. Bellini1,2, F. Bertagna1,2, R. Giubbini1,2;
targeted lymphatic salvage procedure in prostate cancer using 1
Azienda Socio Sanitaria Territoriale degli Spedali Civili di
proof-of concept studies. In the current study, we evaluate Brescia, Brescia, ITALY, 2Università di Brescia, Brescia, ITALY.
the technique in a larger SN patient cohort and make an in-
depth comparison with respect to the traditional laparoscopic
gamma probe and fluorescence guidance. Materials and Aim/Introduction: In the latest update of the European Society
Methods: 25 prostate cancer patients were included, all of Cardiology (ESC) guidelines echocardiography, contrast-
scheduled for a SN procedure, extended pelvic lymph node enhanced CT, radiolabelled leucocyte SPECT/CT and [18F]FDG-
dissection and prostatectomy. After intraprostatic injections of PET/CT are been included in the diagnostic flow chart for the
(indocyanine green-)99mTechnetium-nanocolloid, preoperative management of infective endocarditis (IE). The aim of this study
SN identification was performed using lymphoscintigraphy is to analyse the diagnostic accuracy of [18F]FDG-PET/CT in the
and SPECT/CT. Surgical excision of the SNs was assisted by a detection of IE. Materials and Methods: We retrospectively
combination of DROP-IN radioguidance, traditional laparoscopic analyzed 105 patients (M:F=54:51, mean age 62 years, range 18-
radioguidance and Firefly fluorescence guidance. Results: 44 SNs 88) who underwent 18F-FDG-PET/CT scan for suspicious of IE,
were resected under DROP-IN gamma probe guidance (average diabetic patients were excluded. PET/CT images were analyzed
of 1090 counts in vivo and 1681 ex vivo). 91% of these could also qualitatively and semi-quantitatively by measuring maximum
be detected using fluorescence imaging in vivo (95% ex vivo). and mean Standardized Uptake Value (SUVmax and SUVmean)
17 SNs (39%) were also surgically pursued with a laparoscopic of the suspected lesion. These results were compared with the
gamma probe (average of 742 counts in vivo and 969 counts echocardiographic findings, according to major Duke criteria,
ex vivo). As a result of the restricted maneuverability in specific and the clinical final diagnosis. Results: Comparing PET/CT
anatomical locations (i.e. right cloquet, right paravesical, right report and clinical final diagnosis revealed a Sensitivity of 96,3%
communis and left iliaca externa regions), one quarter of these (87.25-99.55 95%Cl), Specificity of 92.59% (82.11-97.94% 95%Cl),
nodes could not be (clearly) identified without the help of either Negative Predictive Value of 96,15% (86.49-98.99% 95%Cl),
the DROP-IN or Firefly modalities Conclusion: This clinical study Positive Predictive Value of 92.86% (83.49-97.10% 95%Cl) and of
further underlines that the DROP-IN gamma probe technology Accuracy 97.22% (92.10-99.42 95% Cl), in presence of adequate
has the potential to bring radioguided surgery within reach of preparation to reduce the physiological myocardial uptake
robot-assisted procedures. Due to improved maneuverability, of 18F-FDG: a low carbohydrate, high protein, high fat diet
the DROP-IN probe even indicated an increased detection rate starting 72 hours before the examination. The transthoracic
with respect to the traditional laparoscopic gamma probe. and/or transesophageal echocardiograph findings showed
References: [1] M.N.vanOosterom et al., Am_J_Nucl_Med_ a Sensitivity of 48.84% (33.31%-64.54% 95%Cl), Specificity of
Mol_Imaging, 2016 [2] B.Fuerst et al., IEEE_Trans_Med_Imaging, 52.23% (40.12%-66.02% 95%Cl), Negative Predictive Value
2016 [3] P.Meershoek et al., Eur_J_Nucl_Med_Mol_Imaging, of 60% (50.79%-68.55% 95%Cl), Positive Predictive Value of
2019 [4] F.W.B.vanLeeuwen et al., Clin_Nucl_Med, in_press. 42% (32.57%-52.06% 95%Cl)and of Accuracy 51.43% (41.47%-
61.30% 95%Cl). The echocardiograph accuracy in the detection
of IE is considerable reduced in presence of prosthetic valves
(PVE) due to the artefacts. PET/CT has shown greater accuracy
than the echocardiograph in the evaluation of the response
of antimicrobial therapy (97% vs 62%) and in the study of
cardiovascular implantable electronic device (CIED) infections
or local device infection the accuracy is not comparable.
Furthermore, PET/CT confirmed its ability to identify extra-
cardiac sites of [18F]FDG uptake in patients with other
diseases (pneumonias, vasculitis, vascular prosthesis infections,
S161 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

spondylodiscitis, mediastinitis, etc). In two cases PET/CT allowed OP-412


to diagnose unknown tumors. Conclusion: Our preliminary Diagnostic and therapeutic impact of wholebody FDG
results suggested the high accuracy of PET/CT in the diagnosis PET/CT in patients suspected of infective endocarditis on
and follow-up of IE on native valve (NVE), prosthetic valve native or prosthetic valve: the prospective multicenter
(PVE) and CIED; PET/CT ability to provide other diagnoses and/ TEPvENDO study
or incidental diagnosis. An adequate preparation strategy for F. Rouzet1, B. Mahida1, S. Tubiana1, M. Esposito-Farese1, E. Ilic-
cardiac PET/CT imaging is critical to the accuracy of IE detection Habensus1, A. Bourdon2, E. Chevalier3, N. Piriou4, O. Morel5, O.
because complete suppression of physiologic 18F-FDG uptake Humbert6, A. Devillers7, B. Grégoire8, C. Laouenan1, B. Iung1, X.
by normal myocardium facilitates the detection of inflammation Duval1;
in the heart. References: None. 1
Bichat hospital, Paris, FRANCE, 2Lapeyronie Hospital, Montpellier,
FRANCE, 3Nancy hospital, Nancy, FRANCE, 4Nantes hospital,
Nantes, FRANCE, 5Besançon hospital, Besancon, FRANCE,
OP-411 6
Dijon hospital, Dijon, FRANCE, 7Centre Eugène Marquis,
Quantitative analysis of 18F-Fluorodeoxyglucose uptake Rennes, FRANCE, 8Hospices Civils de Lyon, Lyon, FRANCE.
by PET/CT for detection infective endocarditis
M. Gazzilli1, R. Durmo1, D. Albano1, E. Cerudelli1, M. Bonacina1, F.
Dondi1,2, A. Mazzoletti1,2, P. Bellini1,2, F. Bertagna1,2, R. Giubbini1,2; Aim/Introduction: FDG-PET/CT has been integrated in the
1
Azienda Socio Sanitaria Territoriale degli Spedali Civili di 2015 European society of cardiology (ESC) guidelines as a major
Brescia, Brescia, ITALY, 2Università di Brescia, Brescia, ITALY. Duke criterion in patients suspected of infective endocarditis (IE)
on prosthetic valve (PV). The benefit with native valves (NV) is
not well established. The aim of the study was to prespectively
Aim/Introduction: Infective endocarditis (IE) outcome assess the diagnostic and therapeutic impacts of systematic
largely depends on early diagnosis and treatment, despite whole-body FDG PET/CT in patients suspected of IE on PV or
developments in the imaging and microbiological techniques NV. Materials and Methods: Consecutive patients referred for
the final diagnosis of IE often remain a challenging. 18F-FDG high suspicion of IE in 8 french tertiary care hospitals underwent
PET/CT was recently introduced as a new tool for the diagnosis FDG PET/CT. ESC-2015-modified Duke criteria were applied
of IE, especially in patients with prosthetic valve and ICD. The and therapeutic plans were established jointly by two experts
aim of this study is to demonstrate that higher accuracy can immediately before and after FDG PET/CT completion. The
be obtained using quantitative methodology to analyze PET/ final diagnosis was established as the Duke classification at 6
CT. Materials and Methods: A series of 108 consecutive months Results: 140 patients have been enrolled in the study
patients (M:F=57:51, mean age 62 years, range 18-88) with (70 PV and 70 NV; 34 and 46 classified as definite IE before
suspected IE were analyzed; diabetic patients were excluded. FDG PET/CT, respectively). FDG abnormal cardiac uptake was
After clinical assessment and echocardiographic exams, the present in 64 (45.7%) patients (47 [67.2%] PV and 17 [24.3%]
patients underwent to FDG PET/CT imaging after adequate NV) but was considered related to IE in 42.9% and 15.7%,
preparation to reduce the physiological myocardial uptake of respectively (p<0.001). FDG extracardiac uptake was present
18F-FDG (a low carbohydrate, high protein, high fat (LCHPHF) in 44.3% and 51.4% of PV and NV, respectively. IE classification
diet starting 72 hours prior the scan). PET/CT images were was modified in 24.3% and 5.7%, respectively (p=0.005); net
analyzed qualitatively: 2 nuclear physicians indipendently reclassification index as compared to final diagnosis was 20%
reviewed fusion and maximum intensity projection images and and 4.3%, respectively. Therapeutic plans were modified in
they classified suspect lesions uptake of FDG into 3 patterns 21.4% and 31.4% (p=0.02) in PV and NV patients, respectively.
(none, focal or diffuse). For quantitative analysis, we obtained Taken together, patients for whom FDG PET/CT modified
SUVmax, heart-to-blood pool (H/BP) SUV ratio, and heart-to- care had more frequently an inconclusive echocardiography
liver (H/L) SUV ratio. The SUVmax in the suspect lesions, H/BP (p<0.001) or were classified as possible IE at inclusion (p=0.04).
SUV ratio, H/L SUV ratio were analyzed using receiver operating The nature of the cardiac valve was not a determinant of
charateristic (ROC) curves, displaying sensitivity and specificity the overall benefit. Conclusion: Systematic FDG PET/CT
at various cut-off values. Results: Of the 108 patients enrolled significantly impacted diagnostic classification and therapeutic
in the study, 53 had a clinical final diagnosis of IE. The SUVmax plans in patients suspected of IE with both PV and NV.
of the suspect lesion was significantly higher in patients with References: Clinical Trials: NCT02287792.
IE compared with non-IE patients (8,6 ± 6,02 vs 4,42 ± 2,03).
The area under the ROC curve was 0.976 for SUVmax. Using
a cut-off value of 3,32, the sensitivity was 90,6 (79,3-96,8 95% OP-413
Cl) and specificity was 94,5 (84,9-98,8 95%Cl) for diagnosing IE, Advanced texture features analysis of [18F]FDG-PET/CT
wich could be more accurate than visual analysis. Conclusion: imaging in patients with infective endocarditis
When evaluated by quantification of myocardial suspect lesions R. Zanca1, A. Marciano1, F. Bartoli1, S. Vitali1, R. Doria2, U. Conti3, E.
FDG PET/CT imaging, in patient with adeguate diet preparation, Lazzeri1, R. Slart4, A. Glaudemans4, P. Erba1;
provides high sensitivity and specificity for diagnosing IE. 1
Regional Center of Nuclear Medicine, Department of Translational
References: None. Research and New Technology in Medicine, University of Pisa
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S162

and AOUP, Pisa, ITALY, 2Unit of Infectious Diseases, Univerisity of Research and New Technology in Medicine, University of Pisa
Pisa and AOUP, Pisa, ITALY, 3Division of Cardiology, Univerisity of and AOUP, Pisa, ITALY, 2Medical Imaging Center, Department of
Pisa and AOUP, Pisa, ITALY, 4Medical Imaging Center, Department Nuclear Medicine and Molecular Imaging, University of Groningen,
of Nuclear Medicine and Molecular Imaging, University of University Medical Center Groningen, Groningen, NETHERLANDS.
Groningen, University Medical Center Groningen, Pisa, ITALY.

Aim/Introduction: Several studies have shown that the


Aim/Introduction: [18F]FDG-PET/CT has been recently semiquantitative parameters are influenced by the distortion of
introduced in the diagnostic algorithm for the diagnosis of the signal generated by valve prosthesis, especially mechanical
infective endocarditis (IE). [18F]FDG PET/CT positivity at the (PVEm), in the diagnosis of Endocarditis with [18F]FDG PET/CT.
valve site, which is a major criteria of the 2015 ESC criteria, is Accordingly, the use nonattenuation-corrected (NAC) images
generally characterized by visual analysis, but sometimes it for a correct diagnosis is recommended. Our group is currently
can be difficult to differentiate between infection and reactive working on radiomics analysis of [18F]FDG PET/CT images in IE.
inflammation. The advantage of semiquantitative assessment Thus, we are interested in understanding the possible impact
is still matter of discussion. In this study we evaluated the of metal artifacts on images analysis. In this preliminary study
value of advanced texture features analysis for diagnosing we aim to investigate the influence of image artifacts on
IE. Materials and Methods: In this work we prospectively radiomic analysis in prosthetic valves endocarditis. Materials
evaluated a series of [18F]FDG PET/CT scans in 226 patients and Methods: This is a preliminary analysis of the first 20
(M:F =139:87, mean age 66 ± 18 years, median age 72, range consecutive patients (M:F =15:5, mean age 57 ± 16.20 years,
13-86 ) with suspected IE (native valve endocarditis (NVE) =52, median age 56, range 26-80 ) with PVEm studied prospectively
prosthetic valve endocarditis (PVE) biological =116 and PVE with [18F]FDG PET/CT at AOUP Pisa in January 2017. We
mechanical =58) studied at the AOUP Pisa and the University performed semiautomatically segmentation of [18F]FDG PET/
Medical Center Groningen between January 2015 to April CT attenuation-corrected images and NAC images on the same
2019. Images were analysed (1) visually to define different patients with LIFEx software (www.lifexsoft.org). Texture features
patterns of uptake (focal versus diffuse), (2) by semiquantitative was also performed using LIFEx package. Statistical analysis
parameters (SUVmax, SUVmean ,SUVstd, TLA) and (3) with was performed with JMP Statistical Discoverytm. Results: No
advanced texture features (a total of 44 features). To this aim we significant difference in the texture features analysis (total of 44
used LIFEx software (www.lifexsoft.org) from semiautomatically features) in attenuation-corrected images and NAC images were
segmented PET images with Advantage Workstation GE. Results found. On the contrary, semiquantitative parametetrs (SUVmax,
were compared based on the confirmed diagnosis of EI, type SUVmean, SUVstd, TLA) were significantly different in the two
of valve, microbiology and biochemical markers. Presence and groups (SUVmean p- value <0.001; SUVstd p- value <0.001;
duration of antimicrobial treatment at the time of PET/CT was SUVmax p- value <0.001; TLA p- value <0,001). Conclusion:
also considered. Statistical analysis was performed with JMP Despite preliminary and in a small number of patients, our data
Statistical Discoverytm. Results: Texture features analysis allowed suggest that texture features analysis is much less influenced
to identify a different signature in patients with confirmed by image artifacts as compare to semiquantitative parameters.
IE and without IE (sensitivity 84%, specificity 84%), in patients Therefore, the use of texture features is feasible also in presence
with IE on native valve and prosthetic valve (sensitivity 97%, of metal artifacts, representing a more accurate analysis. The
specificity 97%), in presence of focal versus diffused pattern of next steps of this work will be the analysis of motion effects
uptake, as shown in Table 1. Ongoing antimicrobical treatment artifacts on texture analysis results. References: None.
and its duration has significant impact on texture features, in
particular when long lasting. In addition, patients with MSSA
infection also presented with a specific signature (sensitivity OP-415
89%, specificity 89%). Conclusion: Our results demonstrated 18
F-FDG PET/CTand Radiolabeled Leukocyte Scintigraphy
the feasibility of the textural feature analysis in patients with for the Diagnosis of Infected Aortic Aneurysms
suspected. We found added value in the differential diagnosis P. Mention1, L. Omarjee2, J. Brosseau1, O. Couturier1, M. Ammi1, J.
between patients with confirmed IE, both in NVE and PVE and in Picquet1, P. Abgueguen1, V. Rabier1, H. Rakotonirina1, F. Lacoeuille1;
patients with MSSA infection. Ongoing antimicrobical treatment 1
CHU Angers, Angers, FRANCE, 2CHU Rennes, Rennes, FRANCE.
and its duration impact on texture features, in particular when
long lasting. References: None.
Aim/Introduction: Computed tomography angiography (CTA)
plays a key role in the management of patients with aortic
OP-414 aneurysms. But it can be inconclusive in patients whom infected
Effect of image artifacts on texture analysis in mechanical aortic aneurysm is suspected. The incremental diagnostic value
prosthetic valve endocarditis of 18F-FDG PET/CT and radiolabeled leukocyte scintigraphy (RLS)
R. Zanca1, A. Marciano1, F. Bartoli1, S. Vitali1, E. Lazzeri1, R. Slart2, A. has already been reported in endocarditis. The aim of this study
Glaudemans2, P. Erba1; was to compare the respective performance of 18F-FDG PET/
1
Regional Center of Nuclear Medicine, Department of Translational CT and RLS for the diagnosis of IAA. Materials and Methods:
S163 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

18
F-FDG PET/CT and RLS were performed on 18 patients admitted SUVmean(LV) inside the LV. We used t-tests for independent
for clinically suspected IAA and inconclusive CTA results. The samples to compare SUVs and ratios values between MINF+ and
results of 18F-FDG PET/CT and RLS were analyzed separately by NET groups and ROC analysis to assess diagnostic performance.
experienced physicians blinded to both the results of the other Results: Sixteen patients were included, 6 in MINF+ group (4
imaging technique and patient outcome. Final diagnosis of IAA females/2 males ; 50±22y) and 10 in NET group (4 females/6
was established based either on the bacteriological analyses of males ; 57±17y). All patients in MINF+ group had abnormal 68Ga-
excised tissues or by experienced infectious disease specialists DOTATOC myocardial uptake, hence positive scans, whereas
and vascular surgeons. Results: Of the 18 patients, 9 were none was seen in NET group. Acquisition time was similar in
classified as infected. Sensitivity, specificity, positive predictive MINF+ and NET group respectively (105±16 vs. 95.3±4.7min,
value, negative predictive value and accuracy were 89%, 89%, p=0.17). Absolute SUV values did not show consistent significant
89%, 89% and 89% for 18F-FDG PET/CT and 75%, 100%, 100%, differences between groups, for instance at the LV free wall:
79% and 89% for RLS respectively. Discrepancies between the SUVmax and SUVpeak in MINF+ vs NET patients: 1.4±0.4 and
results of 18F-FDG PET/CT and RLS occurred in 4 patients (22%). 1.2±0.4 vs 2.2±1.0 and 1.1±0.3 respectively, (p>0.05 for both).
In patients with IAA, 2 had true positive 18F-FDG PET/CT results Conversely, SUVmax(M)/SUVmean(LV) and SUVpeak(M)/
(Coxiella Burnetti and Yersinia Enterolitica) and 1 had true positive SUVmean(LV) ratios were significantly greater in all myocardial
RLS results (Coxiella Burnetti). The last patient with a discrepancy regions (p<0.0001 for both) in MINF+ vs NET patients, with the
(non-IAA) had false positive 18F-FDG PET/CT. Conclusion: latter showing the best accuracy on ROC analysis (Table 1).
18
F-FDG PET/CT offers higher sensitivity while RLS offers higher Conclusion: 68Ga-DOTATOC PET/CT appears as a reliable option
specificity for the detection of active infection in patients with to visualize myocardial inflammation in clinically symptomatic
suspected infectious aortic aneurysms. A sequential strategy patients. A quantitative assessment of myocardial uptake using
consisting of 18F-FDG PET/CT imaging followed by RLS when the SUVpeak(M)/SUVmean(LV) ratio can separate patients with
patients had positive 18F-FDG PET/CT results without obvious from those without myocardial inflammation with optimal
bacteriological data may be of relevance. References: None. accuracy. These results need to be validated prospectively in a
larger population. References: None.

OP-416
Reference values for abnormal uptake of 68Ga-DOTATOC OP-417
in patients with myocardium inflammation Comparison of 68Ga-DOTANOC PET/CT with cardiac MRI
S. Boughdad, M. Meyer, E. Pruvot, P. Pascale, K. Casagrande, J. for imaging inflammation in cardiac sarcoidosis
Costes, J. Delage, M. Jreige, N. Schaefer, J. Prior; P. Kaushik, C. Patel, G. Gulati, S. Seth, N. Parakh, R. Kumar, R.
CHUV, Lausanne, SWITZERLAND. Guleria, C. Bal;
All India Institute of Medical Sciences, New Delhi, INDIA.

Aim/Introduction: Suspicion of myocardial inflammation


(MINF) is a common referral for FDG PET/CT scan, which Aim/Introduction: The diagnosis of cardiac sarcoidosis is
has demonstrated good diagnostic performance to detect often challenging due to lack of a gold standard investigation.
abnormal uptake. However, it requires a strict low-carbohydrate Endomyocardial biopsy has poor sensitivity due to sampling
diet ideally over several days, which prevents its realization errors and other tests like ECG, echocardiography, serum ACE
in the emergency setting. Conversely, 68Ga-DOTATOC, a etc are not very sensitive or specific. FDG PET/CT has been used
somatostatin analogue targeting SSTR 2 (Somatostatin for imaging inflammation in cardiac sarcoidosis for diagnosis,
Receptor 2) without such restrictions, appears as an attractive follow up and prognostication. However, the major limitation
alternative. SSTR 2 is expressed by active inflammatory cells, of FDG PET/CT is the inability to achieve adequate suppression
especially lymphocytes present in MInf. Thus, we compared of physiological FDG uptake in the myocardium in all patients
myocardial metabolic uptake in clinically symptomatic patients despite prolonged fasting, dietary modification or other
with MINF (MINF+) to a control group of patients with neuro- interventions. 68Ga-DOTANOC can be a useful alternative to FDG
endocrine tumors without cardiac symptoms (NET). Materials as it binds to somatostatin receptors expressed on inflammatory
and Methods: Patients were recruited from March-April 2019 cells and does not show any significant physiological uptake.
at our institution and received 2 MBq/kg of 68Ga-DOTATOC The aim of our study was to compare 68Ga-DOTANOC PET/
intravenously with a PET/CT acquisition 90 minutes after. Visual CT and myocardiac perfusion SPECT with cardiac MRI for
and quantitative analyses of myocardial uptake were assessed. detecting inflammation in patients with clinical suspicion of
Visual analysis was considered positive if myocardial uptake cardiac sarcoidosis. Materials and Methods: 21 consecutive
was easily distinguishable from the intracavitary activity of patients with clinical suspicion of cardiac sarcoidosis were
the left ventricle (LV). For quantitative analysis, the following included in the study. Of these, 9 patients had biopsy proven
myocardial SUV measurements Max, Peak and Mean were extracardiac sarcoidosis. All patients underwent cardiac 68Ga-
extracted from different regions: sidewall of the LV, apex and DOTANOC PET/CT and cardiac MRI. Any focal increased uptake
interventricular septum. We calculated ratios for each region on 68Ga-DOTANOC PET/CT was considered as positive. On
between SUVmax(M) or SUVpeak(M) of the myocardium and cardiac MRI, presence of T2 hyperintensity with late gadolinium
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S164

enhancement (LGE) was taken as positive. Considering CMR as 1002


gold standard we calculated sensitivity, specificity, PPV and NPV
of 68Ga-DOTANOC PET/CT for detecting inflammation. Results:
Joint Symposium 15 - Oncology & Theranostics
A total of 14 patients were positive on 68Ga-DOTANOC PET/CT.
Committee / ESMO: Immunological Landscape
CMR revealed both T2 hyperintensity and LGE in 10 patients
in Solid Tumours and its Implications in
(suggestive of ongoing inflammation) and only LGE without T2
Response to Immunotherapy
hyperintensity in 11 patients (suggestive of fibrosis). Therefore,
10 patients were considered as positive on CMR. Both 68Ga- Monday, October 14, 2019, 16:30 - 18:00 Lecture Hall 311
DOTANOC PET/CT and CMR were positive in 9 patients and
both were negative in 6 patients. One patient was positive on
CMR but did not show any abnormal 68Ga-DOTANOC uptake.
There were 5 patients who were categorised as negative on OP-421
CMR but showed abnormal focal 68Ga-DOTANOC uptake. All Prognostic and Predictive Role of Tumour Immune
of these 5 patients had LGE without T2 hyperintensity of CMR. Landscape
Considering CMR as gold standard, the sensitivity, specificity, J. Haanen;
PPV and NPV of 68Ga-DOTANOC PET/CT for detecting ongoing Medical Oncology and Molecular Oncology &
inflammation were 90%, 54.5%, 64.3% and 85.7% respectively. Immunology Divisions, The Netherlands Cancer
The percent concordance between the two modalities was Institute, Amsterdam, NETHERLANDS.
71.4%. Conclusion: 68Ga-DOTANOC is an alternative tracer
which may be used for PET imaging of inflammation in cardiac
sarcoidosis. References: None. OP-422
Immunoscore and its Introduction in Clinical Practice
J. Galon;
1001 INSERM, Laboratory of Integrative Cancer Immunology
(Team 15), Cordeliers Research Center, Paris, FRANCE.
CME 8 - Thyroid Committee: Secondary Effects
of Radioiodine Treatment
OP-423
Monday, October 14, 2019, 16:30 - 18:00 Auditorium Advanced Techniques for the Assessment of Tumour
Immunological Profile
E. Lugli;
Laboratory of Translational Immunology, Humanitas
OP-418 Clinical and Research Center, Rozzano, ITALY.
General Aspects of Radiobiology in Radioiodine
Therapy
OP-424
C. D’Alessandria; Immune-PET, Tumour Metabolism and Patterns of
Nuklearmedizinische Klinik und Poliklinik, Klinikum Rechts der Response to Immunotherapy
Isar, Technische Universität München, Munich, GERMANY. E. Lopci;
Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS),
HUMANITAS (Rozzano), Nuclear Medicine, Milan, ITALY.
OP-419
Deterministic Effects of Radioiodine Treatment
P. Spanjol; OP-425
University Hospital, University of Geneva, Department Discussion
of Nuclear Medicine, Geneva, SWITZERLAND.

OP-420
Stochastic Effects of Radioiodine Treatment
P. Radojewski;
Charité – Universitätsmedizin Berlin, Klinik für Nuklearmedizin,
Berlin, GERMANY & University Hospital, University of
Geneva, Department of Nuclear Medicine, Geneva, SWITZERLAND.
S165 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

1003 OP-430
Generators used in Nuclear Medicine
Joint Symposium 16 - Dosimetry + Translational M. Crosthwaite;
and Molecular Imaging Therapy Committee Virginia Commonwealth University, Richmond,
/ ESTRO: Dosimetry in Preclinical Setting to VA, UNITED STATES OF AMERICA.
Determine Dose Limits and Extrapolation to
Clinical Dosimetry
OP-431
Monday, October 14, 2019, 16:30 - 18:00 Lecture Hall 312 Theoretical Basics of Radiopharmacy
Z. Wimana;
Institut Jules Bordet, Nuclear Medicine/
Radiopharmacy, Brussels, BELGIUM.
OP-426
Variable Proton RBE - Is it Time to Reconsider the Dose
Limits for Normal Tissues? 1005
I. Toma-Dasu;
Stockholm University and Karolinska Institutet,
M2M - Parallel Session: Tumour
Medical Radiation Physics, Stockholm, SWEDEN.
Microenvironment & Cancer Biomarkers

Monday, October 14, 2019, 16:30 - 18:00 Lecture Hall 111


OP-427
The Physics of Radiobiology for Alpha-Particle
Radionuclide Therapy Effects
R. Hobbs; OP-432
Johns Hopkins University, Radiation Oncology, School of The Case for SUV75 as an Imaging Biomarker of Response
Medicine, Baltimore, MD, UNITED STATES OF AMERICA. to Therapy in FDG-PET Imaging of Triple Negative Breast
Cancer (TNBC) Patient-Derived Tumor Xenografts (PDX)
K. Shoghi, S. Li, T. Whitehead, S. Roy, L. Strong, N. Fettig, R. Wahl, M.
OP-428 Savaikar;
The Biology of Radiobiology Markers for Dose-Effects in Washington University School of Medicine, St.
Radionuclide Therapy Louis, MO, UNITED STATES OF AMERICA.
J. Nonnekens;
Erasmus MC, Radiology & Nuclear Medicine and
Genetics, Rotterdam, NETHERLANDS. Aim/Introduction: Inter- and intra heterogeneity of patient-
derived tumor xenografts (PDX) present several challenges in
developing optimal quantitative pipelines to assess response
1004 to therapy. The objective of this work was to perform radiomics
analysis in preclinical FDG-PET of triple negative breast cancer
CTE 4 - Technologist Committee / SNMMI: (TNBC) PDX towards an optimal metric of response to therapy
Technologist’s Guide Launch - Radiopharmacy: Materials and Methods: Three TNBC PDX sub-types served
An Update as a preclinical platform to develop and optimize preclinical
FDG-PET/CT quantitative image metrics of response to therapy.
Monday, October 14, 2019, 16:30 - 18:00 Lecture Hall 117 Considerations in this effort include variability in tumor growth
rate and tumor size, solid tumor vs. tumor heterogeneity and
necrotic tumor, impact of tumor necrosis and whole tumor
vs. optimal selection of tumor slices or volumes-of-interest.
OP-429 Three experiments were performed. In the first experiment, a
Technologist’s Guide Launch test-retest protocol was implemented on consecutive days to
M. Attard; assess the reproducibility of FDG-PET metrics. In the second
Isala, Radiology and Nuclear Medicine experiment, we assessed the impact of repeated imaging on
Department, Zwolle, NETHERLANDS. the survival of PDX under a therapeutic regiment. In the third
experiment, we evaluated optimal image metrics of response
to therapy. FDG-PET imaging was performed at baseline and +4
days and +7 days following therapy. Therapy was administered
at baseline and weekly for a period of four weeks. Tumor volumes
were measured weekly by the caliper. Volumes of interest (VOI)
were drawn on co-registered CT images to define tumors. The
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S166

reproducibility, accuracy, and variability of radiomics metrics doses were 200 µg (one patient), 500 µg (6 patients) and 1000
of FDG-PET were evaluated by Pearson correlation coefficient µg (3 patients). The tomographic imaging was performed at 2,
(PCC), bias correction factor (BCF), and Lin’s concordance 6, 8 and 24 h after injection. Blood samples were taken at 20
correlation coefficient (LCC). Image metrics at baseline and min, 2, 4 and 6 h to evaluate elimination half-life of the tracer.
change in FDG-PET uptake from baseline were used to predict/ The health status was monitored during imaging. Results: No
assess response to therapy. The sensitivity, specificity, precision, adverse effects were observed after injection of [99mTc]-ADAPT6.
accuracy, and negative predictive value (NPV) of baseline Elimination half-life in blood was 180 min.The highest uptake in
and change image metrics were used to identify predictors normal tissues was in kidney followed by uptake in liver. Some
of response to therapy. Results: Repeated imaging had an uptake was also visualized in salivary glands. Primary tumours
impact on the survival of PDX mice undergoing therapy. Not were visualized in all 10 patients, although a small tumour (less
surprisingly, measures of SUVmax exhibited poor precision in than 8 mm) was visualized with lower contrast. Auxiliary lymph
test-retest studies while SUVmean exhibited highest precision node metastases were visualized in three patients. Conclusion:
in solid tumors. Image metrics which capture the top 75% of This first-in-human study shows that [99mTc]-ADAPT6 is safe, has
tumor voxels (SUV75) yield consistent test-retest performance in favourable dosimetry characteristics and can provide images of
both solid and tumors with necrotic phenotype. In agreement HER2-expressing primary breast tumours and auxiliary lymph
with these findings, image metrics of SUV75 also scored highest node metastases. Thus, [99mTc]-ADAPT6 is a promising tool for
in sensitivity, specificity, precision, and accuracy in assessing evaluation of HER2 expression in breast cancer using SPECT. The
response to therapy. Conclusion: SUV75 is an optimal imaging novel scaffold-based format of targeting probes, ADAPT, is very
biomarker of response to therapy in FDG-PET imaging of TNBC promising for development of targeting agents for radionuclide
PDX References: None. molecular imaging. References: None.

OP-433 OP-434
First-in-humans Evaluation of [99mTc]-ADAPT6, a Novel Enhanced apoptosis in response to glucose metabolism
Scaffold Protein for Visualizationof HER2 Expression and oncogene driver co-targeting in non-small cell lung
V. Tolmachev1, O. Bragina2, E. von Witting3, J. Garousi1, R. Zelchan2, cancer
I. Sinilkin2, A. Medvedeva2, A. Doroshenko2, A. Vorobyeva1, S. V. De Rosa1, C. Terlizzi2, F. Iommelli1, E. Leggiero3, L. Pastore4, S. Del
Lindbo3, J. Borin3, N. Tarabanovskaya2, S. Hober3, V. Chernov2; Vecchio2;
1
Uppsala University, Uppsala, SWEDEN, 2Tomsk National 1
Institute of Biostructures and Bioimaging, National
Research Medical Center of the Russian Academy of Science, Research Council, Naples, ITALY, 2Department of Advanced
Cancer Research Institute, Tomsk, RUSSIAN FEDERATION, Biomedical Sciences, University of Naples “Federico II”,
3
KTH-Royal Institute of Technology, Stockholm, SWEDEN. Naples, ITALY, 3CEINGE Advanced Biotechnologies, Naples,
ITALY, 4Departement of Molecular Medicine and Medical
Biotechnology, University of Naples “Federico II”, Naples, ITALY.
Aim/Introduction: Transmembrane receptor tyrosine kinase
human epidermal growth factor 2 (HER2) is a molecular target
for the monoclonal antibodies trastuzumab and pertuzumab, Aim/Introduction: Inhibition of MET and EGFR signaling in
the antibody-drug conjugate trastuzumab-DM1 and the oncogene-driven non-small cell lung cancer (NSCLC) causes
tyrosine kinase inhibitor lapatinib. High expression of HER2 is modulation of proliferation, apoptosis and glucose metabolism.
a predictive biomarker for response of breast cancer to HER2- The aim of the present study was to test whether co-targeting
targeting therapies. Evaluation of the HER2 levels in breast of glucose metabolism and oncogene drivers enhances tumor
tumours can be done by radionuclide molecular imaging response to tyrosine kinase inhibitors (TKIs) in NSCLC. To this
which is a non-invasive and effective approach. ADAPTs are end, pyruvate dehydrogenase kinase 1 (PDK1), a key glycolytic
novel class of engineered affinity proteins created using the enzyme favoring the conversion of pyruvate to lactate, was
scaffold of the albumin-binding domain of protein G (42 stably downregulated in oncogene-driven NSCLC cell lines
amino acids). Using a combinatorial library, the molecule exposed or not to selective TKIs. Materials and Methods:
ADAPT6 was selected and shown to bind HER2 with an affinity H1993 and H1975 cells were stably transfected with scrambled
of 1.3 ± 0.4 nM. For imaging purpose, the affinity to albumin (shCTRL) or PDK1-targeted (shPDK1) shRNA and then treated
was obliterated by the introduction of three point mutations. with MET inhibitor crizotinib (1 µM), double mutant EGFRL858R/
Preclinical studies demonstrated that the use of [99mTc]-Tc(CO)3 T790M
inhibitor WZ4002 (1 µM) or vehicle for 48 h. Effects of PDK1
provides stable labelling with a radiochemical purity of over knockdown on glycolytic cascade was evaluated by western
95 %. [99mTc]-ADAPT6 provided high-contrast specific imaging blotting and biochemical assays. Furthermore, levels of cyclin
of HER2-expressing xenografts in mice. The aim of this first-in- D1, PARP, cleaved caspase 3, lamin a/c along with several
human study was to evaluate safety and dosimetry of [99mTc]- members of Bcl-2 family were determined by western blot
ADAPT6. Materials and Methods: Ten patients with primary analysis in shCTRL and shPDK1 transfected cells in response to
breast tumours were included in the study. The injected activity treatment or vehicle. Finally, to understand the mechanisms
was 397±117 MBq (range, 318-450 MBq). The injected protein underlying tumor response to PDK1 knockdown and oncogene
S167 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

driver inhibition, we also analyzed protein-protein interactions days. Results: Longitudinal PET/CT imaging showed selective
at the mitochondrial/endoplasmic reticulum interface by uptake and retention of [86Y]Y-NM600 in MyC-CaP tumors that
immunoprecipitation. Results: Both shPDK1 H1993 and H1975 allowed the delivery of an estimated [90Y]Y-NM600 dose to
cells showed a dramatic reduction of PDK1 protein levels as the tumor of 1.97 Gy/MBq. Mice treated with [90Y]Y-NM600 at
compared to shCTRL cells. Knockdown of PDK1 in both cell lines 4, 10, or 20 Gy showed a marked reduction in CD45+ tumor-
did not cause significant changes in glycolytic cascade, ATP infiltrating lymphocytes (TIL). Both CD8+ and CD4+ TIL
production and glucose consumption. The same decrease of populations declined, but only CD8+ numbers recovered at
cyclin D1 was observed in shCTRL and shPDK1 cells exposed to day 14 post-injection. Notable changes in the phenotype of
crizotinib or WZ4002 indicating that downregulation of PDK1 did surviving CD8+ T-cells were observed with a marked reduction
not significantly affect proliferation. Conversely, increased levels in the expression of 4-1BB activation marker and the checkpoint
of apoptotic markers were found in shPDK1 cells as compared molecules LAG-3, CTLA-4, and PD-1. Recovery to pre-treatment
to shCTRL cells, both treated with TKIs. These findings indicate CD8+ phenotype was seen at day 14. PD-L1 expression in tumor
that PDK1 downregulation is able to potentiate the effects of cells also increased indicating the induction of IFN-γ related
TKIs thus enhancing apoptotic tumor response. Analysis of response to radiation. TME immunomodulation was achieved
mitochondrial fractions showed a PDK1-dependent pattern of without systemic hematopoietic toxicity. Combination of
protein-protein interaction suggesting the assembly of large [90Y]Y-NM600 and anti-PD-1 immunotherapy resulted in
macromolecular complexes at the mitochondrial/endoplasmic enhanced anti-tumor response compare to each monotherapy.
reticulum interface. Conclusion: Our findings indicate that co- Conclusion: Our preliminary data suggest that TRT induces
targeting of PDK1 and oncogene driver is able to potentiate profound immunological effects in TME by modifying the
the effects of TKIs thus enhancing apoptotic tumor response. phenotype and abundance of TIL populations and upregulating
References: None. checkpoint ligands in tumors cells, effects that can be leveraged
to enhance the response of PC tumors to checkpoint blockade
immunotherapy. References: None.
OP-435
Y-NM600 targeted radionuclide therapy
90

immunomodulates the tumor microenvironment of OP-436


prostate tumors Podocalyxin, a new target for radioimmunotherapy of
R. Hernandez, C. Zahm, E. Aluicio-Sarduy, H. Potluri, J. Grudzinski, pancreatic cancers
C. Massey, A. Bitton, J. Engle, D. McNeel, J. Weichert; J. Rousseau1, P. H. W. Chan2, H. Merkens1, K. Gitschtaler1, L. Li3,4,
University of Wisconsin, Madison, WI, UNITED STATES OF AMERICA. P. Bergqvist2, N. Colpo1, C. Uribe1, C. Orvig3, C. Roskelley5, K. M.
McNagny6, K. Lin1, I. Samudio2, F. Benard1;
1
Molecular Oncology, BC Cancer, Vancouver, BC, CANADA,
Aim/Introduction: Immunotherapies are potentially curative 2
Biologics Division, CDRD, Vancouver, BC, CANADA, 3Medicinal
treatments for metastatic cancers but are ineffective against Inorganic Chemistry Group, Department of Chemistry,
metastatic prostate cancer (PC) due to an immunosuppressive UBC, Vancouver, BC, CANADA, 4Life Sciences Division,
tumor microenvironment (TME). External-beam radiation TRIUMF, Vancouver, BC, CANADA, 5Department of Cellular
therapy can elicit a proinflammatory response in irradiated and Physiological Sciences, UBC, Vancouver, BC, CANADA,
tumors but is prohibitively toxic in a scenario of disseminated 6
Department of Medical Genetics, UBC, Vancouver, BC, CANADA.
disease. Our goal is to employ [90Y]Y-NM600 targeted
radionuclide therapy (TRT) to systemically condition the
tumor microenvironment of PC for an enhanced response to Aim/Introduction: Podocalyxin (PODXL) is a sialoglycoprotein
immunotherapy. Materials and Methods: Immunocompetent involved in mobility and invasiveness of pancreatic tumor cells
male FVB mice were implanted with syngeneic prostate cancer and thus a promising target to treat advanced pancreatic cancer
(MyC-CaP) tumors (n=3). Tumor-bearing mice were administered and/or metastases by radioimmunotherapy (RIT). PODXL-447 is
9.25 MBq of the positron-emitting [86Y]Y-NM600 and static PET/ a high affinity monoclonal antibody that recognizes a PODXL
CT scans were acquired at 3, 24, 48, and 72 h post-injection. [86Y] tumor-selective glyco-epitope. The aim of this study was to
Y-NM600 uptake in MyC-CaP tumors and normal tissues was develop a RIT strategy to treat pancreatic cancer using PODXL-447.
quantified via a region-of-interest analysis of the images, from Materials and Methods: H4pypa conjugated PODXL-447
which [90Y]Y-NM600 TRT dosimetry was estimated. The radiation (H4pypa:PODXL-447 ratio 3:1) was radiolabeled with 177Lu.
dose and time dependency of the immunomodulatory effects Radiochemical purity and specific activities were determined by
of [90Y]Y-NM600 in the TME of MyC-CaP tumors was determined iTLC-SG chromatography and size exclusion chromatography
by flow cytometry and immunohistochemistry, while systemic using HPLC. Immunoreactivity was determined using MIA PaCa-
hematopoietic toxicity was monitored via CBC analysis. In 2 cells. Biodistribution studies were performed at 4, 24, 72, 168
treatment studies, mice bearing MyC-CaP grafts (200 mm3; and 240h post-injection (p.i) in MIA PaCa-2 tumor-bearing mice
n=5) were administered 1.85, 5.55, or 11.1 MBq [90Y]Y-NM600 (13.9±0.3 μg, 3.2±0.1 MBq, n=8/group). Dosimetry was also
monotherapy or in combination with an anti-PD-1 mAb (100 performed. To determine the maximum tolerated dose (MTD),
µg) weekly for 3 weeks and tumor growth was monitored for 45 increasing activities of 177Lu-pypa-PODXL-447 were injected in
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S168

healthy mice and blood cell counts were monitored p.i (4.1, 8.4, produced in common cyclotrons. This would offer centralized
17.8 MBq, 25.7±0.6 μg, n=8/group). A RIT assay was performed in radiopharmaceutical production and distribution as well as
MIA PaCa-2 tumor-bearing mice at 2/3 of the MTD as compared longer time slots for application. Materials and Methods:
to controls injected with unlabeled H4pypa-PODXL-447 Ten FAPI-derivatives were synthesized as precursors for
(14.6±0.3 μg, n=6-7/group). Results: H4pypa-PODXL-447 was incorporation of F-18 as aluminum fluoride complexes or as
effectively radiolabeled with 177Lu (radiochemical purity >99%, 6-fluoronicotinamides. The radiolabeled compounds were
0.6-2.5 MBq/μg, immunoreactivity >85%). Significant tumor tested in vitro for their ability to bind FAP transfected HT-1080
uptakes, with high tumor to background ratios, were observed cells and their respective EC50-value. Additionally the specificity
4h and until 72h p.i (15.6±4.7 and 13.5±4.4 %ID/g, respectively), was affirmed by a negative control with DPP4 transfected HEK
and dropped at Day 7 (5.0 ± 0.9 %ID/g, p=0.0001). The absorbed cells. The most promising tracer was identified by PET imaging
dose to the tumor was 1.2 Gy/MBq. 177Lu-H4Pypa-PODXL-447 in HT-1080-FAP xenografts. Further characterization included
showed a dose-dependent hematological toxicity with a MTD an organ distribution study and a test for stability in serum.
of 8.4 MBq (transient toxicity: 11 and 12% of platelets and Finally a first clinical application was performed. Results: All
leukocytes remaining at nadir, recovery observed at 56 and compounds showed excellent performance in vitro. The initial
40 days p.i, respectively). As compared to H4pypa-PODXL-447 6-flouronicotinamide derivatives showed a disadvantageous
(controls), the MIA Paca-2 tumor volumes treated with 5.8 MBq biliary excretion. Although this could be averted by insertion of
of 177Lu-pypa-PODXL-447 remained unchanged up to 14 days p.i hydrophilic amino acids into the linker region, the accumulation
(415±180 versus 62±45 mm3, respectively, p=0.0004). After 14 in the xenografted tumor was also suppressed. The AlF-labeled
days, 177Lu-pypa-PODXL-447 treated tumors began to increase compounds FAPI-42 and -52 also revealed an unfavorable biliary
in size and remained significantly smaller than the controls 26 excretion in PET experiments, while these tracers showed fast
days p.i (196±100 versus 870±245 mm3, respectively, p=0.0001). renal clearance if labeled with Ga-68. The lower lipophilicity
At 40 days p.i the survival rate was 71.4% for the 177Lu-pypa- of FAPI-74, -75 and -76 reduced the fraction of the biliary
PODXL-447 group versus 16.7% for the controls (tumor elimination and enabled high tumor-to-background ratios for
size: 519±139 and 1108±204 mm3 for the remaining mice, FAPI-74 and -75. This result could also be confirmed in a clinical
respectively, p=0.0026). Conclusion: 177Lu-pypa-PODXL-447 application of FAPI-74 for PET/CT imaging of a lung cancer
enabled control of tumor growth in a preclinical RIT study patient. Conclusion: The different elimination pathways of Ga-
using a PODXL-positive pancreatic cancer model. The use of a 68 and AlF-18 labeled NOTA-compounds show the sensitivity
fractionated protocol, a pretargeting strategy and/or α-emitters of FAPI-tracers towards changes of physicochemical properties.
might decrease toxicity and increase the radiation dose that The interfering biliary excretion could be suppressed in case of
could be delivered to tumors. References: None. AlF-18 complexes while maintaining high tumor accumulation.
This was achieved by reducing the lipophilicity via insertion of
additional charges or incorporation of the 2-cyanopyrrolinine
OP-437 residue of FAPI-02. Possessing excellent performance in PET
Fluorine-18 Labeled FAPI-Tracers For PET Imaging imaging as well as a feasible synthesis, FAPI-74 is a promising
T. Lindner1, A. Altmann1,2, F. L. Giesel1, C. Kratochwil1, C. Kleist1, S. precursor for clinical F-18 based FAPI-imaging. References:
Kraemer1, J. Debus3,4, W. Mier1, U. Haberkorn1,2,5; None.
1
Nuclear Medicine, University Hospital Heidelberg, Heidelberg,
GERMANY, 2Clinical Cooperation Unit Nuclear Medicine,
German Cancer research Center (DKFZ), Heidelberg, GERMANY, OP-438
3
Dept. of Radiation Oncology, University Hospital Heidelberg, Theranostics targeting fibroblast activation protein in
Heidelberg, GERMANY, 4Clinical Cooperation Unit Radiation the tumor stroma: [64Cu] and [225Ac] labelled FAPI-04 in
Oncology, German Cancer research Center (DKFZ), Heidelberg, pancreatic cancer xenograft mice
GERMANY, 5Translational Lung Research Center Heldelberg, T. Watabe1, Y. Shirakami2, K. Kaneda-Nakashima3, Y. Liu1, T.
German Center for Lung Research, Heidelberg, GERMANY. Lindner4, K. Ooe1, A. Toyoshima2, S. Naka5, E. Shimosegawa1, U.
Haberkorn4, F. Giesel4, J. Hatazawa6;
1
Osaka University Graduate School of Medicine, Suita,
Aim/Introduction: Recently the DOTA-based radiotracers FAPI- Osaka, JAPAN, 2Institute for Radiation Sciences, Osaka
04 and -46 which target the fibroblast activating protein (FAP) University, Suita, Osaka, JAPAN, 3Osaka University Graduate
of cancer associated fibroblasts were successfully tested for School of Science, Suita, Osaka, JAPAN, 4University Hospital
PET imaging and targeted radionuclide therapy. This imaging Heidelberg, Heidelberg, GERMANY, 5Osaka University
method is especially valuable in case of malignancies with low Hospital, Suita, Osaka, JAPAN, 6Research Center for Nuclear
glucose uptake, which are not easily detectable by FDG-PET/ Physics, Osaka University, Suita, Osaka, JAPAN.
CT such as pancreatic cancer. Since the use of Ga-68 limits
batch-sizes to 2-4 GBq and the half-life of 68 min is relatively
short, Ga-68 FAPI tracers have to be produced on site and Aim/Introduction: Fibroblast activation protein (FAP),
in time. To overcome these disadvantages radiotracers for which is known to promote tumor growth and progression,
labeling with the longer-lived F-18 were developed, which is is overexpressed in cancer associated fibroblasts of many
S169 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

human epithelial cancers. Since its expression is minimal in previously developed trifunctional ligands that bind prostate-
normal organs, FAP is an excellent target for the theranostics in specific membrane antigen (PSMA) and serum albumin to
oncology. In this study, we used longer half-life radionuclides, improve dose to tumor and therapeutic index6,7. Our aim was
[64Cu] (half-life = 12.7 hrs) and [225Ac] (half-life = 10 days), for the to develop a trifunctional small molecule ligand with improved
labelling of FAP inhibitor (FAPI), to evaluate the biodistribution tumor uptake and retention for FAP-targeted radiotherapy.
and treatment effect in mice with human pancreatic cancer Materials and Methods: RPS-309 comprises a 7-quinolynoyl)-
xenografts. Materials and Methods: Male nude mice were glycyl-2-cyanopyrrolidine group derivatized with DOTA and
prepared by subcutaneous injection with human pancreatic 2-(4-iodophenyl)acetic acid using a polyethylene glycol (PEG)
cancer cells (PANC-1 or MIAPaCa2, n=4 for each, respectively). linker group. The IC50 was determined by a competition binding
Dynamic and delayed PET scans 2.5 hrs after injection of [64Cu] assay in SW872 cells. The ligand was radiolabeled with 68Ga
FAPI-04 (7.9 ±0.6 MBq), and static scans one hour after injection and evaluated by microPET/CT imaging and biodistribution in
of [68Ga]FAPI-04 (3.6 ±1.4 MBq) were acquired using the same female BALB/c nu/nu mice bearing SW872 xenograft tumors.
cohort mice. Immunohistochemical staining was also performed Specificity for FAP was determined by co-administration of non-
to confirm the FAP expression in the tumor xenograft using FAP- radioactive ligand (35 nmol). Results: RPS-309 potently inhibited
alpha antibody. For the radioligand therapy, [225Ac]FAPI-04 (34 FAP. 68Ga-RPS-309 clearly demarcated SW872 xenograft tumors
kBq) was injected into PANC-1 xenograft mice (n=3). Tumor size (5.4±0.3 %ID/g at 30 min p.i.), and was retained for up to 3 h p.i.
was monitored and compared to control mice (n=3). Results: (5.0±0.3 %ID/g). Renal clearance was the predominant route of
Dynamic imaging of [64Cu]FAPI-04 showed a rapid clearance excretion, and activity in the blood remained high at 3 h p.i. The
through kidneys and a slow washout of the tumors. Delayed tumor-to-kidney ratio increased from 1.05±0.16 at 30 min p.i. to
PET imaging of [64Cu]FAPI-04 showed mild uptake in the tumors 1.73±0.11 at 3 h p.i. Uptake in bone and pancreas was consistent
and relatively high uptake in the liver and intestine. SUVmean with native murine FAP expression8, and was eliminated by co-
of [64Cu]FAPI-04 and [68Ga]FAPI-04 were 0.13 ± 0.03 and 0.08 ± administration of a blocking dose of non-radiolabeled ligand.
0.01 in the PANC-1 xenograft, 0.14 ± 0.03 and 0.08 ± 0.02 in the By this method, tumor uptake was also dramatically reduced.
MIAPaCa2 xenograft, 0.04 ± 0.01 and 0.02 ± 0.01 in the muscle, Conclusion: 68Ga-RPS-309 shows high affinity and specificity for
0.12 ± 0.03 and 0.10 ± 0.01 in the heart, 1.46 ± 0.33 and 0.21 ± FAP. Uptake in SW872 xenograft tumors is high in spite of the
0.08 in the liver, 0.40 ± 0.19 and 0.06 ± 0.02 in the intestine, 0.34 modest expression of FAP in this cell line, with tumor-to-tissue
± 0.07 and 0.19 ± 0.03 in the kidneys, and 4.36 ± 2.93 and 21.92 ratios exceeding 1 as early as 30 min p.i. Sustained tumor retention
± 21.47 in the bladder, respectively. Accumulation in the tumor over 3 h suggests that RPS-309 may be suitable for FAP-targeted
or normal organs were significantly higher in [64Cu]FAPI-04 radiotherapy with longer-lived radionuclides. References: [1]
compared to [68Ga]FAPI-04 except for the heart, and excretion Siveke JT. J Nucl Med. 2018;59:1412-1414. [2] Puré E, Blomberg
in the urine showed higher trend in [68Ga]FAPI-04 compared to R. Oncogene 2018;37:4343-4357. [3] Loktev A, et al. J Nucl Med.
[64Cu]FAPI-04. Immunohistochemical staining using FAP-alpha 2018;59:1423-1429. [4] Lindner T, et al. J Nucl Med. 2018;59:1415-
antibody revealed the abundant FAP expression in the stroma of 1422. [5] Giesel FL, et al. J Nucl Med. 2019;60:386-392. [6] Kelly J,
both PANC-1 and MIAPaCa2 xenografts. [225Ac]FAPI-04 injection et al. Eur J Nucl Med Mol Imaging. 2018;45:1841-1851. [7] Kelly
showed significant tumor growth suppression in the PANC- JM, et al. J Nucl Med. 2018. doi:10.2967/jnumed.118.221150. [8]
1 xenograft mice compared to the control mice. Conclusion: Roberts EW, et al. J Exp Med. 2013;210;1137-1151.
This study showed the feasibility of theranostics using [64Cu]
FAPI-04 and [225Ac]FAPI-04 for the treatment of FAP-expressing
pancreatic cancer. References: None. 1006
Do.MoRe - Parallel Session: Dosimetry for PSMA
OP-439
Radiopharmaceuticals
A Small Molecule Trifunctional Ligand for Fibroblast
Activation Protein-α (FAP)-Targeted Theranostics Monday, October 14, 2019, 16:30 - 18:00 Lecture Hall 112
J. M. Kelly, S. Ponnala, T. M. Jeitner, A. Nikolopoulou, C. Williams Jr.,
B. Hu, J. W. Babich;
Weill Cornell Medicine, New York, NY, UNITED STATES OF AMERICA. OP-440
Patient-specific 3D Monte-Carlo-based bone marrow
dosimetry for Lu-177-PSMA therapy and the potential
Aim/Introduction: Fibroblast activation protein-alpha (FAP) value of Tc-99m-anti-granulocyte antibody SPECT/CT for
is a marker of cancer-associated fibroblasts, a major regulator image-based 3D active bone marrow localisation
of the tumor microenvironment1. FAP is upregulated in many A. Gosewisch1, H. Ilhan1, S. Tattenberg1, A. Mairani2, K. Parodi3,
cancers and is minimally expressed in normal tissue2. The J. Brosch1, L. Kaiser1, F. Gildehaus1, A. Todica1, S. Ziegler1, P.
radiometallated small molecule FAP inhibitors FAPI-02 and FAPI- Bartenstein1, G. Böning1;
04 show promising tumor delineation and minimal background 1
Department of Nuclear Medicine, University Hospital
accumulation in human cancer patients3,4, but significant tumor Munich, Munich, GERMANY, 2Heidelberg Ion Beam
washout is evident even by 3 h post injection (p.i.)5. We have Therapy Center, University Hospital Heidelberg, Heidelberg,
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S170

GERMANY, 3Department of Medical Physics, Ludwig- Aim/Introduction: The emerging PSMA-targeted radionuclide
Maximilians-Universität München, Munich, GERMANY. therapy (RLT) is an effective treatment for metastatic castration-
resistant prostate cancer (mCRPC). The European council
mandates that treatments should be planned according to the
Aim/Introduction: The bone marrow (BM) is a main risk organ radiation doses delivered to individual patients [1,2]. However,
during Lu-177-PSMA therapy of mCRPC patients. Classical there is no clinically simple but practical method to predict
BM dosimetry relies on phantom-based S-values, however, the dosimetry before RLT, which hampers the realization of
mCRPC patients often present with a high bone lesion load, treatment planning. Therefore, we aimed to prove the concept
which leads to a heterogeneous and patient-specific activity to employ machine learning methods to predict the post-
accumulation close to potentially BM-bearing sites and which therapy dosimetry. Materials and Methods: Retrospectively
may significantly interfere with the distribution of active BM. 17 patients with metastatic castration-resistant prostate cancer
The aim was to investigate Monte Carlo (MC) simulations of the (mCRPC) treated with 177Lu-PSMA I&T RLT were included in
BM absorbed dose and the potential value of image-based BM this study. Only those cycles with 68Ga-PSMA-HEBD-CC PET/
localisation. Materials and Methods: This study is based on CT directly before the treatment and at least 3 planar and 1
the first therapy cycle of 11 patients (3.7-6 GBq Lu-177-PSMA- SPECT/CT dosimetry imaging were selected. Totally 30 cycles
DKFZ-617). Each patient obtained a pre-therapeutic Ga-68- of treatments were considered for this proof-of-concept study.
HBED-CC-PSMA PET/CT, therapeutic quantitative Lu-177 SPECT Organ-based mean and max SUV uptake were obtained from
acquisitions of the abdomen 24 (CT), 48, and 72 h p. i., a Lu- pretherapy PET/CT scans. Dosimetry was calculated for kidney,
177 whole-body planar scintigraphy 24 h p. i., and five blood liver, spleen and salivary glands using Hermes Hybrid Dosimetry
samples 30 and 80 minutes p. i. and 24, 48, and 72 h. Lesions, 4.0. Two machine learning methods, a 3-layer fully connected
kidneys and the remainder of the body (ROB) were segmented neural network artificial neural network (ANN) and a random
from the Ga-68 PET/CT volume and filled with the respective forest regression (RFR) model, were established. 10-folder
Lu-177 activities. BM absorbed doses were simulated using cross validation was applied to verify the trained network. Our
FLUKA, assuming first, an unaltered BM distribution (MC1), or results were compared with population-based dosimetry from
second, a displacement of active BM from the direct location literature. Results: ANN has better performance than RFR in
of bone lesions (MC2). Results were compared to absorbed the dose prediction for liver and salivary glands, while worse
dose estimates from S-values (SMIRD), with ROB (including performance for kidney and spleen. Combining the advantages,
tumors), kidneys and blood considered as source regions, and machine learning achieved the dosimetry prediction error
correlated with the post-therapeutic decrease of lymphocytes, of 18.7±16.0% for kidney, 31.4±27.0% for liver, 24.3±16.2%
total white blood cells, haemoglobin level and platelets. For two for salivary glands and 32.1±31.4% for spleen. In contrast, the
patients, an additional pre-therapeutic Tc-99m-anti-granulocyte prediction based on literature population mean has significantly
antibody SPECT/CT was performed for BM localisation. Results: larger error (p<0.01), 46.2±50.4% for kidney, 99.5±238.7% for
Median BM absorbed doses were 130, 37, and 11 mGy/GBq liver, 705.7±377.7% for salivary glands, 62.3±58.9%. Conclusion:
for MC1, MC2, and SMIRD. Significant correlation with the The proof of concept study shows that machine learning can
decrease of platelet counts was found, with highest correlation significantly reduce the prediction error compared to generally
for MC2 (MC1: r=-0.60, p=0.05, MC2: r=-0.75, p<0.01, SMIRD: r=- population-based estimation. Artificial intelligence may provide
0.62, p=0.04). For both investigated patients, BM localisation a practical solution to improve the dosimetry-guided treatment
via Tc-99m-anti-granulocyte antibody SPECT/CT indicated a planning for RLT. References: 1. Stokke et al. EJNMMI Phys 2017
displacement of active BM from the direct location of lesions 2. Flux et al. Eur J Nucl Med Mol Imaging 2018.
similar to model MC2, and led to a reduction in the BM absorbed
dose of 40 and 41 % compared to MC1. Conclusion: Higher
absorbed doses were observed for MC-based models than for OP-442
SMIRD, however, for MC2 all BM absorbed dose values were still Lu-177 PSMA Radioligand therapy: Does the
below the threshold of 2 Gy. MC1 partialy resulted in critical pretherapeutic SUV in Ga-68 PSMA PET/CT predict the
values, but this method may lead to too exaggerated absorbed therapeutic tumor uptake and absorbed tumor dose?
doses by neglecting BM displacement by the metastasis. Image- C. Schuchardt, S. Wiessalla, A. Singh, J. Zhang, H. R. Kulkarni, D.
based BM localisation might be beneficial for identified risk Mueller, R. P. Baum;
patients. References: None. Theranostics Center for Molecular Radiotherapy and
Molecular Imaging, Bad Berka, GERMANY.

OP-441
Machine learning to predict post-therapy dosimetry for Aim/Introduction: Theranostics of metastatic prostate
177
Lu-PSMA I&T treatment cancer is becoming more and more important. Ga-68 PSMA
K. Shi1, S. Xue1, A. Gafita2, C. Dong2, Y. Zhao2, G. Tetteh2, B. H. PET/CT enables accurate detection of metastases with high
Menze2, A. Afshar-Oromieh1, M. Eiber2, A. Rominger1; diagnostic sensitivity and specificity and provides quantitative
1
University of Bern, Bern, SWITZERLAND, 2Technical and reproducible data that can be used to select patients for
University of Munich, Munich, GERMANY. molecular radiotherapy using PSMA-targeted radioligand
S171 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

therapy (PRLT) with Lu-177 PSMA ligands. The aim of our study inhibitors (e.g. PSMA-617, PSMA-I&T) show good tumor-to-blood
was to determine whether the pretherapeutic SUV can be used and kidney ratios but high salivary gland uptake. In contrast,
to predict the therapeutic Lu-177 PSMA tumor uptake and mean antibodies (e.g. huJ591) show high tumor retention with
absorbed dose. Materials and Methods: 57 patients suffering almost no uptake in salivary glands but relevant hematotoxicity.
from metastatic prostate cancer (aged 70+/-8 years) were Ligand-optimization by enhancing blood circulation time
included in the analysis. High PSMA expression was verified with albumin-binding moieties has shown to be feasible [1].
before treatment by Ga-68 PSMA PET/CT and SUVmean and The aim of this study was to evaluate safety and dosimetry of
SUVmax of target lesions were determined. PRLT was performed a single therapeutic dose of the albumin-binding [177Lu]Lu-
with a mean activity of 6.9 +/- 1.4 GBq Lu-177 PSMA. Biokinetics PSMA-ALB-56. Materials and Methods: Ten patients (71±8.3
were determined based on planar whole body scintigraphy & y) with mCRPC and progression under conventional therapies
SPECT/CT and dosimetry calculations were performed (OLINDA participated in laboratory tests and PSMA-PET/CT to evaluate
2.0). SUVs were compared with the tumor uptake at 20h p.i. target expression. After injection of a single dose of 3344±390.5
and absorbed doses per injected activity (D/A). The correlation MBq [177Lu]Lu-PSMA-ALB-56 [2], patients underwent venous
between SUV values and uptake/absorbed doses was tested blood sampling (5, 15, 30 min and 1.5, 6, 24 and 48 h p.i.) and
using Spearman rank correlation analysis. Results: Analyzed 3D SPECT/CT imaging (head to upper thigh at 1.5, 6, 24, 48 h
were 114 metastases of 57 patients; 80 bone, 30 lymph node and 7 d p.i.). Tumor lesions and volumes were defined on pre-
and 4 liver lesions. The SUVmean ranged from 1.7 to 45.1, therapeutic PSMA-PET/CT scans. Red bone marrow uptake was
SUVmax ranged from 2.1 to 253.7. The mean Lu-177 PSMA conservatively estimated from venous blood samples (RMBLR
uptake at 20h p.i. was 0.5 %IA (% of injected activity) and the = 1.0). QDOSE, OLINDA/EXM v1.1 and IDAC-Dose 2.1 were used
mean absorbed dose 7Gy/GBq. The correlation of SUV and D/A for dosimetric evaluation and calculation of mean absorbed
was r=0.40 (SUVmean) and r=0.43 (SUVmax), both significant organ doses for salivary glands, kidneys, red bone marrow, and
with p< 0.001. SUV and uptake also showed positive significant tumor lesions. Results: [177Lu]Lu-PSMA-ALB-56 showed slow
correlations: r=0.33 (SUVmean) and r=0.37 (SUVmax). Because clearance from blood with highest uptake at 24 h p.i. in the
the SUV represents only the uptake at the time of acquisition, kidneys and salivary glands and 24-48 h p.i. in tumor lesions.
while the absorbed dose is based on uptake and associated half- Compared with other therapeutic PSMA radiopharmaceuticals,
life (HL), we distinguished between lesions with short HL<50h [177Lu]Lu-PSMA-ALB-56 showed higher absorbed doses in
and lesions showing long HL>50h. For short HL, the correlation tumor (6.64±6.92 mGy/MBq), but also in kidneys and red bone
of SUV and uptake was r=0.32 (SUVmean) and 0.35 (SUVmax), marrow (2.55±0.93 and 0.27±0.07 mGy/MBq, respectively). The
p<0.05. The strongest correlation was found for SUV and D/A absorbed dose to the salivary glands was lower (0.87±0.43 mGy/
for lesions showing long HL: r=0.45 (SUVmean) and r=0.53 MBq) as compared to the dose delivered by [177Lu]Lu-PSMA-617.
(SUVmax), both p<0.001. Conclusion: Significant correlations The red bone marrow was found to be the dose-limiting organ
between SUV and uptake/ absorbed dose prove that the with injectable mean activities of 7300 MBq without exceeding
pretherapeutic Ga-68 PSMA PET/CT may predict tumor uptake 2 Gy as maximum tolerated dose. Conclusion: Treatment with
and absorbed doses. Indicating lesions with low SUV or high a single dose of [177Lu]Lu-PSMA-ALB-56 delivers higher doses
SUV could help to select suitable or inappropriate candidates for to tumor lesions, but dose calculations imply that the injected
PRLT. However, larger series are needed to confirm and validate activities and number of treatment cycles have to be considered
these results. References: None. carefully with respect to the higher absorbed doses to kidneys
and red marrow. Tumor/salivary glands absorbed dose ratios
was significantly increased, but tumor/kidneys absorbed dose
OP-443 ratios for [177Lu]Lu-PSMA-ALB-56 was significantly lower, in
Biodistribution and dosimetry of a single dose of albumin- comparison to 177Lu-based PSMA radiopharmaceuticals without
binding ligand [177Lu]Lu-PSMA-ALB-56 in patients with albumin-binding properties. References: [1] Lau et al. Bioconjug
mCRPC Chem 2019, 30:487 [2] Umbricht et al. Mol Pharm 2018; 15:2297.
V. Kramer1,2, R. Fernandez1, W. Lehnert3, J. Flores1, E. Eppard2, C.
Soza-Ried1, L. Jiménez-Franco3, M. Benesova4,5, C. Umbricht4, R.
Schibli4,5, M. Meckel6, A. Kluge3, C. Müller4,5, H. Amaral1,2; OP-444
1
Center for Nuclear Medicine & PET/CT Positronmed, Santiago, Optimized sampling schedules for renal dosimetry of
CHILE, 2Positronpharma SA, Santiago, CHILE, 3ABX-CRO, Dresden, 177
Lu-PSMA I&T regarding the hybrid planar-SPECT/CT
GERMANY, 4Center for Radiopharmaceutical Sciences ETH- method
PSI-USZ, Villingen, SWITZERLAND, 5Department of Chemistry A. Rinscheid1,2, P. Kletting1,2, J. Allmann3, A. Allmann3, M. Eiber3, A. J.
and Applied Biosciences, ETH Zurich, Zürich, SWITZERLAND, Beer2, G. Glatting1,2;
6
Isotope Technologies Garching, München, GERMANY. 1
Medical Radiation Physics, Department of Nuclear
Medicine, Ulm University, Ulm, GERMANY, 2Department
of Nuclear Medicine, Ulm University, Ulm, GERMANY,
Aim/Introduction: PSMA-targeted radioligand therapy with 3
Department of Nuclear Medicine, Klinikum Rechts der Isar,
lutetium-177 is an effective treatment option for metastatic, Technische Universität München, Munich, GERMANY.
castration-resistant prostate cancer (mCRPC). Small molecule
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S172

Aim/Introduction: Kidneys are an organ at risk in 177Lu- Aim/Introduction: Personalized dosimetry in nuclear medicine
PSMA therapy. For renal dosimetry, time-integrated activity relies on many individual steps: Points of time-activity-curve
coefficients (TIACs) of the kidneys are determined. However, (TAC) are derived from emission imaging, models are fit to TAC,
in practice the sampling schedules are not optimized for this area-under-the-curve (AUC) is extracted and converted to organ-
purpose. A modified version of a recently developed method wise absorbed dose by application of S-values, derived from
was used to determine optimal sampling schedules for 177Lu- MIRD phantoms. Current clinical dosimetry is predominantly
PSMA I&T therapy. Materials and Methods: Biokinetic data of manual, time-consuming, and non-standardized. Its complexity
13 patients with metastatic castration-resistant prostate cancer hinders its extension to fully 3-D based one. Siemens developed
(mCRPC) during 177Lu-PSMA I&T therapy and a whole-body a dedicated 3-D, voxel-based dosimetry tool-chain, consisting
physiologically based pharmacokinetic (PBPK) model were of xSPECT Quant technique and Dosimetry Research Tool (DRT),
used to create virtual patients. The virtual patients were used to which automates and integrates all steps of 3-D dosimetry.
generate renal time-activity curves considered as ground-truth. Aims of our study were to evaluate factors causing deviations
The 2640 investigated sampling schedules consisted of three of manual and automatic dosimetry. We introduce the
planar whole-body images to determine the patient-specific experimental setup enabling this investigation and first results,
biokinetics and a quantitative SPECT/CT to correctly scale the which characterize differences between TAC data obtained by
determined biokinetics, i.e. compensating for the systematic standardized NIST-traceable xSPECT Quant (xQ) technique and
error of the planar image data. All investigated sampling facility-specific phantom-calibrated Flash3D (fQ). Materials
schedules were clinically feasible regarding working hours, and Methods: In 21 patients undergoing either Lu-177-PSMA
comprised of time points < 200 h, had a planar image up to 4 h (n=12) or -DOTATOC (n=9) therapy, dosimetry of kidneys, liver,
after administration of the radiopharmaceutical and a SPECT/ and spleen was performed. Image data were acquired from
CT simultaneously to one planar image. For each sampling SPECT at 4h, 24h (as SPECT/CT), 48h, 72h p.i. on a Symbia T2.
schedule for the planar images, noise was added to the virtual Organ-VOIs were defined manually on CT data. 3-D SPECT data
patients’ time-activity data (log-normally distributed, total in absolute units (Bq/ml) were obtained based on xQ and fQ.
standard deviation: 20 %, ratio of systematic to stochastic error Siemens’ DRT was used to automatically co-register data with
rsyst/stoch: 1:3, 1:1, 3:1). A mono-exponential fit function was fitted the VOI-defining CT, for extracting organ-wise TAC, fitting
to the simulated data. The analytically calculated “planar” TIACs (mono-exponential), and calculating AUC. Additionally, fitting
were subsequently scaled with the activity value (log-normal, and AUC determination were carried out with commercial
standard deviation: 5 %) of the simulated SPECT/CT. For each software (Graphpad PRISM 5). Deviations between following
virtual patient and each sampling schedule, 10,000 replications items were analyzed: -TAC-fit parameters and AUC as calculated
were performed. The optimal sampling schedule was defined by DRT and PRISM 5 -TAC points and resulting AUCs obtained
based on the lowest variability of all simulated TIACs averaged from xQ and fQ. Results: Seven of 80 organ-fits resulted in
over all virtual patients. Results: Planar images at (4, 68-72, 116- implausible half-lives (>physical) and were excluded from
124) h with an additional quantitative SPECT/CT at 68-72 h were further analysis. Deviations between TAC-fit parameters derived
the optimal sampling schedules for all investigated ratios rsyst/ by DRT and PRISM were in remaining cases <0.03% for effective
stoch
. Using this measurement scheme and assuming rsyst/stoch half-life / intercept and <0.2% for AUC. Average deviations
= 1:1, a median of 13 % (range: 6 %, 19 %) of the determined between xQ and fQ data were 4.8±5.2%, 5.7±4.6%, 3.3±4.5%,
TIACs of the investigated population deviated more than 10 % and 8.9±13.8% for left kidney, right kidney, liver, and spleen,
from the ground-truth values. Variations of the second planar respectively. Resulting AUC deviation was 6.2±6.3% (0.3-24.3%),
measurement including the SPECT/CT from the optimal time 7.6±5.6 (1.2-22.5%), 3.3±3.4% (0.1-12.1%), and 11.1±11.6% (1.3-
point to e.g. about 24 h results in higher percentage values 20.9%) for left kidney, right kidney, liver, and spleen, respectively.
of 27 % (13 %, 60 %). Variations of the third time point in the Visual assessment of higher-deviation datasets hinted towards
range of 96 h and 124 h had negligible effects. Conclusion: This residual inaccuracies in registration between reconstructed
simulation study showed that an accurate dosimetry with the SPECT data and CT. Conclusion: Deviations in TAC fitting were
hybrid planar-SPECT/CT method is feasible using three planar negligible, consequently these sub-routines of DRT could be
images around (4, 68-72, 116-124 ) h and one SPECT/CT at 68- considered validated. Relatively low deviations between xQ
72 h. References: None. and fQ were found. These deviations directly propagate to
absorbed dose values, if these are obtained by multiplication
with S-values. References: None.
OP-445
Evaluation of a Highly-Automated Dosimetry Tool-Chain
for Lu-177-Therapies OP-446
P. Ritt1, M. Cachovan2, A. H. Vija3, T. Kuwert1; 225
Ac-PSMA prediction dosimetry: the role of mannitol and
1
Clinic for Nuclear Medicine, Erlangen, GERMANY, 2Siemens glutamate tablet for organ at risk preservation
Healthcare GmbH, Molecular Imaging, Forchheim, GERMANY, A. Sarnelli1, M. L. Belli1, F. Cesarini1,2, E. Mezzenga1, V. Di Iorio1, M.
3
Siemens Medical Solutions USA, Inc., Molecular Imaging, Monti1, P. Caroli1, F. Matteucci1, E. Tardelli1, S. Nicolini1, S. Severi1, G.
Hoffman Estates, MI, UNITED STATES OF AMERICA. Paganelli1;
1
Istituto Scientifico Romagnolo per lo Studio e la Cura
S173 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

dei Tumori (IRST) IRCCS, Meldola, ITALY, 2Alma Mater 1007


Studiorum - Università di Bologna, Bologna, ITALY. Teaching Session 4 - Interactive Clinical Cases
- Translational and Molecular Imaging Therapy
+ Drug Development Committee: Chemical
Aim/Introduction: For novel alpha particle Peptide Receptor Entities that can Induce a Therapeutic Response
Radio Therapy treatments, dosimetry evaluation is of paramount in Vivo ? Light vs Radioisotopes
importance for toxicity evaluation prevision. Dose limiting
organs in PSMA (Prostate-Specific Membrane-Antigen) based Monday, October 14, 2019, 16:30 - 18:00
Lecture Hall 113
PRRT therapy are salivary glands and kidneys. A strong and
unexpected xerostomia toxicity was observed for 225Ac-PSMA
therapy [1]. A phase-II trial is ongoing at our Institute, with the
administration of 177Lu-PSMA treatments in combination with OP-447
mannitol intra-venous infusion and iron mineral glutamate PDT General Overview
oral administration (candy) combined with ice-pack external T. Hasan;
application in order to reduce kidneys and salivary glands Wellman Center for Photomedicine, Harvard
uptake, respectively. Based on 177Lu-PSMA data, we evaluated Medical School, Massachusetts General Hospital,
the impact of administered organ preservation drugs on 225Ac- Boston, MA, UNITED STATES OF AMERICA.
PSMA uptake, assuming a similar uptake guided by PSMA
substrate. Materials and Methods: 225Ac-PSMA prediction
dosimetry was performed on 10 patients treated with 5.5 OP-448
GBq(5pts) and 4.4 GBq(5pts) of 177Lu-PSMAPRRT. Sequential PDT Strategies for Recurrent Head and Neck Cancer
whole-body planar images and blood samples were acquired at B. Karakullukçu;
1h,16-24h,36-48h and 120h post-injection. Data were corrected The Netherlands Cancer Institute, Antoni van Leeuwenhoek
for scatter, attenuation, background and anterior/posterior view Hospita, Department of Head and Neck Surgery
geometric mean. 177Lu time-activity curves were corrected and Oncology, Amsterdam, NETHERLANDS.
for 225Ac physical decay, and assumed in equilibrium for all
daughters. OLINDA adult male phantom was used for whole
body(WB), kidneys, liver and red marrow(RM) dose estimation OP-449
with remainder of the body inclusion, while spherical model PDT and the Dosimetry of Light
was used for parotid and submandibular glands (PGs,SGs). M. Konijnenberg;
Absorbed dose for each daughter was calculated and summed Erasmus MC, Radiology and Nuclear Medicine,
for the total dose estimation. Correction for single mass organ Rotterdam, NETHERLANDS.
(based on pre-PRRT PET-CT) and patient weight was introduced.
Results: 10 patients were enrolled, Dosimetry was performed
on first cycle for all patients except 3 (second cycle); median
age was 68y(range:53-85). Single or bi-exponential time-activity
curve fitting were considered. Median(range) effective half- 1008
life were 30.9h (27.2-67.4) for PGs, 34.0h (16.1-70.1) SGs, 48.3h
(12.9-70.7) kidneys, 67.0h (15.0-240) liver, 6.90h (2.60-15.2) RM
Clinical Oncology - Featured: Hybrid PET/MRI -
and 79.5h (17.5-110) for remainder WB. For dose calculation,
Quo Vadis?
RBE=5 was used for alpha particle weight, 1 for beta/photon
component. Median(range) doses were 0.50 SvRBE=5/MBq (0.28- Monday, October 14, 2019, 16:30 - 18:00 Lecture Hall 114
2.73) for PGs, 0.62 SvRBE=5/MBq (0.26-1.19) SGs, 0.72 SvRBE=5/
MBq (0.25-1.82) kidneys, 0.11 SvRBE=5/MBq (0.05-017) liver, 0.05
SvRBE=5/MBq (0.03-0.14) RM and 0.04 SvRBE=5/MBq (0.02-0.11) for
WB. A reduction more than 50% for salivary gland mean dose is OP-450
observed compared to previously published data (2.33 SvRBE=5/ 10 Years PET/MRT – Was it Worth the Effort?
MBq[1]). Conclusion: The possibility to reduce salivary glands P. Veit-Haibach;
uptake in 225Ac-PSMA PRRT treatment with the administration University of Toronto, Department Medical
of combined therapy was estimated. Our results are promising, Imaging, Toronto, ON, CANADA.
but should be confirmed with effective 225Ac-PSMA therapy and
post-injection evaluation in terms of toxicities and treatment
outcome. References: [1]Kratochwil 2017;JNM:58(10),1624-
1631.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S174

OP-451 Medical College, Beijing, CHINA, 3Center for Biomedical Imaging


Texture analysis of 2-point Dixon Images acquired during Research, Department of Biomedical Engineering, School of
PET/MRI: Technique and Initial Experience in Colorectal Medicine, Tsinghua University, Beijing, CHINA, 4Division of
Cancer Nuclear Medicine, Department of Biomedical Imaging and
B. Ganeshan, D. Walls, L. Hoy, S. Wan, K. Miles, A. Groves; Image-guided Therapy, Medical University of Vienna, Vienna,
University College London Hospital, London, UNITED KINGDOM. AUSTRIA, 5Department of General Surgery, Peking Union
Medical College Hospital, Chinese Academy of Medical Science
& Peking Union Medical College, Beijing, CHINA, 6Department
Aim/Introduction: To describe the technique and initial of Doppler Ultrasonic, Peking Union Medical College Hospital,
results obtained from MR texture analysis (MRTA) of 2-point Chinese Academy of Medical Science & Peking Union Medical
Dixon images acquired during PET/MRI in patients with College, Beijing, CHINA, 7Department of Gastroenterology, Peking
colorectal cancer. Materials and Methods: Simultaneous Union Medical College Hospital, Chinese Academy of Medical
Fluorodeoxyglucose PET/MRI was performed prospectively Science & Peking Union Medical College, Beijing, CHINA.
in 30 consecutive patients with primary colorectal cancer (20
male, 10 female; mean age: 63.9 years; range 42-83 years). MRI
acquisitions included 2-point Dixon sequences and diffusion Aim/Introduction: Cystic lesions of the pancreas are common
weighted imaging with mapping of apparent diffusion and increasingly detected in the primary care setting.
coefficient (ADC). Parametric images of fractional water content Noninvasive determination of malignancy is of major interest
(FWC) generated from Dixon sequences underwent MRTA using for patient therapeutic management. We aim to evaluate the
commercially available software (TexRAD, Feedback Medical Ltd, diagnostic performance of 18F-FDG PET/MRI in preoperative
Cambridge, UK). A filtration step highlighting image features of assessment of patients with pancreatic cystic neoplasms
specified sizes as determined by the spatial scaling factor (SSF) (PCNs). Materials and Methods: Twenty-seven Patients (9
preceeded quantification of texture using statistical parameters male, 54.1 ±12.8 yrs) with suspected PCNs underwent 18F-FDG
derived from histograms of filtered images of FWC within the PET/MR using a GE Signa PET/MRI scanner prior to resection
primary colorectal cancer. FWC and MRTA were assessed for or endoscopic ultrasound-guided fine-needle aspiration. MR
inter-operator agreement and correlated against tumor stage, protocol included T1-weighted, T2-weighted and diffusion-
ADC histogram analysis and overall survival. Results: Tumor weighted sequences. 18F-FDG was injected with 3.7-7.4mbq/
FWC (mean: 0.889; range: 0.180 - 0.978) correlated significantly kg 144 ± 56 min before scan. According to the revisions of
with the kurtosis of the ADC histogram (rs=-0.429, p=0.018) but international consensus Fukuoka guidelines 2017 and European
not with ADCmean (rs=0.164, p=0.388). The standard deviation evidence-based guidelines on pancreatic cystic neoplasms
of tumor FWC correlated with tumor stage (rs=0.419, p=0.021). 2018, cystic lesions were characterized and classified to
Inter-operator agreement for MTRA was excellent (intra- subtypes of intraductal pancreatic mucinous neoplasm (IPMN),
class correlation coefficients > 0.8) for all parameters except serous cystic neoplasm (SCN), mucinous cystic neoplasm
skewness at SSF=2 and was superior to histogram analysis of (MCN) and solid pseudopapillary neoplasm (SPN) based on
unfiltered FWC images. MRTA expressed as entropy correlated MRI anatomical features including lesion size and main duct
with the kurtosis of ADC histograms at multiple SSF values (rs involvement. Tumor with high-grade dysplasia and invasive
= 0.399, p=0.029 for SSF=6) and was associated with overall pattern were defined as malignance based on the histological
survival (p=0.0089 for SSF=2). Conclusion: MRTA of tumor examinations. Patients were grouped into malignant (n = 8,
water fraction images shows good inter-operator agreement, IPMN=7, pancreatic ductal adenocarcinoma=1) and benign
correlates with ADC histogram analysis and relates to overall (n=16, IPMN=6, SCN=7, MCN=3) groups. Pancreatic pseudocyst
survival in primary colorectal cancer. MRTA can potentially (n=3) were excluded from analysis. Regions of interest (ROIs)
assess tumor heterogeneity from MR images acquired routinely were defined on the lesions on MRI. The maximum standardized
during simultaneous PET/MRI evaluation of primary colorectal uptake value (SUVmax) of placed RIOs was assessed on PET. The
cancer. References: None. uptake ratio (SUVR) was calculated by SUVmax of the lesion
targeted to the liver (mean of SUV of 1 cm ROI). Corresponding
calculation of sensitivity, specificity, and accuracy of SUVR to
OP-452 differentiate malignance and benign tumors, and the Receiver
18
F-FDG PET/MR in discriminating between malignant and Operating Characteristic curve analysis (ROC) were performed.
benign pancreatic cystic neoplasms (PCNs) Results: SUVR values (4.97 ± 3.72) in malignant group were
H. Xing1, B. Hou2, W. Zhu1, H. Ding3, X. Li4, Y. Hu5, H. Xue2, F. Feng2, K. significantly elevated than those in benign group (0.87 ± 0.32) (P
Lv6, X. Wu7, F. Li1, Z. Jin2, D. Li5, L. Huo1, Y. Zhao5; = 0.017) To differentiate malignance from benign, the threshold
1
Department of Nuclear Medicine, Peking Union Medical College value of SUVR=1.75 was associated total sensitivity, specificity,
Hospital, Chinese Academy of Medical Science & Peking Union and accuracy were 75%, 100% and 91.7% respectively. Area
Medical College, Beijing Key Laboratory of Molecular Targeted under the ROC curve was 0.852 with significance level of P =
Diagnosis and Therapy in Nuclear Medicine, Beijing, CHINA, 0.0047. Conclusion: FDG/MRI PET might provide incremental
2
Department of Radiology, Peking Union Medical College diagnostic value in differentiation between benign and
Hospital, Chinese Academy of Medical Science & Peking Union malignant pancreatic cystic neoplasms. References: None.
S175 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

OP-453 technique with clinical relevance. References: None.


Fully hybrid PET/MRI with 18F-FDG in preoperative
staging of endometrial cancer: initial experience
P. Mapelli1,2, G. Ironi3, A. Bergamini1,4, F. Fallanca2, L. Bocciolone4, OP-454
P. Scifo2, V. Bettinardi2, R. Cioffi1,4, G. Taccagni5, M. Petrone4, E. The role of PET/MR imaging, PSA and patient age in risk
Rabaiotti4, L. Gianolli2, G. Mangili4, F. De Cobelli1,3, M. Picchio1,2; prediction for lesions from prostate cancer
1
Vita-Salute San Raffaele University, Milan, ITALY, 2Nuclear L. Papp1, C. P. Spielvogel2, M. Grahovac3, T. Beyer1, M. Hacker3;
Medicine Department, IRCCS San Raffaele Scientific Institute, 1
QIMP team, Center for Medical Physics and Biomedical
Milan, ITALY, 3Radiology Department, IRCCS San Raffaele Scientific Engineering, Medical University of Vienna, Vienna, AUSTRIA,
Institute, Milan, ITALY, 4Unit of Obstetrics and Gynaecology, 2
Christian Doppler Laboratory for Applied Metabolomics, Medical
IRCCS San Raffaele Scientific Institute, Milan, ITALY, 5Pathology University of Vienna, Vienna, AUSTRIA, 3Division of Nuclear
Unit, IRCCS San Raffaele Scientific Institute, Milan, ITALY. Medicine, Medical University of Vienna, Vienna, AUSTRIA.

Aim/Introduction: 18F-FDG PET/CT and Magnetic resonance Aim/Introduction: PET/MRI together with clinical values, such
imaging (MRI) have complementary roles in the management as PSA and patient age play an important role in prostate cancer
of patients with endometrial cancer. Aim of the present study management. Nonetheless, the importance of PET and MRI
is to present the emerging clinical value of fully hybrid 18F-FDG modalities in low-high risk prediction is still unknown. This study
PET/MRI in preoperative assessment of endometrial cancer. compared PSA and patient age with modality-specific in-vivo
Materials and Methods: Twelve patients with endometrial features to estimate their relative importance in risk prediction.
cancer candidate to surgery underwent 18F-FDG PET/MRI Materials and Methods: 74 prostate patients were included
(SIGNA PET, General Electric Medical Systems, Wakesha, having a multi-parametric PET/MRI with 8 modalities: 18F-FMC
Wisconsin, USA) for staging purpose from December 2018 to and 18F-FMC+68Ga-PSMAHBED-CC (dual-tracer) PET, furthermore,
April 2019. A dedicated PET/MRI protocol has been optimized: T2, ADC, iAUC, KEP, Ktrans and Ve MRI. Based on annotated,
a simultaneous PET/MR whole-body (WB) scan started full-mount histopathological slices, 120 lesions representing
approximately 60 minutes after 18F-FDG injection; a second different Gleason patterns were delineated from the PET/MRI
PET/MRI study, corresponding to a single PET-FOV, has been dataset (Hermes Nuclear Diagnostics, Sweden). Clinical PSA
acquired centered over the pelvis at the end of the WB scan. This value and patient age features were merged with 56 highly
latter acquisition provided: high statistic PET scan and large FOV repeatable (multi-centric variation <5%) in vivo features (7
axial T2w and high-resolution small FOV T2-w FSE (fast spin echo) feature x 8 modality) [1]. A low risk (<=Gleason 3) vs. high risk
PROPELLER of the pelvis; a small field of view (FOV) diffusion- (>=Gleason 4) predictive model was established over the 58
weighted acquisition (DWI) on primary tumor; dynamic contrast features [2]. Predictive performance was estimated by 1000-
enhances (DCE) MRI of the primary tumor; large FOV axial fat- fold Monte Carlo (MC) cross-validation with 80% training
saturated T1-weighted sequence of the pelvis before and after and 20% validation sets in each fold. The PSA, patient and
contrast agent administration; a small FOV high-resolution 3D modality-specific feature weights of the established predictive
fat-saturated T1-weighted sequence of the uterus after contrast models over the MC folds were averaged and normalized to
agent administration. Six out of 12 patients already have the sum of 1.0. This way, relative importance of PSA, patient
histological data available. Results: Patients’ median age was 65 and the 8 imaging modalities in predicting low-high risk could
yrs (range: 52-86). All patients well tolerated the 18F-FDG PET/ be compared. Results: The low-high risk predictive model
MRI scan although the duration time of the study (approximately performance was: SENS 72%, SPEC 77%, ACC 75%, PPV 76% and
60 minutes). 18F-FDG PET/MRI identified the primary tumour in NPV 73%. The feature weight ratios were the following: PSMA
all 12 patients. Using a threshold of 40%, mean value (range) (50%), PSA (10%), patient age (10%), T2 (8%), ADC, and VE (5%
of SUVmax, SUVmean, MTV and TLG of the primary tumours each), iAUC, KEP, Ktrans and FMC (3% each). Conclusion: PSMA
were 25.5 (5.1-72.4), 15.5 (2.6-44), 18.7 (0.8-71.2), 277.7 (3.9- PET-derived features together with PSA and patient age features
1026.1). Additionally, in 4/12 patient lymphnodal involvement appear to be highly important to predict low-high risk of prostate
has been detected. Mean value (range) of SUVmax, SUVmean, cancer lesions. FMC and MRI modalities had a significantly
MTV and TLG of the positive lymphnodes were 8.5 (3.9-16.5), 4.8 lower importance (overall 30%) in predicting low-high risk
(2-9.4), 3.3 (0.8-8.4), 10.1 (4.6-17.2). Regarding the 6 patients with of prostate lesions. As the FMC PET had 3% importance, we
available histology, 4/6 had endometrial type tumour, 1/6 had consider that the dual-tracer PET acquisition did not introduce
mixed-serous carcinoma and 1/6 presented a malignant mixed- significant bias to PSMA-derived features. References: Papp
mullerian tumour. Among the 4/12 patients with lymphnodal L., et al: Optimized feature extraction for radiomics analysis of
involvement detected by PET/MRI, for 3/4 histology confirmed 18F-FDG-PET imaging. JNM 2018, 10.2967/jnumed.118.217612
lymphnodal metastases while in 1/4 histology showed chronic Papp L., et al: Glioma Survival Prediction with Combined Analysis
reactive lymphadenitis. Conclusion: Simultaneous 18F-FDG of In Vivo 11C-MET PET Features, Ex Vivo Features, and Patient
PET/MRI scan is feasible and well tolerated in patients with Features by Supervised Machine Learning. JNM, 2018(59):892-
endometrial cancer candidate to surgery. This preliminary 899.
experience highlight an emerging clinical role of this hybrid
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S176

OP-455 OP-456
Ga68 PSMA PET/MRI in newly diagnosed prostate Can the number of tumour feeding vessels predict hypoxia
cancer patients: Correlation of Ga68 PSMA uptake in in breast cancer? A study using combined 18F-FMISO PET-
intraprostatic lesion with disease stage MRI
U. Aydos1, U. Akdemir1, S. Gulbahar1, I. Gonul2, N. Karabacak1, T. J. Carmona-Bozo1, R. Manavaki1, G. Baxter1, R. Woitek1, A.
Alkibay3, L. Atay1; Patterson1, E. Provenzano1,2, T. Frayer1, M. Graves1, F. Gilbert1;
1
Gazi University Medical Faculty Department of Nuclear 1
University of Cambridge, Cambridge, UNITED
Medicine, Ankara, TURKEY, 2Gazi University Medical Faculty KINGDOM, 2Cambridge University Hospitals NHS
Department of Pathology, Ankara, TURKEY, 3Gazi University Foundation Trust, Cambridge, UNITED KINGDOM.
Medical Faculty Department of Urology, Ankara, TURKEY.

Aim/Introduction: To investigate the relationships between


Aim/Introduction: Our purpose in this study was to evalute hypoxia (18F-FMISO-PET), tumour perfusion (DCE-MRI) and the
the clinical value of the degree of Ga68 PSMA uptake in number of feeding vessels in breast cancer. Materials and
intraprostatic lesions for the prediction of nodal and distant Methods: Imaging was performed using a GE Signa PET-MRI
metastases in newly diagnosed prostate cancer patients. scanner on 28 patients with biopsy-confirmed breast cancer.
Materials and Methods: The data of 62 newly diagnosed A 60-min simultaneous PET-MRI scan was performed following
prostate cancer patients who underwent pretreatment whole injection of 300 MBq 18F-FMISO and a 2-hour uptake period.
body Ga68 PSMA PET/MRI were analyzed retrospectively. For Hypoxic status was assessed using the influx rate constant Ki
the quantitative analysis, the highest SUVmax of intraprostatic determined through Patlak-plot analysis, using a population-
lesions were used. We also studied a visual assessment of Ga68 based arterial input function derived from existing data. Perfusion
PSMA uptake to evaluate the presence of local lymph node and parameters were derived from DCE-MRI data using the extended
distant metastases in PET/MRI images. Distant metastases were Tofts model (Ktrans). Tumour feeding vessels (FV) were counted
divided into two groups according to the number of metastatic on maximum intensity projection (MIP) images generated from
lesions (oligometastatic if ≤3 lesions and multimetastatic if >3 the maximally enhancing phase of the DCE-MRI (approximately
lesions). Pretreatment PSA values, Gleason scores, medium corresponding to phase 22). Tumours positive for oestrogen or
and high risk groups according to Gleason scores (7 and 8-10, progesterone receptors were classified as hormone receptor
respectively) were also noted. Results: The median age of our positive (HR+). Associations between imaging parameters
patient group was 65,0 ± 7,6 years. SUVmax of intraprostatic and FV were assessed via Spearman correlation. Results: 28
lesions were moderately correlated with the Gleason scores (R= patients/ 31 primary breast cancers were assessed (HR+: n=30;
0.461; p=0.001). PSA levels also showed a moderate correlation HR-: n=1; ductal: n=20; lobular: n=6; mixed: n=3; mucinous;
with both Gleason scores (R= 0.367; p=0.014) and SUVmax (R= n=2; Grade: I: n=3; II: n=15; III: n=13). Tumour longest diameter
0.372; p=0.018). When SUVmax measurements were analyzed ranged between 11 and 53-mm. The median number of tumour
according to Gleason risk groups, significantly higher values feeding vessels was 9 (range: 1-39). An inverse correlation was
were observed in the high risk group compared to the medium observed between Ki and the number of feeding vessels (rho=-
risk group (14.8 ± 8.6 vs 7.2 ± 4.6; t: 3.947 and p<0.001). SUVmax 0.10; p=0.58). A positive relationship was observed between
of intraprostatic lesions were higher in the multimetastatic Ktrans and FV (rho=0.10; p=0.56). There was a significant positive
group (22.4 ± 10.6) than the oligometastatic group (11.3 ± 6.2) correlation between tumour size and the number of tumour
and the nonmetastatic group (11.1 ± 7.4), but the differences feeding vessels (rho=0.45; p=0.01). Conclusion: Ki mean, which
reached statistical significance only for the comparison between is a marker of hypoxia, had a negative relationship with breast
the multimetastatic and the nonmetastatic groups (One-way cancer feeding vessels and a positive relationship with tumour
ANOVA, post-hoc test: Bonferroni p=0.019). In the medium risk vascularity (Ktrans). A statistically significant relationship was
group (n=25), there were no metastatic patients and all of the found between the number of feeding vessels and tumour size.
metastatic patients were seen in the high risk group (n=31). References: None.
When the relationship between risk groups and the presence
of local lymph node metastases was analyzed, the patients with 1009
multiple pathological lymph nodes were in the high risk group.
In medium risk group there was only one patient with lymph
Neuroimaging - Parallel Session: TAU Imaging
node metastasis. Conclusion: The degree of Ga68 PSMA uptake
in intraprostatic lesions in newly diagnosed prostate cancer Monday, October 14, 2019, 16:30 - 18:00 Lecture Hall 115
patients correlated with the presence of lymph node and distant
metastases. Ga68 PSMA SUVmax levels of intraprostatic lesions
were found to be approximately two fold higher in the high risk OP-457
group compared to medium risk group and in multimetastatic Tau-PET Correlates with Neuropathology Findings
group compared to nonmetastatic group. References: None. V. Lowe1, E. S. Lundt1, S. M. Albertson1, H. Min1, P. Fang1, S. A.
Przybelski1, M. L. Senjem1, C. G. Schwarz1, K. Kantarci1, B. Boeve1, D.
T. Jones1, J. F. Tranovich2, F. S. Hanna Al-Shaikh2, D. Knopman1, C. R.
S177 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

Jack Jr.1, D. W. Dickson2, R. C. Petersen1, M. E. Murray2; OP-458


1
Mayo Clinic, Rochester, MN, UNITED STATES OF AMERICA, Changes in synaptic density in relation to tau deposition
2
Mayo Clinic, Jacksonville, FL, UNITED STATES OF AMERICA. in prodromal Alzheimer’s disease: a dual protocol PET-MR
study
H. R. J. Vanhaute1, J. Ceccarini2, L. Michiels3, S. Sunaert4, R.
Aim/Introduction: Correlation of tau positron emission Lemmens3, L. Emsell4, M. Vandenbulcke5, K. Van Laere2;
tomography findings to autopsy data is important to 1
Nuclear Medicine and molecular imaging, Department of
understand the sensitivity and specificity of tau positron Geriatric Psychiatry, University Hospitals Leuven; department
emission tomography for neurofibrillary pathology and the of imaging and pathology, Catholic University Leuven, Leuven,
relationship of this neuroimaging method to commonly BELGIUM, 2Nuclear Medicine and molecular imaging, University
used neuropathologic schemes (1). We evaluated a group of Hospitals Leuven; department of imaging and pathology,
participants who had brain autopsy to assess tau deposition Catholic University Leuven, Leuven, BELGIUM, 3Department
and its relationship with tau-positron emission tomography of Neurology, University Hospitals Leuven; Laboratory for
signal seen antemortem. Materials and Methods: Autopsies neurobiology, Catholic University Leuven; Center for Brain and
were performed on 26 participants from the Mayo Clinic who disease research, VIB-KU Leuven, Leuven, BELGIUM, 4Department
had antemortem tau-positron emission tomography with of Imaging and pathology, Translational MRI; Catholic
flortaucipir within 30 months. Flortaucipir positron emission University Leuven, Leuven, BELGIUM, 5Department of Geriatric
tomography standardized uptake value ratios were determined Psychiatry, University Hospitals Leuven, Leuven, BELGIUM.
by a composite brain meta-region (amygdala, entorhinal
cortex, fusiform, parahippocampal, and inferior temporal and
middle temporal gyri) normalized to the bilateral cerebellar Aim/Introduction: Synaptic loss and deposition of
crus gray matter. An optimal flortaucipir uptake ratio cut-point neurofibrillary tangles (NFT) are known, early pathophysiological
to identify those with Alzheimer’s disease primary or secondary changes in the AD course, already detectable in prodromal
neuropathologic diagnoses was determined. Autopsy diagnosis stages1,2. Both events correlate with early cognitive
and Braak tangle stage of the participants were compared impairment2,3. Hyperphosphorylated tau could cause loss
to flortaucipir imaging findings. Comparison of quantitative of synaptic connections4, leading downstream to cognitive
tau burden at autopsy to regional flortaucipir signal was also dysfunction, but the exact neuropathological sequence
performed. Results: Autopsy diagnoses included Alzheimer’s remains largely unknown. In a multitracer PET-MR study we
disease (n=11), pathological aging (n=1), globular glial tauopathy simultaneously assessed synaptic density, by 11C-UCB-J, and
(n=1), primary age-related tauopathy (n=3), Lewy body disease deposition of NFT, by 18F-MK-6240, in patients with amnestic
(n=9), and hippocampal sclerosis (n=1). A flortaucipir cut-point of mild cognitive impairment (aMCI) and healthy controls (HC)
1.29 was determined to be optimal. Flortaucipir was elevated in to gain insight in the temporal distribution of these two
all participants with Alzheimer’s disease. Those with Braak tangle hallmarks of cognitive decline. Materials and Methods:
stages of IV or greater all had elevated flortaucipir signal. Three Nine aMCI patients (70.1±5.5years, 3F/6M, MMSE 22-28) and
Lewy body disease participants and a globular glial tauopathy 9 HC (68.0±6.3years, 5F/4M, MMSE 28-30) underwent static
participant also had elevated flortaucipir signal. Quantitative 11
C-UCB-J (60-90min post-injection (p.i.), 221.2±83.7MBq), 18F-
measurement in temporal lobe regions of tau burden at MK-6240 (90-120min p.i., 139.1±22.7MBq) and 11C-PIB PET scans
autopsy and flortaucipir signal were highly correlated (rho’s (40-60min p.i., 197.3±52.5MBq) on a GE Signa 3T PET-MR and
from 0.61 to 0.70, p <0,002). Conclusion: Elevated flortaucipir neuropsychological tests. We studied SUVR images for 11C-UCB-J
signal seen with an Alzheimer’s disease specific cortical meta- and 18F-MK-6240 using respectively the centrum semiovale5 and
region reflects Braak stage IV or greater neuropathology. Some the cerebellar grey matter6 as reference region. Grey matter
participants with Lewy body disease had elevated flortaucipir (GM) atrophy was assessed with voxel-based morphometry
signal in the meta-region but the signal intensity was low (not using T1-weighted MR images (Puncorr<0.001,Kext>200 voxels).
greater than 1.5 in this group) and was likely due to minimal Voxelwise group analysis (SPM12) and volume-of-interest (VOI)
or early tau pathology in this group. Participants with primary based correlation analyses (Hammers N30R83 atlas PMODv3.9)
age-related tauopathy, and hippocampal sclerosis did not show were conducted. We expressed the relationship between
elevated flortaucipir signal above the cut-point. A secondary regional changes in synaptic density and tau deposition by
neuropathologic diagnosis in the Alzheimer’s disease spectrum VOI-based Z-scores of SV2A and tau. Results: We observed
can be represented by a minimally positive flortaucipir signal. GM reductions in the aMCI group in the superior and inferior
Flortaucipir signal is a valid biomarker of the neurofibrillary temporal gyrus, hippocampus, precuneus, middle occipital
tangle pathology of Alzheimer’s disease. References: 1. Braak gyrus and parietal cortices. Compared to HC, aMCI patients had
H, Braak E. Neuropathological stageing of Alzheimer-related a decrease in SV2A binding in the medial temporal lobe (MTL),
changes. Acta Neuropathol 1991; 82(4): 239-59. adjacent lateral temporal gyri and insula (T>5.3; decrease: 13-
20%). We revealed increased 18F-MK-6240 binding in the MTL,
spreading to the parietal and occipital cortex (T>3.5; increase:
51-102%). The decrease in synaptic density and increase
in tau deposition remained present in the mesotemporal
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S178

regions after correcting for PVE. In the MTL, higher tau were stronger for SCD subjects than MCI/AD patients (r=0.76 for
accumulation was inversely related to lower synaptic density p-tau; r=0.81 for t-tau vs. r=0.38 for p-tau; r=0.42 for t-tau). Voxel-
(Z-scores;p=0.02,r=-0.79). Decreased performance on cognitive wise analyses across all subjects showed significant associations
screening and episodic memory tests was highly significantly between widespread cortical [18F]flortaucipir binding
associated with decreased SV2A binding and increased tau (right>left) and CSF-tau, whereas in SCD a temporoparietal
deposition in the hippocampus(MMSE:p<0.0001,r=0.80; pattern was seen. When entered simultaneously (model 2),
RAVLT delayed recall:p<0.0004,r>0.75). Conclusion: aMCI global [18F]flortaucipir BPND, but not CSF tau biomarkers, was
subjects have high tau deposition and synaptic density loss associated with MMSE and all four cognitive domains across
mainly in key regions known to be involved in early cognitive all subjects. In MCI/AD, worse MMSE, attention and executive
impairment, indicating that these early pathological changes functions were only associated with global [18F]flortaucipir
are interrelated in the MTL. Longitudinal data will provide BPND. Conclusion: There is a strong relationship between tau
further insight in the temporal aspects of this relationship. CSF and [18F]flortaucipir PET, particularly in cognitively normal
References: 1Scheff,S.W.et al;Biochem.Pharmacol;88,517(2014) subjects. Independently of CSF-tau, [18F]flortaucipir PET strongly
2Nelson,P.T.et al;J.Neuropathol.Exp.Neurol;71,362-81(2012) correlates to cognition in AD, but not in SCD. This suggests that
3Terry,R.D.et al;Ann.Neurol;30,572-580(1991) 4Pooler,A.M.et tau PET may more accurately reflects the disease stage than CSF
al;Neuropharmacology;76PtA,1-8(2014) 5Koole,M.et tau. References: None.
al;Eur.J.Nucl.Med.Mol.Imaging;46,396-406(2019) 6Pascoal,T.A.et
al;Alzheimers.Res.Ther;10,74(2018).
OP-460
Cortical Binding Characteristics of 18F-PI-2620 Differentiate
OP-459 the Clinically Predicted Tau Isoform in Suspected
[18F]flortaucipir PET strongly correlates to cognition across 3/4-Repeat and 4-Repeat Tauopathies
the clinical Alzheimer’s disease continuum, independently M. Song1, H. Barthel2, T. van Eimeren3, K. Marek4, L. Beyer1,
of CSF tau C. Palleis1, J. Sauerbeck1, J. Hammes3, F. Jessen3, D. Saur2, M.
E. Wolters1, R. Ossenkoppele1,2, S. C. J. Verfaillie1, E. M. Coomans1, T. Schroeter2, A. Schildan2, O. Barret4, D. Russell4, A. Stephens5, J.
Timmers1, D. Visser1, H. Tuncel1, A. D. Windhorst1, R. Boellaard1, W. Levin1, J. Classen2, G. Hoeglinger6, P. Bartenstein1, V. Villemagne7, A.
M. van der Flier1, C. E. Teunissen1, P. Scheltens1, B. N. M. van Berckel1; Drzezga3, J. Seibyl4, O. Sabri2, M. Brendel1;
1
Amsterdam UMC VUmc, Amsterdam, NETHERLANDS, 1
LMU, Munich, GERMANY, 2University of Leipzig, Leipzig,
2
Lund University, Lund, SWEDEN. GERMANY, 3University of Cologne, Cologne, GERMANY, 4Molecular
NeuroImaging, New Haven, CT, UNITED STATES OF AMERICA,
5
Life Molecular Imaging, Berlin, GERMANY, 6DZNE, Munich,
Aim/Introduction: Tau pathology can be measured in GERMANY, 7University of Melbourne, Melbourne, AUSTRALIA.
cerebrospinal fluid (CSF) and by [18F]flortaucipir PET in vivo. The
aim of this study was twofold. First we examined associations
between CSF total tau (t-tau) and phosphorylated tau(p-tau) Aim/Introduction: Pathological accumulation of
with [18F]flortaucipir PET across the clinical Alzheimer’s disease hyperphosphorylated microtubule-associated tau protein
(AD) continuum, and second we investigated associations of underlies a wide range of neurodegenerative disorders. Tau
CSF-tau and [18F]flortaucipir PET with cognitive performance. proteins consist of different isoforms, characterized by the
Materials and Methods: We included 51 MCI/ AD patients (all number of repeats (R) of microtubule binding sites. Preliminary
amyloid-positive, age: 65±6 years, MMSE: 24±4) and 24 subjective evidence suggests the novel second-generation tau PET tracer
cognitive decline(SCD) subjects (28% amyloid-positive, age: 18
F-PI-2620 is able to visualize the predominantly 3/4R-tauopathy
65±6 years, MMSE: 28±1). Dynamic 130 minute [18F]flortaucipir Alzheimer’s disease (AD) and the mainly 4R-tauopathies
PET scans were performed to generate global binding potential corticobasal syndrome (CBS) and progressive supranuclear palsy
(BPND) images using receptor parametric mapping. Cognitive (PSP), but - apart from the obvious topographical differences -
assessment consisted of MMSE and composite scores of four likely with a different magnitude of affinity among them. The
cognitive domains. Pearson’s partial correlations and voxel-wise aim of this study was to determine whether, in PET-positive
linear regressions were used to investigate associations between cortical regions, the presence of 3/4R- vs. 4R-tauopathies can
CSF-tau and tau-PET; both adjusted for age, sex and time lag be differentiated by the binding characteristics of 18F-PI-2620.
between lumbar puncture(LP) and tau-PET. Linear regression Materials and Methods: 18F-PI-2620 PET data of twenty-three
models were used to assess the relationships between CSF-tau patients (72±9y) with suspected 3/4R-tauopathy (clinical AD;
and tau-PET with cognition(model 1; separate models for CSF n=12) and suspected 4R-tauopathy (clinical CBS/PSP; n=11),
and PET) and assessed the independent effects of CSF t-tau and all visually PET-positive in cortical regions, were included in
tau-PET on cognition(model 2, with both CSF t-tau and [18F] this project. 18F-PI-2620 PET scans were acquired 0-60min p.i.
flortaucipir BPND as predictor). Models were adjusted for age, sex, and distribution volume ratios (DVR, cerebellar reference) were
education and time lag between assessments. Results: Overall, calculated after coregistration to an 18F-PI-2620 template in the
global [18F]flortaucipir BPND was positively correlated with CSF MNI space. Visually presumed tau-positive cortical volumes of
p-tau (r=0.55) and t-tau (r=0.59). Within groups, correlations interest (VOIs) in frontal, parietal, temporal or occipital regions
S179 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

were delineated as target regions by semi-automatized BPND and [18F]Flortaucipir BPND (age and sex adjusted), II) [18F]
thresholding. Target-to-cerebellum ratios in six 5-min frames (30- Florbetapir BPND and cognition and III) [18F]Flortaucipir BPND
60min p.i.) were plotted as a linear function of time to calculate and cognition (models II & III age, sex and education adjusted).
the individual slope in the late binding phase. Mean DVR values, Results: Participants were 66±7 years old, 47% female, Mini
mean 30-60min SUVRs, and slopes were compared between Mental State Examination (MMSE) was 29±1, and 38% were
suspected 3/4R- and 4R-tauopathies. Receiver operating amyloid-β positive on visual read of [18F]Florbetapir PET. Global
characteristics were used to calculate the area under the curve [18F]Florbetapir BPND was correlated with [18F]Flortaucipir BPND in
(AUC) for discriminating suspected 3/4R- vs. 4R-tauopathy by all ROIs (range βs: 0.61-0.74, all p<0.001). Higher [18F]Florbetapir
all three read-outs. Results: Tau-positive cortical regions in BPND was associated with lower memory scores (β=-0.31,
suspected 3/4R-tau cases had significantly higher mean 18F- p<0.05). In addition, higher entorhinal (β=-0.28, p<0.05), but
PI-2620 DVR (1.61±0.17 vs. 1.25±0.08, p<0.001) and mean 30- not LTL or neocortical [18F]Flortaucipir BPND were associated
60 min SUVR (2.13±0.31 vs. 1.44±0.18, p<0.001) values when with worse memory performance (β=-0.17, p=0.22 and β=-0.12,
compared to suspected 4R-tau cases. Slope of the late binding p=0.32). When we modeled [18F]Florbetapir BPND and entorhinal
phase was steeper in suspected 3/4R-tau cases when compared [18F]Flortaucipir BPND simultaneously, the associations with
to suspected 4R-tau cases (0.75 ±0.69 vs. -0.19±0.55, p=0.002). memory were no longer significant ([18F]Flortaucipir: β=-0.18,
AUC for prediction of a suspected 3/4R-tauopathy was highest p=0.26; [18F]Florbetapir BPND: β=-0.19, p=0.25). Non-memory
for SUVR 30-60 min (AUC: 0.970), followed by DVR (AUC: 0.962), domains were not related to [18F]Florbetapir or [18F]Flortaucipir
and the slope (AUC: 0.845). Conclusion: 18F-PI-2620 binding BPND. Conclusion: In cognitively unimpaired individuals with
characteristics in tau-positive cortical brain regions differentiate SCD, amyloid-β and tau are tightly linked across brain regions.
clinically suspected 3/4R-tauopathies from 4R-tauopathies. Increased global amyloid-β and tau in early AD-related regions
Unequal slopes of SUVR in the late binding phase when were both associated with worse memory performance. These
comparing 3/4R- and 4R-tauopathies might reflect different 18F- associations were strongly dependent on each other, providing
PI-2620 binding properties to different tau isoforms. The impact support for the notion that in this early stage, amyloid-β and tau
of variable tau extent and disease severity on these results will are associated with symptoms equally. References: None.
need to be addressed in this ongoing evaluation. References:
None.
OP-462
Longitudinal Dynamic [18F]Flortaucipir PET Reveals
OP-461 Increased Early Stage Tau Pathology in Individuals with
Amyloid and tau PET relate to memory loss in cognitively Subjective Cognitive Decline
normal individuals: the SCIENCe project D. Visser1, R. Ossenkoppele2,3, S. C. J. Verfaillie1, T. Timmers1,2, E. E.
E. Wolters1, T. Timmers1, R. Ossenkoppele1, S. C. J. Verfaillie1, Wolters1,2, H. Tuncel1, E. M. Coomans1, M. E. Schmidt4, R. Boellaard1,
D. Visser1, P. Scheltens1, M. E. Schmidt2, K. van den Bosch1, R. B. Windhorst1, P. Scheltens2, W. M. van der Flier2,5, B. N. M. van
Boellaard1, S. S. V. Golla1, W. M. van der Flier1, B. N. M. van Berckel1; Berckel1;
1
VUmc, Amsterdam, NETHERLANDS, 2Janssen 1
Department of Radiology & Nuclear Medicine, Amsterdam
Research and Development, Beerse, BELGIUM. Neuroscience, Vrije universiteit Amsterdam, Amsterdam
UMC, Amsterdam, NETHERLANDS, 2Alzheimer Center
Amsterdam, Department of Neurology, Amsterdam
Aim/Introduction: Subjective cognitive decline (SCD) may Neuroscience, Vrije Universiteit Amsterdam, Amsterdam
reflect the earliest changes associated with Alzheimer’s UMC, Amsterdam, NETHERLANDS, 3Clinical Memory
disease (AD). The aim of this study was to investigate the Research Unit, Lund University, Lund, SWEDEN, 4Janssen
regional associations between tau pathology, amyloid-β Research & Development, Beerse, BELGIUM, 5Department of
and cognition in cognitively unimpaired individuals with Epidemiology and Biostatistics, Vrije Universiteit Amsterdam,
subjective cognitive decline (SCD). Materials and Methods: Amsterdam UMC, Amsterdam, NETHERLANDS.
We included 53 participants with SCD who underwent both
dynamic [18F]Flortaucipir (tau) and [18F]Florbetapir (amyloid-β)
PET scans and neuropsychological testing. We used receptor Aim/Introduction: Tau pathology is related to clinical
parametric mapping to create [18F]Flortaucipir and [18F] progression in Alzheimer’s disease (AD). Longitudinal tau
Florbetapir binding potential (BPND) images with cerebellar PET imaging in preclinical stages of AD may help to identify
gray matter as reference region. Data were analyzed using individuals at risk of progression. Individuals with subjective
a global cortical region-of-interest (ROI) for [18F]Florbetapir cognitive decline (SCD) may suffer from preclinical AD. As
and ROIs reflecting early (entorhinal), intermediate (lateral dynamic scanning protocols allow for accurate quantitative
temporal (LTL)) and late tau deposition (global cortical) for [18F] measures of tracer retention over time, the aim of this study was
Flortaucipir. Neuropsychological test scores were z-transformed to investigate whether there is a change in tau pathology, as
and combined into composite scores for memory, attention, measured with dynamic [18F]Flortaucipir (FTP) PET, in subjects
executive functions and language. We used linear regression with SCD over a time period of two years. Materials and
analyses to assess associations between I) [18F]Florbetapir Methods: In an ongoing sub-study of the SCIENCe project,
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S180

we included 20 SCD subjects (age 66±8, 45% female, MMSE 11


C-PIB and 18F-T807 PET. 11C-PIB SUVRamyloid>=1.30 and 18F-T807
29±1, 25% [18F]Florbetapir PET positive based on visual read). SUVRtau>=1.14 were taken as the cut-off for diagnosis of AD by
All subjects underwent a 90 minute dynamic [18F]Florbetapir our prior reported studies. 18F-FDG PET was assessed visually and
PET scan at baseline and a 130 minutes dynamic [18F]FTP PET by z-score (MIMNeuro) for regional hypometabolism. AD severity
scan at baseline and 2±0.06 (1.9-2.1) year follow-up. Parametric was assessed by 4-degrees of 18F-FDG hypometabilism to assess
images were generated using receptor parametric mapping neuronal injury:normal, mild, moderate, marked. Correlation
(RPM; reference region cerebellar grey matter) to extract analysis was performed between 4-degrees of AD severity and
non-displaceable binding potential (BPND). For [18F]FTP three SUVRtau & SUVRamyloid respectively. Results: 30/54 patients had
non-overlapping regions-of-interest reflecting early (medial negative 11C-PIB PET (SUVRamyloid=1.12±0.06), as well as negative
temporal), intermediate (limbic) and late stage (neocortical) 18
F-T807 (SUVRtau=1.04±0.05) and 18F-FDG, thus effectively
tau pathology were selected. Analyses were performed using excluded from AD. 24/54 patients were found to have abnormal
ANOVA for repeated measures, adjusting for age and sex. To Aβ (SUVRamyloid=1.52±0.16), of whom 18/24 also had abnormal
examine the interaction effect of amyloid pathology, global tau (SUVRtau=1.39±0.22), thus classified as biological AD (PIB+/
[18F]Florbetapir BPND was added in additional analyses. Results: T807+), while 6/24 without abnormal tau (SUVRtau=1.06±0.04) as
We found a significant increase in [18F]FTP BPND in the medial AD-pathologic-change (PIB+/T807-). 18F-FDG PET was negative
temporal region, F(1,17)=5.205, p=0.036, reflecting an average in all (6/6) patients with AD-pathologic-change. Based on the
increase in tau pathology from 0.01 to 0.02 BPND over the two predefined 4-degrees of 18F-FDG hypometabolism, 5/18 AD
year period. No significant [18F]FTP BPND changes were found patients had no neuronal injury, 6/18 mild, 6/18 moderate,
for the limbic and neocortical regions, F(1,17)=1.654 and 1.660, 1/18 marked. The tau burden strongly correlated with AD
p>0.05. Addition of global [18F]Florbetapir BPND to the model severity measured by the 4-degrees of neurological impairment
revealed an interaction effect in the limbic and neocortical (r=0.828, P<0.05); but Aβ burden correlated poorly (r=0.160,
regions (both p<0.05), attributable to a larger increase in [18F] P>0.05). One-way ANOVA showed significant difference in tau
FTP BPND in amyloid positive individuals. Data collection is still among patients with AD-pathological-change and 4-degrees
ongoing. Conclusion: Over a two year period, quantitative of AD severity (SUVRtau=1.06±0.04, 1.21±0.03, 1.30±0.12,
imaging revealed an increase in tau pathology only in early 1.57±0.16, 1.84±0.00, P<0.05); but no significant difference
stage tau pathology regions in SCD subjects. Individuals with in Aβ (SUVRamyloid=1.42±0.08, 1.56±0.19, 1.46±0.07, 1.68±0.19,
higher amyloid load showed relatively higher levels and 1.43±0.00, P>0.05). Conclusion: 11C-PIB PET/CT is valuable
larger increases in intermediate and late stage tau pathology, for excluding AD and predicting AD pathology at an earlier
supporting the hypothesis that amyloid facilitates the spread of phase. Concomitant 18F-T807 PET/CT may provide quantitative
tau pathology. References: None. assessment of tau burden to allow serial measurement and
longitudinal tracking of AD pathology, thus useful not just for
pre-symptomatic diagnosis, but also for monitoring severity and
OP-463 progression of AD. References: None.
Incremental Value Of Tau Burden Quantified By 18F-AV-
1451 PET/CT Over Conventional 11C-PIB And 18F-FDG PET/
CT For Alzheimer’S Disease OP-464
S. Chen1, Y. Leung1, L. Au2, Y. Lau2, V. Mok2, C. Ho1; Early-Phase 18F-PI-2620 Tau-PET Imaging as a Surrogate
1
Hong Kong Sanatorium & Hospital, Hong Kong, HONG KONG, Marker of Neurodegeneration
2
The Chinese University of Hong Kong, Hong Kong, HONG KONG. L. Beyer1, A. Nitschmann1, H. Barthel2, T. van Eimeren3, K. Marek4,
C. Palleis1, J. Sauerbeck1, M. Song1, J. Hammes3, F. Jessen3, D. Saur2,
M. Schroeter2, A. Schildan2, O. Barret4, D. Russell4, A. Stephens5, J.
Aim/Introduction: Recommended by the Alzheimer’s Levin1, J. Classen2, G. Hoeglinger6, P. Bartenstein1, V. Villemagne7, A.
Association, diagnosis of Alzheimer’s disease (AD) is now based Drzezga3, J. Seibyl4, O. Sabri2, M. Brendel1;
on in vivo biomarkers of abnormal β-amyloid (Aβ) and tau 1
LMU, Munich, GERMANY, 2University of Leipzig, Leipzig,
burden. In Aβ+ patients, tau burden is a continuous variable, GERMANY, 3University of Cologne, Cologne, GERMANY, 4Molecular
not only for AD diagnosis but also useful for tracking disease NeuroImaging, New Haven, CT, UNITED STATES OF AMERICA,
progression. In this study, we investigated the capability of 5
Life Molecular Imaging, Berlin, GERMANY, 6DZNE, Munich,
18
F-AV-1451 (18F-T807) tau PET/CT to quantify the severity of GERMANY, 7University of Melbourne, Melbourne, AUSTRALIA.
neurological impairment by correlation with 18F-FDG PET/
CT. Materials and Methods: From Feb 2018 to Feb 2019, 54
patients (M:22, F:32; age range:43-79years, mean=65.9±8.2years) Aim/Introduction: Tauopathies are a collective of
with decreased short-term memory, with/without cognitive neurodegenerative diseases with the uniting feature of misfolded
impairment, and no history of stroke or other neurodegenerative and accumulated tau protein in different parts of the brain. For
disease, were recruited. They all underwent 3-tracers PET/CT the first-generation tau and several amyloid PET tracers, it has
within 1 week: 18F-FDG at 30 minutes, 11C-PIB at 35 minutes, 18F- been shown that early after tracer administration PET images
T807 at 85 minutes, each with a 10-min static acquisition. Global reflect perfusion and can as such, due to the neurovascular
cortical-to-cerebellum SUV ratio (SUVR) was calculated for both coupling evident in the brain, act as a surrogate of glucose
S181 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

metabolism as determined by 18F-fluorodeoxyglucose (FDG)- Petretta2, W. Acampa1, A. Cuocolo1;


PET. Thus, we aimed to analyse the early-phase PET images of the 1
Department of Advanced Biomedical Sciences, Federico
second-generation tau tracer 18F-PI-2620 to explore its potential II University, Naples, ITALY, 2Department of Translational
as a neurodegeneration biomarker surrogate. Materials Medical Sciences, University Federico II, Naples, ITALY.
and Methods: Patients (n=20) were referred from dementia
experts for imaging with different suspected tauopathies
(n=7: Alzheimer’s disease; n=6: progressive supranuclear palsy; Aim/Introduction: Myocardial perfusion reserve (MPR) is
n=7: corticobasal syndrome). All patients underwent 18F-FDG- a sensitive indicator of vascular damage in patients with
PET in a clinical setting and data had been reconstructed in a cardiovascular risk. It has been suggested that pericoronary fat
static 30-50 min frame. 18F-PI-2620 PET was performed in a full thickness (PCFT) may have a local pro-atherosclerotic effect.
dynamic 0-60 min setting. Single frames (6x30s, 4x60s, 4x120s, However, the association between PCFT and coronary vascular
9x300s) and regional cerebral blood flow estimate R1 maps function has not been fully investigated. We evaluated the
were likewise computed from the dynamic 18F-PI-2620 images. relationships of PCFT and hyperemic myocardial blood flow
Volumes of interest (VOIs) were placed in the bilateral frontal, (MBF) and MPR in patients with suspected CAD and normal
parietal, temporal, and occipital cortices, as well as in the central myocardial perfusion imaging. Materials and Methods: From
region and the striatum. Associations between the resulting a pool of 1550 subjects referred to stress-rest Rb-82 PET/CT, 582
semi-quantitative early-phase 18F-PI-2620 and 18F-FDG-PET patients with suspected CAD and normal myocardial perfusion
standard uptake value ratios (cerebellar reference region) were imaging (summed stress score<3) were considered. Regional
investigated by calculating Pearson’s correlation coefficients (Rs). PCFT, defined as the maximum fat thickness (mm) between the
Results: Highest agreement of single 18F-PI-2620 frames and surface of the heart and the visceral epicardium surrounding
18
F-FDG-PET was found for frames between 60 and 180 seconds the 3 main coronary arteries, and CAC score were measured on
(all R of all regions >0.6). The agreement strongly deteriorated CT images. The mean value of the 3 regional PCFT was used to
after 420 seconds p.i. (mean R<0.4). Summed 1-3 min frames calculate the mean PCFT. Myocardial perfusion was assessed
indicated a significant agreement between early phase 18F- using standardized segmentation of 17 myocardial regions.
PI-2620 frames and 18F-FDG-PET in all target regions (mean Absolute MBF was computed from dynamic rest and stress
R: 0.66±0.13) with highest agreement in the parietal cortex imaging series. MPR was defined as the ratio of hyperemic to
(bilateral R=0.81, both p<0.001) and lowest agreement in the baseline MBF and considered reduced when<2 Results: Among
right frontal cortex (R=0.47, p=0.038). 18F-PI-2620 R1 maps also 582 patients included, 106 (18%) had reduced and 476 (82%)
indicated a good agreement with 18F-FDG-PET in most target normal MPR. Compared to patients with normal MPR, those
regions (mean R: 0.58±0.13) with highest agreement in the with impaired MPR were older (64±13 years vs. 59±13 years,
left temporal cortex (R=0.76, p<0.001) and lowest agreement P<0.001) and showed higher prevalence of hypertension (89%
in the right frontal cortex (R=0.36, p=0.117). Comparisons of vs. 74%, P<0.002) and diabetes mellitus (40% vs. 22%, P<0.002).
visual clinical reads are pending. Conclusion: Early-phase Baseline MBF did not differ between patients with normal
images of the second-generation tau tracer 18F-PI-2620 show and impaired MPR. On the contrary, patients with impaired
high accordance with FDG PET images and can, thus, be used MPR had a blunted response to pharmacological stressor
as a surrogate of neurodegeneration. If also valid for clinical (1.99±0.61 vs. 2.89±0.70, P<0.001) and higher mean PCFT
assessment, this could provide the opportunity to classify two values (11.6±1.9 mm vs. 10.93±1.9 mm, P<0.005) compared to
(tau and neuronal injury) biomarkers with one procedure in a those with normal MPR. At univariate linear regression analysis,
dual-phase “one-stop shop” PET imaging protocol. References: age, hypertension, diabetes, CAC score, and mean PCFT were
None. significant predictors of reduced hyperemic MBF and impaired
MPR, while male gender predicted only a reduced hyperemic
MBF (all P<0.005). Although baseline MBF was not associated
1010 with PCFT, a significant correlation of global and regional
PCFT and corresponding hyperemic MBF was found for left
Cardiovascular - Parallel Session: Myocardial
anterior descending, left circumflex, and right coronary arteries
Blood Flow Quantification with PET
(all P<0.001). Such a relationship was also seen between left
circumflex coronary artery PCFT and corresponding MPR
Monday, October 14, 2019, 16:30 - 18:00 Lecture Hall 116 (P<0.001). Conclusion: In patients with suspected CAD and
normal MPI, there is a significant association of global and
regional hyperemic MBF with PCFT suggesting a local effect
OP-465 of pericoronary fat on underlying coronary vascular function.
Association between pericoronary fat thickness and References: None.
coronary vascular function in patients with suspected
coronary artery disease and normal myocardial perfusion
imaging
C. Nappi1, V. Gaudieri1, R. Assante1, E. Zampella1, G. De Simini1, A.
Giordano1, T. Mannarino1, A. D’Antonio1, R. Green1, V. Cantoni1, M.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S182

OP-466 OP-467
Quantitative myocardial perfusion 82Rb-PET assessed by Prognostic value of coronary vascular dysfunction
hybrid PET/coronary-CT: normal values and diagnostic assessed by hybrid rubidium-82 PET/CT imaging in
performance patients with resistant hypertension
M. T. Freitag, J. Bremerich, D. Wild, P. Haaf, M. J. Zellweger, F. V. Gaudieri1, W. Acampa1, R. Assante1, E. Zampella1, C. Nappi1, T.
Caobelli; Mannarino1, M. Panico2, A. D’Antonio1, M. Raddi1, M. Petretta3, M.
University Hospital Basel, Basel, SWITZERLAND. Memmott4, P. Arumugam4, A. Cuocolo1;
1
Department of Advanced Biomedical Sciences, University
Federico II, Naples, ITALY, 2Institute of Biostructure and Bioimaging,
Aim/Introduction: No conclusive data exist on normal National Council of Research, Naples, ITALY, 3Department of
values of quantified myocardial blood flow on 82Rb-PET/ Translational Medical Sciences, University Federico II, Naples,
CT under stress (sMBF) and rest (rMBF). We aimed to assess ITALY, 4Nuclear Medicine Centre, Manchester University
normal reference values for MBF on a hybrid PET/coronary-CT NHS Foundation Trust, Manchester, UNITED KINGDOM.
scanner and to test their diagnostic performance in patients
with suspected coronary artery disease (CAD). Materials and
Methods: Patients underwent sequential cardiac 82Rb-PET/CT Aim/Introduction: Aim of this study was to evaluate if impaired
(Siemens Biograph mCT 128) with stress/rest (Adenosine) and vasodilator function, assessed by 82Rubidium (82Rb) PET/CT
integrated CT-based coronary angiography (CTCA). Patients imaging, carries to an increased cardiovascular risk in patients
were classified as normal (<50% stenosis on CTCA and summed with resistant hypertension (RH). Materials and Methods:
stress score [SSS]=0) and with CAD (>50% stenosis, any SSS). A total of 518 hypertensive patients without overt coronary
sMBF, rMBF and myocardial flow reserve (MFR) were calculated artery disease and normal myocardial perfusion (summed
both globally and in each vascular territory by Syngo MBF stress score <3) at stress-rest 82Rb PET/CT imaging were studied.
(Siemens). On static PET images, ischemia was visually assessed Hypertension was defined as resistant when the concurrent use
and defined as summed difference score ≥2. Mann-Whitney-U of three different antihypertensive agents failed to lower blood
test was used for comparison of non-parametric data across pressure to target values. Coronary artery calcium (CAC) score
groups, ROC-analysis was performed to determine diagnostic were categorized into 4 groups (0, 0.1-99.9, 100-399.9 and ≥400).
accuracy in identifying ischemia. Flow values are given in ml/g/ Left ventricular (LV) ejection fraction reserve was calculated as
min as mean±SD. Results: Of overall 357 patients included the difference of stress and rest ejection fraction. Baseline and
(male/female 53%/47%, aged 61.1±10.3 years, body-mass-index hyperemic myocardial blood flow (MBF) were automatically
28.9±6.3 kg/m2, 21% diabetics, 57% with arterial hypertension), measured. Myocardial perfusion reserve (MPR) was defined
225 patients were classified as normal and 132 as with CAD. as the ratio of hyperemic to baseline MBF and considered
sMBF and MFR were significantly higher in normal patients reduced when <2. The endpoints were cardiac death, nonfatal
than in patients with CAD (3.64±0.68 vs. 3.05±0.77, p<0.0001; myocardial infarction, coronary revascularization, and admission
3.09±0.86 vs. 2.73±0.77, p=0.0002). rMBF was not different for heart failure. Results: Over a median of 38 months
(1.28±0.40 vs 1.19±0.34, p=0.06). In the right coronary artery (interquartile range 26 to 50 months), 22 cardiac events (4.2%
(RCA), sMBF[RCA] in normal vessels was higher than in stenotic cumulative event rate) occurred: 3 cardiac deaths, 4 myocardial
ones (3.84±0.89 vs 3.31±1.14, p=0.008). Both rMBF[RCA] and infarctions, 5 revascularization procedures and 10 admissions for
MFR[RCA] were not different (1.27±0.44 vs. 1.19±0.48, p=0.14; heart failure. Patients with events compared to those without
3.29±1.03 vs. 3.06±1.23, p=0.13). In the circumflex artery (RCX), were older (70±14 vs. 61±12 years, P<0.001) and had a higher
sMBF[RCX] and MFR[RCX] in normal vessels were significantly prevalence of RH (59% vs. 24%, P<0.001), a higher prevalence
higher than in stenotic ones, (3.26±0.76 vs. 2.50±0.86, of CAC ≥400 (36% vs. 18%, P<0.05), a lower hyperemic MBF
p<0.0001; 2.84±0.83 vs. 2.17±0.69, p<0.0001). rMBF[RCX] was (2.15±0.74 vs. 2.58±0.82 ml/g/min, P <0.05) and a lower MPR
similar between normal and stenotic vessels (1.24±0.38 vs. (2.14±0.86 vs. 2.58±0.70, P<0.01). At univariable Cox regression
1.19±0.24, p=0.99). In the left anterior descending artery (LAD) analysis, age (P<0.001), RH (P=0.001), MPR (P<0.005), and LV
sMBF[LAD] and MFR[LAD] in normal vessels was higher than ejection fraction reserve (P<0.05) were significant predictors of
in stenotic ones (3.53±0.72 vs. 2.89±0.79, p<0.0001; 3.00±0.83 events. At multivariable analysis, age (P<0.01), RH (P<0.05), and
vs. 2.46±0.75, p<0.0001). rMBF[LAD] was similar (1.26±0.38 MPR (P<0.05) were independent predictors of events. Patients
vs. 1.25±0.35, p=0.99). Global sMBF yielded superior accuracy with RH and impaired MPR showed the worst outcome. Event-
in identifying myocardial ischemia over MFR (AUC 0.75 vs. free survival was lower in patients with RH and impaired MPR
0.63, p<0.003). Optimal threshold for sMBF was 3.5 ml/g/min compared to those with controlled hypertension and impaired
(sensitivity 87.5%, specificity 48.7%, negative predictive value MPR (P<0.001). Differently, the best outcome was observed
(NPV) (96%). Conclusion: The assessed normal reference values in patients with controlled hypertension and preserved MPR.
for global sMBF provided higher diagnostic accuracy than MFR Conclusion: Coronary vascular dysfunction by 82Rb PET/
with respect to stenosis detection. Using sMBF-threshold of 3.5 CT in patients with RH can help in identify a higher risk of
ml/mg/min on 82Rb-PET/CT yielded similar NPV (96%) as CTCA cardiovascular events. Thus, MPR could be useful in the risk
to rule out ischemia (1). References: (1) Meijboom et al. JACC assessment and for patient’s management, guiding alternative
2008;52:2135-44. potential therapeutic strategies aimed to directly improve MPR.
References: None.
S183 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

OP-468 OP-469
Quantitative PET with [13N] -Ammonia in the Detection Combined evaluation of regional coronary artery calcium
of Functional Significance of Intermediate Stenoses of and myocardial perfusion by 82Rb PET/CT in predicting
Coronary Arteries lesion-related outcome
D. Ryzhkova, D. Zverev; E. Zampella1, W. Acampa1, R. Assante1, T. Mannarino1, A. Genova1,
National Almazov Medical Research Centre, C. Nappi1, A. D’Antonio1, V. Gaudieri1, M. Panico2, M. Petretta3, P.
St.Petersburg, RUSSIAN FEDERATION. Arumugam4, A. Cuocolo1;
1
Department of Advanced Biomedical Sciences, University
Federico II, Naples, ITALY, 2Istitute of Biostructrure and Bioimaging,
Aim/Introduction: The assessment of diagnostic National Council of Research, Naples, ITALY, 3Department of
and prognostic values of quantitative PET with [13N] Translational Medical Sciences, University Federico II, Naples,
-ammonia to identify the functional significance ITALY, 4Department of Nuclear Medicine Central Manchester
of intermediate stenoses of coronary arteries. Foundation Trust, Manchester, UNITED KINGDOM.
Materials and Methods: 80 patients (М:F 61:19, 63±10,1
years) with intermediate stenoses of one and more coronary
arteries (50%-70%) were included in the study. Dynamic PET/ Aim/Introduction: Cardiac imaging with PET/CT allows
CT scanning with [13N] -ammonia was performed twice at rest measurement of coronary artery calcium (CAC), myocardial
and during pharmacological test with adenosine. Low-dose CT perfusion and myocardial perfusion reserve (MPR). We evaluated
scan was used for attenuation correction of PET data. Regional the prognostic role of the combined assessment of regional
absolute myocardial blood flow and coronary flow reserve (CFR) CAC score, ischemic total perfusion defect (ITPD) and MPR in
were quantified automatically using commercially available predicting lesion-related outcome in patients with suspected
Corridor4DM CFR software (Invia, Ann Arbor, Michigan). coronary artery disease (CAD). Materials and Methods: We
Fractional flow reserve (FFR) measurement was applied to studied 206 patients referred to 82Rb PET/CT and with available
assess the functional significance of intermediate coronary coronary angiographic data. At coronary angiography a
stenoses. According to the guidelines we considered the normal stenosis ≥50% was considered significant. Regional CAC score
value of CFR >2.3 [1] and FFR ≥ 0.8 [2]. Results: 91 coronary was categorized as <300 and ≥300 and regional ITPD in <5%
arteries with intermediate stenosis (50%-70%) were included and ≥5%. Regional MPR was considered reduced when <2.
in analysis. We observed the agreement between CFR and FFR The outcome end points were cardiac death, target vessel-
data in identification of functional significance of intermediate related myocardial infarction, or unstable angina requiring
stenoses of coronary arteries in 78% of all cases. The sensitivity of coronary revascularization (ischemia-driven target vessel
PET with [13N] -ammonia was 82%, specificity - 77%, accuracy - revascularization). When identification of culprit vessel was not
78%. FFR and CFR disagreed in 22% of all cases, mainly when FFR possible the endpoint was assigned to all the stenotic vessels
remained normal, but CRF was below the reference values. The of those patients. Results: During a median follow-up of 34
positive prognostic value of [13N] -ammonia PET was 53%. We months, 41 events occurred in vessels with significant stenosis
found the significant correlation between CFR and myocardial (n=199), while only 6 events were observed in vessels without
mass index (r=0,68, р<0,05). Moreover, patients with 2 type of stenosis (n=419) (P<0.001). Compared to vessels without event,
diabetes mellitus had CFR below the normal values while FFR those with event showed higher CAC score and ITPD, and lower
was ≥ 0.8 . The negative prognostic value of [13N] -ammonia hyperemic myocardial blood flow and MPR (all P<0.001). At Cox
PET was high - 93%. Conclusion: Quantitative [13N] -ammonia regression multivariable analysis, CAD ≥50% (P<0.001), CAC score
PET is an effective method to rule out the functional significance ≥300 (P<0.01) and MPR <2 (P<0.01) resulted as independent
of intermediate coronary stenoses. Ventricular myocardial predictors of events. At incremental analysis, the addition of
hypertrophy and 2 type of diabetes mellitus contribute on CAC score ≥300 to coronary angiography findings, significantly
impairment of coronary microcirculation and leads to decrease increased global χ2 of the model (P<0.001). The addition of MPR
CFR in territory supplied by coronary artery with intermediate <2 to coronary angiography findings and CAC score, further
stenosis and normal FFR. References: 1. Dilsizian, V., Bacharach, increased the χ2 (P<0.01). In vessels with significant stenosis,
S.L., Beanlands, R.S. et al. ASNC imaging guidelines/SNMMI the recursive partitioning and regression trees analysis for the
procedure standard for positron emission tomography identification of events produced five terminal groups. The initial
(PET) nuclear cardiology procedures J. Nucl. Cardiol. (2016). split was on CAC score values. For vessels with CAC <300 and
doi:10.1007/s12350-016-0522-3 2. 2014 ESC/EACTS Guidelines MPR ≥2, no further split was performed, while vessels with MPR
on myocardial revascularization / European Journal of Cardio- <2 were further stratified by ITPD. For vessels with CAC ≥300
Thoracic Surgery. - 2014. - V. 46. - P. 517-592. a further stratification was performed only by MPR. The worst
prognosis was observed in vessels with CAC ≥300 and MPR <2
and in vessels with CAC <300, MPR <2 and ITPD ≥5% (both P
<0.001) Conclusion: A combined use of CAC score and MPR
can help to predict more accurately the lesion-related outcome
in the presence of significant CAD. Thus, these measurements
may be useful in the identification of stenotic vessels at higher
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S184

risk of events, in which a more aggressive treatment should be perfusion with cardiac PET prior to intervention. Materials and
taken into account. References: None. Methods: Thirty-three patients (10 females) with suspected or
established CAD who had been referred for a clinical coronary
angiography (CA) with possibility for PCI were included.
OP-470 Adenosine stress and rest 13N-NH3 positron emission tomography
Evaluation Of Quantitative Cmr Perfusion Imaging By (PET), cardiac magnetic resonance (CMR) and cardiopulmonary
Comparison With Simultaneous15O-water-pet exercise test were performed 4±3 weeks before and 5±1 months
T. Kero1, E. Johansson2, M. Engström3, K. Eggers1, L. Johansson2, H. after CA. The angiographer was blinded to the PET, CMR and
Ahlström1, M. Lubberink1; exercise test results. The decision to perform PCI in conjunction
1
Uppsala University, Uppsala, SWEDEN, 2Antaros Medical, with CA was based on available clinical data and CA findings,
Mölndal, SWEDEN, 3GE Healthcare, Uppsala, SWEDEN. according to clinical routine. Regional and global coronary flow
reserve (CFR) by PET, left ventricular function by CMR, presence
of myocardial infarction by CMR and peak oxygen uptake (VO2
Aim/Introduction: We assessed the quantitative accuracy peak) were quantified before and after the CA. CFR<2.0 was
of cardiac perfusion measurements using dynamic contrast- considered abnormal. Results: A PCI was performed in 19/33
enhanced MRI with simultaneous 15O-water PET as reference patients. In 41% (11/27) of the revascularized vessel territories,
with a fully integrated PET-MR scanner. Materials and Methods: a normal regional CFR was found prior to the PCI and no
15 patients underwent simultaneous DCE MRI and 15O-water improvement in CFR was found at follow-up (p=0.9). However,
PET scans at rest and adenosine-stress on an integrated PET- vessel territories with regional CFR<2.0 at baseline improved
MR scanner. Correlation and agreement between MRI- and significantly after PCI (p=0.003). No significant change was
PET-based global and regional MBF values were assessed using found between baseline and follow-up regarding global CFR,
correlation and Bland Altman analysis. Results: Three subjects left ventricular ejection fraction or VO2 peak. Of the 14 patients
were excluded due to technical problems. Global mean (± SD) not undergoing PCI, 5 had CFR<2 in one or more coronary
MBF values at rest and stress were 0.97 ± 0.27 and 3.19 ± 0.70 territories. Conclusion: Assessment of quantitative myocardial
mL/g/min for MRI and 1.02 ± 0.28 and 3.13 ± 1.16 mL/g/min for perfusion, by cardiac PET, prior to revascularization could
PET (p=0.66 and p=0.81). The correlations between global and lead to more appropriate use of coronary angiography when
regional MRI- and PET-based MBF values were strong (r=0.86 and managing patients with stable coronary artery disease. Thereby,
r=0.75). The biases were negliable for both global and regional unnecessary angiographies and subsequent revascularizations
MBF comparisons (0.01 and 0.00 mL/min/g for both), but the can be avoided. References: 1. Task Force M, Montalescot
limits of agreement were wide for both global and regional G, Sechtem U, Achenbach S, Andreotti F, Arden C, et al. 2013
MBF, with larger variability for high MBF-values. Conclusion: The ESC guidelines on the management of stable coronary artery
correlation between simultaneous MBF measurements with disease: the Task Force on the management of stable coronary
DCE MRI and 15O-water PET measured in an integrated PET-MRI artery disease of the European Society of Cardiology. Eur Heart
was strong but the agreement was only moderate indicating J. 2013;34(38):2949-3003.
that MRI-based quantitative MBF measurements is not ready for
clinical introduction. References: None.
OP-472
Preserved stress myocardial flow can predict of
OP-471 improvement of contractile function in the patients with
Appropriate Coronary Revascularization Can Be non ischemic dilated cardiomyopathy
Accomplished If Myocardial Perfusion Is Assessed With E. Kong, I. Cho, C. Lee, D. Shin;
Cardiac PET Prior To Treatment Decision Yeungnam university hospital, Daegu, KOREA, REPUBLIC OF.
S. Akil1,2, F. Hedeer1, J. Oddstig1, T. Olsson1, J. Jogi1, D. Erlinge1, M.
Carlsson1, H. Arheden1, C. Hindorf1, H. Engblom1;
1
Lund university, Lund, SWEDEN, 2Princess Norah Bint Aim/Introduction: NH3 myocardial perfusion PET(N-PET) not
AbdulRahman University, Riyadh, SAUDI ARABIA. only has a high diagnostic power for coronary artery disease,
but also enables quantitative analysis of myocardial blood flow,
thus enabling diagnosis of microvascular disease. We decided
Aim/Introduction: Current guidelines for coronary to investigate whether adenosine stress (Ad-St) N-PET can
revascularization in stable coronary artery disease (CAD) provide clinically useful information to predict prognosis in
recommends the use of non-invasive stress-testing prior to patients with dilated cardiomyopathy (DCM). Materials and
treatment (1). Still, many patients undergo percutaneous Methods: From Oct 2015 to Aug 2018, 92 patients underwent
coronary intervention (PCI) based on clinical symptoms and both Ad-St N-PET and cardiac MRI for the evaluation of DCM.
angiographic findings. The aim of this study was to investigate After except for patients with incomplete initial testing, loss of
if appropriate revascularizations are accomplished in clinical follow-up, or severe systemic disease, 63 patients (46 males)
routine and to determine the potential added value of guiding was finally enrolled. Patients were measured stress myocardial
revascularization by quantitative assessment of myocardial flow with Ad-St N-PET and myocardial fibrosis by LGE MRI.
S185 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

LVEF and LV end diastolic diameter (LVEDD) were measured by OP-475a


echocardiography. We evaluated the factors that can predict the When and How Should I Look for Cardiac Dyssyn-
improvement of cardiac function (LVEF 10%) based on follow chrony?
- up echocardiography. Results: Fifty (57 y-o) patients with
nonischemic (Nis) DCM and 13 (65 y-o) with ischemic(Is) DCM, M. Hacker;
baseline LVEF was 27.5% and 29.2%, and LVEDD was 62.5 mm Department of Biomedical Imaging and Image-
and 61.8 mm, respectively. LGE was observed in 67% of Nis-DCM guided Therapy, Vienna, AUSTRIA.
patients and 100% in Is-DCM. Stress flow was 1.52 and 1.15,
respectively, and 42% and 65% of patients showed functional
improvement. In Nis-DCM patients, function improving patients OP-475b
group (n=21) had more female ratio (48% vs. 24%), younger When and How Should I Look for Cardiac Innervation?
patients (51.5 y-o vs 61.4 y-o) 86%), less LGE (38% vs 86%) and H. Verberne;
higher stress flow (1.74 vs 1.36) than non-improving group. Academic Medical Center, Department of Nuclear
However, there was no significant difference in baseline LVEF Medicine, Amsterdam, NETHERLANDS.
and LVEDD. For prediction of functional recovery, LGE was sn
62%, sp 86%, PPV 76.5% and NPV 75.7%, and the stress flow
was 62%, 86%, 76.5% and 75.7%, respectively. Of the 7 patients 1102
with no LGE but low stress flow, 4 had no functional recovery
and one expired within one year. Of the 4 patients with LGE but
Joint Symposium 17 - Oncology & Theranostics
maintained stress flow, 2 had no improvement, but one of them
Committee / AIO: Challenge Pancreatic Cancer
had a 19% decrease in LVEDD, so clinically improved 3 patients.
If LGE and stress flow were mismatched, stress flow predicted Tuesday, October 15, 2019, 8:00 - 9:30 Lecture Hall 311
better at 7/11. Conclusion: We can predict of improvement of
LVEF by the stress myocardial blood flow rate was over 1.9 mL /
min / g or absence of LGE in patients with non-ischemic dilated
cardiomyopathy. Stress ammonia PET was able to provide OP-476
additional information on prognosis prediction compared with Diagnostic Challenges of PDAC
LGE in cardiac MRI. References: None. A. Scarpa;
University of Verona, Department of Pathology
and Diagnostics, Verona, ITALY.
1101
CME 9 - Cardiovascular Committee: Non- OP-477
Invasive Imaging Strategies in Heart Failure Treatment Algorithm of PDAC
J. Siveke;
Tuesday, October 15, 2019, 8:00 - 9:30 Auditorium Universitätsklinikum Essen, Department of
Medical Oncology, Essen, GERMANY.

OP-473 OP-478
When and How Should I Look for Myocardial Ischemia or Challenge Diagnostic Imaging of PDAC
Viability? P. Veit-Haibach;
F. Hyafil; University of Toronto, Department Medical
Department of Nuclear Medicine, Bichat Imaging, Toronto, ON, CANADA.
University Hospital, Paris, FRANCE.

OP-479
OP-474 Is PDAC an Indication for Radioligand Therapy?
When and How Should I Look for Cardiac Amyloido- F. Giesel;
sis? University of Heidelberg, Department of Nuclear
Medicine, Heidelberg, GERMANY.
R. Slart;
University Medical Center Groningen, University
of Groningen, Groningen, NETHERLANDS.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S186

1103 Leipzig, GERMANY, 8Department of Pediatric, Hamatology


and Oncology, University of Gießen, Gießen, GERMANY.
Joint Symposium 18 - Thyroid + Inflammation
& Infection Committee / ETA: Imaging on
Thyroiditis Aim/Introduction: FDG accumulation in activated brown
adipose tissue (ABAT) complicates PET assessments in children
Tuesday, October 15, 2019, 8:00 - 9:30 Lecture Hall 312 and adolescents. Preventive measures (PM) as warming or the
administration of non-selective beta-blockers (BB) have been
described. The aim of our German-wide study was the evaluation
of the effectiveness of these PM to prevent ABAT. Materials
OP-480 and Methods: The study included 267 children or adolescents
Thyroiditis - Clinical Appraisal and Ultrasound Features with Hodgkin lymphoma treated in 48 German hospitals within
C. Buffet; the EuroNet-PHL-C2 trial. The severity of ABAT was assessed
Hopital Pitie Salpetriere, Thyroid Unit, Paris, FRANCE. in 589 PET-CT or PET-MRI examinations by two experienced
technologists using a five point scale (none, low, intermediate,
strong (s) and very strong (vs)). In addition, the thickness of the
OP-481 pelvic soft tissue and the weather at the time point of the PET
Thyroid Scintigraphy and Uptake in Patients with scan were determined. The individual PM (warming, BB (with
Thyroiditis - Is there a Current Role? dose), both, others) were delivered by the 48 local PET centers.
L. Giovanella; Results: In 528/589 cases, the PMs were determinable. 165
Imaging Institute of Southern Switzerland, Clinic for patients (31%) did not receive any PM, 243 patients (46%) were
Nuclear Medicine, Bellinzona, SWITZERLAND. warmed only, 36 patients (7%) received BB only, and 84 patients
(16%) got both warming and BB. ABAT was detected in 28 % of
the PET without PM, in 14% with warming, in 14% with BB and
OP-482 in 8% with both warming and BB. S or vs ABAT was detected
Thyroiditis at PET Imaging with Different Tracers - in 14% without PM, in 5% with warming, in 3% with BB and
Interpretation Criteria and Reporting in 0% with combined BB and warming. Presence of ABAT was
G. Treglia; strongly correlated with the outdoor temperature (p= 0.000235)
Imaging Institute of Southern Switzerland and Health but not with the thickness of the pelvic soft tissue layer (p=
Technology Assessment Unit, Ente Ospedaliero 0.787). Conclusion: In Germany, very different PMs are used to
Cantonale, Bellinzona, SWITZERLAND. avoid ABAT. Without PM, more than every fourth PET study was
affected by ABAT. Both, warming and the administration of BB
proved to be effective measures; the combination of both was
1104 the most effective way to reduce ABAT. References: None.
Technologists: Oral Presentations 2
OP-484
Tuesday, October 15, 2019, 8:00 - 9:30 Lecture Hall 117 Combined 18F-Fluorocholine and 11C-Methionine PET-CT
for parathyroid adenoma localization: a pilot acquisition
protocol
A. Pereira Gomes, L. Silva;
OP-483 Erasme Hospital, Anderlecht, BELGIUM.
Prevention of activated brown adipose tissue in F18-FDG-
PET-imaging in children and adolescents - Which measures
are effective? Aim/Introduction: Aim: Localization of parathyroid adenomas
C. Pötzsch1, S. Naumann1, L. Kurch1, T. W. Georgi1, M. Weckesser2, S. is now possible with 18F-Fluorocholine (18F-FCH) PET-CT
Klutmann3, D. Schmidt4, K. Herrmann5, J. Sciuk6, D. Hasenclever7, C. imaging, although very limited data are available in literature
Mauz- Körholz8, D. Körholz8, O. Sabri1, R. Kluge1; about this subject. This prospective study aims to describe an
1
Department of Nuclear Medicine, University of Leipzig, Leipzig, acquisition protocol for parathyroid adenoma localization using
GERMANY, 2Department of Nuclear Medicine, University of 18F-FCH. Materials and Methods: Methods: Twenty patients
Münster, Münster, GERMANY, 3Department of Nuclear Medicine, with hyperfunctioning parathyroid were enrolled in this study
University Hospital Eppendorf, Hamburg, GERMANY, 4Department and underwent two different exams, both performed using
of Nuclear Medicine, University of Erlangen, Erlangen, GERMANY, a Philips Gemini Dual PET-CT. The first one (as our standard
5
Department of Nuclear Medicine, University of Essen, Essen, of truth) was performed with 555 MBq of 11C-Methionine
GERMANY, 6Department of Nuclear Medicine, University (11C-MET) administered intravenously (IV). An emission scan, 20
of Augsburg, Augsburg, GERMANY, 7Institute for Medical min post IV, was obtained for 7 min at each of 3 bedpositions
Informatic, Statistics and Epidemiology, University of Leipzig, centred to the neck, upper and medium mediastinum and co-
S187 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

registered with a low-dose CT. The second one, and with the the standard duration of 20 minutes. Images both for EPH and
patient positioned inside of the PET tunnel, 4 MBq/Kg 18F-FCH LPH were reconstructed using an ordered subset expectation
was injected on IV at the same time of the first scan: a dynamic maximization iterative algorithm (OSEM-SV, VUEPoint HD; GE
emission scan centered on the neck (1 bed-position) during Healthcare, 2 iterations, 30 subsets), matrix 256x256; full width
15 min. Immediately after, a second emission scan centered at half maximum: 5 mm. EPH images were visually evaluated.
to the neck, upper and medium mediastinum for also 7 min at LPH images were evaluated by visual and quantitative (CortexID
each of 3 bed-positions. Subsequently, 60 min post IV, a third Suite, GE Healthcare) examination. Results: Among the 16
emission scan was acquired equally to the second one. The total patients, five presented perfusion defects typical for AD at EPH,
of three emissions scans were co-registered with a second low- the remaining subjects did not show any relevant perfusion
dose CT. The dynamic images were reframed by summing up defects. All the subjects, who showed hypoperfusion at the
images every 5 min to facilitate interpretation and all images EPH, were positive for amyloid burden at the LPH. Of note, three
were reconstructed by iterative method (2 iterations and 21 of them had previously performed perfusional SPECT (n= 1) or
subsets). Three experienced observers started to analyse all FDG PET (n= 2) that revealed hypoperfusion or hypometabolism
images in which the highest value of lesion contrast should patterns substantially in agreement with the results obtained
be expected at the optimal scan time. Results: Results: We with amyloid PET at EPH. At LPH, nine patients were positive
succeeded to set up a one-day protocol for both 18F-FCH for amyloid burden both at visual and quantitative analysis.
and 11C-MET PET acquisitions for patients with a suspicion None of the patients who were negative at the EPH presented
of parathyroid adenoma. The protocol included a dynamic significant amyloid deposition at the LPH. Conclusion: These
acquisition for the 18FFCH, which allows data acquisition on preliminary results suggest that our dual-time point protocol for
the washout kinetics. Dynamic data might indeed improve the FMM PET might represent a reliable tool for the dual imaging of
diagnostic value of the procedure. Conclusion: Conclusion: To neurodegenerative and amyloid biomarker in MCI. References:
the best of our knowledge there are no studies describing an None.
acquisition protocol for parathyroid adenoma localisation using
two tracers in a single session. This study suggested that the
acquisition protocol mentioned is possible and might reinforce OP-486
the diagnostic. Notwithstanding a larger database is needed for Further Reduction Of [18F]-fdg Activity Applied In Clinical
further investigation. References: None. Routine For State-of-the-art 3d Tof Pet/ct Systems: Is It
Feasible?
J. Pilz, L. Hehenwarter, J. Holzmannhofer, G. Schweighofer-Zwink,
OP-485 C. Pirich;
Dual time-point 18F-Flutemetamol PET protocol for the Department of Nuclear Medicine and Endocrinology,
imaging of neurodegenerative and amyloid biomarkers in University Hospital Salzburg, Paracelsus
mild cognitive impairment Medical University, Salzburg, AUSTRIA.
A. Ruzza, L. Filippi, G. Cicco, P. Basile, R. Pirisino, O. Bagni;
Santa Maria Goretti Hospital, Latina, ITALY.
Aim/Introduction: A reduction of the [18F]-FDG activity
applied may become feasible in the clinical setting due to
Aim/Introduction: According to recently published international the ongoing technical innovation implemented into PET/CT
recommendations, diagnosis of Alzheimer’s Disease (AD) systems. Currently, the [18F]-FDG activity applied is 4 MBq per
should be based on a specific pathological biomarker network kg bodyweight and the acquisition time is set to 75 seconds
termed AT(N), including detectable bioumoral or imaging per bed position at our nuclear medicine department. The aim
hallmarks of amyloid burden (A), tau protein aggregates (T) and of this study is to investigate the performance of a 3D state-
neurodegeneration (N). Our aim was to evaluate a dual time- of-the-art PET/CT scanner including TOF technology with
point protocol for Positron Emission Tomography (PET) with respect to the minimum acquisition time where adequate
18
F-flutemetamol (FMM) for the contextual evaluation of both image quality is still maintained. The minimum acquisition time
blood flow impairment (as hallmark of neurodegeneration) and could be translated to a reduced [18F]-FDG activity. Materials
amyloid burden in patients with mild cognitive impairment and Methods: A NEMA NU2 body phantom containing a lung
(MCI). Materials and Methods: We enrolled 16 patients (9 insert in the center, six spheres varying in size and a background
women, 7 men, mean age 66,6 + SD) with clinical diagnosis of compartment, was filled with [18F]-FDG according to the
MCI. All the subjects were injected intravenously with 18F-FMM European Association of Nuclear Medicine Research Ltd. (EARL)
(dose 185 MBq) and hydrated with 500 ml of saline (0.9 % specifications. A Philips Ingenuity TF PET/CT system was used
sodium chloride). In all cases PET-CT was acquired through to scan the phantom with two bed positions of five minutes.
a Discovery ST device (GE Healthcare). Dual time-point brain Various datasets with different acquisition times were analyzed
PET/CT was acquired according to the following protocol: an afterwards. The PET datasets were reconstructed by a blob-
early phase (EPH) consisting of a short acquisition with the based ordered-subsets expectation maximization (OSEM) TOF
duration of 6 minutes, starting immediately post injection, algorithm using a matrix of 144×144 pixels. Image data were
followed by a late phase (LPH) at 90 minutes post injection with evaluated by the calculation of mean and maximum activity
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S188

concentration recovery coefficients (RCs) for each sphere of manual process. OSL pellets (LANDAUER) were used to measure
the NEMA phantom and the determination of the coefficient the cumulative dose. Dosimeters are placed on fingers pulp and
of variation (COV) of the background compartment. Adequate base. Results: Regarding the preparation step, the volume of
image quality was predefined by RCs meeting EARL criteria and buffer has been set to 0.6 ml that allows a variation of the elution
a COVmax < 0.15. Results: The following RCs were achieved volume of 4 to 5.8 ml while remaining within the pH range
for the image data with an acquisition time of 57 seconds per [3.2-3.8]. The heating setpoint (110°C during 510 s) has been
bed position: 37mm sphere (meanRC 0.85; maxRC 1.09), 28mm adjusted in order to obtain the same endpoint temperature into
sphere (meanRC 0.78; maxRC 1.04), 22mm sphere (meanRC the vial as compared to the manual preparation. Concerning
0.77; maxRC 1.09), 17mm sphere (meanRC 0.63; maxRC 0.89), the dosimetric impact to extremities, the median [min, max]
13mm sphere (meanRC 0.53; maxRC 0.75) and 10mm sphere radiation exposure per syringe was 132 µSv [70, 273] vs. 315
(meanRC 0.36; maxRC 0.49). The COVmax of the image dataset µSv [28, 875] respectively for the automated vs. the manual
was equal to 0.136. All EARL criteria were met by the 3D TOF practice. The extrapolated annual equivalent dose lead to 86
Philips Ingenuity TF PET/CT system using a reduced scan time mSv [46; 177] and 205 mSv [18; 569], respectively for automated
of 57 seconds. Conclusion: Minimizing the scan time/activity vs. manual 68Ga-DOTATOC labeling. Conclusion: Automation
applied for [18F]-FDG studies is feasible in clinical routine. of 68Ga-DOTATOC preparation and dispensation is effective to
Experimental imaging data reveal that the Philips Ingenuity reduce technologist’s extremities exposition by a factor 2 to 3.
TF system still shows adequate image quality in terms of EARL This automation is applicable to other kits and permit the wide
criteria using a reduced acquisition time of 57 seconds per bed spread of the 68Ga use with low dosimetric impact for the
position. This implies a [18F]-FDG activity reduction from 4 MBq technologists. References: None.
to 3 MBq per kg BW in clinical routine. Patient studies validating
these assumptions are currently under way. References: None.
OP-488
PET/CT SiPM: Feasibility of a breath-hold acquisition in a
OP-487 clinical routine
Automated preparation and dispensation of 68Ga- M. Pappon, M. Jreige, C. Beigelman, P. Genoud, J. Prior;
DOTATOC on the same synthesizer - impact on the CHUV, Lausanne, SWITZERLAND.
dosimetric exposure of technologists compared to manual
practice
M. Frindel1, N. Varmenot1, A. Rauscher1, P. Baumgartner1, F. Aim/Introduction: Recently introduced high-resolution
Delaunay1, C. Rousseau1, F. Kraeber-Bodere1,2; SiPM PET/CT allows high-sensitivity pulmonary breath-hold
1
Institut de Cancérologie de l’Ouest, Saint-Herblain, acquisition, which is of particular interest in lung nodule
FRANCE, 2CHU de Nantes, Nantes, FRANCE. characterization. This technique helps to overcome long
acquisition time and image quality degradation secondary
to breath movements. Herein, we report our first practical
Aim/Introduction: The use of gallium-68 in nuclear experience with an additional breath-hold PET/CT acquisition
medicine imaging is continuously increasing. integrated in clinical routine. Materials and Methods: We
In a previous study, we have evaluated the dosimetric impact of retrospectively reviewed all PET/CT examinations between
radiolabeling with 68Ga, and have shown for the DOTATOC that January 2019 and March 2019 that were acquired on our SiPM
it could lead to significant equivalent doses for technologists. PET/CT (Siemens Biograph Vision 600) with an additional breath-
As the SOMAKIT-TOC® kit requires manual preparation as well hold (BH) acquisition applied in clinical routine for lung nodules/
as dispensation of the patient dose, in this work, we have metastasis investigation. We reported the lung apnea duration
evaluated the dosimetric benefit of automating these processes. achieved by patients (=combined time of consecutive CT and
Materials and Methods: SOMAKIT-TOC® was purchased from PET acquisitions). The total time added to the examination,
Advanced Accelerator Applications and Galliapharm® (1850 as well as the dose differences between total body PET/CT
MBq) generator from Eckert&Ziegler. Manual preparation of and lung breath-hold PET/CT were also reported. Results: A
68Ga-DOTATOC was performed according to the instructions in total of 28 patients were included (16M/12F), with an average
the SOMAKIT-TOC® SPC. Automated preparation was developed BMI of 24.4±4.3kg/m2 and an injected dose of 145±35MBq of
on the ModularLab PharmTracer® synthesizer (Eckert&Ziegler) 18
F-FDG (2MBq/kg). All patients managed to maintain a success
with slightly customized C1-EL-01 cassette. This includes the apnea for a duration of 30.8±7.7s, independently of their BMI
elution, the injection of the buffer, the heating and finally (Spearman’s rho=-0.30, p=0.12) or gender (p=0.116). We
a transfer from the reaction kit vial to a sterile/shielded vial. observed a significant positive correlation between BH-apnea
The dispensation step only requires to connect a shielded duration and age (rho=0.40, p=0.036). All BH CT scans were
syringe to a tubing of the cassette and to enter the volume acquired using an ultra-low dose setup with mA modulation
corresponding to the prescribed activity (150 MBq/patient) in resulting in a significantly lower DLP of 15.3±9.2mGy·cm
the program starting parameters. Exposures of extremities of compared to 416±109mGy·cm for the whole-body acquisition
the technologist were measured for automated preparation (p<0.005) with averaged added dose of 3.7%. The average time
and dispensation for three runs and compared to those with difference between the BH and whole-body acquisitions were
S189 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

15.2±1.4min. Conclusion: All patients managed to maintain OP-490


the relatively short apnea time necessary to obtain BH PET/CT The role of ultra-low dose (0.04mCi/kg) 18F-Sodium
acquisition. Use the ultra-low dose CT protocol resulted in a very Fluoride (NaF) PET/CT in the evaluation of metastatic bone
low additional dose to patients; high speed acquisition with disease
notably short time between BH and whole-body exams allowed M. Al-Daas, T. Al-Ahmad, A. Esmail, S. Usmani, F. Marafi;
to maintain comparable results between both sequences, which Jaber Al-Ahmad Center for Molecular Imaging, Shuwaikh, KUWAIT.
is especially important for quantification purposes. References:
None.
Aim/Introduction: Fluorine-18-sodium fluoride (18F-NaF)
PET/CT have been widely used in the detection of metastatic
OP-489 bone cancer. We have previously demonstrated that 18F-NaF
Clinical Benefit Of Routine True-whole-body 18F-fdg Pet/ct PET/CT has high diagnostic accuracy in with low dose of 0.06
For Patients With Malignant Melanoma mCi/kg [[i]]. In the present work, we investigate whether these
A. M. van den Berk, J. P. Esser; superior imaging characteristics are preserved in ultra-low dose
Meander Medical Centre, Amersfoort, NETHERLANDS. of 0.04mCi/kg. Materials and Methods: We prospectively
enrolled 16 patients with (mean BMI 30.11 ± 6.48 kg/m2; mean
age 48 years [range 18 - 72]) and referred for 18F-NaF PET/CT
Aim/Introduction: Malignant melanoma (MM) is one of for the osseous metastatic staging. All the patients underwent
the most lethal carcinomas worldwide and its incidence is 18
F-NaF PET/CT scan using an advanced digital PET/CT system
increasing. It is an aggressive tumour with often lymphatic and in JACMMI (GE Discovery MI) after injection of 0.04 mCi/kg
haematogenous spread to any part of the body. Therefore, for of 18F-NaF. Images were acquired for 2 minutes per bed then
screening it is recommended to make an 18F-FDG PET/CT scan reconstructed using different time intervals (2 min, 1:30 min
from vertex to toes (true-whole-body) instead of the typical and 1 min/bed). Images were also reconstructed using Bayesian
scan in oncology from vertex to thigh (partial-whole-body). penalized likelihood reconstruction (Q.Clear) with beta (β) value
Consequences of extending the scan are increased patient’s of 700. Signal-to-noise-ratio was measured in the third lumber
radiation exposure and doubled scan-time. By doubling scan- vertebra (L3) and analyzed semi-quantitatively. Diagnostic test
time, fewer patients can be scanned per day and the chance characteristics were calculated using traditional methods. Means
of motion artefacts increases. We retrospectively looked if with standard deviations and proportions with 95% confidence
there is indeed a clinical benefit for true-whole-body scanning. intervals are reported. Results: The results of the 16 patients
Materials and Methods: 18F-FDG PET/CT scans and their show that when comparing 2 min/bed images with 1 min/bed
reports, performed between March 2006 and March 2018 at a highly significant difference in the Signal-to-noise ratio (SNR)
the Meander Medical Centre in Amersfoort, the Netherlands, with a p-value of 0.018 using Wilcoxon Signed-Rank Test. On the
were retrospectively reviewed. Criteria for inclusion into the other hand, the 2 mins/bed compared with the 1:30 mins/bed
study were: 18F-FDG PET/CT performed for staging, restaging or shows a non-significant change with the SNR with a p-value of
surveillance of proven MM. 18F-FDG PET/CT performed as true- 0.509. Conclusion: 18F-NaF PET/CT retains its high diagnostic
whole-body scan (from vertex to toes). Availability of complete accuracy and confidence with ultra-low dose of 0.04 mCi/kg.
patient care reports. We reviewed all 18F-FDG PET/CT scans as Dose can be reduced to this level by using ultra-sensitive digital
well as the reports. Location of primary tumour, metastases PET/CT cameras. References: [1]. Usmani S, Marafi F, Ahmed A,
located in the region vertex to thigh and/or in the lower et al. Diagnostic challenge of staging metastatic bone disease
extremities were registered. Results: We reviewed 284 18F-FDG in the morbidly obese patients: A primary study evaluating the
PET/CT examinations. A total of 212 scans, performed in 165 usefulness of 18F-Sodium Fluoride (NaF) PET-CT. Clin Nucl Med.
patients, met the inclusion criteria. We excluded 15 scans, as they 2017;42:829-836.
did not image patient’s lower extremities. Clinical information
was incomplete in another 57 scans, these patients came from
other hospitals. No metastases were found in 78 scans (36.8%). OP-491
Metastases in the region vertex to thigh were found in 102 scans Experiences from the Technologist Point of View:
(48.1%). Another 24 scans (11.3%) showed metastases in at least Automatic Nuclear Medicine DICOM Image Observer Tool
one lower extremity as well as in the partial-whole-body-region. for Quality Management
Lower extremity metastases only, were found in 8 scans (3.8%). M. Szoliková, F. Nagy, Á. K. Krizsán, K. Kukuts, S.Barna, Z. Hascsi, I.
In all of these 8 cases, the primary tumour was also located in Garai, A. Forgác;
the lower extremities. No scan showed metastases in the lower ScanoMed Kft., Debrecen, HUNGARY.
extremities when the primary tumour was not located in the
lower extremities. Conclusion: True-whole-body 18F-FDG PET/
CT (vertex-toes) has no useful additional information in patients Aim/Introduction: The header of a stored DICOM (Digital
with MM compared to partial-whole-body 18F-FDG PET/CT Imaging and Communications in Medicine) file comprise a
(vertex to thigh) unless the primary tumour is/was located in number of data elements, including information related to
the lower extremities. References: None. the patient, the imaging system as well as the acquired data
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S190

set. Quality Management Bot (Q-Bot), a software tool was rapidly developing technology that has great potential to
developed at our institute, which is capable to give feedback ameliorate human disease. One fundamental challenge in the
to the technologists about improper injected activity, successful development and clinical application of cellular
radiopharmaceutical uptake time and patient ID mismatches. Our therapeutics is the need to better understand the in vivo
aim was to introduce the Q-Bot in the clinical routine, to inspect behaviour of adoptively infused cell products. We envisage
the DICOM records regularly for quality assurance (QA) purposes. that a dual PET and fluorescent cell labelling reagent will
Materials and Methods: DICOM files acquired on three PET/ harness the synergistic property of both imaging modalities
CT systems (GE, Philips, Mediso) and on three SPECT systems to visualise the labelled cells across the cellular to whole body
(Mediso) were included in this study. Metadata regarding scales. By placing the dual imaging reagent extracellularly,
to patient data (patient ID, patient weight and height, age), the cytotoxicity and radiation damages to the cells would be
radiopharmaceutical (radionuclide, injected amount of minimised. Materials and Methods: We radiosynthesised a
radioactivity, measurement time), acquisition parameters (scan novel dual-modality trifunctional labelling reagent, 124I-Green-
start, acquired counts) were monitored continuously for five dithiophenolmaleimide. It equips with: (i) a long half-life
months. The Q-Bot tool provides evaluated information on positron emitter, iodine-124 (t1/2=4.2 days) for longitudinal cell
unexpected outliers compared to the standardized protocol tracking with PET; (ii) a clinically approved green fluorescent
parameters of the above mentioned categories, while allowing reporter, fluorescein for micro-scale fluorescence cell imaging;
the correction of them by the assigned staff members. 4358 (iii) a dithiophenolmaleimide moiety for cell membrane thiol
bone 99mTc scintigraphy and 3416 18F-FDG PET/CT DICOM bioconjugation. The cellular distribution of the dual labelling
images were evaluated with the Q-Bot. Results: When reagent, its cell radiolabelling efficiency, and radiolabel
considering all the inspected patient scans approximately 4% of retention were evaluated on Jurkat, murine multiple myeloma
all cases showed outliers compared the standardized protocols. 5T33, and human T cells, respectively, in vitro. The in vivo
Several simple typo errors (patient ID, weight, height, injected migration of the dual labelled Jurkat cells was investigated
activity) were found and repaired continuously. The revealed using sequential PET/CT imaging in male NSG mice (n=3) over
deviations from the acquisition protocol (e.g. uptake time delay) 7 days. Results: The 124I-Green-dithiophenolmaleimide was
were identified and discussed. Applied dose to the patient in prepared with radiochemical yields of 71±1% (n=3) determined
case of manual injection of radiopharmaceutical was identified by HPLC. The confocal images revealed the cell surface
as a high risk point for the occurrence of systematic error by the localisation of the 124I-Green-dithiophenolmaleimide on both
Q-Bot tool. Conclusion: Q-Bot as an automatic inspector has Jurkat and 5T33 cells. The radiolabelling efficiency of Jurkat,
significant potential in QA, especially when large amount of 5T33, and human T cells (5 x 106) were 20.4±2.9%, 61.7±1.1%,
patient data is generated on a daily basis. Continuous feedback and 27.0±2.0% (n=3), respectively. Notably, 67.6±1.7%
from such a QA tool enables the detection of both systematic (n=3) of total radioactivity still retained in Jurkat cells 7 days
and random errors, and therefore, ensures high quality work of post labelling without apparent impact on its viability and
the staff members of a nuclear medicine center. References: reproducibility. When 124I-Green-dithiophenolmaleimide dual
None. labelled Jurkat cells were intravenously injected to NSG mice,
the cell migration from lung to liver was detected with PET over
7 days. Conclusion: A dual PET and fluorescent cell labelling
1105 reagent, 124I-Green-dithiophenolmaleimide was prepared
in excellent RCYs. It labelled various cell lines through their
M2M - Featured Session: Immune Therapy membrane thiols with good labelling efficiency and prolonged
radiolabel retention. The cell membrane localisation of the
Tuesday, October 15, 2019, 8:00 - 9:30 Lecture Hall 111 124
I-Green-dithiophenolmaleimide was confirmed by confocal
fluorescence imaging. The longitudinal monitoring of the in vivo
distribution and migration of the dual labelled Jurkat cells was
OP-492 achieved with PET/CT imaging. These promising results warrant
TBA future labelling of the therapeutic cells with the 124I-Green-
M.Kneilling; dithiophenolmaleimide for in vivo tracking study using PET/CT.
Eberhard Karls Universtiy, Werner Siemens Imaging Center, References: None.
Department of Preclinical Imaging and Radiopharmacy,
Department of dermatology, Tübingen, GERMANY.
OP-494
OP-493 Evaluation of [18F]FDG uptake after anti PD-1 therapy in
In vivo Cell Tracking with A Cell Membrane Thiol Targeting mice
Dual PET and Fluorescent Bioconjugation Reagent M. Ogawa, M. Tomita, H. Yasui, K. Higashikawa, K. Nakajima, T.
T. T. Pham, C. Davis, J. Maher, R. Yan; Shiga, Y. Kuge;
King’s College London, London, UNITED KINGDOM. Hokkaido University, Sapporo, JAPAN.

Aim/Introduction: Cell-based therapies offer a novel and


S191 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

Aim/Introduction: Immune checkpoint inhibitors such as PD-1 University of Medical Center of Groningen, Dept. of Hospital
inhibitors have attracted attention in cancer therapy. However, and Clinical Pharmacy, Groningen, NETHERLANDS.
PD-1 inhibitors are not effective to all patients. In anti PD-1
therapy, it is important to evaluate metabolism in the cancer
microenvironment, as this helps to clarify the pathological Aim/Introduction: Interleukin-2 is glycoprotein that binds
conditions. Herein, we evaluate the early effects of PD-1 therapy with high affinity to IL2 receptors (IL2R) that are overexpressed
on [18F]FDG uptake in vivo in mice, focusing on cell distribution on activated T-cells. These activated T-cells are involved in
and glycolysis in cancer cells. Materials and Methods: Mice autoimmune diseases but also play a major role in the tumor
melanoma cells (B16F10) was inoculated subcutaneously to immune response. Previously we have developed N-(4-[18F]-
C57BL/6 mice. Anti PD-1 antibody treatment was started when Fluorobenzoyl)interleukin-2 ([18F]FB-IL2) which has been
tumor presence was confirmed. Anti-mouse PD-1 antibody successfully used for detecting activated T-cells in rodents [1]. The
(250 μg) was administered twice (i.p, 5 days apart) to the mice. complexity and time-consuming GMP-compliant production of
FDG-PET/CT imaging was performed just prior to initiating [18F]FB-IL2 led us to develop the simplified PET tracer, [18F]AlF-
therapy and at 7 days after the initiation of anti PD-1 treatment RESCA-IL2 [2]. Here we present its affinity for activated T-cells
initiation. After PET imaging on day 7, the mice were sacrificed, in comparison to [18F]FB-IL2. Materials and Methods: The
and their organs were dissected. For ex vivo validation, tissues stability of [18F]AlF-RESCA-IL2 was tested in human serum (TCA
were weighed, and radioactivity was measured. Also, flow- precipitation) over time (n=3). Its affinity for activated T-cells
cytometry was performed to assess immune cell (CD8+ T cells, was tested: i.) in vitro, in an binding assay containing activated
CD4+ T cell, Treg, macrophage and dendritic cell) populations, peripheral blood mononuclear cells (PBMCs) (48h, n=3); non-
and expression of GLUT1 and hexokinase II in tumors. Results: activated PBMCs (48h, n=3) and freshly non-activated PBMCs
Anti PD-1 antibody treatment did not significantly inhibit tumor (0h, n=3) ii.) in vivo, where a 60 min dynamic PET scan of [18F]AlF-
growth during our observation period (7 days). [18F]FDG uptake RESCA-IL2 (2.10±2.41 MBq) followed by ex-vivo biodistribution
to tumor was significantly higher in anti-PD-1 antibody treated was performed in SCID mice inoculated with activated PBMCs
mice (8.06 ± 0.48 %ID/g) than non-treated mice (4.02 ± 1.03 in Matrigel in the absence/presence of an excess of IL2 (PBMCs,
%ID/g) after anti PD-1 treatment. Difference in [18F]FDG uptake n=6 and PBMCs+IL2, n=6) and in SCID mice inoculated only
to tumor was negligible between anti-PD-1 antibody treated with Matrigel (Controls, n=6). Similar assays were performed
mice and control mice before the treatment. Ex vivo validation with [18F]FB-IL2 for comparison. Results: Al[18F]F-RESCA-IL2
shows that [18F]FDG uptake in the spleen and blood did not was obtained with a radiochemical yield of 2.4±1.6% (c.f.d.
differ between treatment group and non-treatment group. from the start of synthesis) and radiochemical purity (>95%)
Flow-cytometry analysis showed that CD8+ T cells and CD4+ T within 90 min.[18F]AlF-RESCA-IL2 showed high stability in
cells were slightly increased by anti-PD-1 antibody treatment, human plasma with >90% of the tracer remaining intact after
however, infiltration of immune cells (CD8+ T cells, CD4+ T cells, 60 min. PET images clearly showed the presence of activated
Tregs, macrophages and dendritic cells) was around 1%, and PBMCs in the SCID mice injected with [18F]AlF-RESCA-IL2 or
thus, immune cells should not be responsible for the increase [18F]FB-IL2. Biodistribution of [18F]AlF-RESCA-IL2 in mice (60
in [18F]FDG uptake. Anti PD-1 treatment significantly increased min, p.i) showed higher uptake in activated PBMCs (2.00±1.37
glucose transporter 1 (GLUT1) and hexokinase II expression in %ID/g) than in the Matrigel without PBMCs (0.52±0.37 %ID/g,
CD45− cancer cells, indicating that anti PD-1 treatment increased p=0.017). [18F]FB-IL2 showed similar higher uptake in activated
glucose metabolism in cancer cells. Conclusion: This study is PBMCs (2.03±0.52 %ID/g) than in the Matrigel without PBMCs
the first to assess early changes in [18F]FDG uptake by anti PD-1 (0.86±0.25%ID/g, p=0.016). [18F]AlF-RESCA-IL2 (0.65±0.26 %ID/g,
treatment in a mouse B16F10 melanoma model. We found that p=0.06) an [18F]FB-IL2 (1.15±0.49 %ID/g, p=0.048) showed
anti PD-1 therapy increases glucose metabolism in cancer cells, reduced uptake in activated PBMCs when blocked with an
at the point when anti PD-1 therapy does not cause significant excess of IL2. Conclusion: : [18F]AlF-RESCA-IL2 can be obtained
inhibition of tumor growth. References: None. in similar yields as [18F]FB-IL2, but in a shorter time (90 vs. 150
min). The new [18F]AlF-RESCA-IL2 showed increased binding
towards activated T-cells, indicating that this tracer might be
OP-495 used to image activated T-cells. References: [1] Di Gialleonardo
[18F]AlF-RESCA-IL2 for imaging activated T-cells et al., J. Nuc. Med., 2012, 53(5):679-86 [2] Antunes et al., Eur. J.
I. Antunes1, E. L. van der Veen2, F. V. Suurs2, F. Cleeren3, G. Bormans3, Nucl. Med. Mol. Imaging, 2018, 45 (Suppl 1):S78.
P. H. Elsinga1, R. A. J. O. Dierckx1, M. N. Lub-de Hooge4, E. G. E. de
Vries2, E. F. J. de Vries1;
1
University of Groningen, University of Medical Center of Groningen, OP-496
Dept. of Nuclear Medicine and Molecular Imaging, Groningen, Imaging CD8+ T cell tumor infiltration following
NETHERLANDS, 2University of Groningen, University of Medical radiotherapy
Center of Groningen, Dept. of Medical Oncology, Groningen, P. Wierstra, R. Raavé, G. Sandker, M. Boswinkel, J. Molkenboer-
NETHERLANDS, 3University of Leuven, Dept. of Pharmacy Kuenen, G. Adema, J. Bussink, M. Gotthardt, E. Aarntzen, S.
and Pharmacology, Laboratory for Radiopharmaceutical Heskamp;
Research, Groningen, NETHERLANDS, 4University of Groningen, Radboudumc, Nijmegen, NETHERLANDS.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S192

Aim/Introduction: Immunotherapy is considered a new Aim/Introduction: The development of cell-based therapy and
cornerstone in cancer treatment by its profound and durable cancer immunotherapy would benefit from noninvasive and
clinical responses in patients with various types of cancer. systemic cell tracking methods. In this study, we report a cell
However, only a subgroup of patients respond to immunotherapy labeling method with 89Zr to track immunologically competent
and methods for accurate early response monitoring are lacking. cells in vivo and evaluate their whole body distribution by
Noninvasive quantitative imaging of CD8+ cytotoxic T cells can positron emission tomography (PET) imaging. Materials and
provide dynamic and spatial information of anti-tumor response. Methods: [89Zr]oxinate4 was synthesized and its uptake was
Therefore, we developed an 111In-labeled antibody to image measured in splenocytes and CD8+ T cells isolated from spleens
influx of CD8+ T cells in irradiated tumors in a syngeneic mouse of C57BL/6 mice. [89Zr]oxinate4 was synthesized by modifying
tumor model. Materials and Methods: An anti-mouse CD8 a previously reported method (1). Zirconium-89 in 0.1 M oxalic
antibody (clone: YTS 169.4) was conjugated with NCS-DTPA and acid was neutralized to pH 7- 8 with 1.0 M Na2CO3 and added
labeled with indium-111. Immunoreactivity, IC50, internalization, to a glass reaction vial containing 1 mg/ml 8-hydroxyquinoline
and Kd were determined using CD8+ TK1 mice lymphoma solution. After being rotated at room temperature overnight,
cells. Subsequently, CT26 tumor bearing BALB/c mice were the organic phase was separated by centrifugation and
intravenously injected with 8.5 µg (8.5 MBq) [111In]In-DTPA-CD8 concentrated under the reduced pressure to give the [89Zr]
antibody. SPECT/CT imaging was performed at 4h, 24h, 48h oxinate4, which was dissolved in 10-20 μl dimethyl sulfoxide
and 72h after injection. In a separate experiment, C57Bl/6 mice and diluted with saline. [89Zr]oxinate4 (1.4-7.1 MBq) in 500 μl
bearing bilateral B16-F1 tumors received right-side external saline was added to 500 μl of the cell suspension (1.0 - 4.0 ×
beam irradiation (1x10Gy). After 24h, mice received either: 8.1 107 cells) and incubated for 30 min at room temperature.
MBq [111In]In-DTPA-CD8 antibody (8.5 µg, n=10) or 8.7 MBq After incubation, the tubes were centrifuged (5 min, 500 ×g)
[111In]In-DTPA-Isotype control (8.5 µg, n=10) followed by SPECT/ twice, supernatant was removed and the activities of the
CT at 48h post irradiation. Results: In vitro assays showed the supernatant and the cell pellet were measured for calculating
immunoreactive fraction was 44%, IC50 was 1.77 nM and Kd was labeling efficiency and specific activities. Radiolabeled cells
3.83 nM. CD8+ T cell containing organs (lymph nodes, spleen were injected intravenously into C57BL/6 mice and PET/CT
and duodenum) were clearly visible on SPECT scans at all time images were acquired 0 to 10 days after administration. Results:
points. SPECT quantification showed significantly increased Labeling efficiencies were determined ranging from 8.0 to 38.2
uptake of [111In]In-DTPA-CD8 antibody in irradiated B16-F1 % and the specific activity ranged from 18.9 to 34.5 mBq/cell.
tumors compared to non-irradiated tumors in the radiation Splenocytes and CD8+ T cells were visualized with PET imaging
naïve mice (13.65 ± 0.83 vs. 9.95 ± 1.65 %ID/g ± SD, p = 0.005). and kinetics of immunologically competent cells were assessed
Uptake of control IgG showed no differences between irradiated in mice. Splenocytes and CD8+ T cells were mainly distributed
or non-irradiated tumors (4.70 ± 1.04 vs. 5.06 ± 0,96, p = 0.92). in the spleen 1 to 10 days after injection. Conclusion: We
Further analysis of the SPECT scans indicated the presence of have developed long half-life PET tracers for immunologically
tertiary lymphoid structures in the tumor periphery also showing competent cells. Zirconium-89 was taken up by splenocytes and
increased CD8 uptake in irradiated tumors, which was confirmed CD8+ T cells and whole body distribution of these radiolabeled
by immunohistochemistry. Further immunohistochemical cells was detectable in mice for a long duration. References:
analysis tumor and normal tissues is ongoing. (1) Eur J Nucl Med Mol Imaging (2015) 42:278-287 DOI 10.1007/
Conclusion: The anti-CD8 antibody showed specific uptake s00259-014-2945-x.
in CD8+ T cell containing tissues in vivo, but tumor uptake
was limited due to low number of CD8+ T cells present. We
demonstrated that irradiation induces a significant increase OP-498
in tracer uptake in B16-F1 tumors. These differences were Is [89Zr]PD-L1 a useful tool to capture an immune response
shown to be specific for an increase in CD8+ T cells. In the to oncolytic virotherapy?
future, this tracer has potential for in vivo evaluation of CD8+ J. Hoebart, C. Da Pieve, F. Raes, D. M. Ciobota, G. Smith, A. Melcher,
T cell infiltration and could assist in immunotherapy response K. J. Harrington, G. Kramer-Marek;
monitoring. References: None. The Institute of Cancer Research, London, UNITED KINGDOM.

OP-497 Aim/Introduction: Oncolytic virotherapy (OV) has recently


PET Imaging For Tracking Immunologically Competent attracted a lot of attention in the field of cancer immunotherapy
Cells With Zirconium-89 Labeling Method In Murine as several studies have indicated its potential to enhance the
Syngeneic Transplantation Model therapeutic response of immune checkpoint blockade when
T. Sasaki1, M. Akehi1, T. Sadahira1, K. Hagihara2, R. Watanabe2, Y. both were used in a combination regimen[1]. However, little
Ishimoto2, N. Komatsu2, K. Wakita2, M. Watanabe1; is still known about the immunological impact of oncolytic
1
Okayama university, Okayama, JAPAN, viruses on the tumour and the body as a whole. Therefore, we
2
Daiichi Sankyo Co., Ltd., Tokyo, JAPAN. aimed to investigate the effect of OV by imaging programmed
death receptor ligand 1 (PD-L1), which is considered as a major
marker of an interferon-driven, antiviral immune response. PD-
S193 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

L1 PET performed during and after OV might elucidate the Aim/Introduction: The 131I treatment is an effective option
dynamics of the anti-viral immune response and ultimately help for metastatic thyroid cancer. Lesion dosimetry is suggested
to optimise the clinical application of this therapeutic strategy. by EU Directive 59/2013 and national regulations to optimize
Materials and Methods: The murine head and neck cancer the patient’s management but commercial software are not
cell line MOC2, and its variants MOC2-Luc and MOC2-Luc- always accessible. Aim of this project granted by our Regional
PD-L1, were used in vitro and grown as subcutaneous tumours Oncological Network is to develop an in-house software to
in immunocompetent mice. An anti-mouse PD-L1 mAb was standardize dosimetric method among centers. Materials and
conjugated with desferrioxamine (DFO) and labelled with Methods: Lesion dosimetry is performed after the 131I therapy
zirconium-89 (89Zr). The radiotracer specificity was characterised (4 SPECT-CT @ 4,24,48, 96 h p.a. ,Siemens SymbiaIntevoT2, 64
in vitro (0.3-0.5 MBq) and in vivo (biodistribution via automated views, 256x256, ITSCAC, partial volume effect and dead-time
γ-counting and autoradiography) at multiple time points post- corrected, absolute calibration). In the standard approach
injection (2.0-10.0 MBq). Reovirus, a non-genetically modified both lesions definition and doses (MIRD sphere model) are
dsRNA virus, administered intratumourally or intravenously was manually performed. An in-house MATLAB tool was developed
used for OV (repeated dosing) which was followed up by PET to automatized the process: images co-registration, automatic
imaging with [89Zr]PD-L1. Results: [89Zr]PD-L1 showed high lesion segmentation, cumulated-activity curve fitting, mean
receptor specificity in vitro. In vivo studies demonstrated high dose calculation. The software was tested on a spheres phantom
accumulation of the tracer in MOC2 tumours at 48 hr (%ID/g = filled with liquid 131I (13 MBq/ml, volumes: cylinder 130 ml,
29.4±2.9) and at 96 hr (%ID/g = 25.1±1.9) post-injection, with spheres 11.5, 5.6, 2.6, 0.5 ml) and on 6 patients (37 lesions, mean
tumour-to-blood ratios of 5.4±0.5 and 18.0±4.9, respectively. activity 6061 MBq, 3716÷9286 MBq). Volumes, activity and doses
Autoradiograms of tumour sections confirmed heterogeneous calculated with MATLAB code were compared to the standard
tracer distribution within the tumour and IHC staining of calculation method. For 4 patients (29 lesions) texture features
consecutive sections the presence of PD-L1. The pilot-study (LIFEx) and mean doses were correlated to the treatment
investigating OV showed markedly increased [89Zr]PD-L1 uptake response in the ROC curve analysis. Results: Phantom analysis
in the spleen, a major organ of systemic immune response, as confirmed a good agreement between standard method and
well as in the tumour of reovirus-treated animals at 96 hr post- MATLAB tool. Percentage variations were in mean (±1SD) -1±2
treatment. The radioactivity level in the blood, i.e. circulating % for the volumes of cylinder and spheres, -9.5±11.6 % for the
activated immune cells, remained relatively low among both cumulated-activity and becomes 10.3±7 % when doses were
groups. In addition, IHC staining of PD-L1 on tumour and spleen compared (limit volume > 2.7 ml to avoid not acceptable
sections confirmed the PET findings. Conclusion: Our results variations ~ 105%). Also patient dosimetry comparison suggests
suggest that [89Zr]PD-L1 PET has great potential to capture that the automatized tool is effective for dose calculation: mean
changes of systemic and intratumoural PD-L1 status and further variation (±1 SD) were -0.1 ± 1.6 % (max 3 %), 0.1 ± 48 % (max
support PD-L1 as an imaging biomarker of immune response 7%) and 1.2 ± 4.8 % (max -13 %) for volume, activity and dose
to OV. References: [1] Samson, A., et al., Intravenous delivery respectively. Mean doses correlate with treatment outcome
of oncolytic reovirus to brain tumor patients immunologically (AUC 0.61, threshold 81 Gy) but some texture features seem to
primes for subsequent checkpoint blockade. Sci Transl Med, better predict the tumor response (HGZE: AUC 0.72, HGRE: AUC
2018. 10(422). 0.68, skewness and kurtosis 0.67) in these preliminary results.
Conclusion: Lesion dosimetry and texture-analysis in metastatic
thyroid cancer 131I treatment are effective tools for patient
1106 management. The standardization of the dose calculation was
achieved and verified with the software. This allowed to share
Do.MoRe - Parallel Session: I-131 Dosimetry and the dosimetric protocol to other nuclear medicine unit to the
DNA Damage during Different Therapies aim of dose comparisons. Preliminary dose-response correlation
investigated both for dose and texture features needs further
Tuesday, October 15, 2019, 8:00 - 9:30 Lecture Hall 112 investigations with a larger dataset. References: None.

OP-499 OP-500
Lesion dosimetry in metastatic thyroid cancer treated with Retrospective evaluation of a single time point dosimetry
131
I:standardization of SPECT-TC calculation method with method for radioiodine treatment of hyperthyroidism
an in-house software tool and preliminary texture analysis E. Amato1,2, A. Campennì1,3, R. M. Ruggeri4, L. Auditore1,2, S.
results Baldari1,3;
E. Richetta1, M. Poli1, A. Rienzo1, D. Valentini2, B. Peiretti Paradisi1, V. 1
Department of Biomedical and Dental Sciences and
Garbaccio3, R. Pellerito1, A. Muni2, D. Deandreis3, M. Stasi1; Morphofunctional Imaging, University of Messina, Messina,
1
AO Ordine Mauriziano, Torino, ITALY, 2Ospedale Civile ITALY, 2Istituto Nazionale di Fisica Nucleare, Catania, ITALY,
Santi Antonio e Biagio e Cesare Arrigo, Alessandria, ITALY, 3
Nuclear Medicine Unit, University Hospital “G. Martino”, Messina,
3
AOU Citta della Salute e della Scienza, Torino, ITALY. ITALY, 4Department of Clinical and Experimental Medicine,
Unit of Endocrinology, University of Messina, Messina, ITALY.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S194

Aim/Introduction: The treatment of hyperthyroidism with differentiated thyroid cancer patients (DTC) after thyroidectomy.
131
I radioiodine is a safe and effective therapy, in which a Several studies have reported salivary gland hypofunction and
diagnostic uptake curve is used to pre-determine the patient- xerostomia after treatment with 131I-NaI but controversy remains
specific activity to be administered. Aim of this study was to over whether absorbed doses correlate with clinically observed
retrospectively evaluate the accuracy of a dosimetric approach toxicity. The aim of this study was to assess inter- and intra-
based on a model presented in Ref. 1 of mono-exponential patient variability of effective half-lives and absorbed doses
clearance following instantaneous uptake, relying on a to parotid and submandibular salivary glands. Materials and
single time uptake measurement. We extended the model to Methods: 19 patients with DTC were treated with 3000 MBq
account for a non-instantaneous uptake phase. Materials and of 131I-NaI following near-total thyroidectomy. SPECT scans
Methods: Our population consisted in 69 mixed hyperthyroid of the head and neck were performed at 24, 48, 72 and 96
patients, of which 43 were affected by Plummer Disease, 13 hours and the maximum absorbed dose to the left and right
by Toxic Multi-Nodular Goiter and 13 by Graves Disease. They parotid and submandibular salivary glands estimated. The
were treated according to the results of a dosimetric protocol voxel with maximum uptake was used for the calculations to
based on six times of measurement (3-6-24-48-72/96-168 avoid issues due to volume delineation. Instantaneous uptake
hours). Time-integrated activity and radiation absorbed was assumed and time activity curves were fitted with a single
doses were estimated using a unique uptake measurement exponential decay function to obtain cumulated activities and
at 168 hours, both exploiting the original model considering half-lives. Unpaired and paired t-tests were used to identify any
an instantaneous uptake followed by mono-exponential statistical significant inter- and intra-patient variability of half-
clearance, and our extended model for non-instantaneous lives and cumulated activity of parotid and submandibular
uptake. Results were compared with the dosimetric protocol salivary glands. Results: Median effective half-lives of 131I-NaI in
based on six points and with a simplified time schedule based the parotid and submandibular salivary glands were found to
on a three time points schedule at 6-24-168 hours. Results be 16.3 hours (Range: 4.8 - 39.7 hours) and 14.8 hours (Range:
were also compared to patients’ final functional status (i.e. 7.2 - 43.9 hours), respectively. The difference in half-life between
euthyroidism, hypothyroidism or hyperthyroidism). Results: parotid and submandibular salivary glands was found to be not
Time-integrated activity calculated by the single time approach statistically significant (p=0.63). Median cumulated activity in
provide relative per cent differences up to ±20% with respect the maximum pixel was measured to be 2.6 MBq.h (Range: 1.1
to the reference dosimetric protocol, whereas errors expected - 8.8 MBq.h) and 2.0 MBq.h (Range: 0.9 - 7.5 MBq.h) in parotid
from the model presented in Ref. 1 should be within ±10%. This and submandibular salivary glands, respectively. No significant
difference can be partly ascribed to the variability of the average difference in cumulated activity between the two types of
population half-lives with type of hyperthyroidism, and partly salivary glands was observed (p=0.06). Paired t-tests showed
on the intrinsic limitations of the model. On the other hand, a no significant difference between half-lives and cumulated
fit procedure based on a simplified time schedule at 6-24-168 activities of left and right parotid salivary glands (p=0.17 and
hours showed errors within ±5%. Conclusion: The dosimetry p=0.13) or submandibular salivary glands (p=0.83 and p =
based on three time measurements confirms to be the most 0.07)) of individual patients. Conclusion: Effective half-lives and
accurate choice.From the operational point of view, the three cumulated activities in salivary glands are comparable between
times schedule requires only one more appearance of the patients. No significant inter-patient variability between left
patient at the nuclear medicine center (at 24 hours); differently, and right parotid and submandibular salivary glands could be
the single late time measurement approach, needs twice the identified. References: None. Acknowledgments: The MEDIRAD
presence of the patient, namely for administration and late project has received funding from the Euratom research and
measurement. Consequently, when, for practical reasons, three training programme 2014-2018 under grant agreement No
time measurements are not achievable, the single time point 755523.
may be an acceptable alternative. References: Madsen, et al.
Technical Note: Single time point dose estimate for exponential
clearance. Med Phys. 2018;45:2318-2324. OP-502
The MEDIRAD multi-national I-131 dosimetry study for
thyroid ablation and adjuvant therapy: current status
OP-501 F. Leek1, J. Taprogge1, R. Gregory2, K. Newbold1, F. Verburg3, M.
Salivary gland dosimetry of differentiated thyroid Luster3, T. Schurrat3, J. Trans-Gia4, U. Eberlein4, C. Lapa4, A. K. Buck4,
cancer patients treated with 131I-NaI after near-total M. Lassmann4, E. Mora-Ramirez5,6,7, A. Vergara-Gil5,6, M. Bardies5,6,
thyroidectomy D. Vallot8, F. Courbon9, L. Vija9, G. Flux1;
J. Taprogge1,2, F. Leek1,2, J. Gear1,2, I. Murray1,2, G. Flux1,2; 1
The Royal Marsden NHS Foundation Trust & Institute of
1
Royal Marsden Hospital NHSFT, London, UNITED KINGDOM, Cancer Research, London, UNITED KINGDOM, 2Barts Health
2
The Institute of Cancer Research, London, UNITED KINGDOM. NHS Trust, London, UNITED KINGDOM, 3University Hospital
Marburg, Marburg, GERMANY, 4University Hospital Würzburg,
Würzburg, GERMANY, 5INSERM, UMR 1037, Université Toulouse
Aim/Introduction: Salivary glands have sodium iodine III Paul Sabatier, Toulouse, FRANCE, 6Centre de Recherches en
symporters and can take up 131I-NaI which is used in Cancérologie de Toulouse, Toulouse, FRANCE, 7University of
S195 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

Costa Rica, Physics School, CICANUM, San Jose, COSTA RICA, OP-503
8
Institut Universitaire du Cancer, Toulouse, FRANCE, 9IUCT- Dosimetric analysis and clinical outcome for patient with
Oncopole, Toulouse Oncology Institute, Toulouse, FRANCE. High-Risk Neuroblastoma administered with high-activity
therapy of 131I-mIBG
B. Cassano1, C. Polito1,2, E. Genovese1, M. Longo3,4, S. Donatiello1, A.
Aim/Introduction: Current practice for post-thyroidectomy Napolitano1, T. Insero1, S. Valeri5, M. F. Villani6, A. Castellano7, M. C.
radioiodine therapy (RAIT) in the treatment of differentiated Garganese6, V. Cannatà1;
thyroid cancer (DTC) is based on activity administered resulting 1
IRCCS Bambino Gesù Children’s Hospital, Medical Physics Unit,
in a wide range of absorbed doses being delivered to the Rome, ITALY, 2Sapienza University of Rome, Molecular Medicine
remnant and normal organs. As internal dosimetry is seldom Department, Rome, ITALY, 3Arcispedale Sant’Anna Hospital,
routinely performed there is currently very little evidence for Medical Physics Unit, Ferrara, ITALY, 4Sapienza University of Rome,
the correlation between the absorbed dose delivered and Ph. D. Program in Morphogenesis & Tissue Engineering, Rome,
response. This Horizon 2020 MEDIRAD1 multi-centre multi- ITALY, 5Tor Vergata Postgraduate School of Medical Physics,
national prospective observational study aims to accurately Rome, ITALY, 6IRCCS Bambino Gesù Children’s Hospital, Nuclear
determine the absorbed doses to healthy organs and thyroid Medicine Unit/Imaging Department, Rome, ITALY, 7IRCCS Bambino
remnants from radioiodine ablation. The relation between Gesù Children’s Hospital, Oncoemathology Unit, Rome, ITALY.
patient biokinetics, patient-specific radiosensitivity and the
success of thyroid ablation and acute to mid-term toxicity will
be assessed. Materials and Methods: One hundred patients Aim/Introduction: Patients with relapsed/refractory metastatic
with histologically proven DTC and a clinical indication for RAIT high-risk neuroblastoma (rrmHRNBL) are very difficult to treat
will be recruited. Three centres will recruit low-risk patients, and they have a very poor prognosis. High-activity therapy is
the fourth intermediate-risk; 1.1 or 3.7GBq I-131-NaI will be a useful and safe treatment for children with rrmHRNBL and
administered, according to local protocol. Gamma cameras tandem modality administration consists of two administrations
have been calibrated for high activity quantitative I-131 of 131I-metaiodobenzylguanidine (131I-mIBG). The aim of this
imaging, characterising count losses due to dead-time and study was to report the absorbed dose to whole-body (WB), red
partial volume effects (PVE). A flexible patient data acquisition marrow (RM) and tumours in order to correlate them with clinical
protocol for dosimetry has been developed to allow for inter- outcome of the patients. Materials and Methods: 15 patients
centre variabilities with respect to access to hybrid imaging, (9 boys and 6 girls, age range [3;20] years) with rrmHRNBL
existing camera workloads and local radiation protection treated between 2016-2019 with tandem high-activity therapy
regulations. The imaging protocol mandates a minimum of giving in total 29 administrations of 131I-mIBG (one patient
four WB planar scans (24-96 hours post-administration) plus a was administered once) were enrolled. WB and RM dosimetry
SPECT(/CT) at 48 hours between the base of skull and upper has been performed according to MIRD and EANM guidelines,
thighs. A comprehensive compartmental model is being collecting WB data, with an external probe at 2 meters distance,
developed for high activity radioiodine biokinetics following and blood samples at 0.5-h, 6-h, 24-h, 30-h, 48-h, 72-h and
thyroidectomy. Biomarker studies will be performed for 20 144-h after the administration. The first administration was
patients with gamma-H2AX as a marker of both radiation weight-based (444 MBq/kg) [6.6;17.5] GBq, while the second
damage to the DNA and of radiosensitivity. Results: All four one was dosimetry-based, achieving 4 Gy to WB. For ten
centres participating in this study have been set-up. Three patients five static images were acquired in the time window
Siemens Intevo SPECT/CTs, one Siemens Symbia S SPECT and [2;144] h and the absorbed dose to lesions have been assessed
one GE Discovery 670 SPECT/CT were characterised. The GE following the conjugated view method. The response was
SPECT/CT system had a system volume sensitivity of 57.8cps/ visually assessed by comparing the CT and 123I-mIBG-SPECT/
MBq compared to Siemens SPECT/CTs with sensitivities ranging CT scans obtained before therapy with those obtained between
from 79.1-91.9cps/MBq. Recovery curves for count losses due to 8-10 weeks after 123I-mIBG, and it was graded according to
the PVE were determined. The mean system dead-time factor the semiquantitative SIOPEN mIBG score system. Results:
at 1.1 GBq was 1.07±0.0266. Conclusion: The first European The injected activity at the second administration varies from
network able to perform standardised quantitative radioiodine 12.6 to 17.9 GBq while the dose per activity remains constant
imaging for dosimetry has been established with the potential between first and second administration. The cumulative
for expansion to other centres. The dosimetric methods and absorbed dose ranging from [2.5;4.8], [0.7;2.4], [13;464] Gy
tools developed will provide the basis for a subsequent large- for the WB, the RM and lesions respectively. After 131I-mIBG
scale observational epidemiological study of acute, mid- and therapy, combined with chemotherapy, 4 patient achieved
long-term risk from absorbed doses delivered to normal organs. partial remission, 7 showed stable disease and 3 had progressive
References: [1] EC Horizon 2020 NFRP-9. disease. All patients showed grade 3 of haematological toxicity
(neutropenia, anaemia and thrombocytopenia). At the end of
the study, 5 patients died after 7-24 months from treatment.
Conclusion: The dosimetric approach is necessary to perform
a patient-specific treatment. The dose per administered activity,
performed at the first administration, is a good predictor for
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S196

the second treatment in order to inject the maximum tolerable to [177Lu]Lu-DOTATATE irradiation. Conclusion: [111In]In-anti-
activity to the patients. High-activity therapy, in combination γH2AX-TAT allows monitoring of DNA damage following [177Lu]
with chemotherapy treatment, is well tolerated and effective in Lu-DOTATATE therapy, and reveals heterogeneous damage
patients with rrmHRNBL. We observed benefits in the treatment responses. References: None.
of relapse/progression, improving survival rates without severe
toxicities. References: None.
OP-505
Alpha Particles Induce DNA Damage in Leukocytes during
OP-504 Treatment with Ra-223
Imaging DNA Damage in vivo following [177Lu] S. Schumann1, M. Lassmann1, C. Lapa1, R. Muhtadi2, H. Scherthan2,
Lu-DOTATATE therapy in a model of pancreatic U. Eberlein1;
neuroendocrine cancer 1
Department of Nuclear Medicine, University of Würzburg,
E. O’Neill1, V. Kersemans1, P. Allen1, S. Terry2, J. Baguña Torres1, S. Würzburg, GERMANY, 2Bundeswehr Institute of Radiobiology
Smart1, B. Quan Lee1, N. Falzone1, K. Vallis1, M. Konijnenberg3, M. de affiliated to the University of Ulm, Munich, GERMANY.
Jong3, J. Nonnekens3, B. Cornelissen1;
1
University of Oxford, Oxford, UNITED KINGDOM,
2
King’s College London, London, UNITED KINGDOM, Aim/Introduction: Irradiation with the α-emitter Ra-223 creates
3
Erasmus MC, Rotterdam, NETHERLANDS. densely packed DNA damage tracks along particle trajectories
(α-tracks) in exposed cells. These α-tracks can be visualized by
immunofluorescent staining with γ-H2AX+53BP1 antibodies
Aim/Introduction: Molecular Radiotherapy (MRT) using [177Lu] and used as a biomarker for α-particle exposure. The aim of
Lu-DOTATATE is an effective treatment against somatostatin this study was to investigate the time- and dose-dependency
receptor expressing neuroendocrine tumours (NETs). This of the number of α-tracks in blood leukocytes of patients
beta-particle emitting radiopharmaceutical binds to receptors undergoing their first therapy with Ra-223. Materials and
on tumour cells, irradiating the tumour locally, causing DNA Methods: Blood samples from prostate cancer patients (n=9)
damage, tumour cell death, and tumour regression. Despite were taken before the administration of Ra-223 dichloride (55
its frequent and successful use in the clinic, little or no kBq per kilogram bodyweight) and nominally 1.5 h, 3 h and 4 h
radiobiological considerations are taken into account at the after the administration. One or two blood samples were taken
time of treatment planning or delivery, and treatment is usually on subsequent days (n=4; 24 h up to 96 h after administration)
administered as a standard dose and number of cycles without and one sample four weeks after treatment (n=3). In each blood
consideration for peptide uptake, dosimetry, or radiobiological sample, the activity was quantified using a calibrated, high purity
and DNA damage effects in the tumour. Here, we visualise germanium detector and integrated time-activity curves were
and quantify the extent of DNA damage following [177Lu]Lu- used to calculate the absorbed doses to the blood, assuming
DOTATATE therapy using SPECT imaging with [111In]In-anti- that the complete energy by α- and β-particles emitted by Ra-
γH2AX-TAT, which visualises the well-studied DNA double strand 223 and its progeny is deposited locally in the blood. For the
break signalling protein, γH2AX. This work is a proof-of-principle quantification of γ-H2AX+53BP1 positive α-tracks, leukocytes
study of this in vivo non-invasive biodosimeter, for use with were separated, fixed in ethanol and immunofluorescently
therapeutic radiopharmaceuticals. Materials and Methods: stained. The number of α-tracks was evaluated manually in
Six cell lines were exposed to external beam radiotherapy 100 nucleated cells per sample in a fluorescence microscope.
(EBRT) or [177Lu]Lu-DOTATATE, after which the number of γH2AX Results: The absorbed doses to the blood up to 4 h after
foci and clonogenic survival were measured. Mice bearing administration were below 6 mGy in all samples. For the three
CA20948 somatostatin receptor positive tumour xenografts patients with five time-points, it was possible to calculate the
were treated with [177Lu]Lu-DOTATATE or sham-treated, and co- total absorbed dose to the blood, which ranged between 4
injected with [111In]In-anti-γH2AX-TAT, [111In]In-IgG-TAT control, mGy and 16 mGy. The number of α-tracks in 100 cells ranged
or PBS. Results: Clonogenic survival following EBRT was cell from 0 to 7. In the samples taken before the administration,
line specific, indicating varying levels of intrinsic radiosensitivity. only one α-track was observed in one patient’s sample, while
In vitro, cell lines treated with [177Lu]Lu-DOTATATE, clonogenic the other eight patients did not show any α-tracks. The average
survival decreased and γH2AX foci increased in cells expressing number of α-tracks 4 h after administration was 2.9 per 100 cells.
high levels of somatostatin receptor subtype 2 (SST2). Mice In all late samples (24 h up to 4 weeks after administration), the
treated with [177Lu]Lu-DOTATATE resulted in a significant number of α-tracks was still elevated (minimum 1 and maximum
increase in [111In]In-anti-γH2AX-TAT uptake compared to non- 6 per 100 cells). Conclusion: Even at absorbed doses to the
treated mice (P=0.0033) at 72 h, or the non-specific control blood < 16mGy, there was an increased frequency of α-particle-
compound [111In]In-IgG-TAT, with or without 177Lu treatment induced DNA damage carrying leukocytes, which in some
(P<0.0001). Ex vivo measurements revealed a partial correlation cases, persisted even four weeks after the treatment. Our results
between [177Lu]Lu-DOTATATE uptake and γH2AX foci induction highlight the sensitivity of the γ-H2AX+53BP1 DNA damage test
between different regions of CA20948 xenograft tumours, even after internal exposure to extremely low absorbed doses.
suggesting different parts of the tumour may react differentially References: None.
S197 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

OP-506 1107
Determination of S-values and characterization of
direct damage to DNA induced by Auger electrons from
Pitfalls & Artefacts 5 - Interactive Clinical Cases
Copper-64
- Neuroimaging + Technologists Committee:
J. Carrasco1, J. Ramos-Mendez2, M. Avila-Rodroguez3;
Brain PET and SPECT ? Patients? Preparation and
1
Instituto Politécnico Nacional, CDMX, MEXICO, 2University of
Acquisition
California, San Francisco, CA, UNITED STATES OF AMERICA,
3
Universidad Nacional Autónoma de México, CDMX, MEXICO. Tuesday, October 15, 2019, 8:00 - 9:30 Lecture Hall 113

Aim/Introduction: The radioisotope Cu-64 possesses


unique propierties that can serve the dual rol of diagnostic OP-507
and theraphy [1]. The therapeutic potential of Cu-64 lies on Challenges Related to Acquisition of Brain PET and SPECT
its emissions of Auger electrons, provided its internalization in Patients with Neurological Diseases - A Technical
to the cell nucleus, but to date, have not been evaluated in Overview
detail. The Monte Carlo Track Structure (MCTS) simulations are M. Mada;
recognized as the most accurate theoretical tools to evaluate MRC Cognition and Brain Sciences Unit,
the biological effects of ionizing radiation at the DNA-scale. Cambridge, UNITED KINGDOM.
The aim of this research work was to determine the S values
and evaluate the number of double-trand-breaks caused by
Auger electrons from CU-64. Materials and Methods: TOPAS- OP-508
nBio was used to simulate the complete trajectories of Delta Pitfalls and Artefacts Related to Preparation and
rays, Auger and Coster Kroing electrons generated from the Acquisition of Brain FDG PET
decay of Cu-64 on water. The S-values were calculated for M. Bauckneht;
different target-source configurations simulating the cell (C) Nuclear Medicine Unit, San Martino Hospital,
and the cell nucleus (N) as concentric spheres of 5μm and 4μm University of Genoa, Genoa, ITALY.
, respectively, the cytoplasm (Cy) as intermediate region, and
the cells surface (Cs). For estimation of the direct damage to the
DNA, the DBSCAN algorithm was used to calculate the number OP-509
of double strand breaks that are produced in the nucleus cell. Pitfalls and Artefacts Related to Preparation and
Additionally, ionization clusters were calculated in a model of Acquisition of Dopaminergic Imaging
10-base-pair segment of DNA to obtain the average ionization E. van de Giessen;
cluster produced by a source of Cu-64 as a function of distance Department of Nuclear Medicine, Academic Medical Center,
to the DNA segment. Results: The determined S values are in University of Amsterdam, Amsterdam, NETHERLANDS.
good agree with the values reported by the MIRD Committee
To the best of our knowledge this is the first time that S values
are obtained for Cu-64 by using MCTS calculations. The number OP-510
of double breakings obtained for Cu-64 for the configuration Pitfalls and Artefacts Related to Preparation and
N←N, N←C, and N←Cs were 0.0187±0.001, 0.0317±0.0005, Acquisition of PET AA-Imaging in Brain Tumours
and 0.0125±0.0002, respectively. The cluster size shows a direct I. Law;
dependence on the position of the source in relation to the DNA, Department of Clinical Physiology, Nuclear Medicine and
showing a fast decrease as the source gets apart from the DNA PET, University of Copenhagen, Copenhagen, DENMARK.
segment. Conclusion: Micro and nanodosimetric parameters
of Cu-64 were characterized with track-structure simulations,
these quantities can be used to calculate absorbed dose when
Cu-64 is internalized in the cell, in addition to the total number
of double breaks within the nucleus cellular through data of
biodistribution of Cu-64 in the cell. References: [1] M.A. Avila
Rodriguez, C. Rios, J. Carrasco Hernandez, et al., Biodistribution
and Radiation Dosimetry of [64Cu]Copper Dichloride: First in
Human Study in Healthy Volunteers, Eur J Nucl Med Mol Imaging
Research. 7, 98 (2017).
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S198

1108 involvement. PET/CT-guided biopsy is a practical approach for


isolated lesions with no discernible morphological change on
Clinical Oncology - Parallel Session:
CT images. References: None.
Radioguided Surgery

Tuesday, October 15, 2019, 8:00 - 9:30 Lecture Hall 114 OP-512
Sentinel Lymph Node Biopsy in breast cancer with 99mTc-
Tilmanocept (LYMPHOSEEK®): A descriptive analysis of our
experience in 9 centers in Spain
OP-511 S. Vidal Sicart1, M. Rioja-Martin2, A. Prieto3, E. Goñi4, I. Gómez5, M.
Diagnostic values of real time F-18 FDG PET/CT guided Albalá6, L. Lumbreras7, L. León8, J. Gómez9;
metabolic biopsy for diagnosis of Lymphoma 1
Hospital Clinic Barcelona, Barcelona, SPAIN, 2Hospital
B. Mittal, R. Kumar, H. Singh, A. Bhattacharya, G. Prakash, P. Universitario Ramon y Cajal, Madrid, SPAIN, 3Hospital
Malhotra; Puerta de Hierro, Madrid, SPAIN, 4Complejo Hospitalario de
Postgraduate Institute of Medical Education Navarra, Pamplona, SPAIN, 5Hospital General Universitario
& Research, Chandigarh, INDIA. Gregorio Marañón, Madrid, SPAIN, 6Hospital Universitario
Reina Sofia, Córdoba, SPAIN, 7Hospital Regional Universitario
de Málaga, Málaga, SPAIN, 8Hospital Rey Juan Carlos,
Aim/Introduction: Conventional image guided biopsy is Madrid, SPAIN, 9Hospital Torrecárdenas, Almería, SPAIN.
subjected to sampling error with varying diagnostic accuracy.
In this prospective study, we aimed to evaluate the diagnostic
values of real time PET/CT guided metabolic biopsies from the Aim/Introduction: Sentinel lymph node (SLN) biopsy is
FDG avid nodal or extra-nodal sites in clinically suspected cases the standard of care in axillary staging of clinically node-
of lymphoma or suspected cases of relapse. Materials and negative breast cancer patients. 99mTc-Tilmanocept is a novel
Methods: In this prospective study, patients were recruited for receptor-targeted radiopharmaceutical in Europe indicated for
PET/CT guided metabolic biopsy in proven or suspected cases imaging and intraoperative detection of SLNs in breast cancer,
of lymphoma. The site of biopsy was planned from the most melanoma or oral cavity squamous cell carcinoma. Aim: To
accessible FDG avid lesion in each case. The biopsies were done describe results in clinical practice with 99mTc-Tilmanocept in
using a dedicated automated-robotic-arm assisted device, and breast cancer patients scheduled for SLN biopsy. Materials
a real-time samples were retrieved after confirming the position and Methods: Retrospective multicenter analysis of 352
of the needle-tip within target lesion with regional PET/CT. To patients (98.9% women, mean age 59 years, mean body
check the accuracy of the procedure, histopathology reports mass index (BMI) 27), with T1-T3 N0-N1 breast cancer, who
were reviewed. For confirmation of negative results, clinical or underwent SLN biopsy from September 2017 to October 2018
imaging follow-up was done and the diagnostic values of the in 9 Spanish centers. An average dose of 87.4 (± 28.4) MBq
procedure was calculated. The procedure related complication was administered in patients with two-day protocol and 57.7
were also evaluated. Results: Ninety-six patients (56 males, 40 (± 19.5) MBq with one-day protocol. SLN biopsy was identified
female) with age 39.6±17.1 (range 17-85) years were enrolled using preoperative lymphoscintigraphy and intraoperative
for biopsies from nodal or extra-nodal sites. Of these 51 patients gamma probe. Local protocols used for SLN localization were
were suspected cases of lymphoma, while 45 patients had not changed throughout the study. Statistical analysis was
suspected recurrence on prior PET/CT images. Biopsy target done with SPSS v25.0. Differences were considered significant
were nodal in 59 patients while extra-nodal in 37 patients (bone when the value was < 0.05. Results: Two-day protocol was
or marrow lesions - 28, lung-1, liver- 1, and pancreas 3, spleen-1, used in 89.2% of cases. Forty-five (12.8%) of patients received
cutaneous soft tissue mass-3). Adequate tissue was obtained neoadjuvant systemic therapy previously to SLN biopsy. Final
in all the patients to yield a pathological diagnosis except report was unavailable in 17 patients (4.8%). SLN detection rate
three (93/96) and repeat biopsy confirmed the lymphomatous with 99mTc-Tilmanocept was 96.1% (96.5% in those clinically N0
involvement. Pathology revealed lymphoma in 86/93 patients and 94.9% in N1 patients). More than 78% of patients showed
while tuberculosis in four, plasmacytoma, IgG4 related disease 1 or 2 SLN (mean 1.73) in lymphoscintigraphy (range 0-8).
and sarcoidosis one each. The findings revealed 84 true-positive, Intradermal injection results in better SLN detection rate than
zero false-positive, seven true-negative and three false-negative peri-intratumoral injections. In 3.9% of the patients, a SLN could
lesions. The procedure revealed a sensitivity, specificity, PPV, not be detected in lymphoscintigraphy and it was significantly
NPV and accuracy of 96.6%, 100%, 100%, 70.0% and 96.9% related to the radiotracer’s injection area. Her2 tumor patients
respectively for establishing a diagnosing of lymphoma. No had 3.33 times higher probability to non-visualization of SLN. No
procedure related complications were encountered during or significant differences in successful identification of a SLN were
after the procedure. Conclusion: PET/CT guided metabolic found due to patient age, BMI, sex or tumor localization. During
biopsy from nodal and extra-nodal site is safe and accurate surgery 6/13 patients without SLN visualization achieved a SLN
method for a pathological diagnosis and shown a very high retrieval with gamma probe. Pathology report showed negative
diagnosis performance for evaluation of lymphomatous SLN in 239 patients (71.3%). The percentage of positive SLN was
S199 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

higher in patients below 50 years old (31.9%) versus those with identified clearly. Conclusion: According to our experience,
more than 50 years (23.7%). Overall sensitivity was 97.7% and false the radiotracer 99mTc-Tilmanocept is a good option for oral
negative rate was 2.3%. No adverse side-effects were reported. cavity cancer selective SLNB, improving the shine-through
Conclusion: 99mTc-Tilmanocept is a new radiotracer for lymphatic phenomenon, with better delimitation between the injection
mapping and SLN biopsy that shows good results in breast site and nearby SLN, mainly levels 1A and 1B, proving high value
cancer SLN biopsy whatever protocol is used in a heterogeneous in floor-of-mouth tumors. References: None.
breast cancer population with a sensitivity better than expected
and false negative rate lower than expected. References: None.
OP-514
Image-guided Occult Lesion Localization for Non-Palpable
OP-513 Breast Cancer Tumors
Sentinel lymph node biopsy with 99mTc- Tilmanocept in oral J. R. Orozco Cortés, A. Badenes Romero, G. Garrigos Ortega, B.
cavity cancer: Our experience Cueto Cañadas, I. Latorre Agraz, P. Abreu, T. Mut, D. Balaguer,
M. Albala Gonzalez, A. Santos Bueno, A. Dean Ferrer, M. Estero R. Vila, S. Pelaez, E. Caballero Calabuig, M. Plancha, M. Reyes, R.
Serrano De La Cruz, M. Sanchez Frias, A. Acosta Collado, J. Marquez Martinez;
Fernandez, J. Prieto Prieto, V. Guiote Moreno, J. Vallejo Casas; Hospital Universitario Dr Peset, Valencia, SPAIN.
Hospital Universitario Reina Sofia, Cordoba, SPAIN.

Aim/Introduction: The use of gamma probes and Tc-99m


Aim/Introduction: In oral cavity cancer, the presence of cervical colloids for radioguided occult-lesion localization (ROLL) is
lymph node metastases reduces survival by up to 50%. Selective replacing guidewire localization in breast cancer in Europe.
sentinel lymph node biopsy (SLNB) can detect metastases in However, ROLL could be further improved by adding
patients without clinical or radiologic lymph node disease. intraoperative SPECT imaging to assess tumor margins
99m
Tc-Tilmanocept is a novel receptor-targeted radiotracer, Materials and Methods: 19 patients with non-palpable breast
whose smaller molecular size and its specific binding to CD206 cancer tumors (<1.5 cm diameter) were injected intratumorally
receptors on the surfaces of macrophages within lymph nodes with 37 - 148 MBqof 99m-Tc-nanocolloids 24 hours before
allow faster injection site clearance than 99mTc-nanocolloids. surgeryunder ultrasound targeting the lesion center. Early planar
Our aim is to evaluate the use of 99mTc-Tilmanocept administration scintigraphy and freehand SPECT (fhSPECT) were obtained
in oral cavity cancer SLNB. Materials and Methods: A to control no leakage. Intraoperatively, fhSPECT was used to
prospective study of patients with oral cavity tumors measuring obtain 5 images: pre-incision, during resection, tumor bed and
less than 4cm, T1(73%) & T2 with clinical/radiological N0 stage, twice on specimen. The first, to define the incision site. During
attending our unit and scheduled for SLNB. Four peritumoral resection, to decide surgery extension of all 6 borders guided by
99m
Tc-Tilmanocept injection were administered. Planar images the distance from the center of maximum activity to the border
were obtained immediately and 2 hours post-injection and in with the gamma probe provided by system. After resection,
a late phase SPECT/CT. Surgery was performed the next day. fhSPECT was used to image specimen and to estimate security
Results: 13 patients (mean age 72; 8 men), were recruited. margins. If distance from the center of maximum activity to
Surgery was performed in only 11 patients, one was ruled out the margins was <10 mm, resection was extended. Specimens
for clinical reasons, and the other was rescheduled and switched were further imaged using mammography (RxM). Histology
to 99mTc-nanocolloids. Tumor location was 54% tongue, 23% was considered gold standard for margins involvement. We
mouth floor, 15% buccal mucosa and 8% lip. At least one SLN compared the time spent intraoperatively with fhSPECT vs RxM
was detected in all patients. A mean of 2,4 nodes were removed and assessed the concordance of fhSPECT with RxM, and both
per patient (range 1-5). Only one patient presented positive with histology. Predictive values (PPV and NPV) were calculated
bilateral SLN’s as isolated tumoral cells and for clinical reasons Results: Preoperative imaging showed no leakage in any patient.
was treated with cervical radiotherapy. Disease progression was Every fhSPECT scan lasted 2 minutes, resulting in acceptable
only detected in the patient with positive lymph nodes after a image quality (total imaging time 10 minutes). RxM time was
mean follow-up of 8.7 months (6-12 months). Disease relapse 20min. Surgery total time was 85 min (40-129min).Compared
has not been detected in the others patients. Currently the false- to histology, fhSPECT/RxM resulted in 5/6 false negatives
negative rate is 0%. In static imaging and in SPECT/CT there was (margin considered sufficient, but histologically affected (R1));
less activity in the injection site, providing a clear differentiation 1/0 true positive (margin considered too small and R1); 7/7
between the SLN, especially levels 1A and 1B and the injection false positive (margin considered too close, but unaffected
site. This clear differentiation has been observed in all tumor (R0)); and 9/9 true negative (margin considered sufficient and
locations, including mouth floor. In one patient, the procedure R0). NPV was 64.3% vs. 60%. PPV, 14.3% vs. 0%. Concordance
was performed with both radiotracer. The same lymphatic between fhSPECT and RxM was 13/19 (68.4%). Concordance of
drainage patterns was observed, with a better visualization of fhSPECT versus histology was 10/19 (52.6%), and of RxM versus
1B bilateral lymph nodes with 99mTc-Tilmanocept, because in histology was 9/19 (47.3%). Conclusion: Border delimitation
level 1B bilateral lymph nodes 99mTc-nanocolloids presented using SPECT-Portable is a useful and efficient procedure,
shine-through phenomenon, and the left one could not be requiring an optimized and multidisciplinary protocol. fhSPECT
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S200

does not prolong surgery because the time used for patient OP-516
is 10 minutes. Provided non-inferiority of fhSPECT compared Sentinel lymph node status versus tumor characteristics,
to RxM in this short group, it could potentially replace RxM for neutrophil to lymphocyte ratio, C-reactive protein levels
specimen control. Modifying this protocol by adding tumor to and C-reactive protein to albumin ratio-prognostic factors
margins distance could reduce false negative rate for fhSPECT. for primary cutaneus melanoma
Such modification is being evaluated in a larger patient group S. Stojanoski, N. Manevska, T. Makazlieva, D. Miladinova;
References: None. Medical Faculty, Skopje, NORTH MACEDONIA.

OP-515 Aim/Introduction: The aim of this study was to identify tumor


Sentinel Lymph Node Biopsy After Neoadjuvant characteristics of primary malignant melanoma, neutrophil to
Chemotherapy In Breast Cancer Patients; Correspondence lymphocyte ratio (NLR), C - reactive protein (CRP) levels and
With Molecular Subtypes C - reactive protein to albumin ratio (CRP/Alb) predictive of
P. de la Riva Pérez, C. Calvo Moron, T. Cambil Molina, F. García sentinel lymph node (SLN) positive status and their impact on
Gómez, A. Agudo MartÍnez, G. Sabatel Hernández, M. Molina Mora; disease recurrence, melanoma specific survival (MSS), disease
Hospital Macarena, Sevilla, SPAIN. free survival (DFS) and overall survival (OS) period. Materials
and Methods: 100 patients with primary malignant melanoma,
Aim/Introduction: To present both the results obtained clinically staged T1b/T2+ (1-4mm thick) N0, M0 underwent SLN
by the Sentinel Lymph Node Biopsy (SLNB) technique after detection procedure. Tumor characteristics, NLR, CRP levels and
neoadjuvant chemotherapy in patients with breast cancer and CRP/Alb ratio were analyzed in correlation with SLN status. The
initial N (+)/(-), and the existing connection with the different optimal cutoff values of NLR and CRP/Alb were determined by
molecular subtypes. Materials and Methods: We included the receive operative characteristics (ROC) analysis. Univariate
167 breast cancer patients(mean age 52.4 years). Intending and multivariate Cox regression analyses, t - test for continuous or
to perform conservative surgery, we treated the patients with X2 test for categorical variables and Kaplan-Meier curve analyses
neoadjuvant chemotherapy to try to reduce the tumor size. were performed to assess factors predicting SLN positive status,
The nodal state at the beginning was N(-) in 119 patients and regional recurrence rate, DFS, MSS and OS period. Results:
N(+) in 48. It was necessary to demonstrate axillary negativity We identified Breslow`s thickness (OR=1,51; 95% CI 1,02-
in the last group after ultrasound. Molecular subtypes: 5(2,7%) 2,01; p=0,034), presence of ulceration (p=0,041), lymphocytic
luminal A, 59(35,3%) luminal B, 48(28,64%) luminal-HER2+, infiltration (OR=0,42; 95% CI 0,18-0,99; p=0,02), high mitotic
18(11,11%) HER2+ and 37(22,15%) triple(-). We carried out rate (p=0,031), high Ki67 index (p<0,01), high NLR (HR=2,45;
lymphoscintigraphy after the injection of 3 mCi of 99mTc- 95% CI 1,52-3,34; p<0,01), increased CRP levels (HR=1,53; 95%
nanocolloids the day before the intervention. We located the CI 1,33-1,75; p<0,001) and high CRP/Alb ratio (HR=2,01; 95% CI
sentinel node intraoperatively with mixed technique(radiotracer 1,15-3,52; p=0,016) as independent predictors of SLN positive
and blue dye) using gammaprobe and intraoperative portable status. SLN status was the strongest predictor (HR=0,241; 95%
gamma camera. Once we analyzed the SN (OSNA), we decided CI 0,45-1,01; p=0,04) of DFS, MSS and OS period. Conclusion:
intraoperatively whether to perform or not lymphadenectomy We confirmed Breslow’s thickness, presence of ulceration,
depending on indications from last consensus. We classified all lymphocytic infiltration extent, high mitotic rate, high Ki67
data analyzed (identification rate (IR), presence of SN (+)/(mic+) index, high NLR, increased CRP levels and high CRP/Alb ratio
and performing lymphadenectomy) by the initial state of the as factors predictive of SLN metastatic involvement. We also
axilla and the molecular subtypes. Results: Result according to confirmed SLN status to be the most significant independent
N (initial) and molecular subtypes: IR was 72.9% in the N (+) inital predictor of DFS, MSS, OS and risk of regional recurrence. Key
group and 96.6% in the N (-) group (2.06 SN removed/patients). words: neutrophil to lymphocyte ratio, c - reactive protein to
We obtained the lowest identification rates in the luminal albumin ratio, prognostic factors, melanoma, sentinel lymph
groups with initial N (+) (see table). We avoided unnecessary node References: None.
lymphadenectomy were in 58,3% of the N (+) initial patients.
With respect to the 30 dissections made, 40% (12/30) were
(+). 53.84% of the ALND after failure of the technique in the N
(+) initial group were positive (7/13). Conclusion: SLNB after
neoadjuvant chemotherapy is still subject of debate. This is
mainly because, according to the literature, the identification
rates of the sentinel node and the rate of false negatives involved
in the validation of the test fluctuate heavily, especially in N +
initial.We obtained the lowest IR in the luminal groups, although
the luminal A group would be biased due to its small sample
size.We avoided unnecessary lymphadenectomy in 58,3% of
N(+) initial patients. Long-term monitoring of patients will be
necessary because of lack of TFN. References: None.
S201 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

OP-517 OP-518
The value of 99mTc-nanocolloid reinjection in vulva cancer Head-to-head comparison of two radiocolloids with
patients with non-visualisation of a contralateral sentinel different particle size for sentinel lymph node imaging
node using lymphoscintigraphy and SPECT/CT
C. Brouwer1, H. J. M. A. Zijlmans2, M. P. M. Stokkel2, B. van der Hiel2; D. Rietbergen1, P. Meershoek1, M. Donswijk2, M. Klop2, R. Valdes
1
The Netherlands Cancer Institute-Antoni van Leeuwenhoek, Olmos1,2, F. van Leeuwen1, J. vd Hage1,2;
Amsterdam, NETHERLANDS, 2the Netherlands Cancer Institute- 1
Leids Universitair Medisch Centrum (LUMC), Leiden,
Antoni van Leeuwenhoek, Amsterdam, NETHERLANDS. NETHERLANDS, 2NKI-AVL, Amsterdam, NETHERLANDS.

Aim/Introduction: The aim of this study was to evaluate Aim/Introduction: The purpose of this study was to compare
whether in vulva tumors located within 1 cm of the midline but the drainage patterns of two radiotracers with different particle
not involving the midline 99mTc-nanocolloid reinjection after size (PS) in melanoma patients scheduled for sentinel lymph
initial non-visualization of a sentinel lymph node (SLN) in the node (SLN) biopsy. Based on a head-to-head comparison of
contralateral groin has clinical value. Materials and Methods: ICG-99mTc-nanocolloid (PS 5-80nm) with 99mTc-Senti-Scint (PS
From November 2013 until November 2018 patients with vulvar 100-600nm), we evaluated their drainage pattern and sentinel
carcinoma underwent preoperative SLN lymphoscintigraphy lymph node localization using lymphoscintigraphy and SPECT/
including planar imaging and SPECT/CT after four intradermal CT. Further, we studied whether the increased particle size
injections of 99mTc-nanocolloid surrounding the tumor. could reduce the amount of non-SLNs, while preserving the SLN
Demographic data, visualization of sentinel nodes ipsi- and identification. Materials and Methods: Twenty-five patients
contralateral, reinjection, surgical procedures, pathology (mean age: 56.9y, range: 25-79y) with a melanoma scheduled
results and follow up was registered retrospectively. Data was for SLN biopsy prior to (re)excision of the primary lesion (scar)
categorized by primary tumor location as midline, within 1 were prospectively included. The localisation of the primary
cm of the midline but not involving the midline and more lesion was as follows: head and neck region (n=6), the trunk
than 1 cm of the midline. Results: Eighty patients with stage (n=11) and extremities (n=8). All patients followed a two-day
T1b vulvacarcinoma and mean age of 67 years underwent procedure. On the first day, 99mTc-Senti-Scint was injected in 4
SLN lymphoscintigraphy, of which thirty-nine patients had a intradermal depots around the primary lesion or scar. Injection
tumor within 1 cm of the midline but not involving the midline. points were marked on skin with indelible ink to facilitate
In this category, eight cases had initially non-visualization reproducibility in the administration of the second tracer. The
of a contralateral SLN. After reinjection in six patients, four second day, after planar images to control resting lymph node
contralateral sentinel node biopsies (SNB) were performed radioactivity, ICG-99mTc-nanocolloid was injected following
and two contralateral lymph node dissections (LND). In none the same protocol. The paired planar and SPECT/CT images of
of these six patients metastases were found. In two remaining both tracers were evaluated with respect to drainage to lymph
patients with non-visualization and without reinjection, follow node basins, SLN visualisation and non-SLN uptake. Results:
up of 18 months did not show any disease recurrence. Of Twenty-four out of 25 patients were evaluable. One patient
the thirty-one patients with visualization of a contralateral was excluded since the SPECT data were not completed. SLN
SN after first injection, no SNB contained metastases, neither visualisation rate was 100% for ICG-99mTc-nanocolloid and 96%
were contralateral lymph node metastases found in follow for 99mTc-Senti-Scint, whereas uptake in non-SLNs was found
up.In contrast, in four out of thirty-one patients with a midline in respectively 71% (17/24) and 61% (14/23). Concordance rate
tumor, metastases were found in a contralateral sentinel node in drainage to 45 lymph node basins was 91% (41/45) with
which were all visualized after first injection. In three patients discordant findings for two melanomas in head/neck and one
with non-visualization of the contralateral SN, no metastases in clavicular area. Unique lymph node basins were seen in 44/45
were found after reinjection followed by SNB, LND or SNB (98%) for ICG-99mTc-nanocolloid and 42/45 (93%) for 99mTc-
without reinjection. Conclusion: In this retrospective analysis, Senti-Scint. Conclusion: Although ICG-99mTc-nanocolloid led
no metastases in contralateral lymph nodes were found in any to SLN visualisation in all patients this was accompanied by a
of the patients with vulvar carcinoma localized within 1 cm tendency to visualize more non-SLNs. The high reproducibility
of the midline but not involving the midline, either by SNB, of both tracers appears to minimize the difference in particle
LND or during follow-up. In this respect, reinjection after non- size as a factor influencing SLN imaging in melanoma. However,
visualization of a contralateral SLN may not have clinical value. some caution mainly for lesions located in head and neck, which
References: None. needs to be evaluated in a separate head-to-head comparison
including a larger series of patients, is necessary. References:
None.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S202

1109 in the stenosed complicated plaque sample. Both radiotracers


were able to significantly accumulate in complicated and
Cardiovascular - Parallel Session: Imaging the non-complicated parts of atherosclerotic carotid samples.
Vessel Wall Conclusion: Two Lp-PLA2 [18F]-ligands were successfully
obtained on automated module through a Cu-mediated [18F]-
Tuesday, October 15, 2019, 8:00 - 9:30 Lecture Hall 115 fluorodeboronation of aryl-BPin with excellent RCP and specific
activities. The preclinical and ex vivo studies have shown the
suitability of these two candidates for the detection of Lp-PLA2
within the atherosclerotic plaque. References: Guibbal F et al.
OP-519 Bioorg Med Chem Lett. 2018;28(4):787-792.
Fully-automated production of [18F] ligands of
Lipoprotein-associated phospholipase A2 for PET imaging
of atherosclerosis OP-520
E. Jestin1, F. Guibbal2, S. Bénard1, V. Meneyrol1, I. Ait-Arsa1, F. Gimié1, Functional and Metabolic Reprogramming of Bone
O. Meilhac2; Marrow Myeloid Cells in Patients with Atherosclerosis
1
GIP CYROI, Sainte Clotilde, FRANCE, 2Université de la M. P. Noz1, S. Bekkering1, L. Groh2, T. Nielen2, E. Lamfers2, S. El
Réunion/ UMR DéTROI, Sainte Clotilde, FRANCE. Messaoudi1, N. Van Royen1, E. Rutten1, H. Dolstra1, E. M. M. Smeets1,
E. H. J. G. Aarntzen1, M. Bremmers1, W. Van der Velden1, E. Huys1, F.
Preijers1, L. A. B. Joosten1, M. E. Gomes2, M. G. Netea1, N. P. Riksen1;
Aim/Introduction: Atherosclerosis and its associated clinical 1
Radboud University Nijmegen Medical Center,
complications are major health issues in industrialized Nijmegen, NETHERLANDS, 2Canisius Wilhelmina
countries. Accurate diagnostic methods for early detection of Hospital, Nijmegen, NETHERLANDS.
atherosclerotic plaque remains a major challenge to providing
appropriate medical care. Lipoprotein-associated phospholipase
A2 (Lp-PLA2) was demonstrated to play an important role Aim/Introduction: Atherosclerosis is the major cause of
in atherogenesis and is overexpressed in plaques prone to cardiovascular diseases. Monocyte-derived macrophages play a
rupture. Various Lp-PLA2 inhibitors have been developed but central role in the development and progression of atherosclerotic
failed to prevent plaque complication. We diverted the use plaques. Monocytes can adopt a long-term pro-inflammatory
of these high-affinity ligands for PET imaging. We report here phenotype after brief exposure to atherogenic stimuli, which
the automated radiosynthesis of Lp-PLA2 [18F]-ligands. These has been termed trained immunity. In animal models, this occurs
radiotracers were tested in vivo and ex vivo. Materials and due to functional and metabolic reprogramming at the level of
Methods: Starting from two aryl-BPin precursors, alcohol- myeloid progenitors in the bone marrow. We recently reported
enhanced Cu-mediated 18F-fluorination was performed in a that circulating monocytes of patients with atherosclerosis
Tracerlab FXFN. [18F]KF was eluted from QMA cartridge with have a long-term pro-inflammatory phenotype associated with
KOTf/K2CO3 and dried with MeCN. Precursors, Cu(OTf )2 and an increased glycolytic metabolism. In this study, we explored
Pyridine were added to the reaction vessel in NMP/n-BuOH and whether innate immune reprogramming in patients with
heated at 110°C for 20 min. The radiotracers were isolated by atherosclerosis occurs in bone marrow progenitors. Materials
prep-HPLC and formulated in Saline/EtOH (5%). Quality controls and Methods: Patients with and without severe coronary
were realized prior mice injections. Stability studies were atherosclerosis (calcium score 400+ on CT-scan and total
performed in buffer and plasma. ApoE KO mice were chosen as plaque score 4+ on CCTA) underwent vene puncture, bone
atherosclerosis models and C57Bl/6 as control mice. 15±5MBq marrow aspiration and 18F-FDG PET-CT scanning. Cytokine
were injected intravenously in 3 ApoE KO and 3 C57Bl/6. PET production capacity was assessed after ex vivo stimulation of
imaging acquisitions were performed during 15 min after PBMCs from peripheral blood, and mononuclear cells (MNC’s)
injection. Heart and aorta were dissected, blood-flushed and from the bone marrow aspirate. In addition, cellular metabolism
imaged. Human atherosclerotic carotids samples were tested was assessed with Seahorse technology. With flow cytometry,
by incubating 30±5MBq of radiotracers at 37°C. After washing cells of the peripheral blood and bone marrow compartment
the samples with saline, PET acquisitions were carried out. All were characterised. Vascular wall inflammation and bone
the in vivo and ex vivo experiments were compared with [18F] marrow tissue activation were determined in specified regions
FDG. Results: Starting from 45GBq, two Lp-PLA2 [18F]-ligands of interests, and expressed as target to background ratios (TBR).
were obtained with an automation system yielding 99±0.5% Results: 13 Patients and 13 controls were included (60±10;
radiochemical purities and up to 270GBq/µmol. Stability studies 52±10 years, all men). Cytokine production capacity of PBMCs
have shown no degradation, confirming their suitability for mice and MNCs was higher in patients with atherosclerosis (e.g. LPS
injection. PET imaging with radiolabeled ligands has shown a TNFα, p-value less than 0.05). Similarly, oxygen consumption
strong accumulation in ApoE KO aortas that was not observed and extracellular acidification rates of MNCs was increased (max
with [18F]FDG. No accumulation was observed in C57Bl/6 aortas ECAR p-value less than 0.05), but no difference in circulating
either with Lp-PLA2 [18F]-ligands or with [18F]FDG. In carotid monocytes was observed. No significant changes in monocyte
endarterectomy samples, [18F]FDG displayed a weak signal only subsets or expression markers were observed. Vascular
S203 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

wall, splenic and bone marrow 18F-FDG uptake revealed p < 0.001; AscAo 2.56±0.11 vs 3.07±0.09, p = 0.001) whereas
no differences. Conclusion: Patients with severe coronary no significant differences were observed in the lean cohort
atherosclerosis, in addition to the circulating monocytes, the (ArchAo: 2.45±0.09 vs 2.56 ± 0.14, p = 0.55 and AscAo: 2.71±0.11
mononuclear cell fraction from the bone marrow also shows vs. 2.81±0.21, p = 0.70). Furthermore, in obese subjects, we
pro-inflammatory functional reprogramming. With regard to noticed strong negative correlations between BAT activation
underlying mechanisms, both oxygen consumption as well as parameters (volume, SUVmean) and arterial inflammation in
glycolysis are increased in these cells. This study confirms pro- ArchAo (volume R = -0.54, p = 0.02; SUVmean R = -0.53, p = 0.02)
atherogenic reprogramming of myeloid precursors in the bone and AscAo (volume R = -0.6, p = 0.01; SUVmean R = - 0.32, p =
marrow, which reveals a potential novel target for preventive n.s). Conclusion: There is a strong negative correlation between
pharmacotherapy in these patients. References: None. brown fat activity and arterial inflammation suggesting a
protective role of brown adipose tissue against atherosclerosis in
young, healthy subjects. This effect was particularly pronounced
OP-521 in obese subjects. References: None.
The Presence Of Brown Adipose Tissue Protects Against
Arterial Inflammation In Young Healthy Adults
O. Hedesan1,2, A. Gruber1,3, C. T. Herz2, M. E. Mayerhöfer4, F. Langer5, OP-522
G. Prager5, M. Hacker1, F. W. Kiefer2, A. R. Haug1,3; The birth of calcific plaques: the significance of focal
1
Department of Biomedical Imaging and Image-guided Therapy, 18F-NaF hot spot within the arterial walls, analyzed on
Division of Nuclear Medicine, Medical University of Vienna, Vienna, sequential PET/CT
AUSTRIA, 2Clinical Division of Endocrinology and Metabolism, F. Fiz1, C. Campi2, S. Morbelli3, A. Piccardo4, C. la Fougère1, M.
Department of Medicine III, Medical University of Vienna, Vienna, Piana5, G. Sambuceti3;
AUSTRIA, 3Christian Doppler Laboratory for Applied Metabolomics 1
Nuclear Medicine Unit, Department of Radiology, University
(CDL AM), Medical University of Vienna, Vienna, AUSTRIA, of Tübingen, Tübingen, GERMANY, 2Nuclear Medicine Unit,
4
Department of Biomedical Imaging and Image-guided Therapy, Department of Medicine, University of Padua, Padua, ITALY,
Division of General and Pediatric Radiology, Medical University of 3
Nuclear Medicine Unit, Department of Healt Sciences,
Vienna, Vienna, AUSTRIA, 5Division of General Surgery, Department University of Genoa, Genoa, ITALY, 4Nuclear Medicine Unit,
of Surgery, Medical University of Vienna, Vienna, AUSTRIA. Ente Ospedaliero Ospedali Galliera, Genoa, ITALY, 5Department
of Mathematics, University of Genoa, Genoa, ITALY.

Aim/Introduction: Energy dissipation through the promotion


of brown adipose tissue (BAT) has recently evolved as a Aim/Introduction: Vascular uptake of 18F-Natrium Fluoride
promising concept in the fight against obesity and metabolic (NaF) on PET/CT has been linked to active calcium deposition
disease. Upon activation, BAT combusts fatty acids and thus within arterial calcifications (AC). However, it is unclear whether
lowers plasma lipid levels protecting thereby against the focal NaF uptake in segments without evidence of calcification
development of atherosclerosis. Recent data have shown a can predict the future appearance of AC in the same area.In this
negative correlation between the presence of BAT and arterial study, we analyzed the density of the arterial wall in areas with
inflammation. Here, we aim to investigate the degree of arterial or without focal NaF uptake. Furthermore, we tested whether
inflammation in young, healthy adults undergoing a 18F-FDG an increase in mean density or the appearance of a visible
PET/CT study for the detection of BAT. Materials and Methods: calcification can be observed on a follow-up PET/CT Materials
: 94 healthy participants (age 30.1±0.8; 50 females, 44 males; and Methods: 55 patients (25 females, mean age 71±7 years)
38 lean and 56 obese) enrolled in a prospective imaging study were retrospectively enrolled. Each patient had undergone 2
underwent two consecutive 18F-FDG PET/CT examinations at consecutive NaF-PET for clinical reasons (spaced 18±11 months
thermoneutrality and after BAT activation using personalized apart). On each baseline PET, a VOI was created on all focal
cooling protocols. BAT was segmented according to BARCIST uptakes with no evidence of calcfications within the abdominal
criteria. Based on these criteria the participants were classified aorta wall, (hot-spot, HS1). A ROI with the same area was created
as BAT-positive (n = 42; 25 lean and 17 obese) and BAT-negative on a control segment of the aorta wall, with neither focal NaF
(n = 52; 13 lean and 39 obese). The arterial inflammation was uptake nor calcification (CS1). Both HS1 and CS1 were then
assessed in accordance with the EANM guidelines. Results: Lean copied on the corresponding position of the follow-up PET/
subjects showed lower aortic inflammation compared to obese, CT: these VOIs were labeled HS2 and CS2, respectively. Mean
both in the aortic arch (2.5±0.07 vs. 2.7±0.06, p = 0.04) but not and maxiumum Hounsfield density (HUmean and HUmax)
and in the ascending aorta (2.8±0.1 vs.2.9±0,08, p = 0.23). The as well as bloodpool-corrected SUV (target-to-background
presence of BAT was associated with significantly lower arterial ratio, TBR) were calculated in all VOIs; in case of appearance of
inflammation in the aortic arch (ArchAo) and in the ascending focal calcification in HS2, an Agastone-like calcium score was
aorta (AscAo) (BAT+ vs. BAT-: 2.40±0.07 vs. 2.81±0.06, p < 0.001 calculated with a dedicated software tool. Results: A total of
and 2.68±0.08 vs. 3.02±0.09, p = 0.003). In obese subjects, the 125 HS1 were identified; a focal calcification appeared on 54
differences in arterial inflammation between BAT+ and BAT- of HS2 (43,2%). In patients were new calcifications appeared,
were even more pronounced (ArchAo: 2.31±0.1 vs 2.88±0.07, interval between the first and the second PET/CT was 25±12
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S204

months. Baseline HS1 TBR correlated with the calcium score of in the bone marrow was higher in patients, which coincided
the AC within HS2 (R=0.7, p<0.01). HUmean and HUmax were with a higher monocyte-to-lymphocyte ratio. While circulating
higher in HS1 than in CS1 (48±8 Vs. 40±7, p<0.001; 122±53 inflammatory markers, ex vivo cytokine production, and the
and 88±17, p<0.01, respectively). HUmean increased from HS1 transcriptome of circulating monocytes were similar between
to HS2 (up to 61±14, p<0.01); conversely, no density variation patients and controls, macrophages from PA patients showed
could be described between CS1 and CS2. Conclusion: Focal significantly higher TNFA expression. Moreover, macrophages
NaF accurately describes the microscopic calcium deposition from healthy donors cultured in serum of PA patients showed
within the vessel wall: high-uptake areas have higher density increased pro-inflammatory cytokine production compared to
than the ones without visible uptake; moreover, mean density macrophages cultured in EHT serum. Conclusion: We show
tends to increase in focal uptake segments. Focal uptake can that patients with PA have a higher 18F-FDG uptake in the
predict the appearance of visible calcifications; however, a arterial wall than EHT controls. This associates with enhanced
longer observation period might be required to demonstrate hematopoietic activity in the bone marrow, changes of the
this phenomenon. References: None. peripheral blood cell composition and increased inflammatory
activity of monocyte-derived macrophages. These mechanisms
explain, at least in part, the increased CVD risk in patients with
OP-523 PA and reveal novel pharmacological targets. References: None.
Arterial Wall Inflammation, Increased Hematopoiesis
and Macrophage Activation in Patients with Primary
Aldosteronism OP-524
C. D. C. C. Van der Heijden1, E. M. M. Smeets1, E. H. J. G. Aarntzen1, Alterations of peripherial micorcirculation in Diabetes
M. P. Noz1, H. Monajemi2, S. Kersten1, C. Kaffa1, A. Hoischen1, J. mellitus and Obesity
Deinum1, L. A. B. Joosten1, M. G. Netea1, N. Riksen1; M. Miko1,2, J. Varga3, F. Nagy2, M. Emri3, M. Kaplar4, A. Forgacs2, I.
1
Radboud University Nijmegen Medical Center, Nijmegen, Garai2,2;
NETHERLANDS, 2Rijnstate Hospital, Arnhem, NETHERLANDS. 1
Deparment of Medical Imaging, University of Debrecen, Debrecen,
HUNGARY, 2Scanomed Ltd., Debrecen, HUNGARY, 3Division of
Nuclear Medicine and Translational Imaging, Medical Imaging
Aim/Introduction: Primary hyperaldosteronism (PA) is the Department, Faculty of Medicine, University of Debrecen,
most common form of secondary hypertension. Patients with Debrecen, HUNGARY, 4Department of Internal Medicine, Faculty
PA have a strongly increased risk of cardiovascular diseases of Medicine, University of Debrecen, Debrecen, HUNGARY.
(CVD), which is independent of blood pressure. Animal models
showed that aldosterone induces pro-inflammatory changes
in innate immune cells and accelerates atherosclerosis, but Aim/Introduction: The number of people with obesity and
human data are scarce. Here, we aimed to assess arterial wall diabetes is continously growing. These are important metabolic
inflammation, bone marrow activation, and innate immune drivers of cerebrovascular and cardiovascular diseases as well as
cell activation in patients with PA. Materials and Methods: peripheral neuropathy. Damage to the microcirculation is the
We performed 18F-FDG PET/CT imaging in 15 patients with PA basis for these conditions.In our study we investigated peripheral
and 15 matched controls with essential hypertension (EHT) perfusion in these two metabolic diseases and its correlation
after a 24h low carbohydrate diet and overnight fasting prior with laboratory parameters and neuropathy. Materials and
to infusion of 18F-FDG (2 MBq/kg) and 120 minutes incubation Methods: In this prospective study, 57 patients with controlled
time. 18F-FDG uptake was assessed in 8 regions of interest type 2 diabetes mellitus (T2DM) (mean age:52±9.6) and 46
(ROIs): carotid arteries, wall of the ascending, descending and patients with obesity (50.6±7.9) were recruited. BMI was
abdominal aorta, iliac arteries, bone marrow (L2-L3), spleen 34.1±5.9 in T2DM and 38.1±6.1 in the obese group. Quantitative
and liver. The maximal standardized uptake value (SUVmax), and Tc99m HMPAO (Mediradiopharma, Hungary) SPECT/CT
target-to-background-ratio (TBR) were assessed. The TBR was (AnyscanFlexSC, Mediso, Hungary) studies were performed
calculated from arterial SUVmax and background activity in the to assess peripheral microcirculation in the legs. Patients with
low-thoracic aortic blood pool. For the hematopoietic ROIs, TBR known symptomatic peripheral circulation abnormalities were
was calculated as the ratio of the splenic or bone marrow SUVmax excluded from the study. For the SUVmean calculation, fixed
and the mean background activity in the liver. We assessed sized spheric VOIs (volume of interest) were drawn in the calf
several circulating markers of inflammation in plasma and ex musculature bilaterally. Neurometer testing (NM-01/CPT) was
vivo cytokine production of peripheral blood mononuclear cells used for evaluating sub-clinical peripheral nerve dysfunction.
(PBMC) with ELISA. Furthermore, flow cytometry was used to For statistical analysis, Shapiro normality test, Wilcoxon test and
classify monocyte subsets. CD14posMACS-isolated monocytes paired Spearman correlation was done. Results: There were no
stored at baseline were processed for RNA sequencing. Results: significant differences of calculated SUVmean values in right and
18
F-FDG uptake was significantly higher in the carotid arteries, left legs in both groups, neither were there any in neurometer
descending and abdominal aorta, and iliac arteries of patients testing. However, leg perfusion was significantly lower in the
compared to controls; and 18F-FDG uptake correlated with diabetic group predominantly on the left side (p=0.015 right
aldosterone level in both cohorts. Moreover, 18F-FDG uptake leg, p=0,00065 left leg). Neurometer data showed correlation
S205 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

with HBA1C in the diabetic group, but none with leg perfusion. in 8/62, widespread inhomogeneous in 25/62 and widespread
There was no correlation between neurometer test results and homogeneous in 9/62 patients. In positive PET patients, mean
leg perfusion in the obese group. We also investigated the CRP value was 7.9 mg/L (range: 0.0-39.6), mean ESR value was
correlation of BMI, age and leg perfusion. BMI showed positive 21 mm/1h (range: 1-73), and mean PTX3 value (13/28 patients)
correlation with mean leg perfusion (rho=0,36, p=0,001) and no was 5.69 ng/ml (range: 2.16-15.70). In negative PET patients,
correlation with age was found. Conclusion: Quantitative leg median CRP was 9.0 mg/L (range: 0.3-65.5; p-value: 0.421), mean
perfusion SPECT/CT with Tc99m HMPAO is a sensitive method ESR value was 28 mm/1h (range: 2-78; p-value: 0.195), and
for evaluating subclinical perfusion abnormalities, providing mean PTX3 (18/34 patients) value was 7.74 ng/ml (range: 2.93-
complementary information for early assessment of peripheral 22.70; p-value: 0.132). Conclusion: PET/CT provide additional
neuropathy in diabetes. Further investigation is needed to information on functional characterization of the vascular lesions
understand the background of correlation of leg perfusion and in TA patients over disease activity measures, mainly based on
BMI. References: None. systemic inflammation. Further prospective study is necessary
to correlate FDG PET uptake with MRI enhancement in vascular
lesions, and to clarify the clinical relevance and the predictive
OP-525 value of this imaging approach for the disease progression and
FDG PET/CT Provides Additional Information on the best treatment strategy. References: None.
Characterization Vascular Lesions in Addition to Clinical
Assessment in Takayasu Arteritis Patients
E. Incerti1, F. Fallanca1, U. Pajoro1, E. Tombetti2, M. Papa3, G. OP-526
Ironi1,3, E. Baldissera4, P. Mapelli1,5, F. De Cobelli3,5, L. Gianolli1, A. A. Aorta Inflammation spatial heterogeneity in Erdheim-
Manfredi4,5, M. Picchio1,5; Chester Disease: 18F-Fluorodeoxyglucose Positron
1
Unit of Nuclear Medicine, IRCCS San Raffaele Scientific Emission Tomography-Computed Tomography
Institute, Milan, ITALY, 2Department of Biomedical and Clinical M. Nikpanah, F. Farhadi, M. Ahlman, B. R. Gochuico, W. A. Gahl, J. I.
Sciences, “L. Sacco” Hospital, Milan, ITALY, 3Unit of Radiology Estrada Veras, E. C. Jones, K. J. O’Brien, B. Saboury;
and Experimental Imaging Center, IRCCS San Raffaele Scientific National Institutes of Health, Bethesda,
Institute, Milan, ITALY, 4Unit of Internal Medicine and Clinical MD, UNITED STATES OF AMERICA.
Immunology, IRCCS San Raffaele Scientific Institute, Milan,
ITALY, 5Vita-Salute San Raffaele University, Milan, ITALY.
Aim/Introduction: To quantitatively investigate whether
vascular inflammation is uniform across the length of the aorta
Aim/Introduction: Takayasu arteritis (TA) is a rare in patients with Erdheim-Chester Disease (ECD). Materials and
granulomatous disease of unknown etiology, affecting the Methods: This retrospective study was performed on 11 ECD
aorta and its major branches. The first goal of therapy is prevent patients. FDG-18 PET/CT images acquired at presentation to our
progression of inflammation in vascular lesions. Disease activity institute were used for data analysis. For each patient, the aorta
evaluation defined according to National Institutes of Health was segmented from aortic valve to aortic bifurcation using
criteria is very important for therapeutic decision. The aim is 2mm slice thickness CT images. Binary masks were extracted and
to verify if activity PET and functional lesion characterization resized to 256x256 to fit dimensions of attenuation corrected
provide more additional information to clinical assessment in TA PET images for image multiplication. Pixel values were exported
patients. Materials and Methods: Sixty-two patients according and standardized using blood pool in vena cava as a measure
to American College of Rheumatology Criteria was recruited in for Target to Background Ratio (TBR), a previously published
this retrospective monocentric study at the IRCCS San Raffaele method1. Mean of pixel values in each slice standardized with
Hospital from April 2013 to April 2017 (56 women and 6 men; background was used to quantify aortic inflammation in each
mean age: 48 years, range: 18-81 years). All patients underwent slice. Aorta was divided into 4 anatomic locations (1. Ascending
FDG PET/CT and MRI examinations, with a median interval of 1 2. Thoracic 3. Supra-renal abdominal (diaphragm-renal artery);
month (range: 0-6 months). All vascular lesions was evaluated in and 4. Infra-renal abdominal (renal artery-bifurcation)). Repeated
PET/CT with both qualitative (positive/negative, visual scale 0-3, measures analysis of variance was used to investigate differences
uptake aspect), and semi-quantitative (maximum standardized in aortic inflammation among these 4 anatomic locations.
uptake value - SUVmax) methods. Correlation of PET evaluation Results: Median TBR (inter-quartile range) was 1.34 (1.11, 1.66),
versus serum biomarkers values as C-reactive protein (CRP), including 1.41 (1.04, 1.7), 1.32 (1.08, 1.62), 1.36 (1.16, 1.69), and
erythrocyte sedimentation rate (ESR) and pentraxin 3 (PTX3) 1.34 (1.11, 1.7) for ascending, thoracic, supra-renal, and infra-
was also performed. Results: PET was positive in 28/62 and renal aorta, respectively. Repeated-measure analysis of variance
negative in 34/62 patients, but all patients showed at least one showed differences (P < 0.001) in TBR values between 4 sections
vascular lesions at MRI. PET has detected 108 positive vascular of aorta. Conclusion: The extent of aortic inflammation in ECD
lesions with a median SUVmax value of 2.8 (range: 1.1-7.0). patients may vary across the length of the aorta, from the aortic
Visual scale analysis showed score 3.0 (> liver uptake) in 22/62, valve to the aortic bifurcation. References: Rudd, J. H., Myers, K.
2.0 (= liver uptake) in 7/62, 1.0 (< liver uptake) in 14/62, and 0 S., Bansilal, S., Machac, J., Woodward, M., Fuster, V., ... & Fayad, Z.
(no uptake) in 19/62 patients. Aspect of FDG uptake was focal A. (2009). Relationships among regional arterial inflammation,
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S206

calcification, risk factors, and biomarkers: a prospective NEC rate was 182.5 kcps (range, 168.5-199.5) and mean activity
fluorodeoxyglucose positron-emission tomography/computed concentration at which peak NEC was reached was 22.8 kBq/mL
tomography imaging study. Circulation: Cardiovascular Imaging, (range, 21.2-25.3). Mean scatter fraction was 41.1% (range, 39.9-
2(2), 107-115. 42.1), and mean maximum count loss below peak NEC was 3.4%
(range, 1.8-5.4). Hot sphere contrast ranged from 52.5% (range,
44.7-61.8) for the 10 mm sphere to 78.3% (range, 73.0-84.1) in
1110 the 22 mm sphere, and cold sphere contrast as measured in
the 37 mm sphere was 89.5% (range, 87.7-91.4). Conclusion:
Do.MoRe - Parallel Session: Performance, Variability in NEMA NU 2-2012 measurements was highest for
Standardisation & Quality Control the count loss measurement (coefficient of variation 28%) and
lowest in the spatial resolution measurement at 10 cm in radial
Tuesday, October 15, 2019, 8:00 - 9:30 Lecture Hall 116 direction (1.2%). Variability in sensitivity values was 4.3%. Further
measurements will be conducted to assess to what extend
these variations can be attributed to experimental uncertainty
rather than true variations between scanners. References: 1.
OP-527 Hsu et al, J Nucl Med 2017.
Variability in NEMA NU 2-2012 performance
measurements of all sixteen Discovery MI digital time-of-
flight PET-CT systems in the Nordic countries OP-528
M. Lubberink1,2, E. Ilan1,2, A. Moreno2, J. Oddstig3, S. Leide Harmonisation of PET/CT Performance for Brain Studies
Svegborn4, P. Braad5, M. Nowak Lonsdale6, T. Hjørnevik7, L. Gyland E. E. Verwer1, S. V. S. Golla1, A. Kaalep2, M. Lubberink3, F. H. P. van
Mikalsen7, V. Gjervan8, T. Tolvanen9, O. Sipilä10, C. Hindorf3, E. Velden4, V. Bettinardi5, M. M. Yaqub1, T. Sera6, S. Rijnsdorp7, A. A.
Trägårdh4; Lammertsma1, R. Boellaard1;
1
Uppsala University, Uppsala, SWEDEN, 2Uppsala University 1
Amsterdam University Medical Centers, location VUmc,
Hospital, Uppsala, SWEDEN, 3Skåne University Hospital, Amsterdam, NETHERLANDS, 2North Estonia Medical Center
Lund, SWEDEN, 4Skåne University Hospital, Malmö, SWEDEN, Foundation, Tallinn, ESTONIA, 3Uppsala University hospital,
5
Odense University Hospital, Odense, DENMARK, 6Bispebjerg Uppsala, SWEDEN, 4Leiden University Medical Center, Leiden,
Hospital, Copenhagen, DENMARK, 7Oslo University NETHERLANDS, 5IRCCS Scientific Institute San Raffaele,
Hospital, Oslo, NORWAY, 8Østfold Hospital Kalnes, Grålum, Milan, ITALY, 6EANM Research Limited (EARL), Vienna,
NORWAY, 9Turku University Hospital, Turku, FINLAND, AUSTRIA, 7BovenIJ hospital, Amsterdam, NETHERLANDS.
10
Helsinki University Hospital, Helsinki, FINLAND.

Aim/Introduction: For clinical brain PET studies, performed


Aim/Introduction: Sixteen 4-ring Discovery MI PET-CT within multi-center or longitudinal settings, harmonisation
scanners (GE Healthcare; 1) were installed in the Nordic of image quality and quantification is imperative. Given the
countries (Sweden, Denmark, Norway and Finland) during different characteristics of brain PET versus oncology PET,
the last two years. During all installations the manufacturer’s current EARL criteria may be inadequate. In this study, prototype
clinical specialist, in collaboration with a local medical physicist, standards specific for brain PET harmonisation were developed.
performed the acceptance testing. This presented a unique Materials and Methods: A Hoffman 3D Brain Phantom,
possibility to address inter-scanner variability of test results with modelling a human brain with grey matter (GM) recovery
minimal influence of experimenter variation and variation in coefficient (RC) of 1 and white matter (WM) RC of 0.25, filled
local customs and workflows. The aim of the present work was to with ~35 kBq∙mL-1 [18F]FDG, was scanned on 12 clinical PET/CT
assess the variability between NEMA performance results across systems (4 GE, 4 Philips, 4 Siemens, including a digital system
scanners. Materials and Methods: NEMA NU 2-2012 tests for of each vendor). Data were reconstructed into 30 min frames
spatial resolution, sensitivity, count rate performance and scatter using various reconstruction protocols: with/without resolution
fraction, and image quality of 16 4-ring Discovery MI PET-CT modelling (PSFon/PSFoff ), time-of-flight and vendor specific
scanners, installed between September 2016 and September settings. The resulting 81 images were co-registered to a PET
2018, were included. This scanner contains 36 rings of 3.95 x 5.3 image template (voxel size 1.17x1.17x2.00 mm3) containing
x 25 mm LYSO detectors coupled to silicone photomultipliers in volumes of interest (VOI) for deriving various metrics, e.g. total
a block detector configuration (4x9 LYSO crystals to 3x6 SiPMs). phantom activity, RCGM, RCWM, RCmid-phantom-cold-spot, GM/WM ratio
Detector ring diameter is 74.4 cm and transaxial and axial field (GMWMr) and left/right hemisphere activity ratio (LRr). To
of view (FOV) are 70 and 20 cm, respectively. Results: Spatial address inaccuracies in calibration and activity measurements,
resolution (mean of all directions) using OSEM (without time of RC were calculated based on both injected activity and
flight and resolution recovery) was 3.9 mm (range, 3.8-4.1) at 1 image derived total phantom activity. Harmonisation criteria
cm, 4.3 mm (range, 4.2-4.5) at 10 cm, and 5.4 mm (range, 5.2-5.6) were defined such that for each PET/CT system at least one
at 20 cm from the centre of the FOV. The mean sensitivity of reconstructed image complied. Results: Bias and its variability
all scanners was 13.6 cps/kBq (range, 12.7 to 14.8). Mean peak among systems were smaller for image based RC than injected
S207 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

activity based RC (0.97±0.03 vs 0.92±0.04). Notable differences sphere-shaped volumes of interests with the same diameter as
were observed between PSFON and PSFOFF: RCGM=0.98±0.02, the hot spheres. Images of hot and cold rods were inspected
0.95±0.03; GMWMr=4.05±0.22, 3.63±0.26; RCmid-phantom-cold- visually to assess spatial resolution. Coefficient of Variations
spot
=0.030±0.011, 0.043±0.013; Vendor specific differences were (CoV) were measured in the uniform background of the Jaszczak
found for all metrics. Based on these results, RCGM for both Phantom. Results: For the Vision (4 iterations, 5 subsets, 2 mm
PSFON and PSFOFF were defined as harmonisation standards. Gauss filter, voxel size 1.65x1.65x1.65mm3) and MI-5 (3 iterations,
Minimum RCGM bandwidths, ensuring at least one compliant 16 subsets, 2 mm Gauss filter, voxel size 1.82x1.82x2.80mm3) the
scan per system, were PSFON-RCGM=[0.95-1.00] leading to PSFON- RC ranges were respectively: (NEMA) RCmean 0.61-0.88, RCmax
GMWMr=[3.73-4.67], PSFON-LRrGM=[0.94-1.03], PSFON-RCmid-phantom- 1.04-1.46 vs RCmean 0.59-0.88 and RCmax 1.11-1.47; (Jaszczak)
cold-spot
=[0.020-0.065]; and PSFOFF-RCGM=[0.87-0.98], leading to RCmean 0.30-0.67, RCmax 0.32-1.42 vs RCmean 0.35-0.63 and
PSFOFF-GMWMr=[3.25-4.67], PSFOFF-LRrGM=[0.94-1.03], PSFOFF- RCmax 0.42-1.16; (Wall-less gel phantom): RCmean 0.07-0.65
RCmid-phantom-cold-spot=[0.020-0.071]. In addition, each image was and RCmax 0.09-1.09 vs RCmean 0.06-0.63 and RCmax 0.08-1.21.
compared with an average reference image, derived from one In both images, 6.6 mm hot rods and 4.8 mm cold rods could
scan per system with RCGM nearest to the mid-bandwidth value. be separated. CoV were 7.8% vs 9.3%. Conclusion: The scanners
An upper limit to the root mean squared difference over all can produce similar SUV recoveries as function of sphere
brain region voxels (RMSD) <0.08 compared with the average size with CoV well below the commonly accepted 15% level.
reference image was found to further harmonise image quality. Preliminary results indicate that Vision produced slightly higher
Conclusion: A combination of an RCGM bandwidth of [0.95-1.00] RCmean with lower CoV. More sets reconstruction parameters
for PSFON and [0.87-0.98] for PSFOFF with RMSD<0.08 was found will be explored including using continuous bed motion scans
to identify scans of comparable image quality. RCmid-phantom-cold- (Vision) and Q.Clear image reconstruction (MI-5). References:
spot
showed SD>35%, which may preclude the use of a low None.
uptake reference region. These prototype standards can now
be tested prospectively to validate and/or refine the underlying
harmonisation criteria. References: None. OP-530
Quality Control of PET/MRI systems: Consensus
Recommendations from a European Network of Hybrid
OP-529 Imaging Sites (HYBRID)
Imaging performance of Siemens Vision 600 and GE A. Valladares1, S. Ahangari2, T. Beyer1, R. Boellaard3, Z.
Discovery MI-5 evaluated on phantoms with focus on Chalampalakis4, C. Comtat4, L. DalToso5, A. E. Hansen2, M. Koole6, J.
detection and quantification of sub-centimeter lesions Mackewn5, P. Marsden5, J. Nuyts6, S. Poth7, E. Solari8, I. Rausch1;
O. L. Munk, L. P. Tolbod; 1
Medical University of Vienna, Vienna, AUSTRIA, 2Department of
Aarhus University Hospital, Aarhus, DENMARK. Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet,
University of Copenhagen, Copenhagen, DENMARK, 3Department
of Radiology and Nuclear Medicine, VU University Medical
Aim/Introduction: Our aims were: 1) to evaluate imaging Centre, Amsterdam, NETHERLANDS, 4Service Hospitalier
performance of the new Siemens Vision 600 (Vision) and GE Frédéric Joliot, IMIV, CEA, INSERM, CNRS, Univ. Paris-Sud,
Discovery MI-5 (MI-5) ’digital’ PET/CT systems; 2) to optimize Orsay, FRANCE, 5King’s College London & Guy’s and St
image reconstruction parameters for clinical scans with focus Thomas’ PET Centre, School of Biomedical Engineering and
on detection of small lesions and quantification of their tracer Imaging Sciences, King’s College London, London, UNITED
uptake; and 3) to evaluate recovery coefficients (RCs) using KINGDOM, 6Nuclear Medicine and Molecular Imaging,
different reconstruction settings to harmonize image quality University Hospitals Leuven and KU Leuven, Leuven, BELGIUM,
from the two scanners. Materials and Methods: Four phantoms 7
Department of Nuclear Medicine, University Hospital
were filled with 18FDG in the 4:1 activity concentration ratio Tuebingen, Tuebinguen, GERMANY, 8Department of Nuclear
recommended in the NEMA NU2-2018 standard. (1) NEMA Image Medicine, Technical University of Munich, Munich, GERMANY.
Quality Phantom with 6 hot spheres with inner diameter range
(IDR) 10-37 mm; (2) Jaszczak SPECT Phantom with 6 hot spheres
IDR 4-12 mm and a hot rod insert IDR 4.8-12.7 mm; (3) custom- Aim/Introduction: Dual-modality PET/MR imaging provides
made wall-less gel phantom with 12 hot spheres IDR 3-12 mm information valuable for patient management and, moreover,
in a cold background; and (4) Mini Deluxe SPECT phantom for novel applications of radiomics and machine learning.
with cold rods IDR 1.2-4.8 mm. The four phantoms were first The highest quality of PET/MR image data is required to fuel
scanned on MI-5 and then on Vision. We scanned with full bed- subsequent single site and multi-centre data pooling and
overlap to have uniform counting statistics and reconstructed analysis. This contribution aims at developing a consensus on
images corresponding to 1.5 minute per bedposition. The time the minimum level of QC required for routine PET/MRI as seen
per bedposition was prolonged on the Vision to adjust for by a consortium of experienced hybrid imaging sites. Materials
radioactive decay. Images reconstructed using clinically relevant and Methods: The HYBRID consortium is an innovative training
sets of reconstruction parameters were evaluated using PMOD network funded by the European Commission (MSCA #764458)
4.0. For all spheres, RCmean and RCmax were measured inside involving 23 partner organizations including eight imaging sites
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S208

highly experienced in clinical PET/MRI as well as three vendors whole-body oncological PET/CT studies of the same model of
of PET/MRI systems. All PET/MRI centres within HYBRID were NEMA/IEC image quality phantom. In the standard approach
surveyed to collect information about local QC tests and testing the phantom background and spheres were filled with a 18F
frequencies for the PET/MRI systems. The survey was based on solution by local imaging experts. In the other approach the
QC tests for the PET and MR imaging systems by international phantom’s background and the six spheres were all pre-filled
guidelines and recommendations. These tests include, for with a 68Ge epoxy. All the images were analysed by Cuneo
example, image uniformity, normalization, image quality for the CoreLab. Background activity concentration (BAC) was defined
PET component, and central frequency, coil check, geometry as the difference between the average activity concentration
accuracy for the MRI modality. Survey responses and information in a large homogenous region and the expected activity
provided by the vendors about implemented QC measures concentration. Sphere to background ratio (SBR) was defined as
as well as existing recommendations on QC for PET and MRI, the ratio between the maximum of the activity concentration in
served as the basis for discussions to reach a consensus on QC the largest 37 mm diameter sphere and the BAC. Inter-scanner
procedures for PET/MRI. Results: The survey revealed that all variability (ISV) was estimated as the 95% confidence level of
sites perform the PET daily QC test implemented by the vendor; BAC and SBR. The 18F phantom was used in IELSG, GELTAMO
however, significant variations were noted for other routine PET and FIL-1 (first phase) clinical trials while the 68Ge phantom was
QC tests and testing frequencies. Furthermore, higher variability used in SAKK and FIL-2 (second phase). Results: 122/151(81%)
of QC measures between the centres was reported for the MRI PET/CT scanners fulfilled the CTQ with the first procedure. CTQ
component. Based on the survey results as well as existing was reached at the first round in 38% of the cases, while in 32%,
recommendations by professional imaging associations, a 12% and 18%, two, three or more than three iterations, were
consensus on QC measures for PET/MRI was reached; it includes required, respectively. The ISV were 21.4%, 51.6% and 56.9%
the daily QC as implemented by the vendor, a quarterly cross- for BACUQP, BACIQ and SBR respectively. 34/34(100%) PET/
calibration measurement also including the assessment of CT scanners fulfilled the CTQ with the second procedure. The
uniformity and a yearly IQ test for the PET component of the CTQ was reached at the first round in 82% of the cases, while
systems. For the MRI component, the consensus includes regular in 15%, 0% and 3%, two, three or more than three iterations,
coil checks and a quarterly MR IQ test including the assessment were required, respectively The ISV were 22.7%, 21.4% for BACIQ
of signal-to-noise ratios and artefacts. Conclusion: Significant and SBR. Iteration to reach CTQ was defined as an interaction
variations in currently implemented QC measures for PET/MRI between the Cuneo CoreLab and the local personnel regarding
are seen between PET/MRI centres. Therefore, we propose a the data, phantom preparation, infrastructural problems.
set of QC measures to ensure the proper function of the PET/ Conclusion: 68Ge approach permits to achieve a lower inter-
MRI system as a consensus recommendation for PET/MRI QC in scanner variability respect to 18F one. Indeed, ISV of both BAC
the HYBRID consortium. (This work has received funding from and SBR are reduced of 2-3 times. This is mostly due to the
the European Union’s Horizon 2020 research and innovation difficulty in phantom preparation (in particular in sphere filling)
programme under the MSCA No. 764458.) References: None. for 18F phantom. Moreover, the number of iterations required to
achieve the clinical trial qualification is much lower. References:
None.
OP-531
Clinical trial qualification of PET-CT scanners in onco-
haematological clinical trials performed with 68Ge pre- OP-532
filled phantom permits to achieve a lower inter-scanner Low dose CT for attenuation correction in PET. Validation
variability respect to standard 18F phantoms of quantification for different patient sizes
F. Bergesio1, A. De Maggi1, F. Dalmasso1, M. Coronado2, L. Ceriani3, A. Törnblom1,2, J. Siikanen1, D. Thor1, M. Bolin1;
L. Guerra4, S. Chauvie1; 1
Karolinska University Hospital, Department of Medical
1
Medical Physics Unit, S. Croce e Carle Hospital, Cuneo, ITALY, Radiation and Nuclear Medicin, Stockholm, SWEDEN,
2
Nuclear Medicine Department,La Paz University Hospital, 2
Stockholm University Fysikum, Department of
Madrid, SPAIN, 3Nuclear Medicine Department, Oncology Institute Medical Radition Physics, Stockholm, SWEDEN.
of Southern Switzerland, Bellinzona, SWITZERLAND, 4Nuclear
Medicine Department, S. Gerardo Hospital, Monza, ITALY.
Aim/Introduction: Despite the relatively low dose generated
by Attenuation Correction CT (ACCT) (0.5 mSv - 1 mSv) in
Aim/Introduction: The aim of this study was to compare PET examinations, the ALARA principle is still applicable. The
the Clinical Trial Qualification (CTQ) adopted by the Italian currently used ACCT standard protocol in our clinic uses 7.6
Foundation on Lymphoma (FIL), the Grupo Espanol de effective mAs (eff-mAs) and 120 kVp, but reducing eff-mAs and/
Linfomas/Transplante Autologo de Medula Osea (GELTAMO), the or kVp would decrease patient dose and facilitate an increased
International Extranodal Lymphoma Study Group (IELSG) and number of research subjects. A CT reconstruction algorithm
the SwissGroup for Clinical Cancer Research (SAKK). Materials called Quantification Achieved Consistently (Q.AC.) (Lonn, 2012)
and Methods: The CTQ process consisted in the scanning with has recently been developed to enable reduced doses from
the default acquisition and reconstruction parameters used for ACCT, while preserving quantitative PET data. The purposes of
S209 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

this study were to investigate possible limitations of the Q.AC. reconstructed with iterative OSEM3D reconstruction with point-
with respect to patient size, and to optimise protocols, aiming spread-function and time-of-flight (OSEM3D+PSF+ToF). Some
at minimising ACCT dose in terms of CTDIvol. Materials and patients underwent a longer scantime/bed to compensate for
Methods: Measurements were performed with a GE PET/CT radioactive decay during schedule delays. The mean and standard
Discovery system, which offers Q.AC. reconstruction. The NEMA deviation (SD) for a volume of interest in a homogeneous part of
NU-2 protocol was followed to quantify PET quality, including the liver were determined and the signal-to-noise ratio (SNR =
evaluations of background variability (N), hot- and cold-sphere Mean/SD) was used as a measure for image quality. Corrections
contrast (Q) and relative count error in the artificial lung in the were performed for scantime: SNRL=SNR/√(time) as well as scan
phantom centre (DClung).Two phantoms were used; the NEMA time and activity: SNRnorm=SNR/√(A*time). A linear regression
body phantom (30 cm laterally/23 cm anterior posterior), here between SNR (and SNRL) and BM was performed to test whether
representing paediatric patients and small-sized adults, and the image quality varied with BM. p<0.05 was considered significant.
same phantom with an additional (20 cm laterally/4 cm anterior SNRnorm was fitted with a power function: SNRfit=a*BM-b. Note
posterior) ellipsoid plastic (PMMA) extension ring, representing that image quality would become independent of BM, if A*time
mid- and large-sized patients. ACCTs were acquired with 15 scales as BM2b. Results: Where BM of children and adults
eff-mAs values, range [2.3 - 260], in combination with four kVp overlapped, SNR, SNRL and SNRnorm values were consistent
values [80, 100, 120, 140] and reconstructed with two algorithms with literature. SNR slightly, but significantly, decreases with
(Q.AC. and a regular soft CT algorithm). PET reconstructions were body mass: SNR=8.8-0.034*BM (p=0.022). However, SNRL does
performed based on each eff-mAs, kVp and CT-reconstruction not: SNRL=5.5-0.010*BM (p=0.22). The optimal fit was found to
combination. Results: Quantitatively similar results to the be SNRfit=3.2*BM-0.52. Conclusion: Contrary to adult FDG-PET/
standard protocol were achieved with the Q.AC. using (2.3 eff- CT[1], the results of this pilot study indicate that in pediatrics
mAs and 80 kVp) for the NEMA body phantom, respectively image quality is constant for a linear relationship between BM
(2.3 eff-mAs and 120 kVp) for the phantom with additional and administered FDG dose. Accordingly, the EANM guidelines
extension ring. Accordingly, the CTDIvol may be reduced to 1/10 for pediatric FDG-PET/CT seem accurate. It should be noted that
of that for the standard protocol for paediatric patients and this is a preliminary study that includes only twenty patients and
small-sized adults, respectively to 1/3 for mid- and large-sized it should be further investigated with a larger group to confirm
patients. Conclusion: This study indicates that the Q.AC. CT these initial findings. References: [1]. de Groot et al. Optimized
reconstruction algorithm enables accurate PET results at lower dose regimen for whole-body FDG-PET imaging. EJNMMI Res.
ACCT eff-mAs and kVp settings than the currently used clinical 2013;3:63. [2]. Amthauer et al. Guidelines for 18F-FDG PET and
standard protocol. For paediatric patients and small-sized PET-CT imaging in paediatric oncology. Eur J Nucl Med Mol
adults, a reduction of CTDIvol by approximately 90% may be Imaging. 2008;35:1581-8.
achieved, while for mid- and large-sized patients, the CTDIvol can
be reduced by approximately 70% without loss of quantitative
PET data. References: None. OP-534
Optimization of Yttrium-90 PET/CT Acquisition Time on a
SiPM-PET/CT during Selective Internal Radiation Therapy
OP-533 J. Labour1,2, A. Martin1, P. Boissard1, T. Baudier1, P. Veyrat Durebex1,
Dose optimization for pediatric FDG whole body PET/CT D. Delliage1, D. Sarrut1,2, J. N. Badel1;
M. van Gent, V. C. Hamming, J. E. Schaar, A. W. J. M. Glaudemans, 1
Centre Léon Bérard, Lyon, FRANCE, 2CREATIS, Lyon, FRANCE.
A. T. M. Willemsen;
University of Groningen, University Medical Center
Groningen, Groningen, NETHERLANDS. Aim/Introduction: We investigated the impact of acquisition
time on the quantification of Yttrium-90 PET images acquired
with a SiPM-based PET/CT for post-selective internal radiation
Aim/Introduction: It was shown by De Groot et al.[1] that therapy (SIRT). The aim is to reduce acquisition time without
a quadratic relationship between body mass (BM) and compromising the image quality and quantification accuracy[1].
administered FDG dose (A) is required to ensure a constant The work presents preliminary results towards achieving a
image quality of FDG-PET/CT in adult patients (≥18 years). standard protocol for post-SIRT PET imaging[2]. Materials and
However, the EANM guidelines for pediatric FDG-PET/CT Methods: List-mode data for 6 patients who underwent PET/
prescribe a nearly linear relationship between BM and dose[2]. CT imaging after SIRT was gathered. Data for each patient were
The aim of this pilot study was to investigate whether a linear analyzed regarding 90Y uptake in several regions of interest (ROI)
BM and dose relationship results in constant image quality in defined as: the total liver drawn on the CT image, three perfused
pediatric FDG-PET/CT scans. Materials and Methods: Twenty regions obtained from PET thresholding at 10, 20 and 40 % of the
whole body FDG-PET/CT scans of patients (median age 9.5 maximum value, non-perfused regions defined as the total liver
years, range 0 to 18 years) were included. Scans were acquired minus each respective threshold-based perfused ROI. Thanks to
on either a Siemens Biograph mCT40 (n=7) or mCT64 (n=13) the list-mode data, reconstructions were performed at different
between November 2017 and February 2019 using the standard time intervals ranging from 1 to 15 minutes for 1 bed position.
local protocol i.e. 3 MBq/kg FDG, 2 min/bed position and Images were reconstructed with pixels of 2mm using OSEM
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S210

iterative algorithm with 15 updates (3 subsets, 5 iterations), 1301


time of flight and point spread function modeling. A post- CME 10 - Neuroimaging Committee / EAN:
reconstruction Gaussian filter of 2mm full width at half maximum EANM-EAN Recommendations for the Use
(FWHM) was used in all reconstructions. The aim of 90Y-PET is of Brain 18 F-FDG-PET in Neurodegenerative
to quantitatively estimate the absorbed dose delivered to the Cognitive Impairment and Dementia
perfused region. Therefore, voxel-level quantitative information
for each ROI was assessed, including the total number of Tuesday, October 15, 2019, 11:30 - 13:00
Auditorium
counts and the mean of the activity concentration (Bq/mL)
for each ROI. The noise present in the images were evaluated
as the standard deviation on the mean activity concentration
for each patient. The relative percentage differences of each OP-538
reconstructed image according to the reference 15 minutes Assessing FDG-PET Diagnostic Accuracy Studies to
acquisition were computed. Results: For each patient, 9 min Develop Recommendations for Clinical Use in Dementia
acquisition was found to be necessary to obtain less than 10% F. Nobili;
difference in the mean activity concentration with 15 min University of Genoa and Polyclinic San Martino Hospital,
acquisition.This percentage falls below 5% when 11 minutes Department of Neuroscience (DINOGMI), Genoa, ITALY.
acquisition was used. Below 9 min, large differences appears
(up to 20% for 7 min acquisition). Down to 11 min, the relative
percentage difference on standard deviation stays below OP-539
5%. Conclusion: Image acquisition duration can be reduced Clinical Utility of FDG-PET for the Differential Diagnosis
by up to 40% if a 10% difference with the reference image is Among the Main Forms of Dementia
tolerated, improving patient comfort during scan. References: J. Arbizu;
[1]Zhang et al. “Feasibility of accelerating Yttrium-90 PET by University of Navarra, Clinica Universidad de Navarra,
Optimizing PET Volume Overlap”, J Nucl Med, 57:1425-2016 [2] Department of Nuclear Medicine, Pamplona, SPAIN.
Wright et al. “Theranostic Imaging of Yttrium-90”, BioMed Res Int,
2015:481279-2015.
OP-540
Clinical Utility of FDG-PET in Parkinson’s Disease and
1201/1204 Atypical Parkinsonism Associated with Dementia
S. Morbelli;
Plenary 3: Next Generation PET Technology in San Martino Hospital, Nuclear Medicine, Genoa, ITALY.
the Clinical Setting

Tuesday, October 15, 2019, 10:00 - 11:15 Auditorium 1302


Joint Symposium 19 - Oncology & Theranostics
Committee / EHA: PET/CT Guided Treatment in
OP-535
Non-Hodgkin Lymphoma
Cardiovascular Molecular Imaging Beyond Perfusion -
Ready for Prime Time? Tuesday, October 15, 2019, 11:30 - 13:00 Lecture Hall 311
F. Hyafil;
Department of Nuclear Medicine, Bichat
University Hospital, Paris, FRANCE. OP-541
Response Assessment - The Haematologist’s Perspective
J. Zijlstra;
OP-536 Amsterdam UMC, Afdeling Hematologie,
Cardiac PET/MRI Amsterdam, NETHERLANDS.
C. Rischpler
University Hospital Essen, Essen, GERMANY.
OP-542
Staging - The Radiotherapist’s Perspective
OP-537 G. Mikhaeel;
DAT Markers - Should PET replace SPECT? Guy’s Cancer Centre, Department of Clinical
A. Varrone; Oncology, London, UNITED KINGDOM.
Karolinska Institutet, Department of Clinical
Neuroscience, Stockholm, SWEDEN.
S211 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

OP-543 Aim/Introduction: The field of nuclear medicine has changed


Impact of Metabolic Tumour Volume and expanded rapidly since its inception in the mid-20th century.
A. Segolène Cottereau; A surge of new radiopharmaceuticals and increased demand
Cochin Hospital, Department of Nuclear Medicine, Paris, FRANCE. for nuclear medicine procedures, particularly in the United
States, has led to a growing interest in occupational radiation
exposure doses and associated health risks to nuclear medicine
1303 technologists. However, data on this topic have been extremely
limited. Materials and Methods: We evaluated trends in work
Joint Symposium 20 - Thyroid Committee / history practices and badge doses and assessed radiation-
ETA-CG / EFSUMB: Thyroid Cancer Imaging and related risks in a large cohort of more than 110,000 radiologic
Biomarkers technologists, the U.S. Radiologic Technologists (USRT) study.
Results: In the USRT cohort, technologists who reported
Tuesday, October 15, 2019, 11:30 - 13:00 Lecture Hall 312 ever working with nuclear medicine procedures (n=22,039
in 1994-1998) had modest but significant elevated risks of all-
cause and all-cancer mortality, myocardial infarction incidence,
incidence of squamous cell carcinoma of the skin, mortality
OP-544 from cancers of the breast and lung, and cataracts during the
Molecular Biomarkers follow-up period. Among 4,406 technologists who completed
C. Colombo; a detailed nuclear medicine work history survey in 2013-14, the
Università di Milano, Milan, ITALY. reported weekly frequency of performing diagnostic nuclear
medicine procedures, particularly cardiac and positron emission
tomography (PET), increased over calendar time, while the
OP-545 frequency of performing therapeutic procedures remained
Ultrasound and Cross-Sectional Radiology stable. Trends in annual badge doses through 2015 mirrored
M. Radzina; these practice patterns, with consistently higher doses to
Pauls Stradins Clinical University Hospital, Institute of technologists performing cardiac and PET scans versus those
Diagnostic Radiology, Department, Riga, LATVIA. performing general nuclear medicine and, to a much greater
extent, general radiologic procedures, particularly within the
last two decades. Estimation of organ-specific occupational
OP-546 radiation doses for individual technologists (in progress)
Molecular Imaging and Circulating Biomarkers will allow for comprehensive retrospective and prospective
L. Giovanella; investigations of radiogenic cancer and other disease risks. We
Imaging Institute of Southern Switzerland, Clinic for also recently conducted a pilot study evaluating work history
Nuclear Medicine, Bellinzona, SWITZERLAND. practices and dosimeter readings for an independent sample
of U.S. technologists first certified in nuclear medicine in 1980
or later. Doses were slightly higher than the USRT sample but
1304 still well below established occupational limits (median: 1.4 to
3.3 mSv/year since 1992); like the USRT, doses were increasingly
Technologists: Oral Presentations 3 variable over time and higher doses were associated with PET
versus general nuclear medicine. Conclusion: Our results
Tuesday, October 15, 2019, 11:30 - 13:00 Lecture Hall 117 suggest that nuclear medicine technologists may be among
the most highly-exposed medical radiation worker populations
in the United States currently, and that these higher doses may
OP-547 be related to increased radiation-related risks. These findings
Long-term trends in occupational radiation exposure and may inform radiation protection and dose monitoring efforts in
associated health risks among technologists performing nuclear medicine departments. References: None.
nuclear medicine procedures: new findings and future
research directions
C. Kitahara1, M. Bernier2, M. Van Dyke3, C. Yoder4, M. Doody1, S.
Simon1, M. Linet1, B. Alexander5, D. Villoing1; OP-548
1
National Cancer Institute, Rockville, MD, UNITED STATES 177Lu peptide receptor radionuclide therapy, availability,
OF AMERICA, 2Institute for Radiological Protection and radioprotection, cost: comparison of two administration
Nuclear Safety, Laboratory of Epidemiology, Fontenay- methods
aux-Roses Cedex, FRANCE, 3Emory University, Atlanta, GA, F. Herbaut1, S. Boukhlef1, N. Lheureux2, J. Legrand1, B. Dekyndt1;
UNITED STATES OF AMERICA, 4Independent consultant, 1
CHRU Lille, Lille, FRANCE, 2CHU Amiens, Amiens, FRANCE.
Weddington, NC, UNITED STATES OF AMERICA, 5University of
Minnesota, Minneapolis, MN, UNITED STATES OF AMERICA.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S212

Aim/Introduction: Lutathera® (177Lu peptide receptor radiopharmaceutical Lutathera, which is manufactured by


radionuclide therapy) indication is the treatment of somatostatin Advanced Accelerator Applications. In addition, Radiomedix,
receptor-positive gastroenteropancreatic neuroendocrine is manufacturing Lutetium-177-PSMA to treat patients with
tumors (GEP-NETs) inoperable or metastatic. The summary of metastatic prostate cancer as part of a phase III clinical trial
the product characteristics references an administration method which is run by Endocyte. Each company uses a different
consisting in gravity method from its original vial, which requires process to manufacture the Lutetium, one of which adds a
no preparation step. Since 2017, for almost 100 infusions, this small amount of metastable Lutetium-177 which has a 160.4
one hasn’t been adopted in the Lille University Hospital for the day half-life. Without the metastable component, Lutetium-177
respect of infusion’s good practices. So, a syringe infusion pump has a 6.65 day half-life. The difference in manufacturing
(SIP) has been set-up, which leads to a preparation constraint methods may lead to differences in handling and disposing of
(transfer to a 50 mL syringe). A “reference-like method” is used in the radioactive material. The purpose here is to share a single
the Amiens Hospital Center, which requires a thorough rinsing institution’s experience, OHSU, with Lutetium-177 from different
corresponding to 10 times the vial volume. The aim of this manufacturers. Materials and Methods: After administration
study is to compare the two administration methods with: the of the radionuclide therapy, any radioactive waste is stored in
percentage of administrated activity, the staff hand dosimetry a secure area to decay in storage. With a half-life of 6.65 days,
and devices costs. Materials and Methods: Respectively 20 our process is to check for any residual activity at approximately
and 11 Lutathéra®‘s preparations have been studied for Lille and 65 days or 10 half-lives. After this decay period, we compared
Amiens. The initial vial, syringe and residual devices activities residual activity in multiple vials between manufacturer’s which
have been measured with a dose calibrator and expressed had the same calibration date or were within one or two days
in percentage of total vial activity. Staff hand dosimetry is of each other. For this comparison, we measured the vial in
estimated on 3 preparation procedures for both administration a dose calibrator and also withdrew 1cc from each vial and
methods. In the Lille Center, the dosimetry has been calculated measured the counts per minute using a Perkin Elmer Wizard
thanks to dose rate measured. In Amiens center, the dosimetry well counter. Results: When comparing waste from each
has been measured on three fingers with single point radiation manufacturer which had the same calibration date or were
monitoring nanoDot dosimeters. The devices cost were within one or two days of each other, we noticed that measured
calculated for preparation/administration steps. Results: The 50 counts per minute from the well counter were 200% higher for
ml syringe of SIP contains 94.6% (+/-3%) of total vial activity, with vials from AAA. This phenomenon is consistent across all vials
residual activity estimated at 3.2%. The “reference-like method” that were compared. We believe this is directly correlated to
leads to an infusion of 98.9% (+/-0.2%) of total activity. With SIP, the metastable component that can be found in Lutetium-177
a theoretical staff hand dose of 29.41µSv has been calculated. from AAA. The prolonged presence of radioactivity in the vials
For “reference-like method”, dosimetry measured from 18.83 to from AAA have required us to use a third-party company for
43.57µSv, according to concerned finger. The devices cost was disposal of this radioactive waste, which has led to increase in
2.77€ for “reference method”. For SIP, devices costs of preparation space needed for decay in storage and an additional operating
and administration steps have been separated, and represent cost to properly handle this material. Conclusion: In summary,
respectively 2.93€ and 1.53€. Conclusion: The SIP does not Lutetium-177 has become a vital tool for radionuclide therapy,
increase staff exposure. However, a loss of medication results of however, there are important considerations for decay and
the syringe conditioning, but all doses are included in the 5% disposal of the radioactive waste which vary based on the
acceptable range. The rinsing volume is essential to obtain the method of production. Having this information available when
percentage of total activity infused for “reference-like method”. starting new programs and service lines is critical to long term
The total devices cost is nearly equivalent for both infusion success and compliance with regulatory agencies. References:
methods and low in contrast on the drug cost. The syringe None.
preparation could be optimized to reduce staff hand exposure :
the use of anti-reflux valve will reduce the three-way stop cock
manipulation. References: None. OP-550
Analysing and improving working procedures in
radiopharmacy laboratories in three European countries
OP-549 G. De Mol1, H. François1, T. Säilä2, T. Starc3, T. Taatila2, S. Rep3, H.
The Impact of Metastable Lutetium-177 on a Nuclear Mol1;
Medicine Department 1
Odisee vzw, Brussel, BELGIUM, 2Department of
A. Brown; Radiography and Radiotherapy, Tampere University of
Oregon Health and Science University, Portland, Applied Sciences, Tampere, FINLAND, 3Faculty of Health
OR, UNITED STATES OF AMERICA. Sciences, University of Ljubljana, Ljubljana, SLOVENIA.

Aim/Introduction: In the United States, Lutetium-177 Aim/Introduction: The finger doses of technologists preparing
is being used to treat patient’s with gastro-entero- radiopharmaceuticals can be quite high, exceeding the annual
pancreatic neuroendocrine tumors with the FDA approved dose limits. Recommendations to reduce radiation exposure
S213 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

for standard nuclear medicine procedures were developed. the patient’s experience. Materials and Methods: Audience
Despite these efforts, differences in preparing and administering members will be reminded of the importance of practicing
radiopharmaceuticals exist. The aim of the project was to excellence in their work and will realize that meticulous work
improve a daily routine in three European countries focusing on habits can have a profound impact on patient outcomes.
radiation protection and aseptics in radiopharmacy. Materials The presentation will examine the effect of waiting time and
and Methods: All together 15 healthcare professionals from waiting room design on patient satisfaction and cooperation
10 hospitals in three countries participated in the project. and give options for improving the waiting room experience.
In a first-round participants were asked to film their daily The phenomenon of “awfulizing” will be introduced and I will
radiopharmaceutical preparation. These films were analysed identify how time management and technologist efficiency
using a checklist based on the human health campus of the can calm this behavior. Results: Research shows that changes
IAEA, with a focus on sterility and radiation protection. A score to waiting room design can have a significant impact on
was given on 56 items during the different stages. Participants patient satisfaction and cooperation. Technologist attention to
wore finger dosimeters over a period of three to four weeks to work habits and more effective time management can reduce
see if a correlation could be found between the procedures awfulizing. Conclusion: Becoming a patient provides a unique
used and the dose to the fingers. In February 2019 participants perspective on how to optimize patient care. It is hoped that
started an eight weeks on-line refresher-course which sharing the knowledge gained through this experience will be
addressed different aspects of radiopharmacy work. The course of value to all medical professionals. References: None.
contained tasks, readings, videos and discussions. In a second
round the filming process and finger dosimetry were repeated.
Results: The baseline results varied between countries. Based OP-552
on analysed films 57% scores were positive. This means that in Amyloid Positron Emission Tomography (PET) scanning:
the three countries 43% of the manipulations in the hot lab did Process and pathway pitfalls and review
not comply with the IAEA guidelines. For some items only a few L. Alves, B. Williams, D. Vilic, Z. Win;
complied with IAEA guidelines. When only the manipulations Imperial College Healthcare NHS Trust, London, UNITED KINGDOM.
related to radiation safety are considered 56% of all participants
comply with the guidelines. Regarding the manipulations
related to sterility 46% of all technologists complied to the Aim/Introduction: Alzheimer’s disease(AD) is the most
guidelines. These results ask for attention since there is a strong common cause of dementia in elderly and its global burden
urge for sterility when preparing material for injecting patients. is expected to grow with the increase of life expectancy.
The results from finger dosimeters are not yet available. Course Definitive diagnosis of AD is a complex process requiring a
feedback will be available in summer and second round finger plethora of neuropsychological and imaging tests. One of the
dosimeter results in late summer. Conclusion: The results of the common features of definitive AD diagnosis is the presence
first-round show that there is a need to improve daily routines of extracellular plaques composed of insoluble beta-amyloid
in the radiopharmacy laboratories in the participating countries. (amyloid deposits). The identification of amyloid plaques, with
The results also show that the IAEA guidelines might need PET and 18F-labeled radiopharmaceuticals (18F-florbetapir,
an update. An online refresher course on daily routine in the 18F-florbetaben, and 18F-flutemetamol) is now considered
radiopharmacy laboratory was presented to the participants. a powerful tool for assisting in AD diagnosis(1). Materials and
We expect to have data on the impact of this course on daily Methods: At Imperial College Healthcare NHS Trust we have
routine and finger doses of the participants in late summer or successfully scanned over 350 Amyloid PET patients since
early autumn 2019. References: None. 2016. The aim of this project is to analyse the process in place,
from the tracer production to the report and assess its benefits
and pitfalls, from a technologist point of view: the booking
process and information dissemination to the patient/carer;
OP-551 the waiting time for appointments; the patient experience
An MRT Shares Her Experience: When Health Care Provider during preparation and injection; and facilities compared to
Becomes the Patient dementia friendly environments.Data regarding the number of
L. Rimanic; scans performed versus cancelled and cancellation reasons was
British Columbia Institute of Technology, Burnaby, BC, CANADA. also retrieved and analysed Results: Being in hospital can be
a disorientating and frightening experience for a person with
dementia, even in early stages. Although the scan is not invasive
Aim/Introduction: As an experienced NM technologist and (except for venepuncture) the full process can be quite difficult,
educator I was confident in my ability to provide excellent starting with appointment booking. Straightforward information
patient care. In 2014, I was diagnosed with breast cancer and I is given to the patient/carer previously to the appointment but
transitioned from health care provider to patient. Being on the we still experience a high rate of same-day cancellations. This
opposite side of the health care equation has taught me valuable happens mainly due to memory problems. Another observed
lessons that I will share with the audience. This presentation distressing moment is short notice cancellations related to
will demonstrate how best practice can be utilized to optimize tracer availability and/or delivery. This issue also increases
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S214

waiting lists and the worry that comes with that prolonged and professionals. Workshop participants evaluated provided
wait. We have also perceived that patients, due to behavioral training actions positively and showed motivation to engage
problems inherent to dementia (fear, panic, disorientation), participation in future sessions. Conclusion: Students have
also contribute to same day cancellations and artifacts and expressed great interest about Lean Philosophy, reflected in 3
poor quality images due to movement during the acquisition. major points: the large number of students who participated
Conclusion: In conclusion we assess that although the (voluntarily) at Lean workshops; good results obtained in the
department has been very successful in amyloid PET scanning, satisfaction surveys; students considering doing their final
a more dementia-friendly environment (colour coding rooms course work in LEAN Philosophy by submitting projects in
and doors, large clocks on the walls, a more relaxing waiting this subject to viability analysis. We sow the seeds of Lean
area) and developed training in dementia awareness for staff management on their minds and we are already reaping the
would definitely improve patient experience and consequently first fruits. References: None.
lead to a more efficient department. References: 1. Filippi,
L. et al. ‘18F-labeled radiopharmaceuticals for the molecular
neuroimaging of amyloid plaques in Alzheimer’s disease’, Am J OP-554
Nucl Med Mol Imaging, 2018, vol.8, no.4, pp. 268-281. Barriers And Limitations For Nuclear Medicine
Technologists’ Research In Spain
R. García Gorga1,2, C. Romero Magdalena3, N. Vega de Andrea1, L.
OP-553 Rincon Gayán1, I. Herrera Peco3;
Opening minds to Lean management in Nuclear Medicine 1
Sociedad Española de Graduados y Técnicos en Radiología,
J. Lemos, D. Vieira, N. Arantes, P. Costa; Madrid, SPAIN, 2Servei de Medicina Nuclear, Hospital
Nuclear Medicine Department, School of Health, Polytechnic Universitari Parc Taulí, Sabadell, SPAIN, 3Health Sciences
Institute of Porto (ESS|P.Porto), Porto, PORTUGAL. College, Alfonso X El Sabio University, Madrid, SPAIN.

Aim/Introduction: Nuclear Medicine (NM) is in constant Aim/Introduction: We conducted a qualitative cohort study
technological evolution, challenging often professionals to be aimed at detecting possible determinants of the low scientific
up to most recent standards and practices. In this sense, teaching production of Spanish radiographers. A survey was designed
NM should not be limited on the transmission of technical and to characterize the profile of the professionals and the work
scientific knowledge but also on opening minds to, for example, environment. We also sought to establish a relationship between
different management philosophies. Therefore, Nuclear perceived barriers and different variables such as work experience,
Medicine students should be capable to change behaviours/ contractual situation and type of work center. Materials and
practices and be concerned to search continuous improvement. Methods: After receiving the acceptance of the research ethics
To reach this standard, NM Department at our institution committee of the Alfonso X El Sabio University, an online survey
decided to implement the application of Lean Philosophy (Google Forms) was distributed from January to February 2019.
(management culture/philosophy focused on reducing various The global sample was composed of 595 Medical Imaging and
types of waste) in NM, in a process involving students, teachers NM Technologists recruited from Spanish Hospitals. For the
and alumni. Materials and Methods: We used several Lean statistical analysis we use the SPSS 20.0. Results: Results showed
tools: Gemba walk to detect problems; Brainstorming to “label” that 37% (n=220) of participants detect the existence of research
12 wastes (1.Over production, 2.Stock, 3.Transport, 4.Waiting, barriers meanwhile 63% (n=375) couldn’t identify any kind of
5.Motion, 6.Over processing, 7.Defects, 8.Human capital, research barrier in hospitals where they carry out their activity.
9.Design of products and services, 10.Inappropriate systems, Participants identify 17 different research barriers related to
11. Energy, 12.Materials); A3 thinking, 5S (Sort, Set in order, environment situation (extrinsic barriers) and personal situation
Shine, Standardize, Sustain) and Visual management to solve/ (intrinsic barriers). It was found that 35% (208) of the participants
minimize the problems/wastes detected. Surveys were used were men, compared to 63.2% (376) who were women, 1.8% (11)
to assess satisfaction degree amongst students, teachers and preferred not to indicate their gender. Grouped by age intervals,
alumni related to changes implemented in NM laboratory and 61.4% of the participants were older than 36 years (p <.001).
office, and with Lean Philosophy Workshops. Results: Students Regarding the ability to find barriers, we observed significant
and teachers walked in NM laboratory (place of practical classes) differences when analyzing years of experience (p <.000), type of
and identified many problems or “wastes” (such as wasting contract (p <.000) and work in a University Hospital (p <.001). No
time looking for materials or excess of material boxes). After differences were found, both by sex and type of management of
applying 5S and visual management, students and teachers the work center or job position performed by the professionals
considered that Laboratory use was optimized resulting in more (p> .05 in all cases). Based on years of experience, we observed
productive practical classes. Teacher’s office was also a Lean that starting in the 21st year, a greater number of barriers are
intervention target. This approach developed a Communication detected. The most significant are; Access to research resources
Board that contributed to improve communication between (p <.016); Lack of funding (p <.043); Lack of dedicated time
teachers (reflected in shorter and more productive meetings). to clinical level (p <.003). On the other hand, a significative
We organized two Lean Philosophy Workshops open to alumni relation was found between work in a University Hospital
S215 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

and negative perception by others of NMT ability (p <.001). were not yet available in Portugal. The proof that leadership
Finally, when comparing the type of contract it was observed mediates the relationship between how we are integrated into
a significative relation to Negative perception by other, lack of our workplaces and the way we perceive these same places in
support for leaders, workload and lack of recognition (p<.001 terms of their performance, brings new importance in betting
applicable in all cases). Conclusion: Our results have shown on training and discuss leadership as the theme for obtaining of
that work experience, years as NM technologist, and work new human resources policies and professional solutions in the
in a University Hospital, were related to the capability to find area of Nuclear Medicine. This information can be used to help
and describe barriers and limitations to research projects. develop strategies to meet those needs through work redesign
References: None. and leadership behavior development. References: None.

OP-555 1305
Nuclear Medicine Technologists: Professional Identity -
Can leadership profiles makes a difference?
M2M - Parallel Session: Preclinical
A. Martins1,2,3, I. Faro de Albuquerque4, G. Cunha3;
Developments in Infectious Diseases
1
Higher School of Health of the Portuguese Red Cross,
Lisbon, PORTUGAL, 2Joaquim Chaves Saúde, Lisbon, Tuesday, October 15, 2019, 11:30 - 12:45 Lecture Hall 111
PORTUGAL, 3Lisbon School of Health Technology,
Lisbon, PORTUGAL, 4NOVA-SBE, Lisbon, PORTUGAL.
OP-556
111
In-PCTA-VRC07 a Radiolabeled Broadly Neutralizing
Aim/Introduction: The aim of the study is to identify, provide Antibody For HIV Imaging in Mice
and explore some management outputs data on Nuclear D. Viertl1, T. Denoël1, F. Cicone1, C. Müller2, C. Fenwick1, G. Pantaleo1,
Medicine Technologists (NMT) in Portugal like professional J. O. Prior1;
identity, work engagement, leadership profiles and analyze 1
Lausanne University Hospital and University of
their impact on perceived organizational performance. There Lausanne, Lausanne, SWITZERLAND, 2University
is no data about management outputs on NMT in Portugal. Hospital of Zürich, Zürich, SWITZERLAND.
Leadership profiles characterization and assessment of their
influence on motivation and effective outputs of professional
performance have been demonstrated an important role in Aim/Introduction: Broadly neutralizing antibodies (bNAbs)
human resources management. Materials and Methods: 67 targeting several HIV-1 envelope (Env) epitopes are currently
NMT answered an online survey that assesses their perceptions being investigated as a new curative approach against
about their leadership styles, their professional identity, work HIV-1 infection. Radiolabeled bNAbs are prospective novel
engagement and perceived organizational performance. tracers for translational investigation of HIV-1 infection in vivo
Data were statistical treated and one theoretical model that imaging. In this study, the bNAb VRC07 was conjugated with
correlates the variables studied has been proposed and tested. the versatile macrocyclic ligand p-SCN-Bn-PCTA. The construct
The wished leadership profile also was assessed. Results: These was radiolabeled with indium-111 and evaluated in vitro and
professionals have revealed a professional identity that reflects in vivo in a tumour bearing mice HIV-1 model. Materials and
a moderate to great integration between their personal identity Methods: VRC07 was conjugated with ten equivalents of
and their identity in the profession. Higher values of work p-SCN-Bn-PCTA at pH 9.5. The immunoaffinity of PCTA-VRC07
engagement were obtained than those found in other health was tested by flow cytometry using HeLa243 cells that stably
professions such as nursing. The perceived performance was express the HIV-1 NL4.3 Env and Tat proteins. Chelation of
also high in most cases. The leadership profile with the highest PCTA-VRC07 was obtained with 113 MBq indium-111 for one
scores was the “Mentor Leader” in the case of Nuclear Medicine. hour at 37 °C and pH 4.5 in NH4OAc. Immunoreactive fraction
With the application of the proposed theoretical model, we can assay with 111In-PCTA-VRC07 was done using serial dilution of
prove that work engagement moderate the relation between HIV-1 Env glycoprotein gp120 heptamer coated on microplate.
professional identity and perceived organizational engagement, Biodistribution of 111In-PCTA-VRC07 was studied in female
and we have also been able to prove statistically assesses BALB/c nude mice bearing xenografts of HeLa243 and control
focused on flexibility (focused on people and teamwork and HeLa tumours. Three animals per time point were sacrificed
focused on innovation, change and professional performance) at 24, 48 and 120 hours after injection of 0.5 Mbq 111In-PCTA-
positively measure the relationship between work engagement VRC07. SPECT/CT scans were acquired at the same time points
and perceived organizational performance. On the other hand, after injection of 15 Mbq 111In-PCTA-VRC07 in three additional
convergent, control-focused leadership models (focused on mice. Expression of gp120 was confirmed by immunoblotting ex
the hierarchy or the achievement of results) negatively mediate vivo in the same tumours. Results: Flow cytometry histograms
the relationship between work engagement and perceived of immunolabeled HeLa243 with PCTA-VRC07 and VRC07 were
performance. Conclusion: This study allowed obtaining overlapping showing retained affinity for HIV-1 Env proteins
characteristics of the NMT professionals of the for which data after PCTA conjugation. As shown in SEC-HPLC and iTLC, the
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S216

radioimmunoconjugate 111In-PCTA-VRC07 was obtained in nmol DPAH-UBI29-41.The stability assay, including analysis in
99% radiolabeling yield and thus used without purification. An the presence of histidine excess, showed no adverse effects
immunoreactive fraction of 111In-PCTA-VRC07 for gp120 greater on radiochemical purity. Scan after 99mTc-DPAH-UBI29-41
than 70% was calculated. At 48 hours, 111In-PCTA-VRC07 uptake administration showed accumulation of radionuclide in
was significantly higher in the HeLa243 tumours than in HeLa femur of rats with microbial bone inflammation, whereas no
tumours (control), respectively 16.8 ± 1.0 versus 11.7 ± 2.0 % signals change are observed in rats with sterile LPS-induced
IA/g (t test, P = 0.017, n = 3). At 120 hours, 9.8 ± 2.0 % IA/g of inflammation. Quantitative analysis revealed a maximum mean
111
In-PCTA-VRC07 was found in the HeLa243 tumour, 10.0 ± 0.9 target-to-nontarget ratio of 2.72 [1.96-2.87] at 35 min, which
% IA/g in the liver, 5.1 ± 2.0 % IA/g in the control tumour, 4.3 decreased to 2.35 [1.71-2.42] at 60 min. No adverse reactions
± 0.3 % IA/g in the spleen and 3.5 ± 0.4 % IA/g in the blood. were observed during image acquisition and within 3 day after
SPECT images confirmed the preferential uptake of 111In-PCTA- the study. Conclusion: Antimicrobial peptides derived from
VRC07 in HeLa243 tumours compared to HeLa control tumours. ubiquicidine (UBI29-41) were successfully labeled by 99mTc
Conclusion: Using the innovative radioimmunoconjugate 111In- using chelator DPAH-NHS ester. 99mTc-DPAH-UBI29-41 with
PCTA-VRC07 directed against gp120, in vivo SPECT imaging of high radiochemical purity (96%) and stability was produced.
HIV-1 Env proteins was possible in a HeLa243 tumour bearing The scintigraphy with 99mTc radiolabeled UBI29-41 peptides
mice model. References: None. provided highly accurate detection and differentiation of
infection and sterile inflammation in rat model of osteomyelitis.
References: None.
OP-557
Imaging infections: evaluation of antimicrobial peptide
99mTc-DPAH-UBI29-41 as a specific agent OP-558
M. Zorkaltsev1, A. Pershina1, V. Udodov1, V. Ivanov1, M. Larkina1, E. In vivo imaging of infection with 99mTc-Labelled Human
Stasyuk2, A. Rogov2, A. Lushchyk3, N. Shevtsova1, V. Zavadovskaia1; Beta-Defensin-3 in a Rat Model
1
Siberian State Medical University, Tomsk, RUSSIAN FEDERATION, G. A. Follacchio1,2, A. Pala1, S. Scaccianoce3, F. Monteleone1, M.
2
National Research Tomsk Polytechnic University, Tomsk, RUSSIAN Liberatore1;
FEDERATION, 3Institute of Bioorganic Chemistry, Minsk, BELARUS. 1
Sapienza University of Rome, AOU Policlinico Umberto
I, Nuclear Medicine Unit, Rome, ITALY, 2Department of
Molecular Medicine, Sapienza University, Rome, ITALY,
Aim/Introduction: Development of radiopharmaceutical for 3
Sapienza University of Rome, Department of Human
detection septic inflammation using the original approach to Physiology and Pharmacology, Rome, ITALY.
radiolabelling of antimicrobial peptide UBI29-41. Materials
and Methods: UBI29-41 was produced by solid phase peptide
synthesis using Fmoc-protected amino acids. Succinimid-1-yl Aim/Introduction: In clinical practice, differentiation of
6-(bis(pyridin-2-ylmethyl)amino)hexanoate (DPAH-NHS ester) infection from aseptic inflammation represents a major issue.
was used as the chelating agent for 99mTc. DPAH-NHS ester in Nevertheless, none of the commercially available compounds
ethanol was added to UBI29-41 in PBS and incubated for 2 hours (labelled granulocytes, anti-granulocyte antibodies, 67Ga-
at room temperature and then for 24 hours at 4°C. DPAH-UBI29-41 citrate, labelled immunoglobulin-G, 18F-FDG) is capable of this
was purified using a PD Minitrap™ G-10 column (GE Healthcare, differentiation, producing a not negligible false-positive rate.
UK). The radiolabeling was accomplished in two steps using CRS The current gold standard imaging procedure, scintigraphy
KIT to form the [99mTc(CO)3(H2O)3]+ intermediate, which was with labelled leukocytes, is furthermore characterized by a
neutralized before UBI29-41 addition. The vial was heated at 70°C time-consuming sequence of cell separation and radiolabelling
for 60 min, and then, the radiolabeled peptide UBI29-41 was requiring highly-trained personnel due to the hazard of blood-
purified using columns С18 Sep-Pak. The radiochemical yield borne infections. Recently, our group evaluated the antimicrobial
and radiochemical purity were determined by iTLC in PBS. The in peptide Human β-Defensin-3 (HBD-3) as a potential radiotracer
vitro stability test was performed by incubating the radiolabeled for specific infection imaging, reporting a reliable labelling
peptide with 5000-fold molar excess of histidine in PBS for 3 h. procedure with 99m-technetium and testing its toxicity in a rat
Control samples were incubated in PBS. The osteomyelitis (n=6) model [1,2]. Aim of the present study was to evaluate 99mTc-
and sterile bone inflammation models (n=6) were developed in HBD-3 in vivo imaging potential in differentiating infection
rats. 99mTc-DPAH-UBI29-41 was intravenously injected into the from sterile inflammation in a rat model. Materials and
tail vein at a dose of 18.5 mBq. Then sequential recording of 5 Methods: Recombinant HBD-3 was radiolabeled with 99mTc.
minute images was performed for 1 hour using SPECT Philips Radiolabelling yield and specific activity of the compound were
BrightView. Scans were interpreted on the basis of bacterial calculated. An experimental model involving S.aureus-induced
culture, laboratory tests and three-phase bone scanning. infection and carrageenan-induced aseptic inflammation was
Results: The radiochemical yield of 99mTc-DPAH-UBI29-41 was realised in five Wistar rats. Serial planar scintigraphic acquisitions
80% and radiochemical purity was 96%. Each milliliter 99mTc- were performed from 15’ to 180’ after 99mTc-HBD-3 intravenous
DPAH-UBI29-41 of in physiologic saline at the end of synthesis administration. Radiotracer uptake in infected versus non-
contained approximately 50 MBq of 99mTc activity and 3.8 infected sites was evaluated qualitatively and semiquantitatively.
S217 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

ROIs were drawn on the infection site, inflammation site and administered intravenously. Dual-isotope SPECT imaging, %ID/g
background. Radiotracer uptake in each ROI was expressed and fluorescence studies were performed at 4 h (model 1) or
in terms of average counts and Target-to-NonTarget (T/NT) 24 h (model 2) allowing multi modal imaging of the individual
ratios were calculated. Results: Radiolabelling yield of 99mTc- vectors and assessment of the host-guest complexation in vivo.
HBD-3 was 70% with a specific activity of 6-8 MBq/μg. Despite Imaging of guest vector 111In-Cy50.5CD9PIBMA39 in mice without
an intense activity in the abdominal region, a significant and an infection served as control. Results: Dual-isotope SPECT
progressive 99mTc-HBD-3 uptake was observed in S.aureus- imaging of host-guest interactions revealed pre-targeting was
induced infection site compared to sterile inflammation and efficient in both colonization models as binding of the guest
background. Maximum average T/NT ratio (5.7-fold higher vector to the host was seen in both the liver and the muscle.
in infection site vs inflammation site) was observed at 140’. Quantitative assessment revealed that after intra-hepatic
Conclusion: In vivo imaging with 99mTc-HBD-3 in a rat administration the hepatic accumulation of the host vector was
model of S.aureus-induced infection showed a favourable nearly 4 times higher at 4 h post-injection (27.1 ± 11.1 %ID/g,
uptake in the infection site compared to sterile inflammation p < 0.001) compared to hepatic uptake of the host vector in
and background. These promising findings, together with mice that did not received an injection with the bacterial host
previous in vitro and ex vivo results on 99mTc-HBD-3 targeting (7.6 ± 2.3 %ID/g). In the intra-muscular model, the accumulation
capacity and toxicity, further confirm 99mTc-HBD-3 as a novel of the host vector in the infected muscle at 24 h post-injection
potential candidate for specific infection imaging. References: was two-fold higher (4.4 ± 0.7 %ID/g, p < 0.001) than in control
1. Liberatore M, Pala A, Scaccianoce S, et al. Microbial Targeting muscle (2.1 ± 0.3 %ID/g). Fluorescence imaging confirmed
of 99mTc-Labeled Recombinant Human Beta-Defensin-3 in an co-localization in the liver or infected muscle. Conclusion:
Animal Model of Infection: a Feasibility Pilot Study. J Nucl Med Supramolecular host-guest complexation can efficiently be
2009; 50:823-826 2. Liberatore M, Anagnostou C, Scaccianoce S, used as pretargeting strategy during bacterial infection models.
et al. Toxicity assessment of 99m-Technetium-labeled human The obtained results demonstrate the feasibility of using such
beta-defensin-3 in CD1 mice. Hell J Nucl Med 2015; 18:233-237. an approach during bacterial colonization studies, thereby
highlighting the technologies potential to advance the field of
nanomedicine. References: M. Rood et al., Sci Rep 2017; 7:39908.
OP-559 S. Spa et al., Theranostics 2018; 8(9):2377-2386. M. Welling et al.,
Multiplexing during host-guest mediated pre-targeting of J Contr Rel 2019;293:126-134.
bacteria
M. Welling1, N. Duszenko1,2, D. M. van Willigen1, W. K. Smits3, M.
Roestenberg2, T. Buckle1, F. W. B. van Leeuwen1,4; OP-560
1
Interventional Molecular Imaging Laboratory, Department An animal model of foreign body infection for the
of Radiology, Leiden University Medical Center, Leiden, development of quantitative infection imaging
NETHERLANDS, 2Department of Parasitology and Department B. Mahida1, R. Aid2, J. Aerts1, F. Andreata3, L. Louedec2, F. Chau4, F.
of Infectious Diseases, Leiden University Medical Center, Leiden, Rouzet5;
NETHERLANDS, 3Department of Medical Microbiology, Section 1
Department of Nuclear Medicine, Bichat University Hospital,
Experimental Bacteriology, Leiden University Medical Center, Assistance Publique– Hôpitaux de Paris, Paris, FRANCE,
Leiden, NETHERLANDS, 4Laboratory of BioNanoTechnology, 2
INSERM Unité 1148 Bichat University Hospital, Paris,
Department of Agrotechnology and Food Sciences, Wageningen FRANCE, 3INSERM, Bichat University Hospital, Paris, FRANCE,
University & Research, Wageningen, NETHERLANDS. 4
University Paris Diderot-Paris 7, Paris, FRANCE, 5Department
of Nuclear Medicine, Bichat University Hospital, Assistance
Publique– Hôpitaux de Paris, University Paris Diderot-Paris
Aim/Introduction: Cyclodextrin (CD)-based host-guest 7, Inserm Unité Mixte de Recherche 1148, Paris, FRANCE.
interactions with adamant have demonstrated value during Aim/Introduction: The diagnosis of foreign body infection such
the functionalization of stem-cells and to generate a pre- as prosthetic material or implanted cardiac device is challenging.
targeting-based alternative for hepatic radioembolization 1-3. Many animal models of infection were reported but usually lack
An obvious next step in the technological validation of this standardization and reproducibility (size and concentration
approach is the pre-targeting of transplanted cells in vivo. We of the septic inoculum) preventing a quantitative approach
validated this concept using a bacterial colonization study to infection imaging. 99mTc-labelled polymorphonuclear cells
with Staphylococcus aureus. Materials and Methods: Bacteria (PMNs) SPECT is acknowledged as the current benchmark of
(Staphylococcus aureus) were labeled with a radiolabeled, infection imaging. Our study aimed to design a standardized
adamantane-containing antimicrobial peptide (99mTc-(Ad- experimental rat model of chronic infection and to validate this
Gly)2-Lys-UBI29-41; guest). An 111In-labeled Cy50.5CD9PIBMA39 approach using 99mTc-labelled PMNs SPECT/MRI. Materials and
polymer served as host vector, yielding the bimodal agent Methods: Experiments were performed in Lewis (syngenic) rats.
111
In-Cy50.5CD9PIBMA39. Mice were either (1) intra-hepatically or Foreign body consisted in a disc-shaped (6 mm diameter x 3
(2) intra-muscularly infected with 1x108 viable 99mTc-(Ad-Gly)2- mm width) polysaccharide bioscaffold (AlgiMatrixTM 3D Culture
Lys-UBI29-41-labeled S. aureus (n=6 mice per model). Twenty System). Septic inoculum consisted of Staphylococcus aureus
four hours after host administration, 111In-Cy50.5CD9PIBMA39 was (strain HM1054), a major opportunistic pathogen. Bioscaffolds
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S218

were incubated with 20 μL of either HM1054 solution (10E4 CFU/ intravenous injection of engineered attenuated Salmonella
ml corresponding to 200 CFU/ scaffold) or 0.9% NaCl solution typhimurium (SLΔppGpp/lux) to total 15 male BALB/c mice
for controls. Two septic bioscaffolds (M1,M2) were implanted with tumor (CT26 cells) in their right thigh. Scanning with
on the right flank of 4 rats (n=8), control bioscaffolds (C) were animal PET/CT with F-18 FDG was done at various time points
implanted on the opposite flank for aseptic inflammation (n=4). after injection. Tumor volume was observed till 16-17 DPI. FDG
Separated (PMNs) were obtained from bone morrow of syngenic uptake (SUVmax, SUVmean), tumor volume, and growth rate
animals and labelled with 99mTc-HMPAO. Labelling efficiency were analyzed. Results: FDG tumor uptake was decreased
was measured over 24 hours, after labeling. 99mTc-labelled PMNs on 1-2 DPI (day post injection). It increased again from 4 DPI.
were injected 9 days after bioscaffolds implantation, SPECT/MRI Amount of SUVmean decrease on 1-2 DPI is strongly correlated
was acquired 24 hours later. Quantitative analysis compared with tumor volume suppression (rank correlation rho 0.867,
the uptake of infected vs. control bioscaffolds. Reproducibility p=0.0025). With cutoff value >0.43 (change of SUVmean at 1-2
was assessed by comparing ratios of uptake intensity between DPI) we can expect tumor volume increase would be no larger
each infected bioscaffold in the same rat (M1/C vs. M2/C). Then than 500 mm^3 at 16-17 DPI (sensitivity 100% & specificity
quantitative autoradiography and histologic staining (Massons’s 83.3%). Conclusion: After BCT, FDG tumor uptake decreased on
trichrome) of bioscaffolds were performed. Results: Labelling 1-2 DPI and increased again from 4 DPI. We can predict the result
efficiency was stable over time (89% at 24 hours). 99mTc-labelled of BCT with F-18 FDG PET by change of SUVmean. References:
PMNs uptake was visually detectable on SPECT around all 1.Kim, K., et al., A novel balanced-lethal host-vector system
infected bioscaffolds and none on control bioscaffolds. There based on glmS. PLoS One, 2013. 8(3): p. e60511.2.Zheng, J.H. and
was a significant difference between infected and control J.J. Min, Targeted Cancer Therapy Using Engineered Salmonella
bioscaffolds Σ(M1,M2)= 2.3±0.9 vs. ΣC=0.27±0.9 (p=0.004). typhimurium. Chonnam Med J, 2016. 52(3): p. 173-84.3.Nguyen,
There was no significant difference between ratios of infected V.H. and J.J. Min, Salmonella-Mediated Cancer Therapy: Roles
bioscaffolds M1/C =9.6[7.9-12.5] vs. M2/C =9.9[6.7-11.9] (p=0.9 and Potential. Nucl Med Mol Imaging, 2017. 51(2): p. 118-126.
Mann Whitney test).Autoradiography confirmed diffuse
uptake in all infected bioscaffolds. Comparative analysis of
autoradiography and histopathologic staining showed the 1306
co-localization of tracer uptake and granulocytes infiltration.
Bacteriological analysis of explanted bioscaffolds showed
Do.MoRe - Parallel Session: SPECT/CT
living bacteria on infected bioscaffolds and none on controls.
Quantification & Data Analysis
Conclusion: This study validates the experimental infection
model with standardized and reproducible parameters, Tuesday, October 15, 2019, 11:30 - 12:45 Lecture Hall 112
detectable with 99mTc-labelled PMNs. These results pave the way
to further comparison between the conventional 99mTc-labelled
PMNs SPECT and quantitative approach based on novel PET
agents. References: None. OP-562
Convolutional neural network-based denoising allows
67% reduction of scan time or tracer dose in dopamine
OP-561 transporter SPECT
FDG uptake pattern can predict the success of bacterial M. Nazari1,2, S. Kimiaei1, M. Ehrenburg3, A. Kluge1, R. Bucher4;
cancer therapy 1
ABX - CRO advanced pharmaceutical services, Dresden,
A. Chong1, J. Min2, H. Nguyen2, J. Ha1, K. Kim2; GERMANY, 2TU-Dresden, Dresden, GERMANY, 3Pinax
1
Chosun University Hospital, Gwangju, KOREA, Pharma, Bad Liebenwerda, GERMANY, 4University Medical
REPUBLIC OF, 2Chonnam National University Center Hamburg-Eppendorf, Hamburg, GERMANY.
Hospital, Gwangju, KOREA, REPUBLIC OF.

Aim/Introduction: Dopamine transporter (DAT) SPECT is the


Aim/Introduction: The number of studies about cancer most frequent nuclear medicine brain imaging procedure.
therapy with engineered bacteria (BCT) such as Salmonella or Typical scan duration of 30-50 minutes presents a burden for
Escherichia is increasing including phase I clinical studies [1, 2]. many patients. It is also associated with considerable risk of
Not only by deliver therapeutic agents, but also those bacteria head motion during the scan resulting in artefacts that might
themselves have some cancer-suppression effect[2]. One of compromise the interpretation of the reconstructed SPECT
the mechanisms of BCT is via immune stimulation [2, 3]. In our images. Deep learning-based methods have been found
lab, we have studied BCT for several years and we found that in promising for enhancement / denoising of medical images. Aim
some objects, their response to BCT was less than others. F-18 of the present study was to test a convolutional neural network
FDG is widely used for cancer and inflammation evaluation. (CNN) for denoising of DAT SPECT images. Materials and
The aim of this study is to find out whether F-18 FDG uptake Methods: Reconstructed DAT SPECT images in the anatomical
pattern can predict the result of BCT and to find out FDG uptake space of the Montreal Neurological Institute of 656 different
pattern after BCT. Materials and Methods: BCT was done by subjects were obtained from the database of the Parkinson’s
S219 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

Progression Markers Initiative, 446 patients with Parkinson’s Gondara et al. [2] and a custom U-Net that had a depth of 4 layers
disease (PD) and 210 healthy controls. Two-dimensional slab with 2 convolutions, Batch Normalization and ReLU in each layer.
view images of 12mm thickness were obtained by averaging Training of the networks was done with the hyperparameters
transversal slices through the striatum. A 67% reduction of scan as described in the original publications. Results: The best
time was simulated by adding white Gaussian noise to each slab denoising performance of the neural networks was achieved
view. The corresponding noise level was estimated from dynamic by either the CNN DAE when measured with the Structural
DAT SPECT scans in which the total scan duration had been split Similarity (SSIM) index of 0.933 or by the custom U-Net with a
into 3 frames. Ten 60/20/20 random splits of the subject sample Peak Signal to Noise Ratio (PSNR) of 30.03 dB. This corresponded
were used to train, validate, and test a CNN (inspired by Alex-Net to a signal quality improvement of 0.09 compared to the noisy
and denoising auto-encoder methodology) with a combination input when measured with the SSIM, or 5.9 dB when measured
of loss functions based on the pixel value differences and the with the PSNR. The denoised SPECT images showed improved
structural difference between the estimated image (from the visual appearance, however, gain in image quality was not as
noisy one) and the true image. The area under the receiver distinct as on low-dose CT data. We assume this was due to the
operating characteristic curve (AUC) of the specific putaminal image characteristics of SPECT images, which are characterized
binding ratio (SBR, mean of both hemispheres) for identification by few distinct image values and a more heterogeneous pixel
of PD patients in the test set was used as clinically relevant intensity distribution compared to CT data. Conclusion: Image
performance measure (putamen ROI of the AAL atlas). Results: characteristics in SPECT pose a special challenge to deep
The mean absolute pixelwise difference between the CNN- learning-based image denoising methods, as the signal is
denoised images and the true images was 1.8% (compared to sparse and contains a high degree of noise. We believe this, in
6.7% for the noisy images). The CNN-denoised images provided conjunction with the limited number of samples explains the
a small AUC improvement not only compared to the noisy weaker benefit in performance in SPECT when compared to
images but also compared to the ground truth: 0.994±0.005, low-dose CT data. We assume that with a more diverse training
0.986±0.009, and 0.990±0.007, respectively. Conclusion: These set and specialized loss function suitable for SPECT data , we
results suggest that CNN-based denoising allows considerable can further increase performance. References: [1] Gondara, L.
reduction of scan time and/or tracer dose in DAT SPECT. Further (2016). Medical image denoising using convolutional denoising
improvement might be achieved by training the CNN using autoencoders. IEEE ICDMW-2016. [2] Heinrich, M. , Stille, M.,
larger datasets and/or use raw projection data prior to image Buzug, T. (2018). Residual U-Net Convolutional Neural Network
reconstruction for denoising. References: None. Architecture for Low-Dose CT Denoising. CDBME-2018.

OP-563 OP-564
Deep Image Denoising in SPECT Optimization of myocardial perfusion imaging protocol
M. Reymann1,2, T. Würfl1, P. Ritt3, B. Stimpl1, M. Cachovan4, H. A. for digital SPECT/CT imaging system
Vija5, A. Maier1; R. Hirvilammi1, M. Seppänen1,2, J. Knuuti2, T. Noponen1,3;
1
Friedrich-Alexander University Erlangen-Nürnberg, Pattern 1
Department of Clinical Physiology and Nuclear Medicine,
Recognition Lab, Erlangen, GERMANY, 2Erlangen Graduate Turku University Hospital, Turku, FINLAND, 2Turku PET Centre,
School in Advanced Optical Technologies (SAOT), Erlangen, Turku University Hospital, Turku, FINLAND, 3Department of
GERMANY, 3Clinic for Nuclear Medicine, University Hospital Medical Physics, Turku University Hospital, Turku, FINLAND.
Erlangen, Erlangen, GERMANY, 4Siemens Healthineers,
Erlangen, GERMANY, 5Siemens Medical Solutions USA,
Inc., Malvern, PA, UNITED STATES OF AMERICA. Aim/Introduction: Digital SPECT/CT scanner offers better
spatial resolution and sensitivity compared to traditional
analogical SPECT/CT. Myocardial perfusion imaging (MPI) is
Aim/Introduction: Single Photon Emitted Computed somewhat challenging imaging procedure which has several
Tomography (SPECT) images are characterized by a high degree parameters affecting the images. New features of digital SPECT/
of image noise, which is due to the low photon count at the CT allows optimization of clinical image acquisition protocols.
detector. Recently, several deep learning-based approaches The aim of this study was to develop optimal MPI imaging
for image denoising have been proposed for low-dose protocol for digital NM/CT 670 CZT SPECT/CT (GE Healthcare,
Computed Tomography (CT). We investigate their suitability for Tirat Hacarmel, Israel). Materials and Methods: Data of 30 MPI
SPECT denoising. Materials and Methods: In order to have a patients imaged using list-mode acquisition in Turku University
groundtruth for training the networks, a Monte Carlo Simulation Hospital were used retrospectively. Sinograms were reformatted
was set up with the SIMIND software, where in total 24 SPECT with Xeleris 4.0 Lister software using 15 parameter combinations
acquisitions of brains, lungs, livers and skeleton were simulated and total of 900 new sinograms were reconstructed with QPS/
with the XCAT phantom. Pairs of noisy and clean SPECT images QGS software (Cedars Sinai Medical Center, Los Angeles, USA).
were then used for training the neural networks. The networks Statistical analysis was carried out using SPSS (IBM, Armonk,
tested were the U-Net as proposed by Heinrich et al. [1], the USA). Visual analysis was performed by comparing bull’s eye
convolutional denoising autoencoder (CNN DAE) proposed by pictures. Results: Using 16 gates instead of 8 gated-SPECT
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S220

results in significantly higher ejection fraction (EF) (rest: 50.00 quality for the same number of acquired counts. Conclusion:
± 11.89% vs. 53.63 ± 13.20% (p < 0.001) and stress: 51.23 ± The energy resolution of the CZT system is significantly better
11.00% vs. 54.47 ± 12.41% (p < 0.001)). Using narrower ±3% than for conventional systems, potentially improving image
energy window instead of ±7.5% results in significantly larger quality due to reduction in scatter. The collimator fitted to the
ischemic regions (rest: 0.5% (0 - 4%) vs. 3.5% (1 - 6.75%) (p < CZT system gives an 18% increase in sensitivity compared to
0.020) and stress: 2% (0.25 - 5.75%) vs. 6% (1 - 9.75%) p < 0,001)). using LEHR collimators on the conventional camera with similar
Decreasing time per view from 20 to 15 s in stress study does resolution at 10 cm. However it would appear the resolution
not significantly chance the size of ischemic region (p = 0.792). drops off rapidly with distance so that reconstructed resolution
Optimal setting combination using 16 gates, ±3% energy may be significantly poorer in clinical tomographic images.
window and 30 s / 15 s (rest / stress) time per projection results Simulating clinical Myocardial Perfusion images demonstrated
in significantly larger EF (rest: 50.00% ± 11.89 % vs. 52.90% ± that the overall effect of system differences mean that an 18%
14.57% (p < 0.001) and stress: 51.23% ± 11.00% vs. 54.07 ± 11.3 reduction in acquisition time would be justifiable. References:
% (p < 0.001)) and significantly larger ischemic region (rest: 0.5% (1)Performance Measurements of Gamma Camera NU 1-2007,
(0% - 4%) vs. 4.5% (2% - 7.75%) (p < 0.001) and stress 2% (0.25% NEMA. (2)Evolution for cardiac White Paper, GE Medical Systems.
- 5.75%) vs. 5.5% (2% - 11%) (p < 0.001)). Visual analysis verified
the clinically meaningful increase of ischemic region mostly
in stress study. Conclusion: Using more gates in gated-SPECT OP-566
allows better tracking of cardiac volumes which results in more Lutetium-177 SPECT Quantification: A Multi-Center, Multi-
accurate assessment of EF. The increase of ischemic regions in Vendor Comparison
stress studies seems to be caused by the decreased amount of S. Meyer Viol1, S. M. B. Peters2, N. R. van der Werf3,1, F. H. P. van
scattered photons due to narrower energy window. It seems to Velden4, N. de Jong4, M. Konijnenberg3, A. Meeuwis2, M. Gotthardt2,
be possible also to reduce imaging time or injected activity by C. Beijst1, H. W. A. M. de Jong1, M. Segbers3;
25% in our cardiac protocol. References: None. 1
UMC Utrecht, Utrecht, NETHERLANDS, 2Radboudumc, Nijmegen,
NETHERLANDS, 3Erasmus MC, Rotterdam, NETHERLANDS,
4
Leiden University Medical Center, Leiden, NETHERLANDS.
OP-565
Optimisation Of A General Purpose CZT SPECT/CT For
Tomography Aim/Introduction: Quantitative SPECT imaging in targeted
N. Bird, D. Gillett; radionuclide therapy with lutetium-177 holds great potential for
Addenbrooke’s Hospital, Cambridge, UNITED KINGDOM. individualized treatment based on dose assessment. Application
of universal dose targets requires a standardized method for
Aim/Introduction: The aim was to investigate whether image SPECT quantification. The purpose of this multi-center study is
quality improvements with a general purpose solid state to evaluate quantitative accuracy and inter-system variations of
gamma camera, compared to a conventional camera, would different SPECT/CT systems with corresponding commercially
allow reduction in acquisition times. The focus was myocardial available quantitative reconstruction algorithms, as part of an
perfusion tomography which will be the majority of the workload important step towards a vendor independent standard for
for this camera. Materials and Methods: The camera under quantitative lutetium-177 SPECT. Materials and Methods: Four
investigation was a GE Discovery NM/CT 670CZT comparisons state-of-the-art SPECT/CT systems were included: Discovery™
were made with a NM/CT 670 fitted with LEHR collimators. NM/CT 670Pro (GE Healthcare), Symbia Intevo™ and two
Energy resolution, planar spatial resolution and sensitivity were Symbia™ T16 (Siemens Healthineers). Quantitative accuracy and
measured conforming to NEMA (1) protocols as far as possible. inter-system variations were evaluated by repeatedly scanning
Reconstructed resolution in scatter was measured using a a cylindrical phantom with 6 spherical inserts (0.5-113mL). A
NEMA SPECT Triple line source phantom using a radius 21 cm, sphere-to-background activity concentration ratio of 10:1 was
reconstructing with and without resolution recovery correction used. Acquisition settings were standardized: medium energy
(2). Clinical myocardial perfusion images were simulated using a collimator, body contour trajectory, photon energy window
torso phantom with a cardiac insert, CT was used for attenuation of 208 keV (±10%), adjacent 20% lower scatter window, 2x64
correction. Images were reconstructed with and without projections, 128x128 matrix size, and 40s projection time.
scatter correction and resolution recovery correction Results: Reconstructions were performed with vendor/center specific
Comparing the CZT system results with the conventional reconstruction and quantification algorithms GE Q.Metrix™,
system: Energy resolution for Tc-99m was 6.0% compared with Siemens xSPECT Quant™, Siemens Broad Quantification™ and
9.3%. Planar spatial resolution @ 10 cm was 7.3 mm compared Siemens Flash3D™ using vendor recommended settings. In
with 7.4 mm. Sensitivity was 82 cps/MBq compared to 70 addition, raw data was reconstructed using Hermes SUV SPECT™
cps/MBq. Reconstructed resolution was 14.1/14.3/11.0 mm with standardized reconstruction settings to obtain vendor
for central/radial/tangential measurements compared with neutral quantitative reconstructions for all systems. Volumes
12.3/11.9/8.6 mm. With resolution recovery the resolution was of interest (VOI) for the spheres were obtained by applying a
9.9/9.0/7.5 mm compared with 8.3/7.2/5.9 mm. Analysis of the 50% threshold of the sphere maximum voxel value corrected
cardiac phantom images showed very similar overall image for background activity. For each sphere the mean recovery
S221 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

coefficient (RCmean) of three repeated measurements was methods the activity within the VOI were derived. For the latter
calculated, defined as the mean imaged activity concentration method, the optimal margins were defined when the expected
divided by the actual activity concentration. Accuracy was activity was reproduced, and the overall best margin chosen for
defined as the inter-system average of RCmean. Inter-system all quantitations. The relative difference between the maximum
variations (%) were defined as the range of RCmean divided by the and the minimum activity found for the three repeated scans was
accuracy. Results: Accuracy of RCmean decreased from 0.79 to used as a measure of interscan reproducibility. The difference
0.13 with decreasing sphere volume for vendor/center specific between the two methods was tested with a Wilcoxon signed-
reconstructions, while accuracy of RCmean decreased from 0.84 to rank test. Results: For the margin-based method, the additional
0.14 for vendor neutral reconstructions. Inter-system variations margins reproducing the sphere activity best were 8.16, 9.91,
of RCmean with vendor/center specific reconstructions were and 11.5 mm (approximately 4, 5, and 6 voxels) for background
between 4-58% depending on sphere size, and improved to contrast ratios of 1:0, 32:1 and 16:1, respectively. The mean
6-11% with vendor neutral reconstructions. These results are relative interscan differences across all background ratios were
preliminary, as the Discovery™ NM/CT data must still be analyzed 0.31, 0.12, 0.08, 0.07, 0.04, and 0.02 for spheres of increasing
and included. Conclusion: Despite using a standardized diameters for the RC-method, and 0.28, 0.08, 0.06, 0.06, 0.04, and
approach for acquisition and image analysis of multi-vendor 0.01 for the margin-based method using an overall considered
lutetium-177 SPECT/CT, inter-system variations in quantification optimal margin of 9.98 mm. There was an overall significant
of up to 58% remain. By standardizing reconstruction methods, difference between the two methods (p=0.006). Conclusion:
inter-system variations in quantification can be reduced Both methods provide interscan reproducibility in the order
drastically, paving the way for application of individualized of 1-10 %, except for the smallest sphere which may prove
treatment and universal dose limits. References: None. challenging to quantify accurately. Further work will include
investigations of motion effects, to more closely simulate the
patient scanning. References: None.
OP-567
Reproducibility and Accuracy for a Phantom with
Lutetium-177 Filled Spherical Inserts Using two Different OP-568
SPECT/CT Quantitation Methods; Implications for Tumour Automated, robust and agile organ segmentation for
Dosimetry After 177Lu-lilotomab satetraxetan Treatment voxel-based dose planning
J. Blakkisrud1,2, L. T. G. Mikalsen1, A. Løndalen1,3, C. Stokke1,4; M. Nazari1,2, A. Kluge1, S. Kimiaei1;
1
Division of Radiology and Nuclear Medicine, Oslo University 1
ABX - CRO advanced pharmaceutical services, Dresden,
Hospital, Oslo, NORWAY, 2Dept. of Physics, University of GERMANY, 2TU-Dresden, Dresden, GERMANY.
Oslo, Oslo, NORWAY, 3Faculty of Medicine, University of
Oslo, Oslo, NORWAY, 4Dept of Life Sciences and Health, Aim/Introduction: Voxel-based dose planning systems require
Oslo Metropolitan University, Oslo, NORWAY. delineation of organs at risk. Today, segmentations are either
done manually or in a semi-automated manner which is time-
consuming, error prone, operator-dependent and require
Aim/Introduction: Accurate quantitation of radioactivity is significant expertise. The main goals of this work are: a) to
fundamental for tumour dosimetry. At our centre, we treat extend, combine and/or optimize the architecture of an existing
lymphoma patients with 177Lu-lilotomab satetraxetan, targeting Convolutional Neural Network (CNN) to obtain a fast, robust
the CD37 antigen. Multiple post-therapy SPECT/CT-scans are and accurate CT-based organ segmentation method. b) to train
obtained with the aim of performing tumour dosimetry. The the CNN with an inhomogeneous set of CT scans and validate
amount of activity administrated is relatively low (approximately the CNNs usability for daily practice. Materials and Methods:
1 GBq), and the lesions are often small (down to a few milliliters). Our CNN was a modified attention based neural network and
Consequently, the images can be prone to intrascan motion Recurrent-CNN executed in two stages inspired by MASK r-cnn
due to prolonged acquisition periods. In this work, we used a operated in 2.5 mode. In the first step, the network calculates a
phantom to evaluate accuracy and interscan reproducibility Region of Interest (ROI) covering the sought organ. In the second
for two candidate quantitation methods. Materials and step, the ROI is fine-tuned. Two steps network eliminated the
Methods: A NEMA IEC Body Phantom Set without the lung- prerequisite of preprocessing of the images. The designed CNN
insert was used. Spheres with diameters of 10, 13, 17, 22, 28, was trained and evaluated using a database of 200 3D CT scans
and 37 mm were filled with 0.25 MBq/ml of lutetium-177. with the livers and kidneys segmented obtained from various
Sphere to background ratios of 1:0 (no background), 32:1 and sources. The data sets were hence acquired with different
16:1 were used. The chosen activity level and ratios reflect our scanners and acquisition protocols. Overall, the matrix size was
patient acquisitions for the described treatment. The scans were 512 x 512 with the slice spacing ranging from 0.4 to 6.5 mm and
repeated three times for each ratio. Two quantitation methods the in-plane resolution from 0.55-1.0 mm. 150 of the CT scans
were explored. Recovery-coefficient (RC) method: A volume were selected randomly for training, 10 sets for validation and
of interest (VOI) was placed around the physical boundary of 40 sets for final testing. Results: The global Dice-Coefficient
each sphere. Margin-based method: Spherical VOIs with radial accuracy obtained for the segmented livers was 93.0% and
margins of 0-15.6 mm were placed around the spheres. For both 94.1% for kidneys. The average CPU time required to segment
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S222

each of the 2.5 D slices on a 1.7 GHz Intel Core i7 was 2.5 1308
seconds. The time to segment an entire liver and kidneys using
a standard gaming GPU (approx. price €600) was less than 1 sec.
Clinical Oncology - Parallel Session: Therapy
Conclusion: Based on our preliminary evaluation, we conclude
Response Assessment - Conventional Criteria
that the proposed approach provides a fast and adequately
and More
accurate way to accelerate voxel-based dosimetry. Our fully
automated, yet robust method can also facilitate the broader Tuesday, October 15, 2019, 11:30 - 13:00 Lecture Hall 114
acceptance of 2.5D and 3D dosimetry in the routine practice.
Finally, the general ability of our segmentation algorithm,
using transfer learning, will allow us to extend its usage to
delineation of other organs such as spleen, heart and bladder OP-573
with moderate efforts. References: This project has received Value Of FDG PET/CT To Evaluate The Efficacy Of
funding from the European Union’s Horizon 2020 research and Regorafenib In Locally Advanced Non_Resectable/
innovation programme under the Marie Skłodowska-Curie Metastatic Biliary Tract Tumors: The REACHIN Study
grant agreement No 764458. R. Lhommel1, L. Guillaume1, I. Borbath1, S. Goldman2, J. Van
Laethem2, A. Demols2;
1
Cliniques Universitaires Saint-Luc, UCLouvain, Brussels, BELGIUM,
1307 2
Hôpital Universitaire Erasme - ULB, Brussels, BELGIUM.
Pitfalls & Artefacts 6 - Interactive Clinical Cases -
Cardiovascular Committee: Pitfalls & Artefacts in Aim/Introduction: The REACHIN study is a double blinded
Cardiac Imaging randomized placebo controlled phase II trial aiming to
evaluate the safety and efficacy of regorafenib for patients
Tuesday, October 15, 2019, 11:30 - 13:00 Lecture Hall 113 with locally advanced (non-resectable)/metastatic biliary tract
tumors progressing after gemcitabine and platinum based
chemotherapy. Primary endpoint was PFS and secondary
endpoints were response rate (using RECIST 1.1), OS and
OP-569 safety. The tumor early response-to-treatment was evaluated
SPECT/CT separately by DWI-MRI and FDG PET/CT. The result of the FDG
C. Nappi; PET/CT sub-study is presented here. Materials and Methods:
Institute of Biostructures and Bioimaging, Naples, ITALY. Between May 2014 and February 2018, 66 patients were recruited
OP-570 and randomized (1:1) to received either Best Supportive Care
PET/CT (BSC)+Placebo (Control arm) or BSC+Regorafenib (160mg
R. Sciagra; per day 21 days on, 7 days off, treated arm) until progression/
Department of Experimental and Clinical Biomedical unacceptable toxicity. From them, 29 patients (control n=15/
Sciences, University of Florence, Florence, ITALY. Rego n=14) were willing and eligible to participate to the PET/
CT window sub-study, comparing the FDG tumor metabolism at
baseline and after two weeks of arm-regimen-based treatment.
OP-571 The main inclusion criteria was at least one FDG positive lesion
Cardiac-Centered Gamma Cameras (primary/metastases) at baseline, with a Tumor/Liver-uptake-
O. Lairez; ratio ≥1.4. Two independent PET/CT readers were blinded
University Hospital Toulouse, Toulouse, FRANCE. of the patient’s randomization and clinical results during the
scans review and tumor sites delineation (MIMvista software).
Metabolic parameters considered for the statistical analysis
OP-572 (PRISM 8) were SUVbw_max, SUVbw_peak, Metabolic-Tumor-
Hybrid Imaging Volume (MTV) and Total-Lesion-Glycolysis (TLG=MTVx SUVbw_
C. Rischpler; mean). A 3cm diameter sphere was also placed within the non-
University Hospital Essen, Essen, GERMANY. tumor healthy liver as reference. Results: Primary endpoint was
met with significantly increase of the PFS from 1.5 to 3 months,
p=0.004 (ASCO GI 2019). For the PET window study, both
∆SUVmax, ∆MTV and ∆TLG (%change from baseline) show a
significant decline between baseline and FU scan for the treated
group (P=0.0151*;0.037**; 0.0056**) compared to the placebo
arm. The main tumor SUVmax was significantly decreased in the
treated group but not in the control arm (P=0.0353* vs 0.5614).
Both TLG and MTV significantly progressed in the control arm
(p= 0.0004***; 0.0002***; ) while a stabilization/NS progression
S223 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

was observed in the treatment arm (P=0.3910 ; 0.2412). There months, and overall survival (OS) was 18.5 months. Baseline
was no relevant treatment’s related impact on the reference- [18F]fluciclatide uptake was predictive of long PFS. Elevated
liver-uptake (P=0.381(ctrl); 0.6149(rego)). Conclusion: Despite a baseline circulating angiopoietin and fibroblast growth factor
limited number of patients, FDG PET/CT seems performant to (FGF) were predictive of greater reduction in SUV60,mean following
discriminate early positive metabolic tumor changes in patients pazopanib. Kinetic modelling of PET data indicated a reduction
treated with regorafenib as compared to the control/placebo in K1 and Ki following pazopanib indicating reduced radioligand
group. Additional analysis are ongoing to estimate if these early delivery and retention. Conclusion: In a phase 1b study of
changes also correlate with the final clinical output parameters combination therapy of the anti-angiogenic pazopanib and
(PFS, OS). References: Regorafenib after failure of gemcitabine paclitaxel followed by maintenance pazopanib, [18F]fluciclatide-
(...). Demols A. et al. ASCO GI 2019, abstract 345. PET uptake parameters were observed to be predictive clinical
outcome indicating an anti-angiogenic response. References:
None.
OP-574
[18F]fluciclatide Pet As A Biomarker Of Response To
Combination Therapy Of Pazopanib And Paclitaxel In OP-575
Platinum-resistant/refractory Ovarian Cancer Combination of 18F-FDG PET/CT-based Metabolically
R. Sharma1, P. O. Valls1, M. Inglese1, S. Dubash1, M. Chen1, H. Active Tumor Volume and Early Metabolic Response
Gabra1, A. Montes2, A. Challapalli1, M. Arshad1, G. Thakaran1, Significantly Improves Outcome Prediction in Metastatic
E. Chambers1, T. Cole1, J. Lozano-Kuehne1, T. D. Barwick1, E. O. Colorectal Cancer: results from two prospective
Aboagye1; development and one external validation cohort
1
Imperial college london, London, UNITED KINGDOM, 2Guys E. Woff1, A. Hendlisz1, L. Salvatore2, F. Marmorino3, A. Falcone3,
and St Thomas’ NHS Trust, London, UNITED KINGDOM. D. Genovesi4, A. Giorgetti4, G. Critchi1, T. Guiot1, H. Levillain1, N.
Plouznikoff1, P. Flamen1;
1
Institut Jules Bordet, Brussels, BELGIUM, 2Fondazione
Aim/Introduction: Angiogenesis is a hallmark of cancer and Policlinico Universitario Agostino Gemelli IRCCS, Rome,
a therapeutic target in a number of tumour types including ITALY, 3Azienda Ospedaliera Universitaria Pisana, Pisa, ITALY,
ovarian, colorectal and renal cell carcinoma. Despite their 4
Fondazione Toscana “Gabriele Monasterio”, Pisa, ITALY.
therapeutic activity, anti-angiogenic agents are associated with
significant side-effects, a key consideration in the palliative
setting. The main limitation of anti-angiogenics is the paucity Aim/Introduction: This study aimed to develop and validate
of imaging response biomarkers allowing early identification a model integrating baseline metabolically active tumor
of non-responders and cessation of ineffective, potentially volume (MATV) and early metabolic response (mR) among
toxic treatment. Integrins αvβ3 and αvβ5 are both up-regulated clinical prognostic factors in metastatic colorectal cancer
in tumor-associated vasculature. [18F]Fluciclatide is a novel PET (mCRC) patients. Materials and Methods: The development
tracer that has high affinity for integrins αvβ3/5. We performed cohort included chemorefractory mCRC patients enrolled in
a phase Ib study of combinatorial therapy with pazopanib and two prospective Belgian multicenter non-randomized trials
weekly paclitaxel, followed by maintenance pazopanib in patients evaluating multikinase inhibitors as last line therapy. The
with platinum-resistant/refractory ovarian cancer. The primary validation cohort prospectively included mCRC patients from
outcome of which was to ascertain whether [18F]fluciclatide-PET Italian centers treated with chemotherapy and bevacizumab as
could be used as a pharmacodynamic (PD) marker of pazopanib first line. Baseline MATV was defined as the sum of metabolically
effect following 1 week of single agent therapy. The secondary active volumes of all target lesions identified on the baseline
endpoints were to assess the relationship between [18F] 18
F-FDG PET/CT. Early metabolic non-responder patients were
fluciclatide uptake with pharmacokinetics (PKs) of pazopanib identified when at least one target lesion showed no significant
and with circulating markers of angiogenesis. Materials and decrease of SUVmax (<15%). Univariate analyses for overall and
Methods: We conducted an open-label, phase Ib study in progression-free survival (OS/PFS) were performed to assess
patients with platinum resistant/refractory ovarian cancer. the prognostic values of MATV and early mR and multivariate
Patients received 1 week of single agent pazopanib (800mg analyses to assess their prognostic independency along with
daily) followed by combination therapy with weekly paclitaxel clinical factors (age, gender, BMI, ECOG PS, and KRAS status).
80mg/m2. Following completion of 18 weeks of combination Results: MATV, early mR, and clinical factors were evaluable
therapy, patients continued with single agent pazopanib until respectively in 216 and 122 patients of the development and
disease progression. Dynamic [18F]Fluciclatide-PET imaging was validation cohorts. In univariate analyses, baseline MATV and
conducted at baseline and after 1 week of pazopanib. Response early mR were strongly related to outcome (OS/PFS) in both
(RECIST 1.1), toxicities and survival outcomes were recorded. cohorts. Multivariate analyses identified in the development
Circulating markers of angiogenesis were assessed with therapy. cohort two independent negative predictors for OS (high MATV
Results: Fourteen patients were included in the intention-to- and BMI<30) and PFS (high MATV and early mNR), and in the
treat analysis. Complete and partial response was seen in seven validation cohort three for OS (high MATV, early mNR, poor
patients (54%). Median progression free survival (PFS) was 10.63 PS) and PFS (high MATV, early mNR, KRAS mutated). A model
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S224

combining baseline MATV and early mR allowed to identify from the primary tumor at each time point separately. Delta
three risk groups for OS and PFS respectively with different radiomics/values ([posttreatment feature value − pretreatment
median OS/PFS in the development (12.1 vs 6.7 vs 3.8 months feature value]/pretreatment feature value) following treatment
for the low, intermediate and high-risk groups; p<0.001 for OS were calculated for each parameter (PET2, CE-CT2, PET3, CE-
and 4.9 vs 2.9 vs 1.3 months; p<0.001 for PFS) and validation CT3). Association of features to non-/recurrence, progression
cohorts (40 vs 25.3 vs 15.7 months; p<0.001 for OS and 15.3 vs free survival (PFS), and between the different modalities
10.6 vs 7.7 months; p<0.001 for PFS). Conclusion: This study was evaluated (Spearman’s Rho “ρ”). A p-value of <0.05 was
demonstrates the robustness of combined baseline MATV considered statistically significant. Results: 38 patients were
and early mR as prognostic biomarkers for OS/PFS in mCRC, free of recurrence during follow-up period (52+/-22 month;
independently of patients’ treatment. As independent predictors range 8-89). PFS was 38+/-26 month (range 2-83). There was
of outcome, combining these biomarkers allowed to improve no significant correlation between patients with/without
risk stratification for OS and PFS in both the development and recurrence, and SUVmax (p=0.17, 0.65, 0.94) or HUmean (p=0.17,
validation cohorts. References: None. 0.40, 0.05) at the 3 imaging time points. None of the PET/CE-CT1,
but delta radiomics of 4 PET2 (0.02<p<0.04), 1 CE-CT2 (p=0.03),
9 PET3 (0.001<p<0.02), and 6 CE-CT3 (0.01<p<0.04) features
OP-576 could significantly predict the development of a recurrence.
Multimodal Radiomic Imaging: Evaluation of 18F-FDG- SUVmax and HUmean at 3 imaging time points were not
PET and CE-CT as an early Imaging Biomarker for significantly correlated to PFS (ρ=-0.25,-0.06,-0.11 for SUVmax
Prognostication and Response Prediction after and ρ=0.10,-0.07,-0.27 for HUmean). Pre-treatment values
Radiochemotherapy using Cetuximab in Head and Neck and proportional differences of selected significant radiomic
Squamous Cell Carcinoma features showed weak (PET1: -0.29<ρ<0.32; CT1: -0.31<ρ<0.30),
B. Sah1,2,3, M. Bogowicz4, S. Tanadini-Lang4, O. Riesterer4,5, C. weak to moderate (PET2: -0.44<ρ<0.39; CT2: -0.38<ρ<0.26), and
Leissing6, J. Heverhagen2, G. Studer4,7, M. W. Huellner1, P. Veit- moderate (PET3: -0.47<ρ<0.60; CT3: -0.36<ρ<0.38) correlation
Haibach1,3,8; to PFS. Comparison of respective radiomic features between
1
Department Nuclear Medicine, University Hospital Zurich and PET and CE-CT showed weak to moderate correlation at 3
University of Zurich, Zurich, SWITZERLAND, 2Department of imaging time points (0.24<ρ<0.76, -0.05<ρ<0.55, -0.02<ρ<0.39).
Diagnostic, Interventional, and Pediatric Radiology, Inselspital, Conclusion: Radiomics in a multimodality approach might
University of Bern, Bern, SWITZERLAND, 3Department of be a complementary tool for response prediction and
Diagnostic and Interventional Radiology, University Hospital prognostication of patients with HNSCC as early as 1 week after
Zurich, Zurich, SWITZERLAND, 4Department of Radiation primary radiochemotherapy. References: None.
Oncology, University Hospital Zurich, Zurich, SWITZERLAND,
5
Department of Radiation Oncology, Kantonsspital Aarau, Aarau,
SWITZERLAND, 6University of Zurich, Zurich, SWITZERLAND, OP-577
7
Department of Radiation Oncology, Kantonsspital Luzern, Prediction Of Therapeutic Response And Long-term
Luzern, SWITZERLAND, 8Joint Department of Medical Outcomes By EORTC Criteria And Percist In Breast Cancer
Imaging, University of Toronto, Toronto, ON, CANADA. Following Two Courses Of Neoadjuvant Chemotherapy

W. Lian, C. Liu, Z. Yang, S. Song, Y. Zhang;


Aim/Introduction: This study investigated the value of F-18- Fudan University Shanghai Cancer Center, Shanghai, CHINA.
Fluorodeoxyglucose-positron-emission-tomography (PET)
radiomics in comparison to contrast-enhanced-computed-
tomography (CE-CT) radiomics in a) evaluation of progression Aim/Introduction: To investigate the predictive value of 18F-FDG
free survival after radio-chemo-therapy, and b) identifying PET/CT for pathological response and disease recurrence in
patients who will be free of recurrence of head and neck breast cancer patients during neoadjuvant chemotherapy
squamous cell carcinoma (HNSCC) as early as one week after (NAC). Materials and Methods: Consecutive PET/CT scans in
end of radiochemotherapy. Materials and Methods: Following 128 operable breast cancer female patients at baseline and after
Institutional Ethics Committee approval and informed two courses of NAC were retrospectively analyzed using the
consent, a total of 59 patients with histologically proven and European Organization for Research and Treatment of Cancer
locoregionally advanced HNSCC were prospectively enrolled in (EORTC) criteria and Positron Emission Tomography Response
this single-center randomized study, and scheduled for curative Criteria in Solid Tumors (PERCIST). The concordance between
radiochemotherapy including cetuximab and cisplatin. PET and these criteria was determined using Cohen’s &#954; coefficient.
CE-CT were acquired on the same machine. Patients underwent Metabolic changes between scans for predicting pathological
PET/CE-CT imaging at 3 time points: pre-treatment (PET/CE- complete response (pCR) were evaluated with diagnostic test
CT1), 1 week post primary radiochemotherapy (PET/CE-CT2) and receiver operating characteristic (ROC) analysis. Molecular
and 3 months post primary radiochemotherapy (PET/CE-CT3). subtypes were taken into consideration in the analysis. Kaplan-
154 radiomic features of first, second, and higher order, glucose Meier plots and Cox regression analysis for the correlation
uptake (SUVmax), and Hounsfield units (HU) were extracted with progression-free survival (PFS) were performed. Results:
S225 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

Ninety-two patients were finally enrolled. CMR was determined determine which method best predicts the possibility to
in 36 patients with EORTC criteria and 35 with PERCIST, and achieve an optimal surgery. Materials and Methods: Thirty-
the &#954;coefficient was 0.988. Thirty-three patients showed eight women diagnosed with primarily inoperable high-grade
postoperative pCR. The sensitivity, specificity, positive predictive serous ovarian cancer (FIGO IIIB-IV) were retrospectively studied.
value (PPV), negative predictive value (NPV), and accuracy All of them underwent two PET/CT scans: one at diagnosis
for pCR prediction were 69.7% (23/33), 77.9% (46/59), 63.9% (PET1) and another one after 3 or 4 cycles of standard NACT
(23/36), 82.1% (46/56), and 75.0% (69/92) with EORTC criteria, with taxol/carbo (PET2). Metabolic parameters for response
respectively, and 69.7%(23/33), 79.7%(47/59), 65.7%(23/35), evaluation (SUVmax for EORTC and SULpeak for PERCIST 1.0)
82.5%(47/57), and 76.1%(70/92) with PERCIST, respectively. The were obtained both at PET1 and at PET2. Response to treatment
decline percentage of maximum standardized uptake value was classified as complete metabolic response (CMR), partial
(SUVmax), total lesion glycolysis (TLG), and metabolic tumor metabolic response (PMR), stable metabolic disease (SMD), and
volume (MTV) were found to be moderately distinguished progressive metabolic disease (PMD). Concordance between
pCR from non-pCR with the area under the curves (AUCs) of both evaluation criteria was assessed using Cohen’s kappa.
0.715, 0.743, and 0.754, respectively (p = 0.001, p < 0.001, and Relation between the type of response and optimal surgery
p < 0.001). Nineteen (20.7%) of the 92 patients relapsed at a for each method was calculated using the Chi-square test.
median follow-up period of 48.7 months (20.6-84.1 months). Results: Final response analysis was performed considering
The univariate Cox analysis indicated that complete metabolic only infradiaphragmatic disease, as supradiaphragmatic lesions
response (CMR) by EORTC (p = 0.017) and PERCIST (p = 0.021), (detected in 60.5% of patients) did not modify the surgical
and HER2 overexpression (p = 0.037) were significantly related decision. According to EORTC criteria, 11 patients (28.9%)
to a longer PFS. The multivariate analysis suggested that CMR reached a CMR, 25 (65.8%) a PMR, 1 (2.6%) showed SMD, and 1
by EORTC was considered to be an independent predictor to PMD. Considering PERCIST 1.0 criteria, 11 patients (28.9%) had
disease recurrence (p = 0.017). Conclusion: The sensitivity and a CMR, 23 (60.5%) a PMR, 3 (7.9%) had SMD, and 1 had PMD.
specificity of both EORTC criteria and PERCIST were relatively Concordance between both methods was excellent (k=0.90),
suboptimal to predict pCR. However, EORTC criteria were more with inconsistent results in 2 patients (5.3%), both changing
valuableapproaches than PERCIST for predicting progression- from PMR with EORTC to SMD with PERCIST 1.0. Optimal surgery
free survival in operable breast cancer patients following two was achieved in 30 patients (78.9%). Chi-square test showed no
cycles of NAC. References: None. differences between reaching a CMR or a PMR and the possibility
to achieve an optimal surgery, neither considering EORTC
criteria (p=0.418), nor when applying PERCIST 1.0 (p=0.523).
OP-578 Conclusion: EORTC and PERCIST 1.0 criteria have an excellent
EORTC versus PERCIST 1.0 Criteria In The Evaluation Of correlation to evaluate response to NACT in inoperable high-
Response To Neoadjuvant Chemotherapy In Inoperable grade serous ovarian carcinoma. None of the two methods
High-grade Serous Ovarian Carcinoma. Which One Best shows significant differences between reaching a CMR or a PMR
Predicts An Optimal Interval Surgery? and the possibility to achieve an optimal surgery. References:
A. Sabaté-Llobera1, J. Robles-Barba2, A. Palomar-Muñoz2, J. None.
Mestres-Martí2, B. Pardo3, M. T. Climent4, E. Llinares-Tello2, J. Ponce4,
C. Gámez-Cenzano2;
1
PET Unit, Nuclear Medicine Department-IDI. Gynecologic OP-579
Oncology Multidisciplinary Team. Hospital Universitari de Response Assessment to Immunotherapy with PD1
Bellvitge-IDIBELL, L’Hospitalet de Llobregat (Barcelona), Inhibitors Using Metabolic Tumor Volume on 18F-FDG PET/
SPAIN, 2PET Unit, Nuclear Medicine Department-IDI. Hospital CT
Universitari de Bellvitge-IDIBELL, L’Hospitalet de Llobregat G. Ferreira, S. F. Castro, I. L. Sampaio, L. S. Violante, J. P. Teixeira, H.
(Barcelona), SPAIN, 3Department of Medical Oncology-ICO. Duarte;
Gynecologic Oncology Multidisciplinary Team. Hospital Instituto Português de Oncologia do Porto
Duran i Reynals-IDIBELL, L’Hospitalet de Llobregat (Barcelona), Francisco Gentil, Porto, PORTUGAL.
SPAIN, 4Department of Gynecology. Gynecologic Oncology
Multidisciplinary Team. Hospital Universitari de Bellvitge-
IDIBELL, L’Hospitalet de Llobregat (Barcelona), SPAIN. Aim/Introduction: Immunotherapy with checkpoint inhibitors
(CPIs) directed towards the programmed cell death protein
1 (PD1) produces durable responses in a variable yet small
Aim/Introduction: Debulking surgery is the primary staging proportion of metastatic melanoma patients. While response
and treatment procedure for patients with ovarian cancer. assessment based on 18F-FDG PET/CT may be able to early
However, maximal debulking is not always possible in high identify non-responders, inflammatory response induced
stage disease, so neoadjuvant chemotherapy (NACT) followed by CPIs could limit the accuracy of currently used PET-based
by interval cytoreduction is a therapeutic alternative. This criteria. We evaluated the association between response based
study aims to evaluate the response to NACT by FDG-PET/ on total metabolic tumor burden and prognosis in patients with
CT, applying both EORTC and PERCIST 1.0 criteria, trying to metastatic melanoma treated with PD-1 inhibitors. Materials
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S226

and Methods: We analyzed patients with metastatic melanoma mean age 75) with NSCLC and treated with ICI from April 2017
treated with pembrolizumab and nivolumab between 2017 to December 2018. Complete blood cell counts before and
and 2018. From this cohort, 30 consecutive subjects performing after 8 weeks of treatment were measured. Likewise, all patients
18
F-FDG PET/CT scans before and after treatment initiation were underwent 18F-FDG PET/CT at baseline, while 25 patients after
included and followed until last observation or death (median 8.1 8 weeks of treatment. Response assessment was according
months, IQR 8.03). Median time between start of treatment and to EORTC criteria. Progression-free survival (PFS) and overall
response assessment was 11.0 weeks (IQR 3.07). Response was survival (OS) were determined and compared using the Kaplan-
defined according to interval change in total-body metabolic Meier method and the log-rank test. Multivariate analysis for
tumor volume (MTV), adopting the same thresholds to define PFS and OS were performed using the variables that were
response as PET Response Criteria in Solid Tumors (PERCIST). significant on univariate analysis by Cox proportional hazard
Unlike PERCIST, appearance of new lesions was not necessarily regression analysis. Median follow-up was 11.3 months (range
considered disease progression. Chi-square and Log Rank tests 1-17 months). Results: We found a progressively increase of
were used to compare overall survival (OS) between groups and neutrophil-to-lymphocyte ratio between baseline and after 8
multivariable cox regression to determine prognostic factors. weeks (ΔNLR) among response groups (median ΔNLR -19.8%
Agreement between MTV-based and PERCIST criteria was for partial metabolic response, +29.6% for stable metabolic
assessed. Results: According to MTV-based criteria, 18 (60.0%) disease, and +180.8% for progressive metabolic disease,
patients had progressive disease (PD), 7 (23.3%) partial response p=0.03). In multivariate analysis, low post-treatment NLR (<
(PR) and 5 (16.7%) complete response (CR). In patients with PD, 4.9) and total lesion glycolysis (post-TLG< 541.5 ml) were
OS at 6 months was 55.6%, vs 100% (p=0.009) in responders independently associated with both PFS (HR 0.273; 95%CI,
(PR and CR). Moreover, none of the responders died during 0.92-0.806 and HR, 0.295; 95%CI, 0.092-0.806, respectively) and
the entire follow-up time, while patients with PD had a median OS (HR 0.044; 95%CI, 0.007-0.275 and HR, 0.204; 95%CI, 0.042-
OS of 6.9 months (95% CI 3.8-10.0, p<0.001). Multivariable 0.988, respectively). Afterwards, we developed an immune-
analysis identified MTV quantitative decrease between scans to metabolic prognostic index (IMPI), based on post-NLR < 4.9 and
significantly associate with survival (HR 1.06, 95% CI 1.02-1.09, post-TLG < 541.5 ml, classifying 3 groups: high risk, 2 factors;
p=0.001), independently of age, gender and baseline total-body intermediate risk, 1 factor; low risk, 0 factors. Median PFS for low,
tumor load. There was substantial agreement between MTV- intermediate and high risk was 7.8 months, 5.6 months, and 1.8
based and PERCIST criteria (κ=0.689, p<0.001). Importantly, 2 months, respectively (p<0.001). Likewise, median OS was 15.2
patients with PR according to MTV-based criteria were classified months, 13.2 months, and 2.8 months, respectively (p<0.001).
as PD in PERCIST due to the appearance of new lesions. These Conclusion: Combination of both immune (post-NLR < 4.9)
regressed spontaneously during follow-up, accounting for a and metabolic (post-TLG < 541.5) biomarkers, was associated
phenomenon of pseudoprogression. Conclusion: In patients with longer PFS and OS. This result could better characterize
with metastatic melanoma treated with anti-PD1 agents, the tumor biology and aid oncologists for identifying NSCLC
response assessment according to MTV interval change on patients who likely need to change therapy. However, further
18
F-FDG PET/CT imaging was significantly associated with OS. larger studies are warranted to establish IMPI as predictor of
This method may overcome the problems associated with outcome. The Italian Association for Research on Cancer (AIRC -
pseudoprogression, allowing for better stratification of patients Associazione Italiana per la Ricerca sul Cancro) is acknowledged
with progressive disease based on standard PERCIST criteria. for the support on research. References: None.
References: None.

YDF3
OP-580 EANM Young Daily Forum
Immune-Metabolic-Prognostic Index (IMPI): Combination
of 18F-FDG PET/CT and Peripheral Blood Biomarkers in
Patients with NSCLC Treated with Checkpoint Inhibitors Tuesday, October 15, 2019, 13:00 - 14:30 Lecture Hall 113
A. Castello1, L. Toschi2, S. Rossi2, E. Mazziotti1, E. Lopci1;
1
Nuclear Medicine, Humanitas Clinical and Research Hospital -
IRCCS, Rozzano (MI), ITALY, 2Oncology and Hematology, Humanitas
Clinical and Research Hospital - IRCCS, Rozzano (MI), ITALY. YDF-3
Be Stronger - Managing Work Stress and Building Your
Resilience
Aim/Introduction: To investigate whether metabolic R. Sheppard;
parameters evaluated by 18F-FDG PET/CT and peripheral blood EANM Moderator, London, UNITED KINGDOM.
biomarkers can be associated with clinical outcomes in patients
affected by metastatic NSCLC and treated with immune
checkpoint inhibitors (ICI). Materials and Methods: The trial
was registered at http://www.clinicaltrials.gov (NCT03563482).
We prospectively enrolled 33 patients (21 male, 12 female,
S227 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

1401 OP-589
Response Assessment with Imaging - The Clinician’s Point
CME 11 - Physics + Cardiovascular Committee: of View
Advances in Quantitative Cardiac Imaging M. Rosendahl;
Rigshospitalet - Copenhagen University
Tuesday, October 15, 2019, 14:30 - 16:00 Auditorium Hospital, Copenhagen, DENMARK.

OP-590
OP-581 Response Assessment with PET/CT and PET/MR - The
Quantification in SPECT - Current State and Perspectives Nuclear Medicine Physician’s Point of View
M. Hakulinen; N. Aide;
Kuopio University Hospital, Imaging Centre, Department of University Hospital, Department of Nuclear Medicine
Clinical Physiology and Nuclear Medicine, Kuopio, FINLAND. and Medical Physics, Caen, FRANCE.

OP-582 1403
Quantification in PET - Current State and Perspectives
I. Armstrong;
Joint Symposium 22
Nuclear Medicine Department, Manchester University
Hospital NHS Trust, Manchester, UNITED KINGDOM. Tuesday, October 15, 2019, 14:30 - 16:00 Lecture Hall 312

OP-583 Session details not finished as per date of publishing


Quantification in CT - Current State and Perspectives
M. Dewey;
Charité, Radiology, Berlin, GERMANY. 1404
CTE 5 - Interactive - Technologist Committee:
1402 Patient Communication
Joint Symposium 21 - Oncology & Theranostics Tuesday, October 15, 2019, 14:30 - 16:00 Lecture Hall 117
Committee / ESGO: Ovarian Cancer

Tuesday, October 15, 2019, 14:30 - 16:00 Lecture Hall 311


OP-596
Health Communication - Design Thinking
D. Miranda;
OP-587 National School of Public Health, Lisbon, PORTUGAL.
Staging, Prognosis and Relapse Detection - The Clinician’s
Point of View
A. Ferrero; OP-597
Academic Division Gynaecology and Obstetrics - University Patient Welfare and Advocacy - A View from the Inside
of Torino, Mauriziano Hospital, Torino, ITALY. M. Lee;
EANM, Patient and Public Involvement and
Engagement, London, UNITED KINGDOM.
OP-588
Staging, Prognosis and Relapse Detection with PET/CT and
PET/MR - The Nuclear Medicine Physician’s Point of View OP-598
R. Delgado Bolton; Risk Communication - Why and How to Communicate
San Pedro Hospital - Centre for Biomedical Research about Ionizing Radiation?
of La Rioja (CIBIR), Servicio Riojano de Salud (SERIS), T. Perko;
Department of Diagnostic Imaging (Radiology) and Belgian Nuclear Research Centre, Mol, BELGIUM.
Nuclear Medicine, Logroño - La Rioja, SPAIN.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S228

1405 showed favorable properties for imaging α7-nAChR despite the


relatively lower brain uptake. Acknowledgements: Support from
M2M - Parallel Session: Targeting the Brain the Swedish Foundation for Strategic Research (SSF, RB13-0192)
References: None.
Tuesday, October 15, 2019, 14:30 - 16:00 Lecture Hall 111

OP-600
Synthesis and bioevaluation of a novel TSPO-selective
OP-599 PET probe, [18F]BS224 with low binding sensitivity to TSPO
Development of novel 11C- labeled ASEM analogs for polymorphism
detection of neuronal nicotinic acetylcholine receptors I. Song1, S. Lee2, B. Lee1,3, S. Kim1,2,3;
(α7-nAChR) 1
Department of Nuclear Medicine, Seoul National University
S. Nag1, Z. Jia1, P. Datta1, P. M. Azpiazu1, R. Arakawa1, K. Varnäs1, L. Bundang Hospital, Seongnam, KOREA, REPUBLIC OF, 2Graduate
Lemoine1, G. Kuang2, H. Ågren2, B. Långsträm3, C. Halldin1; School of Convergence Science and Technology, Seoul National
1
Karolinska Institutet, Stockholm, SWEDEN, 2Royal University, Suwon, KOREA, REPUBLIC OF, 3Center for Nanomolecular
Institute of Technology, Stockholm, SWEDEN, Imaging and Innovative Drug Development, Advanced Institutes
3
Uppsala University, Stockholm, SWEDEN. of Convergence Technology, Suwon, KOREA, REPUBLIC OF.

Aim/Introduction: The homo-pentameric alpha 7 receptor Aim/Introduction: Selective TSPO-ligand could provide
is one of the major types of neuronal nicotinic acetylcholine a powerful imaging tool to detect and monitor several
receptor (α7-nAChR) related to cognition, memory formation, inflammatory brain disorders1. However, single nucleotide
and attention processing. The mapping of α7-nAChR by polymorphism in the TSPO gene influences the binding
PET draws a lot of attention to understand mechanism and affinity of TSPO ligands, eventually leading to a binding profile
the progress of CNS diseases such as AD, PD, schizophrenia. classification according to each genotype2. Thus, novel ligand,
Several PET ligands have been explored for imaging of the α7- which has no dependency of the polymorphism on the binding
nAChR, but [18F]ASEM is so far the most interesting for in vivo affinity for TSPO, is urgently needed. This study aimed to develop
quantification of α7-nAChR in human. The aims of this study and evaluate a novel TSPO-selective PET imaging agent, [18F]
were i) to explore the binding profile of ASEM derivatives by BS224, which is unaffected from TSPO polymorphism. Materials
in silico methods ii) label the suitable derivatives with 11C/3H and Methods: [18F]BS224 were synthesized by two different
and to evaluate some binding characteristics in vitro and precursors, respectively: i)diaryliodonium salts (condition A);
in vivo. Materials and Methods: All molecular dynamics ii)pinacol boronate ester (condition B). Both conditions for
simulations were carried out using the GROMACS 4.6.7 code. aromatic [18F]fluorination was optimized in various phase
The Glide utility of the Schrodinger software package was transfer catalysts, solvents, temperatures, and catalysts. [18F]
used for molecular docking and the Bennett Acceptance Ratio BS224 (Rt=34 min) was collected from semi-preparative
(BAR) method was used to carry out free energy calculations. HPLC(Xterra Semi-preparative C18 column, 10x250 mm, 10 µm;
Five analogs of ASEM (KIn 74, KIn 75, KIn 84, KIn 85 and KIn 83) 50% acetonitrile-water, UV 250 nm, flow rate: 5.0 mL/min). We
were labeled with 11C and Kln 83 was additionally labeled with prepared 294FT cell transfected with wild TSPO gene(TSPO wild)
3
H. Binding properties were evaluated using autoradiography or A147T point mutant gene(TSPO mutant). Cellular uptake
(ARG) and PET measurements in a few non-human primates assay of [3H]PK11195, [18F]PBR28, and [18F]BS224 was performed
(NHPs). Radiometabolites were measured in NHPs plasma using and the radioactivity of the samples was normalized by the
gradient radio HPLC. Results: Five ASEM analogs were chosen protein concentration of each sample. Results: A new aromatic
for radiolabeling depending on the docking score, free energy fluorine-substituted imidazo[1,2-a]pyridine analogue, BS224,
calculation and feasibility of the radiolabeling. All compounds showed a subnanomolar affinity(Ki=0.51 nM). Using condition
were successfully radiolabeled with purity >99%. Evaluation A, [18F]BS224 was synthesized with 18-25% radiochemical
with ARG showed that only [11C]Kln83 (0.01 MBq/ml) binds yield(RCY). In condition B, much higher RCY of [18F]BS224(63.6%)
to α7-nAChR in rat brain. Competition studies showed that was shown in the presence of copper(II)triflate and pyridine in
80% of the total binding was displaced by adding 10 μM of dimethylformamide. Finally, the radio-synthesis of [18F]BS224 was
unlabeled KIn83 and ASEM. Further ARG were performed with optimized by using condition B including HPLC purification. The
[3H]KIn83, replicating the results obtained with [11C]KIn83. In RCY of the final product was 39±6.8 % (n=3, decay-corrected)
vivo [11C]KIn83 brain uptake was relatively low (1.6 SUV at peak) with high molar activity(127 GBq/µmol) and radiochemical
compared to [18F]ASEM (4.4 SUV). Regional distribution of [11C] purity(>99 %). Log D and in vitro human serum stability were
KIn83 was similar to [18F]ASEM, with relatively high uptake in 2.78±0.04 and >99% after 2 h incubation, respectively. Cellular
thalamus, cortex and basal ganglia. Low uptake was observed uptake ratios (Wild/Mutant) of [3H]PK11195, [18F]PBR28, and [18F]
in cerebellum and white matter. Radiometabolism of [11C]KIn83 BS224 were 1.29, 4,79 and 1.24, respectively. Cellular uptake of
was relatively fast. Conclusion: Preliminary evaluation of KIn 83 [18F]BS224 in TSPO mutant was significantly reduced compared
by ARG with both 11C and 3H as well as in vivo evaluation in NHP to that in TSPO wild. However, in the case of [3H]PK11195 and
S229 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

[18F]BS224, the cellular uptakes were similar between TSPO wild cerebral cell proliferation appear after a bilateral vestibular lesion
and mutant. Conclusion: Aromatic [18F]fluorination of BS224 in the VN, hippocampal DG and SVZ. [18F]FLT imaging is a feasible
was successfully performed by nucleophilic substitution of method to depict differential regulations in these neurogenic
the corresponding pinacol boronate ester precursor using [18F] niches over time in vivo. As the number of proliferating cells is
fluoride. [18F]BS224 was showed with a little dependency of the rather small in the adult brain, [18F]FLT-based experiments need
polymorphism on the cellular uptake. Based on these results, to be done in larger groups and with probenecid pre-treatment
[18F]BS224 is a promising TSPO PET imaging agent overcoming to depict changes in neurogenesis. References: Tamura, Y., et al.
the TSPO polymorphism. References: [1] G. Kreutzberg, et al. Noninvasive Evaluation of Cellular Proliferative Activity in Brain
(1997) Journal of neurocytology, 26, 77-82.[2] Owen DR, et al. Neurogenic Regions in Rats under Depression and Treatment by
(2012) J Cereb Blood Flow Metab. 32, 1-5. Enhanced [18F] FLT-PET Imaging. Journal of Neuroscience 36,
8123-8131 (2016).

OP-601
In Vivo Visualization Of Cerebral Cell Proliferation And OP-602
Neurogenesis After Bilateral Labyrinthectomy In The Rat Preclinical comparison of the first generation Tau PET
By Serial [18F]FLT Imaging tracer AV1451 and two next-generation Tau PET tracers,
C. Branner1,2, A. Krämer1,2, M. Lindner1,2, A. Gosewisch1,2, M. MK-6240 and PI-2620
Grosch1, S. Lindner2, R. Oos2, P. Bartenstein2, S. Ziegler2, A. Zwergal1,3; A. Mueller1, H. Kroth2, F. Oden1, F. Capotosti2, M. Berndt1, J. Molette2,
1
German Center for Vertigo and Balance Disorders (DSGZ), H. Schieferstein1, E. Vokali2, J. Castillo-Melean1, H. Schmitt-Willich1,
University Hospital, LMU Munich, Munich, GERMANY, D. Hickman2, A. Pfeifer2, S. Poli2, L. Dinkelborg1, A. Stephens1;
2
Department of Nuclear Medicine, University Hospital, LMU 1
Life Molecular Imaging, Berlin, GERMANY, 2AC
Munich, Munich, GERMANY, 3Department of Neurology, Immune SA, Lausanne, SWITZERLAND.
University Hospital, LMU Munich, Munich, GERMANY.

Aim/Introduction: Intracellular Tau deposition is a key


Aim/Introduction: Neurogenesis contributes to plasticity in pathologic feature of Alzheimer’s disease (AD) and other
the adult brain and is considered to be involved in structural neurodegenerative disorders. Positron emission tomography
remodelling following inner ear lesions. The current study could be an important tool for the detection of Tau aggregates in
aimed at examining changes in cerebral cell proliferation in the the brain in AD and other tauopathies. Several tracers have been
rat following bilateral labyrinthectomy (BL) by serial [18F]FLT- described and are being administered clinically. First-generation
µPET and histochemistry. Materials and Methods: 12 SD rats Tau PET tracers have reported limitations, particularly off-target
underwent BL through transtympanic injection of bupivacaine binding. Here we present a preclinical comparison of the first-
and arsanilic acid. Rats were followed up until 9 weeks post BL. generation tracer AV1451 and two next-generation tracers,
Spatial orientation and locomotion were tested in a rewarded PI-2620 and MK-6240. Materials and Methods: Compounds
T-maze task to monitor behavioural changes. A [18F]FLT-µPET were evaluated for affinity and selectivity to aggregated Tau
scan with probenecid pre-treatment (following a modified using human brain homogenates and 4R-Tau fibrils. The non-
protocol by Tamura et al., 2016) was acquired once weekly to specific component was measured using homogenate binding
depict cerebral cell proliferation in vivo. Histochemistry after assays with brain tissue from non-demented controls. Specific
BrdU-injection was performed on corresponding days in a off-target binding was measured in competition assays using
subgroup of animals to verify neurogenesis in vitro. The results radiolabeled MAO-A/B and beta-amyloid binders. Compounds
were compared to a dataset of healthy controls. Results: were further characterized by autoradiography (ARG) on AD
T-maze testing revealed differences between BL rats and brain sections. The binding was compared to the corresponding
healthy controls: Locomotor velocity was significantly higher signals on brain tissues of non-demented control subjects. The
and the spatial orientation performance significantly worse pharmacokinetic profiles of the 18F-labeled test compounds were
in BL rats compared to controls until 9 weeks post-surgery. evaluated in mice. Results: All three compounds showed high
Histochemistry showed a decreased number of BrdU-labeled affinity for Tau-aggregates in AD brain homogenate competition
proliferating cells in the hippocampal dentate gyrus(DG) and assays (IC50: AV1451 <1 nM; MK-6240 1nM, PI-2620 1.8 nM). None
subventricular zone(SVZ) at 2 to 6 weeks post BL (p<0.05). In the of the compounds displayed binding to beta-amyloid. However,
BL group cell proliferation remained 40% lower in DG compared AV1451 showed also significant, high-affinity binding in brain
to controls, while it recovered to the levels of controls in the SVZ homogenates of non-demented controls. The ratio of specific
until 9 weeks post BL. In the vestibular nuclei(VN) BrdU-positive to non-specific binding was 2, 15, and 28 for AV1451, MK-6240
cells were twice as frequent in BL animals as in controls on day3 and PI-2620, respectively. In contrast to AV1451 and MK-6240, PI-
post-surgery. In relatively good accordance with histochemical 2620 also showed high affinity binding to recombinant 4R-Tau
results, BL rats displayed a reduced [18F]FLT-uptake in the SVZ fibrils IC50 (4 nM). PI-2620 binding to 4R-Tau was confirmed by
until 9 weeks and in the DG until 6 weeks post-surgery (p<0.005). homogenate binding-assays and autoradiography on PSP brain
The VN showed an increase in [18F]FLT-uptake especially directly slices. Binding to MAO-A (IC50 22 nM) as well as to MAO-B (78 nM)
after and 9 weeks after BL (p<0.005). Conclusion: Changes of was found for AV1451, but not for the other two compounds. PI-
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S230

2620 and MK-6240 showed excellent PK characteristics in mice OP-604


PET studies (peak uptake-to-60 min of 24 and 29 respectively). Preclinical validation of [18F]2FNQ1P, a specific PET
The brain washout of AV1451 was slower (ratio peak-to-60 radiotracer of 5-HT6 receptors in rat, pig, non-human
min: 7). Minor defluorination was found in this experiment primate and human brain tissues
for MK-6240 and AV1451, but not for PI-2620. Conclusion: All S. Emery1,2, S. Fieux3, B. Vidal3, F. Liger4, T. Billard5, P. Courault2,1, S.
three tracers demonstrate high affinity binding to human tau- Bouvard2, L. Zimmer2,1,4, S. Lancelot2,1,4;
aggregated in AD. The first-generation tracer AV1451 showed 1
Hospices Civils de Lyon, Neurological Hospital, Lyon, FRANCE,
significant binding in control tissue lacking tau-aggregates 2
Lyon Neuroscience Research Center (UMR 5292, U 1028),
which can be attributed partly to MAO-A/B. This off-target University of Lyon, University Lyon 1, Lyon, FRANCE, 3Lyon
binding is probably also responsible for reduced brain wash- Neuroscience Research Center (UMR 5292, U1028), Lyon,
out in mice. In contrast to the other two compounds, PI-2620 FRANCE, 4Cermep-In Vivo Imaging, Groupement Hospitalier
demonstrated the ability to bind to 4R-Tau using recombinant Est, Lyon, FRANCE, 5Institute of Chemistry and Biochemistry
fibrils, PSP brain homogenate and ARG. References: None. (ICBMS-UMR CNRS 5246), University of Lyon, Lyon, FRANCE.

OP-603 Aim/Introduction: Subtype 6 of serotonin receptor (5-HT6) is


Hyperactivation of neutrophils in Alzheimer’s disease one of the more recently serotonin receptor identified, first in
transgenic mice by 68Ga-PEG-cFLFLFK PET imaging rat and then in human brain. The distribution of 5-HT6 receptors
Y. Kong, Y. Guan; in human is mainly in the striatum, but also in the pre-frontal
PET Center, Huashan Hospital, Fudan University, Shanghai, CHINA. cortex and the hippocampus. The 5-HT6 receptor is a G protein-
coupled receptor that as recently emerged as a new target for
neuropharmacology since it plays a vital role in memory and
Aim/Introduction: Neutrophils play a critical role in the cognitive processes, reinforcing its status as an emerging target
innate immune system. Neutrophil hyperactivation has been in antidementia therapeutic agents. The aim of this study is to
identified as a biomarker of Alzheimer’s disease (AD)1. However, perform in vitro and in vivo pharmacological characterization
there is still no in vivo imaging tool to study the activation of of [18F]2FNQ1P, a new radiotracer of 5-HT6 receptors, in rat,
neutrophils in AD dynamically. 68Ga-PEG-cFLFLFK, an antagonist pig, non-human primate, and human tissues. Materials and
of the neutrophil formyl peptide receptor (FPR) with a high Methods: In vitro autoradiography and saturation binding
binding affinity, has been developed as a specific tracer to assays were performed in post-mortem brain tissues from, rat,
probe the activation of neutrophils. In this study, we aim to pig, non-human primate and healthy controls. Serum stability of
detect the variation of neutrophil in the AD transgenic mice [18F]2FNQ1P after incubation in serum at 37°C for 2h was assess
by 68Ga-PEG-cFLFLFK. Materials and Methods: In this study, in all species. We studied brain unmetabolized radiotracer
we used the B6;129-Psen1tm1Mpm Tg(APPSwe,tauP301L)1Lfa/ fraction and biodistribution in rats. Results: In all species,
Mmjax mouse model, which was confirmed by RT-PCR. Open autoradiography revealed high binding levels in regions whith
field test, morris water maze, high plus maze and Y-maze test high density of 5-HT6 receptors as striatum or pre-frontal cortex.
were performed to evaluate the status of the mice. 68Ga-PEG- A blocking effect was observed using an excess of antagonist
cFLFLFK was synthesized by the previously reported2. Serial specific ligand (SB258585), suggesting that the binding was
microPET was used to investigate the uptake of tracer in the AD specific. In binding assays, KD and Bmax values were respectively
transgenic mice and control at different ages. Results: Behavior 1.34 nM and 0.03 fmol.mg-1 in rat, 0.60 nM and 0.04 fmol.mg-1
test results confirmed the impairment of learning and memory in pig, 1.38 nM and 0.07 fmol.mg-1 in non-human primate, and
in AD transgenic mice. PET imaging 60 min after tracer injection 0.93 nM and 0.17 fmol.mg-1 in healthy controls. Excellent serum
indicated that %ID/g mean of brain for AD transgenic group stability of [18F]2FNQ1P was observed for 2h. In rat, the amount
that was higher, respectively, compared with control group. of radioactivity from unmetabolized [18F]2FNQ1P in brain was
Furthermore, the radioactivity uptake of heart in AD transgenic superior 99% at 5 minutes and decreased to 87% at 40 minutes
group was significantly higher than control. Conclusion: These with pre-injection of ciclosporin. In biodistribution studies, the
results indicated that increased activation of neutrophil in the highest concentration of radioactivity was found in the lungs
heart and brain of AD mice. 68Ga-PEG-cFLFLFK PET imaging is (up to 3.5+/- 1.2 %ID/g) and kidneys (up to 2.0 +/- 0.7 %ID/g)
a sensitive approach for studying the status and mechanism at 15 minutes p.i but theses concentrations decreased after 60
of neutrophil on AD. References: 1. Dong Y, Lagarde J, Xicota minutes to 0.7 +/- 0.1 %ID/g and 0.9 +/- 0.1 %ID/g, respectively.
L. Ann Neurol. 2018 Feb;83(2):387-405 2. Landon W. Locke, Conclusion: The new data confirm the interest of [18F]2FNQ1P
Mahendra D. Chordia, Yi Zhang. J Nucl Med. 2009 May ; 50(5): as the first fluorinated and specific radiotracer for molecular
790-797. imaging of serotonin 5-HT6 receptors. A first in man PET study
will ultimately determine the utility of [18F]2FNQ1P as a PET
radioligand. References: None.
S231 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

OP-605 intruder-resident interaction, instead of mild interaction). Only


Exploring the impact of different aggression access levels D2 receptor binding in NA was related with the attack latency of
in striatal dopaminergic system: a 11C-raclopride PET study the animals, a brain region extensively associated with addiction
R. Moraga-Amaro1, P. K. Feltes1, B. L. Giacobbo1, I. L. Alves2, S. F. de and rewarding experiences. Therefore, we hypothesize that
Boer3, C. M. Moriguchi-Jeckel4,5, R. A. J. O. Dierckx1, J. Doorduin1, E. F. access to repetitive winning confrontations might lead to habit-
J. de Vries1; forming escalated forms of aggression. References: None.
1
Department of Nuclear Medicine and Molecular Imaging,
University Medical Center Groningen, University of Groningen,
Groningen, NETHERLANDS, 2Department of Radiology OP-606
and Nuclear Medicine, VU Medical Center, Amsterdam, Clinical applicability of a mathematical model for FET PET
NETHERLANDS, 3Behavioural Neuroscience Unit, Neurobiology uptake kinetics in brain tumor patients
Department, Groningen Institute for Evolutionary Life C. Lerche1, T. Radomski1, P. Lohmann1, C. Regio-Brambilla1, L.
Sciences, University of Groningen, Groningen, NETHERLANDS, Tellmann1, J. Scheins1, E. Rota Kops1, H. Herzog1, K. Langen1, J. N.
4
Biomedical Gerontology, Pontifical Catholic University of Rio Shah1,2,3;
Grande do Sul (PUCRS), Porto Alegre, BRAZIL, 5Brain Institute 1
Institute of Neuroscience and Medicine 4, INM-4,
of Rio Grande do Sul (BraIns), Pontifical Catholic University Forschungszentrum Jülich GmbH, Jülich, GERMANY,
of Rio Grande do Sul (PUCRS), Porto Alegre, BRAZIL. 2
Institute of Neuroscience and Medicine 11, INM-11, JARA,
Forschungszentrum Jülich GmbH, Jülich, GERMANY, 3JARA
- BRAIN - Translational Medicine, Aachen, GERMANY.
Aim/Introduction: Excessive aggression is a major source of
death and social stress, constituting a significant problem for
public health. Understanding the mechanisms underlying the Aim/Introduction: Several studies have demonstrated that
development of aggressive behaviour could help to control it. changes of the tracer accumulation of O-(2-[18F]fluoroethyl)-L-
Interestingly, winning aggressive confrontations results in self- tyrosine (18F-FET) in cerebral gliomas during the first hour after
reinforcing pleasurable effects, suggesting a role for the reward injection are variable depending on their grade of malignancy.
system. The aim of this study was to compare the impact of Extraction of the parameter that describes the dynamic uptake
two protocols of aggression with different levels of intensity on behaviour is currently not possible in a clinical setting. The aim
dopaminergic D2 receptor availability in the brain. Materials of this work was the evaluation of a recently developed method
and Methods: Repeated social defeat model was used to train for extracting dynamic behaviour using a non-linear model
animals for aggression. 16 weeks old male outbred Long Evans for the 18F-PET time activity curve (TAC). Emphasis was placed
rats (residents) were housed together with a tubal-ligated female on enabling the use of the method in a clinical setting with
Long Evans rat at least one week before the experimental phase. limited acquisition times of about 20 to 40 min. Materials and
During aggression trials, females were removed from the cage Methods: The class of functions given by log(u)=log(A)+0.5
and Wistar rats (intruders; 8 weeks old) were introduced. Attack log(t)-κ √t successfully reproduces all typically observed uptake
latency (AL) was measured and used as a proxy for aggression. kinetics of 18F-FET, where u=u(t) is the 18F-FET uptake as a
After submission, the intruder was either placed inside a wire function of time, A is the amplitude parameter and κ is the curve
mesh cage to allow closer resident-intruder interaction (close shape parameter. The model was fitted to the average TACs
interaction group), or by a plexiglass partition, allowing visual and obtained from all voxels inside the segmented tumour volume.
olfactory interaction, but not physical (mild interaction group). The PET acquisition was started with the injection of the tracer,
Residents with an AL higher than 60s were defined as non- but only TAC data points obtained from reconstructed time
aggressive control group. All animals underwent 11C-raclopride frames lying between 20 and 40 min p.i. were included in the
PET scans (D2-receptor), either at least 2 weeks after the last fit. We evaluated the model in PET images from 11 low-grade
resident-intruder interaction (control and close interaction (LGG) and 16 high-grade (HGG) gliomas and with different
group), or one day after an intruder exposure (mild interaction dynamic framing schemes: 5 x 240 s, 6 x 200 s, 7 x 170 s, and
group). Binding potential (BPND) values in the striatal areas were 8 x 150 s. Results were also compared to a linear model and
obtained through the simplified reference region (SRTM) model to results obtained using the complete 4-50 min p.i dynamic
, using the cerebellum as reference. Results: A significantly PET data. Diagnostic performance for identification of HGG
increased tracer uptake was found in the Nucleus Accumbens was assessed by ROC curve analyses (with LOOCV) using the
(NA) of close interaction animals when compared to controls results from neuropathology as reference. Results: Diagnostic
(p<0.05), but not in mild interaction animals. Additionally, an performance for HGG identification was best (accuracy=0.89,
increased tracer uptake was found in the Caudate Putamen sensitivity=0.94, specificity=0.82, false rate (LOOCV)=0.15) when
(CPu) of close (p<0.05) and mild interaction animals (p<0.001), using the empirical model together with the complete PET
as compared to the control group. Correlations between BPND in data. Diagnostic performance for HGG identification for 20-40
NA and AL were found only in the control and close interaction min p.i. was best when using the linear model with 7x170sec
groups (p<0.05). Conclusion: Increased levels of D2 receptor framing (accuracy=0.78, sensitivity=0.63, specificity=1, false
tracer binding in the NA and CPu were demonstrated when rate=0.22). Results for using the non-linear model with the same
animals have access to higher levels of aggression (i.e. close framing were slightly worse (accuracy=0.74, sensitivity=0.63,
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S232

specificity=0.91, false rate=0.26). Conclusion: The linear model effect of settling of the active microspheres within the glass vial.
fit and the non-linear model fit can be used in a typical clinical Results: The density tests demonstrated that differences of up
setting to assess the 18F-FET uptake kinetics with an accuracy to 30% can be observed for different commercial radionuclide
of 78% and 74%, respectively. However, using the entire calibrators. Settling tests showed discrepancies of up to 10%
dynamic PET data allows a more reliable identification of HGG. depending on the time of the measurement after shaking
References: None. the vial. Volume tests indicate corrections of up to 5%. New
dial settings and respective uncertainties were determined for
both geometry types. Conclusion: Similarly, to the findings
1406 for 90Y-microspheres, this study showed significant differences
in calibration factors for 166Ho-MS and 166Ho-chloride solution
Do.MoRe - Parallel Session: Radiobiology and for various commercially available radionuclide calibrators,
Dosimetry for Radioembolisation Therapy highlighting the need to calibrate them individually for different
measurement geometries. References: [1]Smits, et al. Lancet
Tuesday, October 15, 2019, 14:30 - 16:00 Lecture Hall 112 Oncology. 2012 Nov;13(11):e464. [2]Prince,J.F. et al. J Nucl Med.
59(4): 582-588(2018) [3]Radosa,C.J. et al. Cardiovascular and
Interventional Radiology 42(3):405-412(2019) [4]Ferreira,K.M. et
OP-607 al. Appl. Radiat. Isot. 109, 226-230(2016).
The need for standardised activity measurements of 166Ho-
poly (L-lactic acid) microspheres for radioembolization
therapy OP-608
K. M. Ferreira1, A. J. Fenwick1,2, N. C. Ramirez1, S. Chen3; Ho-Only Versus 166Ho-DI: A Qualitative And Quantitative
166

1
National Physical Laboratory, Teddington, UNITED Assessment
KINGDOM, 2Cardiff University, Cardiff, UNITED KINGDOM, M. Stella, A. Braat, M. Lam, H. de Jong, R. van Rooij;
3
Quirem Medical B.V., Deventer, NETHERLANDS. University Medical Center, Utrecht, NETHERLANDS.

Aim/Introduction: Radioembolization with Holmium-166 Aim/Introduction: With the increase in radioembolization


poly (L-lactic acid) microspheres (166Ho-MS) is used to treat procedures, the need for accurate dosimetry is compelling. To
patients with inoperable liver tumours[1-3]. The total activity this purpose, an automatic protocol for healthy liver dosimetry
administered to the patient is typically determined using a based on dual-isotope (DI) SPECT imaging combining
radionuclide calibrator at the hospital. For each radionuclide, the Holmium-166 (166Ho) and Technetium-99m phytate (99mTc),
radionuclide calibrator has a dial setting which is determined was developed: 166Ho-microspheres being used as scout and
for a specific well-defined geometry in a standard position. A therapeutic particle and 99mTc to identify the healthy liver1.
previous study highlighted the differences in the radionuclide However, image quality is potentially compromised due to
calibrator response for liquid and microspheres forms when crosstalk: 99mTc influences 166Ho image due to downscatter
measuring radionuclides such as 90Y[4]. In this work, the and vice versa. This study investigates the effect 99mTc
differences between measuring 166Ho-chloride solution and downscatter has on 166Ho dosimetry, by comparing 166Ho-
166
Ho-MS were investigated to consequently improve activity SPECT reconstructions of patient scans acquired before and
measurement of 166Ho-MS. Calibration factors and volume after additional administration of 99mTc (referred to as 166Ho-
correction factors were determined for the glass V-vial that only and 166Ho-DI respectively). Materials and Methods: The
will be used for delivery of 166Ho-chloride solution,166Ho-MS 166
Ho-only and 166Ho-DI SPECT scans were performed in short
pre-therapy scout and 166Ho-MS therapy vials. Materials and succession, minimizing patient motion between acquisitions.
Methods: To understand the differences between chloride Images were reconstructed using clinically available iterative
solution and microspheres, a series of glass vials with known reconstruction software, including attenuation and scatter
activities were prepared at different densities (1.005g/cm3- correction. To compensate for 99mTc downscatter, its influence in
1.437g/cm3) to mimic the density of 166Ho-chloride and 166Ho- the 166Ho photopeak window was accounted for in the DI image
MS. The vials were measured on an Atomlab-500, Capintec CRC- reconstruction using energy window based scatter correction
12 and the NPL secondary standard ionisation chamber (NPL IC). methods. The qualitative comparison was performed by
To confirm the results obtained from the density tests, additional independent blinded comparison by two experienced nuclear
vials were prepared by adding 166Ho-chloride to inactive medicine physicians (>5 years) which assessed 65 pairs of SPECT/
microspheres to mimic the scout and therapy geometries. For CTs, expressing their preference for either 166Ho-DI or 166Ho-only
the volume correction factors a glass vial was prepared with SPECT. Inter-observer agreement was tested by Cohen’s kappa
0.1g of 166Ho-chloride solution and measured on each system. coefficient. For the quantitative analysis, two small volumes
Incremental volumes of inactive carrier were then added to the of interest, VOITUMOR and VOIHEALTHY, were manually delineated
vial with measurements being taken on each system between on the 166Ho-only reconstruction and then transferred to the
fills. Additional tests were performed using both scout (60mg co-registered 166Ho-DI reconstruction. Absorbed dose within
166
Ho-MS) and therapy (600mg 166Ho-MS) vials to determine the the resulting VOITUMOR and VOIHEALTHY was calculated based
S233 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

on the planned therapeutic activity. Results: The qualitative used to describe OS curves. Results: A tumor Dmean cutoff of
assessment showed no distinct preference for either the 166Ho- 112 Gy (sensitivity 0.65, specificity 0.85 and accuracy 0.79) was
only or 166Ho-DI SPECT with a kappa value = 0.093. Quantitative determined to predict tumor response. Dmean was substantially
analysis indicated that the difference in mean absorbed dose lower in healthy liver and showed an important variability
between 166Ho-DI and 166Ho-only in the tumor region was (42+/-22 Gy) without occurrence of radioembolization-induced
-7.88 ± 9.75 Gy and -4.68 ± 3.77 Gy in healthy region. These liver disease. In patients bearing multiple liver lesions Dmean
differences were regarded as acceptable by treating physicians, values were pooled and a patient-based cutoff was determined.
considering the different aims within tumor and healthy liver: Patients with Dmean pooled > 95 Gy had an OS = 26 months,
maximize treatment effectiveness while minimizing dose to significantly longer (p=0.057) than the others (OS = 6 month).
healthy tissue. The Pearson correlation coefficient between Conclusion: In unresectable HCC patients undergoing SIRT,
166
Ho-only and 166Ho-DI for absorbed dose was 0.99 for VOITUMOR tumor absorbed dose assessed using MAA-based dosimetry
and 0.95 for VOIHEALTHY. Conclusion: The dual isotope protocol clearly correlates with tumor response and is also associated
enables satisfying 166Ho-DI reconstructions within the clinical with prolonged OS. Pretreatment dosimetry may be used
reconstruction framework, which will allow an automatic routinely to achieve a fully patient-adapted approach allowing
estimation of absorbed dose in both tumor and healthy liver and treatment optimization or intensification - including higher
improve the current therapeutic activity calculation method, tumor irradiation and minimizing risks of liver toxicity. Further
thus introducing true personalized dosimetry. References: studies are needed to confirm these findings and to evaluate
1
Braat, A. et al. J. Nucl. Med. 57, 1423 (2016). the maximal tolerated liver dose. References: None.

OP-609 OP-610
MAA-based Dosimetry predicts Tumor Response and Modeling the biological effectiveness of non-uniform dose
Outcome in Patients with Hepatocellular Carcinoma after distributions delivered from selective internal radiation
Selective Internal Radiation Therapy (SIRT) therapy
J. Mutschler1, V. Gumpp2, P. T. Meyer1, C. Goetz1; B. Bednarz;
1
Department of Nuclear Medicine, Medical Center of the University of Wisconsin, Madison, WI, UNITED STATES OF AMERICA.
University of Freiburg, Faculty of Medicine, University of Freiburg,
Freiburg, GERMANY, 2Comprehensive Cancer Center Freiburg
CCCF, Medical Center of the University of Freiburg, Faculty Aim/Introduction: Recently, the SARAH trial, a large randomized
of Medicine, University of Freiburg, Freiburg, GERMANY. phase 3 study in patients with advanced hepatocellular
carcinoma (HCC), showed no benefit in terms of overall survival
after receiving 90Y-loaded resin microsphere selective internal
Aim/Introduction: Radioembolization of liver malignancies radiation therapy (SIRT)1. These negative results could partially
with Y90-loaded microspheres is an effective strategy in be explained by the absence of biologically-based dosimetric
unresectable hepatocellular carcinoma (HCC). In the planning endpoints to prescribe the injected activity. This work describes
of selective internal radiation therapy (SIRT) both Lung- and a general method for assessing the biological effects of non-
Liver-Dosimetry are considered using models assuming a uniform dose distributions on tumors treated with SIRT.
uniform distribution of microspheres but inapt to predict tumor Materials and Methods: The approach is based on the concept
response. In contrast published optimized predictive models of biologically effective dose (BED). Three different BED models
using MAA-based dosimetry prior to therapy can provide good are considered: (1) standard linear-quadratic dependent cell
estimates of absorbed doses in tumor and healthy liver. Our aim kill with dose-rate effects, (2) same as (1) but also accounting
was here to correlate the MAA-based dosimetry with tumor for proliferation, and (3) same as (2) but also accounting for
response and to assess its impact on median overall survival immune system response. Tumor absorbed dose distributions
(OS) in patients treated with SIRT. Materials and Methods: were modeled as normal distributions with means μ [50 Gy,200
79 evaluable HCC lesions were retrospectively included from Gy] and standard deviations σ [0.25 Gy,100 Gy] based on PET/
27 unresectable HCC patients (median age 66 years) who MR data measured at our institution and found in the literature.
underwent SIRT in our department (SIR-Spheres, Sirtex Medical Using these models the equivalent uniform dose (EUD) was
Limited, Sydney, Australia). Three-dimensional predictive calculated for varying levels of non-uniformity. Although
voxelized dose maps were computed from the Tc99m-MAA adjustable, it was assumed that the tumors had a repair half-
SPECT/CT data (PMOD Technologies LLC, Zürich, Schweiz) and time of 0.5 hrs, a repopulation time of 7 days, an α/β = 10 and
the administered Y90-activities. Mean absorbed dose (Dmean) a α=0.35 Gy-1. For the immune system model the immune cell
was evaluated for both tumor and healthy liver. The tumor interaction constant was set to 0.14 day-1 and the probability of
response (assessed by volumetric changes 12 weeks after SIRT) immune cell destruction per immune cell interaction was set to
and the overall survival were evaluated and their relationship unity. Results: The relative effectiveness values range from 1 to
with dosimetry was analyzed. Tumors were dichotomized in 1.23 for the parameters considered. The BED varied only slightly
“responder” and “non-responder” according to the mRECIST between the different models with a maximum difference of
criteria. A cutoff value was determined for Dmean using ROC -1.2% between model (2) and (1) and 0.27% between model (3)
analysis and the Youden-index. Kaplan-Meier estimate was and (1). The EUD changed significantly as a function of the BED
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S234

uniformity index σ/ μ in the tumor. Conclusion: The general at safe values. Thus, we believe there is room for improvement in
method used in this work can be integrated into an image-based the microspheres manufacturer’s protocol by attempting better
dosimetry workflow that could lead to improved prescription treatment personalization, for instance, estimating the dose
strategies for SIRT. The large uncertainties associated with the distribution based on the SPECT-MAA pre-treatment images to
parameters used in this study could potentially be reduced by optimize the 90Y-microspheres activity to be administered. Voxel-
evaluating clinically-relevant biomarkers in patient samples or in based dosimetry may be an important tool in the evaluation of
vitro, which is an active area of ongoing research. References: personalized treatment efficacy and toxicity. References: [1] M.
1
Vilgrain V et al. Lancet Oncol. 2017; 18: 1624-1636. Cremonesi et al., “Radioembolization of Hepatic Lesions from a
Radiobiology and Dosimetric Perspective”, Front Oncol, 4(210):1-
20, 2014.
OP-611
Voxel-based Dosimetry in the Liver: Yttrium-90
Microspheres Radioembolization After SBRT OP-612
P. Ferreira1, F. P. M. Oliveira1, R. Parafita1,2, P. S. Girão3, P. L. Correia3, Key role of personalized dosimetry in dose adjustement
O. Pares1, D. C. Costa1; for selective internal radiotherapy : retrospective study of
1
Champalimaud Centre for the Unknown, Champalimaud patients treated with yttrium-90 resin microspheres
Foundation, Lisbon, PORTUGAL, 2Mercurius Health, Lisbon, C. Subreville1, J. Pinaquy2, J. Miguel1, S. Buj2, L. Bordenave2, F.
PORTUGAL, 3Instituto de Telecomunicações, Instituto Superior Debordeaux1;
Técnico - Universidade de Lisboa, Lisbon, PORTUGAL. 1
Radiopharmacy - Bordeaux University Hospital,
Aim/Introduction: Voxel-based dosimetry of planning tumor Bordeaux, FRANCE, 2Department of Nuclear Medicine -
volume (PTV) and normal liver volume (NLV) has been performed Bordeaux University Hospital, Bordeaux, FRANCE.
for several years in stereotactic body radiotherapy (SBRT). In
this work we propose a methodology to implement voxel-
based dosimetry for liver radioembolization using Yttrium-90 Aim/Introduction: Liver tumors present a high mortality
(90Y) glass microspheres. Voxel-wise biological effective dose rate. Curative treatments aren’t feasible for all patients.
(BED) distributions of a patient previously treated with SBRT Selective internal radiotherapy (SIRT) with yttrium-90-labeled
were combined with newly generated 90Y-microspheres microspheres is widely used for the treatment of patients
liver radioembolization BED distributions for further analysis. with liver cancer. Single-photon and emission computed
Materials and Methods: A patient with pancreatic carcinoma tomography/ computed tomography (SPECT/CT) with 99mTc-
and a single liver metastasis was studied. The metastasis was macroaggregated albumin (MAA) is used for the treatment
previously irradiated with 48 Gy (10 MV SBRT) in three sessions planning. Several methods were proposed to calculate the
and ten months later the patient underwent radioembolization activity of the treatment, but currently there is no real consensus
due to disease progression. Radioembolization followed the in terms of absorbed dose to tumor and healthy liver. A dosimetric
glass microspheres manufacturer’s protocol. This involved analysis using the dosimetry software, Simplicit90Y®, was realized
the assessment of the Technetium-99m (99mTc) labelled to define doses to the tumor and healthy liver, and to determine
macroaggregated albumin (MAA) distribution captured pre- a threshold tumor dose that could predict progression-free
treatment with planar images and single-photon emission survival. Materials and Methods: Patients suffering from
computed tomography (SPECT). Based on the microspheres hepatocellular carcinoma (HCC) and treated with 90Y-labeled
manufacturer’s protocol, a 90Y-microspheres activity of 3.239 resin microspheres between 2013 and 2018 were included in
GBq was administered in one session via the right hepatic artery. a retrospective study. Simplicit90Y® was used retrospectively to
Post-treatment 90Y-microspheres positron emission tomography define the volumes of interest (VOIs) and to calculate the dose
(PET) images were used to verify the 90Y-microspheres in each VOIs based on 99mTc-MAA SPECT/CT. Tumor, liver and
distribution and to calculate the voxel-wise absorbed liver dose healthy liver volumes were delineated with CT. The perfused
distribution. Voxel-wise BED distributions of both treatments volume was determined using adaptive thresholding method
was computed and summed to obtain the total BED [1]. based on 99mTc-MAA SPECT/CT. A threshold tumor dose was
Median BED was then computed in the PTV and NLV defined calculated using receiver operating characteristic analysis with
in the radioembolization volumetric imaging studies. Results: 99m
Tc-MAA SPECT/CT to predict a progression-free period over
SBRT median absorbed doses were 48 Gy and 5 Gy in the PTV 6 months with a sensitivity of 100%. Time to progression of the
(190 cm3) and NLV (1880 cm3), respectively. Regarding the target lesions (TTPL) and overall survival (OS) were evaluated
radioembolization, median absorbed doses were 78 Gy and 10 using Kaplan-Meier tests and this comparison was based on
Gy respectively in the PTV (510 cm3) and NLV (1416 cm3). After a log-rank test. Results: Twenty-two patients were evaluated
computing the voxel-wise BED on both treatment distributions, in retrospective study, including 18 patients with portal vein
the total voxel-wise BED distribution was obtained. The total BED thrombosis (PVT). The mean injected activity was 0,96 ± 0,43
median PTV (510 cm3) and NLV (1416 cm3) were respectively 168 GBq. The mean dose delivered to the tumor was 140,0 ± 71,1
Gy and 22 Gy. Conclusion: In this patient, based on the absorbed Gy and to the healthy liver was 13,3 ± 7,8 Gy. A threshold tumor
dose and BED, at least twice as much activity could have been dose of 105 Gy was determined with a sensitivity of 100% and
administered during radioembolization keeping the NLV dose a specificity of 70%. For patients with tumor dose of less than
S235 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

105 Gy, median OS was 9 months (95% CI: 5-22 months) and dominant. References: 1Corlone MC, Warkentin B, Stavrev P,
TTPL was 3 months (95% CI: 2-6 months) versus 38 months Fallone G. Fundamental form of a population TCP model in the
(95% CI: 22-NC months) and 33 months (95% CI: 19-NC months), limit if large heterogeneity. Med Phys 33:1634(2006).
respectively, for those with a tumor dose of 105 Gy or more (P=
0,004 and P=0,0002). Conclusion: Personalized dosimetry based
on 99mTc-MAA SPECT/CT is predictive of TTPL and OS in patients OP-614
with HCC. The customized dosimetry software is essential to Inter-observer variability of 90Y PET/CT dosimetry in
optimize treatment planning. References: None. hepatocellular carcinoma after glass microspheres
transarterial radioembolization
N. Meyers, A. Jadoul, C. Bernard, R. Hustinx;
OP-613 University hospital of Liege (division of nuclear medicine
Tumor control probability in the limit of high and oncologic imaging), Liege, BELGIUM.
heterogeneity applied to Y-90 radioembolization therapy
P. Roberson, T. Devasia, Y. K. Dewaraja;
University of Michigan, Ann Arbor, MI, UNITED STATES OF AMERICA. Aim/Introduction: Strong correlation has been demonstrated
between tumor dose and tumor response, and between healthy
liver dose and side effects. Individualized dosimetry is increasingly
Aim/Introduction: Radiobiologic modeling in recommended in the current clinical routine. However, hepatic
radioembolization (RE) has had some success in relating and tumor segmentation could be complex in some cases. The
dosimetry estimates to treatment outcome. A challenge is to aim of this study is to assess the reproducibility of the tumoral
incorporate the expected heterogeneity of clonogen number and non-tumoral liver dosimetry in selective internal radiation
and radiosensitivity into the model. Here, we use the formula therapy (SIRT). Materials and Methods: Twenty-three patients
in the limit of high heterogeneity1, applied at the voxel level, to with hepatocellular carcinoma (HCC) who underwent SIRT with
perform a preliminary description of tumor control probability glass microspheres (TheraSpheres&#174;) were retrospectively
(TCP). Materials and Methods: We express the voxel TCP included in the study, for a total of 25 treatments (1,98 +- 1,23
for the ith voxel with biological equivalent dose BEDi using GBq). The mean absorbed doses in tumoral liver (TD) and non-
parameters BED50= the equivalent dose required to control tumoral liver (NTD) were determined using Simplicit90YTM
50% of the tumor population and γ50= the normalized slope software by three independent observers. The tumor and
of the TCP curve at 50% TCP. TCP(BEDi)=1/2*erfc[SQRT(π*(1 and non-tumor volumes were measured on the 90Y PET/
+ξ2)/({BEDi/BED50}2+ξ2)*γ50*(1-BEDi/BED50)]where ξ is the ratio CT performed 24 hours after the treatment. One dosimetry
of relative standard deviations for log clonogen number and dataset was obtained as part of the routine clinical practice
radiosensitivity. The tumor TCP=ΠiM [TCP(BEDi)]ηi where ΣiMηi=1 by a medical physicist helped by a nuclear medicine (NM)
and the {ηi,BEDi} represent the M-voxel tumor BED-DVH. The physician with 10 years of experience in SIRT (A). The second
study population included primary and secondary intrahepatic was performed by a NM physician with 4-year experience (B).
malignancies treated with Y-90 RE using glass microspheres. The third was performed by a resident with limited experience
Patients underwent Y-90 PET/CT imaging and retrospective and who first performed 10 dosimetry assessments as a training
dosimetry. The data set included 51 tumors in 20 treatments, split (C). Inter-observer agreement was evaluated using the inter-
(22 tumors in 10 treatments) hepatocellular carcinoma (HCC) class correlation coefficients (ICC), coefficients of variation (CV),
and (29 tumor in 10 treatments) metastatic (MET). Tumor control and Bland-Altman plots. Results: A strong agreement was
was determined using mRECIST criteria and a mean follow-up observed between all three readers for estimating the healthy
time of 16 weeks (range 7 to 33 weeks). Curve fitting maximized liver volume (ICC: 0.98) and the non-tumoral liver dose (ICC:
Πj[(TCPj)zj*(1-TCPj)(1-zj)] for binary outcome, zj, over all tumors, j. 0.97). Agreement was lower for tumor volume delineation (ICC
Results: The optimum fit was found for large ξ, implying a probit- : 0.94) and particularly for tumor dose (ICC : 0.73), especially for
like fit curve where log-clonogen heterogeneity was dominant. high values as shown by the Bland-Altman plots. Regarding TD,
There was no dependence of TCP on tumor volume. Optimum fit the CV(%) was 26.5, 26.9 and 20.2 between observers A-B, A-C
values were BED50= 187 Gy and γ50= 0.31 for the full data set (51 and B-C, respectively. Regarding NTD, it was 8.5, 12.7 and 9.4.
tumors in 20 treatments, AUC=0.74, sensitivity 82%, specificity With a target dose &gt;200Gy for the tumor and &lt;50 Gy for
65%, calculated using a threshold corresponding to 50% TCP). the non-tumor liver, 7/25 patients (tumor) and 2/25 patients
Optimum fit values for the MET only dataset was BED50=155 (non tumor) fell in different categories, i.e. target reached/not
Gy and γ50=0.44 (29 tumors in 10 treatments, AUC=0.83, reached, depending on the observer. Conclusion: Using a
sensitivity 96%, specificity 71%). mRECIST criteria implies a standardized methodology, the estimation of the NTD is highly
positive response if all but one of 6 partitions are controlled, reproducible. Although the reproducibility of the assessment of
for an apparent radiosensitivity (= ln(6)/BED50) of ~0.01 Gy-1. tumor irradiation is overall quite high, large variations may be
Conclusion: The high heterogeneity formula was successfully observed in a limited number of patients. References: None.
used to describe tumor response as determined by mRECIST
criteria for a voxelized TCP model. Optimum fits required the
heterogeneity parameter set for log clonogen heterogeneity
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S236

1407 administered and dosimetry was carried-out. Materials and


Teaching Session 5 - Interactive Clinical Cases Methods: Pts with histologically confirmed advanced mCRPC
- Neuroimaging Committee: Neuroimaging ? (PCWG3 criteria) previously treated with docetaxel, abiraterone
Before Reading PET Scans or enzalutamide were enrolled in the study if the diagnostic
PET/CT 68Ga-PSMA images showed clear uptake (tumor to
Tuesday, October 15, 2019, 14:30 - 16:00 background ratio >2.5) at tumor sites previously assessed by CT
Lecture Hall 113
or MRI. Folic polyglutamate tablets were orally administered as
parotid glands (PGs ) protectors and 500 mL of a 10% mannitol
solution was intravenously infused to reduce kidney uptake
OP-615 before the injection of 3.7-5.5 GBq of 177Lu-PSMA-617 repeated
Introduction to PET/CT Acquisition of the Brain 4 times at interval of 8-12 weeks. The adsorbed dose calculation
J. Dickson; was performed with MIRD formalism (OLINDA/EXM software).
University College Hospital, Institute of Nuclear Bryant and Day design taking into account the injected activity
Medicine, London, UNITED KINGDOM. and the toxicity was used to estimate the sample size Results:
At February 2019, 43 eligible pts were preliminary evaluated on
response, toxicity and dosimetry. A concomitant decreased of
OP-616 PSA > 30% and objective response at post therapy whole body
Quantification for Dummies scan(pt WBS) was observed in 26 (60 %) pts after the first or 2nd
R. Boellaard; cycle. Fifteen of 26 pts had more than 50% PSA reduction. Early
Dept. of Radiology and Nuclear Medicine, Amsterdam University PD within 4 months was reported in 18 ( 41%) of cases. Two pts
Medical Centres, location VUMC, Amsterdam, NETHERLANDS. (4.8%) had G3 and 8 pts (19.5%) had G2 haematological toxicity.
Only three pts (6.9%) had mild G1 salivary gland toxicity and 8
(19.5%) had G1 renal toxicity. The median adsorbed doses(10
OP-617 pts scanned) were 0.48 mGy/MBq (range: 0.33-2.63) for PGs, 0.70
MRI and CT - Abnormal Findings Relevant for PET Reading mGy/MBq (0.26-1.07) for kidneys, 0.044 mGy/MBq (0.023-0.067)
E. van de Giessen; for red marrow and 0.04 mGy/MBq (0.02-0.11) for the whole
Department of Nuclear Medicine, Academic Medical Center, body Conclusion: In this prospective phase II study, preliminary
University of Amsterdam, Amsterdam, NETHERLANDS. evaluation on response, toxicity and dosimetry confirms that
177
Lu-PSMA-617 RLT is safe and active in mCRPC pts. In advanced
and end-stage patients, 3.7-5.5 GBq of 177Lu-PSMA-617 per cycle
1408 can be safely injected and produced imaging responses at PSMA
ptWBS along with significant PSA decrease. Toxicity outcomes
Clinical Oncology - Parallel Session: Therapy - and dosimetry data would indicate that the co-administration
PSMA and More of polyglutamate tablets and mannitol solution can reduce side
effect for salivary glands and kidneys References: None.
Tuesday, October 15, 2019, 14:30 - 16:00 Lecture Hall 114

OP-619
Tandem PSMA Radioligand Therapy Using Ac-225 and Lu-
OP-618 177 in Advanced Prostate Cancer: Safety and Efficacy
177Lu PSMA-617 in advanced castration resistant prostate H. R. Kulkarni, J. Zhang, A. Singh, A. Mishra, C. Schuchardt, R. P.
cancer patients:dosimetry and preliminary evaluation of Baum;
IRST 185.03 phase II prospective study Theranostics Center for Molecular Radiotherapy and Precision
M. Sansovini1, A. Sarnelli1, S. Severi1, F. Foca1, M. Celli1, M. Monti1, S. Oncology, Zentralklinik Bad Berka, Bad Berka, GERMANY.
Nicolini1, E. Tardelli1, M. Belli1, F. Matteucci1, M. Giganti2, V. Di Iorio1,
U. De Giorgi1, G. Paganellli1;
1
IRST, Meldola (FC), ITALY, 2University of Ferrara, Ferrara (FE), ITALY. Aim/Introduction: PSMA radioligand therapy (PRLT) using
Ac-225 labelled PSMA ligands is very effective, but xerostomia
is dose-limiting. Lu-177 PSMA, on the other hand, is relatively
Aim/Introduction: Introduction/aim: Radio-ligand therapy safe, but there is a failure rate of up to 30 %. Hence an effective
(RLT) with 177Lu-PSMA-617 is a promising option for patients (pts) treatment with limited adverse effects is warranted for Lu-177
with metastatic castration-resistant prostate-cancer (mCRPC). A PSMA-refractory metastatic castration resistant prostate cancer
prospective single arm, open label phase-II study (EUDRACT/ (mCRPC) and for patients with disseminated bone and bone
RSO,2016-002732-32) on mCRPC started at IRST (Meldola, Italy) marrow metastases. The aim of our study was to analyze the safety
in April 2017. The study was designed to define efficacy, toxicity and efficacy of tandem PRLT, administering Lu-177 and Ac-225
and the minimal effective dosage of 177Lu-PSMA-617in mCRPC labelled PSMA ligands concomitantly. Materials and Methods:
pts. Protective agents for salivary glands and kindey were co- Tandem PRLT was performed in 43 patients with mCRPC (median
S237 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

Gleason score 8) applying a combination of Lu-177 and Ac-225 analysis were alkaline phosphatase (ALP), bone-specific alkaline
(mean administered activity 4.0 GBq and 4.5 MBq, respectively) phosphatase (BAP), prostate-specific antigen (PSA), lactate
labelled PSMA ligand concomitantly. All laboratory parameters dehydrogenase (LDH), chromogranin A (CgA), and pro-gastrin-
(including complete blood picture 2-weekly, renal function etc.) releasing peptide (pro-GRP). For the evaluation, we performed
were regularly monitored. The patients were clinically followed blood tests before each PSMA-RLT cycle and during follow-up
up for Karnofsky performance score, visual analog scale for pain, visits (which were 2-3 months apart). All patients were followed
and any other clinical symptoms, as documented on dedicated up until their deaths. To test the correlations between the
patient questionnaires. The objective response was evaluated tumor markers and survival, we conducted log rank tests for the
by Ga-68 PSMA PET/CT. Serum PSA response was documented univariate analysis and the Cox proportional-hazards regression
at least monthly. Results: Eight patients (18.6 %) complained model with stepwise variable addition for the multivariate
of increasing pain (requiring intensification of analgesia for analysis. The significance level was set at p < 0.05. Results:
1-2 days), most probably due to post-therapeutic flare. The The study included 137 patients who received a total of 487
most common symptom noted in 20 patients (46.5 %) was PSMA-RLT cycles between January 2015 and November 2017.
obstipation, requiring laxatives for short time. There was no Of the tested biochemical tumor markers, baseline ALP (120 U/I
worsening of pre-existing mild xerostomia in 2 patients (status cut-off ) and LDH (248 U/l cut-off ) correlated significantly with
post previous Lu-177 PSMA radioligand therapy and after EBRT survival post-PSMA-RLT (p < 0.001 for both markers). Stable and/
of cervical spine metastases. Mild (G1-G2) xerostomia occurred or decreased values in most of the initially abnormal parameters
as a new symptom in 8 patients (18.6 %) after treatment. G3 were associated with significantly better OS; these parameters
thrombocytopenia, G2 anemia and leucocytopenia were noted were ALP (p = 0.009), LDH (p = 0.005), PSA (p < 0.001), and pro-
in 1 patient with progressive disease. Otherwise, there was no GRP (p = 0.013). The BAP and ALP responses also correlated
hematological toxicity; no worsening of counts even in patients significantly with survival in patients with bone metastases (p
with pre-existing anemia or pancytopenia. The median OS is = 0.002 and p < 0.001, respectively). Baseline PSA (400 ng/mL
not yet reached and median PFS was 6.9 months after follow- cut-off ), pro-GRP (63 pg/mL cut-off ) and CgA levels (100 ng/mL
up of 14 months. On Ga-68 PSMA PET/CT, 27 (62.7 %) patients cut-off ), as well as CgA changes after the first cycle, were not
had partial remission, 5 (11.8 %) had a mixed pattern of disease significant predictors of OS. Conclusion: Along with established
and 11 (25.5 %) patients progressed. Conclusion: Tandem tumor marker PSA, ALP, LDH, BAP, and pro-GRP were correlated
PLRT concomitantly administering Ac-225 and Lu-177 PSMA with the OS of the prostate cancer patients who underwent
seems to be feasible, safe and effective in end-stage metastatic PSMA-RLT. References: None.
prostate cancer refractory to Lu-177 PSMA. It eventually permits
dose estimations. The administered radioactivity of Ac-225
PSMA can be lowered and the risk of dose-limiting toxicity be OP-621
minimized. There might be a potential synergistic effect using Response evaluation of 177Lu-PSMA-617 RLT using PSA,
two radionuclides with different emission characteristics. Chromogranin A, and LDH in 100 patients
References: None. H. Rathke1, T. Holland-Letz2, W. Mier1, P. Flechsig1, E. Mavriopoulou1,
M. Roehrich1, K. Kopka3, M. Hohenfellner4, F. Giesel1, U. Haberkorn1,
C. Kratochwil1;
OP-620 1
Heidelberg University Hospital, Heidelberg, GERMANY, 2German
Prognostic Tumor Markers In Men With Prostate Cancer Cancer Research Center, Heidelberg, GERMANY, 3Division of
Undergoing [177Lu]Lu-PSMA-617 Radiopharmaceutical Chemistry, German Cancer Research Center
A. Yordanova1, P. Linden1, S. Hauser1, G. Feldmann1, R. Fimmers1, M. (DKFZ), Heidelberg, Germany, Heidelberg, GERMANY, 4Heidelberg
Essler1, S. Holdenrieder2, H. Ahmadzadehfar1; University Hospital, Department of Urology, Heidelberg, GERMANY.
1
University Hospital Bonn, Bonn, GERMANY, 2Technical
University of Munich, Munich, GERMANY.
Aim/Introduction: Partial neuroendocrine differentiation is
common in prostate cancer (PCa), especially in high risk PCa
Aim/Introduction: Currently, prostate-specific membrane and over time in up to 40 % of PCa patients, caused by selection
antigen-radioligand therapy (PSMA-RLT) is considered a pressure [1]. Neuroendocrine differentiation is associated with
last-line treatment option in advanced castration-resistant poor prognosis [2] and could affect PSMA-expression and
prostate cancer (CRPC). Despite these patients’ poor prognosis, radio-sensitivity. Aim of this work was to evaluate possible
accurate estimation of their overall survival (OS) is essential to predictive lab markers for 177Lu- Prostate specific Membrane
determining whether benefits exist from the treatment and Antigen (PSMA)-617- radioligand therapy (RLT). Materials and
whether loss of valuable time and unnecessary side effects Methods: 100 patients with metastasized castration resistant
can be avoided. The aim of the present study is to evaluate prostate cancer (mCRPC) and PSMA-RLT were selected. Prostate
whether various biochemical markers can predict OS in men specific antigen (PSA) as a secretory marker of prostate cancer
undergoing PSMA-RLT and whether the changes assessed after cells, Chromogranin A as marker for neuroendocrine cells and
the first cycle of PSMA-RLT correlate with the OS. Materials lactate dehydrogenase (LDH) as a marker for cell turnover were
and Methods: The tested tumor markers in this retrospective selected for evaluation. PSA, Chromogranin A and LDH were
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S238

checked before each cycle of PSMA-RLT and for restaging. and laboratory workup according to the protocol. All patients
To assess tumor uptake, post-therapeutic scintigraphy was received a single dose of 5,6 GBq 177Lu-RM2. Laboratory
evaluated visually regarding quantitative tumor uptake and parameters were evaluated at week 1, 4 and 8 post-injection,
its homogeneity. Results: In total, 211 cycles of 177Lu-PSMA including blood count, creatinine serum levels, amylase and
therapy were evaluated. 35 patients had partial remission (PR), PSA values; these were compared to baseline values. A p value
16 patients stable disease (SD), 15 patients mixed response (MR) of < 0,05 was considered statistically significant. Results: Both
and 36 patients progression of disease (PD). All patients with PET/CT scans showed comparable tracer uptake and SUV
partial remission had a normal baseline LDH and in majority a values in tumor lesions, outside the expected physiological
PSA <200 ng/ml. Chromogranin A doubling had an increased biodistribution. As expected, 177Lu-RM2 accumulated well in
risk for progression with an Odds Ratio (OR) of 3.089 (KI 1.302 tumor lesions and showed stable binding for at least seven
- 7.332). Normal LDH implied a reduced risk for progression days, as demonstrated by 3D SPECT/CT and planar images.
with an OR of 0.094 (KI 0.017 - 0.518). Mainly intense tumor Interestingly, 177Lu-RM2 uptake in pancreatic tissue showed
uptake in metastasis (uptake > salivary glands in the 24h p.i. washout and reduced binding after 24-48h. No significant
emission scan) was a prerequisite to achieve PR with an OR of differences were found when comparing basal levels of red
60.265 (KI 5.038-720.922). Conclusion: Elevated LDH had an blood cells, leukocytes, platelets, creatinine or amylase levels
increased risk for progression of disease in PSMA-RLT. Doubling after 1, 4 and 8 weeks from therapy. Although two patients
of Chromogranin A conducted into higher risk for non-response showed a partial response during the first weeks, PSA values at
and PD. Furthermore, an increased risk for liver metastases was 8 weeks remained stable or slightly elevated when compared
detectable with elevated Chromogranin A. Most beneficial to baseline. Conclusion: In this small cohort of patients with
constellation of lab parameters was a high tumor uptake in mCRPC, treatment with a single dose of 177Lu-RM2 was well
combination with a low LDH in patients before PSMA-RLT. tolerated and no adverse effects were observed, proving the
High tumor uptake was a prerequisite to achieve PR. However, feasibility of 177Lu-RM2 PRRT. Despite stable binding to tumor
there were also several patients with PD despite high tumor lesions, no therapeutic PSA-response was observed and
uptake, indicating additional resistance mechanisms beyond additional work is needed to evaluate the real benefit of this
tumor-dose. References: 1. Aparicio A, Logothetis CJ, Maity SN. novel theranostic agent. References: None.
Understanding the lethal variant of prostate cancer: power of
examining extremes. Cancer Discov. 2011;1:466-468. 2. Hong
P, Guo RQ, Song G, et al. Prognostic role of chromogranin A in OP-623
castration-resistant prostate cancer: A meta-analysis. Asian J Efficacy of radium 223 in radioactive iodine refractory
Androl. 2018;20:561-566. bone metastases from thryoid cancer: Preliminary results
of a single arm Phase II trial
S. Zerdoud1, D. Deandreis2,3, A. Maillard4,5, I. Borget4,5, C. Bournaud6,
OP-622 L. Leenhardt7, M. Terroir2, A. Al Ghuzlan8, M. Schlumberger2, S.
Preliminary Evaluation of Tumor Uptake and Laboratory Leboulleux2;
Parameters After a Single Dose of 177Lu-RM2 Radioligand 1
Institut Universitaire du cancer Toulouse Oncopole, Toulouse,
Therapy in Metastatic Castrate-Resistant Prostate Cancer FRANCE, 2Nuclear Medicine and Endocrine Oncology, Gustave
R. Fernández1, V. Kramer2, A. Hurtado de Mendoza1, J. Flores1, H. Roussy and Paris Saclay, Villejuif, FRANCE, 3Department of
Amaral1,2; Medical Science, University of Turin, Turin, ITALY, 4Biostatistics
1
Center for Nuclear Medicine & PET/CT Positronmed, and Epidemiology Department, Gustave Roussy, Villejuif,
Santiago, CHILE, 2Positronpharma SA, Santiago, CHILE. FRANCE, 5Fac. de médecine - UVSQ, INSERM, Université
Paris-Saclay, 94805, Villejuif, FRANCE, 6Nuclear Medicine,
Groupement Hospitalier Est, Lyon, FRANCE, 7Endocrine
Aim/Introduction: RM2 is a synthetic bombesin receptor Oncology, Hôpital Pitié-Salpêtrière, Paris, FRANCE, 8Pathology,
antagonist that targets gastrin-releasing peptide receptors Gustave Roussy and Paris Saclay, Villejuif, FRANCE.
(GRPr). GRPr are highly overexpressed in several human tumors,
including prostate cancer, providing a promising target for
imaging and radionuclide therapy. Initial experiences with 68Ga- Aim/Introduction: Radium 223 is a therapy for symptomatic
RM2 PET/CT showed renal clearance, high physiologic uptake bone metastases from castration resistant prostate
in the pancreas and suggested that this tracer could detect cancer. The aim of this trial was to evaluate the efficacy
relapse of prostate cancer and metastases with high contrast of Radium-223 in patients with bone metastases from
in some patients. Aim: To evaluate early effects on blood tests radioactive iodine refractory (RAIR) thyroid cancer (TC).
after a single dose of 177Lu-RM2 in patients with metastatic Materials and Methods: Multicenter prospective single arm
castration-resistant prostate cancer (mCRPC). Materials and two-stage Simon Phase II trial (NCT02390934). Primary objective
Methods: The local ethical committee approved the study, and establish efficacy of 3 monthly Radium-223 administrations
informed consent was obtained in all patients. Four patients by PERCIST FDG PET/CT criteria in RAIR TC patients with bone
(mean age ± SD, 72 ± 4,3 y) with late-stage mCRPC underwent metastases without visceral metastases or progressive visceral
both, 68Ga-PSMA-11 and 68Ga-RM2 PET/CT for target evaluation metastases. Secondary objectives was to establish efficacy
S239 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

of 6 monthly administrations of Radium-223 by FDG PET/CT tumors resistant to conventional cancer treatments. The aim of
according to PERCIST criteria, response on 99mTc-HMDP bone the study reported herein was to evaluate the feasibility of this
scan and 18 NaF PET/CT after 3 and 6 monthly administrations minimally invasive, percutaneous brachytherapy technique for
of Radium-223, and during treatment: monthly clinical benefits, tumor treatment in the lung. In addition, we assessed the safety
changes serum bone markers and thyroglobulin levels and and efficacy profiles of a novel nano-device derived from [188Re]
assess safety of Radium-223 according to NCI CTCAE version 4. rhenium-ligand as radioactive ligand loaded 5th generation
Results: For first step analysis: 10 patients were prospectively poly-L-lysins dendrimer in patients with unresectable Lung
enrolled between July 2015 and December 2017 (4 M; 6F Malignancies. Materials and Methods: The experiment agent
Median Age 74 y, range 62-76). Papillary (n=5), Follicular (n=3) “ 188Rhenium-ImDendrim” is consisting of 5th generation poly-L-
and Poorly differentiated TC (n=2). Delay between discovered lysins dendrimer (172,3 kDa, 20 nM) mixed with nitro-imidazole-
first bone metastases and inclusion: 6 years (3-10). Bone lesions methyl-1,2,3-triazol-methyl-di-(2-pycolyl) amine at GMP grade
in the axial skeleton: all patients (median number: 4, 1-9) and (Gift from Nano-Gun-Technology NGT) and labelled with
bone lesions in peripheral skeleton 3/10. Median RAI treatments 188
Rhenium. The study was approved by Shanghai East Hospital
before Radium-223: 4 (3-6). Delay between last RAI treatment ethics commette. 5 Patients received “188Rhenium-ImDendrim”
and inclusion was 3 yrs (1-5). Patients received previously directly into lung tumors under CT-guidance, at an activity
external radiation therapy (n=9), interventional radiology level of 162 MBq/cc of tumor (range 2 to 7 cm; mean diameter,
treatment (n=3) and surgery (n=8). 9/10 patients received 6 4 cm) . For voluminous tumors (>65 cc) the dose is given in
cycles of radium 223. At FDG PET/CT PERCIST criteria, after: 3 divided injection spaced 2 weeks apart (Tumor of 115cc: 2
monthly Radium 223 administrations patients presented 6/10 administrations, Tumor of 180cc: 3 administrations). Toxicity
Stable Disease (SD) and 4/10: Progressive Disease (PD). One was assessed by the nature, incidence, and severity of adverse
patient stopped Radium 223 for bone skeletal event needing events (Common Toxicity Criteria scores) and by hematology
urgent surgery. After 6 monthly Radium-223 administrations, and clinical chemistry parameters. At T0.5hr , T4hr, T24hr, T36hr , T72hr
5/9 SD and 4/9 PD. At bone scan and at 18 NaF PET/CT, after 6 post- administration patients get a control scintigraphy with
cycles of Radium 223, patients presented 9/9 SD and 8/9 SD and SPECT gamma camera . The response to treatment is evaluated
1/9 Partial Response (PR) respectively. After 6 cycles of Radium thanks to PET/CT Standardized Uptake Values (SUVs). Results:
not significant and durable reduction thyroglobulin and ALP Stereotactic administrations of “188Rhenium-ImDendrim” were
levels. During the treatment only 1 grade 3 neutropenia, but successfully carried out in all patients under local anesthesia.
during follow up 1 patient developed acute myeloid and 1 The radioactive product diffuses in all tumoral volume and
promyelocitic leukemia. Conclusion: According to metabolic remains 72 hours post-administration with no significant
response at FDG PET, preliminary data suggest no evidence diffusion out site of injection. One of the 5 patients reported
of Radium-223 efficacy in RAI refractory TC patients with bone discrete transitive hemoptysis as adverse events, but no serious
metastases. Long term follow up is ongoing to confirm these events were attributable to the study device. All targeted tumors
preliminary data. Furthermore awareness of long term toxicity is were responding at 12 weeks, with two complete responses.
needed. References: None. Conclusion: Percutaneous single and iterative administrations
of this novel 188Rhenium-Imdendrim brachytherapy device
into lung cancers are safe and well tolerated. The initial data on
OP-624 therapeutic response are promising. References: Belhadj-Tahar
Novel CT guided 188-rhenium Brachytherapy Device For and coll. Journal Clinical Oncology 2018 36:15.
Local Primary And Secondary Lung Malignancies
H. Belhadj-Tahar1, J. Chen2, J. Zhao2, J. Song3, M. Quan2, C. Li1, X.
Gu2, G. Yang1, Y. Gao2; OP-625
1
AFPREMED (French Association of Medical Research First Clinical Experience using 177Lu-Zoledronate for the
Advancement), Toulouse, FRANCE, 2Shanghai East Hospital, Treatment of Skeletal Metastases in Breast Cancer: 68Ga-
School of Medicine, Shanghai East Hospital (China), Shanghai, NODAGA-ZOL PET-CT imaging for patients eligibility and
CHINA, 3Shanghai East Hospital, School of Medicine, follow-up
Shanghai East Hospital (China), Shanghai, CHINA. F. Novruzov1, J. Aliyev2, S. Rahimzade3, R. Shukurov1, J. Šimeček4, L.
Mehmetbeyli1, Z. Allahverdiyeva5, E. Mehdi1;
1
Department of Nuclear Medicine, National Centre Of Oncology,
Aim/Introduction: Stereotactic brachytherapy for extensive Baku, AZERBAIJAN, 2Department of General Surgery, National
local tumors offers a very effective treatment option locally Centre Of Oncology, Baku, AZERBAIJAN, 3Department of Woman
without significant complications in medically impaired Health, National Centre Of Oncology, Baku, AZERBAIJAN, 4Isotope
patients who are not amenable to surgery. In this context, we Technologies Garching GmbH, Garghing, GERMANY, 5Department
have recently developed a new potential anticancer agent of Medical Oncology, Central Clinical Hospital, Baku, AZERBAIJAN.
from Poly-L-Lysins dendrimer as a delivery nano system loaded
with diffusible Imidazolic probes complexed with 188Rhenium
(physical half-life: 17hrs; with β: 2.12MeV, 71.1% and 1.965MeV, Aim/Introduction: Metastatic bone cancer is a common and
25.6% and γ : 155keV, 15.1%) for targeting in particular hypoxic severe complication in advanced diseases. Around 70% of all
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S240

metastatic patients eventually develop bone metastases. In 1409


total, 60% to 75% of metastasis in breast cancer is diagnosed
as bone metastasis at first. Radionuclide therapy is shown to be
Bone & Joint - Featured Session: Bone SPECT/
useful and cost effective in relieving bone pain in metastatic
CT and PET/CT Quantification - A Clinical Tool
diseases and may be more effective when combined with
for Diagnosis and Prognosis in Diffuse and
chemotherapy. Herein we evaluate the response to 177Lu-
Localised Skeletal Diseases
DOTA-Zoledronate treatment and report the 68Ga-NODAGA-
Zoledronate PET/CT findings of a breast cancer patient with Tuesday, October 15, 2019, 14:30 - 16:00 Lecture Hall 115
multiple bone-only metastases in the axial and appendicular
parts of the skeleton. Materials and Methods: A 65-year-old
breast cancer patient with multiple bone-only metastases was OP-626
referred for staging. 18F-NAF PET-CT performed before and 2 Bone SPECT/CT and PET/CT Quantification - A Clinical
months after the pain treatment with 3700 MBq of 177-DOTA- Tool for Diagnosis and Prognosis in Diffuse and Localised
Zoledronic acid. The eligibility for radionuclide treatment was Skeletal Diseases
determined with 68Ga-NODAGA-Zoledronate acid (192 MBq T. Van der Wyngaert;
for 66 kg of weight) PET-CT imaging. The patient’s blood test Antwerp University Hospital, Nuclear Medicine, Edegem, BELGIUM.
results (Hb: 15.1 g/dL, total white cell count: 8.21 × 103/µL,
plt:277 109/L) made her eligible for the therapy with the bone- OP-627
seeking agent. Patient also received 2 cycles of chemotherapy Quantifying skeletal burden in fibrous dysplasia using
(adriamycin and cytoxan). Complete blood count, liver function Sodium Fluoride PET/CT
tests, oncomarkers and blood creatinine were noted before and W. van der Bruggen1,2, M. Hagelstein-Rotman3, L. de Geus-Oei2, F.
during the treatment. Results: The baseline 18-F NAF and 68Ga- Smit4, S. P. D. S. Dijkstra5, N. M. Appelman-Dijkstra3, D. Vriens2;
Zoledronate PET/CT showed multiple intense and identical lytic 1
Dept. of Nuclear Medicine, Slingeland Hospital, Doetinchem,
lesions throughout the axial skeleton. In comparison with the NETHERLANDS, 2Section of Nuclear Medicine, dept. of Radiology,
pre-treatment 18F-NaF PET/CT images the SUVmax values of Leiden University Medical Center (LUMC), Leiden, NETHERLANDS,
lesions were decreased up to 7 times. The patient gradually 3
Center for Bone Quality, dept. of Internal Medicine, division of
reduced the usage of the pain relief medication (fentanyl 50 Endocrinology, Leiden University Medical Center (LUMC), Leiden,
mcg/hr, transdermal patch) which she took every 3 days and NETHERLANDS, 4Dept. of Nuclear Medicine, Alrijne Hospital,
stopped using at all over one month. The main adverse effect Leiderdorp, NETHERLANDS, 5Dept. of Orthopaedic surgery, Leiden
was pancytopenia detected after 5 days, lasted nearly 7 weeks, University Medical Center (LUMC), Leiden, NETHERLANDS.
which was difficult to differentiate whether this was due to the
radionuclide treatment or concurrent/ongoing chemotherapy.
Conclusion: Due to better physical properties of 177Lu Aim/Introduction: To quantify Na18F-PET/CT uptake in relation
compared to other bone pain palliation agents like (153Sm to clinical and biochemical parameters of fibrous dysplasia
and 188Re), 177Lu-Zoledronate could be used as a potential (FD) severity and healthy bone (HB) metabolism. Secondary
new candidate in clinical trials for bone pain palliation therapy. aims: to compare different normalizations for volume of
This case illustrates the benefit of 68Ga-NODAGA-ZOL PET/ distribution, to determine the reproducibility of Na18F-PET/CT
CT in skeletal metastases of breast cancer to assess potential uptake parameters in HB and FD and to relate Na18F-uptake
for radionuclide therapy with 177-Lu DOTA-Zoledronate and to skeletal burden score (SBS) and antiresorptive therapy and
monitor treatment. References: None. pain measured by Brief Pain Inventory (BPI). Materials and
Methods: In a prospective pilot study (n=20), Na18F-PET/CT
parameters of HB and FD were determined by two independent
readers to define the cut-off defining increased bone uptake,
optimized normalization and interobserver agreement. Na18F-
PET/CT FD-parameters were related to SBS, serum biomarkers,
medication, and clinical parameters. Results: Physiological
bone standardized uptake value (SUV) was best normalized,
but displayed large interpatient variation (total range 4.1-13.7
g/mL), with very high interobserver agreement (ICC=0.964).
FD-burden defined by patient-specific SUV-cutoffs reached
near-perfect agreement for SUVpeak (ICC=0.994) and total
lesion fluorination (TLF) (ICC=0.999). TLF correlated weakly with
SBS (R2=0.384, p=0.047). TLF correlated positively with serum
alkaline phosphatase (R2=0.571, p=0.004) and procollagen
type 1 N-terminal propeptide (R2=0.621, p=0.002), SBS did
not (p>0.06). SBS and TLF both correlated with increased
fibroblast growth factor-23 (FGF-23) (R2=0.596, p=0.007 and
S241 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

R2=0.541, p=0.015, respectively). TLF was higher in use of were acquired for localization and attenuation correction
bisphosphonates (p=0.038), SBS was not. Average BPI-scores purposes. FD-related 18F-NaF activity was assessed by using
correlated to increased FGF-23, work-related BPI-scores to MIM vista (version 6.5.9). Firstly, a VOI encompassing the entire
higher SBS (R2=0.518, p=0.024), higher TLF (R2=0.478, p=0.036) skeleton was drawn, and afterwards a SUVmax threshold-based
and to higher levels of FGF-23 (R2=0.567, p=0.034). Conclusion: approach -customized per patient- was employed in order to
Individualized Na18F-PET/CT SUV cut-offs reproducibly include all FD-related bone uptake. Separate VOIs encircling
discriminated HB from FD and were well-normalized. The strong all areas above the SUVmax threshold set by the user, were
relations of bone formation serum markers with Na18F-PET/CT automatically generated and areas with physiologic or non-
FD-burden measurements suggest clinical relevance over SBS as FD related 18F-NaF activity (e.g. activity in the urinary tract,
an adjunct instrument in FD patients before treatment initiation. inflammatory uptake) were manually removed. Subsequently,
The correlation of both imaging modalities with increased work- FD-related 18F-NaF activity in the entire skeleton determined as
related BPI-scores also indicates clinical applicability. Moreover, the product of SUVmean multiplied by the total volume (TV)
SBS is known to remain stationary irrespective of use of of all skeletal 18F-NaF positive FD lesions (TA = SUVmean × TV)
medication, whereas TLF on Na18F-PET/CT was higher in baseline was obtained automatically. Results: Pearson’s correlation test
patients using antiresorptive therapy. This makes Na18F-PET/CT revealed that skeletal FD-related 18F-NaF activity was positively
a promising tool to quantitatively measure treatment efficacy in associated with serum levels of alkaline phosphatase (r =
the follow-up of FD patients. To our experience, the advantages 0.758, P < 0.01), and osteocalcin (r = 0.707, P = 0.01), as well
of Na18F-PET/CT clearly outweigh the disadvantages over as urine levels of NTX (r = 0.739, P = 0.02). (P-values adjusted
technetium bone scintigraphy. Depending on local availability for false discovery rate) Conclusion: Skeletal FD-associated
and cost-effectiveness depending on costs and reimbursement, 18
F-NaF activity strongly correlates with bone turnover markers,
we foresee a more prominent role for Na18F-PET/CT in primary suggesting that 18F-NaF PET/CT accurately reflects underlying
diagnosis and follow-up of FD patients. References: None. bone metabolic processes encountered in FD. These findings
strongly imply the employment of this imaging modality for the
in vivo assessment of FD activity, holding promise to serve as a
OP-628 surrogate endpoint for accurate determination of disease activity.
18
F-NaF uptake by fibrous dysplasia bone lesions is References: None.
positively associated with bone turnover markers (BTMs)
G. Z. Papadakis1,2, G. C. Manikis2, A. H. Karantanas1,2, K. Marias2, U.
Bagci3, P. Florenzano4, M. T. Collins4, A. M. Boyce4;
1
Department of Radiology, Medical School, University of Crete, OP-629
Heraklion, GREECE, 2Computational Biomedicine Laboratory Prognostic utility of 18F-NaF PET/CT imaging for fractures
(CBML), Institute of Computer Science (ICS), Foundation in patients with fibrous dysplasia of bone
for Research and Technology Hellas (FORTH), Heraklion, G. Z. Papadakis1,2, G. C. Manikis2, A. H. Karantanas1, K. Marias2, U.
GREECE, 3Center for Research in Computer Vision, University Bagci3, P. Florenzano4, M. T. Collins4, A. Boyce4;
of Central Florida, Orlando, FL, UNITED STATES OF AMERICA, 1
Department of Radiology, Medical School, University of Crete,
4
National Institute of Dental and Craniofacial Research Heraklion, GREECE, 2Computational Biomedicine Laboratory
(NIDCR), Bethesda, MD, UNITED STATES OF AMERICA. (CBML), Institute of Computer Science (ICS), Foundation
for Research and Technology Hellas (FORTH), Heraklion,
GREECE, 3Center for Research in Computer Vision, University
Aim/Introduction: Fibrous dysplasia (FD) of bone is a benign of Central Florida, Orlando, FL, UNITED STATES OF AMERICA,
skeletal disorder characterized by the replacement of normal 4
National Institute of Dental and Craniofacial Research
bone and normal bone marrow with abnormal fibro-osseous (NIDCR), Bethesda, MD, UNITED STATES OF AMERICA.
tissue leading to significant morbidity. 18F-NaF is a bone seeking
PET-agent, which targets bone processes characterized by
increased bone surface exposed to blood flow, such as the Aim/Introduction: Fibrous dysplasia (FD) of bone is a
processes encountered in FD. Aim of the current study was benign skeletal disorder characterized by the replacement
to explore potential associations between FD-related 18F-NaF of normal bone and normal bone marrow with abnormal
activity in the entire skeleton, with established markers of bone fibro-osseous tissue leading to significant morbidity. 18F-NaF
activity, like serum levels of alkaline phosphatase (Alk Phos) and is a bone seeking PET-agent, which targets bone processes
osteocalcin (OC), and urine levels of N-terminal telopeptide characterized by increased bone surface exposed to
(NTX). Materials and Methods: Fifteen FD patients underwent blood flow, such as the processes encountered in FD. Aim
whole-body 18F-NaF PET/CT studies at the NIH Clinical Center. of the current study was to explore potential prognostic
PET scans from the vertex of the skull to the plantar surface utility of 18F-NaF-PET/CT for fractures in FD patients.
of the feet were obtained 62.36 ± 6.11 (mean ± SD) minutes Materials and Methods: Fifteen FD patients underwent whole-
(range: 58 - 76) after intravenous administration of an average body 18F-NaF-PET/CT studies at the NIH Clinical Center. PET
± standard deviation of 2.81 ± 0.83 mCi of 18F-NaF (range: scans from the vertex of the skull to the plantar surface of the
0.92 - 4.98). Low dose, non-contrast, non-diagnostic CT scans feet were obtained 62.36±6.11 (mean±SD) minutes (range: 58
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S242

- 76) after intravenous administration of an average±standard xSPECT-Bone, with and without iMAR-reconstruction of CT data
deviation of 2.81±0.83 mCi of 18F-NaF. Low dose, non-contrast, which show high Z-material streak artefacts. SUVmax means
nondiagnostic CT scans were acquired for localization and were correlated to intraoperative findings or clinical outcome
attenuation correction purposes. FD-related 18FNaF activity after 1 year (standard of comparison). Cut-off values and accuracy
was assessed by using MIM vista (version 6.5.9). Firstly, a VOI of the different reconstructions were calculated using receiver
encompassing the entire skeleton was drawn, and afterwards operator characteristics (ROC) and compared to the accuracy
a SUVmax threshold-based approach -customized per patient- of visual SPECT/CT readings by a senior physician and a trainee
was employed in order to include all FD-related bone uptake. blinded for the quantitative data and clinical outcome. Results:
Separate VOIs encircling all areas above the SUVmax threshold SUVmax were significantly higher in loose prostheses compared
set by the user, were automatically generated and areas with to stable prostheses, with all methods of quantification used
physiologic or non-FD related 18F-NaF activity (e.g. activity in (p=0.018-0.001). For xSPECT Bone quantification, diagnostic
the urinary tract, inflammatory uptake) were manually removed. accuracy was 91% without iMAR (cut-off SUVmax 13.4,
Subsequently, the following FD-related 18F-NaF parameters sensitivity 88%, specificity 93%). With iMAR, accuracy of xSPECT
were automatically obtained from the extracranial skeleton (i.e., Bone was 95% (Cut-off SUVmax 13.8, sensitivity 100%, specificity
total skeleton without the skull): Total Volume (TV) of all 18F-NaF 93%). For xSPECT Quant without iMAR, accuracy was 85%
positive FD lesions, and total lesions activity determined as the (Cut-off SUVmax 10.3, sensitivity 100%, specificity 83%). For
product of SUVmean multiplied by the total volume (TV) of the xSPECT Quant with iMAR, accuracy was 83% (Cut-off SUVmax
18
F-NaF positive FD lesions (TA = SUVmean × TV) detected in 11.1, sensitivity 88%, specificity 86%). Diagnostic accuracies of
the extracranial skeleton. Results: TV of extracranial FD showed blind-readers were 79% for an experienced reader, and 71%
very strong correlation with lifetime fractures (Spearman’s rank for a trainee. Conclusion: This interims analysis provides first
correlation coefficient rho = 0.897, P < 0.001) and mean fractures evidence that quantitative uptake values of periprosthetic
per year (rho = 0.873, p < 0.001). Similarly, TA of extracranial FD bone metabolism using 99mDPD-SPECT/CT with xSPECT Quant
was strongly associated with lifetime fractures (rho = 0.87, p and Bone reconstructions has a higher accuracy compared to
< 0.001) and mean fractures per year (rho = 0.844, p < 0.001). conventional scan reading underlining the high potential of
Conclusion: Total volume (TV) and total activity (TA) of 18F-NaF quantification as a biomarker for the diagnosis of prosthetic
avid bone lesions in the extracranial skeleton is of prognostic loosening. The use of iMAR reconstructed CT in the xSPECT
utility for fractures in patients diagnosed with FD of the bone. Quant and xSPECT Bone reconstruction only mildly impacts
This data suggests prognostic application of 18F-NaF PET/CT attenuation correction but improves image quality of CT and
imaging for selection of FD patients with increased risk for bone xSPECT Bone. References: None.
fractures. References: None.
OP-631
Prognostic value of NaF-PET/CT in non-instrumented
OP-630 posterolateral lumbar fusion
Quantitative 99mTc-DPD-SPECT/CT for the detection of C. Constantinescu1, R. Piri1,2, O. Gerke3, M. Andersen4, P. Høilund-
prosthetic loosening in patients with hip- and knee Carlsen1,2;
joint replacement - an interim Analysis of a prospective 1
Department of Nuclear Medicine, Odense University Hospital,
imaging study Odense, DENMARK, 2Research Unit of Clinical Physiology
M. Braun1, M. Cachovan2, A. H. Vija3, G. Pagenstert4, D. Wild1, M. and Nuclear Medicine, Department of Clinical Research,
Kretzschmar1; University of Southern Denmark, Odense, DENMARK, 3Odense
1
University Hospital of Basel, Clinic of Radiology and Nuclear University Hospital, Odense, DENMARK, 4Center for Spine
Medicine, Basel, SWITZERLAND, 2Siemens Healthcare GmbH, Surgery and Research, Sygehus Lillebælt, Odense, DENMARK.
Molecular Imaging, Forchheim, GERMANY, 3Siemens Medical
Solutions USA, Inc., Molecular Imaging, Hoffman Estates, IL,
UNITED STATES OF AMERICA, 4University Hospital of Basel, Aim/Introduction: Non-instrumented posterolateral lumbar
Department of Orthopedic Surgery, Basel, SWITZERLAND. fusion is the treatment of choice in Scandinavia for spinal
stenosis patients with degenerative spondylolisthesis. Positron
emission tomography (PET) with 18F-sodium fluoride (NaF)
Aim/Introduction: To evaluate the diagnostic performance of is an imaging modality capable of showing ongoing calcium
standardized quantitative 99mTc-DPD-SPECT/CT with and without deposition in vivo. We aimed to investigate the prognostic value
use of anatomical bone segmentation as well as with and without of NaF-PET/CT performed in this category of patients one month
mitigation for CT metal artefact reduction in patients with after treatment with non-instrumented posterolateral lumbar
painful knee and hip joint prostheses suspicious for loosening. fusion. Materials and Methods: 18 patients (median 66.5 years,
Materials and Methods: Thirteen consecutive patients with a range 60-78, 13 females) underwent 90-minute NaF-PET/CT one
total of 22 prostheses (13 hip and 9 knee prostheses) underwent month after surgery for degenerative spondylosis. Fusion status
99m
Tc-Dicarboxypropandiphosphate(DPD)-SPECT/CT 3h after was determined using high resolution CT within a year of surgery.
injection of 99mTc-DPD (mean dose 697MBq). Quantitative Clinical characteristics including walking distance, VAS score of
reconstruction was performed with Siemens xSPECT-Quant and back pain (VAS-B), Oswestry Disability Index questionnaire (ODI),
S243 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

and European Quality of Life - 5 Dimensions questionnaire (EQ- 15 patients (6 female and 9 male, mean age 59 years, age range
5D) were assessed before surgery and 1 year after. The changes 41-77 years). Administerd activity was 1,5-3,7 MBq/Kg. Images
in clinical parameters between the time points were compared were evaluated by two independent expert nuclear medicine
with the graft NaF uptake in each patient. Results: Only 4 of 18 physicians. Uptake was defined as linear if present along the
patients experienced fusion, which was bilateral and multilevel vertebral contour or focal. Linear (9) or focal (2) uptake was
in all four. The median graft uptake (range) in fused patients revealed in all patients without changes at different acquisition
was 1178(961-1279) SUV compared to 1333(474-27817) SUV in time. In 3 patients tracer uptake was multilevel. SUVmax ranged
non-fused patients (p = 0.93). The corresponding partial volume from 5.8 to 7.3 (mean 6.4, median 6.2). Four patients were
corrected values were 1282(962-9535) SUV and 1341(481- submitted to surgery Conclusion: In this pilot investigation,
27842) SUV (p = 0.35). Fused patients showed a median increase 18
F-NaF PET/CT imaging showed potential utility for evaluation
in walking distance of 737 (0-985) meters compared to 855(360- of recurrent symptoms after spinal fusion surgery by identifying
985) in non-fused patients (p = 0.29), a median decrease in those patients requiring surgical management. 18F-fluoride
VAS-B of 4.3(0-8.3) vs 3.8(0.1-8.5) (p=0.92), a median decrease in uptake was variable at different time between surgery and PET
ODI of 25(12-54) vs 29.5(4-38) (p=0.56), and a median change in scan suggesting a role in understanding osteoblastic reparative
EQ-5D of 0.279(0.53-0.674) vs 0.277(0-0.611) (p = 0.56). Graft NaF bone reaction and its correlation with persistence or recurrence
uptake was not significantly correlated with walking distance of symptoms. References: None.
(p = 0.3), VAS-B (p = 0.62), ODI (p = 0.22) or EQ-5D (p = 0.78).
Conclusion: Total NaF uptake in the graft region measured
one month after surgery was not able to predict change in 1410
any of the measured clinical parameters from baseline to one
year after surgical treatment. However, there was no difference
General Nuclear Medicine - Parallel Session:
either in the change of clinical parameters suggesting that the
General Nuclear Medicine
examined sample of patients and the fraction of patients with
fusion were too small to allow detection of potential differences. Tuesday, October 15, 2019, 14:30 - 16:00 Lecture Hall 116
References: None.

OP-632 OP-633
The role of 18F-NaF PET/CT imaging in the assessment of Renal Clearance Function Index - a New Quantitative
patients undergoing spinal fusion surgery Parameter of a Dynamic Renal Scintigraphy
A. Sammartano, M. Scarlattei, G. Baldari, S. Migliari, F. Tartara, L. K. Filipczak1, P. Cichocki2, M. Surma2, A. Plachcinska1, J. Kusmierek2;
Ruffini; 1
Department of Quality Control and Radiological Protection,
Azienda Ospedaliero-Universitaria di Parma, Parma, ITALY. Medical University of Lodz, Lodz, POLAND, 2Department of
Nuclear Medicine, Medical University of Lodz, Lodz, POLAND.

Aim/Introduction: Lumbar intercorporal fusions are performed


to treat symptomatic segmental degeneration or instability Aim/Introduction: Assessment of a kidney function by the
in the spine. After spinal fusion surgery patients may have dynamic renal scintigraphy (DRS) is based both on the visual
recurrent symptoms requiring standard evaluation by clinical analysis of sequential scintigraphic images and a course of
examination and conventional imaging. However, CT and/or renographic curves with respect to Tmax and T1/2, as well as a
MRI will often show extensive and nonspecific postoperative split function (SF). The relative nature of SF makes it impossible
changes. 18F-fluoride is a PET tracer depicting blood flow to reliably assess the real efficiency of renal parenchyma in
and osteoblastic activity. Aim of this study was to assess some situations. Therefore, a parameter was determined
osteoblastic activity in the spine as sign of local reparative which reflects a kidney function in an absolute way and
process after implantation of intersomatic cages using 18F-NaF could expand diagnostic capabilities of DRS in many clinical
PET/CT imaging Materials and Methods: Fifteen patients with situations. Materials and Methods: The study involved 138
intercorporal fusions were submitted to a PET/CT scan with kidneys, from adult patients with measured serum creatinine
18
F-NaF. Time interval between fusion surgery and the PET/CT level. Standard dynamic renal scintigraphy was performed,
examination was variable according to symptoms recurrence ( with detector field of view covering kidneys as well as heart.
(1 day-3 years). The level of surgery was mainly L4-L5 and L5-S1. A 99mTc-EC radiopharmaceutical, in activity of 111MBq, was
PET dynamic images of the specific spine tract were acquired used. A sequence of 120 images (10s acquisition each) was
immediately after i.v. injection of 18F-NaF on a hybrid scanner acquired, then processed with the in-house developed method.
Discovery IQ (GE Healthcare). Whole-body PET/CT was acquired This method included among others generation of a cardiac
from base of skull to pelvis 60 minutes after tracer injection and curve (from the cardiac ROI), standardization of cardiac and
late image after 90 minutes on the site of cages. In all patients, renographic curves (dividing them by the area under the
a non-diagnostic CT was acquired for attenuation correction. cardiac curve) and calculation of a clearance function index (CFi)
Results: PET imaging with 18F-NaF PET/CT was performed in for each kidney. For the purpose of assessment of inter-observer
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S244

variability of the method, definition of ROIs, curves generation OP-635


and calculation of CFi was done twice, by two operators. In Tailoring the sampling time of single-sample GFR
addition to the renoscintigraphic study, a glomerular filtration according to renal function: is the proposal in the British
rate value was estimated (eGFR) for each patient using the Nuclear Medicine Society GFR guidelines practical and
MDRD formula (taking into account patient creatinine level, supported by evidence?
age and sex). Based on the SF, eGFR coefficients were estimated S. Townrow1, H. McMeekin1, M. Burniston1, F. Wickham2, B.
separately for each kidney (KeGFR). The obtained values of CFi Fongenie2, D. McGowan3, C. Porter3, A. Bradley4, M. Memmott4, N.
and SF were compared with the KeGFRn values. Results: The Vennart5, M. Barnfield6;
correlation coefficient between CFi and KeGFR was high - 0.83 1
Barts Health NHS Trust, London, UNITED KINGDOM, 2Royal
and statistically significant (p<0.0001) - significantly higher than Free London NHS FT, London, UNITED KINGDOM, 3Oxford
the correlation coefficient between SF and KeGFR, which was University Hospitals NHS FT, Oxford, UNITED KINGDOM,
0.65 (p<0.0001). Correlation between CFi values obtained by 4
Manchester University NHS FT, Manchester, UNITED KINGDOM,
two operators was very high (0.99) and statistically significant 5
Gateshead Health NHS FT, Gateshead, UNITED KINGDOM,
(p<0.0001). Conclusion: The generated renal clearance function 6
Leeds Teaching Hospitals NHS Trust, Leeds, UNITED KINGDOM.
index (CFi) is a new absolute, non-relative and reproducible
parameter, describing a clearance function of each kidney Aim/Introduction: In the UK, GFR studies have been routinely
separately, which can be compared between patients. It can be determined using a slope intercept calculation with the
useful in assessment of the damage of a kidney parenchyma, blood plasma samples taken typically in the range from 2 - 6
especially in clinical situations when the usefulness of the hours post injection. The revised 2018 BNMS GFR guidelines
relative percentage uptake is limited. References: None. recommend a single-sample technique with the sampling
time dictated by the expected renal function, but this is not
known with any accuracy before the test. We aimed to assess
OP-634 whether the sampling regime suggested in the guidelines is
Effect of adenosine infusion on renal blood flow (RBF) optimal, and determine the expected error in GFR result if the
during stress Rb-82 PET/CT anticipated eGFR differs significantly from the GFR measured
G. Allenbach, N. Testart, M. Meyer, M. Nicod Lalonde, J. Prior; in the study or venous sampling occurs at the wrong time. We
Lausanne University Hospital, Lausanne, SWITZERLAND. can then infer the degree of flexibility in the sampling regime.
Materials and Methods: Data from over 8000 patients referred
Aim/Introduction: Rb-82 dynamic perfusion PET is used to for GFR assessment at 6 different UK hospitals for a variety of
quantify myocardial blood flow. With the extended field of indications were reviewed. The difference between the single-
view in newest PET scanners it becomes possible to measure sample (Fleming) GFR result at each sample time and the slope-
renal Rb-82 uptake opening the door to renal blood flow intercept GFR result in routine clinical use at each hospital
quantification. Our aim is to measure the effect of adenosine was calculated. Data points were excluded if the sample was
infusion on renal blood flow (RBF) using Rb-82 in patient with taken outside a series of time windows around the intended
coronary heart disease. Materials and Methods: We selected time. A further analysis was performed on 660 patients who
16 consecutive patients referred for suspicion of myocardial had completed a more thorough 9 point area-under-the-
ischemia, 6 with normal myocardial perfusion imaging (no curve study for renal clearance up to 8 hours post-injection, to
ischemia) and normal myocardial flow reserve (>2) and 9 with determine if there was any systematic variation between slope
stress ischemia and a reduced flow reserve (<2). Myocardial intercept and single-sample GFR results. Results: The optimal
6-min adenosine stress and rest PET acquisitions were obtained sampling time is determined based on the accuracy (bias) and
after injection of 300-700 MBq of Rb-82. On the 6-minutes reproducibility (precision) of the result. At low GFR (< 60 ml/
dynamic PET series 3 spherical VOI were placed on the upper min/1.73m2) single-sample measurements are more precise at
pole of each kidney. A VOI on the aorta was used for vascular longer sampling times, but also show a systematic positive bias
input function. Using the PMOD software, a 1-compartment of up to 6 ml/min/1.73m2 compared with the slope intercept
model was used to compute K1 without further corrections values. At intermediate GFR (60 - 100 ml/min/1.73m2) single-
applied. Results: Mean RBF at rest was 1.33±0.39 ml/min/g in sample results are both accurate and precise when the blood
the non ischemic group and 1.03±0.3 0ml/min/g in the ischmic sample is taken between two and four hours post-injection. For
group. Mean RBF at stress was 1.39±0.28 ml/min/g for the non higher GFR values the study becomes imprecise if the blood
ischemic group and 0.85±0.36 ml/min/g (0.91-1.81) for the sample is collected later than 2 hours post-injection, and there is
group with myocardial ischemia with a significant difference a systematic negative bias of up to 10 ml/min/1.73m2 compared
(p=.012). We observed a decrease of 19% RBF under adenosine with the slope intercept values. Conclusion: The data supports
perfusion in the group known for myocardial ischemia and an the approach of the guidelines and demonstrates a reassuringly
increase of 2% in the group without ischemia. Conclusion: wide range of sample times for an acceptably accurate single-
Assessment of RBF during cardiac perfusion scan is possible. sample GFR result. This needs to be further validated with a
Adenosine stress seems to induce a reduction of RBF in patient reference technique out to 24 hours post injection rather than
with myocardial ischemia, and had no effect on RBF in a group a limited sample slope-intercept GFR calculation. References:
without myocardial ischemia. References: None. None.
S245 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

OP-636 lung function in patients with pulmonary malignancies and


Utility Of The Isotopic Renogram And SPECT/CT In The compromised function. However, subdividing lung parenchyma
Urinary Leaks Diagnosis And Management In Patients into rectangular regions of interest, as done on planar images,
With Renal Transplantation poorly reflects true lobar anatomy. SPECT/CT allows analyzing
J. Gómez Hidalgo, M. Ruiz Gómez, P. Turbay Eljach, N. Álvarez pulmonary function based on individual 3D perfusion obtained
Mena, A. Sainz Esteban, M. Alonso Rodríguez, C. Gamazo Laherrán, through low dose CT segmentation. The aim of our study was
B. Pérez López, M. González Soto, R. Ruano Pérez; to determine 3D normal values of perfusion for the whole lungs
Hospital Clínico Universitario de Valladolid. and each pulmonary lobe using SPECT/CT. Materials and
Medicina Nuclear, Valladolid, SPAIN. Methods: We performed a unicenter retrospective analysis
including 20 normal subjects (9 males; mean age 60 years, range
36-84) without history of lung pathology, derived to our center
Aim/Introduction: to evaluate the contribution of the isotopic for pulmonary perfusion scintigraphy with 99mTc-MAA. After
renogram, early and delayed planar image and delayed SPECT/ intravenous injection of 200 MBq planar images in standard
CT to the diagnosis of urinary leakage in patients with kidney projections and SPECT/low-dose CT images were acquired in a
transplantation. Materials and Methods: we studied 394 Mediso AnyScan 16 gamma camera. Data was analyzed using
patients who underwent cadaver kidney transplantation from Mediso Lung Lobe Segmentation software to determine relative
January 2011 to December 2016. Twenty-four hours after perfusion and relative volumes. Results: A total of one hundred
transplantation we performed a 30 minutes renogram study lobes were quantified. In females the results of segmented
focusing on the abdomen in anterior projection after the quantification (mean [CI 95%], perfusion/volume) were: right
administration of 370 MBq of 99mTc-DTPA, followed by planar upper lobe: 36.3(31.9-40.7) / 36.0 (32.2-36.0), middle lobe 5.1
images at 30 and 180 minutes post-injection. In 81 of these (3.9-6.3) / 6.9 (5.4-8.2), right lower lobe 14.0 (11.3-16.7) / 12.6
patients we performed isotopic renogram controls. In addition, (10.4-14.9), total right lung 55.3 (53.0-57.8) / 55.8 (54.3-57.3), left
46 patients underwent delayed abdominal SPECT/CT (22 upper lobe 27.3 (25.3-29.3) / 30.4 (28.4-32.4) left lower lobe 17.3
cases at 24 hours post-transplant and 24 patients in renogram (14.1-20.4) / 15.1 (11.8-18.4) and total left lung 46.4 (42.8-49.9) /
controls). Results: of the 394 patients (age: 59.0+/-13, 275 men), 45.1 (42.5-47.6). In males: 29.9 (25.2-34.6) / 26.8 (23.1-30.4), 9.7
in 46 urine leak was suspected. Isotopic renogram with early and (7.1-12.2) / 12.0 (10.0-14.0), 15.3 (11.2-19.5) / 15.7 (12.4-18.9),
delayed planar images and delayed SPECT/CT were performed 55.1 (52.0-58.2) / 55.2 (53.2-57.3), 28.6 (25.2-32.1) / 28.2 (25.3-
in all of them, confirming urinary leak in 17 (4.3% of the total and 31.1), 16.4 (13.9-18.9) / 17.7 (14.5-20.9) and 44.9 (41.2-48.0) /
36.9% of the diagnostic suspicions) and ruling out the urinary 44.8 (42.7-46.8), respectively. Middle lobe perfusion was lower
leakage in the rest. Of the 17 patients with urinary leak, in 15 in women than in men (p = 0.003). No differences in other lobes
cases the delayed planar image and SPECT/CT were necessary or total lungs were detected. Conclusion: We report normal
for the diagnosis (location and extension) and in the other 2 values of relative total lung and lobar perfusion for hybrid
patients the SPECT/CT confirmed the diagnosis suspicion and SPECT/CT imaging. Tridimensional quantification can provide
improved the localization and extension. Of the 17 patients valuable information to guide surgical decisions and estimate
with urine leakage, 6 were diagnosed in the scintigraphic postoperative outcomes, particularly when a lobectomy is
image performed 24 hours post-transplant and 11 cases in the planned. References: None.
renogram controls performed at 6 days (2 patients), 8, 9, 10 (2
patients), 11, 12, 22, 28 and 40 days post-transplant (mean: 9.88
days and median: 8 days). All cases of urinary leakage resolved OP-638
satisfactorily after scintigraphic diagnosis. Conclusion: the The Role of Tc-99m MAA SPECT-CT in Evaluation of Lung
renogram in transplant patients allows detecting urinary leaks Lobar Perfusion in Patients with Chronic Obstructive
as a surgical complication, facilitating the implementation of Pulmonary Disease (COPD) Prior to Lung Volume
corrective measures at an early stage. Delayed planar imaging Reduction Surgery (LVRS)
and SPECT/CT are especially useful in the diagnosis of urinary E. Trahair, E. Nowosinska, N. Sizer, K. Lau, G. Sotiropoulos, A. Balan,
leakage, improving the assessment of its extension and location. T. O’Shaughnessy, R. Williams, D. Waller, M. Burniston;
References: None. Barts Health NHS Trust, London, UNITED KINGDOM.

OP-637 Aim/Introduction: COPD patients are routinely referred for


Quantification of pulmonary function using hybrid SPECT/ lung perfusion imaging to quantify lobar perfusion prior to lung
CT in normal subjects volume reduction surgery (LVRS). Traditionally planar imaging
C. C. M. Fernandez, E. Silvera, S. Rodriguez, A. Damian, R. Ferrando; is performed and lung perfusion quantification is calculated
Clinics Hospital, University of the Republic, Montevideo, URUGUAY. on anterior and posterior images by dividing the lungs into
three equal size ROIs. Whilst this method gives some indication
of regional lung function, it does not accurately represent the
Aim/Introduction: Planar perfusion scintigraphy with 99mTc- lung lobes. It is accepted that a more useful result for surgical
MAA allows a non-invasive preoperative quantification of regional planning would be accurate lobar perfusion contributions,
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S246

and it is proposed that SPECT-CT would allow for calculation to December 2015 at the Jewish General Hospital, Canada to
of lobar perfusion. Materials and Methods: Patients referred identify patients with small perfusion abnormalities. Subjects
for pre-surgery lung perfusion imaging with Tc99m-MAA were included if the V/Q scan revealed small subsegmental
underwent both planar and SPECT imaging. Diagnostic CT VQ mismatches (defined as <50% of a pulmonary segment).
images were registered with reconstructed SPECT data and Subjects were excluded if there was documented prior PE or DVT
used for segmentation of lung lobes using Hermes Hybrid 3D or if there were any large VQ mismatches (defined as >50% of a
Lung Lobe Quantification software in order to calculate lobar pulmonary segment). In addition to a chart review, we measured
perfusion contributions. Planar perfusion quantification was the number of PE recurrences in addition to PE and bleeding
performed by dividing each lung into three equal size ROIs. related morbidity. Results: Of the 543 VQ scans reviewed,
Additionally, as a complementary result for surgical planning, 44 V/Q scans in 44 subjects revealed only subsegmental VQ
CT scans were analysed using StratX Lung Analysis Platform to mismatches and were included in the study. Of the 44 subjects
quantify emphysema destruction in the lungs. Where available, included, 11 were excluded due to history of PE. Ultimately,
lung function test results were also collected. Results: Within a 26 subjects not anticoagulated and 7 anticoagulated subjects
6 month period 74 patients were evaluated (43 male, 31 female), had follow-up for approximately 900 +/- 400 days from the day
mean age 65 (range 37-82). Perfusion contributions of left and of the VQ scan. Each VQ scan revealed 1 to 4 subsegmental
right lung correlated well between planar and SPECT imaging mismatches. No subjects suffered PE recurrence requiring
methods with no significant difference found. Lobar perfusion medical intervention and 1 anticoagulated subject had a minor
results from planar and SPECT methods differed by an average of bleed (which did not require change in therapy or a transfusion).
11% (range 0-35%), which was statistically significantly different Conclusion: Our study suggests that subjects with small
(p<0.01), and in some cases indicated a different target lobe subsegmental mismatches on VQ scintigraphy do not carry a
for LVRS. Comparison with the results of quantitative analysis significant risk of PE related morbidity or mortality, regardless
of emphysema destruction on CT scans will also be included of anticoagulation status. Therefore, clinicians can potentially
in the presentation. Conclusion: SPECT-CT for lung perfusion forego anti-coagulation therapy in this subset of patients and
provides more anatomically correct delineation of lung lobes, therefore avoid potential hemorrhagic complications, which
leading to more accurate lobar quantification results. This in and of themselves carry a significant risk of morbidity and
technique could have a significant impact on LVRS planning mortality. However, this observation requires validation with a
and critically could prevent mis-targeting a lobe that makes a randomized prospective study. References: None.
significant contribution to lung function. References: None.

OP-640
OP-639 Initial Evaluation of the Protocol to Assess the Function of
Evaluating the Need for Anti-Coagulation Therapy in Future Remnant Liver After Major Hepatectomy by Means
Patients with a Small Pulmonary Thromboembolic Burden of Hepatobiliary Scintigraphy and SPECT/CT Imaging with
on VQ Scan 99mTc-Mebrofenin
P. Maliha1, G. Chaussé1, V. Tagalakis2, A. Ciarallo1; M. Nevares Herrero, P. Mínguez Gabiña, A. Esteban Figueruelo, R.
1
McGill University Health Center, Montreal, QC, CANADA, Valverde Jorge, I. Fernández Tercero, E. Rodeño Ortiz de Zárate, M.
2
Jewish General Hospital, Montreal, QC, CANADA. Prieto Calvo, A. Valdivieso López;
Hospital Universitario de Cruces, Barakaldo, SPAIN.

Aim/Introduction: Introduction of single photon emission


computed tomography ventilation/perfusion (SPECT V/Q) Aim/Introduction: Hepatobiliary scintigraphy (HBS) with 99mTc-
imaging has resulted in the increased detection of small mebrofenin has been used as a quantitative method to evaluate
perfusion defects previously not seen with conventional liver function. The use of SPECT/CT has allowed a more accurate
ventilation/perfusion imaging. This leads to an increased measurement of segmental liver functionality. Materials and
number of patients diagnosed with pulmonary embolism Methods: Since August 2017, in patients with major liver
(PE) and, consequently treated with anticoagulation. Studies resection, except for left hepatectomy with non-compromised
comparing computed tomography angiography (CTA) to planar liver, CT volumetry and HBS+SPECT/CT with 99mTc-mebrofenin
VQ imaging have shown that CTA increases the number of PE have been performed. From the latter test, the function of the
diagnoses without impacting PE mortality, raising the question future remnant liver (FRL-F) (%/min/m2) and the HIBA index (%)
of the relevance of anticoagulation in small PE. We postulate were obtained. For these indexes, cutoff values for liver failure
that anticoagulation therapy may have little impact in patients of 2.7%/min/m2 and 15%, respectively, have been reported.
diagnosed with small PEs on VQ scintigraphy, since a low Morbidity was classified by Dindo-Clavien, and liver failure
embolic burden in absence of other comorbidities is unlikely was measured by the IGSLS and 50/50 scores. Results: A total
to increase the risk of mortality. Our aim is to assess the clinical of 20 patients were included, two of them being excluded
outcome of subjects with subsegmental mismatched defects preoperatively (progression). Cholangiocarcinoma was the
on VQ scintigraphy. Materials and Methods: We performed a most common diagnosis (50%), followed by colorectal liver
retrospective chart review of all VQ studies performed in January metastases (44.4%). Of all patients, 55.6% were female with a
S247 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

median (min-max) age of 68y (35-83). Fifteen patients (83.3%) 1502


were considered preoperatively as compromised liver but only
one patient (5.6%) was cirrhotic. Seven patients (38.9%) had
Joint Symposium 23 - Oncology & Theranostics
a preoperatively biliary drainage and three patients (16.6%)
Committee / ENETS: Theranostic in NEN - What
had right portal vein embolization. In two patients (11.1%) an
is New?
ALPPS procedure was performed. Eight patients (44.4%) had
postoperative morbidity but in only two patients (11.1%) was ≥ Tuesday, October 15, 2019, 16:30 - 18:00 Lecture Hall 311
IIIb. Two patients (11.1%) developed post-resection liver failure,
associated to portal thrombosis. From the CT volumetry, the
median liver remnant weight and percentage of liver remnant OP-644
were 620g (336-1270) and 40% (24-75), respectively. From the Overview on NEN Treatment - Current Options and Clinical
SPECT/CT, the median percentage of liver functionality of the Needs
FLR was 51% (28-89). The median FRL-F and HIBA index were M. Pavel;
2.4%/min/m2 (0.5-8.9) and 19% (7-50), respectively. Both, the Department of Medicine 1 Division of Endocrinology, Friedrich
FRL-F and the HIBA index followed a normal distribution, and Alexander University Erlangen – Nürnberg, Erlangen, GERMANY.
a good correlation was found between them (r=0.75). Of all
patients, 56% had a FLR-F and 33% a HIBA-index below the
cutoff values for liver failure. The two patients that showed liver OP-645
failure had FRL-F below the cutoff value (both patients 2.2%/ Overview on NEN Diagnosis
min/m2) but HIBA-indexes (17% and 26%) above it. Conclusion: V. Ambrosini;
In patients that undergo major liver resection, HBS+SPECT/CT University of Bologna, S.Orsola-Malpighi Hospital,
with 99mTc-mebrofenin is a simple technique to calculate the Department of Experimental Diagnostic and Specialized
function of the future remnant liver (FLR-F and HIBA index). A Medicine, Nuclear Medicine, Bologna, ITALY.
higher number of patients will be needed in order to look for a
correlation between those indexes and the risk of post-resection
liver failure. References: None. OP-646
Update on PRRT - When and How
L. Bodei;
1501 Memorial Sloan Kettering Cancer Center, Department of
Radiology, Targeted Radionuclide Therapy Molecular Imaging
CME 12 - Paediatrics Committee: Response and Therapy Service, New York, NY, UNITED STATES OF AMERICA.
Evaluation of Paediatric Sarcomas

Tuesday, October 15, 2019, 16:30 - 18:00 Auditorium OP-647


New Treatment Options
D. Wild;
University Hospital Basel, Division of Nuclear
OP-641 Medicine, Basel, SWITZERLAND.
Response of Paediatric Sarcomas - Does it Matter?
S. Bielack;
Klinikum der Landeshauptstadt Stuttgart gKAöR – Olgaspital, OP-648
Department of Paediatric Oncology, Stuttgart, GERMANY. Discussion

OP-642
Radiological Response Evaluation of Paediatric Sarcomas
T. von Kalle;
Klinikum der Landeshauptstadt Stuttgart gKAöR – Olgaspital,
Department of Paediatric Radiology, Stuttgart, GERMANY.

OP-643
Response Assessment in Paediatric Sarcomas - Value of
Nuclear Medicine Techniques
M. Parisi;
Seattle Children’s Hospital, Department of Paediatric Radiology
and Nuclear Medicine, Seattle, WA, UNITED STATS OF AMERICA.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S248

1503 OP-654a
The Role of a Technologist in the Preparation of
Joint Symposium 24 - Translational and Acquisition Protocols and the Processing of Image Data
Molecular Imaging Therapy + Oncology & S. Rep;
Theranostics Committee / EAU / ERUS: Image University Medical Centre Ljubljana, Department
Guided Therapies for Prostate Cancer of Nuclear Medicine, Ljubiana, SLOVENIA.

Tuesday, October 15, 2019, 16:30 - 18:00 Lecture Hall 312


OP-654b
The Role of a Technologist in the Preparation of
OP-649 Acquisition Protocols and the Processing of Image Data
Hardware Development for Targeted Prostate Cancer G. Testanera;
Therapies St Bartholomew’s Hospital, Department of Nuclear
F. Collamati; Medicine, London, UNITED KINGDOM.
Istituto Nazionale di Fisica Nucleare,
Department of Physic, Rome, ITALY.
1505
OP-650
M2M - Parallel Session: Preclinical Models in
Molecular Targeting Strategies for Salvage Prostate Cancer
Translational Science
Surgery
T. Maurer; Tuesday, October 15, 2019, 16:30 - 18:00 Lecture Hall 111
University of Hamburg-Eppendorf (UKE), Martini-Klinik
Prostate Cancer Center, Hamburg-Eppendorf, GERMANY.

OP-655
OP-651 Characterization Of The Apolipoprotein E-deficient Rat As
Focal Therapy for Prostate Cancer Novel Model For Atherosclerosis Imaging
J. Walz; J. Sijbesma, A. van Waarde, S. Kristensen, I. Kion, U. J. F. Tietge, J. L.
Institut Paoli-Calmettes Cancer Center, Hillebrands, H. Buikema, D. Nakladal, F. Liu, H. H. Boersma, R. A. J. O.
Department of Urology, Marseille, FRANCE. Dierckx, R. H. J. A. Slart;
UMCG, Groningen, NETHERLANDS.

1504
Aim/Introduction: The apolipoprotein E-deficient (apoE-/-)
CTE 6 - Technologist Committee: Parathyroid mouse is a well-established preclinical model of atherosclerosis.
Imaging Lipoprotein clearance is impaired in this model, resulting in
elevated plasma levels of remnant cholesterol which stimulates
Tuesday, October 15, 2019, 16:30 - 18:00 Lecture Hall 117 the development of atherosclerotic plaques. Positron emission
tomography (PET) plays an important role in visualizing and
understanding plaque development but the small size of the
OP-652 mouse is a limitation. Vessels are hard to detect, formed plaques
Comparison of 99mTc-MIBI and 18F-Cholin Scintigraphy in are often smaller than the camera resolution and rapid arterial
Localization of Hyperfunctioning Parathyroid Tissue blood sampling is technically challenging. ApoE-/- rats have
L. Lezaic; recently become available. Thus, we aimed to answer the
University Medical Centre, Department of following questions: 1.Is the apoE-/- rat suitable for imaging of
Nuclear Medicine, Ljubljana, SLOVENIA. atherosclerosis? 2.At which age become plaques detectable in
this model? Materials and Methods: For a baseline scan (at
age 8 weeks), apoE-/- (n=10) and wild type (WT) rats (Long-
OP-653 Evans) (n=10) were injected with 60 MBq 18F-FDG. Plasma
11C-Methionine PET-CT Imaging in Hyperparathyroidism cholesterol was measured. After 3h a CT scan was performed
G. Pepe; followed by a 20-min static PET scan. Animals received a high
Humanitas Research Hospital, Department fat/cholesterol diet after the baseline scan. The scan procedure
of Nuclear Medicine, Milan, ITALY. was repeated at week 4, 12, 26 and 51. After the final scan, aortic
tissue was collected for future analysis. The CT data was used
to calculate the % of body fat. Uptake of 18F-FDG in the aortic
root and abdominal aorta was calculated. Results: Plasma
S249 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

cholesterol levels in apolipoprotein B-containing lipoproteins that Me4 is less suitable for the brain (although SGLT2 is
were substantially increased after 4 weeks of high/cholesterol expressed), since it does not cross the blood brain barrier [1].
diet in the apoE-/- rats and kept increasing until the end of the SGLT2 can be found in the liver [2], which therefore responds
study versus the WT rats where levels stay stable. Body weight to Dapagliflozin. In the heart, SGLT1 is expressed, playing an
and the % of body fat increased faster in the apoE-/- rats, important role in cardiac protective mechanisms [3]. Although
but were similar for both strains at the end of the study. The only the immunohistological analysis can complete the picture,
SUVmean of FDG in the aortic arch increased in both strains, but an increased FDG and decreased Me4 uptake after Dapagliflozin
was significantly higher (p<0.001) in apoE-/- versus WT rats at treatment might be indirect reactions: as observed in the kidneys
week 26 and 51. Tracer uptake in the abdominal aorta showed [4], SGLT1 expression could be increased due to SGLT2 inhibition.
a similar pattern, but with a significantly higher (p<0.05) uptake References: 1. Yu AS et al, doi: 10.1152/ajpcell.00296.2010.
in the apoE-/- rats already at week 12. Immunohistochemical 2. Sabolic I et al, doi: 10.1152/ajpcell.00450.2011 3. Kashiwagi
staining of the collected tissues is ongoing. Conclusion: The Y et al, doi: 10.1371/journal.pone.0130605 4. Song P et al, doi:
apoE-/- rat is a promising model for atherosclerosis imaging. The 10.1517/14728222.2016.1168808.
model shows elevated plasma circulating levels of cholesterol in
proatherogenic apoB-containing lipoproteins of total and LDL
cholesterol. PET imaging shows differences in FDG uptake in OP-657
aortic arch and abdominal aorta after 12 weeks when feeding a Molecular imaging characterization of Distraction
high fat/cholesterol diet. Immunohistochemical staining has to Osteogenesis model
confirm if this is plaque formation. References: None. L. Balasse1, F. Roseren2,3, A. Moyon1, S. Fernandez4, P. Garrigue1, G.
Hache1, M. Pithioux2,3, B. Guillet1;
1
Aix Marseille Univ, C2VN, CERIMED, Marseille, FRANCE, 2Aix
OP-656 Marseille Univ, CNRS, ISM, Marseille, FRANCE, 3Aix Marseille
Systemic effects of SGLT2-Inhibition in healthy mice Univ, APHM, CNRS, ISM, Sainte-Marguerite Hospital, Institute for
B. K. Geist, T. Balber, S. Bugayong, E. Klebermass, L. Nics, A. Pillinger, Locomotion, Department of Orthopaedics and Traumatology,
S. Rasul, H. Regele, A. Zacher, M. Hacker; Marseille, FRANCE, 4Aix Marseille Univ, CERIMED, Marseille, FRANCE.
Medical University Vienna, Vienna, AUSTRIA.

Aim/Introduction: Distraction osteogenesis (DO) is a surgical


Aim/Introduction: SGLT2 inhibitors such as Dapagliflozin are procedure widely used for limb lengthening to treat limb length
anti-diabetic drugs which primarily inhibit the re-absorption discrepancy. DO procedure is divided into three distinct phases.
of glucose by the sodium-glucose transporter SGLT2 in the The latency period starts after callotasis surgery (A), followed
kidneys, leading to an increased glucose excretion and thus a by the distraction period (B). When the desired elongation is
decreased blood glucose level. Additionally, also positive effects reached, the external fixator is then locked, and consolidation
on other organs have been reported recently. In particular, the period is initiated (C). To date, if limb lengthening is efficient, the
cardio-protective effect of SGLT2 inhibition in the heart is not duration of phase C needed to remove external fixator, remains
fully understood yet. Therefore, a mice study was performed hard to set, causing a high risk of fracture. This work aimed to
with dynamic combined positron emission and computer characterize, using molecular imaging, callus regeneration,
tomography (PET/CT). Materials and Methods: The study angiogenesis and osteoblastic activity in rat model of DO during
ran from autumn 2018 to May 2019, involving one group with Phases A, B and C. Materials and Methods: A DO rat model
16 diabetes type 2 and one with 16 healthy mice, whereby (1) were applied to 6 male rats. Animals were weekly monitored
half of the animals were treated with Dapagliflozin. Dynamic during the phases A (6 days), B (10 days), C (6 weeks) by µCT,
PET/CT scans were performed using one glucose analogue µTEP and µSPECT to quantify the bone density, angiogenesis
with low (FDG: 2-[18F]Fluor-2-desoxy-D-glucose) and one and bone metabolism. Angiogenesis were longitudinally
with high SGLT2 affinity (Me4: α-methyl-4-deoxy-4-[18F]FDG). evaluated using 10±0.5 MBq of [68Ga]-RGD. PET images were
From the fused images, the uptake after 40 minutes of brain, acquired 1h after injection on Mediso-NanoPET-CT. Bone
liver, kidneys, bladder and heart was calculated. Furthermore, metabolism were longitudinally monitored using 30±1.5 MBq
a kinetic modeling and a immunohistological analysis will be of [99mTc]-HMDP. Planar SPECT images were acquired 4h after
performed. Results: So far, the healthy group was evaluated. In injection on Mediso-NanoSPECT-CT. Quantitative region-of-
the brain, Me4 uptake was 70 % lower (p < 0.0001) compared interest (ROI) analysis of PET and SPECT images were performed
to FDG, Dapagliflozin had no impact on both tracers. In the with Vivoquant software (Invicro®) and tissue uptake values
liver, Me4 uptake was higher by 55 % (p = 0.002), Dapagliflozin presented as ratio of fractured bone on contralateral bone
lead to a decrease by 47 % (p = 0.002). In the heart, Me4 (i/c). Results: Molecular imaging showed that activation of
uptake was small and 76 % lower than FDG uptake (p < 0.001). angiogenesis and osteogenesis both started on Day 6 after the
Dapagliflozin decreased Me4 uptake by 46 % (p < 0.001), but surgery during Phase A, increased progressively during Phase
it increased FDG uptake by 35 % (p = 0.04). Further results on B up to the end of the phase to an C : i/c ratios of 5.6±1.2 and
the diabetes group, immunohistological analysis and kinetic 2.59±0.4 respectively for [68Ga]-RGD and [99mTc]-HMDP imaging.
modeling will be presented. Conclusion: The study confirms Then [68Ga]-RGD TEP signal start to decrease and normalized 2
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S250

weeks after the end of phase C and [99mTc]-HMDP SPECT signal 124I-trastuzumab and 18F-FDG (p< 0.0001), which further
normalized 4 weeks after the end of phase C. Conclusion: This confirms the specific binding of 124I-trastuzumab. No toxicities
is the first report of molecular imaging characterization of DO or adverse reactions were observed in any of the patients.
model. DO induced strength and sustained activations of both Conclusion: We successfully synthesized, evaluated the quality
angiogenesis and osteogenesis that persists several weeks after control and applied the 124I-trastuzumab PET radiotracer.
distraction. Osteogenesis activation is more sustained than The findings of the micro-PET imaging study confirmed that
angiogenesis. This work shows that molecular imaging can be 124I-trastuzumab was useful and specifically bound to HER2-
an efficient imaging tool to evaluate new optimization of DO positive tumors. The findings of the clinical study indicated that
procedure and that PET and SPECT imaging could be a valuable the use of 124I-trastuzumab PET was feasible for identifying
tool to determine whether the bone reconstruction phase HER2-positive lesions in patients with primary and metastatic
should be extended and decrease the risk of fracture for which gastric cancer and for the quantitative differentiation of HER2-
occurrence after removal remain frequent. References: (1) M. positive and HER2-negative lesions. References: None.
Pithioux and al., 2017.

OP-659
OP-658 Prospective Theranostic Treatment Planning for Patient-
124I-trastuzumab for noninvasive HER2 detection: From Specific Low-Dose Molecularly Targeted Radiotherapy to
patient-derived xenograft models to gastric cancer PET Enhance Immunotherapeutic Response
imaging I. R. Marsh, R. Hernandez, M. Turek, E. Aluicio-Sarduy, J. J.
X. Guo, N. Zhou, Z. Chen, H. Zhu, Z. Yang; Grudzinski, R. Patel, P. Carlson, M. Otto, P. M. Sondel, J. W. Engle, Z.
Peking University Cancer Hospital & Institute, Beijing, CHINA. Morris, J. P. Weichert, D. Vail, B. P. Bednarz;
University of Wisconsin-Madison, Madison,
WI, UNITED STATES OF AMERICA.
Aim/Introduction: Here we sought to develop the trastuzumab
probe labeled with the positron emission tomography (PET)
radionuclide 124I (T1/2 =100.32 h), which has a long physical Aim/Introduction: External beam radiotherapy (EBRT)
decay time, to evaluate the safety, distribution, internal delivering immunomodulatory dose to localized disease
dosimetry, and initial PET images of human epidermal growth has been shown to enhance tumor response to checkpoint
factor receptor 2 (HER2)-positive lesions in gastric cancer inhibition immunotherapies. In metastatic disease, where
patients. Materials and Methods: In the animal study, we the utility of EBRT is limited, we are investigating the use of
injected 14.8 MBq 124I-trastuzumab/124I-hIgG1 into HER2- molecularly targeted radiotherapy (MTRT) with a radiolabeled
positive (n = 20) and HER2-negative (n=20) gastric cancer alkylphosphocholine analog (86Y/90Y-NM600) to deliver
patient-derived xenograft (PDX) models for micro-PET immunomodulatory dose to all tumor sites. In preclinical murine
imaging and in vivo biodistribution. Then, 124I-trastuzumab models, we have demonstrated a cooperative therapeutic
was successfully translated to clinical PET imaging [ethical effect with immunotherapies and 90Y-NM600 MTRT delivering
approval no. 2018KT48]. Six patients with metastatic gastric as little as 2 Gy to tumors. Here, we present a preliminary report
cancer underwent 124I-trastuzumab PET imaging. Each on patient-specific 86Y-NM600 derived dosimetry for 90Y-NM600
patient received an intravenous injection of 74±17 MBq MTRT treatment planning and delivery in an ongoing first-in-
124I-trastuzumab along with 10 mg trastuzumab, and the PET canine theranostic study. Materials and Methods: A 45 kg
scans were acquired at 1, 24, 48 h. The radioactivity data were canine companion presenting with metastatic osteosarcoma
obtained by drawing regions of interest on the PET images, and was administered 178 MBq of 86Y-NM600, and serial PET/CT
the multiorgan biodistribution and internal dosimetry data of the scans were acquired at 2.5, 24, and 48 h post-injection. Regions
probe were evaluated. Each patient underwent 18F-FDG PET/ of interest (ROIs) were expertly-contoured at each timepoint
CT as a comparison. Results: In the micro-PET imaging study, based on the fused PET/CT images. Decay-corrected 90Y-NM600
124I-tratuzumab exhibited a significantly higher tumor uptake PET/CT biodistributions were modeled in Geant4 Monte Carlo
than 124I-IgG1 (p = 0.0002) in HER2-positive PDX models at 24 simulations to produce absorbed dose rate (ADR) distributions
h postinjection. The low uptake levels of 124I-tratuzumab (p = at each timepoint. Voxel-level ADR distributions were integrated
0.0004) in HER2-negative PDX models at 24 h further confirmed over time to estimate the prescription dose (Gy/GBq) within
the specific binding of the radioprobe. In the clinical study, 29 temporally coregistered ROIs. Following confirmation of tumor-
lesions (18 HER2-positive lesions and 11 HER2-negative lesions) specific uptake, 90Y-NM600 was prescribed to achieve a mean
were selected for image analysis. The PET images showed that dose of 2 Gy to the lowest-uptake lesion while limiting exposure
the best time for assessing 124I-tratuzumab uptake in the to red marrow. Results: PET/CT imaging confirmed specificity
tumors was 24 h postinjection, and 10 mg cold trastuzumab was and persistent accumulation of 86Y-NM600 in tumors (3.4-4.2
adequate to reduce nonspecific liver uptake. There were clear SUV mean at 48 h) and the dosimetry workflow for theranostic
differences in tumor uptake between HER2-positive and HER2- 90
Y-NM600 MTRT was completed within 5 days. The estimated
negative lesions at 24 h (p< 0.0001). In HER2-negative lesions, prescription dose of 3.2 Gy per injected GBq in the lowest-uptake
there were significant differences in tumor uptake between lesion suggested the administration of 0.62 GBq of 90Y-NM600
S251 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

MTRT to deliver 2.0-2.6 Gy to all tumors. Dose delivered by 86Y- OP-661


NM600 imaging studies was negligible. Dose to red marrow was The potential of PET/CT imaging as a clinical evidence
estimated at 1.1 Gy based on lumbar vertebrae marrow. The liver method for the early detection of Duchenne muscular
and kidneys received a tolerable 2.6 and 3.2 Gy, respectively. dystrophy (DMD) in female carriers- a study in genetically
Following treatment with MTRT, the subject exhibited a modified pigs
favorable adverse event profile. Conclusion: We demonstrate M. J. Lindner1, L. M. Fonteyne2, B. Keßler2, A. Bollenbacher1, E.
here the first use of patient-specific prospective dosimetry for Kemter2, A. Todica1, S. Nekolla3, P. Bartenstein1, E. Wolf2, S. Ziegler1;
theranostic 90Y-NM600 MTRT treatment planning in this first- 1
Department of Nuclear Medicine, University Hospital Munich,
in-canine osteosarcoma patient. These preliminary results Munich, GERMANY, 2Gene Center and Department of Biochemistry,
indicate the feasibility of patient-specific theranostic MTRT to Molecular Animal Breeding and Biotechnology, LMU Munich,
deliver optimal immunomodulatory radiation that potentially Munich, GERMANY, 3Department of Nuclear Medicine at
enhances immunotherapeutic response. References: None. Technische Universität München, Munich, GERMANY.

OP-660 Aim/Introduction: DMD is the most common neuromuscular


PET imaging of the glucagon receptor in non-human disease in juvenile age. The x-chromosomally recessive heredity
primate leads to a degeneration of the muscle fiber and substitution of
I. Velikyan1, O. Eriksson1, T. Haack2, M. Bossart2, A. Evers2, I. muscles by fat and connective tissue. Importantly, heart muscle
Laitinen2, P. J. Larsen3, O. Plettenburg2, G. Antoni1, L. Johansson4, S. is affected preclinically and clinically as cardiomyopathy. The
Pierrou4, M. Wagner2; therapy consists of symptomatic treatment. Female carrier
1
Department of Medicinal Chemistry, Uppsala University, Uppsala, subjects may, although not suffering from DMD, also develop
SWEDEN, 2Sanofi-Aventis, Frankfurt, GERMANY, 3Grunenthal GmbH, cardiac symptoms. In this study, quantitative PET/CT imaging
Aachen, GERMANY, 4Antaros Medical AB, Molndal, SWEDEN. of genetically modified DMD carrier pigs was used to test for
presymptomatic detection of muscular dystrophy. Materials
and Methods: The study was performed on 3 months old
Aim/Introduction: The Glucagon receptor (GCGR) is an genetically modified DMD (n=5) and wildtype pigs (n=3) on
emerging target in anti-diabetic therapy. Reliable biomarkers a clinical PET/CT scanner (Siemens Biograph). A non-contrast
for in vivo activity on the GCGR, in the setting of dual glucagon enhanced CT scan was acquired first, followed by a 60 min
like peptide 1/ glucagon (GLP-1/GCG) receptor agonism, are dynamic ECG-triggered PET measurement of the heart, starting
currently unavailable. Positron Emission Tomography (PET) at the time of injection of F18-FDG (300MBq) into the lateral ear
tracer [68Ga]Ga-DO3A-S01-GCG was previously shown to bind vein. Afterwards, whole-body FDG distribution was measured
to the GCGR with high affinity and specificity in vitro and in vivo in 8 bed positions from 60-90 min p.i.. Pigs were monitored by
in rats [1]. Here, we investigated [68Ga]Ga-DO3A-S01-GCG as a ECG, respiratory rate, and blood-glucose-level. The volumes-of-
biomarker for GCGR occupancy in liver in non-human primates Interest (VOI´s) were defined firstly by the left ventricle of the
by PET. Materials and Methods: The GCGR targeting properties heart. Ejection fraction (EF in %), endsystolic volume (EsVol in
of [68Ga]Ga-DO3A-S01-GCG was evaluated by dynamic PET in ml), and enddiastolic volume (EdVol in ml) were determined.
non-human primates by a dose escalation study design where Secondly, FDG uptake in skeletal muscle was determined by
up to 67µg/kg DO3A-S01-GCG peptide mass was co-injected. placing a VOI on the longissimus thoracis muscle. Results:
The test-retest reproducibility in non-human primate, as well Compared to wild type animals, cardiac ejection fraction was 7%
as the effect on [68Ga]Ga-DO3A-S01-GCG by pre-treatment lower in DMD pigs. Mean enddiastolic (endsystolic) volume was
with an acylated glucagon agonist was also investigated by 7 % (15%) less in DMD pigs. Group average of mean standard
PET/CT imaging. Results: [68Ga]Ga-DO3A-S01-GCG bound to uptake value (SUV) in the whole longissimus thoracis muscle was
GCGR rich liver in vivo in a dose-dependent manner. Negligible 0.50 in DMD and 0.32 in wildtype pigs. Mean standard deviation
peptide mass effect was observed for DO3A-S01-GCG doses in the whole-muscle VOI was 0.26 in DMD and 0.16 in wildtype.
of <0.2 µg/kg. In vivo Kd for [68Ga]Ga-DO3A-S01-GCG in liver Further, an asymmetry of SUV between the right and left part of
corresponded to 0.7 µg/kg indicating high potency. The test- the muscle was found (mean group deviation right: 10%; left:
retest reproducibility was 5.7±7.9% and pre-treatment with an 29%). No statistical significance was found in this preliminary
acylated glucagon agonist incurred an occupancy of 61.5±9.1% study with low number of animals. Conclusion: A reduction of
in liver. Predicted human absorbed doses would allow for the cardiac function and an increase of the regional radioactivity
repeated annual [68Ga]Ga-DO3A-S01-GCG PET examinations. concentration in the musculus longissimus thoracis could be
Conclusion: PET radioligand [68Ga]Ga-DO3A-S01-GCG is a measured in the genetically modified DMD pigs compared to
novel quantitative biomarker of in vivo GCGR occupancy wildtype animals. These results may reflect early impairment of
determination in non-human primates. References: Velikyan I, cardiac function and potential changes in muscle metabolism
et al. First-in-class Positron Emission Tomography tracer for the in DMD-carriers. Thus, FDG imaging may guide in identifying
Glucagon receptor. EJNMMI Res (2019) 9(1):17. signs of DMD in carrier subjects. The animal number will be
increased for improved statistics. Further studies will correlate
imaging results with tissue samples. References: None.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S252

OP-662 1506
Pharmacokinetic modelling of P-glycoprotein function at
the blood-brain barrier with [18F]MC225 PET in non-human
Do.MoRe - Parallel Session: New Concepts,
primates
Harmonisation and Standardisation in
L. Garcia Varela1, W. M. Arif1, D. Vállez García1, T. Kakiuchi2, H.
Radiomics
Ohba2, S. Nishiyama2, T. Tago3, P. H. Elsinga1, H. Tsukada2, N. A.
Colabufo4, R. A. J. O. Dierckx1, A. van Waarde1, J. Toyohara3, R. Tuesday, October 15, 2019, 16:30 - 18:00 Lecture Hall 112
Boellaard1, G. Luurtsema1;
1
University of Groningen, Groningen, NETHERLANDS,
2
Central Research Laboratory, Hamamatsu Photonics KK, OP-663
Hamamatsu, JAPAN, 3Research Team for Neuroimaging, A Study of Radiomic Features Robustness for 68Ga-
Tokyo Metropolitan Institute of Gerontology, Tokyo, DOTATOC PET/CT in Neuroendocrine Tumors
JAPAN, 4University of Bari Aldo Moro, Bari, ITALY. V. Liberini1, E. Gallio2, O. Rampado2, B. De Santi3, B. Dionisi1, F. Ceci1,
E. Pilati1, M. Finessi1, M. Bellò1, G. Bisi1, F. Molinari3, D. Deandreis1;
Aim/Introduction: Impaired P-glycoprotein (P-gp) function 1
Nuclear Medicine Unit, Department of Medical Sciences, University
can lead to the onset of neurodegenerative disease or to of Turin, Turin, ITALY, 2Medical Physics Unit, AOU Città della Salute
drug resistance. [18F]MC225 has been developed as a weak e della Scienza, Turin, ITALY, 3Biolab, Department of Electronics
substrate aimed to measure increases and decreases of the and Telecomunications, Politecnico di Torino, Turin, ITALY.
P-gp function. The tracer was initially evaluated in mice and rats.
In this study, we extended these evaluations by investigating
[18F]MC225 kinetics in non-human primates with a particular Aim/Introduction: The use of 68Ga-DOTATOC PET/CT
emphasis on assessing robust parameters to estimate the P-gp as a prognostic and predictive tool of heterogeneity in
function. Moreover, since short PET scans are desirable, the neuroendocrine tumors (NET) is gaining importance.The aim of
pharmacokinetics were explored at different acquisition times this study was to evaluate the impact of different reconstruction
(10-, 20-, 30- and 60-min). Materials and Methods: Three non- and segmentation methods on the identification of repeatable
human primates underwent two 91-min-dynamic PET scans and reliable radiomic features (RFs). Materials and Methods:
with arterial blood sampling, one at baseline and another after To evaluate the robustness of RFs, we retrospectively analyzed
P-gp inhibition (8mg/Kg tariquidar). Metabolite-corrected data from two different cohorts of patients that performed
plasma and whole-blood time-activity curves were used as input a 68Ga-DOTATOC PET/CT scan (Philips Dual GEMINI) for NET
function for pharmacokinetic modeling. For each acquisition disease: “algorithm cohort” including 22 patients to evaluate
time, the preferred model was chosen according to the Akaike the robustness in function of reconstruction algorithms; “naive
Information Criterion (AIC), and the volume of distribution (VT), cohort” including 49 treatment-naive patients, for which the
the overall net influx rate constant (Ki), the influx constant (K1), primary NET location was foregut (7/49), midgut (11/49),
and the Standardized Uptake Values (SUV) were estimated. pancreatic (22/49) and bronchial (9/49). For the “algorithm
Differences were assessed by Generalized Estimated Equations cohort”, all datasets were reconstructed using three different
(GEE). Linear regression analysis and Bland-Altman plots were algorithms: 3D-RAMLA (standard), iterative and filtered
used to measure agreement between the parameters. Results: backprojection. In both the cohorts, contouring was performed
According to AIC, a reversible 2-tissue compartment model (2- on a total of 116 lesions with two different contouring methods:
TCM) is the model of choice for a 91-min scan. For 30- and 60- manual contours using the software LIFEx (v. 4.81, www.
min PET scans, the preferred model was an irreversible 2-TCM. lifexsoft.org) by two operators and semi-automatic edge-based
For 10- and 20-min scans, a 1-TCM resulted in lowest AIC. After method using a MATLAB (MathWorks) homemade code. For
the treatment, the VT increases 31% (p<0.001) and the K1 36% each region of interest (ROIs), SUVmax fixed thresholds (20, 30
(p<0.001) using 91-min scan. The analysis did not find significant and 40%) were applied and three different intensity rescale
differences among the K1 values at different acquisition times, factors were employed (0-60, 0-80, min-max of the SUV of
and their correlations were very good (e.g. K1 at 20-min =0.17 vs. the ROI). 45 RFs (25 texture, 6 histogram, 4 shape indices and
91-min =0.18, p<0.01, R2=0.984). However, the results showed 10 conventional PET features) were extracted using LIFEx. The
a poor agreement between K1 and VT (e.g. 91-min R2=0.116 at impact of the different parameters on RFs was assessed by Intra-
baseline and R2<0.01 after-treatment) and between K1 and Ki class Correlation Coefficients (ICC) using statistical R software
(e.g. 60-min R2=0.613 at baseline and R2=0.114 after-treatment), (www.r-project.org). A RF was considered robust if ICC was > 0.8.
and K1 and SUV (e.g. 91-min R2=0.04 at baseline and R2=0.56 Results: According to the different reconstruction algorithms,
after-treatment). Conclusion: Our results support the use of all 45 RFs were considered robust (ICC > 0.9). According to the
K1 as the parameter of choice to measure P-gp function with different segmentation methods, a moderate inter-observer
[18F]MC225. Although, alterations in the blood flow should variability was observed for manual methods and 80% of 45 RFs
be considered carefully during the study design to minimize appeared to be robust. The comparison of manual and semi-
confounders during K1 estimation. Moreover, a 0-20 min scan automatic contouring methods highlighted robustness for only
seems to be sufficiently reliable to estimate P-gp function using 38% of RFs. Furthermore, ROI-thresholds and intensity rescale
a 1-TCM fit. References: None. factors affected the repeatability of RFs. Only GLZLM-GLNU
S253 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

RF was stable according to all different parameters analyzed, (C-index: 0.55-0.59). For MFS prediction, PET (C-index: 0.69±0.09),
while the GLRLM RFs group and entropy histogram resulted WF0.8 (C-index: 0.69±0.09) and sumMat (C-index: 0.67±0.10)
to be robust according to all different analyzed parameters, showed higher performance than other 8 strategies (C-index:
except for intensity rescale factors. Conclusion: This study 0.62-0.65). For OS prediction, WF0.8 showed highest C-index
allowed to evaluate the impact of methodological aspects on of 0.64±0.02 compared with other 10 strategies (C-index: 0.58-
the assessment of RFs robustness at 68Ga-DOTATOC PET/CT. 0.63). Conclusion: Models constructed by image-level fusion
To investigate different biological behaviours of NET with a outperformed matrix- and feature-level fusion, as well as use
radiomic approach, contouring methods and intensity rescale of single modality, indicating that integrating information at
factors should be carefully evaluated in order to use repeatable earlier stages (i.e. merging metabolic information from PET and
RFs. References: None. anatomic information from CT voxel by voxel) can capture more
useful characteristics. References: 1.Wong, A.J., et al., Radiomics
in head and neck cancer: from exploration to application. Transl
OP-664 Cancer Res, 2016. 5(4): p. 371-382. 2.Lv, W., et al., Radiomics
Multi-level multi-modality fusion radiomics: application to Analysis of PET and CT Components of PET/CT Imaging
PET and CT imaging for improved prognostication of head Integrated with Clinical Parameters: Application to Prognosis
and neck cancer for Nasopharyngeal Carcinoma. Mol Imaging Biol, 2019, doi:
W. Lv1,2, S. Ashrafinia3,4, J. Ma1, L. Lu1, A. Rahmim2,4,5; 10.1007/s11307-018-01304-3.
1
School of Biomedical Engineering, Southern Medical University,
Guangzhou, CHINA, 2Department of Integrative Oncology, BC
Cancer Research Centre, Vancouver, BC, CANADA, 3Department OP-665
of Electrical & Computer Engineering, Johns Hopkins University, Comparison of machine learning-driven lesion classifiers
Baltimore, MD, UNITED STATES OF AMERICA, 4Department of in PET/MR images of prostate cancer patients
Radiology, Johns Hopkins University, Baltimore, MD, UNITED L. Papp1, C. P. Spielvogel2, M. Grahovac3, T. Beyer1, M. Hacker3;
STATES OF AMERICA, 5Departments of Radiology and Physics, 1
QIMP team, Center for Medical Physics and Biomedical
University of British Columbia, Vancouver, MD, CANADA. Engineering, Medical University of Vienna, Vienna, AUSTRIA,
2
Christian Doppler Laboratory for Applied Metabolomics, Medical
University of Vienna, Vienna, AUSTRIA, 3Division of Nuclear
Aim/Introduction: Intra-tumor heterogeneity plays a key role Medicine, Medical University of Vienna, Vienna, AUSTRIA.
in tumor development and responses to therapy. Radiomics
analysis, incorporating measurement of heterogeneity, has
been extensively investigated on individual imaging modalities. Aim/Introduction: Positron Emission Tomography (PET) plays
By contrast, multi-modality radiomics analysis has been much an important role in tumour characterization. Lately, the use
less commonly performed, and if applied, is usually performed of radiomics analysis of PET images has shown potential to
by concatenation of features from different modalities. However, positively impact diagnostic work-up of oncology patients.
such an approach may not be able to effectively integrate the However, various radiomics features were reported to be
supplementary information provided by different modalities. sensitive to multi-centric imaging protocol variations. Here, we
Thus, the purpose of this study was to investigate a multi-level compared different Gleason pattern classifiers in prostate PET/
fusion strategy to combine the information provided by PET and MRI studies built on four multi-centric coefficient of variation
CT at the image-, matrix- and feature-levels towards improved (CoV) radiomic feature groups [1]. Materials and Methods: 74
prognosis of multi-center head & neck cancer. Materials and prostate patients were included in this study having a multi-
Methods: 296 patients scanned with FDG-PET/CT imaging parametric prostate PET/MRI including 8 series: 18F-FMC and
from 4 centers were collected from The Cancer Imaging 18
F-FMC+68Ga-PSMAHBED-CC (dual-tracer) PET, furthermore, T2,
Archive (TCIA). Three outcomes recurrence-free survival (RFS), ADC, iAUC, KEP, Ktrans and Ve MRI. Based on Gleason-annotated,
metastasis-free survival (MFS) and overall survival (OS) were full-mount histopathological slices, 120 lesions were delineated
considered. 127 radiomics features were extracted from (1) PET from each study (Hermes Nuclear Diagnostics, Sweden). Overall
images alone; (2-7) PET and CT images fused via wavelet-based 589 radiomics features were extracted from the 8 series of each
fusion (WF) with CT-weights of 0.2, 0.4, 0.6 and 0.8, gradient of the 120 lesions based on optimized radiomics [1]. Features
transfer fusion (GTF), and guided filtering-based fusion (GFF); were categorized as CoV<5%, CoV<10%, CoV<20% and all-CoV
(8) fused matrices (sumMat), constructed by considering the according to [1]. For each of the four CoV categories, a low risk
voxel relationships in PET and CT simultaneously; (9-10) fused (<=Gleason 3) vs. high risk (>=Gleason 4) machine learning
features constructed via feature averaging (avgFea), and feature predictor was established [2]. 1000-fold Monte Carlo cross-
concatenation (conFea); and finally, (11) use of CT images alone. validation with 20% held-out sets was performed to estimate
Top 10 features with higher concordance index (C-index) in the sensitivity (SENS), specificity (SPEC), accuracy (ACC), positive-
univariate Cox analysis were selected, and multivariate model predictive-value (PPV) and negative-predictive-value (NPV) of
was constructed by Akaike information criteria (AIC). Results: the four predictive models. Results: The accuracy of the low-
For RFS prediction, PET (C-index: 0.62±0.08) and WF0.6 (C-index: high risk predictive models over four CoV feature categories
0.61±0.05) showed higher performance than other 9 strategies were 75% (CoV<5%), 76% (CoV<10%), 78% (CoV<20%) and 77%
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S254

(all-CoV). The performance values of the CoV<5% low-high risk BM-ComBat) slightly but consistently improved the predictive
model were SENS 72%, SPEC 77%, PPV 76% and NPV 73%. The ability of the developed models. In MR with LASSO, B-ComBat
same values for the all-CoV model were SENS 74%, SPEC 80%, outperformed ComBat (AUC 0.92 vs. AUC 0.91 and BAC 84%
PPV 78% and NPV 75%, respectively. Conclusion: The accuracy vs. 82%) and BM-ComBat also outperformed M-ComBat (AUC
of a low-high risk prediction model for prostate cancer PET/MRI 0.92 vs. AUC 0.91 and BAC 84% vs. 82%). With RF, B-ComBat
varied minimally between 75% and 78%, thus, pointing to the outperformed ComBat (AUC 0.93 vs. AUC 0.90 and BAC 85%
ability to effectively reduce the number of features to the most vs. 83%) and BM-ComBat also outperformed M-ComBat (AUC
repeatable ones (CoV<5%). This helps simplifying the complexity 0.93 vs. AUC 0.90 and BAC 91% vs. 83%). Also in SVM, B-ComBat
of relevant prediction models. References: Papp L., et al: outperformed ComBat (AUC 0.93 vs. AUC 0.92 and BAC 84% vs.
Optimized feature extraction for radiomics analysis of 18F-FDG- 83%) and BM-ComBat also outperformed M-ComBat (AUC 0.93
PET imaging. JNM 2018, 10.2967/jnumed.118.217612 Papp L., et vs. AUC 0.92 and BAC 85% vs. 84%). Conclusion: The hybrid
al: Glioma Survival Prediction with Combined Analysis of In Vivo bootstrapped ComBat(B-ComBat and BM-ComBat) versions
11
C-MET PET Features, Ex Vivo Features, and Patient Features by are modifications to an acknowledged method that seem to
Supervised Machine Learning. JNM, 2018(59):892-899. provide slight improvement with the performance of predictive
radiomics models in a multicentric context, whatever machine
learning technique is used. References: None.
OP-666
Harmonization strategies based on ComBat for
mutlicentric radiomics studies OP-667
R. Da-ano1, F. Lucia2, M. Vallières1, P. Bonaffini3, I. Masson4, A. A Concept to Simulate Heterogeneities in a Combined
Mervoyer4, C. Reinhold3, U. Schick1,2, D. Visvikis1, M. Hatt1; PET/CT Phantom for Standardised Radiomic Features
1
LaTIM, INSERM, UMR 1101, Univ Brest, Brest, FRANCE, 2Radiation Analysis
Oncology department, University Hospital, Brest, FRANCE, A. Valladares, T. Beyer, L. Papp, E. Salomon, I. Rausch;
3
Department of Radiology, McGill University Health Centre Medical University of Vienna, Vienna, AUSTRIA.
(MUHC), Montreal, QC, CANADA, 4Department of Radiation
Oncology, Institut de Cancérologie de l’Ouest, Nantes, FRANCE.
Aim/Introduction: Recently, textural features in medical
images have been proposed as potential biomarkers for in-
Aim/Introduction: Multicentric studies are needed to vivo disease characterization. However, standardized imaging
demonstrate the clinical potential value of radiomics as procedures and pre-processing protocols are mandated to
a prognostic tool. However, variability in scanner models, ensure repeatability. Here, we propose a simple concept
acquisition protocols and reconstruction settings are for simulating heterogeneity in a PET and CT phantom for
unavoidable and radiomic features are notoriously sensitive assessing the variability of textural features. Materials and
to these factors. A statistical harmonization method called Methods: Three conical tubes (d=31mm, h=110mm) were
ComBat was developed to deal with the “batch effect” in gene partly filled with different sizes of acrylic spheres (tube 1:
expression microarray data and was used in radiomics studies 1.6mm; tube 2: 50%(1,6mm)/50%(6,3mm) and tube3: 6.3 mm
to deal with the “center-effect”. A modified version called diameter) resulting in a homogeneous (spheres free)- and a
M-ComBat was later introduced. Our goal was to develop and heterogeneous area separated from each other with a plastic
evaluate hybrid techniques based on ComBat, intended to grid. The tubes were filled with an aqueous solution containing
improve the predictive ability of the models developed on data [18F]-FDG (20 kBq/mL). Two identical arrangements (test/retest)
from a “reference” center and validated on others. Materials and of these three tubes were centered in the field-of-view of a
Methods: The hybrid ComBat methods were developed by Siemens Biograph TPTV PET/CT system and scanned using a
adding bootstrap from the obtained initial batch-wise estimates standard oncological protocol. From the resulting CT and PET
and used Monte Carlo method to obtain the final batch-wise images, SUVs and HUs as well as six selected textural features,
estimates, denoting them B-ComBat and BM-ComBat. 92 IBSI- reported as robust features in a PET/CT multi-centre study [1],
compliant radiomic features extracted from FDG-PET and MRI were calculated from volumes-of-interests (2.2 mL) placed in
sequences (T1, T1c, T2 and ADC maps) of 197 cervical cancer the homogeneous and heterogeneous regions of each tube by
patients treated with radiochemotherapy in 3 centers (Brest, n = using the software LIFEx [2]. Changes in extracted parameters
119, Nantes, n = 50 and Montreal, n = 28) were exploited. After between the homogeneous and the heterogeneous areas were
splitting untransformed or harmonized features (harmonized calculated as percentage-differences. Results: Average SUV and
using 4 ComBat versions) 70/30 in training and testing sets, HU for the homogeneous regions were 4.5±0.1 and 11.1±3.8
models to predict recurrence were built using 3 approaches: i) respectively. SUV and HU changed by tube 1 (test/retest): -62%/-
multivariate regression (MR) with 10-fold cross validation after 63% and 652%/688%; tube 2: -65%/-66% and 668%/672% and
feature selection based on LASSO, ii) Random Forest (RF) and iii) tube 3: -61%/-61% and 609%/624%, respectively. The changes in
Support Vector Machine (SVM). They were compared using Area evaluated features from the heterogeneous regions with respect
Under the Curve (AUC) and balanced accuracy (BAC). Results: to the ones extracted from the homogeneous areas were highly
Noticeably, our proposed bootstrap modification (B-ComBat and variable for both, the PET and CT images. For example, PET
S255 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

images presented changes of 24% to 55% for correlation, 24% 90%-96% for FBW discretization). For the scans acquired on the
to 55% for entropy and 16 to 171% for coarseness. Conclusion: same system, the percentage decreased, but the majority of
With using different acrylic spheres as filling material in a features still resulted in a high ICC (FBN: 52%-63%, FBW: 75%-
radioactive aqueous solution, it was possible to alter radiomics 85%). The percentage of features yielding a high ICC decreased
feature values extracted from PET and CT images. Therefore, more in the multicenter setting. In this case, the percentage of
this concept seems promising for building a reproducible an features yielding a high ICC was larger for images reconstructed
easy to handle heterogeneity phantom. (This work has received with (harmonizing) EARL-compliant reconstructions: e.g. 40%
funding from the European Union’s Horizon 2020 research and for EARL1, 60% for EARL2 vs. 21% for the clinically-preferred
innovation programme under the Marie Skłodowska-Curie setting for FBW discretization. When discretized with FBW and
grant agreement No. 764458). References: [1] L Papp et al. J resampled to isotropic voxels, this benefit was more pronounced.
Nucl Med 2018. DOI:10.2967/jnumed.118.217612. [2] C Nioche, Conclusion: EARL-compliant reconstructions harmonize a wide
et al. Cancer Research 2018; 78(16):4786-4789. www.lifexsoft. range of radiomic features. FBW discretization and a sampling
org. to isotropic voxels, pronounces the benefits of EARL-compliant
reconstructions. References: None.

OP-668
Experimental Multicenter And Multivendor Evaluation OP-669
Of Pet Radiomic Features Performance Using 3d Printed Adding the Temporal Domain to PET Radiomic Features
Phantom Inserts W. A. Noortman1,2, D. Vriens1, C. H. Slump2, J. Bussink3, T. W. H.
E. Pfaehler1, J. van Sluis1, B. B. J. Merema1, P. Van Ooijen1, R. C. M. Meijer3, L. F. de Geus-Oei1,2, F. H. P. van Velden1;
Berendsen2, F. H. P. Van Velden3, R. Boellaard4; 1
Leiden University Medical Center, Leiden, NETHERLANDS,
1
University Medical Center Groningen, Groningen, 2
University of Twente, Enschede, NETHERLANDS, 3Radboud
NETHERLANDS, 2Zuyderland Medical Center, Heerlen, University Medical Center, Nijmegen, NETHERLANDS.
NETHERLANDS, 3Leiden University Center, Leiden, NETHERLANDS,
4
VU Medical Center, Amsterdam, NETHERLANDS.
Aim/Introduction: Currently, in PET imaging, textural
radiomic features are derived from static images and express
Aim/Introduction: The sensitivity of radiomic features to heterogeneity in the spatial distribution of radiotracer uptake.
several confounding factors, such as image reconstruction However, changes in uptake over time might contain additional
settings, makes clinical use challenging. To use radiomic information concerning tumour biology. This study introduces
features in a clinical setting, they have to be comparable across novel texture features that are derived from the temporal
institutions and scanner types. In order to investigate the domain using dynamic images, aiming to assess the amount
impact of harmonized image reconstruction settings on feature of information of these dynamic texture features and features
consistency, a multicenter phantom study was performed derived from parametric images compared to conventional
using 3D printed phantom inserts reflecting realistic tumor features derived from static images. Materials and Methods:
shapes and heterogeneity uptake. Materials and Methods: Thirty-five patients with non-small cell lung carcinoma
Tumours extracted from real PET/CT scans of patients with underwent dynamic 18F-FDG-PET/CT scans. The time frame of 50-
non-small cell lung cancer served as model for three 3D 60 min p.i. was used as static scan. Parametric glucose metabolic
printed phantom inserts. Different heterogeneity patterns rate images were created using Patlak analysis (15-60 min). The
were realized by printing separate compartments that can be dynamic images consisted of 16 frames of 150 s acquired 10-
filled with different activity solutions. The inserts were placed 50 min p.i.. Volume of interest (VOI) delineation of lesions was
in the NEMA image quality phantom and scanned repeatedly. performed on static and parametric images; static VOIs were
Firstly, a list-mode scan was acquired and five statistical equal used for dynamic series. 90 intensity, shape and texture features
replicates were reconstructed. Secondly, the phantom was were extracted from static and parametric images, using
scanned four times on the same scanner. Thirdly, the phantom PyRadiomics 2.0. Following the approach of Hu et al. (IEEE ISBI
was scanned on six different PET/CT systems. All images were 2006) in proteomics, 22 dynamic grey level cooccurrence matrix
reconstructed using EARL-compliant and the locally clinically- (GLCM) and 16 dynamic grey level run length matrix (GLRLM)
preferred reconstructions. The EARL-compliant reconstructions features were extracted from the dynamic frames. Static and
were performed without (EARL1) or with (EARL2) point-spread parametric texture features were calculated bidirectionally for
function (PSF). Images were analyzed with and without 13 angles; dynamic features only included the unidirectional
resampling to 2 mm cubic voxels. Images were discretized with temporal domain. Following the approach of Yip et al. (Phys Med
a fixed bin width (FBW) of 0.25 and a fixed bin number (FBN) Biol. 2016), population-based fixed bin widths were dependent
of 64 bins. The intraclass correlation coefficient (ICC) of each on the range of voxel values and number of voxels within the
scan setup was calculated and compared across reconstruction VOI. Comparison of parametric and dynamic features with
settings. An ICC above 0.75 was regarded as good correlation. static features was performed with Spearman rank correlation,
Results: The percentage of features yielding a good ICC was ρ>0.7 is considered to be high. Results: Five dynamic GLCM
the largest for the statistical equal replicates (70%- 91% for FBN, features showed a negligible to moderate correlation with any
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S256

static feature, indicating potential additional information to features with respect to dose-map generation parameters
existing features. All other dynamic features, including GLRLM, was assessed using the intra-class correlation coefficient (ICC).
showed a high correlation with at least one static feature. Three Results: Varying dose calculation methods, among all the
out of 90 parametric features did not show a high correlation segmentation and discretization methods, the mean values
with corresponding static features, but showed a moderate of ICCs were >0.8 for 31/43 features; while, large variations
correlation (ρ>0.61). Conclusion: This study suggests that, were found in 1/13 GLRLM and 6/13 GLSZM features. When
for NSCLC, certain dynamic GLCM radiomic features show varying segmentations, features highly depended on the dose
additional information compared to static features. In extension calculation methods. For M1-M3, only 5/43 features showed
to Tixier et al. (J Nucl Med 2016), equivalent features indicated ICCs>0.8, but 24/43 features showed ICCs>0.8 for M4-M7. Poor
no additional information in radiomics derived from parametric ICCs were observed in all histogram, 5/9 GLCM, 4/13 GLRLM and
images; other features only gave a minimal suggestion of 5/13 GLSZM features. Varying bin sizes of discretization, besides
additional information. Future studies should assess whether 2/3 histogram, 2/9 GLCM and 1/5 NGTDM non-robust features,
there is a clinical benefit of dynamic radiomics over static ICCs for other features were >0.8 for any given segmentation
radiomics. References: None. and dose calculation methods. Conclusion: Radiomics features
in dose-maps from RLT were investigated. Their robustness
to segmentation highly depended on dose-map calculation
OP-670 methods. Features obtained from dose-maps based on organ-
Dose distribution radiomics: a new paradigm for based TACs showed high and consistent reproducibility for
assessment of radioligand therapy most radiomics features. This analysis can serve for selection of
X. Hou1, W. Lv2, J. Buregaurd3,4, A. Celler1, A. Rahmim5,1; reproducible dose-map radiomics features towards improved
1
Radiology Department, University of British Columbia, Vancouver, assessment of RLT and prediction of outcome in future efforts.
BC, CANADA, 2Department of Biomedical Engineering, Southern References: None.
Medical University, Guang Zhou, CHINA, 3Department of Medical
Imaging and Oncology Division of Research Center, CHU de 1507
Québec – Université Laval, Quebec, QC, CANADA, 4Department
of Radiology and Nuclear Medicine and Cancer Research Center,
Teaching Session 6 - Interactive Clinical Cases -
Quebec, QC, CANADA, 5Department of Integrative Oncology,
Radiological Aspects of Abdominal Anatomy
BC Cancer Research Centre, Vancouver, BC, CANADA.
Tuesday, October 15, 2019, 16:30 - 18:00 Lecture Hall 113

Aim/Introduction: Personalized dosimetry in radioligand-


therapy (RLT) is increasingly recognized as an important
procedure for ensuring patient safety and improving treatment OP-671
efficacy. Furthermore, radiomics has gained increasing Radiological Aspects of Abdominal Anatomy
acceptance as a powerful tool for assessment of radiological T. Lynch;
images. Here we propose a paradigm of dose-distribution Belfast, UNITED KINGDOM.
radiomics towards improved assessment of RLT. It is known
that radiomics features can be affected by image generation
and processing methods. In this work, we applied radiomics OP-672
to voxelized dose maps from RLT and investigate features’ Radiological Aspects of Abdominal Anatomy
robustness when varying segmentation, discretization and N. Magee;
dose calculation methods. Materials and Methods: Ten patient Belfast City Hospital, Belfast, UNITED KINGDOM.
kidney datasets (the main organ-at-risk) from 177Lu-DOTA-TATE
therapy were analyzed. Three SPECT/CT scans, acquired at
around 4h(D0), 23h(D1) and 70h(D3) after injection, were used OP-673
for dose estimations. Four fixed-thresholds (20%-50%) were Radiological Aspects of Abdominal Anatomy
employed in kidney segmentations. Voxelized dose-maps were K. McManus;
obtained using seven methods: (M1) from unfiltered images, Belfast, UNITED KINGDOM.
and images processed with 3x3x3(M2) and 5x5x5(M3) box-
filters with time-activity-curves (TACs) determined for each
voxel; and (M4-M7) based on activity distributions from images
on D0, D1, D3 and the mean of all images to scale the TACs
obtained from the entire organs to individual voxels. In total, 280
dose-maps were used in radiomics analysis. Five discretization
(bin=16/32/64/128/256) with 43 radiomics features (from
histogram and GLCM, GLRLM, GLSZM, NGTDM matrices) were
applied to each dose-map. Reproducibility of the radiomics
S257 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

1508 prognostic factors for OS for patients receiving TAREalone was


alpha fetoprotein (AFP) levels (<400 vs ≥400; HR = 0.345 (95%CI
Clinical Oncology - Parallel Session: Liver
0.12-0.97), p=0.04) and for patient receiving TARE+sorafenib
Selective Therapy - 90Y and Beyond
was tumor involvement (tumor≤50% vs tumor>50%; HR =
0.52 (95%CI 0.29-0.93), p=0.03). Conclusion: OS of individual
Tuesday, October 15, 2019, 16:30 - 18:00 Lecture Hall 114 HCC patients undergoing TARE strongly related to AFP,
disease burden, and ADF. Intolerance of patients to sorafenib
substantially decreased median OS by 9.6 months for patients
OP-674 with tumor≤50% and ADF and by 4.1 months for patients with
Survival outcomes for transarterial Y-90 radioembolization tumor>50%. References: None.
with glass microspheres in hepatocellular carcinoma
patients: a single-institution experience
S. C. Kappadath, A. Mahvash, J. Long, M. Abdelsalam, R. Avritscher, OP-675
B. Chasen, A. Kaseb, J. Kuban, R. Murthy, B. Odisio, A. Teyateeti, H. Effect of transarterial Re188 lipiodol therapy on survival
Macapinlac, A. Teyateeti; outcome in hepatocellular carcinoma with portal vein
UT MD Anderson Cancer Center, Houston, thrombosis
TX, UNITED STATES OF AMERICA. S. Datta Gupta, S. Shamim, S. Gamanagatti, Shalimar, P. Gupta, M.
A. Khan, M. B. Mallia, V. Chirayil, A. K. Dash, C. S. Bal;
All India Institute of Medical Sciences, New Delhi, INDIA.
Aim/Introduction: Y90 transarterial-radioembolization
(90Y-TARE) with glass-microspheres has shown efficacy in
patients with unresectable hepatocellular carcinoma (HCC). The Aim/Introduction: Hepatocellular carcinoma (HCC) is the sixth
aim of this study is to investigate prognostic factors and stratify most common malignancy globally with a rising trend owing to
the overall survival (OS) for unresectable HCC patients in our increase in non-alcoholic liver cirrhosis. At presentation nearly
institution who underwent 90Y-TARE. Materials and Methods: 40% of patients are inoperable with existing portal vein tumor
A retrospective study on HCC patients that underwent thrombosis. Recommended treatment in this group of patients
90Y-TARE at our institution from November 2010 to November is tyrosine kinase inhibitors (TKIs), which improve overall
2018 (n=181). According to institutional algorithm, 90Y-TARE survival from 3-4 months to 6-9 months. However, tolerability
(TAREalone) is an option for patients with tumor involvement and compliance to TKIs is poor. Our objective was to assess the
≤50% of liver (tumor≤50%). 90Y-TARE with sorafenib efficacy and survival outcome of Re188 lipiodol trans arterial
(TARE+sorafenib) was reserved for tumor involvement >50% of radionuclide therapy in HCC with PVT. Materials and Methods:
liver (tumor>50%) and/or more advanced/aggressive disease Patients of HCC with PVT with baseline radiological diagnosis
features (ADF, defined as infiltrative/ill-defined HCC, presence on MRI with Eastern Co-operative Oncology Group (ECOG)
of macrovascular invasion, portal vein tumor thrombus (PVT), performance status ≤2 and Child Pugh score A or B were recruited
or extrahepatic disease (EHD)). Patients having contraindication from Liver Cancer Clinic. Baseline serum alpha-fetoprotein (AFP)
to sorafenib would receive 90Y-TARE alone (TAREpalliative) or was obtained for biochemical follow-up. Lipiodol was labeled
other treatments (TARE+other). OS was defined as time from with Re-188 using either HDD or N-DEDC kits and empirical
date of first 90Y-TARE to death from any cause or last follow- dose of Re188-lipiodol was estimated. Patients underwent an
up. Survival function was estimated by Kaplan-Meier analysis. initial scout scan (~185MBq Re188 lipiodol) to look for dose
Multivariate Cox proportional-hazards was used to identify distribution in lungs and normal liver parenchyma, prior to
prognostic factors. Results: Median (range) of patient age was injection of therapeutic dose. Thereafter, therapeutic dose
65 (15-85) with 136 (75%) males. Majority of patients were BCLC was injected trans-arterially as close to tumor feeding vessel
stage B (25%) or stage C (71%), multifocal HCC (84.5%), bi-lobar as possible. Planar and SPECT imaging was done at 12, 24 and
involvement (64%), and tumor≤50% (65%). EHD and PVT were 48hrs. Radiological response on MRI (mRECIST) and biochemical
present in 20% and 24% of patients. The median follow-up time response with serum AFP was assessed every three months and
was 49.4 months (range 2.4-96.4). Median OS for the patient survival was assessed at the end of 6 months from last therapy.
cohort was 13.4 months (95%CI 9.7-17.2) with no significant Results: Fifteen therapies were given in fourteen patients (12
difference when stratified by treatment strategy: TAREalone vs male, 2 female) with median age of 62 years (range: 41-70 years).
TARE+sorafenib vs TARE+other vs TAREpalliative. OS stratified In eight out of fifteen therapies Re188-HDD lipiodol was injected
by disease burden and treatment strategy were: 1) tumor≤50% and in seven therapies Re188-N-DEDC lipiodol was injected,
without ADF treated with TAREalone (n=58) 21.6 months (95%CI with overall mean injected dose of 2.6GBq±0.4. Radiological
5.9-37.3); 2) tumor≤50% with ADF treated with TAREalone (n=17) response was assessed in 13 patients and biochemical in
8.8 months (95%CI 5.9-11.7) or with TARE+sorafenib (n=36) 18.4 10. Radiological complete response was noted in 3 patients,
months (95%CI 3.6-33.2), p=0.04; 3) tumor>50% irrespective of objective response rate was 31% and disease control rate was
ADF treated with TAREalone (n=12) 6.2 months (95%CI 2.6-9.8) 85%. Biochemical response (fall of s. AFP≥50%) was noted in
or with TARE+sorafenib (n=42) 10.3 months (95%CI 5.8-14.8), 6 patients. Median follow-up period was of 7 months. Survival
p=0.22. On multivariate analysis, the significant independent assessed at 3 and 6 months was 93% and 80% respectively.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S258

Conclusion: In patients of HCC with PVT, Re188 lipiodol therapy an optimized resin Y90-μs treatment with a better tumor control
appears to be effective in disease control as well as prolonging and lower toxicity. References: None.
survival, comparable to TKIs. Further studies at a larger scale may
be appropriate to determine its efficacy in comparison to TKIs
and establish its role as an alternative treatment option in these OP-677
patients. References: None. Survival Analysis of Advanced HCC Treated with
Yttrium-90 Radioembolization: A 10-year single-center
experience
OP-676 S. Bilgiç, M. S. Sağer, B. Akovali, O. E. Şahin, E. Kaymak, R. L. Uslu
Impact of personalized treatment in HCC patients treated Beşli, S. Asa, L. Kabasakal, H. B. Sayman, K. Sönmezoğlu;
with resin 90Y-microspheres: preliminary results of a Istanbul University-Cerrahpasa, Istanbul, TURKEY.
randomized clinical trial
L. Strigari1,2, S. Ungania1, S. Rea1, A. Annovazzi1, G. Pizzi1, G. Vallati1,
G. Iaccarino1, S. De Niccolo’1, R. Sciuto1; Aim/Introduction: Yttrium-90 treatment is widely used in
1
Regina Elena Institute IFO, Rome, ITALY, 2St. Orsola patients with hepatocellular cancer. Patients who had no
Malpighi University Hopital, Bologna, ITALY. chance of surgery and were not eligible for transarterial
chemoembolization were included in our study. This study was
planned to determine the effectiveness of the treatment and to
Aim/Introduction: The aim of the study is to demonstrate evaluate the overall survival. Materials and Methods: A total
a survival benefit in HCC patients treated with resin of 127 patients with HCC who presented to our department
90Y-microspheres (μs) when a dosimetry-based patient-specific between January 2009 and December 2018 were reviewed.
activity is administered compared to a standard treatment 50 of these patients with appropriate hepatic arterial perfusion
with BSA method in a randomised clinical study. Materials findings were treated. This study presents data of a retrospective
and Methods: A prospective double- blinded RCT on 140 cohort. Overall survival was estimated using Kaplan-Meier
HCC patients is now ongoing comparing patients receiving method Results: The average age was 66.67 years (46 - 83
the resin Y90-microspheres activity based on BSA methods years). The median time of overall survival was 11.18 months (1-
(Arm 1: 70 pts) or personalized dosimetry (Arm 2: 70 pts). 77). Two- and five- year survivals are 20% and 6%, respectively.
Patients are also stratified by BLCB stage. CT and PET imaging In stage of BCLC B, median survival period calculated as 16.08
are acquired before and after therapy. For each enrolled HCC ±4.63 months. The median survival period BCLC C stage, on the
patient both previsional dosimetry, performed using 99mTc- other hand, calculated as 9.31 ±3.06 months (p=0.32). When
MAA, will be calculated using SPECT-CT imaging and MIM the distribution was analyzed, survival was observed as 18.04
tool, as well as the post-SIRT dosimetry will be determined. (± 5.55) months in the unilobar group and 8.84 (± 2.98) months
Patient blood samples will be also collected before, 30 days in the group with bilobar distribution (p = 0.02). Survival rate
and 3 months after SIRT treatment. AFP and PIVKA-II will be was found to be 15.21 (± 4.05) months in the extrahepatic
determined at baseline and post-SIRT at different time points. metastasis group and it was 23.92 (± 4.99) months in the non
Based on dose response models developed by IRE-IFO group, metastatic group. Conclusion: In the literature, treatment-free
the association between patient outcome (overall survival, time survival in BCLC B and C group HCC patients was reported as 9.5
to progression, local tumor control and toxicity) and accurate and 3.4 months, respectively (1). The mean survival of 16.08 and
dosimetry and biomarkers will be investigated. Results: Until 9.31 months in the patients whom we provide treatment shows
now 14 unresectable HCC patients (age range 51-84 yrs) with the benefit of the treatment.Median overall survival in studies
a minimum follow-up of three months were enrolled in the on Y-90 SIRT treatment varies significantly from other sources (7-
study: six patients in Arm 1 and eight patients in Arm 2. Nine pts 27 months) (2, 3). This problem is based on clinical experiences,
were in BCLC stage B and five pts in BCLC stage C. Administered patient selection and the variety in practice. References:
Y90 activity ranged from 1.2 GBq to 2.7 GBq (mean value 1.52 1.Khalaf, N., et al., Natural History of Untreated Hepatocellular
GBq). Mean activity calculated by BSA resulted 1.71 +/- 0.26 SD; Carcinoma in a US Cohort and the Role of Cancer Surveillance.
mean activity calculated by 3D dosimetry resulted 1.3 +/- 0.37 Clin Gastroenterol Hepatol, 2017. 15(2): p. 273-281.e1.2.Salem, R.,
SD. The administered activity was statistically different between et al., Institutional decision to adopt Y90 as primary treatment for
the two methods (p<0.05) with a trend of lower activity by hepatocellular carcinoma informed by a 1,000-patient 15-year
using the 3D dosimetric approach. Post- treatment dosimetry experience. Hepatology, 2018. 68(4): p. 1429-1440.3.Vilgrain,
evidenced that administered activity in Arm 2 provided at V., et al., Efficacy and safety of selective internal radiotherapy
least therapeutic dose to lesion (>120Gy) while sparing normal with yttrium-90 resin microspheres compared with sorafenib
liver (<40Gy in all patients). At clinical follow-up only 1/8 pts of in locally advanced and inoperable hepatocellular carcinoma
Arm 2 presented transient liver toxicity while 2/6 pts of Arm (SARAH): an open-label randomised controlled phase 3 trial.
1 presented a significant and persistent liver flure. Objective Lancet Oncol, 2017. 18(12): p. 1624-1636.
response was observed in 3/6 pts of Arm 1 and in 9/9 pts of Arm
2. Conclusion: The selection of administered activity based on
an accurate previsional patient specific dosimetry may result in
S259 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

OP-678 Center, Houston, TX, UNITED STATES OF AMERICA, 4Emory Rollins


Clinical Follow-up after Imaging and Dosimetry for School of Public Health, Atlanta, GA, UNITED STATES OF AMERICA.
Yttrium-90 (90Y) Liver Radioembolization Using a SiPM-
based PET/CT Scanner
H. Duan, M. H. Khalaf, L. Baratto, S. Srinivas, D. Sze, A. Iagaru; Aim/Introduction: To determine the utility of low-dose
Stanford University, Stanford, CA, UNITED STATES OF AMERICA. yttrium-90 (Y-90) for liver radioembolization (RE) treatment
planning using SPECT/CT and PET/CT. Specifically, 1) to
calculate lung shunt fraction (LSF) and 2) to determine tumor
Aim/Introduction: To evaluate the response rate and survival to normal liver activity ratio (TNR). Materials and Methods: A
of patients treated with Yttrium-90 (90Y) radioembolization torso anthropomorphic phantom with lung and liver chambers
following personalized dosimetry and high-quality imaging was filled initially with 148 MBq and 510 MBq liquid Y-90
using SiPM-based PET/CT. Materials and Methods: Thirty solution in the lungs and liver respectively for LSF of 22.4%. Liver
patients (19 males, 11 females; 47 - 88 years old) with advanced activity included 2 fillable spheres simulating hypervascular
hepatic malignancies were prospectively enrolled. According to tumors with initial TNR of 13.9. After imaging with SPECT/CT
their tumor, they were treated with resin or glass microspheres. and PET/CT, more activity was added to the non-tumor liver,
Pre-therapy 99mTc MAA SPECT/CT and post-therapy 90Y PET/CT lowering the LSF to 14% and TNR to 7. Imaging was repeated
images were analyzed.Tumor and normal liver dose was calculated and more activity was again added to the liver, lowering the
using SurePlan (MIM) software. 90Y PET/CT scans were obtained LSF to 10% and TNR to 4.6. Liver activity ranged from 222-877
in a single bed position for 20 minutes using a SiPM-based MBq throughout the study (~10-30% of usual Y-90 therapeutic
PET/CT scanner and reconstructed as 10- and 15-min datasets. dose depending on glass vs. resin microspheres used). SPECT/
Image quality was evaluated using the 5-point Likert scale. CT imaging was obtained with medium energy collimation
Results: The mean administered activity was 2.3 GBq 90Y and dual energy windows (primary: 108 keV, 32%; secondary:
microspheres. Mean tumor dose estimated from 99mTc MAA 360 keV, 28%) for 40 minutes total imaging time. A fraction of
SPECT/CT was 99.13 Gy vs. 111.53 Gy from 90Y PET/CT. For the counts from the secondary window was subtracted from
normal liver, a mean dose of 28.41 Gy was estimated from 99mTc the primary window to compensate for septal penetration of
MAA SPECT/CT and 21.04 Gy from 90Y PET/CT. 99mTc MAA SPECT/ high energy bremsstrahlung as scatter correction. PET/CT with
CT yielded great accuracy as there was no significant divergent time-of-flight was obtained with 15 minutes/bed position over
tumor or normal liver dose between 99mTc MAA SPECT/CT 2 bed positions. Volumes of interest were placed over the lungs,
and 90Y PET/CT (p=0.667 vs. 0.134). Image quality for 90Y PET/ liver, the spheres (simulating tumors) on the corresponding CT
CT was similar at 10 min and 15 min scan time (Likert-scale images and activities were then calculated using MIM V5.6 (MIM
4.4 ± 0.6 vs. 4.6 ± 0.5). Our preliminary data show 12 (66.7%) Software Inc., Cleveland, Ohio, USA). Results: For the true LSF’s
patients had partial response, 1 (5.5 %) stable disease and 5 of 22.5%, 14%, and 10.2%, the SPECT/CT estimated the LSF’s to
(27.8%) had progressive disease at 3 months follow up. Five be 18.1%, 10.6% and 7.2%, respectively, and PET/CT estimated
patients passed away after a mean of 5 months. Median survival them to be 25.2%, 16.1% and 15.5%, respectively. Quantitative
was 11.5 months. In a sub-analysis, patients treated with resin evaluation of TNR was compromised because Y-90 came out of
microspheres vs. glass microspheres had a mean survival of 12.6 suspension and adhered to walls and the sphere mounting rods
vs. 10.3 months, respectively. Conclusion: Our preliminary data which was apparent on PET due to superior spatial resolution.
show a high response rate and median survival of 11.5 months For the true TNR’s of 13.9, 7 and 4.6, SPECT/CT estimated TNR’s
in this cohort. The administered activity may be adjusted to to be 6.2, 4.2 and 3.2, respectively and PET/CT estimated them
yield the desired 120 Gy in the tumor based on the estimated to be 9.6, 5.7 and 3.9, respectively. Conclusion: Low-dose Y-90
tumor dose from 99mTc MAA SPECT/CT. The SiPM-based PET/CT can be used as a direct surrogate marker for Y-90 RE treatment
scanner showed excellent image quality even at a reduced scan planning. The under and over estimation of LSF by SPECT and
time of 10 min, acquired with only one bed position. That may PET, respectively and the underestimation of TNR by both
allow for inclusion of 90Y PET/CT in routine clinical workflow. imaging modalities are in part likely related the artificial milieu
However, more patients have to be evaluated to confirm these of the phantom study. Further in-vivo studies are warranted.
findings. References: None. References: None.

OP-679 OP-680
Evaluation of Utility of Low Dose Yttrium-90 for HCC Radioembolization with Yttrium-90 Polymer Beads
Radioembolization Treatment Planning Using SPECT/CT (SIR-Spheres):99mTc-MAA SPECT/CT based dosimetry
and PET/CT - A phantom study correlation with survival and tumor response
N. Kokabi1, I. Sethi1, D. Mir1, D. M. Schuster1, J. S. Lee2, S. M. Rodari1, G. Tosi1, V. Pedicini1, D. Poretti1, E. Lanza1, R. Muglia2, K.
Kappadath3, B. Risk4, J. R. Galt1; Marzo1, M. Sollini2, A. Chiti2,1;
1
Emory University School of Medicine, Atlanta, GA, UNITED STATES 1
Humanitas Clinical and Research Hospital, Milan,
OF AMERICA, 2Radiology Associates of Florida, Sarasota, FL, UNITED ITALY, 2Humanitas University, Milan, ITALY.
STATES OF AMERICA, 3University of Texas MD Anderson Cancer
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S260

risk of treatment-associated morbidity. Therefore we evaluated


Aim/Introduction: Aim of this study was to evaluate correlation the role of dynamic 18F-FET PET as prognostic biomarker in
of 99mTc-MAA SPECT/CT based dosimetry with survival and oligodendroglioma. Materials and Methods: Seventy-five
tumor response in HCC patients treated with 90Y-labelled patients with newly diagnosed, untreated oligodendrogliomas
polymer (SIR-Spheres). Materials and Methods: A retrospective with IDH-mutation and 1p/19q-codeletion (WHO grade II n=58
analysis was performed on 49 consecutive patients (8 females, and III n=17) and dynamic 18F-FET PET were included. 18F-FET
41 males, mean age 69) affected by advanced HCC, treated with PET parameters (maximum/mean tumor-to-background
radioembolization (TARE). Before treatment, all patients were ratios [TBRmax, TBRmean], minimal time-to-peak [TTPmin]) were
subjected to a preliminary study with 99mTc-MAA SPECT/CT to correlated with the clinical outcome in terms of progression-
evaluate tumor and organ at risk (OAR) absorbed doses and free survival (PFS) as defined by RANO criteria using Kaplan-
to predict the number of microspheres that could pass to the Meier estimates and uni-/multivariate analyses. Results:
systemic blood circulation. Tumor absorbed dose was calculated During a median follow-up time of 67.5 months, 43/78 patients
using a partition model method. Forty-nine procedures were showed tumor progression. The median PFS was 57.0 months.
performed, including dual-lobe treatments in eight patients. In the univariate analysis, WHO grade (II vs. III: median PFS 64.0
Overall survival (OS) was evaluated using Kaplan-Meier curve and vs. 39.0 months, p=0.035) and TTPmin (≤25 vs. >25 min: median
objective response was assessed using modified RECIST criteria PFS 50.0 vs. 104.0 months, p=0.021) were associated with
assessed on CT performed two and six months after treatment. the clinical outcome, whereas age, contrast enhancement,
Results: Median OS of the entire cohort was 15.1 months. The Karnofsky-Performance-Score, surgical procedures, TBRmax/mean
median tumor absorbed dose was 193 Gy. Twenty-nine patients and BTV were not (p>0.05). In the multivariate analysis both
who received tumor absorbed dose > 150 Gy had significantly WHO grade (hazard ratio 2.4 (CI: 1.2-4.9), p=0.019) and TTPmin
longer survival when compared to those receiving a dose <150 (hazard ratio 2.4 (CI: 1.1-5.2), p=0.021) remained significant
Gy (median 17.5 months versus 11.5 months). Moreover, Overall prognostic factors for PFS. Conclusion: In IDH-mutant, 1p/19q-
survival (OS) correlated to the presence and degree of portal codeleted oligodendrogliomas, the WHO grade and TTPmin are
venous invasion. Patients without portal venous invasion had independent prognostic parameters for the PFS. A TTPmin of >25
longer OS when compared to those with portal venous invasion min identified patients with a favourable outcome (PFS twice
(median 18.2 months versus 11.8 months). Patients with main as long). Therefore, the evaluation of dynamic 18F-FET PET in
portal venous invasion had 8.9 months OS, while those with addition to histopathology and the molecular genetic profile
segmental venous invasion had 13 months OS. Objective seems useful for the characterization of gliomas and might help
response rate (OR) was 36 % and associated with higher tumor to individualize the treatment. References: None.
absorbed dose. Conclusion: In our series, we found a better
overall survival (OS) in patients that received tumor absorbed
dose >150 Gy. Main portal venous invasion was correlated with OP-682
poor overall survival (OS). References: None. Prognostic value of FDG-PET/CT in recurrent/refractory
CNS lymphoma receiving Ibrutinib-based therapies
S. Krebs, J. Wolfe, I. Mellinghoff, C. Grommes, H. Schoder;
1509 Memorial Sloan Kettering Cancer Center, New
York, NY, UNITED STATES OF AMERICA.
Neuroimaging - Parallel Session: Brain Tumours

Tuesday, October 15, 2019, 16:30 - 18:00 Lecture Hall 115 Aim/Introduction: Quantitative PET imaging biomarkers
for primary central nervous system lymphoma (PCNSL) have
not yet been established. This study evaluated the prognostic
OP-681 value of pretreatment FDG PET/CT-based measurements for
Prognostic value of dynamic 18F-FET PET in treatment response, progression-free survival (PFS) and overall
oligodendrogliomas survival (OS) to ibrutinib-based treatment regimen in recurrent/
F. J. Vettermann, M. Unterrainer, B. Suchorska, J. Herms, P. refractory (r/r) PCNSL and secondary CNS lymphoma (SCNSL).
Bartenstein, J. Tonn, N. L. Albert; Materials and Methods: Eligible patients had r/r PCNSL/
Ludwig-Maximillians-University, Munich, GERMANY. SCNSL, age≥18, ECOG≥2, normal end-organ function, and
unrestricted number and type of prior therapies. In patients
with SCNSL disease, systemic disease needed to be absent.
Aim/Introduction: In the updated 2016 WHO classification Participants received either single agent ibrutinib (560 mg, 840
gliomas are stratified into separate entities according to mg) or ibrutinib in combination with methotrexate (HD-MTX; at
their molecular genotype with different prognoses. IDH- 3.5g/m2 every 2 weeks) with or without rituximab. Pretreatment
mutant, 1p/19q-codeleted gliomas (oligodendrogliomas) FDG-PET/CT scans were prospectively analyzed. Lesion volumes
have a favourable outcome compared to astrocytic tumors or were measured by three-dimensional threshold-based volume
glioblastomas. With regard to the longer survival, treatment of interest (VOI) analyses for FDG-PET uptake and referring
decisions have to be made carefully and have to weigh up the to PET/CT images in all patients. The VOIs were overlaid on
S261 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

the tumors covering the entire lesion. We determined the (DSC 0.33±0.21) and a moderate spatial correlation of BTV and
maximum standardized uptake values (SUVmax), MTV (volume eBTV (DSC 0.75±0.19). The DSC was significantly lower in WHO
encompassed by a 42% isocontour around the voxel with the grade III compared to WHO grade IV gliomas correlating CE /
highest PET uptake), and TLG (calculated by multiplying MTV BTV (DSC 0.22±0.21 vs. 0.34±0.21, p=0.005) and CE / eBTV (DSC
by SUVmean). Results: 46 patients underwent single agent 0.26±0.21 vs. 0.36±0.21, p=0.024). Conclusion: In IDH-wildtype
therapy, 15 combination therapy. FDG PET/CT scans of 57/61 gliomas, the PET-derived BTVs distinctly exceed the CE on MRI in
patients with (r/r) PCNSL and SCNSL were analyzed. 16 patients both standard and early summation images with a poor spatial
had no measurable disease on PET. A total of 85 lesions were correlation only; especially in WHO grade III gliomas. Moreover,
identified, and maximum standardized uptake values (SUVmax), eBTV also exceeds BTV with a moderate spatial correlation.
metabolic tumor volume (MTV), total lesion glycolysis (TLG), These vast spatial discrepancies suggest that metabolically
were measured, lesion sum determined and correlated with active tumour on 18F-FET PET should be implemented into
progression free survival (PFS). Median SUVmax was 19.7 (3.7- resection and radiotherapy planning. References: None.
47.9), MTV 1.8 (0.3-32.4) and TLG 18.8 (0.5-709.5). High SUVmax
was correlated with lower PFS. In patients with a SUVmax >20,
PFS has 3.4 months, whereas patients with a SUVmax <20 OP-684
had a PFS of 10.8 months. Conclusion: In patients with CNS The Role of 11C-methionine PET in Patients with Negative/
lymphoma receiving an ibrutinib-based regimen, SUVmax of Undetermined Diffusion-Weighted Magnetic Resonance
>20 appears to be a prognostic factor. Validation in a larger Imaging (DWI-MRI): Correlation with Histology and
clinical trial will be performed. References: None. Molecular Biomarkers in Operated Glioma
A. Castello1, A. Bizzi2, M. Riva3, M. Rossi3, F. Pessina3, B. Fernandes4,
M. Grimaldi5, E. Mazziotti6, P. Navarria7, L. Bello3, E. Lopci1;
OP-683 1
Nuclear Medicine, Humanitas Clinical and Research Hospital -
Biological-tumour-volumes in standard and early IRCCS, Rozzano (MI), ITALY, 2Neuroradiology, Fondazione IRCCS
summation18F-FET PET images distinctly exceed contrast- Istituto Neurologico Carlo Besta, Milan, ITALY, 3Oncological
enhancementin patients with IDH-wildtype glioma Neurosurgery, Humanitas Clinical and Research Hospital -
M. Unterrainer, K. von Rohr, L. Kaiser, C. Diekmann, V. Ruf, J. Herms, IRCCS, Rozzano (MI), ITALY, 4Pathology, Humanitas Clinical
P. Bartenstein, M. Niyazi, J. Tonn, N. L. Albert; and Research Hospital, Rozzano (MI), ITALY, 5Neuroradiology,
University of Munich, Munich, GERMANY. Humanitas Clinical and Research Hospital, Rozzano (MI),
ITALY, 6Nuclear Medicine, Humanitas Clinical and Research
Hospital, Rozzano (MI), ITALY, 7Radiotherapy and Radiosurgery,
Aim/Introduction: In patients with IDH-wildtype glioma, the Humanitas Clinical and Research Hospital, Rozzano (MI), ITALY.
contrast-enhancement (CE) on MRI usually represents the target
of local treatments such as resection and radiotherapy. PET
using 18F-FET enables detection of metabolically active tumour Aim/Introduction: Our aim was to assess 11C-methionine PET
parts beyond CE on MRI. Especially, even larger metabolically and Diffusion-Weighted Magnetic Resonance Imaging (DWI-
active tumour parts were seen in early 18F-FET PET summation MRI) diagnostic accuracy and the prognostic value in patients
images. However, the spatial correlation of CE and PET-derived with gliomas candidate to neurosurgery. Materials and
tumour volumes in IDH-wildtype gliomas remains unknown Methods: Patients (n=124) who underwent 11C-methionine
and was analysed in this study. Materials and Methods: PET and DWI-MRI in the diagnostic and preoperative stage were
Patients with de-novo IDH-wildtype glioma WHO grade III/IV retrospectively enrolled. The reference standard was established
undergoing 18F-FET PET and MRI prior to any further therapy by histology after neurosurgery. Images were interpreted by
were included. On 18F-FET PET, the biological-tumor-volume visual evaluation for DWI-MRI and by both visual and semi-
(BTV) was assessed (1.6 x background-activity) within standard quantitative analysis, expressed by SUVmax, SUVratio (ratio of
(20-40 minutes) and early (5-15 minutes) summation images SUVmean in the tumor to SUVmean in contralateral normal
(eBTV). On MRI, the volume of CE was delineated. The spatial cortex) and metabolic tumor burden (MTB), for 11C-methionine
correlation between CE, BTV and eBTV was assessed using the PET. Kaplan-Meier survival analysis was performed. The median
Dice-similarity-coefficient (DSC). Results: 164 patients with follow-up was 14.3 months (range 2-73 months). Correlations
IDH-wildtype glioma were included (99/164 (60%) glioblastoma between metabolic parameters and Ki-67 were evaluated.
WHO grade IV, 65/164 (40%) anaplastic astrocytoma WHO grade Results: 47 high-grade gliomas (HGG), 77 low-grade gliomas
III). Of these, 157/164 (96%) were 18F-FET-positive and 130/164 (LGG) were diagnosed. On visual assessment, sensitivity and
(79%) showed CE on MRI. 27/34 (79%) patients without CE were specificity for differentiating HGG from LGG were 80.8% (38/47)
18
F-FET-positive; vice versa, 0/7 (0%) 18F-FET-negative patients and 59.7% (46/77) for DWI-MRI, and 95.7% (35/47) and 41.5%
showed CE on MRI. Overall, CE was significantly smaller than (32/77) for 11C-methionine PET. On semi-quantitative analysis
BTV (13.6±18.5 vs. 26.6±24.8 ml, p<0.001) and eBTV (32.1±26.7 the sensitivity, specificity and the area under the curve by ROC
ml, p<0.001), whereas eBTV was significantly larger than BTV analysis, respectively, were 78.7%, 71.4%, and 80.4% for SUVmax,
(32.1±26.7 vs. 26.6±24.8 ml, p=0.001). Hence, there was a poor 78.7%, 70.1%, and 81.1% for SUVratio, and 74.5%, 61%, and
spatial correlation of CE / BTV (DSC 0.31±0.22) and CE / eBTV 76.7% for MTB. In patients with negative DWI-RMI, median PFS
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S262

was longer in those with SUVmax<3.6 (median not reached reversible 2TCVB model was preferred (Akaike). While TBR20-40 was
vs 34.2 months, p=0.004), SUVratio<2.4 (median not reached strongly correlated with DVR (ρ=0.92), an increasing kinetic was
vs 21.5 months, p<0.001), and MTB<7 (median not reached vs associated with an elevated net-influx-rate Ki from Patlak plots
45.7 months, p=0.018). When we analyzed patients with LGG (ρ>0.8), and an early peak or negative slope was associated
and negative DWI-RMI, only SUVratio<2.4 and MTB<7 were with an elevated K1 (ρ>0.53) and k2 (ρ>0.72) from 1TCVB, and
associated with longer PFS (p=0.016 and p=0.024, respectively). K1 (ρ>0.34) and k4 (ρ>0.56) from 2TCVB. Despite significantly
Regarding molecular profile, in patients with negative DWI-RMI elevated distribution-volumes (VT) in tumour tissue compared
and IDH wild type, SUVmax and SUVratio were higher compared to background, VT was not able to differentiate between glioma
to those with IDH mutated (p=0.025 and p=0.01, respectively). grades in univariate analysis (AUC for identification of IDHwt
In the same cohort, patients with 1p/19q codeletion showed <0.59; AUC for identification of HGG <0.52). Relative values
a tendency to have higher SUVmax (p=0.067) compared (DVR or TBR20-40) yielded slightly better results. The highest AUC
to those without codeletion. No significant difference was values were obtained for TBR5-15 (0.78; 0.80), TTP (0.78; 0.72),
found regarding MGMT promoter methylation status. Finally, Slope15-40 (0.83; 0.78), and the parameters from Patlak plots (0.82;
we demonstrated a positive correlation among metabolic 0.79) and 1TCVB (K1: 0.75; 0.75 and k2: 0.72; 0.73). Multivariate
parameters by 11C-methionine PET and Ki-67, in all gliomas as analysis yielded an AUC of 0.86 for the identification of IDHwt
well as in those with negative DWI-MRI (SUVmax rho=0.515, and 0.82 for the identification of HGG gliomas. Conclusion: The
SUVratio rho=0.488, and MTB rho=0.477). Conclusion: characteristic kinetics of aggressive gliomas could be described
11
C-methionine PET was highly sensitive for the differentiation with pharmacokinetic model parameters. The best results for
between LGG and HGG both by visual and semi-quantitative molecular-genetic and histologic glioma classification were
evaluation. In patients with negative DWI-MRI, 11C-methionine obtained with multivariate analysis incorporating static and
PET was predictive of PFS, hence allowing to identify gliomas kinetic 18F-FET PET parameters. A validation study based on
with worse prognosis and helping clinicians to tailor therapy stereotactic biopsies is ongoing. References: None.
approach. 11C-methionine PET metrics correlated significantly
with proliferative index and the IDH status. References: None.
OP-686
Dynamic 68Ga-DOTATATE PET/MRI and Patlak analysis for
OP-685 enhanced diagnosis of intracranial meningioma
Molecular-genetic and histologic differentiation N. Karakatsanis, M. Skafida, E. Lin, M. Roytman, B. Liechty, T.
of gliomas based on characteristic 18F-FET PET Schwartz, S. Pannullo, J. Osborne, J. Ivanidze;
pharmacokinetics Weill Cornell Medical College, New York,
L. Kaiser1, M. Unterrainer1, A. Holzgreve1, M. Grosch2, S. A. Ahmadi2, NY, UNITED STATES OF AMERICA.
E. Mille1, A. Gosewisch1, J. Brosch1, B. Suchorska3, J. C. Tonn3, S.
Ziegler1, P. Bartenstein1, N. L. Albert1, G. Böning1;
1
Department of Nuclear Medicine, University Hospital, Aim/Introduction: Meningiomas are the most common
LMU Munich, Munich, GERMANY, 2German Center for intracranial tumors. They are often slow-growing tumors without
Vertigo and Balance Disorders, University Hospital, LMU noticeable early symptoms, but potentially life threatening
Munich, Munich, GERMANY, 3Department of Neurosurgery, with increasing size and high likelihood of recurrence. Contrast
University Hospital, LMU Munich, Munich, GERMANY. enhanced MRI is the gold standard for meningioma diagnosis
and treatment planning but with limitations in accurately
differentiating recurrence from post-treatment effects. 68Ga-
Aim/Introduction: Various static and kinetic parameters DOTATATE is a PET radiotracer with high target affinity in
derived from dynamic 18F-FET PET data have shown clinical somatostatin receptors 2 (SSTR2) previously utilized for the
relevance for glioma classification. The aim of this study was to characterization of gastrointestinal neuroendocrine tumors.
correlate heuristic with pharmacokinetic modelling parameters, Meningiomas exhibit high expression rates of SSTR2. The aim
and to assess the relevance for molecular-genetic and histologic of this study was to evaluate the usefulness of dynamic 68Ga-
glioma classification. Materials and Methods: A total of 322 DOTATATE PET/MRI and Patlak uptake rate (Ki) analysis in a
newly diagnosed gliomas were included: 128 IDH-mutant, prospective clinical cohort of patients with meningioma.
194 IDH-wildtype (IDHmut/wt); 91 low-, 231 high-grade (LGG/ Materials and Methods: A cohort of 20 patients with clinically
HGG). We investigated 1- and 2-tissue compartment models suspected or pathology proven meningioma were imaged
(1/2TC) with/ without blood volume fraction (VB) using an over a period of 6 months. Dynamic PET/MRI was performed
image-derived input function (IDIF), linear models (Logan and at 10-50 +/-5 minutes post 68Ga-DOTATATE injection. For 12
Patlak) with IDIF or reference tissue input, and the following randomly selected patients, the PET list data were binned to
heuristic parameters: early/ late tumour-to-background ratios 5-min frames, followed by reconstruction of the respective
(TBR5-15, TBR20-40), late slope (Slope15-40), and time-to-peak dynamic PET images and subsequent Patlak Ki analysis. SUVmean
(TTP). The ability to identify an IDHwt or HGG glioma was values over post-injection time and Ki scores were extracted
assessed with univariate and multivariate ROC-analysis using from target regions, corresponding to identified meningiomas
5-fold cross-validation with stratified folds. Results: In 63% a or suspected post treatment effects, using the superior sagittal
S263 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

sinus as reference uptake. Post-injection time-SUVmean curves SUVmax 2.30, for SUVmean 0.21 and for SUVpeak 0.63. When
and regional Ki scores were evaluated to determine the rate lesions were grouped as LGG and HGG, the cutoff values were
of 68Ga-DOTATATE uptake in the target against the reference 1.15 for SUVmax, 0.06 for SUVmean and 0.21 for SUVpeak. In
regions. Moreover, the last 10min of PET data were binned the diagnosis of HGG, PET’s sensitivity is higher than MRI but
into a single frame and the respective static PET images were there is no statistically difference in specificity (PET sensitivity
reconstructed. Results: From the static 68Ga-DOTATATE/MR 85.7% specificity 85,7%; MR sensitivity 71.4% specificity 85.4%).
images, 50 meningiomas were identified (median: 2 per patient, Conclusion: 68Ga PSMA PET imaging is found to be particularly
range 0-14). In the sub-cohort of 12 patients, the high Ki scores useful in differentiating Grade IV glial tumors from lower grades.
(Ki>0.015ml/min/g) from Patlak analysis of the dynamic PET This finding is thought to be important in the differentiation
data confirmed the previously identified meningiomas, while in of relapse from postoperative tissue changes and utility of
4 cases a very low uptake rate (Ki<0.009ml/min/g) suggested 177Lu PSMA treatment (2). Thanks to the PET/MRI technique,
post-treatment effects even in presence of suspicious MRI that patients can undergo simultaneous PET and MRI in one
findings. Distinctively higher Ki rates of 68Ga-DOTATATE uptake stop. References: 1. Nomura N, Pastorino S, Jiang P, Lambert G,
were evaluated for meningioma relative to post-treatment Crawford JR, Gymnopoulos M et al. Prostate specific membrane
effects (p<0.01) positively correlated with parenchymal and antigen (PSMA) expression in primary gliomas and breast cancer
osseous invasion. Finally, the contrast of SUVmean in meningioma brain metastases. Cancer Cell Int 2014; 14 :26.2. Sasikumar A,
over post-treatment effect regions continuously increased with Kashyap R, Joy A, Charan Patro K, Bhattacharya P, ReddyPilaka
the maximum ratio attained later than 45min post injection. VK, et al. Utility of 68Ga-PSMA-11 PET/CT in Imaging of Glioma-A
Conclusion: Dynamic 68Ga-DOTATATE PET/MRI and Patlak Ki Pilot Study. Clin Nucl Med. 2018 Sep; 43(9): e304-e309.
analysis can enhance the differentiation between meningioma
and post-treatment effects at no additional scan time relative to
static PET/MR. The unique multi-parametric features of dynamic 1510
68
Ga-DOTATATE PET/MRI may facilitate a more accurate diagnosis
of intracranial meningioma. References: None.
Clinical Oncology - Parallel Session: It’s in the
Blood!

OP-687 Tuesday, October 15, 2019, 16:30 - 18:00 Lecture Hall 116
68
Ga PSMA PET/MRI in THE DIFFERENTIATION of LOW and
HIGH GRADE GLIOMAS
E. Akgun, M. Y. Akgun, C. Isler, M. Uzan, H. B. Sayman; OP-688
IUC Cerrahpasa Medical Faculty, Istanbul, TURKEY. Comparison between tumour metabolism derived from
18F-FDG-PET/CT and accurate cytogenetic stratification in
newly diagnosed multiple myeloma patients
Aim/Introduction: The increased expression of prostate Y. E Silva1, J. Riedinger1, D. Caillot2, M. Chrétien2, J. Corre3, A.
specific membrane antigen on the neovasculature of tumors Cochet1, C. Tabouret-Viaud1;
enables uptake of 68Ga PSMA on brain tumors (1). Based on 1
Unicancer Georges-François Leclerc Cancer Center, Dijon,
this fact, we investigated if there was a relationship between FRANCE, 2University Hospital François Mitterrand, Dijon, FRANCE,
SUV measurements and tumor grades using the images 3
Institut Universitaire du Cancer-Oncopole, Toulouse, FRANCE.
obtained with 68Ga PSMA PET/MR in patients pre-diagnosed
as low grade glioma (LGG) or high grade glioma (HGG).
Materials and Methods: From thirty-five out of 38 patients Aim/Introduction: p.p1 {margin: 0.0px 0.0px 0.0px 0.0px; font:
whose pathological examination revealed glial tumor, a total 12.0px ‘Helvetica Neue’; color: #454545} 18-Fluorodeoxyglucose
of 42 lesions located on separate anatomic localizations were Positron Emission Tomography (18F-FDG-PET/CT) is a useful
evaluated. SUV (max/mean/peak) values and grade relationship tool for baseline staging in newly diagnosed Multiple Myeloma
were evaluated based on each lesion while mitosis, Ki-67 were (MM). This monocentric retrospective study aimed at examining
evaluated for each patient. Endothelial proliferation, necrosis the relation between baseline tumour metabolism and LINEAR
was only evaluated in HGGs, Alpha thalassemia/mental PREDICTOR (LP)-score, a new cytogenetic stratification score.
retardation syndrome X-linked (ATRX) mutation was evaluated Materials and Methods: p.p1 {margin: 0.0px 0.0px 0.0px 0.0px;
in astrocytomas. Results: Grade, Ki-67, mitosis and necrosis font: 12.0px ‘Helvetica Neue’; color: #454545} From June 2011 to
and SUV (max/mean/peak) values were found statistically March 2019, 104 patients addressed to our institution for staging
significant in correlation. The parameter with the highest of newly diagnosed MM were included. Thirty-nine patients
correlation coefficient was mitosis. (For SUVmax r = 0.64, p = were included in a preliminary study in order to determine
0). The correlation of endothelial proliferation in HGGs was which threshold of significance for calculation of total metabolic
not statistically significant. There was no significant difference tumor volume (TMTV) / total lesion glycolysis (TLG) is the most
between the SUV values of ATRX mutant and nonmutant cases. associated with progression rate in MM, between four per-
When Grade II and III were considered as the first group and patient adapted thresholds, absolute threshold at SUVmax2.5,
IV as the second group, the cutoff values were found to be for relative threshold at 41% of SUVmax. For the remaining 65
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S264

patients, LP score was determined on systematic iliac crest bone as an index site to measure tumor burden in diffuse MM
marrow samples. Obtained on CD138-sorted bone marrow validated by prior study). The gold standard was bone marrow
plasma cells, this new composite cytogenetic stratification examination and trephine biopsy with immunohistochemistry.
is a 6-marker based weighted score using FISH+/- single Patients with other hematological disorders found by trephine
nucleotide polymorphism arrays (deletion 17p, translocation biopsy were excluded. Results: 160 patients (M:F=81:79; age
(4;14), trisomy 5, trisomy 21, 1q gain, deletion 1p32). We then range:33-90years, mean=64.2±12.8years) were finally included.
correlated TMTV / TLG calculation and LP-score using a Kruskall- Patho-histochemical examinations confirmed 95 patients
Wallis test, and diffuse bone marrow involvement (DBI) on with active MM (who required treatment), 16 with indolent
PET (based on hepatic background as threshold of positivity) smoldering MM (SMM), 25 with monoclonal gammopathy
and cytogenetic data using a Chi-squared test. Results: of unknown significance (MGUS), 24 with active marrow
p.p1 {margin: 0.0px 0.0px 0.0px 0.0px; font: 12.0px ‘Helvetica with/without reactive plasmacytosis. Of the 95 active MM
Neue’; color: #454545} In the preliminary study, TMTVbm/TLGbm patients, 11C-acetate PET/CT identified 78/95 (82.1%) versus
calculation (with bone marrow threshold) was correlated 18
F-FDG 53/95 (55.8%), P<0.05. All 17/95 patients negative
more significantly to 2-year progression rate than other on 11C-acetate PET/CT were also negative on 18F-FDG PET/
methods (p=0.023 and 0.033 respectively, corresponding AUC CT; however, 11C-acetate could identify 25/42 (59.5%) active
= 0.739+/-0.085 and 0.723+/-0.085 respectively) and was the MM missed by 18F-FDG. Of the 53/95 patients detected by
only method associated with 3-year progression rate (p=0.029 both tracers, 51/53 had MM lesions more avid for 11C-acetate
and 0.039 respectively). The distribution of TMTVbm/TLGbm than 18F-FDG (respectively SUVmax_L3=5.6±1.7 vs. 3.6±1.3,
values among the 3 LP-score categories was almost stochastic, P<0.05) and/or with greater number of 11C-acetate-avid FBLs
without any significant association (p=0.70). There was also no than 18F-FDG. 11C-acetate PET/CT was negative in indolent
significant association between TMTVbm/TLGbm and any of the SMM (16/16=100%), MGUS (21/25=84%), active marrow with/
6 cytogenetic abnormalities included in LP-score calculation without reactive plasmacytosis (23/24=95.8%) with an overall
except for trisomy 21 (trend for significance: p=0.09 and 0.11 specificity 92.3% (60/65). 18F-FDG PET/CT could not correct
respectively). We didn’t find significant association between DBI any of the 5 false positive cases by 11C-acetate and had a
and cytogenetics, either (p=0.29). Conclusion: p.p1 {margin: lower specificity (54/65=83.1%). Conclusion: With a larger
0.0px 0.0px 0.0px 0.0px; font: 12.0px ‘Helvetica Neue’; color: cohort, we found that 18F-FDG offered no incremental value
#454545} There is no significant association between tumour over 11C-acetate and verified that 11C-acetate is the preferred
metabolism assessed with 18F-FDG-PET/CT and LP-score tracer for PET/CT diagnosis of active MM, potentially useful in
cytogenetic stratification in patients with newly diagnosed MM, 3 management scenarios: to confirm or rule out active MM, to
suggesting a potential complementarity of these biomarkers for suggest observation versus initiation of treatment in SMM, or to
prognostic stratification. References: None. observe in simple plasma cell dyscrasia not yet requiring active
treatment. References: None.

OP-689
C-acetate Is The Preferred Tracer Over 18F-FDG In PET/CT
11
OP-690
Evaluation Of Active Multiple Myeloma: A Follow-up Study Prognostic role of baseline 18F-FDG PET/CT metabolic
With A Larger Cohort Of Patients parameters in elderly Hodgking lymphoma
G. C. L. Ho, S. Chen, S. Cheung, Y. Leung, K. Cheng, K. Wong, Y. A. Mazzoletti1, D. Albano2, F. Dondi1, M. Bonacina2, R. Durmo2, E.
Wong, K. Wu, R. Liang; Cerudelli2, M. Gazzilli2, P. Bellini1, F. Bertagna1, R. Giubbini1;
Hong Kong Sanatorium & Hospital, Hong Kong, HONG KONG. 1
Università degli Studi di Brescia, Brescia, ITALY,
2
Spedali Civili di Brescia, Brescia, ITALY.

Aim/Introduction: Our pilot study in 2014 suggested that


11
C-acetate is a more appropriate PET tracer than 18F-FDG Aim/Introduction: Hodgkin Lymphoma (HL) is an aggressive
for early detection of active multiple myeloma (MM) and lymphoma subtype with high 18F-FDG avidity at 18F-FDG-
measurement of MM tumor burden. In this follow-up study, PET/CT but no validated criteria in treatment evaluation and
we extended our investigation to a larger cohort of clinically- prediction of outcome are currently available. The prognosis of
suspected MM patients in order to verify that 11C-acetate is HL in elderly patients (aged over 65 years) is considerably poor
indeed the preferred PET tracer to evaluate the metabolic especially in comparison with young patient and the reason of
pathology of MM. Materials and Methods: From Aug 2014 to this poor outcome is yet unclear. The aim of this study was to
July 2018, 195 patients clinically suspected of MM (M:F=102:93; investigate whether the metabolic baseline 18F-FDG PET/CT
age range:32-90years, mean=64.0±13.4years) were referred by parameters can predict prognosis in elderly HL. Materials and
hematologists for dual-tracer (11C-acetate, 18F-FDG) PET/CT. The Methods: Between January 2006 and January 2019, 73 (average
PET criteria for active MM were defined as: (1) focal bone lesions age 73,5; 38 men and 35 women) patients with histologically
(FBLs) with visually increased 11C-acetate or 18F-FDG uptake; and/ proven Hodgkin Lymphoma who underwent baseline 18F-FDG-
or (2) diffusely increased marrow metabolism with L3 vertebra PET/CT were retrospectively enrolled. Seventy-two patients
11
C-acetate SUVmax_L3>=3.8 or 18F-FDG SUVmax_L3>=3.0, (L3 diagnosed with HL were cured with standard chemotherapy
S265 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

regimens, 13 of them received also radiation therapy and just applied using an in-house developed software “Accurate”: two
1 patient received only radiation therapy. PET images were fixed thresholds (SUV4.0 and SUV2.5), two relative thresholds
analyzed visually and semi-quantitatively by measuring the (A50P: a contrast corrected 50% of SUVpeak, and 41max: 41% of
maximum standardized uptake value body weight (SUVbw), the SUVmax), and 2 majority vote methods, MV2 and MV3 selecting
maximum standardized uptake value lean body mass (SUVlbm), delineations of ≥2 and ≥3 of previously mentioned methods,
the maximum standardized uptake value body surface area respectively. After removing regions with physiological uptake,
(SUVbsa), total metabolic tumor volume (MTV) and total lesion quality scores (QS) were given to each segmentation by two
glycolysis (TLG). For the entire population, receiver operating reviewers (JD, GZ): QS-1, complete selections containing all
characteristic curve analysis was used to identify the optimal visible tumor localizations after minimal observer-interaction;
cutoff point of semiquantitative parameters in the light of and QS-2 for incomplete selections. Besides, quality of the
progression free survival (PFS) and overall survival (OS). Survival segmentation was rated: A, for good visual delineation of lesions;
curves were plotted according to the Kaplan-Meier method. B, for too narrow delineation; and C, for too large delineation.
Results: All baseline PET/CT were positive showing increased Semi-manual segmentation was done by adjusting the most
18F-FDG uptake in nodal and/or extranodal lesions. At a median complete semi-automatic method. We used Spearman’s
follow up of 31,4 months (range 1-101), the median PFS and correlations to compare all semi-automatic methods. Bland-
OS were respectively 20,7 and 31,4 months with a 2-year and Altman analysis was performed to compare semi-automatic
3-year PFS of 54% and 42% and a 2-year and 3-year OS of with semi-manual segmentation. Results: SUV2.5, A50P, MV3,
68% and 41% respectively. Relapse or progression of disease 41max, SUV4.0 and MV2 had QS-1 in respectively 65%, 55%,
occurred in 29 patients with an average time of 14,8 months 55%, 50%, 45% and 40% of cases, with QS-1A in 45%, 25%,
from the baseline PET/CT and death occurred in 21 patients 30%, 35%, 40% and 15% of all scans. Segmentation quality was
with an average time of 17,2 months. SUVbw, SUVlbm and not significantly different in patients with advanced stage or
SUVbsa were significantly related to PFS (respectively p=0,03; primary refractory disease. However, in scans containing lesions
p=0.003; p=0,009) and only SUVbw was related to OS (p=0,03). close to regions with physiological uptake (n=8), only 37.5%
Metabolic tumor volumes (MTV and TLG) were not related with (SUV4.0 and 41max), 25% (SUV2.5), 13% (MV3) and 0% (MV2 and
outcome survival. Conclusion: In conclusion, in our study we A50P) had QS-1A. The median bMTV was 39.3, 35.8, 35.3, 31.0,
demonstrated that several metabolic tumour features (SUVbw, 21.7 and 21.5 mL for A50P, MV2, MV3, 41max, SUV2.5 and SUV4.0,
SUVlbm and SUVbsa) were significantly correlated with PFS, and 39.2 mL with semi-manual segmentation. Spearman
while only SUVbw with OS. MTV and TLG were not related with coefficients were lowest for SUV2.5 (0.39-0.61). High correlations
outcome survival. References: None. were shown between all other methods (0.70-0.92, p-values
<0.001). Bland-Altman analysis showed the highest agreement
between 41max and semi-manual segmentation. Conclusion:
OP-691 Semi-automatic bMTV segmentation often does not result in
Determining the optimal segmentation method for good quality segmentations. This indicates that semi-automatic
assessing metabolic tumor volume in 18FDG-PET-CT scans segmentation should be supervised and manually adapted.
in relapsed/refractory classical Hodgkin lymphoma Since bMTV using different segmentation methods correlated
J. Driessen1, G. J. C. Zwezerijnen2, J. J. Eertink3, M. J. Kersten1, O. S. well, the optimal method may be best identified based on ease
Hoekstra2, J. M. Zijlstra3, R. Boellaard2; of use and clinical performance. References: None.
1
Department of Hematology, Amsterdam UMC, University
of Amsterdam, Cancer Center Amsterdam and LYMMCARE
(Lymphoma and Myeloma Center), Amsterdam, NETHERLANDS, OP-692
2
Department of Radiology and Nucleair Medicine, Amsterdam Prognostic Value of Baseline Total Metabolic Tumor
UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, Volume Measured on FDG PET in Patients with Richter
Amsterdam, NETHERLANDS, 3Department of Hematology, Syndrome
Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer X. Palard1, A. Girard1, H. Mesbah1, A. Tempescul2, A. Devillers1, P.
Center Amsterdam, Amsterdam, NETHERLANDS. Salaün2, L. Haumont1, T. Lamy3, F. Le Jeune1, C. Pontoizeau1;
1
Centre Eugène Marquis, Rennes, FRANCE, 2CHRU,
Brest, FRANCE, 3CHU, Rennes, FRANCE.
Aim/Introduction: Baseline metabolic tumor volume (bMTV)
is increasingly studied as a prognostic factor for relapsed/
refractory classical Hodgkin lymphoma (R/R cHL). However, Aim/Introduction: Richter syndrome (RS) derives from the rare
there is no consensus on a standard segmentation method for transformation of chronic lymphocytic leukemia (CLL) into an
assessing bMTV. The aim of this pilot study was to derive bMTV aggressive lymphoma, most commonly of the diffuse large B
with 6 semi-automatic segmentation methods and a manual cell lymphoma (DLBCL) type. It is a rare complication with an
approach and to investigate the correlation of bMTV among all unfavorable prognosis, so the identification of prognostic factors
segmentation methods. Materials and Methods: We selected at diagnosis is needed. Extracted from the FDG PET, the baseline
20 EARL compliant baseline 18FDG-PET-CT scans of R/R cHL Total Metabolic Tumor Volume (TMTV) is a known independent
patients. Six semi-automatic segmentation methods were predictor of outcome in aggressive de novo lymphoma. The aim
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S266

of the study was to investigate the prognostic value of TMTV retrospectively reviewed. BMI was identified by a positive-BMB
for patients with transformation of CLL into DLBCL. Materials result and/or focal skeleton FDG uptake in PET/CT (BM-positive
and Methods: We performed a retrospective review of 28 by PET) irrespective of the BMB result. We assessed the correlation
consecutive patients with transformation of CLL into DLBCL of PET findings with BMB results, progression free survival (PFS),
who had undergone baseline FDG PET from January 2012 to and overall survival (OS). Results: In total, 247 patients with FL
April 2018. Overall survival rates were estimated using the were included, of whom 111 (44.9%) were judged to have BMI;
Kaplan-Meier method. Univariate analysis was perfomed 80 were identified by BMB and 76 were identified by FDG-PET/
using log-rank tests with an optimal cut-off point for binary CT. PET identified BMI cases that were not identified by BMB and
outcomes and compared with others prognostic factors for upstaged 24 patients to stage IV, of those, 10 patients from I or II
multivariate analysis using Cox proportional hazards models. to IV. In contrast, BMB identified BMI not identified by FDG-PET/
The parameters (at the time of diagnosis) tested were: gender, CT, which changed-stage 32 patients to stage IV, of whom, 6
age, performans status, IPI score, serum LDH level, serum patients from I or II to IV. The sensitivity, negative predictive value
platelet count, the presence or not of prior therapies for CLL, (NPV), and accuracy of FDG-PET/CT to detect BMI by BMB were
Ann Arbor stage, Bulky or not, SUVmax, SUVmean and TMTV. 56%, 80%, and 73%, respectively. However, if BM-positive by PET
Results: The median age of patients was 71 years old. During and positive BMB were both considered separately sufficient to
the follow-up period (median 19 months), 14 patients died. detect true BMI, the sensitivity, negative predictive value (NPV),
Median baseline TMTV was 80 cm3 (5 - 2500 cm3). Only low and accuracy were 68% 80% and 86% for FDG-PET/CT, and 72%
serum platelet count, high serum LDH level, and high TMTV 81%, and 87% for BMB, respectively. As a secondary aim, we
at the time of the transformation were predictive of overall compared the prognosis of BMI, as detected by FDG-PET/CT or
survival. The 4-year estimates of overall survival were 75 % in BMB. Sixty-one patients had progressive disease or died, and 25
the low metabolic burden group (TMTV ≤1200 cm3) and 35 % patients died during the follow-up period. Univariate analysis of
in the high metabolic burden group (TMTV >1200 cm3). The PFS demonstrated that high FLIPI (>2), BM-positive by PET, and
estimated median overall survival time was 11 months for the positive BMB were associated with lower PFS (p = 0.05, 0.001, and
high metabolic burden group compared to 191 months for the 0.01). Also, high FLIPI and BM-positive by PET were associated
low metabolic burden group (p=0.02). The multivariate analysis with lower OS (p = 0.009 and < 0.001). In multivariate analysis,
did not found any significant association of these parameters BM-positive by PET was the only independent predictor of PFS
with the overall survival. Conclusion: The TMTV extracted from and OS (p = 0.002). Conclusion: Combined FDG-PET/CT and
FDG PET at the moment of the transformation of CLL into DLBCL BMB have greater accuracy for identifying BMI in FL than BMB
is a predictor of overall survival. References: None. alone does. Thus, baseline FDG-PET/CT contributes to accurate
staging of FL, with potential impact on treatment choice. BMI by
PET also provides relevant prognostic information. References:
OP-693 None.
Baseline FDG-PET/CT detects bone marrow involvement
in follicular lymphoma and provides relevant prognostic
information OP-694
R. Nakajima1, A. J. Moskowitz2, L. Michaud3, A. Mauguen4, H. Quantitative Assessment of [18F]FDG PET Images in
Schöder1; Patients with Hodgkin Lymphoma: Is It Affected by
1
Memorial Sloan Kettering Cancer Center, Department of Contrast-Enhanced CT Attenuation Correction?
Radiology, Molecular Imaging and Therapy Service, New C. Voltin1, J. Mettler1, R. Boellaard2, G. Kuhnert1, M. Dietlein1, P.
York, NY, UNITED STATES OF AMERICA, 2Memorial Sloan Borchmann1, A. Drzezga1, C. Kobe1;
Kettering Cancer Center, Department of Medicine, Division 1
University Hospital of Cologne, Cologne, GERMANY, 2VU
of Hematologic Oncology, Lymphoma Service, New York, University Medical Centre, Amsterdam, NETHERLANDS.
NY, UNITED STATES OF AMERICA, 3Memorial Sloan Kettering
Cancer Center, Molecular Imaging and Therapy Service,
New York, NY, UNITED STATES OF AMERICA, 4Memorial Sloan Aim/Introduction: The reliability of visual and quantitative
Kettering Cancer Center, Department of Epidemiology and response assessment may be impaired due to inconsistent
Biostatistics, New York, NY, UNITED STATES OF AMERICA. scanning protocols and image reconstruction methods of
2- deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) positron emission
tomography (PET). Hence, this study investigates the impact
Aim/Introduction: To evaluate the diagnostic performance of contrast-enhanced computed tomography (CT) attenuation
of 18F -FDG PET/CT images for the detection of bone marrow correction in patients with Hodgkin lymphoma. Materials and
involvement (BMI) and determination of prognosis in patients Methods: In 10 consecutive patients undergoing either staging
with follicular lymphoma (FL) before treatment. Materials or response assessment, [18F]FDG PET images were attenuation
and Methods: Patients were identified from our institutional corrected once on the basis of unenhanced CT and additionally
database, records of patients with FL diagnosed from 2002- using contrast-enhanced CT. Reconstruction was performed
2016 in a single hospital and who had undergone both FDG- in both cases with ordered subset expectation maximization
PET/CT and bone marrow biopsy (BMB) prior to treatment were (OSEM) and ultra high definition (UHD) algorithm. While SUVmax
S267 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

and SUVpeak were obtained from tumour tissue, SUVmax and the same lymph node region Results: In total 41 patients were
SUVmean were determined within the background regions liver included. From those, 27 were monomorphic PTLD and 14 were
and mediastinal blood pool. Results: After switching to contrast- “other PTLD morphologies”, including non-destructive (n=4),
enhanced CT attenuation correction, SUVmax and SUVpeak in polymorphic (n=9) and Hodgkin-like PTLD (n=1). Median SUVmax,
lymphoma tissue increased on average by 2.55±3.24 (p=0.018) SUVpeak, SUVmean values were statistically significantly higher in
and 3.64±3.22% (p=0.008) with OSEM and by 4.59±5.49 (p=0.005) monomorphic PTLD than in “other PTLD morphologies (p<0.05):
and 3.84±5.65% (p=0.005) with UHD reconstruction. In the liver, SUVmax, 17 (range 3.3-64) for monomorphic PTLD vs 6.1 (2.9-24)
SUVmax and SUVmean showed a mean rise of 7.15±4.27 (p=0.005) for other PTLD morphologies; SUVpeak 15 (range 2.7-53) vs 4.8
and 6.97±2.18% (p=0.005) after OSEM, compared to 7.24±6.59 (range 2.2-19) and SUVmean 7.3 (range 2.4-16) vs 4.3 (range 1.9-
(p=0.017) and 6.29±2.83% (p=0.005) after UHD reconstruction. 9.3). Conclusion: Semi-quantitative FDG-PET/CT measurements
Mediastinal SUVmax and SUVmean increased on average by may be helpful to discriminate monomorphic from “other PTLD
10.82±4.89 (p=0.005) and 12.40±3.73% (p=0.005) in the OSEM subtypes”. However we observed a wide range of values for all
data sets and by 13.11±14.93 (p=0.005) and 11.50±12.19% semi-quantitative measurements explored, with value overlap
(p=0.005) in the UHD images. Conclusion: Since the use of between monomorphic PTLD and “other PTLD morphologies”.
CT contrast fluids results in a stronger SUV increase within Semi-quantitative quantification may provide an indication
the liver and mediastinal blood pool than within lymphoma of PTLD classification but biopsy is still warranted for definite
tissue, this may have clinical consequences regarding visual classification. References: Swerdlow, S. H. et al. International
and quantitative response assessment. Ideally, CT scans for PET Agency for Research on Cancer, 2017. Krishnamurthy et al, Int. J.
attenuation correction should therefore be performed in the Surg. Pathol. 2010. Trappe, R. et al. Lancet Oncol. 2012. Chiou, F.
absence of a contrast agent. References: None. K. et al. Transplantation 2018. Dierickx, D. et al. Blood 2015

OP-695 1601
Characterization Of Post-transplant Lymphoproliferative
Disorder With Semi-quantitative FDG-PET/CT
CME 13 - Drug Develeopment + Radiopharmacy
F. Montes de Jesus, W. Noordzij, X. Kahle, M. Nijland, E.
Committee: Current and Future of
Verschuuren, R. Dierckx, T. van der Meerten, W. van der Bij, G. Huls, T.
Radiopharmaceuticals
Kwee, A. Glaudemans;
University Medical Center Groningen, Groningen, NETHERLANDS. Wednesday, October 16, 2019, 8:00 - 9:30 Auditorium

Aim/Introduction: One of the most dire complications of OP-696


hematopoietic stem cell (HSCT) and solid organ transplantation PET Radiopharmaceuticals of Recent Years from a
(SOT) is the development of post-transplant lymphoproliferative Radiopharmaceutical Chemist’s Perspective
disorder (PTLD). PTLD compromises a broad spectrum of A. Windhorst;
disorders classified by the 2017 World Health Organization (WHO) VuMc, Amsterdam, NETHERLANDS.
in non-destructive, polymorphic, monomorphic and classic
Hodgkin lymphoma. Distinct morphologies are associated with
a more favorable clinical course and better response to initial OP-697
treatment. Reduction of immunosuppression, commonly used Current Value of PSMA-Targeting Ligands in Diagnostic
as first-line treatment, has been associated with higher response and Therapeutic Nuclear Medicine
rates in non-destructive and polymorphic PTLD, while a more C. Kratochwil;
aggressive therapy is advised for monomorphic PTLD. Biopsy Heidelberg University Hospital, Heidelberg, GERMANY.
is the reference standard for PTLD diagnosis and classification,
but may not always be safely possible. Therefore, there is a need
for non-invasive imaging-based tools. Materials and Methods: OP-698
All patients with histopathologically proven PTLD at the UMC Established, Emerging and Future Radionuclides - Which
Groningen were included in this study between January will we use in 2030?
2010 to March 2019. FDG-PET/CT scans were performed on a U. Köster;
Siemens Biograph mCT camera, according to EANM procedure ILL, Grenoble, FRANCE.
guidelines for tumor imaging and reconstruction parameters
compliant with EARL recommendations. Semi-quantitative
measurements (SUVmax, SUVpeak and SUVmean) were performed
using dedicated Hermes Hybrid 3D software with the “Tumor
Finder” application. Semi-quantitative measurements were
obtained from the biopsy site or in cases in which a biopsy was
performed before the scan from the nearest lymph node in
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S268

1603 POLAND, 3Department of Endocrinology, Jagiellonian


University, Medical College, Krakow, POLAND.
EANM Symposium 26: Implementation of the
new EANM Guideline for Pulmonary Embolism
and Beyond Aim/Introduction: Cholecystokinin-2 receptors (CCK2R) are
expressed at high incidence in different tumours including
Wednesday, October 16, 2019, 8:00 - 9:30 Lecture Hall 312 medullary thyroid carcinoma (MTC), small cell lung cancer,
gastroenteropancreatic neuroendocrine tumours and others.
CCK2R based PET imaging keeps high promise to improve the
staging and follow-up of patients with persistent disease or
OP-700 recurrence. Evaluation of the CCK2R status additionally forms
Pulmonary Embolism, Clinical Probabilities, Difficulties the basis for the selection of patients for peptide receptor
and Challenges radionuclide therapy with therapeutic radionuclides. CCK2R
M. Monreal Bosch; targeting represents a highly personalised theranostic approach
Hospital Universitario Germans Trias, Badalona, Barcelona, SPAIN. for different tumours with limited treatment options. A kit for
68
Ga-labelling was developed for a new minigastrin analogue
in order to facilitate the clinical translation. Materials and
OP-701 Methods: The kit formulation was based on a new DOTA-
V/P SPECT-Performance and Gamuts. Importance of follow conjugated minigastrin analogue with site-specific amino acid
up Patients with PE substitutions in the C-terminal receptor specific sequence.
G. Schembri; The receptor affinity and targeting profile was evaluated using
University of Sydney, Nuclear Medicine and PET, Sydney, AUSTRALIA. A431 human epidermoid carcinoma cells stably transfected
with human CCK2R (A431-CCK2R) as well as mock transfected
cells (A431-mock). In displacement assays the CCK2R affinity
OP-702 of the unlabelled peptide and of the chelates with different
When should we use Hybrid Imaging? trivalent metals was analysed. The tumour uptake and
H. Verberne; pharmacokinetics of the peptide radiolabelled with Ga-68, as
Academic Medical Center, Department of Nuclear well as In-111 and Lu-177, was studied in female BALB/c nude
Medicine, Amsterdam, NETHERLANDS. mice with subcutaneous tumour xenografts. The performance
of the kit for 68Ga-labelling was tested for up to one year. First
clinical translation of PET imaging was pursued in patients with
OP-703 advanced MTC. Results: The peptide analogue with C-terminal
Importance of Ventilation SPECT for Diagnosing other amino acid substitutions displayed retained high CCK2R affinity.
Cardiopulmonary Diseases and Calculating the Total Lung The modifications in the linear peptide analogue also enhanced
Function the stability against enzymatic degradation improving the
M. Bajc; targeting properties. Rapid clearance from non-target tissue
University Hospital Lund, Department of together with highly improved tumour uptake was observed
Clinical sciences, Lund, SWEDEN. in the mouse tumour model. A tumour uptake of >20% IA/g
was observed in A431-CCK2R xenografts, whereas the uptake
in A431-mock xenografts was <1% IA/g. Labelling with Ga-68
1605 within a long-term kit storage of up to one year was carried
out with a radionuclide incorporation of 98.4±0.3% and a
M2M - Parallel Session: Radiolabelled Peptides radiochemical purity of 95.7±0.8% at preparation. Within 3 h
after preparation, a radiochemical purity of 91.4±0.7% was met.
Wednesday, October 16, 2019, 8:00 - 9:30 Lecture Hall 111 The injection of 68Ga-DOTA-MGS5 was well tolerated by the first
patient examined. Besides physiological uptake in stomach a
focal uptake was observed in the liver. Conclusion: A new highly
OP-704 specific peptide analogue targeting CCK2R was developed for
Gallium-68 labelled minigastrin analogue for high PET imaging. The successful application for PET imaging lays the
sensitivity PET imaging of cholecystokinin-2 receptor basis for the future therapeutic use. References: None.
expressing tumours
E. von Guggenberg1, M. Klingler1, P. Garnuszek2, R. Mikołajczak2, B.
Janota2, A. Hubalewska-Dydejczyk3, M. Kieć-Klimczak3, E. Przybylik- OP-705
Mazurek3, I. Virgolini1; Novel Radiolabelled CCK2R Antagonists: Design, Synthesis
1
Department of Nuclear Medicine, Medical University and In Vitro Evaluation
of Innsbruck, Innsbruck, AUSTRIA, 2Radioisotope Centre D. Novak1,2, M. Anderluh2, R. Mansi3, T. Tomašič2, M. Krošelj1, P.
POLATOM, National Centre for Nuclear Research, Otwock, Kolenc Peitl1;
S269 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

1
University Medical Centre Ljubljana, Ljubljana, SLOVENIA, OP-706
2
University of Ljubljana, Faculty of Pharmacy, Ljubljana, One step closer to clinical translation: Notably enhanced
SLOVENIA, 3Division of Radiopharmaceutical Chemistry, localization of [111In]SG4 in CCK2R-positive xenografts in
University Hospital Basel, Basel, SWITZERLAND. mice treated with Entresto®
P. Kanellopoulos1,2, A. Kaloudi1, M. de Jong3, E. P. Krenning4, B. A.
Nock1, T. Maina1;
Aim/Introduction: The cholecystokinin-2/gastrin receptor 1
Molecular Radiopharmacy, INRASTES, NCSR “Demokritos”,
(CCK2R) is (over)expressed in several tumour types and therefore Athens, GREECE, 2Molecular Pharmacology, School of Medicine,
represents a suitable target for the development of the University of Crete, Heraklion, GREECE, 3Department of Radiology
radiolabelled ligands. To bypass the possible adverse pentagastrin & Nuclear Medicine, Erasmus MC, Rotterdam, NETHERLANDS,
test-like effects of currently evaluated CCK2R agonists, we 4
Cyclotron Rotterdam BV, Erasmus MC, Rotterdam, NETHERLANDS.
considered the transition to antagonists (CCK2R-ANTs),
supported by the fact that the agonist-induced internalization
is not required for successful imaging. The low molecular weight Aim/Introduction: We have recently proposed the
antagonist Z-360 offers a solid base for the development of administration of the neprilysin (NEP) inhibitor phosphoramidon
radiolabelled CCK2R-ANTs due to its subnanomolar affinity and (PA) to increase the in vivo stability and tumor targeting
high selectivity for CCK2R1. The aim of the present study was to of biodegradable peptide radiotracers. This methodology
design, synthesize and evaluate novel DOTAconjugated CCK2R- turned out to be very effective in stabilizing radiolabeled des-
ANTs, followed by comparison to the selected agonist CP04 Glu6-10 gastrin analogs in peripheral mouse blood, leading
(DOTA-(D-Glu)6-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2) in in vitro to remarkable enhancement of radiotracer uptake in CCK2R-
pre-clinical studies. Materials and Methods: Structurebased expressing xenografts while renal accumulation remained
in silico drug design using the calculated homology model favorably low. Translation of this promising concept in the clinic
of CCK2R (PDB code: 2RH1) was applied to define the optimal requires the use of a NEP-inhibitor that is safe and effective.
distance between the targeting (Z-360) and the chelate (DOTA) In the present study, we investigated the biological profile of
moieties. A series of 10 compounds with different hydrophilic [111In]SG4 ([111In-DOTA,Nle15]MG11) in mice bearing CCK2R-
spacers were synthesized manually on solid phase, while positive tumors treated with the FDA approved drug Entresto®
DOTA coupling was performed in solution. After purification compared to non-treated controls. Materials and Methods:
by RP-HPLC, the compounds were characterized by ESIMS [111In]SG4 was injected in healthy Swiss albino mice without
and analytical RP-HPLC. The inositol monophosphate-based or with co-injection of the NEP-inhibitor sacubitrilat (0.3 mg
functional assay (IPOne®) on A431CCK2R+ cell line was used sacubitrilat/kg body weight); a third mice group received
for screening and SAR optimization of the (DOTA)conjugates orally a slurry of the FDA-approved drug Entresto® (containing
and their corresponding cold-labelled compounds. LogD 50 mg of the sacubitrilat-prodrug sacubitril/kg body weight)
experiments on radiolabelled CCK2R-ANTs were performed by by gavage 30 min in advance. Blood samples collected 5 min
shake-flask method. Selected radioligands, based on the lowest postinjection (pi) were analyzed by RP-HPLC. Biodistribution
IC50 values and optimal hydrophilicity, were chosen for protein was conducted in SCID mice bearing a double A431-CCK2R(+/-)
binding and serum stability studies. In vitro evaluation on A431- tumor model. [111In]SG4 was injected alone in mice 30 min
CCK2R+ cells was performed for the most promising conjugates. after gavage of Entresto®, or in untreated mice, or together with
Results: Due to the lipophilic character of Z-360, conjugates sacubitrilat; animals were sacrificed at 4 h pi and biodistribution
with hydrophilic spacers were designed. Based on the values of was conducted. For SPECT/CT mice were treated or not with
the scoring function and visual inspection of docked structures, Entresto® 30 min prior to radioligand injection and were likewise
the minimal spacer length of three amino acids was determined. sacrificed at 4 h pi. Results: While 11.5±3.2% (n=4) of [111In]SG4
All conjugates showed purities >95% and exhibited antagonistic were detected intact in peripheral mouse blood at 5 min pi,
properties assessed by the functional assay (IC50: from 0.08±0.01 by Entresto® or sacubitrilat-treatment the percentage of intact
nM to 64.9±15.7 nM). The logD values varied between -1.51±0.01 radiotracer reached 78.4±2.5% (n=3) and 72.7±2.4% (n=3),
and -2.57±0.03. Selected radiolabelled CCK2R-ANTs exhibited respectively. A likewise impact of orally administered Entresto®
high metabolic stability (>90% intact compounds at 24h) and or iv-injected sacubitrilat was observed on the uptake of [111In]
<10% of radioactivity detected in protein bound fraction. In SG4 in the A431-CCK2R(+) xenografts, which notably increased
preliminary studies, the best candidate 111InCCK2RANT1 showed at 4 h pi from 2.2±0.6%ID/g (n=3) to 9.6±1.7%ID/g (n=5) and
lower cell associated radioactivity but higher Bmax as compared 8.1±1.4%ID/g (n=3), respectively. In contrast, renal values as
to 111In-CP04. Conclusion: A series of novel radiolabelled CCK2R well as uptake in the A431-CCK2R(-) tumors remained low and
ligands with confirmed antagonistic properties was successfully unaffected by such treatment. These results could be visualized
designed, synthesized and brought to cell based in vitro by SPECT/CT. Conclusion: This study has shown that per
evaluation. Further in vitro comparison studies are on-going. os administration of the FDA-approved drug Entresto® or iv-
References: 1. Grabowska, AM. Regul. Pept. 2008; 146: 46-57. coinjection of the respective NEP-inhibitor sacubitrilat in mice
impressively improved the stability of circulating [111In]SG4.
Consequently, the radioligand localization in CCK2R-expressing
tumors was effectively enhanced whereas renal values remained
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S270

low. These results are very significant for the translation of the in- 68
Ga-JMV6659, 70.1 ± 9.7% for 68Ga-JMV6660 and 66.8 ± 25.1%
situ NEP-inhibition concept in the clinic. References: None. for 68Ga-JMV6661, whereas 68Ga-JMV6658 did not internalize.
The efflux of 68Ga-JMV6659 was 45.6 ± 1.2% at 1h, while the
other 68Ga-radiolabelled peptides showed higher efflux (60.4 ±
OP-707 7.3% - 76.2 ± 9.3% at 1h). In mice, 68Ga-JMV6659 showed urinary
Novel radiolabelled neurotensin analogues containing excretion, as well as early and unprecedented high uptake in HT-
silylated amino acid for improved neurotensin receptor-1 29 tumor beginning at 3min and reaching 7.58 ± 0.54%ID/g at
(NTS1) targeting 2h. Co-injection of neurotensin (180µg) significantly decreased
A. Chastel1,2,3, R. Fanelli4, S. Previti4, D. Vimont2,3, P. Zanotti- tumor uptake to 1.4 ± 0.7%ID/g (p<0.05). Kidneys, blood and
Fregonara5, B. Guillet6,7, P. Garrigue6,7, L. Balasse6, P. Fernandez1,2,3, E. spleen showed also NTS1-mediated uptake of 68Ga-JMV6659.
Rémond4, E. Hindié1,2,3, F. Cavelier4, C. Morgat1,2,3; Mean effective dose was 0.023 ± 0.006 mSv/MBq. Conclusion:
1
Nuclear Medecine Department, University Hospital of Bordeaux, Following introduction of silylated amino acid TMSAla, we
Bordeaux, FRANCE, 2University of Bordeaux, INCIA, UMR5287, identified 68Ga-JMV6659 as a lead compound for PET imaging
Bordeaux, FRANCE, 3CNRS, INCIA, UMR5287, Bordeaux, FRANCE, of tumors expressing NTS1 due to its very favorable properties.
4
Institut des Biomolécules Max Mousseron, IBMM, UMR-5247, References: None.
CNRS, Université de Montpellier, ENSCM, Montpellier, FRANCE,
5
Houston Methodist Research Institute, Houston, TX, UNITED
STATES OF AMERICA, 6Aix-Marseille University, INSERM, Institut OP-708
National de la Recherche Agronomique, Centre de Recherche cCPE Peptides for SPECT Imaging of Claudin-4
en Cardiovasculaire et Nutrition, Marseille, FRANCE, 7Centre Overexpression in Pancreatic Cancer
Européen de Recherche en Imagerie Médicale, Marseille, FRANCE. J. Baguna Torres1, M. Mosley1, S. Koustoulidou1, S. Hopkins1, S.
Knapp2, A. Chaikuad2, M. Kondoh3, K. Tachibana3, V. Kersemans1, B.
Cornelissen1;
Aim/Introduction: The neurotensin receptor-1 (NTS1) is 1
Radiobiology Research Institute, University of Oxford,
overexpressed in numerous cancers such as pancreatic Oxford, UNITED KINGDOM, 2Structural Genomics, University
cancer, lung cancer or breast cancer. To date, radiolabelled of Oxford, Oxford, UNITED KINGDOM, 3Graduate School of
neurotensin analogues suffer from low plasmatic stability and Pharmaceutical Sciences, Osaka University, Osaka, JAPAN.
thus insufficient availability for high uptake in tumors. We
report the development of new 68Ga-radiolabelled neurotensin
analogues with improved properties through introduction of Aim/Introduction: Overexpression of tight junction protein
silylated amino acid (DOTA-APAC-Lys-Lys-Pro-Tyr-TMSAla-Leu- claudin-4 has been detected in primary and metastatic
OH = JMV6658 and DOTA-APAC-Lys-Lys-Pro-Tyr-Ile-TMSAla-OH pancreatic cancer tissue, and is associated with better
= JMV6659) or introduction of natural amino acids (DOTA-APAC- prognosis in patients1,2. Non-invasive measurement of claudin-4
Lys-Lys-Pro-Tyr-Ile-Leu-OH = JMV6660) in the minimal bioactive expression by imaging methods could provide a means for
sequence NT[8-13]. JMV6661, based on the unmodified accelerating detection and stratifying patients into risk groups.
sequence (DOTA-APAC-NT[8-13]), serves as reference compound. Clostridium perfringens enterotoxin (CPE) is a natural ligand
Materials and Methods: Affinity of precursors JMV6658, for claudin-4 and holds potential as a targeting vector for
JMV6659, JMV6660 and JMV6661 was studied by competition molecular imaging of claudin-4 overexpression. A GST-tagged
experiment in recombinant CHO cells over-expressing NTS1. All version of the C-terminus of CPE (cCPE) was previously used
analogues were then radiolabelled with 68Ga. Plasmatic stability to delineate claudin-4 overexpression by SPECT, but showed
was determined in human plasma. Cellular uptake, efflux and modest binding affinity and slow blood clearance in vivo3.
saturation binding assays (regarding NTS1 and NTS2) were Materials and Methods: Based on the crystal structure of
performed on HT-29 cells. Finally, the most potent analogue cCPE, a series of smaller-sized cCPE194-319 mutants (S313A,
was studied in nude mice bearing HT-29 xenograft using µPET/ H194, S307A+N309A+S313A, D284A and L254F+K257D) with
CT imaging up to 2h. Biodistribution was assessed on sacrificed putatively improved binding affinity for claudin-4 were generated
animals after imaging. Estimation of human absorbed doses by site-directed mutagenesis4. All peptides were conjugated
was calculated using OLINDA/EXM software. Results: Affinity site-specifically on a C-terminal cysteine using maleimide-
of precursors JMV6658, JMV6659, JMV6660 and JMV6661 were DTPA to enable radiolabelling with 111In. The binding affinity of
4877 ± 1173 nM, 34.5 ± 1.4 nM, 1919 ± 1253 nM and 540 ± 129 all radioconjugates was evaluated in claudin-4-overexpressing
nM, respectively. Plasmatic half-lives for 68Ga-JMV6658, 68Ga- Panc-1 cells and HT1080 negative controls. The specificity of all
JMV6659, 68Ga-JMV6660 and 68Ga-JMV6661 were 10.95, 11.09, cCPE mutants to claudin-4 was assessed in hCLDN3/hCLDN4-
1.77 and 3.75 minutes, respectively. In saturation binding assays, HT1080 stably transfected cell lines. SPECT imaging of BALB/c
68
Ga-JMV6659 showed the highest NTS1-affinity and selectivity nude mice bearing Panc-1 or HT1080 xenografts was performed
(KdNTS1 = 6.29±1.37 nM, KdNTS2 = 225.5±34.0 nM), whereas 68Ga- to determine the claudin-4-targeting ability of these peptides
JMV6660 and 68Ga-JMV6661 showed only moderate affinity in vivo. Results: Uptake of all cCPE-based radioconjugates was
and selectivity for NTS1 and 68Ga-JMV6658 showed no affinity. significantly higher in Panc-1 cells compared to HT1080 negative
NTS1-mediated internalization in HT-29 cells was 61.5 ± 1.6% for controls. All peptides showed a marked improvement in affinity
S271 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

for claudin-4 in vitro when compared to 111In-cCPE.GST (Kd PET images with excellent contrast at 1 h post injection (p.i.).
values of 2.2±0.8, 3±0.1, 5.5±1.1, 8.3±2.8 and 9.4±0.5 vs. 14.8±1.3 [68Ga]Ga-ProBOMB2 was excreted primarily through the renal
nM). Blood clearance of all cCPE probes, as measured by SPECT, pathway with minimal background radioactivity accumulation
was considerably faster when compared to that of 111In-cCPE. Based on biodistribution studies, the tumor uptake of [68Ga]
GST (t1/2<2 min). All radiopeptides showed significantly higher Ga-ProBOMB2 was 10.43 ± 1.25 percent injected dose per gram
accumulation in Panc-1 xenografts than HT1080 tumours at 90 (%ID/g) at 1 h p.i., without significant normal organ uptake.
min post-injection (2.7±0.7, 2.3±0.9, 2±0.4, 2±0.2 and 6.3±0.6 Importantly, pancreas and kidney uptake remained low at 1.06
vs. 0.4±0.1, 0.5±0.1, 0.3±0.1, 0.7±0.1 and 0.7±0.1 %ID/g; P<0.01, ± 0.22 and 1.82 ± 0.26 %ID/g. The tumor-to-blood and tumor-
P<0.01, P<0.05, P<0.05 and P<0.001 respectively). Conclusion: to-muscle uptake ratios of [68Ga]Ga-ProBOMB2 were 20.31 ±
These optimised cCPE-based SPECT imaging agents show great 2.35 and 88.73 ± 46.51 at 1 h p.i.. Co-injection with the blocking
promise as claudin-4-targeting vectors for in vivo imaging of agent reduced average uptake of [68Ga]Ga-ProBOMB2 in tumors
claudin-4 overexpression in pancreatic cancer. References: 1. by 66% at 1 h p.i. Conclusion: Our data suggest that with a
Nichols et al, 2004, Am J Clin Pathol 121:226-30; 2. Tsutsumi et cationic linker, [68Ga]Ga-ProBOMB2 showed improved tumor
al, 2012, Ann Surg Oncol 19:491-99; 3. Mosley et al, 2015, J Nucl uptake and minimal normal organ uptake, particularly in the
Med 56:745-51; 4. Van Itallie et al, 2008, J Biol Chem 283(1):268- pancreas. This compound is a promising radiotracer for PET
74. imaging of GRPR expression in cancers. References: [1] Lau J, et
al. ACS Omega 2019; 4: 1470.

OP-709
The Effect of a Cationic Linker on the Pharmacokinetics of OP-710
ProBOMB2, a Novel Bombesin Derivative Evaluation of [68Ga]Ga-BL02 for Imaging the C-X-C
I. Bratanovic, C. Zhang, Z. Zhang, H. Kuo, N. Colpo, J. Pan, K. Lin, F. Chemokine Receptor 4: Leveraging a Glutamate-based
Bénard; Linker
British Columbia Cancer Research Center, Vancouver, BC, CANADA. D. Kwon1, Z. Zhang1, J. Zeisler1, C. Uribe2, C. Zhang1, J. Lau3, K. Lin1,4,
F. Benard1,4;
1
Department of Molecular Oncology, BC Cancer, Vancouver,
Aim/Introduction: Gastrin-releasing peptide receptor (GRPR), a BC, CANADA, 2Functional Imaging, BC Cancer, Vancouver,
G-protein coupled receptor, is aberrantly expressed in prostate, BC, CANADA, 3National Institute of Biomedical Imaging and
breast and lung cancers, among others, and has been targeted Bioengineering, National Institutes of Health, Bethesda, MD,
for molecular imaging with bombesin (BBN) derivatives. We UNITED STATES OF AMERICA, 4Department of Radiology,
recently developed [68Ga]Ga-ProBOMB1 [1], based on the University of British Columbia, Vancouver, BC, CANADA.
[Leu13ψAA14]BBN family, which showed faster radioactivity
clearance from background organs compared to [68Ga]Ga-
NeoBOMB1. Moderate normal organ uptake, particularly in Aim/Introduction: Based on LY2510924, a peptide targeting
the pancreas, was still observed with [68Ga]Ga-ProBOMB1. the C-X-C chemokine receptor type 4 (CXCR4), we developed
Herein, we designed ProBOMB2, a novel ProBOMB1 derivative [68Ga]Ga/[177Lu]Lu-BL01, a theranostic pair for PET imaging
with a cationic linker, radiolabeled with 68Ga, and evaluated its and radiotherapy. We hypothesized that the addition of a tri-
pharmacokinetic properties in tumor-bearing mice with positron glutamate linker between the targeting pharmacophore and
emission tomography (PET) imaging and biodistribution studies. DOTA chelator (BL02) would reduce liver uptake and promote
Materials and Methods: ProBOMB2 (DOTA-Pip-D-Phe-Gln-Trp- renal clearance. Materials and Methods: BL02 was synthesized
Ala-Val-Gly-His-Leu-ψ(CH2N)-Pro-NH2) was synthesized by solid- via solid phase peptide synthesis. A Lys(ivDde) residue was
phase peptide synthesis. A cationic 4-amino-(1-carboxymethyl) added at the C-terminus of LY2510924 (cyclo[(Phe-Tyr-Lys(iPr)-
piperidine (Pip) linker and a 1,4,7,10-tetraazacyclododecane- D-Arg-2-Nal-Gly-D-Glu]-Lys(iPr)-NH2). The ivDde protecting
1,4,7,10-tetraacetic acid (DOTA) chelator were conjugated to the group was removed with hydrazine and 3 Glu residues and a
N-terminus of the peptide sequence. Fmoc-Leu-ψ(CH2N)-Pro-OH DOTA chelator were added sequentially to the ε-amine. BL02
was synthesized in solution phase prior to solid-phase peptide was radiolabeled with [68Ga]GaCl3 and biodistribution studies
synthesis via the STAB-H mediated reductive amination of Fmoc- were performed on immunocompromised mice inoculated
leucine aldehyde with L-proline. ProBOMB2 was radiolabeled with Daudi Burkitt lymphoma cells. PET imaging studies were
with 68Ga in acetate buffer followed by HPLC purification. PET performed with [68Ga]Ga-BL02, with blocking studies performed
imaging for [68Ga]Ga-ProBOMB2 and biodistribution studies with pre-injection of LY2510924. An unpaired t-test with unequal
were performed in immunocompromised mice bearing PC-3 variances was performed using Microsoft Excel. Results: [68Ga]
prostate cancer xenografts. To verify the specificity of the tumor Ga-BL02 was synthesized with a 71±5% (n=4) radiochemical
uptake, blocking experiments with co-injection of [D-Phe6,Leu- yield, >99% radiochemical purity and 216±106 GBq/µmol (n=4)
NHEt13,des-Met14]Bombesin(6-14) were also performed. Results: molar activity. Imaging/biodistribution studies demonstrated
[68Ga]Ga-ProBOMB2 was obtained with 56% decay-corrected primarily renal clearance, with negligible liver uptake. Daudi
radiochemical yield and > 95% radiochemical purity. Using [68Ga] xenografts were clearly visualized on PET images at 1 and 2 h
Ga-ProBOMB2, PC-3 tumor xenografts were clearly visualized in post-injection (p.i.), with biodistribution data showing uptake
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S272

values of 9.14±2.95 %ID/g and 8.66±2.15 %ID/g respectively. compartment model compared to a single one as indicated by
No other organs demonstrated higher uptake. The tumour- a lower Akaike information criterion (21 ± 4 vs. 54 ± 14). Binding
to-blood, tumour-to-liver, tumour-to-spleen, and tumour- potential in obese was one-tenth (0.024395 ± 0.000523) of
to-muscle ratios at 2 h p.i. were 123.97±39.91, 15.16±2.88, that observed in lean subjects (0.2056 ± 0.00328) primarily as
39.28±16.86 and 219.05±58.12 respectively, showing agreement a consequence of reduction in K1 (0.0406 ± 0.00072 vs 0.0092
with PET images. Finally, pre-injection of LY2510924 reduced ± 0.000149 ml/ccm/min in lean vs obese). Conclusion: The use
tumour uptake by 91.6% (0.767 %ID/g at 1 h p.i.), demonstrating of 68Ga labeled GLP-1 receptor agonist allow to demonstrate a
the target specificity of [68Ga]Ga-BL02. Despite lower absolute massive down-regulation of GLP-1 receptor within the pancreas
tumour uptake at 2 h p.i. compared to [68Ga]Ga-BL01 (10.2±2.56 of obese versus lean adult pigs. While this lower binding
%ID/g and 15.3±1.86 %ID/g at 1 and 2 h p.i. (p<0.0001)), [68Ga] potential might explain the clinically reduced efficacy of GLP-1
Ga-BL02 had higher tumour-to-organ ratios at 2 h p.i. than receptor agonist, it also opens a new pharmacological avenue
[68Ga]Ga-BL01 (13.33±2.14, 1.66±0.22, 1.83±0.29 and 52.87±2.26 aimed towards weight reduction. References: (1) - Ericksson
for blood (p<0.0005), liver (p<0.0001), spleen (p<0.005) and O et al, Species differences in pancreatic binding of DO3A-VS-
muscle (p<0.0005), respectively). Conclusion: [68Ga]Ga-BL02 Cys40-Exendin4. Acta diabetes, 2017, 54: 1039-1045.
with a tri-glutamate linker demonstrates markedly enhanced
imaging properties over previously reported [68Ga]Ga-BL01 due
to improved pharmacokinetics and tumour-to-non target ratios. 1606
[68Ga]Ga-BL02 shows significant promise as a CXCR4-targeting
PET imaging agent. References: None.
Do.MoRe - Parallel Session: PET/CT & SPECT/CT
Instrumentation

OP-711 Wednesday, October 16, 2019, 8:00 - 9:30 Lecture Hall 112
Lower binding potential of GLP-1 receptor in the pancreas
as a consequence of diet-induced obesity
C. Malbert1, A. Chauvin2, F. Le Gouevec2, J. Georges2, M. Genissel2;
1
Aniscan, INRA, Saint-Gilles, FRANCE, 2UEPR, OP-712
INRA, Saint-Gilles, FRANCE. Head-to-head comparison of a Si-photomultiplier-based
and a conventional photomultiplier-based PET-CT system
J. Oddstig1, G. Brolin1, E. Trägårdh2, D. Minarik3;
Aim/Introduction: GLP-1 receptor agonists are capable 1
Radiation Physics, Lund, SWEDEN, 2Clinical
of effective weight reduction in obese subjects. However, Physiology and Nuclear Medicine, Malmö, SWEDEN,
the weight loss in response to treatment is heterogeneous 3
Radiation Physics, Malmö, SWEDEN.
depending on BMI. This might be the consequence of a lower
GLP-1 receptor density since the reduced expression of the
receptor has been already demonstrated at the vascular level in Aim/Introduction: Recently, a novel generation of PET-
obese. This study aimed to evaluate the hypothesis of lower GLP- scanners, based on silicon (Si)-photomultiplier (PM) technology,
1 receptor density in obese vs. lean using a preclinical model of was introduced. Concurrently, there has been a development
diet-induced obesity. Materials and Methods: GLP-1 receptor of new reconstruction methods, with the aim of increasing
density was quantified in the pancreas of 16 adult miniature pigs, the detection of small lesions without increasing the noise
eight being obese (80 ± 5 kg) while the remaining lean (42 ± 3 level. The combination of new detector technology and new
kg). PET-CT (Discovery ST, GE) dynamic imaging was performed reconstruction algorithms have been found to increase image
for one hour in anesthetized animals after the IV administration quality. However, it is currently unknown to what extent the
of [68Ga]Ga-DO3A-VS_Cys40-Exendin-4 (1), (7 ± 4.2 MBq; 0.1 improved image quality is due to hardware improvements or
µg/kg). The radiolabelled compound was produced using an improved reconstruction algorithms. The aim of this study was
automated GRP synthesizer (Scintomics - GRP series 2013), and to compare the ability to detect small hotspots in phantoms
quality control was performed with UV-radioHPLC. Input arterial using a SiPM-based (GE Discovery MI) and a conventional
function was continuously recorded using an extemporaneous PM-based PET-CT scanner (GE Discovery 690), with identical
external arterial -venous loop between the femoral artery and reconstruction protocols in order to isolate the properties of the
the saphenous vein. Abdominal organs VOIs were drawn from hardware. Materials and Methods: Two different phantoms
CT and PET images using ITK-snap software. Pancreas PET data (NEMA-body and Jasczcak) with small fillable spheres (31µl-
were fitted to a single and two tissues compartment models 26.5ml) and different sphere-to-background ratios (SBR) were
using Pmod software, and binding potential was calculated scanned in one bed position of 10minutes on both scanners.
as the ratio between K1*k3 and k2*k4. Results: [68Ga]Ga-DO3A- The acquired data were rebinned into sinograms corresponding
VS_Cys40-Exendin-4 showed a clear pancreatic uptake in lean to different acquisition durations (15s - 600s) and reconstructed
animals but the difference in uptake between the pancreas using identical reconstruction parameters on both scanners.
and the other abdominal organs was less in obese. The fitting ROI were drawn in all images in spheres and in background.
of the time-activity curve is more accurate with a two tissues The recovery coefficient (RC) and spherepeak/backgroundpeak-
S273 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

value were calculated and compared between the scanners. mediastinal lesion on the phantom studies and on the clinical
The detectability of each sphere at each acquisition time was scans where there was more confident detection of small sites
graded on a three-level scale: clearly visible (2), visible but not of disease. For 68Ga-PSMA studies when there were high SUVs
distinguishable from background noise (1), and not visible (0). in the kidneys and bladder there was a more marked artefact on
The sensitivity was calculated as the sum of the scores divided the Vision 600 that was not corrected by the prompt gamma and
with the highest possible score. Results: RC-curves for the NEMA scatter correction. Conclusion: The Biograph Vision has superior
body phantom was near-identical for both scanners at SBR 10:1 image quality at a lower injected activity when compared to the
and acquisition times 90-600s. For smaller spheres (31-500µl) mCT for FDG whole body PET-CT scans. Image quality, however,
in the Jaszczak phantom, the sphere/background-ratio was for 68Ga-PSMA scans was inferior to the mCT when tracer
1.22 higher for the MI scanner at SBR 15:1. The ratio decreased excretion was high which suggests further optimisation of the
for lower SBR, with a ratio of 1.03 at SBR 3.85:1. Regarding the reconstruction parameters are required. References: None.
detectability of spheres, the sensitivity was 99% and 97% for the
MI and 690, respectively, for SBR 15:1. For SBR 7.5, the sensitivity
was 91% and 96% for the MI and 690, respectively. For SBR 3.85:1, OP-714
the sensitivity was 68% and 62% for the MI and 690, respectively. Continuous Bed Motion Acquisition for Clinical PET
Conclusion: Marginally better detectability in small spheres at Systems With a Sparse Block Rings Configuration
low noise levels was seen for the SiPM-based scanner but the N. A. Karakatsanis, S. A. Zein, S. A. Nehmeh;
difference was smaller at higher noise levels. It was difficult to Weill Cornell Medical College, New York,
detect differences between the scanners, suggesting that the NY, UNITED STATES OF AMERICA.
SiPM-based detectors are not the primary reason for improved
image quality. References: None.
Aim/Introduction: To implement continuous bed motion
(CBM) acquisition for clinical PET systems with sparse block
OP-713 rings configuration, and assess its value on image quality (IQ).
Comparison of Siemens Biograph Vision 600 and Biograph Materials and Methods: The Siemens BiographTM mMR is a
mCT PET-CT scanners clinical PET/MR scanner consisting of 8 compact block rings
S. Eberl, J. Verschuer, A. Waugh, A. Hughes, M. J. Fulham; with 3.2cm axial block dimension and 25.8cm axial field-of-view
Royal Prince Alfred Hospital, Sydney, AUSTRALIA. (AFOV). List-Mode PET data of the NEMA IQ phantom with 4:1
spheres-to-background ratio were acquired for 30min. A sparse
block rings configuration (sparse-mMR) was adopted by setting
Aim/Introduction: Our aim was to compare the latest to zero all counts measured at detector pair positions associated
generation Siemens Biograph PET-CT, the SiPMT-based Vision with at least one even block ring. Sparse CBM acquisitions with
600, to the previous generation, traditional PMT-based Biograph constant speeds were implemented along an axial distance of
mCT. Materials and Methods: We used the Biograph Vision two blocks (16 detector rings, 6.4cm) to compensate for the axial
600 Edge (128-slice CT) with an axial PET FOV of 26 cm and the gaps. Sparse CBM acquisitions were simulated by axially shifting
Biograph mCT (128-slice CT) with a PET axial FOV of 21 cm. We the stationary mMR projection data by a different number of
compared: i) NEMA NU-2 acceptance tests, ii) Hoffman brain detector rings each time, from 0 (reference axial position) to 15,
phantom acquisitions, iii) SNMMI chest phantom acquisitions then removing the counts associated with even block rings at
and, iv) clinical image quality for patients who had scans on both each shifted position and shifting back the sparse data to the
scanners, using 18F-FDG / 68Ga-PSMA / 68Ga-Dotatate, within a reference position. This process was repeated for all 16 positions
3-month period. All FDG PET-CT scans were done using a FDG- and the corresponding output data were added to produce the
dose based on BMI and scanner sensitivity. All acquisitions were sparse CBM sinogram. The input data for each step was sampled
undertaken using continuous bed motion (CBM). Bed speed, CT from independent PET lists corresponding to 16 different
parameters and PET reconstructions were identical /matched periods of equal duration. Sparse-mMR CBM data of 304, 608,
for both scanners; ‘matched’ since the Biograph Vision is limited 912 and 1216 seconds and the respective PET image quality
to 5 subsets. Hence we used 16 iterations 5 subsets on the Vision metrics were compared against that achieved with stationary
600 and 4 iterations 21 subsets on the mCT. Results: The Vision 304sec acquisitions using the mMR and a compact-½mMR
600 Edge had a sensitivity of 15.2 cps/kBq when compared to configuration. The latter included only the 4 central block rings.
9.44 cps/kBq for the mCT which was 1.6 times higher hence All PET data were reconstructed with 3D-OSEM (1 iteration, 21
the injected dose of FDG was reduced by a factor of 1.6. FWHM subsets, 4mm FWHM Gaussian post-filtering, no Time-of-Flight)
transverse resolution @10cm was 5.0 mm for the mCT and 4.2 using the component-based normalization factors of each
mm for the Vision 600. In the clinical activity range, the NECR at configuration. Results: In all images, no artifacts were observed,
the same activity was 1.6 times higher for the Vision 600 and the and all spheres were detected. Contrast recovery differences
activity required to achieve same NECR was a factor of about 2 between the three scanner configurations were within 7% for
lower on the Vision 600. The TOF resolution was 217 ps for the 304sec scans. The image background variability for 304sec scans
Vision 600 and 530 ps for the mCT. There was improved image increased on average from 4.03% for mMR to 6.80% and 7.60%
quality in the cortical gyri, posterior fossa nuclei and central for the compact-½mMR and sparse-mMR with CBM, respectively.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S274

A 4.12% background variability was achieved with the sparse has interesting applications for molecular imaging research: by
configuration for 1216sec scans. Image noise uniformity across translating the patient head to the middle of the system, brain
the AFOV subscribed by the compact-½mMR was superior in scans can be performed with very high resolution, sensitivity
mMR and sparse-mMR CBM images relative to compact-½mMR. and with simultaneous body imaging. The system has very high
Conclusion: CBM compensates for the gap effects in the axial resolution, high sensitivity and is adaptive so it can outperform
sensitivity of PET systems with sparse block rings configurations and replace organ specific PET systems, making it a general-
thereby improving uniformity in image noise and detectability purpose PET system. References: None.
across the AFOV. References: None.

OP-716
OP-715 Digital SPECT: Collimator Design and CZT Crystal
PET2020 HRS: Maximization of sensitivity and resolution Thickness Affect General Purpose Solid State Camera
using axial extension and patient adaptive rings in a high Characteristics Facilitating Dual Isotope 99mTc/123I
resolution long axial FOV scanner Quantitation
S. Vandenberghe1, M. Geagan2, N. Efthimiou3, M. Stockhoff1, C. J. Kennedy1,2, R. Lugassi1, Z. Keidar1,2;
Thyssen1, M. Akl1, V. Keereman1, C. Vanhove1, M. Koole4, R. Van 1
Rambam - Health Care Campus, Haifa, ISRAEL, 2B.
Holen1, J. Karp2; and R. Rappaport School of Medicine, Technion –
1
Universiteit Gent, Ghent, BELGIUM, 2University of Pennsylvania, Israel Institute of Technology, Haifa, ISRAEL.
Philadelphia, PA, UNITED STATES OF AMERICA, 3University of
Hull, Hull, UNITED KINGDOM, 4KU Leuven, Leuven, BELGIUM.
Aim/Introduction: To compare the characteristics of a digital
general purpose solid state cadmium zinc telluride (CZT)
Aim/Introduction: We propose a whole-body imager SPECT/CT camera (CZTC), for three hardware configurations, to
with transformable geometry that allows optimal detector a standard SPECT sodium iodide camera (NaIC), and to compare
positioning and has superior spatial resolution and sensitivity dual isotope 99mTc/123I quantitation. Materials and Methods:
for a reasonable number of detectors. The proposed European Spatial resolution, sensitivity, and energy resolution were
PET system (PET2020) is based on high resolution monolithic compared for CZTC (Discovery 670 CZT) and NaIC (Discovery
detector technology and has in standard mode a 70-cm 670). CZTC comprised 5 mm thick CZT crystals with 50 mm
transverse diameter and axial FOV of 70 cm, optimized for long collimator holes (CZTC50). Reconfigurations gave 45 mm
cost, single organ and high throughput body scan imaging. long collimator holes (CZTC45) and then the same with 7.25
Here we present an additional upgrade or research mode mm thick CZT crystals (CZTC7p25). Additional spatial resolution
(High Resolution Sensitivity, HRS) for this system with axial measurements beyond National Electrical Manufacturers
and transverse adaptation by linear motors and advanced Association (NEMA) methods included using an adaptive filter
mechanics. Materials and Methods: To accommodate the for CZTC and acquiring at distances 0 to 24 cm from each
increasing interest in total body imaging research, we depart detector. Dual isotope 99mTc/123I SPECT images of a Jaszczak
from the fixed diameter ring design of most PET systems. The first phantom with an Esser lid were acquired on CZTC7p25 and
step is an axial extension of the 70 cm long scanner into a 140 NaIC for a 40 kBq/mL background radiotracer concentration and
cm long scanner (without any additional detectors). By splitting target-to-background ratios of 8:1 for the hot vials. The phantom
each initially fully populated ring into two half-populated acquisitions were repeated for separate 99mTc and 123I single
rings (even or odd detectors), gaps are evenly spread over thr tracer acquisitions and standardized uptake values (SUV) were
detector surface. The additional advantage of this design is that compared. Results: The CZTC7p25 planar sensitivity (84.8 cps/
the gaps enable to reduce the bore diameter to a radius of 35 MBq per head) was superior to NaIC (75.9 cps/MBq), CZTC45
cm per detector ring. The proposed mechanics for this adaptive (70.5 cps/MBq), and CZTC50 (56.6 cps/MBq). The NEMA spatial
ring system is one motor per ring driving one mechanical resolution for CZTC7p25 (7.1±0.1 mm) was comparable to NaIC
aperture (similar to the shutter mechanism in optical cameras), (7.3±0.1 mm). The spatial resolution of CZTC7p25 was superior
on which the detectors are mounted. Results: Even for 50 % to NaIC for distances within 11 cm of the detector head, giving
gaps in the 140 cm configuration with 70 cm diameter, results 2.5±0.2 mm and 4.0±0.1 mm respectively at closest approach.
show that there is sufficient redundancy to obtain high quality Measured with an adaptive filter, the spatial resolution of CZTC45
data with iterative reconstruction methods. By adapting to (5.3±0.1 mm), CZTC50 (5.6±0.4 mm), and CZTC7p25 (5.9±0.1
the closest circle enclosing the patient, resolution is improved mm) were comparable. The energy resolution of CZTC50 (5.6
(less acolinearity) and the sensitivity is further enhanced. In %), CZTC45 (5.5 %), and CZTC7p25 (5.4 %) were all superior to
the limit of a completely closed 35 cm diameter system with NaIC (9.2 %). The SUV of the largest hot vials of the dual isotope
140 cm axial length, the sensitivity will be even higher than a 99m
Tc image was 8.7 g/mL for both CZTC7p25 and NaIC, with a
2m long PET system as it has a larger solid angle. In this mode, background of 1.6 g/mL instead of 1.0 for both. The 60 % extra
an isotropic (DOI information) spatial resolution of 1.5 mm is background counts were attributable to down-scatter from the
expected over the complete field-of-view as acolinearity will 123
I energy window. In the dual isotope 123I image, 4 % extra
have a smaller contribution. Conclusion: The adaptive design counts were attributable to the 99mTc energy window for NaIC
S275 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

and <0.2 % for CZTC7p25. Conclusion: Decreasing collimator nucleus, clearly superior to LEHRHS SPECT. Conclusion: MPH
hole length and increasing CZT crystal thickness substantially DAT SPECT provides improved count sensitivity and striatum-
improved the sensitivity of a clinical digital SPECT camera to-background contrast recovery compared to DAT SPECT with
without significantly degrading its spatial resolution or energy parallel-hole and fan-beam collimators. Improved sensitivity
resolution, and provided no crosstalk into the 123I image for dual opens the possibility to reduce scan time and/or tracer dose.
isotope 99mTc/123I quantitation. References: None. References: None.

OP-717 OP-718
Performance Evaluation of a Novel Multi-Pinhole Evaluation of general-purpose CZT SPECT/CT scanner for
Collimator for Dopamine Transporter SPECT dual-isotope parathyroid imaging
K. Tecklenburg, I. Apostolova, S. Klutmann, R. Buchert; T. E. Noponen1,2, R. Hirvilammi2, M. Seppänen2, V. Tunninen3;
University Medical Center Hamburg- 1
Department of Medical Physics, Turku University Hospital,
Eppendorf, Hamburg, GERMANY. Turku, FINLAND, 2Department of Clinical Physiology
and Nuclear Medicine, Turku University Hospital, Turku,
FINLAND, 3Department of Clinical Physiology and Nuclear
Aim/Introduction: There is a general tradeoff between count Medicine, Satakunta Central Hospital, Pori, FINLAND.
sensitivity (-> statistical noise) and spatial resolution (-> contrast
recovery) in conventional SPECT associated with photon
collimation using parallel-hole or fan-beam collimators. Multi- Aim/Introduction: Dual-isotope SPECT/CT with 99mTc-
pinhole (MPH) collimator technology, very successful in small sestamibi and 123I is highly sensitive and specific for parathyroid
animal SPECT, has potential for concurrent improvement of scintigraphy for the localization of hyperfunctioning parathyroid
count sensitivity and contrast recovery also in clinical SPECT adenomas. Cadmium zinc telluride (CZT) gamma-camera
of ‘small’ organs. This study evaluated a novel MPH collimator provides a superior energy resolution compared to conventional
specifically designed for clinical dopamine transporter (DAT) NaI(Tl) scintillator camera, which can be especially beneficial
SPECT. Materials and Methods: The 3-dimensional count in the dual-isotope imaging of 99mTc and 123I. We studied the
sensitivity profile of a triple head SPECT system (Mediso capabilities of CZT SPECT camera on parathyroid imaging
AnyScan® TRIO) equipped with the MPH collimator was using a synthetic thyroid-parathyroid phantom. Materials
measured with a Tc-99m point source placed on the lattice and Methods: A standard Jaszczak phantom including a
points of a 1 cm grid covering the whole field-of-view (FOV). thyroid-parathyroid insert was used. The synthetic thyroid
Measurements of an anthropomorphic striatum phantom was eccentrically attached in the middle of phantom. On the
were performed with varying striatum-to-background activity thyroid surface, four synthetic spherical parathyroid adenomas
concentration ratios. MPH projection data were reconstructed with the inside diameter of 7.9, 6.2, 5.0 and 4.0 mm were taped.
using the iterative reconstruction algorithm (TeraTomo™) of All adenomas had the 99mTc activity concentration of 2.1 Mbq/
the SPECT system software with default parameter settings for ml and the thyroid 99mTc concentration of 451.0 kBq/ml and
patient scans. Recovery of the striatum-to-background (S/B) 123
I concentration of 395.6 kBq/ml. The background activity
contrast was assessed by the contrast recovery coefficient concentration was 36.2 kBq/ml. The phantom was scanned
(CRC = (measured S/B - 1) / (true S/B - 1)). Count sensitivity and using standard clinical protocols with Discovery NM/CT 670
phantom measurements were also performed with a 2-head CZT camera (GE Healthcare, Tirat Hacarmel, Israel) and with
SPECT system with LEHRHS collimators (filtered backprojection) Symbia T6 SPECT/CT camera (Siemens Healthineers, Erlangen,
and fan-beam collimators (OSEM reconstruction with ENC- Germany). Energy windows in Symbia were 140 keV ± 5.0% for
DAT settings). Finally, a patient referred to DAT SPECT because 99m
Tc and 159.0 ± 5.0% for 123I and in CZT 139.7 keV ± 7.3% for
of suspicion of Parkinson’s disease was scanned with both the 99m
Tc and 160.4 keV ± 6.5% for 123I. The Lister program of Xeleris
2-head LEHRHS and the 3-head MPH system. Results: The 4.0 server (GE Healthcare) was used to regenerate the CZT
FOV of the 3-head MPH system is shifted about 8 cm towards data sets with the ±3% energy windows. A SPECT subtraction
the patient to simplify positioning. Nevertheless, the MPH software (Hermes Medical Solutions, Stockholm, Sweden)
sensitivity profile is almost symmetrical around its peak. Total was employed to remove the thyroid background activity
sensitivity in the peak is 620 cps/MBq compared to 225 cps/ from the reconstructed parathyroid 99mTc-image utilizing the
MBq and 190 cps/MBq for the 2-head fan-beam and LEHRHS reconstructed thyroid 123I-image. Finally target-to-background
system, respectively. Sensitivity of the MPH system decreases ratios (TBRs) were calculated from the subtracted parathyroid
towards the edges of the FOV. The full width of the sensitivity adenoma images. Results: CZT camera provided higher TBRs for
profile at 200 cps/MBq is 21 cm (transaxial) and 11 cm (axial), all sizes of parathyroid adenomas when compared with Symbia
which requires precise patient positioning in the FOV. Average images. When images scanned with a standard protocols and
contrast recovery in putamen (left/right) is 0.74 with MPH reconstructed with a FWHM = 7 mm post-filter were compared,
SPECT, 0.56 with fan-beam SPECT and 0.48 with LEHRHS SPECT. the adenomas of CZT images had 38,1 - 46,1% higher TBRs than
The patient scan demonstrates very good image quality of MPH those of Symbia images. In the regenerated CZT images with
SPECT with almost PET-like delineation of putamen and caudate the ±3% energy windows, the TBRs were 67,6 - 94,9% higher
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S276

compared to Symbia images. When the FWHM = 3-mm post- varying the slant angle from 0° to 45°. The measured IC and CNR
filtered images were compared, adenomas scanned with CZT of GT reconstructed images demonstrated that it was possible
have 68,9 - 125,1% higher TBRs than the adenomas scanned to obtain significant imaging improvement compared to SPECT.
with Symbia. Conclusion: The general-purpose CZT scanner Conclusion: The proposed GT based SHCS demonstrated the
with high energy-resolution can produce the subtraction potential for superior spatial resolution and contrast compared
SPECT images with much higher TBRs than conventional NaI(Tl) to conventional SPECT acquisition. Differently from the currently
scanner. CZT scanner performance even improves when its used SPECT, a conventional gamma camera equipped with
energy windows are made narrower. References: None. the SHCS could be located in a fixed position at the minimum
distance from the patient, thus improving detection, localisation
and characterisation of sub-centimetre lesions. References:
OP-719 None.
Slant-hole collimation system for high-resolution
molecular imaging gamma tomosynthesis
M. Longo1,2, R. Pani3, R. Pellegrini4, M. Cinti4, V. Frantellizzi4, G. De 1607
Vincentis3;
1
Sapienza University of Rome, Ph. D. Program in Morphogenesis
Pitfalls & Artefacts 7 - Interactive Clinical Cases
& Tissue Engineering, Rome, ITALY, 2Arcispedale Sant’Anna
- Oncology & Theranostics Committee: NET
Hospital, Medical Physics Unit, Ferrara, ITALY, 3Department of
Imaging ? Multiple Endocrine Neoplasias (MEN)
Radiological Sciences, Oncology and Anatomical Pathology,
Sapienza University of Rome, Rome, ITALY, 4Department of Wednesday, October 16, 2019, 8:00 - 9:30 Lecture Hall 113
Molecular Medicine, Sapienza University of Rome, Rome, ITALY.

OP-720
Aim/Introduction: It is well known that without the ability to Genomics of MEN - Diagnostic Strategy and Pitfalls
detect small lesions, indicative of early stage disease, molecular M. North;
imaging technique has limited clinical utility. This study Hôpital Cochin AP-HP, Service de Génétique et
investigates a novel gamma tomosynthesis (GT) method based Biologie Moléculaires, Paris, FRANCE.
on a slant-hole collimation system (SHCS) which, mounting
to a conventional gamma, is able to perform high-resolution
three-dimensional imaging. This study aims to evaluate the OP-721
sensitivity, spatial resolution and imaging potentials of the Imaging MEN 1
SHCS with clinical gamma camera and breast phantom and J. Talbot;
to compare the system with conventional SPECT imaging. Hôpital Tenon AP-HP & Sorbonne Université,
Materials and Methods: The SHCS has the remarkable feature Médecine Nucléaire, Paris, FRANCE.
to be modular, consisting of independent collimation elements
able to tilt according to variable angles [−45° to +45°]. The SHCS
allows to acquire planar images at different angles which are OP-722
then reconstructed using the Shift And Add (SAA) method. The Imaging MEN 2
proposed collimator and reconstruction methodology were S. Balogova;
validated through experimental measurements using the SHCS St.Elisabeth Oncology Institute, Comenius University of
on a clinical gamma camera. Spatial resolutions were measured Bratislava, Nuclear medicine, Bratislava, SLOVAKIA.
in reconstructed GT images of a point source at different source-
to-collimator distances, while sensitivity was evaluated over the
range of slant angles using a disk source. Image contrast (IC) and 1608
contrast to noise ratio (CNR) of sub-centimeters tumors were
evaluated using a breast phantom containing a background
Clinical Oncology - Featured Session: Prostate
activity and two spheres filled with 99mTc to simulate lesions
Translational
at two depths. GT images of the breast phantom were also
compared with those obtained with a circular-orbit scan SPECT Wednesday, October 16, 2019, 8:00 - 9:30 Lecture Hall 114
acquisition. Results: The proposed system allows to reach planar
spatial resolutions ranging from 9 to 14 mm over a depth range
of 6-10 cm; spatial resolution in the depth dimension becomes OP-723
two times greater than the other two dimensions. The gamma Scientific Programme
tomosynthesis has an average spatial resolution better than that F. van Leeuwen;
resulted from circular-orbit SPECT scan where spatial resolutions Leiden University Medical Center, Interventional Molecular
are always restricted between 20 and 30 mm. The measured Imaging Laboratory, Leiden, NETHERLANDS.
sensitivity decreased from approximately 9 cps/μCi to 6 cps/μCi
S277 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

OP-724 OP-725
Bispecific anti-GRPR/PSMA heterodimer for PET and SPECT Introduction of an amylase cleavable linker to PSMA-617 -
diagnostic imaging of prostate cancer a novel strategy for the reduction of salivary gland uptake
B. Mitran1, Z. Varasteh2, E. Puuvuori1, A. Abouzayed1, S. S. Rinne1, V. in endoradiotherapy of prostate cancer
Tolmachev1, M. Larhed1, U. Rosenström1, A. Orlova1; A. Baranski1,2, T. Lindner3, R. Tönnesmann1,2, P. T. Meyer1,2, W. Mier3,
1
Uppsala University, Uppsala, SWEDEN, 2Technische M. Eder1,2;
Universität München, München, GERMANY. 1
Department of Nuclear Medicine, University Medical Center
Freiburg, Faculty of Medicine, University of Freiburg, Freiburg
im Breisgau, GERMANY, 2Division of Radiopharmaceutical
Aim/Introduction: Prostate Specific Membrane Antigens Development, German Cancer Consortium (DKTK), partner site
(PSMA) and Gastrin-Releasing Peptide Receptors (GRPR) are Freiburg, and German Cancer Research Center (DKFZ), Heidelberg,
well-validated biomarkers that are overexpressed in most Freiburg im Breisgau, GERMANY, 3Department of Nuclear
prostate cancers (PCa). Given the complexity and heterogeneity Medicine, Heidelberg University Hospital, Heidelberg, GERMANY.
of PCa, targeting both receptors using bispecific radiotracers
could improve the diagnostic accuracy and therapeutic
outcome. The aim of this study was to develop a GRPR-PSMA Aim/Introduction: The treatment with alpha- or beta-emitter
bispecific heterodimer for SPECT and PET imaging of PSMA and labeled PSMA-617 represents a promising approach in the clinical
GRPR expression in PCa. Materials and Methods: Bispecific management of metastasized, hormone-refractory prostate
anti-GRPR/PSMA dimer NOTA-DUPA-RM26 was produced using cancer. However, the concomitant irradiation of salivary glands
a combination of solid-phase and manual peptide synthesis and remains the main dose-limiting side effect thereby significantly
was labeled with 111In and 68Ga. The heterodimer was evaluated reducing patient’s quality of life. Thus, strategies minimizing
towards stability, targeting specificity, binding affinity, and the salivary gland uptake of PSMA-617 are urgently needed.
cellular processing on PC3pip cell line expressing both PSMA Materials and Methods: After introduction of the amylase
and GRPR. In vivo specificity was studied 1 h pi in mice bearing cleavable linker to PSMA-617, the PSMA-binding properties of
PC3pip xenografts. Biodistribution was studied 1, 3 and 24 h pi the novel compound were analyzed by competitive binding and
for 111In-NOTA-DUPA-RM26, or 1 and 3 h pi for 68Ga-NOTA-DUPA- internalization experiments in human PSMA expressing LNCaP
RM26. Tumor uptake was confirmed by preclinical SPECT/CT cells. To further investigate the cleavability of the linker in vitro
and PET/CT imaging. Results: The heterodimer was successfully the 177Lu-labeled compound was incubated in the presence of
labeled with 111In and 68Ga with radiochemical yields exceeding α-amylases. Biodistribution and µPET studies were performed in
99% for 111In and 98% for 68Ga. The radiolabeled heterodimers LNCaP tumor-bearing mice (BALB/c nu/nu) to determine first
demonstrated high stability and retained binding specificity to data on tumor uptake and pharmacokinetic properties. Results:
PSMA and GRPR. Cellular processing assay revealed a low degree The cleavable derivative of PSMA-617 retained high binding
of internalization for 111In-NOTA-DUPA-RM26. IC50 values for affinity, specific cell uptake and was effectively internalized into
nat
In-NOTA-DUPA-RM26 were 4±1 nM towards GRPR and 0.4±0.2 the PSMA expressing cell line LNCaP. The cleavability of the linker
µM towards PSMA. In vivo binding specificity tests performed was proven by in vitro enzymatic cleavage using α-amylases
at 1h pi revealed partially blockable tumor uptake when co- isolated from human salivary gland. In first in vivo studies
injected with excess of either PSMA- or GRPR-targeting agents. the tumor uptake and pharmacokinetic profile of the novel
A pronounced blocking effect was observed for 111In and 68Ga- modified compound showed only minor changes compared to
labeled heterodimer when co-injected simultaneously with PSMA-617 at 1 h and 4 h p.i.. Conclusion: The introduction of
PSMA- and GRPR-targeting agents. Biodistribution over time an amylase cleavable linker to PSMA-617 was accompanied by
revealed a fast clearance of radioprobes from blood and normal only minor impact on the binding properties, tumor uptake and
organs via renal excretion. Tumor uptake exceeded the uptake the pharmacokinetic characteristics. As the amylase cleavability
in all normal organs including excretory organs for both 111In of the novel compound was shown in the presented in vitro
and 68Ga-labeled analogs at 1h pi. Interestingly, 68Ga-NOTA- proof-of-concept, further studies need to investigate the related
DUPA-RM26 had a significantly lower tumor uptake (8±2%ID/g) in vivo properties. The first preclinical data on a cleavable
compared to 111In-NOTA-DUPA-RM26 (12±2%ID/g), but a two- derivative of PSMA-617 emphasize the potential of this strategy
fold higher uptake in liver at 1h pi. The faster clearance of to minimize dose-limiting side effects for an improved therapy
radioactivity from normal tissues compared to tumor lead to of prostate cancer. References: None.
an overall increase in tumor-to-organ ratios for both 111In and
68
Ga-labeled analogs at 3h pi. At 24h pi, however, tumor-to-
organ ratios decreased for 111In-NOTA-DUPA-RM26. MicroPET/ OP-726
CT and microSPECT/CT scans confirmed the ex vivo data. 68
Ga-RM2 PET/CT in Patients with Newly Diagnosed
Conclusion: Anti-GRPR/PSMA dimer NOTA-DUPA-RM26 labeled Intermediate- or High-Risk Prostate Cancer
with galium-68 (for PET) and indium-111 (for SPECT) is a suitable A. Iagaru, L. Baratto, H. Duan, N. Hatami, C. Mari, G. Davidzon;
candidate for imaging of GRPR and PSMA expression in PCa Stanford University School of Medicine, Stanford,
already at 1h pi. References: None. CA, UNITED STATES OF AMERICA.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S278

(PCa) patients. Materials and Methods: Between January


Aim/Introduction: 68Ga-RM2 is a synthetic bombesin receptor 2017 and March 2019, all patients with primary diagnosed
antagonist that targets gastrin-releasing peptide receptors PCa who underwent a preoperative PSMA PET/CT (68Ga or
(GRPR). GRPR are highly overexpressed in several human tumors, 18
F-DCFPyL) followed by robot-assisted radical prostatectomy
including prostate cancer (PC). In this study we evaluated 68Ga- and extended pelvic lymph node dissection (ePLND) were
RM2 PET/CT in patients with newly diagnosed intermediate- or included. All patients with intermediate- or high-risk PCa, but
high-risk PC Materials and Methods: We enrolled 22 men, without suspected LN metastases on PSMA PET/CT were
50-78 year-old (mean±SD: 62.5±6.7). Images were acquired 42- considered candidates for SN biopsy with indocyanine green-
72 minutes (mean±SD: 54.4±7.6) after injection of 3.3-6.7 mCi 99m
Tc-nanocolloid (ICG-99mTc-nanocolloid) or 99mTc-nanocolloid
(mean±SD: 3.9±0.7) of 68Ga-RM2. 68Ga-RM2 PET/CT findings with free ICG as used tracers. Results: Of 53 patients, 22 had a
were compared to concurrent preoperative pelvic MRI (n=20) positive PSMA PET/CT and 31 received subsequent SN biopsy
and 68Ga-PSMA11 PET (n=10). Findings were also correlated after negative PSMA PET/CT. In total, 23 patients (43%) were pN1,
with prostate saturation biopsy (n=22) and post-prostatectomy of which 17 patients (74%) with positive PSMA PET/CT and 6
whole-mount pathology (n=16). Six participants decided to (26%) with a negative PSMA PET/CT and subsequent SN biopsy.
undergo radiation therapy. Results: The cohort included 9 The combined use of SN biopsy and PSMA PET/CT identified all
participants with intermediate-risk and 13 participants with patients with LN metastases found at ePLND (100% sensitivity)
high-risk PC, with PSA 3.3-28.0 ng/ml (mean±SD: 9.8±6.2) at and performed correct nodal staging in 48 of 53 patients (91%).
diagnosis. Preoperative 68Ga-RM2 PET identified intraprostatic The five incorrectly staged patients had a false-positive PSMA
cancer foci in all 22 patients (45 lesions), whereas mpMRI alone PET/CT, two of whom had a biochemical recurrence with LN
identified PIRADS 4 or 5 lesions in 17/20 patients (21 lesions metastases in the ePLND field seen on repeated PSMA PET/CT,
vs. 35 lesions on 68Ga-RM2 PET) and PIRADS 3 in 1/20 patients implying that an incomplete ePLND was performed. SN biopsy
(2 lesions vs. 1 lesion on 68Ga-RM2 PET). mpMRI was negative identified significantly smaller LN metastases (median diameter
in 2/20 patients (3 lesions on 68Ga-RM2 PET). 68Ga-RM2 PET of 2.0 mm interquartile range [IQR] 1.0-3.8) than PSMA PET/CT
demonstrated focal uptake in non-enlarged pelvic lymph nodes (5.5 mm IQR 2.6-9.3; p=0.007). SNs outside the standard ePLND
in 4 patients. Final pathology confirmed nodal metastases in 3 template were identified and resected in eight cases, of which
patients and follow-up imaging confirmed nodal metastasis in one was positive for metastases. Conclusion: Combining both
1 patient. One patient with normal pelvic nodes on PET/CT had modalities led to a 91% accuracy for nodal staging in primary
nodal metastases on post-surgery histopathology. 68Ga-RM2 diagnosed PCa. Adding SN biopsy in patients with a negative
PET and 68Ga-PSMA11 PET done 1-12 days (mean±SD: 4.4±4.3) PSMA PET/CT increases the combined sensitivity to 100% for
apart identified 19 and 18 intraprostatic lesions, respectively, as detecting nodal metastases at ePLND. References: None.
well as 2 and 3 pelvic lymph nodes, respectively. Non-congruent
findings between 68Ga-RM2 PET and 68Ga-PSMA11 PET were
recorded in 4/10 patients (intraprostatic lesions in 3 patients and OP-728
nodal lesion in 1 patient). Conclusion: Our preliminary results High Repeatability Of Dynamic 82Rubidium-PET/CT For
suggest that 68Ga-RM2 PET can accurately detect intermediate- Tumor Blood Flow Imaging In Prostate Cancer -a Test-
and high-risk prostate cancer. In addition, it appears to have Retest Study
better performance when compared to mpMRI and similar M. Jochumsen1,2, K. Bouchelouche1,2, K. B. Nielsen3, M. Borre4,2, J.
performance to 68Ga-PSMA11 PET. These findings need to be Frøkiær1,2, J. Sörensen1,2, L. P. Tolbod1;
confirmed in larger studies. References: None. 1
Aarhus University Hospital, Dept. of Nuclear Medicine and PET-
Centre, Aarhus, DENMARK, 2Aarhus University, Dept. of Clinical
Medicine, Aarhus, DENMARK, 3Aarhus University, Dept. of Public
OP-727 Health, Section for Biostatistics, Aarhus, DENMARK, 4Aarhus
PSMA PET/CT and Sentinel Node Biopsy for Primary University Hospital, Dept. of Urology, Aarhus, DENMARK.
Lymph Node Staging in Prostate Cancer
F. Hinsenveld1, E. M. K. Wit1, P. J. Van Leeuwen1, O. R. Brouwer1, M.
L. Donswijk1, C. N. Tillier1, E. Vegt1, H. A. M. Van Muilekom1, M. Van Aim/Introduction: Non-invasive tumor blood flow (TBF)
Oosterom2, F. W. B. Van Leeuwen2, H. G. Van der Poel1; measurement may be used for monitoring disease progression
1
Netherlands Cancer Institute Antoni van Leeuwenhoek, in patients diagnosed with prostate cancer. Recently, we
Amsterdam, NETHERLANDS, 2Leiden University validated dynamic 82Rubidium (82Rb) positron emission
Medical Center, Leiden, NETHERLANDS. tomography (PET) for quantification of TBF in prostate cancer
patients (1), but we did not assess the repeatability of this
method. Given the paucity of test-retest data, the potential
Aim/Introduction: To determine the diagnostic capabilities clinical impact of dynamic 82Rb PET cannot be evaluated. We
of combined prostate-specific membrane antigen positron here aim to determine the repeatability of TBF measurement
emission tomography/computed tomography (PSMA PET/CT) with dynamic 82Rb PET. Materials and Methods: Ten prostate
and sentinel node (SN) biopsy in PSMA PET/CT negative patients cancer patients were prospectively included. Each patient
for the primary lymph node (LN) staging in prostate cancer underwent two 82Rb PET scan sessions within one week, each
S279 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

consisting of both a dynamic pelvic and a cardiac 82Rb PET on final GS (prostatectomy). Lesions < 0.1 cm3 were excluded.
to obtain a blood image-derived input function. Results: Results: Using AS, 68Ga-RM2 PET/CT showed better sensitivity
82
Rb PET K1 can be measured in prostate tumors with a (Se) than 68Ga-PSMA-617 PET/CT: (0.85 vs 0.75) and better
repeatability of 31.9%, a within-subject coefficient of variance specificity (Sp) (0.89 vs 0.60). MS found similar Se (0.94 vs 0.93)
of 11.5%, and an excellent intraclass correlation of 0.98. but better Sp (0.89 vs 0.80) with 68Ga-RM2 PET/CT. SNR of
Conclusion: Dynamic 82Rb PET measures TBF in prostate cancer 68
Ga-RM2 PET/CT was high whatever the GS was; while 68Ga-
with a high repeatability that allows detection of actual changes PSMA-617 PET/CT exhibited higher SNR in high GS (p = 0.044).
in blood flow between repeated measurements if the change Finally, in low GS, SNR of 68Ga-RM2 PET/CT was significantly
(relative to the mean) is above 32%. Dynamic 82Rb PET K1 could higher than 68Ga-PSMA-617 PET/CT (p = 0.004). Conclusion:
be precise and consistent enough to draw conclusions on an To our knowledge, this is the first study comparing PSMA- and
individual patient basis. References: 1.Jochumsen MR, Tolbod GRPR-based imaging for initial local staging of prostate cancer.
LP, Pedersen BG, et al. Quantitative tumor perfusion imaging The results showed great diagnostic performance of 68Ga-RM2
with (82)Rubidium-PET/CT in prostate cancer - analytical and PET/CT compared to 68Ga-PSMA-617 PET/CT to characterize low
clinical validation. J Nucl Med. 2019 (epub ahead of print). Gleason score tumors. 68Ga-PSMA-617 PET/CT is promising for
initial staging of high Gleason score tumors. We are enrolling
more patients to confirm the results of these innovative imaging
OP-729 modalities. References: Touijer KA, Michaud L, Vargas Alvares Ha
Prospective comparison of 68Ga-RM2 PET/CT and 68Ga- et al (2019) Eur Urol Oncol. 2(2):166-173 Liu C, Liu T, Zhang n,
PSMA-617 PET/CT for initial staging of prostate cancer Liu Y et al (2018) Eur J Nucl Med Mol Imaging. 45(11):1852-1861
R. Schollhammer1,2,3, H. De Clermont Gallerande4, G. Robert5, M. Minamimoto R, Hancock S, Schneider B et al (2016) J Nucl Med.
Yacoub6, F. Lamare4,7,8, N. Balamoutoff4, D. Vimont7,8, E. Hindie4,7,8, P. 57(4):557-562.
Fernandez4,7,8, C. Morgat4,7,8;
1
Service de Médecine Nucléaire,CHU Bordeaux, Bordeaux, FRANCE,
2
Université de Bordeaux, INCIA, UMR 5287, Talence, FRANCE, 1609
3
CNRS, INCIA, UMR 5287, Talence, FRANCE, 4Service de Médecine
Nucléaire,CHU Bordeaux, F-33076, Bordeaux, FRANCE, 5Service
Radiation Protection - Parallel Session: Radiation
d’Urologie, CHU Bordeaux, F-33076, Bordeaux, FRANCE, 6Service
Protection - Standards, Tools and Models
d’Anatomopathologie, CHU Bordeaux, F-33076, Bordeaux, FRANCE,
7
Université de Bordeaux, INCIA, UMR 5287, F-33400, Talence, Wednesday, October 16, 2019, 8:00 - 9:30 Lecture Hall 115
FRANCE, 8CNRS, INCIA, UMR 5287, F-33400, Talence, FRANCE.

OP-730
Aim/Introduction: PSMA (Prostate Specific Membrane Reporting Incidents In Therapeutic Nuclear Medicine. A
Antigen) and GRP-R (Gastrin Releasing Peptide Receptor) are New IAEA Tool
overexpressed on prostatic cancer cells and can be targeted M. Marengo1, D. Gilley2, J. Vassileva2, F. Fahey3, L. Dimmick4, B. R.
with a PSMA inhibitor such as 68Ga-PSMA-617 (Liu 2018) or Thomadsen5, T. Ell6;
a GRP-R antagonist such as 68Ga-RM2 (Touijer 2019). GRP-R- 1
University of Bologna, Bologna, ITALY, 2IAEA, Vienna, AUSTRIA,
targeting and PSMA-targeting have been compared in patients 3
Children’s Hospital and Harvard Medical School, Boston, MA,
with biochemically recurrent prostate cancer (Minamimoto UNITED STATES OF AMERICA, 4Medical Radiation Safety, Nuclear
2016) but not at primary staging. We aimed to compare 68Ga- Regulatory Commission, Rockville Pike, MD, UNITED STATES
PSMA-617 PET/CT and 68Ga-RM2 PET/CT at initial staging of OF AMERICA, 5University of Wisconsin, Madison, WI, UNITED
prostate cancer. Materials and Methods: We prospectively STATES OF AMERICA, 6Foothills Hospital, Calgary, AB, CANADA.
enrolled 10 treatment-naïve patients with biopsy-confirmed
prostate cancer (two with Gleason score (GS) 6; three with
GS 7(3+4), one with GS 7(4+3) and four with GS ≥ 8). 68Ga- Aim/Introduction: The role of nuclear medicine therapeutic
PSMA-617 PET/CT and 68Ga-RM2 PET/CT were randomly treatments is established and expanding, thanks to new
performed before prostatectomy with imaging at 1 hour and radiopharmaceuticals that allow targeting malignancy with a
2 hours after injection (2MBq/kg). Manual (MS) and automatic high level of selectivity, releasing only limited radiation dose to
(AS) segmentation were performed on each PET imaging using healthy tissues, and considering the potential of the theragnostic
PMOD software and segmentations were then compared to approach. In the vast majority of cases, these treatments are
histology (standard-of-truth). Prostatectomy samples were well tolerated by patients and have limited deleterious effects.
analyzed by an experimented pathologist who identified Nevertheless, in a complex, highly structured discipline like
and staged each lesion according to GS. Each prostatectomy nuclear medicine, there remains the probability of procedural
slice available was scanned for comparison between PET and errors, unexpected events or unforeseeable aspects that may
histologic segmentation. Uptake intensity (SUVmax) and signal- lead to inappropriate delivery of the therapy, undesired patient
to-noise ratio (SNR) relative to non-lesional prostate gland exposure or other consequences potentially harmful to patients.
parenchyma were analyzed. Per-lesion analysis was performed Limited, but significant reports are effectively presented in the
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S280

current scientific literature. Materials and Methods: Incident of 0.3mSv are employed. Further, there is a dearth of work on
reporting systems are a tool in health institutions to monitor patient-specific radiation protection precautions. Accordingly,
unexpected events, incidents and close calls, activate corrective the aim of this work is, firstly, to establish the dose rates from
actions and provide useful information to the clinicians to prevent patients post-therapy, followed by modelling the doses
repetitions. The IAEA introduced SAFRON in 2012, a web-based received to patient family members. Finally, this work will
system for incident reporting in radiotherapy. A meeting on present a personalised radiation protection precautions
prevention of incidents in nuclear medicine held in May 2018, calculator, optimising precautions for family members taking
with participation of an international, multidisciplinary panel into account patient-specific administered activities and living
of experts, produced a series of recommendations including circumstances. Materials and Methods: Dose rates from
extending SAFRON to incidents in nuclear medicine therapeutic patients treated since 2016, measured using a Thermo Electron
applications. These include therapies with radiopharmaceuticals RadEye G-10 immediately after 90Y microspheres infusion
and radioactive medical devices such as SIRT. A specific at various distances will be presented. Normality and Log-
task group convened in November 2018, reviewed existing normality will be investigated using the Shapiro-Wilks test. Dose
reports and experiences, and develop the parameters of the rates will be used to calculate radiation doses received by family
application, define the scheme of incident models, the modality members (partner and child, respectively) and carers based on
of registration and the possible safety barriers. Results: The new interaction patterns described in the literature, and using in-
addition to the SAFRON platform is under development at the house estimates. Results: Examining our SIRT patient cohort as
IAEA with expectations that it will be tested and available in if following interaction patterns with children will demonstrate
the second half of 2019. The introduction of data is easy and the 0.3mSv dose constraint being exceeded in the majority of
anonymous, guaranteeing the privacy of patients and reporting cases. Hence, this work will show the need for RP restrictions
institutions, but nevertheless making possible for professionals considering local dose constraints. Furthermore, by assigning
in the field to obtain relevant information on incidents, their dose contributor weighting factors to each of the distance
modality, consequences and possibilities for mitigation, and components for each proximity model, and accounting for
contributing then to diffuse knowledge and learn from previous duration, a radiation protection precautions calculator will be
lessons. Participating facilities will be able to use SAFRON NM as presented. This will provide a means of optimising patient-
their local incident learning system as well as contributing to an specific precautions taking into account personal circumstances
international incident learning system looking for opportunities and administered activities. Conclusion: We demonstrate the
to improve the safety systems and reduce potential errors. need for radiation protection precautions for those individuals
Conclusion: SAFRON NM is a state of the art, safe and effective in regular contact with SIRT patients. Further, we will present
incident learning tool that the IAEA will make available to the a radiation protection precaution calculator designed for
nuclear medicine community to foster prevention of incidents optimising radiation protection precautions taking the patient-
and improve the safe administration of radionuclide therapy. specific circumstances and administered activities into account.
References: None. References: None.

OP-731 OP-732
Development of a radiation protection precaution Construction of Safety Standards for Short-half-life Alpha
calculator for personalised patient-specific precautions Emitters by Grant of Nuclear Regulatory Agency of Japan
post-SIRT therapy M. Hosono1, T. Yamada2, N. Oriuchi3, N. Ukon3, K. Nagatsu4, T. Ito2,
S. Cournane, J. McCavana, M. Manley, J. McCann, J. Lucey; H. Yamanishi2, T. Matsuda2, A. Hachisuka5, Y. Nakamura6;
St Vincent’s University Hospital, Dublin 4, IRELAND. 1
Kindai University Faculty of Medicine, Osaka-Sayama,
JAPAN, 2Kindai University Atomic Energy Research Institute,
Higashi-Osaka, JAPAN, 3Fukushima Medical University,
Aim/Introduction: Yttrium-90 (90Y) microspheres are used for Fukushima, JAPAN, 4National Institute of Radiological Sciences,
selective internal radiation therapies (SIRTs) to treat patients Chiba, JAPAN, 5National Institute of Health Sciences, Tokyo,
with hepatocellular carcinoma (HCC) or metastatic colon cancer JAPAN, 6Japan Radioisotope Association, Tokyo, JAPAN.
to the liver, with doses of up to 150Gy delivered per treatment.
90Y, a pure beta emitter, with a half-life of 64.2 hours, decay
energy of 0.94 MeV and mean tissue penetration length of Aim/Introduction: Theranostics approaches using
2.5mm, is ideal for delivering high radiation doses to precise radiopharmaceuticals currently continue to develop in nuclear
volumes of diseased tissue. The resultant beta exposure from medicine worldwide, and it is expected that alpha emitters
the patient post-therapy is, thus, negligible; however, there can will enhance substantially the efficacy of radionuclide therapy
be a considerable associated Bremsstrahlung radiation exposure over the next decades as we have seen emerging application
component. There is very little literature on the associated dose of radium-223 dichloride to castration-resistant prostate
rates from SIRT patients post therapy, and none discussing the cancer with bone metastases, Nuclear Regulatory Agency of
challenges of radiation protection (RP) precautions encountered Japan organized and supported projects for application of
within the European Union jurisdiction where dose constraints alpha emitters in basic and clinical researches since 2017. The
S281 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

purpose of this study, granted by the Agency, was to propose licensees (N=24). According to the answers optimisation is
novel principles of radiation safety in laws and guidelines a multidisciplinary process. Nuclear medicine physician and
so that research and development of radionuclide therapy radiologists resources limits frequency of optimisation in
technologies using nuclides including short-half-life alpha some hospitals. Absence of written protocols for optimisation
emitters are carried out under rational safety control based was reported widely. New national or international guidelines
on scientifically accumulated data. Materials and Methods: and recommendations are the most common initiative
We identified and examined major issues on optimization of for optimisation. In many cases optimisation process was
protection from the viewpoint of the personnel engaged in originated from self assessment, collegial interaction and EANM
production and use of radiopharmaceuticals and from that recommendations. Surprisingly, commissioning a new scanner
of the general public in consideration of novel application did not always lead to optimisation. Median optimisation
of therapeutic radiopharmaceuticals by conducting surveys frequencies for ten year period for kidney function SPECT,
at facilities in Japan and overseas. Results: We surveyed total body bone isotope imaging, upper body PET and whole
situations on safety control of alpha emitters at facilities body PET were 2, 1, 1.5 and 2 respectively. Image quality was
including National Institute of Radiological Sciences (Chiba, the main aim in optimisation and it was not compromised
Japan) and Fukushima Medical University (Fukushima, Japan) during optimisation in any reported cases. On the other hand
which own accelerators for producing alpha emitters in Japan. approximately in half of the cases activity and image quality
We also visited University of Göteburg (Göteburg, Sweden), were not changed. Conclusion: Optimisation as a basic
ARRONAX (Nantes-Saint Herblain, France), and IRSN (Institut principle is insufficiently applied. This calls for systematic and
de Radioprotecion et Sûreté Nucléaire, Saclay, France), and documented optimisation as a regular practise. We conclude
investigated use, disposal, technical standards, GMP production, that this would increase optimisation frequencies remarkably.
and regulations regarding of short-half-life alpha emitters Furthermore, as optimisation is a basic principle, it should be
including astatine-211 and actinium-225. We summarized the a integral part of commissioning. Self assessment, collegial
findings by overviewing different situations at the facilities. interaction and EANM recommendations provide foundation
Conclusion: We listed the present and future needs of research for optimisation and sufficient resources for optimisations
and development for alpha radiopharmaceuticals in relation to should be assured. The result that in half of the cases the activity
clinical demands, safety management, and regulatory issues. was not changed aligns with national and European statistics.
As a result, we recognized that scientific evidence should Based on this study, STUK will emphasize optimisation in the
be accumulated in order to establish safety management in inspection program for year 2020. We propose that 1) this
facilities and to revise current regulations in accordance with study should be carried out in other countries as well 2) EANM
the international basic safety standards for conventional and facilitates development of optimisation 3) special attention
novel radiopharmaceuticals. References: Radiation protection should be paid on administrated activities. References: None.
in therapy with radiopharmaceuticals. International Journal of
Radiation Biology 2019 in press. Published online: 28 Sep 2018.
Introduction of the targeted alpha therapy (with Radium-223) OP-734
into clinical practice in Japan: learnings and implementation. Dynamic absorbed dose calculations to the urinary
Annals of Nuclear Medicine 2019;33:211-221. Perspectives for bladder wall for the ICRP compartmental models of iodide
concepts of individualized radionuclide therapy, molecular and technetium
radiotherapy, and theranostic approaches. Nuclear Medicine M. Andersson1, S. Mattsson1, L. Johansson2;
and Molecular Imaging 2019 in press. 1
Medical Radiation Physics, Malmö, SWEDEN, 2Radiation
Physics,Umeå University, Umeå, SWEDEN.

OP-733
Nationwide Survey in Finland: Optimisation Principle Aim/Introduction: The urinary bladder wall is a radiosensitive
Should Not Be Forgotten organ that can receive a high absorbed dose from
J. T. Liukkonen, J. Suutari; radiopharmaceuticals used even in diagnostic nuclear medicine.
Radiation and Nuclear Safety Authority, Helsinki, FINLAND. The commonly used method to calculate the absorbed dose
to the urinary bladder wall is to apply absorbed fractions or
S-values derived for a static volume of the content e.g. 200 mL
Aim/Introduction: Optimisation is a basic principle in radiation for adult males. However, there are some dynamic models to
protection. In this study optimisation is considered as a general estimate the photon and electron absorbed dose contributions
imaging protocol modification, not as a patient-wise. In this to the inner surface or the mean absorbed dose to the bladder
study we investigated the role of optimisation in SPECT-CT wall. These models have only been applied on adults and use
and PET-CT facilities in Finland. The study focused on nuclear descriptive biokinetic models for the transfer of radionuclides.
imaging. Materials and Methods: A Webropol survey was The aim of this work is to estimate the absorbed dose, based
conducted to all nuclear medicine licensees in Finland. In on Monte Carlo-simulated dynamic urinary bladders and
addition optimisation will be assessed by onsite inspections. the ICRP compartmental biokinetic models of iodide and
Results: Answers to the survey were received from all pertechnetate. The calculations include sex specific absorbed
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S282

dose and estimations for preadults of 15- 10- 5- 1-year and The greatest contribution of dose due to electrons is when
newborn. Materials and Methods: S-values were calculated the radiopharmaceutical flows through the catheter. At 50 cm
for different volumes of the content with a fix mass of the distance from the vial axis, the simulated Hp(3) for electron
wall. As an approximation a spherical shape was assumed. varies from 203 uSv h-1GBq-1, at the same height of the vial
Calculations were based on anatomical and physiological data and catheter, to 110 uSv h-1GBq-1at 50 cm height and to 34 uSv
of the reference sets of values given in ICRP Publication 89. The h-1GBq-1at 100 cm height. At the same heights, but at 150 cm
reference values were given for both male and female subjects distance from the vial axis, these values decrease respectively
of six different ages: newborn, 1-, 5-, 10-, 15-years, and adult. The to 22 uSv h-1GBq-1, 17 uSv h-1GBq-1 and 11 uSv h-1GBq-1.
elemental compositions of the urinary bladder wall and content Considering an uncertainty of 5% for the simulations and 10%
were taken from the ICRP Publication 110. Results: For adult for the dosemeters, such values are quite in agreement with the
male assuming a urinary flow rate of 1600 ml/day, an initial urine measurements that varies from a minimum of 10 uSv h-1GBq-1
volume of 100 ml, a voiding volume at 300 ml and a residual and a maximum of 280 uSv h-1GBq-1(mean 89 uSv h-1GBq-1,
volume of 30 ml, the cumulated activity will for intravenously median 48 uSv h-1GBq-1). The variation are consistent with the
administered activity of Tc-99m pertechnetate be 30 % lower intrinsic variability of the practice (different operators, different
than assuming a 3.5 hour voiding interwall. The absorbed dose distance, difficulties during the infusion, etc...). Conclusion: The
to the urinary bladder wall will be 64% lower also applying satisfactory agreement between dosemeters and simulations
the dynamic S-values on the dynamic case. Using the same allows employing the evaluated data to study the exposure
biological parameters for intravenous intake of I-131 iodide, the of the medical personnel performing PRRT. From the general
cumulated activity will be 60 % higher for the dynamic case results, a value of the order of 50 uSv h-1GBq-1can be assumed.
and the mean absorbed dose to the urinary bladder wall 30 % That means that for a single administration of 20 GBq of 90Y, with
lower. Conclusion: This project aims to perform more realistic the operator remaining 15 minutes near the patient, Hp(3) can
calculation of absorbed dose to the urinary bladder calculations. reach 0.25 mSv. With such figures, the maximum dose to the eye
This is done by tracking the activity in the urinary content at lens can be reached after 80 treatments. Further evaluations will
each time on compartment models and applying the time be carried out for 177Lu. References: None.
dependent activity to urinary flow and Monte Carlo simulated
S-values. References: None.
OP-736
Novel Nanotech Antioxidant Cocktail for Protection from
OP-735 Ionizing Radiation during Bone Scans
Eye lens dose estimation in Peptide Receptor Radionuclide M. Gorenberg1, N. Eiza1, M. Ziv1, Y. Hadid1, I. Volovic2, A. Shalata1;
Therapy: Monte Carlo simulations versus experimental 1
Bnai Zion Medical Center-Technion, Haifa, ISRAEL,
measurements 2
Bnai Zion Medical Center, Haifa, ISRAEL.
F. Fioroni1, P. Ferrari2, E. Grassi1, A. Chendi1,3, M. Bertolini1, V.
Piccagli1, A. Filice1, A. Versari1, F. Mariotti2, M. Iori1;
1
AUSL-IRCCS, Reggio Emilia, ITALY, 2ENEA, Radiation Aim/Introduction: Exposure to ionizing radiation produces
Protection Institute, Bologna, ITALY, 3Postgraduate School in oxygen-derived free radicals in the tissue, these free radicals then
Medical Physics, University of Bologna, Bologna, ITALY. interact with nearby DNA, causing double strand breaks (DSB).
These DNA lesions are usually efficiently repaired, however, DSB
misrepair can lead to chromosomal translocations and therefore
Aim/Introduction: The increasing role played by Peptide initiate carcinogenesis (1). A novel nanotech protective
Receptor Radionuclide Therapy (PRRT) has provided a larger use drinkable cocktail (PCK) of non-toxic radical-scavenging of
of unsealed beta-emitter in medicine. The objective of this work 10 potent antioxidants was developed . We investigated the
is to assess eye lens doses using methods of computational protective effect of this novel nanotech antioxidant cocktail
dosimetry and to compare them with experimental in suppressing formation of gamma -ray induced DSBs DNA
measurements performed during PRRT administration. lesions in patients undergoing Bone Scans. Materials and
Materials and Methods: The administration of 90Y/177Lu- Methods: Sixteen patients (5 women, 11 men; mean age,
radiolabelled derivatives is usually performed manually, using 46.9.2 years; range, 27-90 years) undergoing technetium-99m
an infusion system. In the present work only 90Y administration is methylene diphosophonate (99mTc MDP) bone scans were
considered.The vial, the shielding and the polyethylene catheter prospectively recruited. Six patients receive the PCK before
have been reproduced with their specific composition and radiotracer injection (CKT group) and 10 patients receive no CKT
densities. The source was simulated as an electron spectrum of (control group). None of these patients had had any ionizing
0.93 MeV and 2.23 MeV (mean and maximum), generated inside imaging procedures in the past seven days or chemotherapy/
the vial and the catheter. Dose equivalents were scored at 50, radiotherapy within the prior six months before bone scan.
100 and 150 cm distance from the vial and at three different The average radiotracer activity injected was 922 MBq (range:
heights (0, 50,100 cm) from its mid-plane.The eye lens dose 888-925 MBq). Peripheral blood lymphocytes (PBLs) were
of the physician was assessed by 3 dosimeters positioned isolated from blood samples drawn directly before the bone
next to the eyes during the administration phase. Results: scan radiotracer injection and 120 minutes later. DNA DSBs
S283 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

were detected by γH2AX immunofluorescence staining and 1702


quantified (in terms of γH2AX % of doted cells) with automated
digital microscopy in each of the two blood samples to assess
Joint Symposium 27 - Radiation Protection
any significant differences. Statistical analysis was performed
Committee / JSNM: Lessons from Fukushima
with pair t test. The study was approved by the local ethics
- Low Dose Radiation from Environment
committee, and written informed consent was obtained from
Radioisotope
each patient. Results: PBLs from blood taken before radiotracer
injection showed a median of 22% γH2AX doted cells (range Wednesday, October 16, 2019, 10:00 - 11:30 Lecture Hall 311
7.4-58.2) in the control group as compared with a median of
19.5% γH2AX (range 11-24.4) for the CKT group (NS). PBLs from
blood taken 120 minutes after injection increase to a median OP-741
of 39% γH2AX doted cells (range 27.7-70) in the control group Doses and Likely Health Effects in Fukushima
(P< 0.005) as compared with an increase to a median of 21.5 N. Takamura;
% γH2AX (range 15.5-28.6) for the CKT group (NS), consistent Dept of Global Health, Medicine and Welfare, Atomic Bomb
with evidence of CKT radiation protection from a single ionizing Disease Institute, Nagasaki University, Nagasaki, JAPAN.
radiation study. Conclusion: In patients undergoing 99mTc
MDP bone scans, treatment with a novel oral nanotech cocktail
of antioxidants before scanning significantly prevented DNA OP-742
damage in PBLs. References: 1.Ward JF. DNA Damage Produced Controversies and Challenges of the Linear No Threshold
by Ionizing Radiation in Mammalian Cells: Identities, Mechanisms Model
of Formation, and Reparability. Prog Nucleic Acid Res Mol Biol. R. Wakeford;
1988;35(C):95-125. doi:10.1016/S0079-6603(08)60611-X. Manchester University, Newcastle, UNITED KINGDOM.

1701 OP-743
Supporting Fukushima - The Nuclear accident’s
CME 14 - Bone & Joint Committee / IASP: The Consequences on the Region
Diagnosis is Complex Regional Pain Syndrome I K. Kanai;
(CRPS-I a.k.a. Reflex Sympathetic Dystrophy). Or Faculty of Applied Sociology, Kindai University, Osaka, JAPAN.
is it?

Wednesday, October 16, 2019, 10:00 - 11:30 Auditorium OP-744


Special Aspects of Radiation Induced Paediatric Thyroid
Cancer
C. Reiners;
OP-737 University Hospital Würzburg, Würzburg, GERMANY.
Contemporary Consensus and Controversies in Diagnosis
and Management of CRPS-I
R. Atkins; OP-745
University of Bristol, Orthopaedic Surgery, Discussion
Bristol, UNITED KINGDOM.

1703
OP-738 Joint Symposium 28 - Translational and
Role for Imaging in Diagnosis and Management of CRPS-I
F. Paycha;
Molecular Imaging Therapy + Oncology &
Nuclear Medicine Department, University
Theranostics Committee / WMIS: Translational
Hospital Lariboisière, Paris, FRANCE.
Aspects of PSMA Targeting

Wednesday, October 16, 2019, 10:00 - 11:30 Lecture Hall 312


OP-739
Role for Imaging in Alternate Diagnoses Usually Confused
with CRPS-I OP-746
E. Rust; Biology of PSMA
Nuclear Medicine Department, Clinique du J. Grimm;
Diaconat-Roosevelt, Mulhouse, FRANCE. Memorial Sloan Kettering Cancer Centre, New
York, NY, UNITED STATES OF AMERICA.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S284

OP-747 1705
Update on PSMA Tracers
M. G. Pomper;
M2M - Parallel Session: Peptide-Based
John Hopkins Hospital, Radiology, Nuclear Medicine and
Radionuclide Therapy
Molecular Imaging, Baltimore, MD, UNITED STATES OF AMERICA.
Wednesday, October 16, 2019, 10:00 - 11:30 Lecture Hall 111

OP-748
Clinical Relevance PSMA Targeting
F. Giesel; OP-754
University of Heidelberg, Department of Nuclear Intra-tumoral somatostatin receptor 2 heterogeneity
Medicine, Heidelberg, GERMANY. confers differential radionuclide therapy response in
preclinical neuroendocrine tumor models
D. Feijtel1, G. N. Doeswijk1, N. S. Verkaik1, J. C. Haeck1, M.
1704 Konijnenberg1, C. Angotti2, D. Chicco2, D. C. van Gent1, M. de Jong1,
J. Nonnekens1;
CTE 7 - Technologist Committee: Updates in 1
Erasmuc MC, Rotterdam, NETHERLANDS, 2Advanced Accelerator
Lung Imaging Applications, A Novartis Company, Colleretto Giacosa, ITALY.

Wednesday, October 16, 2019, 10:00 - 11:30 Lecture Hall 117


Aim/Introduction: Patients with neuroendocrine tumors (NETs)
often suffer from metastases at the time of diagnosis, which
limits the possibility for resection as an effective treatment.
OP-751 For the localization of NETs, targeting of somatostatin receptor
New PET Radiotracers for Lung Imaging subtype-2 (SST2), that is highly expressed on tumor cells, with
D. Albano; radiolabeled somatostatin analogues is a diagnostic standard.
Spedali Civili of Brescia, Nuclear Medicine By labeling with radionuclides that cause DNA damage, this
Department, Brescia, ITALY. diagnostic tool has been transformed into a treatment: peptide
receptor radionuclide therapy (PRRT). PRRT with [177Lu]Lu-
DOTA-Tyr3-octreotate has been proven effective in improving
OP-752 both progression-free- and overall survival and quality of life,
Metabolic Volumes Delineation for External Beam however complete cure is rare. We conducted this study to
Radiotherapy and its Prognostic Role in Lung Cancer improve the current understanding of the effects of PRRT on
W. Cholewinski; tumor to ultimately increase the therapeutic efficacy. Materials
The Greater Poland Cancer Centre, Nuclear and Methods: BALB/c-nude mice were engrafted with NCI-H69,
Medicine Department, Poznan, POLAND. a SST2-overexpressing cancer cell line. These mice were treated
with 30MBq/0,5μg/mouse [177Lu]Lu-DOTA-Tyr3-octreotate
(non-curative dose, as per previous experience in animal
OP-753a models), scanned using SPECT/MRI and sacrificed at different
Radiomic Features in Non-Small-Cell Lung Cancer FDG- time-points up to 14 days post-treatment. Organs were excised
PET/CT Studies for biodistribution measurement. Biological parameters such as
M. Kirienko; DNA damage response, proliferation and SST2 expression were
Humanitas University, Department of analyzed using immunohistochemical- and immunofluorescent
Biomedical Sciences, Milan, ITALY. stainings. These parameters were also investigated in NCI-H69
in vitro and in Ca20948, a pancreatic NET cell line, in vitro and
in vivo. Finally, pancreatic NETs from patients were analyzed to
OP-753b confirm our findings. Results: In vivo results show intra-tumoral
Discussion heterogeneity in DNA damage and subsequent cell death
induction in NCI-H69 tumors, despite a homogeneous vascular
distribution. We observe that DNA damage response processes
induced by a non-curative dose are transient in nature, after
which tumor relapse occurs. Heterogeneity of the response
in tumor tissue can be attributed to non-homogeneous SST2
expression. We observe that high SST2-expressing regions/
cells show a higher level of DNA damage in vitro and in vivo,
indicating a potential concordance with the therapeutic
response. As we also confirmed SST2 heterogeneity in resected
S285 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

pancreatic NETs from patients, the effects of such parameters in However, the critical dose limit for the pancreas is 50 to 60 Gy,
a clinical setting warrant further investigation. Conclusion: In which is far from limiting the administration of higher activities
this research we investigated direct effects of PRRT in preclinical and the application of further treatment cycles. Our results
NET models and mapped important radiobiological parameters. suggest that the activity administered for each cycle could be
Tumoral intrinsic biological properties, such as regional SST2- increased to maximize absorbed dose of tumors and metastases.
expression levels, appear to be relevant in determining the References: [1] Mansi R et al. EJNMMI. 2011 Jan;38(1):97-107[2]
therapeutic response and efficacy. References: None. Hindorf C et al. EJNMMI. 2010 Jun; 37(6):1238-50.

OP-755 OP-756
First in human dosimetry of [177Lu]RM2: A gastrin-releasing Chemical Conjugation Of Evans Blue Derivative Prolongs
peptide receptor antagonist for targeted radiotherapy of Blood Half-life And Improves The Integrin αVβ3-targeted
metastasized castration resistant prostate cancer 177
lu-radionuclide Therapy In A Patient-derived Xenograft
J. Kurth, B. J. Krause, C. Bergner, S. M. Schwarzenboeck, M. Model Of Lung Adenocarcinoma
Heuschkel; L. Zhao1, H. Chen1, K. Fu1, D. Fan2, Z. Guo3, H. Wu1, O. Jacobson4, Q.
Rostock University Medical Center, Rostock, GERMANY. Lin1, X. Chen5;
1
The First Affiliated Hospital of Xiamen University, Xiamen,
CHINA, 2Beijing Tiantan Hospital, Beijing, CHINA, 3Center for
Aim/Introduction: Besides PSMA prostate cancer cells also Molecular Imaging and Translational Med, Xiamen, CHINA,
express gastrin-releasing peptide receptor (GRPr) which is 4
9000 Rockville Pike, Bethesda, MD, UNITED STATES OF AMERICA,
therefore an attractive target for theranostic approaches. High 5
NIBIB/NIH, Bethesda, MD, UNITED STATES OF AMERICA.
affinity GRPr antagonist (RM2) for use as diagnostic imaging
agent was developed by Mansi et al. [1], offering the opportunity Aim/Introduction: The arginine-glycine-aspartic acid (RGD)
to label it with beta-emitting radiometals for therapeutic peptide has high activity and specificity in various malignancies
purposes. Aim of this study was to calculate absorbed doses as an imaging agent. However, the short blood half-life is the
for critical organs for [177Lu]Lu-RM2 administration in a group of main hurdle of RGD peptide as a radiotherapeutic agent for the
mCRPC patients, that lost or showed lower PSMA accumulation treatment of integrin αvβ3-expressing tumors. In this study, we
after initial [177Lu]Lu-PSMA-617 therapy. Materials and developed an “add-on” molecule Evans blue (EB) to moderate
Methods: 35 patients suffering from mCRPC, without adequate albumin binding that prolongs half-life in the blood, allows
treatment options for approved therapies received [68Ga]Ga- radiolabeling for imaging and targeted radiotherapy. Materials
RM2-PET/CT. 4 patients (mean age of 68y (range:60-80ys)) were and Methods: The EB-RGD were radiolabeled with 177Lu
recruited for therapy; 2 of them also received a 2nd therapy cycle. for SPECT imaging and integrin αvβ3-targeted radiotherapy,
Therapies were conducted in accordance with the German respectively, and compared to the peptides without the “add-
Medicines Law (AMG,§13[2b]). Mean activity was 4.5±0.9GBq. on” (EB) in a patient-derived xenograft (PDX) models of lung
For dosimetry, patients underwent planar WB-scintigraphy and adenocarcinoma (LUAD). Results: Samples of LUAD were
SPECT/CT imaging (Siemens Symbia T6) of the upper and lower obtained from patients undergoing operation, and the PDX
abdomen at approximately 1h, 24h, 48h and 72h p.i. along with (αvβ3 high expression) models of LUAD were subsequently
blood sampling. SPECT/CT was quantitatively reconstructed established by implanting cancer fragments into nude mice. In
with corrections for scatter, attenuation and detector blurring. 177
Lu-DOTA-EB-RGD SPECT imaging, the tumor to background
Absorbed doses for kidneys, pancreas, liver, spleen, gallbladder ratio (T/B) reached 14.63 ± 3.82 at 24 h, and remained 12.02±
and tumor lesions were calculated from SPECT/CT data 1.76 at 72 h post injection. The ex vivo biodistribution result
according to RADAR dosimetry scheme using OLINDA/EXM2.1. showed that tumor uptake of EB-RGD reached the peak (14.96
Individual organ masses were extracted from CT. Absorbed dose ± 6.71 %ID/g) at 48 h post-injection (p.i.) and remained stable
to bone marrow was calculated according to EANM-guideline (14.00 ± 3.18) at 96 h p.i.. Regarding targeted radiotherapy,
[2]. Results: Therapy was well-tolerated by all patients and no starting from day 12 after the treatment, significant differences
side effects were observed. A highly increased uptake in tumor in the tumor volume were observed between 177Lu-DOTA-
lesions and pancreas was seen within the first 1 h. Mean organ EB-RGD treated groups (Group B: 21.6 MBq, tumor volume =
doses were 1.10±0.44Gy/GBq in the pancreas, 0.35±0.14Gy/ 35.6 ± 15.8 mm3; Group D: 13.5 MBq, tumor volume = 125.1
GBq in the kidneys, 0.05±0.02Gy/GBq in the liver, 0.07±0.02Gy/ ± 55.4 mm3) and saline /177Lu-DOTA-RGD monomer treated
GBq in the gallbladder wall, 0.10±0.06Gy/GBq in the spleen and groups (Groups A: saline, tumor volume = 472.8 ± 203.0 mm3
15.9±5.5mGy/GBq for the red bone marrow. The mean dose ; Group C: 21.6 MBq, tumor volume = 305.9 ± 65.6 mm3). These
estimated for tumor lesions was 6.2±3.0Gy/GBq. Conclusion: differences increased over time (P <0.01), and the tumors in
Application of GRPr antagonist [177Lu]Lu-RM2 is suitable for both 177Lu-DOTA-EB-RGD treated group became unmeasurable
targeted radiotherapy of mCRPC, as it shows high tumor by 28 days post initial treatment. No systemic toxicity due to
uptake and rapid clearance from normal organs. Absorbed radiotherapy was observed in all groups by monitoring animal
doses in tumor lesions are therapeutically relevant. Critical body weight.18F-FDG PET imaging 7 days post-injection of 177Lu-
organ receiving the highest absorbed dose was the pancreas. DOTA-EB-RGD showed decreased uptake, indicating reduced
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S286

glucose utilization. Conclusion: Conjugation of our novel “add- Radium-223 using an 18-membered macrocycle. This four alpha
on” molecules to RGD peptides showed a prolonged circulation particle emitting radionuclide is widely available, and has the
half-life and enhanced tumor accumulation in integrin αvβ3- potential to significantly reinforce the emerging targeted alpha
expressing tumors, and can transform drugs into theranostic particle armamentarium. References: None.
entities. Furthermore, our PDX model is the available, validated
PDX model for LUAD, and preclinical data suggests that 177Lu-
DOTA-EB-RGD may be an effective treatment option for LUAD OP-758
patients with high integrin αvβ3 expression. References: None. Alpha Particle Emiting Radium-223 in Combination
Therapy: Potential and Pitfalls
D. L. Thorek1, D. S. Abou1, M. Longtine1, P. Kushwaha2, R. C. Riddle2,
OP-757 B. Baumann1;
Chelation of Radium-223 for Targeted Radionuclide Alpha 1
Washington University School of Medicine, St. Louis, MO,
Particle Therapy UNITED STATES OF AMERICA, 2Johns Hopkins University School
D. Abou1, N. A. Thiele2, M. Longtine1, A. L. Villmer1, J. J. Wilson2, D. L. of Medicine, Baltimore, MD, UNITED STATES OF AMERICA.
J. Thorek1;
1
Washington University School of Medicine, Saint
Louis, MO, UNITED STATES OF AMERICA, 2Cornell Aim/Introduction: Radium-223 dichloride is a first in class alpha
University, Ithaca, NY, UNITED STATES OF AMERICA. particle emitting radiopharmaceutical for treatment of bone
metastatic castrate resistant prostate cancer (bmCRPC). Localizing
to the active bone surface through physicochemical affinity at
Aim/Introduction: There is currently tremendous interest in sites of bone metastases, it produces four potent cytotoxic alpha
targeted alpha particle therapy as these emissions have short particles through its decay scheme. This mechanism of action has
path lengths with high linear energy transfer. Radium-223 been viewed as orthogonal to conventional pharmacological
dichloride is the first approved agent in this space; it is treatments of bmCRPC and multiple ongoing clinical trials are
administered as a free ion with bone seeking properties. Alpha being evaluated to test the value of multi-agent treatment of
emitters delivered directly to cancer cells themselves may have bmCRPC. One trial investigating abiraterone (a CYP17 inhibitor
improved therapeutic properties, and agents are currently that blocks androgen synthesis) with Radium-223, ERA-223
under evaluation using peptides and antibodies as targeting (NCT02043678), was halted early after a higher incidence of
vectors. To date, Radium-223 has not been used as a targeted skeletal events and poorer survival versus each agent alone.
agent because of the challenges in achieving robust chelation We have developed advanced small animal models of bmCRPC
for radiolabeling and in vivo use. We have investigated the to evaluate combination treatments of Radium-223. Our work
coordination of an 18-membered macrocyclic ligand to achieve demonstrates the potential for synergies, as well as significant
rapid and stable chelation of Radium-223 with significant toxicities, in the emerging alpha particle combination space.
biomedical potential. Materials and Methods: Radium-223 Materials and Methods: Radium-223 was produced using
was produced using an in house microgenerator from an in house microgenerator from radiochromatographic
radiochromatographic purification from source Actinium-227/ purification from source Actinium-227/Thorium-227. Hormonal
Thorium-227. MACROPA chelator (10mM) was used to label (dutastaride, enzalutamide, abiraterone acetate, androgens)
approximately 37kBq of Radium-223 and assessed at room and chemo-therapies (docetaxel, mitoxantrone) were tested
temperature; pH 6. Instant thin layer chromatography in alone or in combination with Radium-223 dichloride in animal
running buffers of either 10mM EDTA or 10mM NaOH were used models of bone metastases (FVB bearing Hi-Myc metastases).
for quality control and complexation efficiencies along with Castrate animals were kept on hormonal therapy prior to
autoradiography by phosphor storage screen exposure. Radio/ and after radiopharmaceutical administration. Excised bone
UV FPLC was conducted to test biological stability of chelated tissues were evaluated by high resolution microCT for standard
Radium-223 in biological conditions. Animals (n=5, male, FVB) morphometry, dual labeled calcein/alizuran for bone turnover,
purchased from Charles River Laboratories were administered and gene expression analysis (AR, OCN, RUNX) as well as
3.7kBq activity and biodistribution performed at early (15min) counted ex vivo for administered activity. Results: We show
and late (24h) times after tail vein injection; and were compared that Radium-223 accumulates at sites of bone metastasis in
to Radium-223 dichloride in 30mM citrate. Results: Radium-223 skeletal models of metastasis, with therapeutic benefit. Upon
was rapidly complexed by MACROPA in buffer. RadioTLC were combination, Radium-223 distribution does not significantly
developed and validated to confirm stable complexation of change; and in the case of abiraterone + Radium-223 slightly
the isotope in vitro. Challenge with serum proteins did not but significantly decreases. No significant changes in the
lead to decomplexation. In vivo biodistribution of the complex morphological properties of the bone (including BV/TV, cortical
demonstrated rapid renal clearance and nearly quantitative area or trabecular thickness) are noted. Several combinations
excretion to the urine verifying in vivo stability. In contrast, and lead to changes in gene expression of bone tissue samples,
as expected, Radium-223 dichloride in citrate was found in the in particular abiraterone + Radium-223 with significant
skeletal compartment and gastrointestinal tract. Conclusion: upregulation of resoptive processes indicating severe adverse
We have demonstrated stable and rapid chelation of effects of co-administration of these agents. Conclusion: Our
S287 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

data suggest that rational combinations of Radium-223 can radioisotopic treatment - 5.0months. Conclusion: Intracavitary/
have synergy but that negative outcomes from overlapping intratumoral injection of 225Ac-substance P is tolerated well.
toxicities can be severe. Our findings with abiraterone and Only mild temporary adverse effects (edema, epileptic seizures,
Radium-223 may in part elucidate findings in ERA-223. This work aphasia) were observed. It seems that the presented method
may have import for the expanding number of alpha particle using 225Ac is promising and requires further clinical trials.
therapies in trial, for their real-world use in combination with References: None.
other therapies. References: None.

OP-760
OP-759 Targeted alpha therapy using astatine (211At) labelled
Targeted alpha therapy of recurrent glia tumors : clinical phenylalanine: preclinical study in glioma xenograft mice
experience with 225Ac-Substance-P T. Watabe1, K. Kaneda-Nakashima2, Y. Liu1, Y. Shirakami3, K. Ooe1,
L. Krolicki1, F. Bruchertseifer2, J. Kunikowska1, H. Koziara3, B. A. Toyoshima3, E. Shimosegawa1, T. Nakano4, A. Shinohara5, J.
Krolicki3, M. Jakuciński1, D. Pawlak4, C. Apostolidis2, R. Rola5, A. Hatazawa4;
Merlo6, A. Morgenstern2; 1
Osaka University Graduate School of Medicine, Suita, Osaka,
1
Medical University of Warsaw, Warszawa, POLAND, 2European JAPAN, 2Osaka University Graduate School of Science, Suita,
Commission, Joint Research Centre, Directorate for Nuclear Osaka, JAPAN, 3Institute for Radiation Sciences, Osaka University,
Safety and Security, Karlsruhe, GERMANY, 3Department of Suita, Osaka, JAPAN, 4Research Center for Nuclear Physics,
Neurosurgery, Institute of Oncology, Warszawa, POLAND, Osaka University, Suita, Osaka, JAPAN, 5Graduate School
4
Radioisotope Centre POLATOM, National Centre for of Science, Osaka University, Toyonaka, Osaka, JAPAN.
Nuclear Research, Warszawa, POLAND, 5Department of
Neurology, Military Institute of Aviation Medicine, Warszawa,
POLAND, 6University of Basel, Basel, SWITZERLAND. Aim/Introduction: Upregulation of amino acid transport as
well as glucose transport was generally observed in malignant
tumors. Phenylalanine derivatives are focusing attention for
Aim/Introduction: Treatment of patients with recurrent glioma its specific tumor targeting, especially through L-type amino
is very limited. Introduction of new options of treatment is acid transporter-1 (LAT1). In the present study, we aimed to
critically important for this group of patients. Gliomas are evaluate the treatment effect of alpha emitter astatine labelled
characterized by a high expression of receptors for Substance phenylalanine (211At-Phe) using xenograft model of malignant
-P (SP), regardless of the histological grading. Therefore, SP brain tumor. Materials and Methods: Cellular uptake analysis
labeled with alpha emitters was used for local application into was performed using the cell line of C6 glioma, U-87MG, and
the tumour. Local application reduces systemic adverse effects GL261. Uptake inhibition was evaluated by adding either
of the drug as well as the protective effect of the Blood-Brain- phenylalanine (Phe) or 2-aminobicyclo-(2,2,1)-heptane-2-
Barrier. Moreover, alpha rays have many advantages: tissue carboxylic acid (BCH), an inhibitor of system L amino acid
range is less than 100 µm; hypoxia and cell cycle are not critical transporters. Tumor xenograft models were prepared by
to the effect of radiation. Initially, 213 Bi was used for labeling subcutaneous injection of C6 glioma in immunodeficient nude
of SP; bismuthium is convenient for labeling of peptides, and mice (n=12) and GL-261 in C57BL/6mice (n=12) with preserved
short T1/2 of 213Bi (T1/2 = 46 min) is beneficial for radiation immune function, respectively. 211At-Phe was injected into
protection. Currently, 225Ac was introduced. It seems that a 3 groups (each n=3) of C6 glioma mice (0,1, 0.5, and 1MBq,
diverse range of energy, as well as longer T1/2 (10 days) should respectively) and GL261 mice (n=7, 1MBq). Planar imaging was
favor a better distribution of the radiopharmaceutical into the performed at 30min and 3hr after the administration of 211At-Phe
tumor. Materials and Methods: 13 patients with histologically to evaluate the uptake in the tumor using percent injected dose
confirmed recurrence of the glia tumor grade II-IV were treated: (%ID) and absorbed dose (Gy). Tumor size (mm3) was monitored
group A - patients with grade II - III WHO (5 patients), group by the caliper measurement and compared among the injected
B - patients with grade IV (8 patients). All patients received a groups and control mice. Results: Cellular uptake analysis
standard treatment (surgery + radio-chemo-therapy). When showed significant uptake inhibition in C6 glioma (13.6 ± 6.1
a recurrence/progression was diagnosed, an intracavitary/ %), U-87MG (27.9 ± 3.0 %), and GL261 (4.6 ± 1.0 %) after adding
intratumoral injection of 20-40 MBq 225Ac-SP was applied every BCH, suggesting the large contribution of 211At-Phe uptake via
2 months (1-7 injections). Monitoring of toxicity and overall system L of amino acid transporter. Planar imaging showed early
survival was indicated as the first goal of the study. The study was distribution and wash-out of 211At-Phe in the C6 glioma tumor
approved by the Ethical Committee of the Medical University of (3.7 ± 0.8 %ID at 30min and 1.5 ± 0.2 %ID at 3hrs). Absorbed dose
Warsaw. Results: In group A: PFS was 4.8 (median) months, OS was estimated as 1.7± 0.6 (Gy/MBq) in the C6 glioma tumor. In
from primary diagnosis was 114.7 months, OS from diagnosis the evaluation of treatment effect, tumor growth suppression
of recurrence - 38.0 months, and OS from start of radioisotopic was observed in C6 glioma xenograft in a dose-dependent
treatment - 26.5 months. In group B: : PFS was 3.0 (median) manner. Relative ratios of tumor size compared to the control
months, OS from primary diagnosis was 21.3 months, OS from were 0.56 in 0.1MBq, 0.42 in 0.5MBq, and 0.30 in 1MBq one
diagnosis of recurrence - 10.9 months, and OS from start of month after the injection of 211At-Phe, respectively. In GL261
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S288

xenograft mice, growth suppression effect was also observed Our initial results indicate 225Ac-DOTATATE TAT safe with low
(relative tumor size: 0.24). Conclusion: This study showed and transient side-effects. It add to a new dimension in the
the treatment effect of 211At-Phe in the xenograft models of treatment of end-stage GEP-NET who have exhausted all the
malignant brain tumor, suggesting its potential applicability to standard treatment options. References: None.
the alpha therapy targeting amino acid transporter (system L)
for cancers. References: None.
1706
OP-761
Do.MoRe - Parallel Session: PET/MR Physics
Preliminary results on 225Ac-DOTATATE Targeted
Alpha Therapy in Metastatic Gastroenteropancreatic Wednesday, October 16, 2019, 10:00 - 11:30 Lecture Hall 112
Neuroendocrine Tumors: First Clinical Experience on
Safety and Efficacy
S. Ballal, M. P. Yadav, C. Bal; OP-762
All India Institute of Medical Sciences, New Delhi, INDIA. Zero Echo Time MR Attenuation Correction Method on the
GE SIGNA PET/MR: Comparison with CT Based Attenuation
Correction in Dynamic PET Brain imaging
Aim/Introduction: The objective of this study was to investigate A. Firouzian1, G. Delso2, R. McCutcheon3,4,5, M. Nour3,4,5, O.
and present the early results on the safety and efficacy of Howes3,4,5, W. Hallett1;
225
Ac-DOTATATE targeted alpha therapy (TAT) in patients with 1
Invicro, London, UNITED KINGDOM, 2GE Healthcare, London,
advanced, progressive, 177Lu-DOTATATE refractory, somatostatin UNITED KINGDOM, 3King’s College London, London, UNITED
receptor (SSTR) positive, metastatic gastroenteropancreatic KINGDOM, 4Medical Research Council, London, UNITED KINGDOM,
neuroendocrine tumors (GEP NETs). Materials and Methods: 5
Imperial College London, London, UNITED KINGDOM.
This study was approved by the Institute Ethics Committee (IEC
No:517/2018). We recruited 35 patients (mean age, 55.3±6.3years
range: 46-72 years) who either reached the maximum limit Aim/Introduction: In PET imaging on combined PET/MR
of 177Lu-DOTATATE therapy cycles or were refractory to 177Lu- scanners MR-based attenuation correction (MRAC) methods are
DOTATATE therapy. Systemic TAT was performed in all the used to correct for the effects of scattering and absorption of
patients with 225Ac-DOTATATE (100 KBq/Kg body weight) at gamma radiation as it travels from within the subject’s body to
an interval of 8 weeks . The patients were treated between reach the PET detectors. This is challenging for brain imaging,
April 2018 to April 2019 with a median follow-up duration where the head bones make a significant contribution to
of 9 months (range: 2 - 13 months). Treatment-related side attenuation and scatter but do not produce a strong signal, at
effects were assessed every 2 weeks on the basis of physical least in conventional MR imaging. We present a comparison
examination, vital signs, laboratory results (hematologic, kidney between CT based attenuation correction, as used in a
and liver function levels) and adverse events graded according conventional PET/CT scanner, and an MR method based on a
to the CTCAE v5.0. Efficacy assessment included morphological zero echo time sequence sensitive to bone, as implemented on
and molecular tumor responses measured by diagnostic the GE SIGNA PET/MR, in dynamic PET brain imaging. Materials
contrast-enhanced 68Ga-DOTANOC PET/CT scans according to and Methods: 10 healthy subjects in a study evaluating
RECIST 1.1 and PERCIST 1 criteria, respectively. Results: The most 11
C-PHNO brain uptake gave informed consent to take part in
common adverse effects (AEs) were nausea, vomiting, gastritis, this methodology study. Subjects underwent a 90 min PET/
and appetite loss, but were limited to grade 1 or 2. Majority of MR scan on a GE SIGNA PET/MR scanner, as well as a low dose
the patients experienced these AEs at the time of amino acid head CT scan for attenuation correction purposes, on a Siemens
infusion which was administered during 225Ac-DOTATATE therapy Biograph 6 TruePoint PET/CT scanner on the same day as one
and was resolved after few hours of amino acid infusion. All the of their PET/MR scans. Dynamic PET images were generated
other AEs such as fatigue or asthenia, diarrhoea, appetite loss, using the PET/MR reconstruction pipeline with attenuation
abdominal pain, abdominal distension, weight loss, peripheral correction based on both the CT scan (CTAC), and on a zero
edema, headache, dizziness, and flushing were also identified echo time MR sequence acquired on the PET/MR (MRAC-
which were limited to grade 1 or 2, except for 1 patient with ZTE). Two regional outcome measures were calculated from
grade 3 abdominal distension and fatigue. None of the patients the dynamic PET series above: the non-displaceable binding
experienced grade 3 or 4 hematotoxicity, renal insufficiencies potentials (BPND) estimated from kinetic modelling of 11C-PHNO
or hepatotoxicity. In a median follow-up duration of 9 months, over the 90min scan immediately post-injection, and the
morphological response assessment was assessed in 26 patients standard uptake values (SUVR) averaged over 60-90min post-
which revealed complete remission in 1, partial remission in injection, both with respect to cerebellum grey matter. Results:
16, and Stable disease in 9 patients. Similarly, molecular tumor The average percentage BPND difference between CTAC and
response evaluation in 26 patients revealed complete remission MRAC-ZTE based dynamic PET data is 0.3% ± 0.9% ranging
in 1 patient, partial remission in 18, and stable disease in 7 from -4.6% to 8.8% for brain regions with significant uptake
patients. There were no treatment related deaths. Conclusion: (BPND>0.5). The average percentage SUVR difference between
S289 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

CTAC and MRAC-ZTE based data for the same regions is 0.3% corrected (NAC) PET images are treated as the network input
± 0.4%, ranging from -3.8% to 3.6%. Conclusion: Quantitative in encoder part and decoder part try to reconstruct pixel-wise
measurements on PET images reconstructed using ZTE based continuously-valued of measured attenuated corrected (MAC)
attenuation correction implemented on the GE SIGNA PET/MR PET image. The DeepDAC was trained using 80 randomly-
were very similar to those obtained using CT based attenuation selected data and evaluated in the remaining 10 subjects and
correction, supporting the use of ZTE based attenuation 10 patient as external validation set. Quality of the synthesized
correction for fully quantitative PET brain imaging. This agrees images, was quantitatively assessed by different image quality
with our previous findings using a different PET tracer (11C- parameters. Variability of image quantification was assessed
Ro15-4513) [1]. References: [1] Firouzian A, Delso G, Hallett W, by radiomic features (SUVmax, SUVmean,TLG and and second
Comparison of MR based Attenuation Correction Methods with and high order texture) in 83 brain region delineated based
CT Based Attenuation Correction in Dynamic Brain PET Imaging, on Hammers N30R83 maximum probability atlas. Reliability
EJNMMI (2018) 45 (Suppl 1):S695. of measurement determined by pixel-wise Relative Errors (%)
with respect to radiomics features values (RFV) in CTAC PET
images and t-test statistical analysis. Results: RMSE values
OP-763 were (1.19±0.5) e-2 and (1.19±0.49) e-2 for testing and external
Deep Direct Attenuation Correction of Brain PET images validation set. PSNR and SSIM value for test and external
using Emission Data and Deep Convolutional Encoder- validation were 38.70±3.54, 39.22±3.65 and 0.988± 0.006,
Decoder for application to PET/MR and dedicated brain 0.989±0.006 respectively. RE of SUVmean was -0.1 ± 2.14 for
PET scanners all region and only three region has significant difference with
I. Shiri1, P. Ghafarian2,3, P. Geramifar4, K. Ho-Yin Leung5,6, M. Oveisi7,8, MAC image, however the mean of difference of this region were
A. Rahmim9,10, M. Ay1,11; 0.02 with range of -0.83 - 1.18. SUVmax has mean RE of -3.87 ±
1
Research Center for Molecular and Cellular Imaging, Tehran 2.84 for all brain regions and 17 regions in brain had significant
University of Medical Sciences, Tehran, IRAN, ISLAMIC REPUBLIC difference from MAC image with mean RE of -3.99 with range
OF, 2Chronic Respiratory Diseases Research Center, National of -8.46 - 0.76. Homogeneity from GLCM had highest number
Research Institute of Tuberculosis and Lung Diseases (NRITLD), (Twenty) of sub region with significant difference from MAC
Shahid Beheshti University of Medical Sciences, Tehran, IRAN, with mean RE of 7.22 but in all brain sub region mean RE of
ISLAMIC REPUBLIC OF, 3PET/CT and Cyclotron Center, Masih homogeneity were 2.5 ± 3.65. Conclusion: The present study
Daneshvari Hospital, Shahid Beheshti University of Medical demonstrated that direct AC of PET image using deep auto
Sciences, Tehran, IRAN, ISLAMIC REPUBLIC OF, 4Research Center for encoder decoder is a promising technique for brain PET images.
Nuclear Medicine, Shariati Hospital, Tehran University of Medical Deep learning technique pave the road toward emission-based
Sciences, Tehran, IRAN, ISLAMIC REPUBLIC OF, 5Department of AC in PET images applicable in PET/MRI and dedicated Brain PET
Biomedical Engineering, Johns Hopkins University, Baltimore scanners. References: None.
MD, UNITED STATES OF AMERICA, 6Department of Radiology and
Radiological Science, Johns Hopkins University, Baltimore MD,
UNITED STATES OF AMERICA, 7Department of Biomedical and OP-764
Health Informatics, Rajaie Cardiovascular Medical and Research PET/MRI attenuation correction in the pelvic region with a
Center, Iran University of Medical Science, Tehran, IRAN, ISLAMIC statistical decomposition method
REPUBLIC OF, 8Department of Computer Science, University of E. Wallstén, J. Axelsson, J. H. Jonsson, C. Thellenberg Karlsson, T.
British Columbia, Vancouver, BC, CANADA, 9Departments of Nyholm, A. Larsson;
Radiology and Physics & Astronomy, University of British Columbia, Department of radiation sciences, Umeå
Vancouver, BC, CANADA, 10Department of Integrative Oncology, BC University, Umeå, SWEDEN.
Cancer Research Centre, Vancouver, BC, CANADA, 11Department
of Medical Physics and Biomedical Engineering, Tehran University
of Medical Sciences, Tehran, IRAN, ISLAMIC REPUBLIC OF. Aim/Introduction: Quantification in PET/MRI is of importance,
and its accuracy is currently limited by the MR based attenuation
correction estimate. A common method for attenuation
Aim/Introduction: Attenuation correction (AC) is one of the correction of the pelvic region is based on a 2-echo Dixon
main nontrivial obstacles in PET/MRI and dedicated Brain PET MRI sequence for segmentation of fat and water and does not
systems. Different methods have been proposed to address the account for bone. In this work, we evaluate a new method for
AC of PET images. Recent developments in the field of Machine attenuation correction using an algorithm based on statistical
learning have enable new approaches to cross modality decomposition of a T2 weighted MRI scan. Materials and
mapping. The main aim of this study is to explore the possibility Methods: Substitute CT images (sCTs) were calculated from T2
of inferring the attenuation corrected PET image directly from weighted MRI scans with a statistical decomposition algorithm,
the non-attenuation corrected image using deep convolutional originally developed for MRI-based radiotherapy dose-planning
auto encode decoder. Materials and Methods: In total 100 [1]. These sCTs benefits from having bone density information
patients brain PET data were used in current study. DeepDAC included, in addition to fat and water information. Prostate
consists of a paired encoder and decoder. Non attenuation cancer patients from the PARAPLY study [2] were retrospectively
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S290

selected, scanned with PET/MRI 11C-Acatate and CT the same ongoing prostate cancer study underwent PET/MRI (Siemens
day. The stand-alone CT images were transformed to the Biograph mMR) [single bed, 20 minutes p.i. 200 MBq 68Ga-UPAR].
same geometry as the PET and MR images, using a non-rigid Patients had crossed arms over the chest, and arms did not enter
registration. CT images, generated sCT images, and the Dixon- the FOV at the level of prostate. PET was reconstructed using
based attenuation maps (MRAC), all in the same geometry, vendor-provided Dixon-based MRAC with and without an atlas-
were together with the PET raw data used to reconstruct based bone segmentation, and with relative and absolute SC
attenuation-corrected PET images using the PETrecon toolbox methods (3D OP-OSEM, 3 iterations, 21 subsets, 4 mm Gaussian
[GE Healthcare]. The two MR-based attenuation corrections filter). The halo artifact was defined as the patient volume with
were compared to the CT-based attenuation correction with less than 50% of activity in reference muscle [gluteus maximus
root mean squared error (RMSE). Lesion analysis will also be away from bladder] and excluding adipose tissue. A prostate
reported. PET/MRI images were acquired on a Signa PET/MRI ROI was defined on anatomical MRI excluding a 1 cm margin to
(GE Healthcare), and the CT images on a Brilliance Big Bore the bladder. Results: The appearance of the halo varied greatly
(Phillips Healthcare). The study will include 12 patients and a between patients, with only a few cases showing a severe
subset of 6 patients has been analyzed so far and is presented artifact. Overall, inclusion of bone in MRAC and absolute as
here. Results: Soft tissue in-between pelvic bone structures opposed to relative SC resulted in the best image quality. The
were overestimated with 13% in MRAC-PET, and the error was median size of the halo artifact was 320 cm3 (absolute SC, no
reduced to 5% with sCT attenuation corrected PET (sCT-PET). bone), 1176 cm3 (relative SC, no bone) 130 cm3 (absolute SC,
For the whole patient volume, an average underestimation bone) and 441 cm3 (relative SC, bone). No significant correlation
of 6% was found in the MRAC-PET, compared to 1% for sCT- of relative halo size with SUVmax/SUVmean of bladder, injected
PET. RMSE within the body was reduced with a factor 2.5 with dose per weight or patient cross-sectional area was observed.
sCT-PET (RMSE=3.6%), compared to MRAC-PET (RMSE=8.8%). SUVmean of prostate was 2.3 (absolute SC, no bone), 1.5 (relative
Conclusion: Applying sCT from statistical decomposition as a SC, no bone), 2.3 (absolute SC, bone,) and 1.8 (relative SC, bone).
base for calculation of attenuation maps reduces quantification Conclusion: Halo artifacts were observed for 68Ga-uPAR PET/
errors in PET-images of the pelvic region compared to the MRI. Absolute SC with bone inclusion resulted in the smallest
common Dixon based method. References: [1] Siversson, C., halo. Relative halo size did not depend on SUV of bladder, as
Nordström, F., Nilsson, T., Nyholm, T., Jonsson, J., Olsson, L. E. observed also by Noto et al. [1] but not by Heußer et al [2], which
(2015). Technical Note : MRI only prostate radiotherapy planning however, had much higher bladder uptake. Prostate activity
using the statistical decomposition algorithm. Medical Physics, depended on SC method, and on bone inclusion for relative
10(42), 6090-6097. https://doi.org/10.1118/1.4931417 [2] SC. Including bone in MRAC can be a contributing factor to PET
ClinicalTrials.gov ID NCT01962324 quantification bias in 68Ga-uPAR PET/MRI. References: [1] Noto,
Benjamin, et al. EJNMMI research (2017) [2] Heußer, Thorsten, et
al. PloS one (2017)
OP-765
Evaluating the Effect of Bone Attenuation and Scatter
Correction Methods on PET Quantification in 68Ga-uPAR- OP-766
PET/MRI One-stop-shop fully integrated dynamic PET-MRI for the
S. Ahangari1, M. Ø. Fosbøl1, S. Kurbegovic2, H. H. Johannesen1, B. W. characterization of lung lesions : a feasibility study
Jakoby3, F. Büther4, A. Loft1, A. Kjær1,5, F. L. Andersen1, A. E. Hansen1; F. L. Besson1,2, B. Fernandez3, S. Faure4, A. Seferian5, O. Mercier6,
1
Department of Clinical Physiology, Nuclear Medicine and PET, X. Mignard5, E. Blanchet7, S. Mussot6, S. Bulifon5, D. Mitilian6,
Rigshospitalet, University of Copenhagen, Copenhagen, DENMARK, A. Chetouani7, F. Bouderraoui7, L. Mabille6, H. Cherkaoui8, A.
2
Department of Urology, Copenhagen Prostate Cancer Center, Botticella9, C. Caramella9, P. Pradere6, C. Le Pechoux9, E. Fadel6,
Rigshospitalet, University of Copenhagen, Copenhagen, DENMARK, D. Planchard9, B. Besse9, C. Comtat7, P. Gervais7, V. Lebon7, E.
3
Siemens Healthcare GmbH, Erlangen, GERMANY, 4Department Durand1,2;
of Nuclear Medicine, University Hospital Münster, Albert- 1
Department of Nuclear Medicine Hopitaux Universitaires
Schweitzer-Campus 1, Münster, GERMANY, 5Cluster for Molecular Paris Sud, APHP, Le Kremlin-Bicêtre, FRANCE, 2IR4M unit
Imaging, University of Copenhagen, Copenhagen, DENMARK. UMR8081 Paris Sud-CNRS, Orsay, FRANCE, 3GE Healthcare,
Orsay, FRANCE, 4Laboratoire de mathématiques Université
Paris Sud-CNRS, Orsay, FRANCE, 5Department of respiratory
Aim/Introduction: PET/MRI is a promising diagnostic method medicine, Hopitaux Universitaires Paris Sud, APHP, Le Kremlin-
for prostate cancer patients. In clinical practice, halo artifacts Bicêtre, FRANCE, 6Thoracic Oncology Institute, Université
can occur around bladder due to e.g. suboptimal PET scatter Paris-Sud, Hopital Marie Lannelongue, Le Plessis-Robinson,
correction (SC) [1,2]. Scatter and attenuation correction are FRANCE, 7Service Hospitalier Frederic Joliot, Université Paris
related because the attenuation map is utilized for single scatter Sud, CEA, Orsay, FRANCE, 8CEA-Neurospin, Université Paris-
simulation [1]. The aim was therefore to investigate the effects Saclay, Gif sur Yvette, FRANCE, 9Thoracic Oncology Institute,
of bone inclusion in MRAC as well as varying SC methods on Université Paris-Sud, Gustave Roussy, Villejuif, FRANCE.
PET quantification in pelvis PET/MRI with 68Ga-uPAR (68Ga-NOTA-
AE105). Materials and Methods: Thirty-two patients from an
S291 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

Aim/Introduction: To assess the feasibility of a fully integrated of Otorhinolaryngology, Head & Neck Surgery and
dynamic PET-MRI approach applied to the characterization of Audiology, Rigshospitalet, Copenhagen Ø, DENMARK.
lung lesions specifically. Materials and Methods: A total of
9 patients underwent a one-hour dynamic PET-MRI imaging
protocol for suspected lung cancer. FDG PET and DCE MRI Aim/Introduction: Combined PET/MRI as a one-stop-shop
full kinetic analyses (Sokoloff and extended Toft models imaging modality for radiotherapy (RT) planning holds great
respectively), together with DWI-ADC and T1/T2-mapping potential. However, information about electron density,
were performed. All the PET-MRI data were warped into the normally provided by CT, is a prerequisite for attenuation
same isotropic reference space before analyses. For each lung correction of PET and for RT dose calculations. Here, we create
lesion, voxel-wise 3D maps of 14 biological features / 4 main a deep learning approach for synthetic CT (sCT) generation
categories were computed using an in-house fully integrative based on MR imaging of head and neck cancer (HNC) patients,
multimodal post-processing pipeline developed for this acquired in RT treatment position and evaluate the effect on
purpose specifically : perfusion/vascularization (Ktrans, Kep, Ve dose calculations. Materials and Methods: Eight patients
and Vp); metabolism (SUV, k1, k2, k3, Ki, Vb, and MRGlu); diffusion referred for RT of HNC underwent PET/MRI (Siemens Biograph
(ADC); and tissular characterization (T1 and T2 mapping). For mMR) after routine FDG-PET/CT planning scan. In both scans,
each lesion, voxel-wise monotonic relationships between all the the patients were fixated in treatment position. Rigid registration
PET-MRI features were explored (Spearman correlations). Finally, between planning CT and MR Dixon images was performed. A
all the lesions were partitioned by using multidimensional deep learning convolutional neural network for sCT generation,
unsupervised gaussian mixture approach, and features profiles similar as previously described [1], was implemented. The
/ relationships were explored at the supervoxel regional level. network was trained using full-slice 3D volumes of Dixon (in-
Results: Relationships between the perfusion/vascularization, phase and opposed-phase) images as input, and the voxel-
metabolism, diffusion and tissular feature categories differed to-voxel matched CT as output. The network was initialized
among the lesions. At the feature level, strong correlations by a pretrained model with 811 brain scanned patients and
(absolute r value superior to 0.5) were observed for the perfusion/ then fine-tuned using the HNC patients. Network training
vascularization features pairs and the metabolic feature pairs. At and evaluation was performed in a leave-one-out process. RT
the category level, absolute r values were inferior to 0.5 for the treatment plans (VMAT) were derived in Eclipse (Varian Medical
vast majority of the feature pairs. Combining the 14 features Systems Inc) and optimized on the planning CT. The plans were
together, unsupervised clustering provided 2 to 4 supervoxels copied onto the sCT and dose distributions were recalculated.
depending on the lesion. At the supervoxel regional levels, Cumulative dose volume histograms (DVH) and the relative
feature profiles differed, as well as their monotonic relationships. differences in mean (ΔDmean), maximum (ΔDmax), near-maximum
Conclusion: Our one-stop-shop fully integrative dynamic PET- (ΔD2%), and near-minimum (ΔD98%) absorbed doses for different
MRI protocol provided 14 biological features (4 main categories) organs at risk and planning target volume of primary tumor and
in the same examination. For all lesions, the heterogeneity of involved nodes (PTV1) between the two dose calculations were
features profiles / relationships at the regional supervoxel level calculated. Results: A sCT was derived for each patient in under
highlights the unique capability of PET-MRI to get better insight 10 seconds. Currently, dose calculations were performed on five
of the biological characterization of lung masses. References: of the eight patients. The average relative difference (±standard
Dennis Vriens, Eric P Visser et al. Methodological considerations deviation) in DVH points between dose calculations from CT and
in quantification of oncological FDG PET studies. Eur J Nucl sCT for the different volumes were: PTV1 (ΔD2%= 0.60±0.66%,
Med Mol Imaging 2010;37(7):1408-1425. Khalifa F, Soliman A et ΔD98%= -0.08±1.02%, ΔDmean= 0.40±0.40%), left parotid (ΔDmean=
al. Models and methods ofr analyzing DCE-MRI: a review. Med -0.56±0.67 %), right parotid (ΔDmean= -0.07±0.51%), spinal cord
Phys 2014;41(12):124301. Divine MR, Katiyar P et al. A population (ΔDmax= 0.37±0.71%). Conclusion: These preliminary results
based Gaussian mixture model incorporating 18F-FDG-PET and suggest that our proposed method for sCT generation produces
DW-MRI quantifies tumor tissue classes. J Nucl Med. 2016;57:473- dose calculations that are similar to CT. The low differences in the
79. DVH points and the prospect of using the sCT for attenuation
correction of PET is a promising step towards using PET/MRI for
one-stop-shop RT planning. References: [1] Ladefoged, Claes
OP-767 Nøhr, et al. “Deep learning based attenuation correction of PET/
PET/MRI for Radiotherapy Planning: Dosimetric Evaluation MRI in pediatric brain tumor patients: Evaluation in a clinical
of Deep Learning Synthetic CT from MR for Head and Neck setting.” Frontiers in neuroscience 12 (2018): 1005.
Cancer Patients
A. Olin1, C. N. Ladefoged1, A. E. Hansen1, K. Håkansson2, A. Kjær1,3, J.
H. Rasmussen4, A. K. Berthelsen1,2, B. M. Fischer1, F. L. Andersen1; OP-768
1
Department of Clinical Physiology, Nuclear Medicine & PET, Comparison of simultaneous arterial spin labeling MRI and
Rigshospitalet, Copenhagen Ø, DENMARK, 2Department 15
O-H2O PET measurements of regional cerebral blood flow
of Oncology, Section of Radiotherapy, Rigshospitalet, in rest and altered perfusion states
Copenhagen Ø, DENMARK, 3Cluster for Molecular Imaging, O. Puig, O. M. Henriksen, M. B. Vestergaard, A. E. Hansen, F. L.
Rigshospitalet, Copenhagen Ø, DENMARK, 4Department Andersen, C. N. Ladefoged, E. Rostrup, H. B. W. Larsson, U. Lindberg,
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S292

I. Law; OP-769
Department of Clinical Physiology, Nuclear Medicine Design and performance of a compact preclinical scanner
and PET, Rigshospitalet, Copenhagen, DENMARK. for simultaneous PET/MR acquisitions at 7 T
A. Courteau1, J. McGrath2, P. M. Walker3,1, R. Pegg2, G. Martin2,
R. Garipov2, P. Doughty2, A. Cochet1,4,3, F. Brunotte1,4,3, J. M.
Aim/Introduction: Arterial spin labelling (ASL) is a non- Vrigneaud4,1;
invasive magnetic resonance imaging (MRI) technique that may 1
ImViA laboratory, EA 7535, University of Burgundy, Dijon,
potentially provide fully quantitative regional cerebral blood FRANCE, 2MR-Solutions Ltd, Guildford, UNITED KINGDOM,
flow (rCBF) images. However, before using it in clinical routine 3
CHU François Mitterrand, Dijon, FRANCE, 4Georges-François
it needs to be validated against the clinical gold-standard, fully Leclerc Cancer Centre, Unicancer, Dijon, FRANCE.
quantitative 15O-H2O-positron emission tomography (15O-H2O-
PET). We aimed to compare both techniques by performing
repeated and simultaneous quantitative ASL-MRI and 15O-H2O- Aim/Introduction: Preclinical PET/MR imaging requires a high
PET scans in different perfusion states acquired in a hybrid PET/ field but compact system, easy to install in a preclinical nuclear
MRI scanner. Materials and Methods: 14 healthy young males imaging environment, with a low sensitivity to temperature
were studied twice in resting state, during hyperventilation variations, and a low electric noise. A simultaneous PET/
and after acetazolamide (post-ACZ), yielding a total of 63 (26 MR system has been developed to fit these requirements. It
in resting state, 18 during hyperventilation and 19 post-ACZ) combines a cryogen-free superconducting 7 T magnet and
combined simultaneously acquired PET/MRI datasets in total. SiPM-based PET detectors offering compensation of depth of
Each 15O-H2O-PET was acquired dynamically for 4 min. with interaction effects. Materials and Methods: The 7 T magnet
arterial sampling after the injection of 500MBq 15O-H2O i.v. and has a length of 0.8 m, a diameter of 1 m, and a weight of 600
modelled using a 2-compartment 1-tissue model[1]. The ASL kg. The 5-gauss line is just 1.1 m from the magnet and no
sequence was a 7 min. multi post-labeling delay 2D pseudo- Faraday cage is required around the imaging room. The liquid
continuous ASL (PCASL) with full brain coverage quantified helium-free superconductive magnet avoids the need of
with BASIL in FSL using Buxton’s method[2]. Fully quantitative regular helium and nitrogen supply. The MR gradients strength
measurements of global and regional CBF and CBF reactivity is 240 mT/m. The fully integrated PET insert consists of sixteen
from both techniques were compared. Results: Average global planar modules gathered in two octagons with a 117 mm
CBF by ASL-MRI and 15O-H2O-PET were not significantly different inner diameter. Each module contains a dual layer of LYSO:Ce
in any state (40.0±6.5mL/100g/min and 40.6±4.1mL/100g/ scintillation crystals coupled to 144 Sens-L J-series SiPMs with
min respectively in rest, 24.5±5.1mL/100g/min and high photon detection efficiencies. Temperature correction
23.4±4.8mL/100g/min, respectively during hyperventilation, is integrated to the detectors. Axial fields of view are 103 mm
and 59.1±10.4mL/100g/min and 64.7±10.0mL/100g/min in PET and 80 mm in MR imaging. A specially designed bore
respectively post-ACZ). Average reactivity by 15O-H2O-PET and shield reduces drastically the electric noise both in MR imaging
ASL-MRI were not significantly different. An overall, strong and in rodents monitoring devices. A performance assessment
correlation between the two methods was found across study complying with the NEMA-NU4-2008 standard and a
all states and volunteers (slope=1.01, R2=0.82), while the compatibility study based on the ACR MRI QA Guide were
correlations within individual states, although significant, had performed. Results: Thanks to its dual ring-like geometry, the
a lower slope and poorer correlation (rest: slope=0.26, R2=0.05; microPET offered a peak absolute sensitivity of 7.5% with an
hyperventilation: slope=0.73, R2=0.47; and post-ACZ slope=0.55, energy window of 250-750 keV. No distinguishable difference
R2=0.37). Correlations between the methods for absolute and was found between noise equivalent count rates measured
relative reactivity were also weak, but significant. 15O-H2O PET with and without MR pulsing. PET characteristics remained
and ASL rCBF showed a similar regional distribution, although stable over all tested MR operating conditions. Good count
ASL yielded significantly higher perfusion and absolute rate linearity was observed on the reconstructed images up
reactivity in highly vascularized areas (cingulate and insula) to 50 MBq. Regarding MR imaging, the homogeneity of both
and lower perfusion in areas close to air-bone interface due static magnetic field and radiofrequency were not significantly
to susceptibility induced artifacts in MRI (orbitofrontal cortex, affected by the integration of the PET scanner. Conclusion:
inferior temporal cortex and cerebellum). Conclusion: ASL- As a conclusion, despite a compact magnet design, MR field
MRI and 15O-H2O-PET measurements of global CBF and rCBF homogeneity meets the existing state-of-the-art performances.
are highly correlated across different perfusion states, but Regarding PET, high sensitivity and high counting rates are
with moderate correlation in measurements of hemodynamic the strong points of this integrated system. These results also
reactivity and systematic differences in regional distribution. suggest that mutual interferences between both modalities
Hence, caution is advised when using PCASL for reactivity does not impact imaging data qualitatively nor quantitatively.
studies, and further evaluation in clinical studies is needed. Moreover, simultaneous PET/MR acquisitions on mice and rats
References: 1.Ohta S, et. al.JCBFM.1996;16:765-780. 2.Buxton have been successfully performed on the system using various
RB, et. al.MRM.1998;40:383-396. radiotracers. References: None.
S293 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

1707 Hospital, Turku, FINLAND, 5Department of Radiology, Tampere


University Hospital, Tampere, FINLAND, 6Department of Clinical
Teaching Session 7 - Interactive Clinical Cases Physiology and Nuclear Medicine, Helsinki University Central
- ESMIT: Reading with the Experts - PET/CT in Hospital, Helsinki, FINLAND, 7Department of Diagnostic Radiology,
Neuroendocrine Tumours University of Turku, Turku, FINLAND, 8Department of Clinical
Physiology, Central Hospital of Central Finland, Jyväskylä,
Wednesday, October 16, 2019, 10:00 - 11:30 Lecture Hall 113 FINLAND, 9Department of Clinical Physiology, North Karelia
Central Hospital, Joensuu, FINLAND, 10Department of Clinical
Physiology and Nuclear Medicine, Turku University Hospital, Turku,
FINLAND, 11Department of Clinical Physiology, Nuclear Medicine
OP-770 and Turku PET Centre, Turku University Hospital, Turku, FINLAND.
PET/CT with 68Ga-Radiolabelled SSTR Analogues -
Interactive Clinical Cases Presentation
V. Ambrosini; Aim/Introduction: Current EAU guidelines strongly
University of Bologna, S.Orsola-Malpighi Hospital, recommend abdominopelvic computer tomography and bone
Department of Experimental Diagnostic and Specialized scintigraphy in primary staging of high-risk prostate cancer
Medicine, Nuclear Medicine, Bologna, ITALY. (PCa). Nevertheless, both modalities have limited accuracy for
staging PCa metastases. Several other potentially more accurate
imaging modalities are available including SPECT/CT, PSMA PET/
OP-771 CT and whole-body MRI. This trial aims to compare these imaging
PET/CT with [18F]DOPA - Interactive Clinical Cases modalities to the traditional ones. Materials and Methods: This
Presentation ongoing ethics-approved, prospective, registered, single-center
S. Balogova; trial enrolls patients with primary unfavorable intermediate or
St.Elisabeth Oncology Institute, Comenius University of high-risk PCa according to EAU risk group classification. After
Bratislava, Nuclear medicine, Bratislava, SLOVAKIA. consent, patients undergo 99mTc-HMDP planar bone scintigraphy
(BS) and contrast-enhanced abdominopelvic and chest CT as a
clinical standard. Research scans include 99mTc-HMDP SPECT/CT,
OP-772 18
F-PSMA-1007 PET/CT and 1.5 T whole-body MRI with diffusion
Wrap-up and Conclusions weighted imaging. Two separate modality-based specialists
P. Erba; review each modality blinded for other modalities. Reported
Nuclear Medicine, Department of Translational Research regions include bony skeleton, regional lymph nodes (LN),
and New Technology in Medicine, University of Pisa and extra regional LNs and visceral lesions. In addition to overall
Azienda Ospedialiero Universitaria Pisana, Pisa, ITALY. metastasis-status, regions and lesions are reported either
benign, equivocal or malignant. Pessimistic analysis (equivocal
considered malignant) is performed in case of equivocal
1708 modality consensus. Based on clinical data, including all imaging
modalities and follow-up information (imaging, histology and
Clinical Oncology - Parallel Session: Prostate - PSA), ground truth is defined on patient-level. Results: To date,
Primary Staging and Biochemical Persistance 50 patients have undergone all imaging modalities. Mean age
was 69 years. Eighteen (36%) presented with intermediate and
Wednesday, October 16, 2019, 10:00 - 11:30 Lecture Hall 114 32 (64%) with high-risk PCa. Median PSA was 12 ng/ml (range:
3-2000). Twenty-eight (56%) had metastatic disease and the rest
presented with localized or locally advanced disease. Of the
OP-773 patients with metastasis, 17(34%) had bone-only metastasis,
Comparison of 18F-PSMA-1007 PET/CT, whole-body MRI 3(6%) nodal-only, 4(8%) bone and nodal, 1(2%) bone and
and 99mTc-HMDP SPECT/CT to planar bone scintigraphy visceral, and 3(6%) bone, nodal, and visceral metastases. In
and CT in primary staging of intermediate or high-risk patient-level pessimistic analysis, sensitivity of BS, CT, SPECT/
prostate cancer CT, whole-body MRI, and PSMA PET/CT were 0.23, 0.36, 0.46,
S. Malaspina1, M. Anttinen2, O. Ettala2, I. Jambor3, J. Kemppainen1, 0.42 and 0.86, respectively. The corresponding specificity and
M. Sandell4, I. Rinta-Kiikka5, S. Kajander1, J. Schildt6, E. Saukko7, K. AUC values were 0.75, 0.59, 0.73, 0.81, 0.91 and 0.49, 0.47, 0.59,
Timonen8, P. Rautio9, T. Noponen10, J. Saunavaara4, H. Aronen4, M. 0.62, 0.88, respectively. Furthermore, PSMA PET/CT revealed
Seppänen11, P. Boström2; metastatic disease in 16% (8/50) of patients where all the other
1
Turku PET Centre, Turku University Hospital, Turku, FINLAND, modalities were negative. Conclusion: Compared to traditional
2
Department of Urology, Turku University Hospital, Turku, imaging modalities, 18F-PSMA-1007 PET/CT appears to be a more
FINLAND, 3Department of Radiology, Icahn School of Medicine accurate diagnostic tool for primary staging in intermediate or
at Mount Sinai, New York, NY, UNITED STATES OF AMERICA, high-risk prostate cancer. Therefore this method could serve as
4
Medical Imaging Centre of Southwest Finland, Turku University a new reference standard. References: None.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S294

OP-774 OP-775
Prospective evaluation of 68Ga-PSMA PET/CT in primary arallel comparison of 68Ga-Prostate Specific Membrane
prostate cancer diagnosis - final results of a dedicated trial Antigen PET-CT and PRIMUS in primary prostate cancer
E. Lopci, G. Lughezzani, A. Castello, A. Saita, P. Colombo, N. M. diagnosis
Buffi, N. Lo Iacono, R. Hurle, K. Marzo, L. Leonardi, R. Peschechera, E. Lopci, G. Lughezzani, A. Castello, A. Saita, P. Colombo, N. M.
A. Benetti, S. Zandegiacomo, L. Pasini, P. Casale, P. Diana, G. Buffi, N. Lo Iacono, R. Hurle, K. Marzo, L. Leonardi, R. Peschechera,
Bevilacqua, E. Mazziotti, L. Balzarini, A. Chiti, G. Guazzoni, M. A. Benetti, S. Zandegiacomo, L. Pasini, P. Casale, P. Diana, G.
Lazzeri; Bevilacqua, E. Mazziotti, L. Balzarini, A. Chiti, G. Guazzoni, M.
Humanitas Clinical and Research Hospital - IRCCS, Milano, ITALY. Lazzeri;
Humanitas Clinical and Research Hospital - IRCCS, Milano, ITALY.

Aim/Introduction: The current study is designed to test the


diagnostic performance of 68Ga-PSMA PET/TC for primary Aim/Introduction: To compare the diagnostic performance
diagnosis in a selected subset of patients with suspicious of 68Ga-PSMA PET/TC with PRIMUS (prostate risk identification
prostate cancer (PCa). Materials and Methods: For this using micro-ultrasound) in the primary diagnosis of prostate
prospective trial, from January 2017 till December 2018, we cancer (PCa) in patients with previously negative biopsy.
enrolled and addressed to 68Ga-PSMA PET/CT consecutive Materials and Methods: From September till December 2018,
patients having a persistently elevated PSA and/or PHI we enrolled 28 patients candidate to 68Ga-PSMA PET/TRUS
(prostate health index) suspicious for PCa, negative digital rectal (transrectal ultrasound) fusion biopsy and compared them
examination, and at least one negative biopsy were enrolled. with PRIMUS. The present analysis is embedded into a larger
The cohort comprised patients with either a negative/equivocal diagnostic trial investigating the role of 68Ga-PSMA PET/CT in PCa
mpMRI (PIRADS v2. ≤2) or absolute/relative contraindications diagnosis of patients having a persistently elevated PSA and/or
to mpMRI. All patients underwent whole body 68Ga-PSMA PHI (prostate health index) suspicious for PCa, negative digital
PET/CT 60 minutes after radiopharmaceutical injection (185- rectal examination, with either negative or contraindication
250MBq). Focal PSMA uptake superior to background activity to mpMRI, and at least one negative biopsy. All patients
was considered for the analysis and outlined for target biopsy. underwent parallel 68Ga-PSMA PET/CT and micro-ultrasound for
Semi-quantitative measures for all lesions comprised SUVmax biopsy indication. Focal PSMA uptake superior to background
and SUVratio-to-background. Sensitivities, specificities, and activity was considered for the analysis and outlined for target
accuracy were calculated based on pathology results. Results: biopsy. Semi-quantitative measures for all lesions comprised
Overall, 97 patients were enrolled in the study: 70 patients SUVmax and SUVratio-to-background. PRIMUS classification
(72%) had already performed a mpMRI with either a negative was performed according to standard criteria: score 1&2 benign;
result for PCa (n=22) or positive mpMRI, but previous negative score 3 suspicious, score 4&5 significant disease. The two
biopsy. 68Ga-PSMA PET/TRUS fusion biopsy was performed in imaging modalities were statistically compared and diagnostic
64 patients (66%), total 114 regions of interest (ROIs), whereas performance calculated based on pathology results. Results:
in the remaining cases (34%) the indication for biopsy was not Overall, 20 patients were addressed to 68Ga-PSMA PET/TRUS
confirmed. According to pathology, 23 patients (34%) with fusion biopsy following the examinations. In the remaining
41 ROIs had evidence of PCa: 8 patients (16 ROIs) resulted cases, the indication was not confirmed. Two patients resulted
Gleason score (GS) 6, 13 patients (21 ROIs) resulted GS 7 (3+4 having a GS 6 PCa, 7 patients had a GS 7 (3+4 or 4+3), 1 patient
or 4+3), 1 patient (2 ROIs) GS 8 and 1 patient (2 ROIs) GS 10. In had a GS 8 PCa and 13 patients presented with benign findings
14 patients with previous positive mpMRI and negative biopsy, (prostatitis/BPH). Mean SUVmax and SUVratio for all PCa lesions
PCa presence was demonstrated after 68Ga-PSMA PET/CT: 3 GS resulted statistically significantly higher than in benign lesions
6 and 11 GS 7. Mean SUVmax and SUVratio-to-background for (p=0,041 and 0.011, respectively): in particular, mean SUVmax
all PCa lesions resulted statistically significantly higher than in was 5.5 versus 4.1, and mean SUVratio was 2.3 versus 1.5,
benign lesions (p<0,001): in particular, mean SUVmax and mean respectively for PCa and benign findings. By using optimal cut-
SUVratio were 10.6 versus 4.1, and 4 versus 1.5, respectively. ROC off points as reference, 68Ga-PSMA PET/CT demonstrated an
analysis performed for optimal cut-off points demonstrated overall accuracy of 83% for SUVmax ≥5.4 and 94% for SUVratio
that a SUVmax >5.4 and a SUVratio >2.2 could identify clinically ≥2.2 in the detection of clinically significant PCa (GS≥7). On
significant PCa (GS ≥7) with an accuracy of 81% e 90%, counterpart, PRIMUS results were as follows: score 3 in 9 patients
respectively. Conclusion: In patients with a high suspicion of (45%), score 4 in 10 patients (50%) and 1 patient with score 5.
cancer, despite previously negative biopsy and/or mpMRI, 68Ga- When considering only score 4&5, PRIMUS demonstrated
PSMA PET/CT is capable to detect malignant lesions and identify an overall accuracy of 61% in detecting clinically significant
with a high accuracy clinically relevant PCa. References: Lopci PCa. Conclusion: In comparison to PRIMUS, 68Ga-PSMA PET/
E, Saita A, Lazzeri M, et al. J Urol. 2018 Jul;200:95-103.Lopci E, CT shows a higher diagnostic performance and is capable of
Guazzoni G, Lazzeri M. Radiology. 2018 May;287:725-726.Lazzeri detecting clinically relevant PCa in patients with a high suspicion
M, Lopci E, Lughezzani G, et al. Eur J Hybrid Imaging. 2017;1:9. of cancer. References: Lughezzani G, et al. European Urology
Oncology, 2018, In PressLopci E, et al. J Urol. 2018;200:95-103.
Pavlovich CP, et al. Urol Oncol. 2014;32:34.e27-32.
S295 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

OP-776 OP-778
Validation of gallium-68 PSMA-PET/CT for primary lymph Interobserver Agreement of 68Ga-PSMA-11 PET/CT images
node staging in prostate cancer patients interpretation
L. van Kalmthout1, H. van Melick2, J. Lavalaye2, R. Meijer1, A. C. Derwael1, O. Lavergne2, P. Lovinfosse1, V. Nechifor1, D.
Kooistra3, J. de Klerk3, A. Braat4, P. Kaldeway5, B. de Keizer1, M. Lam1; Waltregny1, R. Hustinx1, N. Withofs1;
1
Academic hospital, Utrecht, NETHERLANDS, 2St. Antonius 1
CHU, Liège, BELGIUM, 2CHR, Liège, BELGIUM.
Ziekenhuis, Nieuwegein, NETHERLANDS, 3Meander Medisch
Centrum, Amersfoort, NETHERLANDS, 4UMC Utrecht, Utrecht,
NETHERLANDS, 5St. Anotnius Hospital, Nieuwegein, NETHERLANDS. Aim/Introduction: Prostate-specific membrane antigen
(PSMA)-ligand PET/CT has already provided promising results in
prostate cancer imaging yet simple and reproductible reporting
Aim/Introduction: In many centers, gallium-68 (68Ga) prostate criteria are still lacking. This study aimed at retrospectively
specific membrane antigen (PSMA)-PET/CT imaging is currently evaluating the reproducibility of 68Ga-PSMA-11 PET/CT images
implemented in the standard diagnostic work-up of prostate interpretation according to prostate cancer molecular imaging
cancer (PCa). However, prospective validation of diagnostic standardized evaluation (PROMISE) criteria and reproducibility
accuracy in initial staging of PCa is lacking. This study evaluates of PSMA-reporting and data systems (RADS) version 1.0 was also
diagnostic accuracy of 68Ga-PSMA-PET/CT in detection of studied1,2. Materials and Methods: Forty-two patients with
lymph node metastases (LNMs). Materials and Methods: newly diagnosed histologically proven intermediate or high-risk
From October 2017 up to October 2018, newly diagnosed prostate cancer, eligible for radical prostatectomy with pelvic
PCa patients with negative bone scan and >10% risk of LNMs lymph node dissection and who underwent 68Ga-PSMA-11 PET/
(MSKCC-nomogram) were prospectively included if tumor CT before surgery were retrospectively included. Three nuclear
board considered them candidates for extended pelvic lymph medicine physicians (2 experienced; 1 trainee) independently
node dissection (ePLND). After informed consent was signed, reviewed PET/CT images blinded to clinicopathologic data.
patients underwent 68Ga-PSMA PET/CT prior to ePLND. Two Interpretation of 68Ga-PSMA-11 PET/CT images was based on
blinded experienced nuclear medicine physicians examined all PROMISE criteria including miTNM classification and lesions
scans; disagreements were solved by the introduction of a third miPSMA expression score visual estimation1. For a given
reader. Scan results were evaluated in a second tumor board scan, findings were further categorised according to PSMA-
meeting for possible change of management (CoM), being either RADS version 1.0 (not applicable to the primary tumour) 2.
ePLND-template extension, ePLND cancellation (e.g. in case of Consensus among reviewers was measured (Cohen’s kappa
positive distant lesions following biopsy) or other management and Krippendorff’s coefficients) and guideline for interpreting
strategies. Histopathological examination was performed by degree of agreement followed Nanni et al. method3. All lymph
dedicated uropathologists. Sensitivity, specificity, positive (PPV) nodes short and long axes were measured and correlation
and negative predictive value (NPV) for the detection of LNMs between lymph nodes size and miPSMA expression score
were calculated using histopathology as reference. Statistical was tested (Spearman Correlation, p &lt 0.05 considered
analyses were performed using SPSS Statistics v24. Results: A significant). Results: Agreement between observers was
total number of 103 patients were eligible for analysis. Ninety- substantial (coefficients 0,61-0.80) for almost all criteria: miTNM
seven ePLNDs were performed. Forty-one patients (42.3%) staging, localisation of metastases and lymph nodes, miRADS
had a total of 89 LNMs. Seventeen of these patients were PET- classification, localisation and evaluation of PSMA’s level of
positive, resulting in a patient-based sensitivity, specificity, PPV expression of the primary tumour and miPSMA expression score
and NPV for the detection of LNMs of respectively 41.5%, 89.4%, of bone and visceral metastases. The only criterion for which
73.9% and 67.6%. Side-based sensitivity, specificity, PPV and NPV interobserver agreement was only moderate (Krippendorff’s
was 37.7%, 92.2%, 64.5% and 79.8%; template-based sensitivity, coefficient = 0,53) was lymph nodes miPSMA expression
specificity, PPV and NPV was 37.3%, 94.3%, 55.0% and 89.0%. score. A statistically significant correlation was found between
CoM due to PSMA findings was observed in 13 patients (12.6%): miPSMA expression score and lymph nodes size (p &lt 0.05). This
In six patients, ePLND-template was extended. ePLND was study pointed out that PSMA expression of reference organs for
cancelled in another six patients, either because of PCa-positive the estimation of miPSMA expression score might be variable
extrapelvic lesions following biopsy (n=2); clinical parameters between individuals, especially for the distinction between
with suspected ≥M1a-disease on PET (n=3) and M1a-disease liver activity (miPSMA expression score 2) and parotid activity
confirmed by CT thorax (n=1). Radiation therapy following (miPSMA expression score 3). Conclusion: This study showed
ePLND (0/18 positive lymph nodes) was given in one patient interobserver substantial agreement of PROMISE criteria for
with a PET-positive rib lesion. Conclusion: This prospective the interpretation of 68Ga-PSMA-11 PET/CT images except for
analysis in newly diagnosed PCa patients shows that 68Ga- the estimation of miPSMA expression score of positive lymph
PSMA PET/CT detects LNMs with high specificity and moderate nodes that can be hampered by the interindividual variability
sensitivity. Furthermore, PET-imaging leads to significant CoM. of reference organs PSMA expression. References: 1. Eiber et
References: None. al. J Nucl Med, 2018 March. 59(3) : 469-478; 2. Rowe SP and al.
Eur Urol. 2018; 73:485-487; 3. Nanni, C. et al. Eur J Nucl Med Mol
Imaging (2018) 45: 712-719.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S296

OP-779 recurrence), and 30% (10/33) were PET negative after RP. Most
Performance of 68Ga-PSMA-11 PET in patients with PSA PET positive pelvic nodes presented with intense tracer uptake
persistence after radical prostatectomy for the detection (median SUVmax=10.1), however 71% were not enlarged by CT/
of residual prostate cancer: a multicenter retrospective MRI criteria (median short diameter=0.80 cm). PSMA-ligand PET
study positive predictive value was 87%. Initiation of systemic therapy
A. Farolfi1, A. Gafita2, J. Calais3, M. Eiber2, A. Afshar-Oromieh4, F. was significantly associated with presence of distant lesions
Spohn5, F. Barbato6, M. Weber6, H. Ilhan7, V. Cervati1, A. Wetter8, on PSMA-ligand PET (p=0.001). According to multivariable
B. Hadaschik9, A. Briganti10, J. Walz11, D. Pianori12, S. Fanti1, U. regression analysis, PSA and ISUP grade were associated with
Haberkorn5, K. Herrmann6, W. P. Fendler6; the presence of Tr/N1 and/or M1 disease; whereas T stage ≥3a
1
Nuclear Medicine Department, S.Orsola Hospital, University was associated only with the presence of M1 disease (OR 7.64,
of Bologna, Bologna, ITALY, 2Department of Nuclear Medicine, CI95% 1.66-35.08; p=0.01). Conclusion: In this multicenter
Klinikum rechts der Isar, Technical University Munich, Munich, retrospective study, PSMA-ligand PET detected disease in more
GERMANY, 3Ahmanson Translational Theranostics Division, than two thirds of patients with PSA persistence after radical
Department of Molecular and Medical Pharmacology, University prostatectomy. Most common sites of persistent disease were
of California Los Angeles (UCLA), Los Angeles, CA, UNITED STATES within the obturator and presacral/mesorectal regions. Extra-
OF AMERICA, 4Department of Nuclear Medicine, Bern University pelvic regions however frequently harbored persistent prostate
Hospital, Bern, SWITZERLAND, 5Department of Nuclear Medicine, cancer. Our data suggests a role for PSMA-ligand PET to identify
Heidelberg University Hospital, Heidelberg, GERMANY, 6Department residual disease in high-risk patients. References: None.
of Nuclear Medicine, University Hospital Essen, Essen, GERMANY,
7
Department of Nuclear Medicine, University Hospital Munich,
Ludwig-Maximilians-Universität (LMU), Munich, GERMANY, OP-780
8
Department of Radiology, University Hospital Essen, Essen, Salvage radiotherapy guided by 68Ga-PSMA-11 PET/CT in
GERMANY, 9Department of Urology, University Hospital Essen, patients with biochemical persistence (BCP) after radical
Essen, GERMANY, 10Department of Urology, Division of Oncology, prostatectomy for prostate cancer
Urological Research Institute, IRCCS Ospedale San Raffaele, Milan, F. Ceci1, D. Nicolotti1, E. Pilati1, A. Guarneri2, S. Bartoncini2, M.
ITALY, 11Department of Urology, Institut Paoli-Calmettes Cancer Finessi1, V. Liberini1, G. Bisi1, U. Ricardi2, D. Deandreis1;
Centre, Marseille, FRANCE, 12Department of Biomedical and 1
Nuclear Medicine, Department of Medical Sciences,
Neuromotor Sciences, University of Bologna, Bologna, ITALY. University of Turin, Turin, ITALY, 2Radiation Oncology,
Department of Oncology, University of Turin, Turin, ITALY.

Aim/Introduction: PSA persistence after radical prostatectomy


(RP) is associated with adverse outcome in patients with prostate Aim/Introduction: Introduction: prostate cancer (PCa) patients
cancer (PCa). Our aims were to define positivity rate, regions of with persistent high PSA levels (BCP) after radical prostatectomy
high risk for residual disease and impact on management of (RP) showed less favourable survival rates. Thus, localizing the
PSMA-ligand PET in patients with PSA persistence. Materials residual disease after surgery is crucial to precisely define the
and Methods: 210 patients were retrospectively selected from planned target volume (PTV) of salvage radiotherapy (SRT).
the 6 participating centers and included in the study according Objective: to evaluate the impact of 68Ga-PSMA-11-PET/CT on
to the following inclusion criteria: a) RP for PCa; b) persistently SRT planning in BCP patients. Materials and Methods: Design:
elevated post-operative PSA levels (≥0.1 ng/mL) ≥6 weeks after 68
Ga-PSMA-11-PET/CT is performed in our institution through
surgery; c) PSMA-ligand PET performed within 12 months after RP. a prospective, single-center, open-label study (prot. P-5315) in
Positivity rate, impact on management and positive-predictive hormone-naïve PCa. We performed a retrospective sub-analysis
value were determined. In patients with additional PSMA-ligand in BCP patients matching these inclusion criteria: 1) RP as
PET before RP (n=33) a subgroup analysis was performed to primary therapy; 2) PSA-nadir >0.1 ng/mL at 8 weeks after RP; 3)
determine PET-based disease persistence and recurrence. No adjuvant/salvage therapy or hormonal-therapy performed
Anonymized imaging datasets were evaluated independently by after RP; 4) all patients considered eligible for SRT in prostate
three experienced nuclear medicine physicians employing the bed; 5) PET scan performed within 12 months from RP. Changes
molecular imaging TNM system PROMISE. Results: PSMA-ligand in clinical management and SRT planning were defined by
PET identified PCa-lesions in 68% (143/210) of patients with PSA a singlecentre multidisciplinary tumour board. Population
persistence at a median PSA level of 1.1 ng/mL. Detection rate characteristics: twenty-eight (n=28) patients matched all
significantly increased in accordance with PSA levels at time inclusion criteria and were analysed. ISUP grade <=3 (n=11/28),
of scan (p<0.001). Overall, 36% (76/210) patients had disease >=4 (n=17/28); stage >=pT3a (n=17/28); pN1 (n=7/28); R1
limited to the pelvis while 30% (64/210) of patients had distant (n=16/28). Median/mean PSA-nadir=0.34/0.48 ng/mL (0.1-3.3);
lesions. The most commonly involved regions were obturator median/mean PSAdt=2.8/7.1 months (0.6-44.6); median/mean
(47%) and presacral/mesorectal (42%). In the subgroup analysis PSAvel=0.8/3.1 ng/mL/year (range 0.1-24.7). Results: Overall
(PSMA-ligand PET before and after surgery), 45% (15/33) of results: 68Ga-PSMA-11-PET/CT detection rate was 57.1% (CI95%
patients had at least one lesion already detected at baseline (PET 37.4%-75.0%). Median/mean PSA at time of imaging=0.53/1.06
persistence), 24% (8/33) had previously undetected lesions (PET ng/mL (range 0.22-8.9). Prostate bed relapse only was detected
S297 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

in 3.6% of cases. Intra-pelvic relapse (pelvic lymph-nodes with/ all patients, 18F-FDG PET/CT and MRI were both positive for
without prostate bed) was detected in 21.4%,.The presence spondylodiscitis in 53/66 (80%) patients, the two techniques
of at least one extra-pelvic lesion (extra-pelvic nodes and/or were both negative in 6/66 (9%),18F-FDG PET/CT was negative
bone) was detected in 32.1%. of cases. Oligometastatic disease while MRI was positive in 7/66 (11%). The agreement was
(1-3 PSMA positive lesions) was detected in 53.6% of cases. SRT moderate (K=0.579). Twenty-eight/66 (42%) patients performed
planning: in 46.4% of patients (13/28), SRT in prostate bed was whole-spine MRI: 18F-FDG PET/CT and MRI were both positive
confirmed as intended before PET scan. In 53.6% of patients in 21/28 (75%), the two techniques were both negative in
SRT planning was changed: 7/28 patients performed SRT in 3/28 (11%), 18F-FDG PET/CT was negative while MRI was
prostate bed and additional stereotactic radiotherapy (SBRT) on positive in 4/28 (14%). The agreement was moderate (K=0.529).
PET positive findings. In 2/28 cases PTV was modified including Considering the 21/28 with positivity of the two techniques,
only PET positive pelvic nodes without standard radiotherapy in 15/21 patients the same lesions were identified, in 5/21 MRI
in prostate bed. SRT was aborted in 5/28 patients and ADT identified lesions in two districts while 18F-FDG PET/CT only in
was administrated instead. In 1/28 case SRT was aborted and one, in 1/21 patients 18F-FDG PET/CT identified one lesion more
pelvic lymph-node dissection was performed. Conclusion: than MRI. Nineteen/66 (29%) patients performed two-districts
In this patient-series, 68Ga-PSMA-11-PET/CT proved its role in MRI: 18F-FDG PET/CT and MRI were both positive in 13/19
BCP setting detecting disease outside prostate bed in 53.5% (68%), the two techniques were both negative in 3/16 (16%),
of cases and SRT planning was modified due to the integration 18F-FDG PET/CT was negative while MRI was positive in 3/16
of 68Ga-PSMA-11-PET/CT results into the decision-making (16%). The agreement was moderate (K=0.574). Considering the
process. These data may suggest the presence of extended 13/19 with positivity of the two techniques, in 11/13 patients
disease not detected by conventional imaging prior to surgery the same lesions were identified, in 1/13 MRI identified lesions
and highlight the importance of PET imaging in BCP setting. in two districts while 18F-FDG PET/CT only in one, in 1/13
References: None. patients 18F-FDG PET/CT identified one lesion more than
MRI. In the subgroup of 19/66 (29%) patients who performed
one-district MRI, 18F-FDG PET/CT and MRI were both positive
1709 and completely concordant for lesions identified that were
respectively: cervical in 1/19 (5%), dorsal in 5/19 (26%), lumbar
Inflammation & Infection - Parallel Session:
in 13/19 (69%). Conclusion: Our results confirm the 18F-FDG
Infection and Inflammation (Beyond
PET/CT diagnostic value in the diagnosis of spondylodiscitis,
Cardiovascular System)
comparable to MRI for the entire spine evaluation. It can be
considered a valid alternative to MRI, in particular in patients
Wednesday, October 16, 2019, 10:00 - 11:30 Lecture Hall 115 who cannot perform it. References: None.

OP-781 OP-782
A comparison of the diagnostic value of MRI and Whole Predictive Potential of Nonstandard Quantitative Imaging
body 18F-FDG PET/CT in diagnosis of spondylodiscitis. Features in Diabetic Foot
A comparison of the diagnostic value of MRI and Whole A. Marciano1, J. Beukinga2, Z. Keidar3, M. Kurash3, R. Zanca1, A. W. J.
body 18F-FDG-PET/CT in diagnosis of spondylodiscitis M. Glaudemans2, P. A. Erba1, R. H. J. A. Slart2;
C. Altini, A. Branca, R. Ruta, G. Santo, C. Ferrari, A. Niccoli Asabella, 1
Regional Center of Nuclear Medicine, Department of
N. Merenda, G. Rubini; Translational Research and New Technology in Medicine,
Nuclear Medicine Unit, Interdisciplinary Department of Univerisity of Pisa and AOUP, Pisa, ITALY, 2Medical Imaging
Medicine – University of Bari “Aldo Moro”, Bari, ITALY. Center, Department of Nuclear Medicine and Molecular
Imaging, University of Groningen, University Medical Center
Groningen, Groningen, NETHERLANDS, 3Department of Nuclear
Aim/Introduction: Magnetic resonance Imaging (MRI) is Medicine, Rambam Health Care Campus, Haifa, ISRAEL.
considered the most accurate technique for the diagnosis of
spondylodiscitis while currently 18F-FDG PET/CT has been
proposed in doubtful cases. The aim of this study was to Aim/Introduction: [18F]FDG PET/CT is an accurate imaging
compare the role of 18F-FDG PET/CT and MRI in the diagnosis modality for the diagnosis of diabetic foot complications.
of spondylodiscitis. Materials and Methods: 66 patients with Currently, images are generally visually assessed and quantitative
suspected spondylodiscitis (48 male, 18 female; mean age 63 analysis is limited to simple metrics like maximum standardized
years; range: 11-90 years) who performed 18F-FDG PET/CT were uptake value, target/background ratio analysis. The goal of this
retrospectively analyzed. MRI were performed on average 19 work was to assess the predictive potential of nonstandard
days before 18F-FDG PET/CT (range: 3-36 days). Cohen’s K was quantitative imaging features in the differentiation between
applied to evaluate the agreement between the two techniques soft tissue and bone infections in diabetic foot. Materials and
in all patients and in subgroups who performed whole-spine, Methods: Within a retrospective trial, we evaluated a series of
two-districts, one-district MRI respectively. Results: Considering 47 patients (mean age 58±9 years, median age 58 years, range
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S298

40-81) with possible diabetic foot infection. PET/CT images does not allow to clearly evaluate the bone; E) small increase of
were acquired about 45-60 mins after [18F]FDG administration activity with time in the suspected region with similar increase
(mean dose 376±107 MBq/kg of body weight, median dose activity in bone marrow; F) residual activity in the suspected
376 MBq/kg, range 185-580). In order to perform the texture region in the follow-up study after therapy; G) unmodified
analysis, we segmented lesions using three different methods, activity with time in the suspected region but with clear
two semiautomatic and one manual. The semiautomatics decrease of medullary and background activity. We performed
segmentations were delineated with a threshold fixed at 20% and semi-quantitative analysis considering as positive findings the
40% of the relative SUVmax on PET; with the manual method, we increase of T/B value between early and delayed images with
delineated the segmentations on CT (LDCT). Radiomics texture four different cut-off values (5%-10%-20%-30%). Results: Semi-
features (46 features) were extracted using the LIFEx package. quantitative analysis using as parameter the increase of T/B
The information resulting from the texture features analysis for all ratio with cut-off of 20% between early and delayed images
the segmentations method were correlated with the presence is the most reliable tool when qualitative analysis is not clear,
of Osteomyelitis, Soft Tissue Infections and Inflammation, using as it shows the highest accuracy (85%) with high negative
microbiological findings as reference. Data were analyzed by predictive value (81%). The region chosen for background
multivariate analysis, linear discriminant analysis. The Spearman calculation should be the contralateral joint by drawing mirror
correlation coefficient two-sided Wilcoxon rank sum test or ROI. Only in cases B or D, when bone marrow activity increases
Kruskal-Wallis test were used and corrected for multiple testing or is stable over time, the background can be chosen on the iliac
using the Bonferroni-Holm method (significance level α = crest or any other bone-marrow site. Combining bone marrow
0.05). Statistical analysis was performed with JMP Statistical scintigraphy with WBC scan showed high positive predictive
Discoverytm. Results: Texture features analysis allowed to value (100%). Conclusion: In case of “doubtful” qualitative
discriminate the presence of osteomyelitis, soft tissue infections analysis a semi-quantitative analysis can be performed on
and inflammation (Table 1). The best overall performance was delayed and late images. If T/B increases of >20% over time, a
obtained using the semiautomatic segmentations with a fixed PJI should be considered. If T/B does not increase >20%, a bone-
threshold at 40%, with the AUCs of 0.93 for Osteomyelitis, 0.90 marrow scintigraphy should be performed in order to rule out
for Soft Tissue Infections, 0.96 for inflammations, respectively. or confirm the PJI. References: None.
Conclusion: Our preliminary results suggest a predictive
potential of nonstandard quantitative imaging features in the
differentiation between inflammation and infection as well OP-784
between soft tissue and bone involvement in diabetic foot Is the18F-FDG-PET/CT able to characterize fibrosing
infection. References: None. diseases?
Y. K. Henao Celada, A. Mari Hualde, J. Orcajo Rincon, D. Zamudio
Rodriguez, A. Rotger Regí, J. J. Ardila Mantilla, J. Atance Garcia de la
OP-783 Santa, J. C. Alonso Farto;
Handling of doubtful WBC scintigraphies in patients with Hospital General Universitario Gregorio Marañon, Madrid, SPAIN.
prosthetic joint infections
G. Lauretti, C. Lauri, D. Riolo, S. Tetti, A. Signore;
Nuclear Medicine Unit, Dept of Medical-Surgical Sciences and of Aim/Introduction: To evaluate the utility of 18F-FDG-PET / CT
Translational Medicine, “Sapienza” University of Rome, Rome, ITALY. in the diagnosis of fibrosing disease. Materials and Methods:
A retrospective descriptive study including all patients who
underwent at least one 18F-FDG-PET/CT, diagnosed of fibrosing
Aim/Introduction: The aim of this study is to find the appropriate disease by conventional image and / or histology, from
protocol in order to evaluate 99mTc-HMPAO-labelled WBC December/2016 to March/2019 in the HGUGM. 20 patients
scintigraphy when the qualitative analysis is uncertain by using were recruited (15M and 5F, 3: 2), whose average age was
alternative tools like semi-quantitative analysis and/or bone 61.2 years. They were categorized into 2 groups based on the
marrow scintigraphy with 99mTc-nanocolloids. Materials presence of IgG4 infiltrate in the fibrous tissue: Group1: IgG4-
and Methods: Retrospective study on 566 patients referred related disease (IgG4-RD) and Group2: non-IgG4 fibrosing
for suspected hip and knee prosthetics infection (PJI). 99mTc- disease (No-IgG4-FD). Clinical, analytical (IgG4 serum levels) and
HMPAO-WBC images were acquired at 30’, 3h and 20h and histology were collected, as well as qualitative (morphologic
image interpreted according to EANM guidelines. Amongst and metabolic) and semi-quantitative (SUVmax) findings of
these, 37 patients had a doubtful scan and 20 performed also the 18F-FDG-PET/CT study. Results: 9 out of 20 patients were
a bone-marrow scintigraphy in order to evaluate match or included in group1 due to the presence of IgG4 infiltration and
mismatch. Inclusion criteria for “doubtful cases” were: A) small 11 were included in group2 due to the absence of it. 100% of
non significant increase of activity in the suspected region at them showed morphological alterations in 18F-FDG-PET / CT
late images; B) increase of medullary activity with time that does concordant with previous conventional images or with clinical
not allow easy visualization of peri-prosthetic bone activity; C) suspicion. 70% (14/20) presented pathological 18F-FDG uptake,
small increase of extent pf uptake in the suspected region at late mostly afecting more than one organ. The highest prevalence
images without increase of activity; D) soft tissue infection that metabolically active locations were: retroconal fat (n: 4),
S299 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

salivary glands (n: 2), pleura / mediastinum (n: 3), periaortic / range 2.1-6.2) (P=0.044, unpaired t-test), even with a substantial
retroperitoneal tissue (n: 3) and visceral (n: 2) . In group1 (IgG4- overlap. 10/25 of the IgG4-RD cases showed inverted-“V” shaped
RD) the following morphological findings were found: 4 orbital prostatic uptake, whereas none of the controls showed this
and facial affectation, 2 visceral (autoimmune pancreatitis pattern (P=0.0008, Fisher’s exact test); the controls with intense
and biliary fibrosis), 2 thoracic (pleural and mediastinal) and 1 FDG uptake showed either punctate or wedge-shaped patterns.
retroperitoneal. 100% (9/9) of the lesions, showed an increase The one-way ANOVA showed significant difference among the
in glycidic consumption, mean SUVmax: 5.1 (range 2.1-9.1). In three groups (P=0.0002), and post-hoc Tukey’s test revealed
group 2 (EF-No IgG4) the CT showed: 4 patients with orbital that the prostate SUVmax of the IgG4-RD cases with inverted-
pseudotumor, 5 retroperitoneal fibrosis, 1 soft tissue fibrosis “V” uptake (4.8±1.2; range 3.1-7.5) was significantly higher than
and 1Erdheim Chester disease. 5/11 patients (46%) presented the prostate SUVmax of the IgG4-RD cases without inverted-“V”
an increase in metabolic activity associated with fibrosing uptake (3.0±1.3; range 2.0-3.8), and was also significantly higher
lesions, SUVmax average: 5.3 (2.9-6.4). All patients were receiving than the prostate SUVmax of the controls with BPH. Conclusion:
immunosuppressant treatment at the time of the study, with Inverted-“V” shaped prostatic FDG uptake, specifically observed
the exception of 2 patients in the group2. Only 1/20 patient in IgG4-RD patients, should be a diagnostic clue for IgG4-related
showed elevation of serum IgG4. Conclusion: 18F-FDG-PET / CT prostatitis, which would be expected to provide an important
is a useful tool for locating fibrosing disease, both with presence information to achieve less-invasive biopsy. References: 1)
or absence of IgG4 infiltration, also adding information about Umehara H et al. Comprehensive diagnostic criteria for IgG4-
its inflammatory activity with respect to other conventional related disease (IgG4-RD), 2011. Mod Rheumatol. 2012;22:21-30
imaging techniques. All patients with IgG4-RD have metabolic 2) Zhang J et al. 18F-FDG PET/CT helps differentiate autoimmune
activity in any of their fibrosing lesions, more frequently than no- pancreatitis from pancreatic cancer. BMC Cancer. 2017;17:695.
IgG4-FD do, although there is no clear difference in the locations
or in its intensity. References: None.
OP-786
Diagnostic validity of (S)-4-(3-[18F]Fluoropropyl)-L-
OP-785 glutamic acid ([18F]FSPG) positron emission tomography/
The Significance Of Inverted-“V” Shaped Prostatic FDG computed tomography (PET/CT) for the assessment of
Uptake As A Diagnostic Clue for IgG4-Related Prostatitis disease activity in patients with inflammatory bowel
K. Nakatani, K. Yoshino, T. Koyama; disease: a phase 2 pilot study
Kurashiki Central Hospital, Kurashiki, Okayama, JAPAN. D. Lee1, M. Seo2, B. Ye3, S. Park3, S. Chae1, S. Hwang3, S. Lee1, S. Oh1, J.
Kim4, S. Na5, N. Koglin6, M. Berndt6, A. Stephens6, D. Moon1;
1
Department of Nuclear Medicine, Asan Medical Center,
Aim/Introduction: FDG-PET/CT has been considered to University of Ulsan College of Medicine, Seoul, KOREA, REPUBLIC
provide functional information about the disease activity OF, 2Department of Nuclear Medicine, Ulsan University Hospital,
in patients with IgG4-related disease (IgG4-RD), and several University of Ulsan College of Medicine, Ulsan, KOREA, REPUBLIC
typical manifestations are well-known in the pancreas as well OF, 3Department of Gastroenterology and Inflammatory Bowel
as submandibular glands and periaortic soft tissue. As for the Disease Center, Asan Medical Center, University of Ulsan College
prostate, much less is known about the specific features of of Medicine, Seoul, KOREA, REPUBLIC OF, 4Department of
IgG4-related prostatitis and about how to differentiate from Nuclear Medicine, Hanyang University Medical Center, Hanyang
benign prostatic hyperplasia (BPH). Recently, inverted-“V” University College of Medicine, Seoul, KOREA, REPUBLIC OF,
shaped prostatic FDG uptake has been reported as helpful to 5
Department of Radiology, Uijeongbu St. Mary’s Hospital, College
diagnose autoimmune pancreatitis. Our aim was to investigate of Medicine, The Catholic University of Korea, Seoul, KOREA,
the significance of this sign in the differential diagnosis of REPUBLIC OF, 6Life Molecular Imaging GmbH, Berlin, GERMANY.
IgG4-related prostatitis from BPH. Materials and Methods: All
the study population underwent FDG-PET/CT scan between
05/2012-01/2019. The cases included were 25 male patients Aim/Introduction: Assessment of disease activity in
(age: 56-83) who met the comprehensive diagnostic criteria for inflammatory bowel disease (IBD), comprising ulcerative
IgG4-RD 2011 (Umehara et al.), histopathologically or clinically; colitis (UC) and Crohn’s disease (CD), is important for guiding
the controls were 22 healthy male individuals (age: 52-80) who subsequent therapy. [18F]FSPG can image xCˉ transporter activity
studied for cancer screening and turned out to have BPH. The with PET. We aimed to explore the validity of [18F]FSPG PET/
visual shape of FDG uptake distribution in the prostate were CT for evaluating ileocolonic inflammation in patients with
compared, as well as their SUVmax, between the cases and IBD. Materials and Methods: We conducted a prospective
the controls. Furthermore, the intensity of FDG uptake in the study enrolling patients with definite UC or CD, aged 19 to
prostatic glands was compared using one-way ANOVA among 79 years, with symptoms suggestive of active IBD. All patients
the IgG4-RD cases with inverted-“V” uptake, those without underwent endoscopy within 7 days prior to or after [18F]FSPG
inverted-”V” uptake, and the controls. Results: The IgG4-RD PET/CT. Abdominopelvic PET/CT imaging was performed after
cases had a slight tendency to show higher prostate SUVmax injection of 200 MBq of [18F]FSPG. Increased [18F]FSPG uptake
(3.7±1.5; range 2.0-7.5) than the controls with BPH (3.0±0.9; in the bowel compared to the liver was interpreted as positive
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S300

for active inflammation. Endoscopic assessment of disease pulmonary infections. However, they can be notoriously difficult
activity was performed using Ulcerative Colitis Endoscopic to interpret as they rely on the presence of nonspecific structural
Index of Severity (UCEIS) for UC (≥ 2 as active disease), and abnormalities that often occur late in the disease process and
Crohn’s Disease Endoscopic Index of Severity (CDEIS) for CD (≥ can mimic other pathologies. Therefore, invasive procedures are
3 as active disease). Results: Between August 2018 to January frequently needed to diagnose infections. Enterobacteriaceae
2019, ten patients with UC (median age 42, 6 males), and 10 (E. coli, Klebsiella spp., Enterobacter sp., Salmonella sp., etc.), a
with CD (median age 28, 9 males) were enrolled. Endoscopic family of rod-shaped Gram-negative bacteria that normally
diagnosis of active inflammation was made in six with UC, inhabit the gastrointestinal tract, are the most common
and eight with CD. [18F]FSPG PET/CT was positive in four of cause of Gram-negative bacterial infections in humans and
six patients with UC (67%), and all eight with CD (100%). [18F] a predominant cause of hospital-acquired pneumonia. We
FSPG PET/CT could correctly diagnose endoscopic remission have previously demonstrated that 2-18F-fluorodeoxysorbitol
in two of four with UC (50%), and all two CD (100%). Summed (18F-FDS), synthesized from 18F-FDG, can be used to specifically
maximum standardized uptake value (SUVmax) of bowel localize infections due to Enterobacteriaceae and monitor the
segments in UC did not show a significant correlation with efficacy of antibiotic treatment in animal models. Therefore, we
clinical and laboratory markers of disease activity (P>0.05), but hypothesized that 18F-FDS PET could be used to noninvasively
it showed a strong correlation with UCEIS (ρ=0.79, P=0.006), detect and monitor Enterobacteriaceae pneumonia in
and histological score (Robarts Histopathology Index: ρ=0.83, patients. Materials and Methods: We prospectively enrolled
P=0.003). In CD, summed SUVmax had a strong correlation with patients with microbiologically confirmed pneumonia due to
C-reactive protein (ρ=0.94, P<0.001), fecal calprotectin (ρ=0.98, Enterobacteriaceae as well as controls with an inflammatory
P<0.001), Crohn’s Disease Activity Index (ρ=0.70, P=0.025), or oncologic pulmonary disease without infection. Patients
and CDEIS (ρ=0.90, P<0.001), but not with histological score were injected with 370 MBq of 18F-FDS and PET/CT performed
(Colonic and Ileal Global Histologic Disease Activity Score: n=6, 1- and 2-hours post-injection. A follow-up 18F-FDS PET/CT
P>0.05). Twelve of 47 bowel segments in patients with UC and was also performed in a subset of infected patients after the
24 of 41 segments in patients with CD showed active lesions initiation of antibiotic to monitor the efficacy of the treatments.
in endoscopy, and sensitivity and specificity of [18F]FSPG PET/ Results: Seven patients, three with Enterobacteriaceae
CT in identifying active bowel lesions were 75% (9/12), and 86% infection and four controls, with a mean age of 64.5 ± 5.2 years
(30/35), respectively for UC, and 71% (17/24), and 94% (16/17), were imaged. The mean administered activity was 322.9 ±
respectively for CD. SUVmax showed a strong correlation with 29.6 MBq (range, 284.9 - 357.42 MBq). There were no adverse
segmental UCEIS (ρ=0.66, P<0.001), and segmental CDEIS or clinically detectable pharmacologic effects in any of the
(ρ=0.61, P<0.001). Conclusion: [18F]FSPG PET/CT imaging may subjects. 18F-FDS PET was able to specifically detect and localize
noninvasively assess disease activity status of IBD. References: pulmonary infections in all the three patients. PET activity was
None. significantly higher in infected lesions compared with sterile,
inflammatory (P=0.004) or neoplastic pulmonary lesions
(P<0.001) demonstrating specificity for infectious lesions. Finally,
OP-787 18
F-FDS PET was also able to monitor the efficacy of antibiotic
Noninvasive Diagnosis and Monitoring of Pneumonia treatment, demonstrating a decrease in signal intensity
using Pathogen-Specific 18F-Fluorodeoxysorbitol (FDS) PET and correlating with clinical improvement. Conclusion: We
U. Granados1, A. A. Ordoñez2,3, L. M. Wintaco4,1, C. A. Bedoya2,3, S. present the first-in-human results of a novel bacteria-class
Frey5, J. D. Sanchez2,3, F. R. D’Alessio6, H. T. Ravert5, D. P. Holt5, R. F. specific PET imaging tracer for rapid and specific detection of
Dannals5, M. G. Pomper5, S. K. Jain2,3,5; pulmonary infections due to Enterobacteriaceae. 18F-FDS clears
1
Unidad de Medicina Nuclear, Hospital Internacional de Colombia, rapidly from the lungs, is safe and well tolerated in patients.
Fundación Cardiovascular de Colombia, Bucaramanga, These preliminary data support the potential role of 18F-FDS
COLOMBIA, 2Center for Infection and Inflammation Imaging as a clinically translatable tracer for the specific detection of
Research, Johns Hopkins University School of Medicine, Baltimore, Enterobacteriaceae infections in humans. References: None.
MD, UNITED STATES OF AMERICA, 3Department of Pediatrics, Johns none
Hopkins University School of Medicine, Baltimore, MD, UNITED
STATES OF AMERICA, 4Universidad del Rosario, Unidad de Medicina
Nuclear, Hospital Internaciona, Bogotá, COLOMBIA, 5Russell H. OP-788
Morgan Department of Radiology and Radiological Sciences, Real-Time Imaging of Human Skin Invasion by
Johns Hopkins University School of Medicine, Baltimore, MD, Fluorescently Labelled (Radiation-Attenuated)
UNITED STATES OF AMERICA, 6Division of Pulmonary and Critical Schistosoma mansoni Parasites
Care Medicine, Department of Medicine, Johns Hopkins University C. de Korne1, B. M. F. Winkel1, M. R. Dalenberg1, D. M. van Willigen1,
School of Medicine, Baltimore, MD, UNITED STATES OF AMERICA. A. W. Hensbergen1, E. C. de Jong2, M. Roestenberg1, F. W. B. van
Leeuwen1;
1
LUMC, Leiden, NETHERLANDS, 2AMC, Amsterdam, NETHERLANDS.
Aim/Introduction: Imaging tools such as chest X-ray, computed
tomography (CT) are frequently used in the management of
S301 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

Aim/Introduction: With around 54 million people infected Plenary 4: Highlights Lecture


with the parasite Schistosoma mansoni (Sm), schistosomiasis
is considered as one of the most devastating parasitic diseases. Wednesday, October 16, 2019, 12:15 - 13:15 Auditorium
After penetrating the skin, Sm larvae, termed cercariae,
transform into schistosomula and stay intradermally for several
days. During the skin stage interaction with the dermal immune OP-789
system can take place, which makes this stage a promising Highlights Lecture
target for schistosomiasis vaccine development. It is, however, V. Garibotto;
unclear how the skin invasion takes place exactly. To allow Nuclear Medicine and Molecular Imaging Division,
for imaging of the initial skin invasion, we have developed a Geneva University Hospitals, Geneva, SWITZERLAND.
tracer-based method that supports real-time tracking of the OP-790
multicellular Sm cercaria. Using this method, we compared Highlights Lecture
the skin penetration of non-attenuated (NA) and radiation- S. Schwarzenböck;
attenuated (RA) Sm cercariae. Moreover, we have studied Rostock University Medical Center, Department
the dermal immune response they induced after invasion. of Nuclear Medicine, Rostock, GERMANY.
Materials and Methods: Sm cercariae were shed from water
snails and half of them were attenuated by irradiating them to
a total dose of 20 krad. To enable tracking of the cercariae, they Scientific e-Poster Presentation Sessions
were labelled with a translocator protein targeting fluorescent
dye. Fluorescence confocal microscopy movies were obtained 111
of NA cercariae (n=45) and RA cercariae (n=35) penetrating
human skin explants, available from plastic surgery, and their
e-Poster Presentation Session 1 - Oncology:
invasion behaviour was analysed. Following infection, the
Oncology - Greatest Hits!
dermal immune response after exposure to RA cercariae was
assessed and compared to the exposure to NA cercariae. Sunday, October 13, 2019, 8:00 - 9:30 Room 133/134
Results: The labelling strategy yielded brightly fluorescent
cercariae. Monitoring the invasion of the cercariae in human
skin explants confirmed the infectious potential of both the NA
and RA cercariae, for both groups 51% of the tracked cercariae EPS-001
entered the human skin within 30 min. Three different types Visualization of sentinel lymph nodes in gynecological
of skin invasion were seen: 1) full body penetration, lodged in cancer patients
epidermis (NA cercariae: 17%, RA cercariae: 28%), 2) full body I. Sinilkin1, V. Chernov1, A. Medvedeva1, R. Zelchan1, O. Bragina1, A.
penetration, reached the basal membrane (NA cercariae: 61%, Chernyshova1, L. Kolomiets1, M. Ochirov1, E. Stasyuk2, V. Skuridin2;
RA cercariae: 22%) and 3) tail shedding, reached the basal 1
Tomsk National Research Medical Center of the Russian
membrane (NA cercariae: 22%, RA cercariae: 50%). Analysis of Academy of Sciences, Tomsk, RUSSIAN FEDERATION, 2Tomsk
the dermal immune response revealed that exposure to NA Polytechnic University, Tomsk, RUSSIAN FEDERATION.
cercariae induced a regulatory immune response (enhanced
production of IL-10, IL-6 and MIP-1α), which was less well
mastered by the RA cercariae. Conclusion: In addition to Aim/Introduction: To evaluate the diagnostic efficacy of a
the more well-known single cell tracking studies we have new radiopharmaceutical 99mTc- aluminum gammoxide for
now demonstrated that similar technologies may apply for the detection of sentinel lymph nodes (SLN) in gynecological
multicellular parasites. As such, imaging studies can be used cancer patients. Materials and Methods: The study included
to help understand the dermal immune response. With that, 60 patients with endometrial cancer T1a-bNxM0 (n = 30) and
molecular imaging provides a valuable tool on the path towards cervical cancer T1a-bNxM0 (n = 30). The day before the operation,
effective vaccine development. References: None. 2-4 submucosal injections of 99mTc-Alotech at a dose of 20 MBq
per injection site were made to the cervix. Patients underwent
single photon emission computed tomography (SPECT) of the
pelvic region 18 hours after administration of the radiocolloid.
Evaluation of the results of the study was carried out both
visually and the intensity of the radiopharmaceutical uptake
in the SLN was compared with the injection site. To improve
the topographic localization of the sentinel lymph nodes, a
multimodal technique was used, consisting in combining
the results of the SPECT and MRI. Radioguide intraoperative
detection of sentinel lymph nodes using a gamma probe was
carried out. After removal of the sentinel lymph nodes, pelvic
lymph node dissection was performed to examine the condition
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S302

of the remaining lymph nodes. Results: Sentinel lymph nodes PSMA-expressing metastases, majority of PSMA-expressing
were detected in all patients by SPECT and radioguide mapping. metastases increasing in intensity, or stable PSMA-expression
In three (5%) cases one SLN were found, in 57 (95%) patients - 2 of the disease) or PSMA-responders (complete disappearance
bilateral SLN were visualized. In 78.3% of cases SLN were located of pathologic PSMA uptake, or majority of PSMA-expressing
in the region of the external and internal iliac vessels, and in all metastases decreasing in intensity). Descriptive statistics and
cases the location of the SLN was determined by SPECT/MRI measures of associations (two-sided Fisher’s exact test and Phi
study. The excised SLNs were evaluated by urgent cytology coefficient) were calculated. Results: For enzalutamide and
with subsequent routine histological examination. By urgent abiraterone, the median delay between the first 68Ga-PSMA
cytology in 9 SLN metastatic lesions were and two patients had PET/CT and the start of therapy was 8 (IQR:7-16) and 24 (IQR:8-
micrometastases. Conclusion: The use of radiopharmaceutical 30) days, respectively. The median delay between the start of
99m
Tc- aluminum gammoxide in patients with gynecological therapy and the second 68Ga-PSMA PET/CT was 110 (IQR:76-124)
cancer allows you to identify SLN with sensitivity and specificity and 87 (IQR:71-242) days, respectively. PSA-response and PSMA-
of 100%. The use of the multimodal SPECT/MRI fusion allows response were perfectly associated for both enzalutamide
accurately indicate the anatomical localization of the SLN. (8 PSA/8 PSMA-non-responders, 3 PSA/3 PSMA-responders;
References: None. p=0.006, Phi=1.000) and abiraterone (11 PSA/11 PSMA-non-
responders, 4 PSA/4 PSMA-responders; p=0.001, Phi=1.000). No
isolated PSMA flare was detected, as PSA-response was always
EPS-002 associated with a decrease in PSMA-expression on the second
Evaluation of PSMA Expression Changes on PET/CT PET/CT. Conclusion: This retrospective study suggests that,
Before and After Initiation of Novel Antiandrogen Drugs after a median follow up of 3 months under enzalutamide or
(Enzalutamide or Abiraterone) in Metastatic Castration- abiraterone, PSMA expression changes on PET/CT are strongly
Resistant Prostate Cancer Patients associated with PSA response. No PSMA-expression flare was
N. Plouznikoff1,2, C. Artigas1, S. Sideris3, T. Gil3, N. Martinez-Chanza3, found, but an early and limited flare phenomenon cannot be
T. Roumeguere4, A. Peltier5, P. Flamen1; excluded. Prospective studies are needed to better understand
1
Department of Nuclear Medicine, Institut Jules Bordet, Université PSMA expression dynamics following the start of enzalutamide
Libre de Bruxelles (ULB), Brussels, BELGIUM, 2Department of Nuclear and abiraterone, along with its potential role in response
Medicine, Centre Hospitalier de l’Université de Montréal (CHUM), assessment. References: None.
Montreal, QC, CANADA, 3Department of Oncology, Institut Jules
Bordet, Université Libre de Bruxelles (ULB), Brussels, BELGIUM,
4
Department of Urology, Hôpital Erasme, Université Libre de EPS-003
Bruxelles (ULB), Brussels, BELGIUM, 5Department of Urology, Institut Neoadjuvant Pazopanib Treatment In High-risk Soft Tissue
Jules Bordet, Université Libre de Bruxelles (ULB), Brussels, BELGIUM. Sarcoma: A Quantitative Dynamic 18F-FDG PET/CT Study
Of The German Interdisciplinary Sarcoma Group
C. Sachpekidis1,2, I. Karampinis3, J. Jakob4, B. Kasper5, K. Nowak6,7, L.
Aim/Introduction: Novel androgen deprivation therapies Pilz8, U. Attenberger9, T. Gaiser10, H. G. Derigs11, M. Schwarzbach12, P.
are currently indicated for castration-resistant prostate cancer Hohenberger3, A. Dimitrakopoulou-Strauss1, U. Ronellenfitsch3,13;
patients. The aim of this study was to retrospectively investigate 1
Clinical Cooperation Unit Nuclear Medicine, German Cancer
the association between 68Ga-labeled Prostate-Specific Research Center, Heidelberg, GERMANY, 2Nuclear Medicine
Membrane Antigen (PSMA) expression changes on PET/CT and Dept, Bern University Hospital, Bern, SWITZERLAND, 3Division
the response to treatment, mainly based on Prostate-Specific of Surgical Oncology and Thoracic Surgery, University Medical
Antigen (PSA) levels, following the start of enzalutamide or Center Mannheim, Mannheim, GERMANY, 4Department of
abiraterone in metastatic castration-resistant prostate cancer General, Visceral and Child Surgery, University Medical Center
(mCRPC) patients. Materials and Methods: We retrospectively Göttingen, Göttingen, GERMANY, 5Interdisciplinary Tumor Center
reviewed all 68Ga-PSMA-11 PET/CT scans performed at our Mannheim, Sarcoma Unit, Mannheim University Medical Center,
institution from November 2014 to March 2019. We included Mannheim, GERMANY, 6Division of Surgical Oncology and
mCRPC patients with a first 68Ga-PSMA PET/CT performed <2 Thoracic Surgery, University Medical Center Mannheim, Heidelberg,
months before the start of enzalutamide or abiraterone, and GERMANY, 7Department of Abdominal, Vascular and Thoracic
a second 68Ga-PSMA PET/CT performed <1 year after (with no Surgery, Romed Klinikum, Rosenheim, AUSTRIA, 8Medical Faculty
modification in therapy between scans). 11 and 15 patients were Mannheim, University of Heidelberg, Mannheim, GERMANY,
included in the enzalutamide and abiraterone arms, respectively. 9
Institute of Clinical Radiology and Nuclear Medicine, University
All associated clinical records were reviewed. The biological data Medical Center Mannheim, Mannheim, GERMANY, 10Institute of
was used to distinguish PSA-non-responders (increasing PSA Pathology, University Medical Center Mannheim, Mannheim,
following the start of therapy or the nadir thereafter) and PSA- GERMANY, 11Department of Hematology and Oncology, Klinikum
responders (decreasing PSA following the start of therapy or Frankfurt-Hoechst, Frankfurt am Main, GERMANY, 12Department
the peak thereafter). The PSMA PET/CT response was assessed of Surgery, Klinikum Frankfurt-Hoechst, Frankfurt am Main,
visually by two independent nuclear medicine physicians. GERMANY, 13Department of Abdominal, Vascular, and Endocrine
Patients were classified as PSMA-non-responders (≥1 new Surgery, University Hospital Halle, Halle (Saale), GERMANY.
S303 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

Aim/Introduction: The outcome of high-risk soft tissue sarcoma Aim/Introduction: To investigate the role of metabolic
(STS) is poor with radical surgery being the only potentially response with 18F-FDG PET/CT in patients with non-small cell
curative modality. Pazopanib is a multikinase inhibitor approved lung carcinoma (NSCLC) treated with Immune Checkpoint
for treatment of metastatic STS. Most recently, the German Inhibitors (ICI). Materials and Methods: The trial was registered
Interdisciplinary Sarcoma Group (GISG-04/NOPASS) trial has at http://www.clinicaltrials.gov (NCT03563482). We analyzed
shown that preoperative pazopanib therapy is not effective for data from 25 patients (16 male, 9 female, mean age 75) with
unselected high-risk STS, using metabolic response in 18F-FDG NSCLC treated with ICI prospectively enrolled from April 2017
PET/CT as primary endpoint; nevertheless, relevant treatment to December 2018. 18F-FDG PET/CT and contract enhanced
effects were observed in selected patients. Herein, we evaluate CT were performed at baseline and after 8 week of treatment
the potential role of kinetic analysis of 18F-FDG data derived in all patients. Response assessment was evaluated according
from application of dynamic PET/CT in response assessment metabolic and morphological criteria based on EORTC and
to pazopanib of STS patients scheduled for surgical resection. iRECIST, respectively. As metabolic parameters, we utilized also
Materials and Methods: Sixteen STS patients treated with metabolic tumor volume (MTV), total lesion glycolysis (TLG), as
pazopanib as neoadjuvant therapy before surgery were enrolled well as their percentage changes (ΔSUVmax, ΔMTV, and ΔTLG ).
in the analysis. All patients underwent dynamic PET/CT prior to With a median follow-up of 11.3 months, response criteria we
and after pazopanib treatment. Data analysis consisted of visual mutually compared and correlated to progression-free survival
(qualitative) analysis of the PET/CT scans, semi-quantitative (PFS). Results: Based on metabolic response, after 8 weeks of
evaluation based on SUV calculations, and quantitative analysis of ICI we identified 8 (32%) partial metabolic response (PMR), 11
the dynamic 18F-FDG PET data based on two-tissue compartment (44%) stable metabolic disease (SMD), and 6 (24%) progressive
modeling as well as on a non-compartmental model based on metabolic disease (PMD). Median values for the other metabolic
the calculation of the fractal dimension of the time-activity parameters resulted ΔSUVmax=+8.21%, ΔMTV=+67.7% and
curves. Resection specimens were histopathologically assessed ΔTLG=+37.6%. On the other hand, 5 (20%) partial response (PR),
and the percentage of regression grade was recorded. Time to 11 (44%) stable disease (SD), and 9 (36%) progressive disease
tumor relapse/progression was also calculated. Results: In the (PD) were identified according to morphological criteria. On
follow up 12/16 patients (75%) were alive without relapse, while log rank test, EORTC response classified as PMR vs SMD/PMD
four patients (25%) relapsed, among them one patient who resulted significantly correlated to PFS (p=0.014). Univariate
died. Mean histopathological regression was 26%. The studied analysis with Cox proportional hazards determined a statistically
population was dichotomized according to mean value of the significant association to PFS also for ΔSUVmax (p=0.009),
percentage of histopathological regression after pazopanib ΔMTV (p=0.03), and ΔTLG (p=0.013). Moreover, in patients
as a cutoff. Using the 30% regression grade as threshold, 6/14 with PR and SD according to iRECIST, there was a significant
patients (43%) showed partial remission (PR), while stable difference in PFS based on metabolic response (median not
disease (SD) was seen in the rest of 8 evaluable patients (57%). reached for PMR vs 6 months for SMD/PMD, p=0.023; HR 0.229).
Although semi-quantitative evaluation showed no statistically Conclusion: Metabolic response by 18F-FDG PET/CT allows
significant change of SUVaverage and SUVmax, 18F-FDG kinetic for the prediction of patients with longer PFS during therapy
analysis revealed a significant decrease of the perfusion-related with ICI. The added value of EORTC criteria is confirmed for
parameter K1. The dichotomization of the studied population patients presenting with a PR or SD according to iRECIST.
according to histopathologic regression grade showed no The Italian Association for Research on Cancer (AIRC -
statistically significant differences between the PR and SD Associazione Italiana per la Ricerca sul Cancro) is acknowledged
groups. Conclusion: Although the widely used PET parameter for the support on research. References: None.
SUV did not show significant response, the perfusion-related
kinetic parameter K1 -reflecting the carrier-mediated transport
of 18F-FDG from plasma to tumor- significantly decreased as a EPS-005
marker of response to pazopanib in STS. This finding could be The evaluation of tumor response to neoadjuvant
due to the anti-angiogenic effect of pazopanib. 18F-FDG PET chemotherapy for esophageal cancer using PERCIST
parameters did not show any association to histopathological 1.0-multicenter study
regression as response to the treatment. References: None. H. Kaida1, K. Kitajima2, M. Nakajo3, M. Ishibashi4, R. Minamimoto5,
K. Hirata6, K. Nakatani7, T. Yasuda1, K. Ishii1;
1
Kindai University Faculty of Medicine, Osaka-Sayama, JAPAN,
EPS-004 2
Hyogo College of Medicine, Nishinomiya, JAPAN, 3Graduate
Role of Metabolic Response by 18F-FDG PET/CT Added School of Medical and Dental Sciences, Kagoshima University,
to iRECIST in NSCLC Patients Treated with Immune Kagoshima, JAPAN, 4School of Medicine, Tottori University,
Checkpoint Inhibitors Yonago, JAPAN, 5National Center for Global Health and Medicine,
A. Castello1, L. Toschi2, S. Rossi2, E. Mazziotti1, E. Lopci1; Tokyo, JAPAN, 6Hokkaido University Graduate School of Medicine,
1
Nuclear Medicine, Humanitas Clinical and Research Hospital - Sapporo, JAPAN, 7Kurashiki Central Hospital, Kurashki, JAPAN.
IRCCS, Rozzano (MI), ITALY, 2Oncology and Hematology, Humanitas
Clinical and Research Hospital - IRCCS, Rozzano (MI), ITALY.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S304

Aim/Introduction: To evaluate tumor response to neoadjuvant 1


Department of Nuclear Medicine and PET/CT Centre,
chemotherapy (NAC) and predict esophageal squamous cell Imaging Institute of Southern Switzerland, Lugano-
carcinoma recurrence using Positron Emission Tomography Bellinzona, SWITZERLAND, 2Department of Medical
Response Criteria in Solid Tumors (PERCIST) 1.0. Materials and Oncology, Oncology Institute of Southern Switzerland,
Methods: Our study population was collected from seven Bellinzona, SWITZERLAND, 3Department of Nuclear
institutions in Japan, and comprised of 180 patients (153 men Medicine, University of Messina, Messina, ITALY.
and 27 women) who underwent fluorodeoxyglucose-positron
emission tomography/computed tomography (FDG-PET/CT)
before and after NAC prior to planned surgical resection. The Aim/Introduction: The aim of this study was to assess response
median age of our population was 66 (range, 38-78) years. to NAC and prognostic value considering dynamic evolution
Patients were divided into responder and non-responder based of metabolic/volumetric parameters measured on 18F-FDG
on pathological response, and the pathological response of PET/CT in TNBC. Materials and Methods: We retrospectively
both primary tumor and lymph node metastasis was evaluated. analyzed 42 patients with TNBC, who performed a staging PET/
The PET parameters including peak standardized uptake CT before and after neo-adjuvant chemotherapy. Treatment-
value corrected for lean body mass (SULpeak) and total lesion related changes in SUVmax, MTV and TLG were evaluated
glycolysis (TLG) were measured to evaluate PERCIST to both (ΔSUVmax, ΔMTV and ΔTLG) in the primary tumor. To identify the
primary lesion and lymph node metastasis. To examine the optimal cut-off value of these parameters a receiver-operating
diagnostic performance of each parameter in discriminating curve analysis was performed. Kaplan-Meier method was
pathological responder, receiver operating curve (ROC) analysis used to evaluate prognostic value. The associations between
was conducted, and the best cut-off point in each parameter early metabolic/volumetric changes, pathological complete
was determined. The difference between responder and non- response (pCR), and event-free survival (EFS) were examined
responder about PET parameters and clinicopathological Results: Of the 42 patients, 10 (24%) achieved pCR, 14 (33%)
variables was investigated using the Mann-Whitney U, Chi- relapsed and 10 of them died (median FU, 33 mo). No relapse
squared or Fisher’s exact test. The Cox proportional hazard was observed in patients with pCR (0.001). An optimal percent
model was used to evaluate the effects of PET parameters and of decrease in SUVmax (cutoff value ΔSUVmax 86%, p 0.0001),
clinicopathological variables for progression free survival (PFS). MTV (cutoff value ΔMTV 99%, p 0.0001) and TLG (cutoff value
Survival curves were drawn using the Kaplan-Meier method and ΔTLG 99%, p 0.0001) had the best predictive value in terms of
the significant difference between survival curves was tested pCR. No significant correlation was found with SUVmax, MTV
with the log-rank test. Results: Complete metabolic response and TLG absolute value. ΔSUVmax 84% (p 0.0026), ΔMTV 59% (p
(CMR), partial metabolic response (PMR), stable metabolic 0.0014) and ΔTLG 70% (p 0.0026) were significantly associated
disease (SMD), and progressive metabolic disease (PMD) were with EFS yielding the best prediction of recurrence Conclusion:
seen in 31 101, 40, and 8 patients, respectively. Seventy-nine Our data suggest that only the dynamic variation of 18F-FDG
(43.9%) of 180 patients showed pathologic responder. An PET/CT metabolic/volumetric parameters is a predictive marker
optimal percent decrease in SULpeak of 52.2% was found to for pCR and EFS following NAC in TNBC. In the future, this could
have a sensitivity of 87.3%, and accuracy of 68.9%, and that of be a further tool to evaluate the response to NAC addressing to
TLG of 87.3% did a sensitivity of 84.8%, specificity of 59.4%, and different therapeutic strategies References: None.
accuracy of 70.6%. There was a significant correlation between
pathologic response and PERCIST (P<0.001). Eighty-three (46.1%)
of the 180 patients developed recurrent disease. Multivaraite Cox EPS-007
regression analysis showed that PERCIST, %SULpeak reduction F-5-FPN: A Strikingly Fascinating and Potential Probe for
18

rate, number of pathological lymph nodes, and resection Monitoring Photothermal Therapy Response in Malignant
level were significantly associated with longer PFS (PERCIST; Melanoma
HR=2.134; P=0.03, %SULpeak reduction rate; HR=1.025; P<0.001, X. Lan, Y. Wang, Y. Zhang, R. An;
number of pathological lymph nodes: HR=2.370; P=0.001, Union Hospital, Tongji Medical College, Huazhong
resection level: HR=0.235; P<0.001). Conclusion: PERCIST University of Science and Technology, Wuhan, CHINA.
1.0 may be useful for predicting pathological response and
prognosis after NAC in esophageal squamous cell carcinoma
patients. References: None. Aim/Introduction: The increasing global burden and the
markedly breakthroughs in therapy of malignant melanoma
(MM) make urgent demands on efficient response evaluation. In
EPS-006 our previous researches, 18F-5-fluoro-N-(2-(diethylamino)ethyl)
18F-FDG PET/CT metabolic/volumetric parameters picolinamide (18F-5-FPN) exhibited high sensitivity, specificity
evaluation to predict response to neoadjuvant and affinity to melanin. Photothermal therapy (PTT) exploits
chemotherapy (NAC) and prognostic value in patients melanin to absorb and convert light energy into heat, which
withTriple-Negative breast cancer (TNBC) could kill tumor cells. The aim of this study was to further explore
G. Paone1, S. Di Lascio2, F. Quattrocchi3, T. Ruberto1, G. Treglia1, L. the feasibility of 18F-5-FPN PET to evaluate PTT therapy for MM,
Ceriani1, L. Giovanella1; and comparing with that of 18F-FDG. Materials and Methods:
S305 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

Nude mice bearing B16F10 (melanoma cell) or MDA-MB-231 improvement in their manual activities as documented by the
(breast cancer cell) were irradiated with an 808 nm laser for decrease of the mean VAS score prior to treatment from 8,3+-
PTT. Survival analysis with Kaplan-Meier plots and Log-rank test 1,6 to 2,8+-1,9 (p<0,05) 12 months after RSV. Conclusion: RSV is
was exploited to observe the therapy efficacy of PTT. 18F-5-FPN a highly effective procedure in elbow’s systemic arthritis active
and 18F-FDG PET imaging were performed before and after PTT synovitis. References: [Radiosynovectomy for the treatment of
for therapy response evaluation in mice bearing B16F10 until rheumatoid arthritis of the elbow joint]. Rozeboom S, Dörr U,
17 days after treatment. Furthermore, three different models, Bihl H. Nuklearmedizin. 2001 Jun;40(3):91-7.
B16F10, MDA-MB-231 bearing nude mice and inflammatory
models were prepared, and performed 18F-FDG and 18F-5-FPN
PET imaging to further assess the specificity of 18F-FDG and 18F-5- EPS-009
FPN. Results: Melanin in B16F10 tumors successfully transformed FDG PET/CT for early prediction of response to
optical energy into heat, and apparently framework destruction neoadjuvant therapy in HER2+ breast cancer: validation in
of tumor tissue and extensive necrosis were discovered by HE a multicentric population
staining after 24 h of PTT. PTT prolonged the median survival of S. Tisserand1, S. Kanoun1, J. Blanc1, B. Coudert1, A. Berriolo-
B16F10 models compared with untreated B16F10 mice (34 d vs. Riedinger1, F. Cachin2, L. Champion3, O. Humbert4, P. Salaun5, T.
9.5 d, P<0.001). The mean tumor uptakes of 18F-5-FPN on Day 2 Mognetti6, K. Kerrou7;
(7.52 ± 3.65 %ID/g) and Day 6 (0.22 ± 6.00 %ID/g) after PTT were 1
Centre Georges François Leclerc, Dijon, FRANCE, 2Centre
much lower than that those of before treatment 18.33 ± 4.98 Jean-Perrin, Clermont-Ferrand, FRANCE, 3Institut Curie,
%ID/g (P < 0.01). However, no significance existed between the Paris, FRANCE, 4Centre Antoine Lacassagne, Nice, FRANCE,
18
F-FDG uptakes on Day 1 after PTT and before treatment (6.18 ± 5
CHU Morvan, Brest, FRANCE, 6Centre Léon Bérard,
1.18 %ID/g vs. 6.54 ± 0.84 %ID/g, P > 0.05), and the tumor uptakes Lyon, FRANCE, 7Hopital Tenon, Paris, FRANCE.
on Day 5 elevated to 8.69 ± 2.75 %ID/g. For the three different
models, 18F-5-FPN only accumulated in B16F10 tumor with 20.36
± 4.38 %ID/g, but not in the MDA-MB-231 tumor (2.72 ± 0.49 Aim/Introduction: Neoadjuvant therapy (NAC) including
%ID/g) and inflammation (1.14 ± 0.30 %ID/g). However, high trastuzumab is a standard treatment in locally advanced
uptakes of 18F-FDG were seen in all three models. Conclusion: breast cancer (BC) overexpressing HER2. Achieving pathologic
Compared with 18F-FDG, 18F-5-FPN PET imaging was capable complete response (pCR) at surgery is linked with better
of estimating PTT response in MM, successfully monitored the clinical outcome. Previous monocentric studies have shown
occult recurrence after therapy, and perfectly distinguished MM the utility of FDG-PET/CT for early prediction of response in this
from inflammation and other carcinomas. This potential probe setting, thanks to a high negative predictive value to identify
may provide a new approach for precise and effective response nonresponders. However, multicentric validation is lacking and
evaluation, timely management of therapeutic regimen and there are contradictory results regarding the best predictor
sensitive follow-up. References: None. of pCR, (early metabolic changes, or low residual metabolism
after 1 or 2 cycles of therapy). The aim of this study was to
determine in a multicentric population, the best metabolic
EPS-008 parameters derived from FDG-PET/CT for early prediction
Clinical Efficacy of Radiosynoviorthesis (RSV) in Elbow of pCR after one cycle of NAC in HER2+ BC Materials and
Joint Systemic Arthritis Methods: Patients were initially recruited in the AVATAXHER trial
I. Iakovou, T. Kotrotsios, E. Giannoula, A. Kalaitzoglou, C. (EUDRACT 2009-013410-26), a prospective phase II multicentric
Sachpekidis, G. Arsos; study (26 participating centres) designed to investigate
Academic Dpt Of Nuclear Medicine, whether the addition of bevacizumab could improve the
Papageorgiou Hsp, Thessaloniki, GREECE. proportion of patients achieving pCR in patients unlikely to
respond to treatment, based on FDG-PET/CT. For this ancillary
study, only patients receiving conventional NAC (6 cycles of
Aim/Introduction: To retrospectively evaluate the long term docetaxel+trastuzumab) were included. Each patient had FDG
efficacy of radiosynoviorthesis (RSV) in patients with systemic PET/CT before the first and second cycle of therapy in order
(rheumatoid or psoriatic) arthritis of the elbow joint. Materials to evaluate baseline and residual tumour metabolism (SUVmax,
and Methods: 29 painful despite pharmacotherapy elbow joints SUVpeak, SUVmean, MTV, TLG). The tumour metabolic response
of 28 patients (22 females, 67+-3 years old enrolled the study. (ΔSUVmax, ΔSUVpeak, ΔSUVmean, ΔMTV, ΔTLG) was also calculated
They were intra-articularly injected with 2mci of 169Er citrate Results: Sixty-one patients were included. Of them, 34 (56%)
under x-ray guidance. In the pretherapeutic bone scan, all joints reached pCR. There was no significant association between
presented an positive blood pool image, indicative for active baseline tumour metabolism and pCR. In univariate analysis, low
local synovitis. Joint functional status and pain were assessed by residual metabolism was significantly associated with pCR when
a visual analog scale (VAS) of ten steps: 1 - lack of any impairment considering SUVmax (p = 0.01, AUC=0.66), SUVmean (p = 0.006,
to 10 - total disability just before (less than a week), a month and AUC=0.66) and SUVpeak (p = 0.003, AUC=0.69). Tumour metabolic
a year after treatment. Results: Twenty five in 28 patients (26 in response was also correlated with pCR when considering
29 joints -90%) responded to therapy reporting a pronounced ΔSUVmax (p = 0.001, AUC=0.71), ΔSUVpeak (p = 0.0009, AUC 0.72),
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S306

and ΔSUVmean (p=0.002, AUC=0.71). Volume-based parameters, another one endometrial carcinoma showed elevated CA-125
either baseline, residual or early changes, did not correlate with Conclusion: Cervical carcinoma was the most common type of
pCR. In multivariate analysis, ΔSUVmax remained an independent gynecologic malignancy with neck node metastasis. Six among
predictive factor of pCR (OR=8.87, p = 0.002) with high SBR 11 patients with neck node metastasis showed only single node
grade Conclusion: Our results confirm the utility of FDG-PET/ metastasis without any metastasis outside the neck. And five
CT for early prediction of pCR after NAC in HER2+ BC. Among patients with only single neck node metastasis had normal
the various metabolic parameters tested, ΔSUVmax appears to be tumor marker level. Cervical carcinoma was the most common
the most robust and appropriate in this multicentric population type of gynecologic malignancy with single node metastasis
References: None. and normal tumor marker. We should attend suspicious neck
node uptake on PET-CT albeit only single node uptake and
normal tumor marker. References: None.
EPS-010
Pathologic neck node metastasis in Patients With
Gynecologic Malignancy with neck node uptake on the EPS-011
F-18 FDG PET/CT Bone marrow FDG uptake and correlation with bone
S. Yoon; marrow plasma cell infiltration rate and plasma cell
Department of Nuclear Medicine, Health Promotion Center, H morphology in Multiple Myeloma patients
plus New Yang-Ji Hospital, Department of Nuclear Medicine, A. Paschali1, E. Panagiotidis1, P. Mitsakis1, N. Papadopoulos1,
Cheil General Hospital, Seoul, KOREA, REPUBLIC OF. T. Triantafyllou2, E. Giannoula1, M. Kotzasarlidou1, E. Verrou2, P.
Konstantinidou2, V. Chatzipavlidou1, E. Katodritou2;
1
Department of Nuclear Medicine, Theageneio Cancer
Aim/Introduction: Metastatic neck nodes limited to the lower Hospital, Thessaloniki, GREECE, 2Department of Hematology,
neck including supraclavicular node are usually associated Theageneio Cancer Hospital, Thessaloniki, GREECE.
with primary malignancies below the clavicle. Prognosis of
neck node metastasis of gynecologic malignancy is considered
significant due to possibilities of combined further distant Aim/Introduction: Multiple Myeloma (MM) is characterized
metastasis. We evaluated the pathologic type of primary by markedly heterogeneous phenotypic, genetic and clinical
malignant lesion and frequency of pathologic proven node presentation. Aim of our study was to investigate possible
metastasis in the patients with neck lymph nodal uptake on correlations between bone marrow (BM) diffuse FDG uptake,
the F-18 fluorodeoxyglucose (FDG) PET-CT in the gynecologic plasma cell infiltration rate and plasma cell morphology.
cancer patients. Materials and Methods: Between April Materials and Methods: Thirty-three patients with MM either
2009 and December 2018, retrospectively 1600 patients with at diagnosis (n=11) or at relapse (n=22) were eveluated (M/F:
pathological-proven gynecologic malignancies including cervix 19/14, median age 62.5, range: 38-80, IgG: 19, IgA: 6, light-
cancer, endometrial cancer and ovarian cancer were evaluated. chain: 7, IgD: 1, ISS1: 12, ISS2: 14, ISS3: 7). Ηigh risk cytogenetics
Thirty patients were suspected of neck lymph node metastasis detected by FISH, including t(4;14), del17p and 1q+ were
in PET/CT and underwent a sono-guided neck lymph node observed in 5 patients and t(11;14) was detected in 2 patients.
biopsies. We evaluated the primary pathologic malignant lesion Whole body 18F-FDG PET/CT studies were evaluated visually
and histologic type of node metastasis in the patients with node and semi quantitatively with the following parameters included
metastasis in the neck. We evaluated the primary pathologic in the analysis: BM metabolic state, number (Fn) and SUVmax
malignant lesion and the tumor marker in the patients with only of focal PET lesions, osteolysis number (Ln), presence and site
single node metastasis in the neck. Results: Metastastic neck of extramedullary disease (EM), paramedullary lesions (PM)
node on the PET-/CT in the patient with gynecologic malignancy and fractures(Fr), according to the IMPeTUs criteria (Nanni et al,
was suspected in 30/1600 patients. 11 patients among 30 EJNM 2018). For each patient we calculated the SUVmax ratio
proven by sono guided aspiration biopsy of the neck nodes pelvis/liver using a circular region of interest (ROI) in the central
had node metastasis, other 19 patients showed benign reactive portion of the liver far away from its edge, and a ROI within the
nodes. Among 11 patients with pathologically proven neck pelvis (to include iliac crests and sacrum/L5) taking care not to
node metastasis, 7 among 17 cervical malignant lesion (41%) include focal areas or other abnormality. Bone marrow aspirates
and 3 among 7 endometrial malignant lesion (43%) showed of the iliac crest were performed within 4 weeks around the
pathologic proven metastatic nodes. Histologic cell types PET/CT examination. According to the plasma cell morphology
showed 3 metastatic adenocarcinoma, 6 metastatic squamous we separated patients in groups of good, moderate and poor
cell carcinoma, 1 metastatic adenosquamous cell carcinoma differentiation. Results: The rate of clonal plasma cells (PCs)
and 1 lymphoma. Six patients (55%) among 11 patients with in the BM at the time of PET evaluation was ≥20% in 27/33
pathological proven neck node metastasis had pathologically patients (PCs of good differentiation: 18/33, PCs of moderate/
only single neck node metastasis without any evidence of poor differentiation:15/33). In these 27 patients the patterns of
other metastatic nodes/lesions. Four cervix carcinoma with skeletal FDG uptake were: diffuse (n=8), diffuse+focal (n=10),
single neck node metastasis had normal tumor marker. One focal (n=6) and negative (n=3). Moderate or poor differentiation
ovarian carcinoma also had normal tumor marker level. Only morphology and BM plasma cell infiltration rate≥20% both
S307 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

positively correlated with increased SUVmax pelvis/liver (p=0.05 age. Further work is needed to establish if PSMA-TL and PSMA-TV
and 0.02, respectively). Limb’s marrow involvement (femurs and is a strong and independent prognostic imaging biomarker able
humerals) was observed in all patients with diffuse axial marrow to determine therapy response. References: 1. Etchebehere
involvement, being more evident in those of moderate/poor EC et. al. Prognostic factors in patients treated with 223Ra: the
differentiation. PM or EM disease significantly correlated with role of skeletal tumor burden on baseline 18F-fluoride PET/CT
PCs’ morphology (p<0.05). Plasma cell morphology or rate of BM in predicting overall survival. J Nucl Med 2015. 2. Schmidkonz
infiltration did not correlate with PET skeletal pattern, focal sites C et. al. 68Ga-PSMA-11 PET/CT-derived metabolic parameters
on PET or lytic lesions on CT. Conclusion: These preliminary for determination of whole-body tumor burden and treatment
data suggest that the sensitivity of PET in the detection of response in prostate cancer. Eur J Nucl Med Mol Imaging 2018.
diffuse BM infiltration is dependant on plasma cell morphology
and increases with the degree of undifferentiation. References:
None. EPS-013
Retrospective cohort study to assess the prognostic
value of baseline necrosis on PET-CT imaging in Hodgkin
EPS-012 lymphoma
Ga-PSMA PET/CT whole-body tumor burden in patients
68
I. Chen, N. Borges, L. Winn, W. Osborne, G. Petrides;
with biochemical recurrence of prostate cancer Freeman Hospital, Newcastle Upon Tyne, UNITED KINGDOM.
A. Biggi Mattiolli, M. C. L. Lima, M. Camacho, C. D. Ramos, A. O.
Santos, E. Etchebehere;
Medicina Nuclear de Campinas, Campinas, BRAZIL. Aim/Introduction: Identifying prognostic markers at diagnosis
is essential to determine optimal tailored therapy for patients.
The presence of necrosis has been shown to be associated with
Aim/Introduction: In solid tumors, metabolic tumor volume inferior outcomes in patients with diffuse large B cell lymphoma
(MTV) and total lesion glycolysis (TLG) in 18F-FDG PET/CT studies (1). This retrospective cohort study assesses whether necrosis
showed to correlate with prognosis. In prostate cancer patients at baseline correlates with clinical outcomes in patients with
submitted to Ra-223 therapy, fluoride tumor volume and total Hodgkin lymphoma. Materials and Methods: All available
fluoride uptake on lesions in 18F-Fluoride PET/CT have shown to baseline PET-CT scans of patients diagnosed with Hodgkin
correlate with prognosis1. However, the determination of PSMA- lymphoma between January 2015 and December 2016 at a large
68
Ga tumor burden of PSMA in lesions (whole-body PSMA tumor UK teaching hospital were reviewed for evidence of tumour
volume-PSMA-TV and the whole-body total uptake-PSMA- necrosis by a consultant radionuclide radiologist with a specialist
TL) in 68Ga-PSMA PET/CT has not been extensively studied2. interest in lymphoma. Potential necrosis identified on PET-CT
The objective of this project is to evaluate whether the serum was then confirmed visually and quantitatively on alternative
PSA values and clinical parameters are associated with PSMA- imaging. The presence or absence of necrosis was correlated with
TV and PSMA-TL. Materials and Methods: We retrospectively prognostic markers (Total Metabolic Volume (TMV), Total Lesion
evaluated 211 patients with prostate cancer submitted to 68Ga- Glycolysis (TLG) International Prognostic Index (IPI) (Hasenclever
PSMA PET/CT due to biochemical recurrence. In 68Ga-PSMA PET/ Index)) and response assessment (metabolic response, current
CT positive studies, the tumor burden parameters PSMA-TV and remission status, relapse outcome and mortality). Results: Fifty
PSMA-TLG were calculated with a semi-automatic software (MFS three patients’ PET-CT scans were reviewed in total. Ten patients
tool; Syngo.Via VB20; Siemens Medical Solutions, Chicago, IL). The were confirmed to have necrosis on both PET-CT and alternative
images were then reviewed to exclude any areas of physiologic imaging. The presence of necrosis was associated with increased
uptake and to include pathologic areas with relatively low total mortality (40%) vs no necrosis (16%); Kaplan Meier survival
uptake. PSMA tumor burden metrics were correlated to clinical analysis demonstrated a significant difference between the
the following parameters age, free PSA levels (PSAf ), total PSA necrosis cohort compared with the no necrosis cohort using
levels (PSAt), Gleason score and the highest SUVmax lesion. the log rank test (p = 0.042). The presence of necrosis did
Results: Among the 140 patients that underwent 68Ga-PSMA not correlate with other prognostic markers (TMV, TLG or IPI).
PET/CT studies, 114 were positive and thus used to calculate the Conclusion: The presence of necrosis on baseline PET-CT scan
PMSA-TV and PSMA-TL tumor burden parameters. The mean in patients receiving frontline treatment for Hodgkin lymphoma
PMSA-TV was 28.54 cm3 and PMSA-TL was 207.99. There was a significantly correlates with increased patient mortality. Tumour
direct correlation between age and the PMSA-TV (p = 0.0056) necrosis did not significantly correlate with other prognostic
and PSMA-TL (p = 0.0004) values. Higher PSAf and PSAt levels markers. Identifying high risk patients at diagnosis is important.
were associated with higher tumor burden values of PMSA- The current UK practice of delivering more intensive frontline
TV (p = 0.0002 and p <0.0001, respectively) and of PSMA-TLV therapy to patients with a high IPI is suboptimal and intensifying
(p <0.0001 and p <0.001, respectively). The SUVmax​​ values treatment after a positive interim PET scan is also associated
only showed a direct and positive correlation with PSMA-TL (p with poor outcomes. Robust prognostic markers at diagnosis
<0.0001). Conclusion: In biochemical recurrence of prostate are a priority for the management of patients with Hodgkin
cancer, the whole-body tumor burden on 68Ga-PSMA PET/CT Lymphoma. This study has identified a new independent
has a direct and positive correlation with serum PSA values and prognostic marker in Hodgkin Lymphoma and prospective
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S308

clinical trials are required. References: 1. Adams HJA, de Klerk EPS-015


JMH, Fijnheer R, Dubois SV, Nievelstein RAJ, Kwee TC. Prognostic [68Ga]Ga-PSMA-11 PET/CT For Monitoring Response to
value of tumor necrosis at CT in diffuse large B-cell lymphoma. Treatment in Metastatic Prostate Cancer - is there an
Eur J Radiol. 2015 Mar;84(3):372-377. Added Value over Standard Follow-up?
J. Kuten, D. Sarid, O. Yossepowitch, N. J. Mabjeesh, E. Even-Sapir;
Tel Aviv Sourasky Medical Center, Tel Aviv, ISRAEL.
EPS-014
Metabolic Tumor Volume Predicts Short-Term Progression
After Immunotherapy in Non Small Cell Lung Cancer Aim/Introduction: The aim of the current study was to assess
D. Chardin, M. Paquet, J. Darcourt, J. Otto, O. Humbert; whether, and to what extent, follow-up PSMA-based PET/
Centre Antoine Lacassagne, Nice, FRANCE. CT studies add value to the routine clinical follow-up during
treatment of patients with metastatic prostate cancer (PCa).
Materials and Methods: The study cohort was composed
Aim/Introduction: Baseline markers are needed to predict of 52 patients with metastatic PCa who underwent [68Ga]
outcome after immunotherapy. This study aimed to investigate Ga-PSMA-11 PET/CT imaging and PSA level measurements
the predictive value of total metabolic tumor volume (MTV) before and during treatment. Response was categorized as
measured from baseline [18F]-fluorodeoxyglucose positron improvement, stable disease and disease progression by
emission tomography/computed tomography (FDG-PET/CT) serum PSA dynamics and compared to change in imaging
in patients with non-small cell lung cancer (NSCLC) treated findings on pre- and post-treatment PET/CT. McNemar’s test
with immunotherapy. Materials and Methods: From February was used to assess agreement between PET/CT- and PSA-
2017 to September 2018, 54 patients scheduled to initiate based response to treatment. Results: Most patients (65.4%)
immunotherapy (pembrolizumab or nivolumab) as their first or had compatible biochemical- and imaging- based response
later systemic treatment for metastatic NSCLC were prospectively to treatment. However, in 18/52 patients (34.6%) imaging and
evaluated in this non-randomized, current-care study in our biochemical response, were discrepant. In 5/52 patients (9.6%)
institution. FDG PET was performed at baseline. Standardized PET/CT “upstaged” and in 13/52 (25%) it “downstaged” disease
uptake values of lesion with the highest uptake (SUVmax) was compared to biochemical assessment. Discrepancy between
measured. Total MTV was obtained using à threshold based on imaging and biochemical response was most prominent in
41% of the SUVmax in each lesion. Short-term progression was biochemically-stable patients (90.9%), followed by patients with
defined as progression and treatment stop within 3 months biochemical-progression (33.3%) and only in 8.7% of patients
after the beginning of immunotherapy. Deaths within a 6 with biochemical improvement. In 22 of 30 patients (73.3%)
month follow up period were recorded. Univariate analyses with longer follow-up, imaging response was relevant for
and ROC analyses were performed to identify predictors of treatment choice. Relevance of imaging response was reflected
short-term progression. Results: Mean patient’s age was 63±10 by its ability to assess individual lesions in case of heterogeneous
years. The pathological subtype was squamous cell carcinoma lesion response, appearance of new lesions, and identification
and adenocarcinoma in 80% and 20% of patients, respectively. of lesions requiring specific attention such as targeting
On PET, median SUVmax was calculated at 14.2 [range: 6.3-64.0] radiotherapy. Conclusion: Results of this retrospective analysis
and median MTV was measured at 31mL [range:2mL-308mL]. show that biochemical response to treatment and [68Ga]Ga-
Sixteen patients presented with short-term progression after PSMA-11 PET/CT-based response assessment differ in a third of
immunotherapy. By univariate analyses, a higher MTV was metastatic PCa patients, often in view of the ability of imaging
significantly associated with short-term progression (cut- to allow for lesion-based and not only patient-based analysis.
off=31mL, HR=7.14; 95% CI: 1.6-45.9; p=0.006). A short-term Monitoring response during treatment by [68Ga]Ga-PSMA-11
progression was observed in 46% of patients with MTV >31 mL PET/CT is relevant for decision-making and choosing treatment
vs 11% of patients with MTV < 31mL. SUVmax did not show any in the majority of patients. References: None.
correlation with short-term progression (p>0.05). ROC curve
analysis of MTV to predict short-term progression revealed an
AUC of 0.81 (95% CI: 0.69-0.92). Concerning overall survival, 7/27 EPS-016
patients with an MTV > 31 mL died during the 6 months follow- Artificial intelligence can discriminate between focal and
up, whereas 3/27 deaths were observed in patients with MTV normal bone/bone marrow uptake in lymphoma patients
< 31mL. Conclusion: MTV has a potential value in predicting staged with FDG-PET/CT- a descriptive study
short-term progression after immunotherapy in patients with M. Sadik1, A. Krupic1, A. Dudás1, J. Lopez Urdaneta1, J. Ulén2, O.
NSCLC. Indeed, a high MTV is associated with a higher risk Enqvist3,2, P. Andersson4, L. Edenbrandt1;
of short-term progression and could predict death within 6 1
Nuclear Medicine, Gothenburg, SWEDEN, 2Eigenvision
months. References: None. AB, Malmö, SWEDEN, 3Chalmers University of Technology,
Gothenburg, SWEDEN, 4Hematology, Gothenburg, SWEDEN.

Aim/Introduction: Localized bone marrow involvement


S309 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

on FDG-PET/CT in newly diagnosed lymphoma patients has Aim/Introduction: Determine if the patient´s pharmacological
prognostic implications. A growing body of evidence suggest treatment influences the labelling procedure of autologous
that FDG-PET/CT can replace bone marrow biopsy in some leucocytes with 99mTc-HMPAO. Materials and Methods:
patients, avoiding unnecessary procedures and pain. As a first We did a prospective study between May 2018 and April
step we aim to study whether artificial intelligence (AI) can 2019 with a total of 72 patients with knee/hip prosthesis. All
discriminate between localized and normal bone/bone marrow patients underwent study with 99mTc-HMPAO autologous
uptake. Materials and Methods: All newly diagnosed Hodgkin leucocytes. Pharmacological treatment was collected from
lymphoma (HL) and diffuse large B-cell lymphoma (DLBCL) the patient’s medical records. The drugs have been classified
patients who had undergone a staging PET/CT between 2011- into 6 groups: 1=NSAID(Non-Steroidal Anti-Inflammatories),
2016 at Sahlgrenska University hospital were retrospectively 2=Statins, 3=Corticosteroids, 4=PPI(Proton-Pump Inhibitor),
included. Information regarding bone and bone marrow 5=BDZ(Benzodiazepines), 6=ACEI(angiotensin-converting
involvement were extracted from the final clinical assessment enzyme inhibitors).Labelling efficiency was calculated by
done by hematologists. In a previous work AI was trained to find dividing the final activity of labelled leucocytes by the activity
the skeletal anatomy (1). Bone less than 7 mm from the bone before removing the wash supernatant. In our Radiopharmacy
surface were removed to isolate the bone marrow. A threshold Unit a 60% limit is tolerable for patients over 12 years of age. The
was defined as the average SUV + 2 SD for the vertebral bone labelling mean activity of 99mTc-HMPAO was 24.5% ±1.80. In
marrow. Any bone marrow voxels with SUV above this threshold all cases % RQP(radiochemical purity) ≥80% with mean %RQP=
were classified as lesion and the total lesion uptake (TLU) was 95.93±2.37. The statistical analysis was performed with SPSS
calculated as (average lesion SUV - threshold) x (total lesion program (descriptive statistical test with frequencies, means
volume in mL). A TLU > 0,8 was considered pathological. and standard deviation) and quantitative comparisons with
Results: The total cohort consisted of 151 patients, of whom the Mann-Whitney and Wilcoxon W tests. Results: The groups
72 (48%) patients were female. Median age was 34 years (10-85 of drugs that showed a statistically significant association with
years). Most patients had HL (87%) and the rest DLBCL. Eighteen the labelling efficiency were: 3=Corticoids and 5=BDZ. In the
patients were classified as having focal uptake by AI. Of those, group of patients who received corticosteroids, mean labelling
14 patients (78%) were classified as true positive and 4 (22%) efficiency was 59.65% ±6,40 with a confidence interval of 95%
as false positive. 133 patients were classified as normal by AI (56.65; 62.65) and p = 0.0001. On the other hand the patients
resulting in 127 (95%) patients classified as true negative and who did not take corticosteroids labelling efficiency had a
six (5%) as false negative. Conclusion: Our results show that AI mean of 67.10% ±6.68 with a 95% confidence interval (65.22;
can differentiate between normal and pathological bone/bone 68.98). The group of benzodiazepines the mean was 62.37%
marrow uptake. This method can highlight pathological regions ±3.54 with 95% confidence interval (60.66; 64.08). The patients
to focus the physician’s attention and in the future standardize who did not take benzodiazepines the mean was 65.96% ±8.17
the PET/CT image reading. References: (1) Lindgren Belal S, with a confidence interval of 95% (63.69; 68.24) with p = 0.017.
Sadik M, Kaboteh R, Enqvist O, Ulén J, Poulsen MH, Simonsen In groups 1,2,4 and 6 no statistical significance was detect:
J, Høilund-Carlsen PF, Edenbrandt L, Trägårdh E. Deep learning 1=NSAIDs: 67.26% ±6.96 decreases to 63.92% ± 7.39; p=0,074
for segmentation of 49 selected bones in CT scans: First step 2=Statins: 65.50% ±7.47 to 64.19% ±7.29; p=0,399 4=PPI: 64.84%
in automated PET/CT-based 3D quantification of skeletal ±7.89 to 65.38% ± 6,15; p=0,82 6= ACEI: 64.92% ±7.95 to 65.19%
metastases. Eur J Radiol. 2019 Apr;113:89-95. ±5.94; p=0,700 Conclusion: According to the results obtained,
we can affirm that, the treatments with NSAIDs, Statins, PPI, ACEI
do not seem to have an influence on the leucocyte labelling
311 and the corticoids and benzodiazepines, produce a decrease in
the labelling efficiency, so that special attention should be paid
e-Poster Presentation Session 2 - Inflammation
to these treatments as they can negatively affect the leucocyte
& Infection + Translational and Molecular
labelling with 99mTc-HMPAO. References: None.
Imaging Therapy: Infection and Inflammation -
Clinical and Preclinical Studies
EPS-018
Sunday, October 13, 2019, 11:30 - 13:00 Room 133/134 Differential diagnosis of Adult-onset Still’s disease and
other connective tissue diseases with FDG PET/CT
Q. Wang, X. Zhou;
Peking University People’s Hospital, Beijjing, CHINA.
EPS-017
Possible pharmacological treatment interactions in
autologous leucocytes labelling technique with 99mTc- Aim/Introduction: Adult-onset Still’s disease (AOSD) is often
HMPAO in patients with knee/hip prosthesis difficult to diagnose because it is lack of characteristic clinical
E. Dobra, B. Martínez de Miguel, E. Orihuela Pantoja, V. Mendi manifestations. In order to explore the value of FDG PET/CT in
Barcina, H. García Ruiz, E. Martínez Montalbán; the differential diagnosis, we retrospectively analyzed the FDG
Hospital Universitario La Paz, Madrid, SPAIN. PET/CT images in AOSD patients and other connective tissue
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S310

diseases(CTD) patients. Materials and Methods: Within the resulting in potentially fatal intracranial complications. This life-
patients with fever of unknown origin who underwent FDG PET/ threatening condition can be difficult to diagnose and treat.
CT examination, data of 46 with AOSD and 53 with other CTD This study aimed to investigate the usefulness of18F-FDG PET/
were retrospectively studied, and 40 subjects with negative PET/ CT co-registered with MRI in determining disease extent and
CT in the same period were taken as the control group. Imaging treatment response in patients clinically diagnosed of MOE.
characteristics of AOSD was firstly observed by visual judgment Materials and Methods: Nine subjects were enrolled in the
and SUVmax was respectively measured as a quantitative study (7 diabetic); mean age: 62 years (range: 22-84 y). Sixteen
parameter in the spleen, bone marrow and blood pool in each FDG PET/CT studies were evaluated: 6 in the initial diagnosis
cases. When abnormal lymph node was found, the SUVmax was and 10 to determinate treatment response. A dedicated head
measured on the lymph node with maximal diameter. ROC and neck (HN) acquisition was performed as well as images
curve was used to analyze the differential diagnosis threshold. from mid-thigh to the base of the skull. FDG PET scans were co-
Significance of FDG PET/CT for the diagnosis of AOSD was registered with MRI when available (69% studies). We evaluated
evaluated, according to the image diagnostic criteria set on the extent of disease on the basis of visual interpretation on PET/
current study. Results: On FDG PET/CT examinations, abnormal CT or co-registered FDG-PET/MRI images. In addition, SUVmax
uptake was found in 45/46 of the AOSD patients, including was measured in the lesions. Results: All the scans showed
spleen (44), bone marrow (45) and lymph nodes (35), while pathological FDG uptake (mean: 7,5; range 3,6-13,4). Imaging
above uptakes can also be seen in 44/53 of other CTD patients. located skull base osteomyelitis or intracranial extension (69%),
However, SUVmax of spleen, bone marrow and lymph nodes in soft tissue involvement and erosive changes of temporal bone
AOSD group was all significantly higher than that in the other (19%) and soft tissue and cartilaginous involvement (12% of
CTD group, although the SUVmax of spleen and bone marrow scans). Ten studies (62,5%) were used to evaluate response
in other CTD group were all significantly higher than that of to treatment. We observed an increase of FDG uptake (50%),
control group. In addition, compared with the control group, a significant decrease/metabolic normalization (40%) or no
FDG distribution was lower in on blood pool and liver in AOSD significant changes (10% of them) .In patients with significant
patients, but no statistic difference was found between the uptake antibiotic treatment was continued and when the
AOSD patients and other CTD patients. If taken the following scan demonstrated no or substantially reduced FDG uptake
two or more as the diagnostic criteria for AOSD, a diagnostic treatment was stopped. MRI alone failed to correctly classify
sensitivity, specificity and accuracy of 95.7%, 94.3% and 94.9% response to treatment in two of these studies. Conclusion:
will be obtained, respectively: (1) spleen SUVmax ≥ 2.6 and/or The diagnostic challenge in MOE lies in the fact that no single
bone marrow SUVmax ≥ 3.1; (2) multiple reactive hyperplastic modality is able to address the scope of the disease. FDG PET/
lymph nodes with a symmetrical distribution mainly in neck CT is a reliable imaging modality for determining disease
and axillary lymph region and SUVmax ≥ 3.1, (3) no abnormal extent and specially treatment response, because it allows an
uptake in other organs except the above nonspecific uptake. objective quantitative measurement for tracer accumulation.
Conclusion: AOSD have characteristic imaging manifestations MRI images alone are less useful than FDG PET/CT for treatment
on FDG PET/CT, and it can help for differentiating AOSD from monitoring. PET co-registered to MRI combines functional and
other connective tissue diseases. References: None. high-resolution anatomical imaging. Further studies are needed
to assess the role of FDG PET/RM as first-line diagnostic imaging
in MOE. References: A.M.J.L. van Kroonenburgh, W.L. van der
EPS-019 Meer. R. J. P. Bothof. Advanced Imaging Techinques in Skull Base
Role of FDG PET/CT and MRI co-registration for diagnosis Osteomyelitis Due to Malignant Otitis Externa. Curr Radiol Rep
and follow-up of malignant external otitis: Preliminary (2018) 6:3. https://doi.org/10.1007/s40134-018-0263-y
results
L. Rodriguez-Bel1,2, M. Cortés-Romera1,2, F. Cruellas-Taischik3,2,
M. Santín-Cerezales4,2, A. Sabaté-Llobera1,2, E. Llinares-Tello1,2, A. EPS-020
Palomar-Muñoz1,2, M. Martínez de Bourio-Allona1,2, C. Gámez- Diagnostic impact of Ga-SPECT/CT using quantitative
Cenzano1,2; analysis for patients with lower-limb osteomyelitis
1
PET-Unit. Department of Nuclear Medicine, L’Hospitalet De Y. Nishikawa, Y. Fukushima, S. Kirinoki, G. Takagi, M. Miyamoto, S.
Llobregat, Barcelona, SPAIN, 2Hospital Universitari de Bellvitge- Kumita;
IDIBELL, Barcelona, SPAIN, 3Department of Otorhinolaryngology, Nippon Medical School Hospital, Tokyo, JAPAN.
L’Hospitalet De Llobregat, Barcelona, SPAIN, 4Deparment of
Infectious diseases, L’Hospitalet De Llobregat, Barcelona, SPAIN.
Aim/Introduction: Lower-limb osteomyelitis is caused by
various conditions, such as diabetes mellitus, collagen diseases,
Aim/Introduction: Malignant otitis externa (MOE) is an and trauma. Since patients with this disease occasionally require
infrequent but severe infectious disorder that is generally amputations, early diagnosis and risk stratification are important
caused by Pseudomonas aeruginosa, mostly affecting elderly to improve their outcomes. While Ga-scintigraphy is commonly
diabetic patients. Progression of the disease from the external used for diagnosing inflammatory diseases, the diagnostic
auditory canal may lead to osteomyelitis of the skull base performance of conventional planar imaging for localized
S311 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

lesions is limited. This study aimed to estimate the diagnostic TLE according to the presence of lead-associated endocarditis
performance of Ga-SPECT/CT using quantitative analyses (LAE). Materials and Methods: We performed a single center
for patients with lower-limb osteomyelitis. Materials and prospective observational study in a population of consecutive
Methods: A total of 103 consecutive patients between April patients referred for TLE to a tertiary hospital for the treatment
2012 and October 2016, who were suspected of lower-limb of CIEDI. Results: We enrolled 105 consecutive patients with
osteomyelitis, were included in this study. All patients underwent confirmed CIEDI, 81% male, aged 72.7 years. LAE was observed
Ga-scintigraphy via both planar and SPECT/CT imaging. The in 49 patients and CIED pocket involvement in 81. 24/49 of
image findings of osteomyelitis were assessed both visually and the patients with LAE were free from pocket involvement
quantitatively. In the visual analysis, localized accumulations (both at inspection and at FDG-PET). Comparing baseline
higher than background were determined as positive lesions characteristics, patients with LAE free from pocket involvement
(planar and SPECT/CT imaging scores). In the quantitative more frequently occurred after first implant (54% vs. 24%;
analysis via SPECT/CT images, the inflammation-to-background p=0.030) and >6 months after last CIED procedure (88% vs. 48%;
ratio (IBR) was calculated by dividing the maximum count in the p=0.003) without any other significant differences in terms of
osteomyelitis lesion by mean count in both distal femur bone implanted hardware or comorbidities. TLE was performed in all
marrow as background. The maximum standardized uptake the patients, requiring powered sheaths in 64/105, two subjects
value (SUVmax) in the osteomyelitis lesion was also calculated experiencing a major complication secondary to a vascular tear
using GI-BONE. The diagnoses were confirmed based on the promptly repaired by the cardiac surgeon who also completed
patients’ outcomes and pathological examinations, and the lead extraction. One year mortality was significantly higher in
diagnostic performances of the planar and SPECT/CT imaging patients with LAE without pocket involvement, while survival
for lower-limb osteomyelitis were compared. For the evaluation was almost superimposable between patients with pocket CIEDI
of the prognostic performances of quantitative indicators, all and patients with LAE and pocket involvement. Conclusion:
patients were observed over 3 years from initial Ga-SPECT/CT Patients with LAE without CIED pocket involvement usually
for the occurrence of major adverse events (MAE), which was develop CIEDI after >6 months after their first device implant.
defined as recurrence of osteomyelitis, major leg amputation, or These subgroup of patients require better characterization in
fatal event. Results: The number of patients with and without view of the bad prognosis despite complete TLE. References:
osteomyelitis was 54 and 49, respectively. Compared with None.
planar imaging (sensitivity: 91% and specificity: 18%), SPECT/
CT imaging showed a higher accuracy (sensitivity: 91% and
specificity: 96%) for the diagnosis of lower-limb osteomyelitis. EPS-022
Whereas the visual planar imaging score showed no difference 99m
Tc-PYP scintigraphy detects transthyretin-related
between patients with and without osteomyelitis, both IBR and cardiac amyloidosis; a substitute for biopsy?
SUVmax were significantly higher in the osteomyelitis patients P. Valsamaki, E. Kastritis, I. Dialoupi, A. Dimopoulos, V.
compared with the patients without osteomyelitis (14.33 vs. Papantoniou;
2.11 and 7.04 vs. 1.71, both p < 0.001). MAE occurred in 36 out University General Hospital “Alexandra”, Athens, GREECE.
of 54 osteomyelitis patients. In the multivariate Cox proportional
hazards regression analysis, both IBR and SUVmax were found
to be the independent prognostic factors (both p < 0.001). Aim/Introduction: Cardiac amyloidosis (CA) is caused by
Conclusion: Ga-SPECT/CT using quantitative parameters, such extracellular deposition of a misfolded and insoluble protein,
as IBR and SUVmax, may have a high diagnostic performance namely amyloid. The underlying pathophysiologic mechanism
for patients with lower-limb osteomyelitis compared with the is hitherto ultimately identified by endomyocardial biopsy
planar imaging. References: None. combined with immunohistochemical parameters/mass
spectroscopy. Imaging with cardiac US/MRI provides non-
specific findings. We herein suggest the use of technetium-
EPS-021 99m pyrophosphate (99mTc-PYP) scintigraphy for defining
One year survival in patients with lead-associated cardiac amyloidopathy subtype, specifically transthyretin-
endocarditis after transvenous lead extraction: the related CA (ATTR), whether familial or wild-type (senile).
importance of pocket involvement Materials and Methods: Sixty-one patients [50 males, aged
R. Bonfiglioli, L. Calderoni, R. Mei, S. Lorenzetti, G. Massaro, J. (mean±SD) 69.4±11.2y; 11 females, aged 73.3±7.6y] with
Frisoni, C. Martignani, S. Fanti, I. Diemberger; suspected ATTR, underwent myocardial scintigraphy (planar
Azienda ospedaliero-universitaria S.Orsola- and tomographic) 1-3h after iv administration of 555-925
Malpighi, Bologna, ITALY. MBq 99mTc-PYP. Myocardial radiotracer uptake was assessed
optically (grade 0-3) and semiquantitatively, using two regions
of interest (ROI); over the heart (H) and over the contralateral
Aim/Introduction: Cardiac implantable electronic device hemithorax (CL), to estimate the H/CL count ratio. We applied
infections (CIEDI) represent a life-treating condition with a poor a cut-off H/CL value of 1.5 to differentiate patients bearing
prognosis even after transvenous lead extraction (TLE). The aim ATTR versus light-chain CA (AL). Diagnosis was confirmed by
of this study was to find the predictors of poor prognosis after biopsy and/or laboratory investigation. Results: Diffuse intense
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S312

myocardial uptake verified semi-quantitatively in 19 men had a prosthetic heart valve and/or an endovascular prosthesis,
and 4 women by 99mTc-PYP scintigraphy, was consistent with with a median of 27 months from surgery to the scan. Prior to
ATTR, 12 men and 3 women bearing the wild-type. Faint or no the study, only 8 transthoracic echocardiograms were suspects.
myocardial tracer uptake with H/CL ratios <1.5, was found in A special preparation for cardiac assessment was performed in
38 patients (16 diagnosed with AL). Detection of ATTR in our 87.5% of the cases. The 87.5% of the cases received antibiotic
study population by 99mTc-PYP scintigraphy was accomplished therapy before the scan. Were considered metabolically positive
with 100% sensitivity and specificity. Conclusion: Our data for IE 19 cases, 9 were negative and 4 were not evaluable due
indicate that 99mTc-PYP scintigraphy, a non-invasive, low-cost, to physiological uptake by the myocardium. In the positive
and widely available modality, identifies patients with the ATTR cases, the average SUVmax was 5.08; the Deauville scale was 4
subtype and may prove a valuable tool for earlier diagnosis in 12 patients and 5 in 7 cases; the scale of uncorrected images
and screening, substituting for biopsy as well as optimizing was 2 in 14 patients and 3 in 5. A delayed image of the thoracic
therapeutic and prognostic implications. References: 1. region was performed in 78,9% of the cases, with persistence
Banypersad SM, Moon JC, Whelan C et al. Updates in cardiac of the focus and an average SUVmax of 6.3, increasing the
amyloidosis: a review. J Amer Hear Assoc 2012; 1: e000364. 2. uptake in 73.3% of the cases. A final diagnosis of suggestive
Chee CE, Lacy MQ, Dogan A et al. Pitfalls in the diagnosis of was obtained in 5, definitive in 14 and rejected in 9. A sensitivity
primary amyloidosis. Clin Lymphoma Myeloma Leuk 2010; 177- of 82.6%, specificity of 100%, positive predictive value of 100%
80. 3. Gonzalez-Lopez E, Gallego-Delgado M, Guzzo-Merello and negative predictive value of 55.5% was demonstrated.
G, et al. Wild-type transthyretin amyloidosis as a cause of Conclusion: Although 18F-FDG PET/CT is included in the
heart failure with preserved ejection fraction. European Heart diagnostic algorithm of IE, there is no consensus in the protocol,
Journal 2015;36:2585-94. 4. Bokhari S, Castaño A, Pozniakoff T, preparation and interpretation of the images. The model that we
et al. 99mTc-pyrophosphate scintigraphy for differentiating light have followed compiled from several research, seems a suitable
chain cardiac amyloidosis from the transthyretin-related familial option to diagnose this disease that warrants a thorough and
and senile cardiac amyloidoses. Circ Cardiovasc Imag2013; early treatment. References: None.
2: 195-201. 5. Castano A, Haq M, Narotsky D, et al. Multicenter
experience of planar technetium pyrophosphate cardiac
imaging: Does preferential cardiac uptake predict survival in EPS-024
patients with ATTR cardiac amyloidosis? ISA INTERNATIONAL Diagnostic accuracy of 67Ga-citrate scintigraphy in left
SOCIETY OF AMYLOIDOSIS 2016; 39. ventricular assist device (LVAD) infection
K. Matsunaga, F. Soeda, D. Katayama, M. Watanabe, T. Watabe, H.
Kato, M. Tatsumi, E. Shimosegawa, J. Hatazawa;
EPS-023 Osaka University, Suita city, JAPAN.
The Utility of 18F-FDG PET/CT In The Diagnosis Of
Infectious Endocarditis
D. Tamayo-Carabaño, I. Acevedo-Bañez, R. Fernández-López, R. Aim/Introduction: LVAD is used in supporting end-stage heart
Álvarez-Pérez, J. Jiménez-Hoyuela-García; failure patients. One of the major complications is infection of
Hospital Universitario Virgen del Rocío, Sevilla, SPAIN. the LVAD or driveline. In Japan 67Ga-citrate scan is reimbursed by
health insurance system in the diagnosis of infection, however
the usefulness of 67Ga-citrate scan in LVAD associated infection
Aim/Introduction: Evaluated the utility of 18F-FDG PET/ has not been examined. The aim of this study was to evaluate the
CT performed in patients with suspected infectious usefulness of 67Ga-citrate scan in the diagnosis of LVAD related
endocarditis(IE). Materials and Methods: Personal history of infection. Materials and Methods: Twenty-nine 67Ga-citrate
each patient was assessed: previous valvular or endovascular scans (27 scans with additional SPECT/CT, 1 scan with additional
surgery or prosthesis, time elapsed since surgery, results of SPECT and 1 scan with only planar image) performed between
transthoracic echocardiography and antibiotic treatment prior January and December 2015 with 19 patients supported with
to the procedure. All patients were administered a 18F-FDG LVAD were retrospectively analyzed. The patients were referred
dose standardized by weight, and by size in pediatric cases, to our department with a suspicion of LVAD related infection
one hour before image acquisition. Images were analyzed or fever of unknown origin. An infection was defined according
measuring the SUVmax of the areas of pathological uptake, to the adverse event definition of the Interagency Registry
describing the character of the uptake, the Deauville scale, a of Mechanically Assisted Circulatory Support. 67Ga-citrate
captation scale of the uncorrected images, the persistence of scintigraphy was performed 3 days following intravenous
the pathological focus and the modification of the SUVmax in administration of 111 MBq 67Ga-citrate. Images were obtained
the delayed images. Results: We included 32 studies between using a dual-head gamma camera (Symbia T6 or Symbia Intevo,
June2016 and October2018, conducted in 29 adult and 3 Siemens Healthcare) and high-resolution, medium-energy
pediatric patients, 25 were men and 7 women with a median collimators. Whole-body anterior and posterior images were
age of 68 years. The reason for requesting the study was fever- acquired with a scan speed of 10 cm/min using 20% window
of-unknown-origin in 19 cases and bacteremia demonstrated energy peaks of 93, 184 and 300 keV. SPECT/CT was additionally
with positive blood cultures in 13. The 93.75% of the patients performed following whole-body scan, focused on the chest
S313 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

and the abdomen. The data acquisition included 180° rotation, echocardiography were negative.PET/CT results allowed to rule
5° angle step, and 30-s-per-frame acquisition time using a 128 x out the infectious process in 88% (7/8) of patients: in prosthetic
128 matrix. CT based attenuation correction was used. Iterative valve (n=5), in generator pocket and along the leads (n=2).
reconstruction was performed. All scans were reviewed by a Of these, in one case the cause of fever was identified - lung
reader experienced in 67Ga scan analysis, who was blinded to inflammation. Other 6 negative results were confirmed by follow-
the final clinical diagnosis. The scans were visually evaluated for up clinical and laboratory data during 6+3 months. Sensitivity,
the presence of an infection along the driveline, conduits and specificity and accuracy of 18F-FDG PET/CT in the diagnosis of
pump housing. The abnormal uptake was graded as positive IE were 93%, 88% and 92%, respectively. Positive and negative
for an infection. Results: Sensitivity, specificity, positive and predictive value - 96% and 78%. Conclusion: 18F-FDG PET/CT
negative predictive value were 85, 94, 92, 88 % for planner proved to be a useful diagnostic tool in patients with suspected
image and 92, 94, 92, 94 % for SPECT/CT. In false negative cases IE after valve replacement and/or cardiac device implantation,
of planner image, the uptake of infection site located near sites and should be included in the algorithm for early diagnosis.
of physiological uptake such as liver. Conclusion: 67Ga-citrate PET/CT results also allow to detect extracardiac complications
scan was useful in the diagnosis of LVAD infection. References: in these patients. References: None.
None.

EPS-026
EPS-025 Diagnostic accuracy of 18F-FDG digital PET/CT in
Role of 18F-FDG PET/CT in Diagnostics of Infective the detection of infective endocarditis on native and
Endocarditis in Patients with Prosthetic Valves and prosthetic valves and intracardiac devices: Preliminary
Implantable Cardiac Devices results in a reference medical center
D. Pursanova, L. A. Bockeria, I. P. Aslanidi, O. V. Mukhortova, I. V. M. Mallón Araujo, E. Abou Jokh, V. Pubul Núñez, M. d. Pombo
Shurupova, T. A. Katunina, T. A. Trifonova; Pasín, M. Garrido Pumar, L. Garcia Bernardo, A. Martínez-Monzonis,
A.N.Bakoulev National Medical Research Center of A. Martínez de Alegría Alonso, Á. Ruibal Morell;
Cardiovascular Surgery of the Ministry of Health of CHUS, Santiago De Compostela, SPAIN.
Russian Federation, Moscow, RUSSIAN FEDERATION.

Aim/Introduction: Infective endocarditis (IE) is a pathology that


Aim/Introduction: 18F-FDG PET/CT has potential to improve remains a medical challenge despite the great technological
the early diagnosis of infectious endocarditis (IE) and its advances, thus requiring a multidisciplinary approach to
complications in patients with fever of unknown origin after improve its fatal prognosis. Digital PET/CT has been recently
valve replacement and/or cardiac device implantation. Purpose: developed to offer an improvement in quality image, volumetric
To investigate the usefulness of 18F-FDG PET/CT in the detection resolution, quantitative accuracy and higher sensitivity. The aim
of IE in patients after cardiac surgery. Materials and Methods: was to evaluate the diagnostic accuracy of 18F-FDG digital PET/
This prospective analysis included results of 18-FDG PET/CT CT in the early diagnosis of IE. Materials and Methods: We
examinations performed in 35 patients with fever of unknown retrospectively evaluated 38 patients (10 women and 28 men)
origin and suspected IE after: heart valve replacement (n=19), with possible IE regarding Duke´s criteria, 8 of them with native
pacemaker implantation (n=9) and both procedures (n=7). valves (NV), 20 prosthetic valves (PV) and 10 intracardiac devices
Examinations were performed on PET/CT scanner (Biograph-64, (ID). All patients underwent analytical and microbiological tests,
Siemens) 90 min after 18F-FDG injection (175-200Mbq). All a transesophageal echocardiogram (TEE) and a 18F-FDG digital
patients were on low-carbohydrate diet for 48 hours before PET- PET/CT scan (Phillips Vereos PET-TC model); the results of each
scan and fasted for at least 15 hours before it. Final diagnosis test were compared between them. The final diagnosis of EI was
was made based on clinical and laboratory (n=35), as well as reached according to the modified Duke´s criteria. All patients
intraoperative data (n=28). Results: Overall, the diagnosis of IE underwent a low carbohydrate diet and the administration
was confirmed in 27 and ruled out in 8 patients. PET/CT results of 50UI of sodium heparin 15 minutes before the injection of
allowed to confirm IE in 93% (25/28) of patients: in prosthetic 18F-FDG. Results: Out of thirty-eight patients suspected of IE,
valve (n=18), in generator pocket and along the leads (n=7). the diagnosis was confirmed in 20 cases (52,6%). 18F-FDG digital
In addition, whole body PET/CT results revealed other foci of PET/CT was positive in 15 patients, 10 showing FDG uptake
infection in these patients: along the ascending aorta prosthesis on cardiac valves (3 native and 7 prosthetic), 2 on intracardiac
(n=4), in native valve (n=2), soft tissue infiltrates of the anterior devices and 3 on both (valves and devices). 18F-FDG PET/CT
chest wall (n=2), sternum (n=2), lung (n=1) and spleen (n=1). had a 33,3% sensitivity (S) for IE on NV and 85.7% on PV and
Importantly, 88% (22/25) patients with true positive PET/CT ID and a 100% specificity (E) on NV and 93.7% in PV and ID.
results had negative or doubtful laboratory and instrumental The TEE had a S and an E for NV of 50% and 100% respectively,
data: sterile blood cultures (n=14) and/or negative (n=7) or and a S and a E for VP and DI of 14.2% and 100% respectively.
doubtful (n=10) results of echocardiography. Moreover, in two Conclusion: 18F-FDG digital PET/CT has proven to be a sensitive
of these patients, the diagnosis of IE was made based on clinical technique with a high diagnostic value in patients suspected
and PET/CT data, while the results of both blood cultures and of IE with prosthetic valves and intracardiac devices. Its utility
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S314

decreases in patients with IE on NV, in which TEE presented a of patient management. Three of 26 patients (11.5%) had
higher sensitivity thus a better diagnostic value. References: recurrence during follow-up related to bacterial resistance.
None. Eighteen patients were considered cured and 6 uncured at
EOT. Fourteen cured patients (77.8%) and all uncured patients
had abnormal PET2. PET1 ∑SUVmax and MSUVmax were
EPS-027 higher in uncured than in cured patients (p<0.01). ∆∑SUVmax
Evaluation of [18F]FDG-PET/CT for initial diagnosis and and ∆MSUVmax between PET1 and PET2 were not different
healing assessment after therapy in extra-pulmonary between cured and uncured patients: -88.3%[-93.7;-55.5] vs
tuberculosis -68.3%[-77.1;-68.8] (p=0.24), and -64.6%[-74.9;-25.8] vs -54.3%[-
L. Sarda-Mantel1, J. Kaoutar2, T. Alfaiate3, A. Lopes4, K. Benali5, L. 57.7;-25.9] (p=0.31). PET2 MSUVmax showed the highest AUC
Vercellino6, N. Mikail5, M. Soussan7, C. Lemarignier6, F. Mechai7, S. Le on ROC curves for the diagnosis of healing or residual disease
Nagat8, F. Montravers9, O. Deradji10, E. Durand11, T. Goulenok12, D. at EOT: (0.79[0.57;1.00]). MSUVmax above 3.7 had a sensitivity of
Ponscarme13, P. Yéni2, C. Laouénan3,14, C. Rioux2; 82.3%, and a specificity of 80.0% to diagnose residual disease
1
APHP Hôpital Lariboisière Service de Médecine Nucléaire, Paris, at EOT. Conclusion: [18F]FDG-PET/CT at diagnosis was positive
FRANCE, 2APHP Hôpital Bichat Service de Maladies Infectieuses, in 97.6% and discovered unknown lesions in 32.4% of cases.
Paris, FRANCE, 3APHP Hôpital Bichat Département d’Epidémiologie ∑SUVmax and MSUVmax clearly decreased on PET2 at EOT in
Biostatistique et Recherche Clinique, Paris, FRANCE, 4APHP Hôpital cured patients, but abnormal hot spots persisted in 77.8% of
Lariboisière Service de Médecine Interne, Paris, FRANCE, 5APHP them. MSUVmax above 3.7 on PET2 was the best criteria to
Hôpital Bichat Service de Médecine Nucléaire, Paris, FRANCE, diagnose residual disease at EOT. References: None.
6
APHP Hôpital Saint-Louis Service de Médecine Nucléaire,
Paris, FRANCE, 7APHP Hôpital Avicennes Service de Médecine
Nucléaire, Paris, FRANCE, 8APHP Hôpital Tenon Service de Maladies EPS-028
Infectieuses, Paris, FRANCE, 9APHP Hôpital Tenon Service de Cardiac Amyloidosis : The Utility Of Tc-99m PYP
Médecine Nucléaire, Paris, FRANCE, 10APHP Hôpital Kremlin- Scintigraphy In Etiologic Evaluation Of Dilated
Bicêtre Service de Maladies Infectieuses, Paris, FRANCE, 11APHP Cardiomyopathy
Hôpital Kremlin-Bicêtre Service de Médecine Nucléaire, Paris, S. Fukuzawa, S. Okino, H. Ishiwaki, Y. Iwata, T. Uchiyama, N.
FRANCE, 12APHP Hôpital Beaujon Service de Médecine Interne, Kuroiwa, N. Oka, S. Furihata, N. Shibayama, M. Inagaki;
Paris, FRANCE, 13APHP Hôpital Saint-Louis Service de Maladies Funabashi Municipal Medical Center, Funabashi, JAPAN.
Infectieuses, Paris, FRANCE, 14IAME UMR 1137, Paris, FRANCE.

Aim/Introduction: Cardiac amyloidosis (CA) presents


Aim/Introduction: In extra-pulmonary tuberculosis forms, initially with mild LV diastolic dysfunction, progressing to
the bacteriological evidence of cure most often cannot be classical restrictive cardiomyopathy and finally even dilated
obtained, the evolution of conventional imaging is poorly cardiomyopathy(DCM) like stage with end-stage heart failure.
understood, raising the need for other tools for therapeutic Tc-99m PYP scintigraphy in the absence of evidence of a
evaluation. The aim of this study was to evaluate [18F]FDG-PET monoclonal gammopathy was diagnostic for transthyretin
before and after antibiotherapy, assuming that it could provide cardiac amyloidosis (ATTR-CA), providing a cost-effective and
useful information for therapeutic management. Materials non-invasive technique with a specificity and positive predictive
and Methods: We performed a multicenter prospective study value of nearly 100%. The aim of study is to identify ATTR-CA
including 55 patients with definite or probable lymph node as a specific cause in which Tc-99m PYP scintigram may be
or bone tuberculosis. Patients were followed until 12 months useful in the etiologic evaluation of DCM patients. Materials
after end-of-treatment [EOT]. Additionally to usual biological, and Methods: 68 patients with the diagnosis as DCM between
histological and morphological explorations, [18F]FDG-PET 2012 Apr. and 2017 Mar. in our heart center were included. All
was performed at diagnosis (PET1) and at EOT (PET2). Patients the subjects were underwent Tc-99m PYP cardiac imaging, also
were considered cured at EOT if adherence to treatment was echocardiographic, MIBG scintigraphic and clinical variables
at least 80% and if they did not relapse one year after EOT. were gathered. Retention of Tc-99m PYP in the heart was assessed
The [18F]FDG-PET variables studied were the sum (ΣSUVmax) using both a semiquantitative visual score (range, 0 [no uptake]
and average (MSUVmax) of the SUVmax measured in each site to 3 [uptake greater than bone]). Results: 4 of 68 patients (5.9%)
considered as lesioned. Results: Eleven of 55 patients were were detected underlying ATTR-CA using Tc-99m PYP imaging
secondarily excluded, 20 were lost to follow-up. PET1 and PET2 (Score of 2~3). Patients with amyloid deposition were older, and
were completed respectively in 42 and 35 patients. PET1 was had a lower left ventricular ejection fraction and H/M ratio of
positive in 41 of 42 (97.6%) patients (ΣSUVmax: 35.5 [19.6-59.9], MIBG scan. During a five-year follow-up period, survival was
MSUVmax: 6.6 [5.7-8.8]). It retrieved unknown lesions in 32.4% of significantly worse if patients had amyloid deposition compared
cases, which induced a modification of therapy duration in 5.4% with no deposition subjects, according to a Kaplan-Meier
of cases. PET2 was positive in 29/35 (82.8%) patients (ΣSUVmax: analysis. Conclusion: Our results demonstrate that Tc-99m
5.5 [2.4-10.5], MSUVmax: 2.8 [1.6-3.6]), and retrieved unknown PYP imaging, when used as a part of a comprehensive clinical
lesions in 7.7% of cases, which did not induce modification evaluation, can help identify transthyretin amyloidosis in 5% of
S315 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

patients presenting with unexplained dilated cardiomyopathy. diverse even within the microbial species. 68Ga-PVDs can be used
References: 1) Bokhari S, Shahzad R, Castano A, et al : Nuclear for imaging of P.a. infections and show better pharmacokinetics
imaging modalities for amyloidosis. J Nucl Cardiol 21 : 175-184, than clinical radiopharmaceuticals. References: We gratefully
2014. acknowledge the financial support of Technology Agency of
the Czech Republic (Project No. TE01020028) and the Czech
Science Foundation (Project No. 19-10907S).
EPS-029
Gallium-68 labelled pyoverdines for Pseudomonas
aeruginosa infection imaging EPS-030
M. Petrik1, E. Umlaufova1, V. Raclavsky2, A. Palyzova3, V. Havlicek3, Radiolabelling and in vivo biodistribution studies of
Z. Novy1, C. Decristoforo4, M. Hajduch1; a lipid-protein based enterotoxigenic E. Coli vaccine
1
Institute of Molecular and Translational Medicine, Faculty of after intranasal and transdermal administration using
Medicine and Dentistry, Palacky University, Olomouc, CZECH polymeric microneedle patches
REPUBLIC, 2Department of Microbiology, Faculty of Medicine G. Quincoces1, Á. Erhard1, M. Collantes1, Y. Pastor2, J. Uranga3, J.
and Dentistry, Palacky University, Olomouc, CZECH REPUBLIC, Simon1, M. Ecay1, C. Gamazo2, I. Peñuelas1;
3
Institute of Microbiology of the Czech Academy of Sciences, 1
University Clinic of Navarra, Pamplona, SPAIN, 2University
Prague, CZECH REPUBLIC, 4Clinical Department of Nuclear of Navarra, Pamplona, SPAIN, 3USCAL, Pamplona, SPAIN.
Medicine, Medical University Innsbruck, Innsbruck, AUSTRIA.

Aim/Introduction: Infections by enterotoxigenic Escherichia


Aim/Introduction: Pyoverdines (PVDs) are highly specific coli (ETEC) are a top cause of children diarrhea and travelers’
siderophores excreted by several Pseudomonas species. diarrhea. The success of an ETEC vaccine will depend on the
Siderophores have potent affinity for iron and are employed appropriate combination of the right antigens delivered
for iron delivery by almost all microorganisms. Iron is an through appropriate routes to produce optimal protective
essential nutrient and is also a key factor in the virulence of immune responses. The objective of this work is to radiolabel
many pathogens. Replacing iron in siderophores by radiometal, the selected vaccine antigens (heat-labile toxin, HT) and analyze
such as gallium-68, opens approaches for targeted imaging of its biodistribution in vivo in mice by two different routes of
infections by means of PET. Pseudomonas aeruginosa (P.a.) is administration: intranasal and transdermal using polymeric
one of the most common pathogens causing life-threatening microneedle patches. Materials and Methods: Radiolabeling
pneumonia, which is associated with high mortality and of HT antigen (1 mg) was performed by 99mTcO4 reduction with
morbidity, especially in immunocompromised patients. Here SnCl2·2H2O. Radiochemical purity was checked by thin layer
we report on the preclinical evaluation of selected Ga-68 chromatography. Microneedle patches were prepared after
labelled PVDs produced by P.a. for imaging of P.a. infections. Wire Electrical Discharge Machining (wire EDM) a stainless-
Materials and Methods: PVDs isolated from different P.a. steel cast of 122 quadrangular pyramid microneedles (11x11
strains were labelled with Ga-68 in sodium acetate. Partition matrix, 250X300 µm). Silicon molds were prepared from the SS
coefficient, protein binding and stability in various media were cast. HT antigen was radiolabeled and added to a 40% Gantrez
determined up to 120min incubation time. In vitro uptake of solution that was poured onto the silicon molds to generate
68
Ga-PVDs was studied in different microbial cultures. In vivo the microneedle patches. After centrifugation solid polymer-
biodistribution was determined in normal Balb/c mice 30 and based patches were created after RT 4h drying. For intranasal
90 min p.i.. PET/CT imaging of 68Ga-PVDs was performed in P.a. administration, 10 µl of the radiolabeled complex were placed
animal infection models and compared with clinically used inside each nostril of Balb-c mice: 99mTc-HT (20 µg/3.14 MBq,
radiopharmaceuticals. Results: Studied PVDs were labelled n=4) and negative control (free 99mTcO4-, 4.99 MBq, n=4). For
with 68Ga with high (>95%) radiochemical purity. The resulting transdermal administration the microneedle patches were
complexes showed hydrophilic properties (log P = -3), low placed on the ear of BALB/c mice and fixed with sticking plaster
protein binding (<5%) and high stability in human serum (>95%). (20 µg/2.40 MBq, n=4; free 99mTcO4-, 2.70 MBq, n=4). In vivo
In vitro uptake of 68Ga-PVDs displayed different levels of uptake biodistribution studies were performed by SPECT/CT 1, 4, and
in studied P.a. strains as well as in other tested microorganisms. 24 hours post-administration and quantified by drawing VOIs
In normal mice, all studied 68Ga-PVDs showed similar results over CT images. Animals were euthanized and extracted organs
manifested by rapid renal excretion and low blood values measured ex vivo in a gamma-counter for the calculation
up to 90min p.i.. PET/CT imaging of 68Ga-PVDs in P.a. infected of the percentage of injected dose (% ID/organ). Results: HT
animals showed different levels of accumulation in infected antigen radiolabeling proceeded with >95-97% yield, thus
tissue corresponding to in vitro results and better distribution avoiding the need for further purification. SPECT / CT images
than other, clinically used radiopharmaceuticals. Conclusion: and the organ count showed that after nasal administration HT-
We have shown that different PVDs can be labelled with Ga-68 antigens remain in the nasal area and move onto the intestine,
with high affinity and radiochemical purity. 68Ga-PVDs revealed with a very different distribution to control animals; 75% of
suitable in vitro characteristics and excellent pharmacokinetics. the dose was eliminated at 6 h. Transdermal administration
In vitro uptake of 68Ga-PVDs in tested microbial cultures was shows a much slower elimination, compatible with very slow
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S316

absorption. Conclusion: The radiolabeling of HT-samples was and chronic PJI has a reduced inflammatory component due to
achieved in an efficient manner. SPECT/CT images and ex vivo low virulence factors, 18F-FDG could provide an in vivo diagnostic
counting confirmed that the intranasal administration achieves tool for this clinical problem. References: None.
a retention of HT samples in the nasal and intestinal mucosa
sufficient for an effective immunization. While additional studies
are needed to achieve good absorption, microneedle patches EPS-032
seem to be a promising route of administration. References: Design and performance evaluation of a fully automated
None. system for the synthesis of the gram-negative specific
radiotracer 18F-fluoro-deoxy-sorbitol
J. Simon, Á. Erhard, G. Quincoces, M. Rúa, M. Collantes, M. Ecay, I.
EPS-031 Peñuelas;
Differential 18F-FDG uptake in bacteria and yeast cells- Clínica Universidad de Navarra, Pamplona, SPAIN.
associated prosthetic joint infection strains
M. Rua, J. Simón, M. Collantes, M. Ecay, F. Carmona-Torre, Á. Erhard,
J. Payo-Ollero, G. Quincoces, J. Leiva, A. Valentí-Azcárate, J. Del Aim/Introduction: [18F]fluorodeoxysorbitol ([18F]FDS) is a gram-
Pozo, I. Peñuelas; negative specific radiotracer that can be obtained by a simple
Clínica Universidad de Navarra, Pamplona, SPAIN. reaction from the widely available [18F]fluorodeoxyglucose. This
tracer could potentially be used in the diagnosis of otherwise
undetectable infections like prothesis-associated infection.
Aim/Introduction: Chronic prosthetic joint infection (PJI) The aim of this work is to design, construct and evaluate the
is associated with significant morbidity and socioeconomic performance of a completely automated system for the synthesis
burden. Since Fluorine-18-fluorodeoxyglucose (18F-FDG) is able of [18F]FDS that yields a high purity product in a short time, while
to pinpoint bacteria and yeast metabolism, our objective was to also allowing the synthesis of other radiotracers. Materials and
quantitatively compare the uptake of PJI-relevant clinical isolated Methods: Five different Eckert&Ziegler modular units were
and reference strains of bacteria and yeast cells using in vitro used: motorized syringe, Peltier reactor, electrovalve, three-way
experiments Materials and Methods: Six different bacteria and valve ramp and a six-way valve module. The user interface and
yeast clinical isolates were selected from patients diagnosed synthesis sequence for the system were programmed using the
with chronic PJI (S. epidermidis, S. aureus, P. acnes, E. ludwigii, P. Modular-Lab software. 250-370 MBq of [18F]FDG were added
aeruginosa and C. albicans) and only in one case from a chronic into the reactor, and subsequently reduced with 0,5 mL of a
prosthetic heart valve infection (E. coli). Identification of clinical 4 mg/mL freshly prepared NaBH4 aqueous solution. After 15
strains was performed using MALDI-TOF (Matrix-Assisted Laser minutes in the reactor at 35 ºC the reaction was stopped with
Desorption/Ionization-Time Of Flight). Additionally five reference 1,4 mL of a HCl/Sodium acetate solution (0,4 and 0,9 M for each
strains (ATCC) were also studied as control. In vitro uptake of respectively). After neutralization to pH 6,5-7,5 with 0,2 mL of
18
F-FDG in reference strains and clinical isolates was compared NaOH 1M, the product was purified through an Alumina N
using three independent experiments and nine replicates. The Light Sep-Pack and sterile-filtered. Thin Layer Cromatografy
radiotracer (37±11 MBq/ml) was incubated with cultures of all using silica-gel based plates and 95:5 acetonitrile-water mixture
the species at 37ºC for 2 hours, pelleted by centrifugation and was used to evaluate the purity of the products (Rf ([18F]FDS):
washed with PBS. Microorganisms were counted by culturing 0,2). Results: A fully functional automatic synthesis system
in agar media before and after the experiment to control the (hardware, user interface and program) for the synthesis of the
growth. 18F-FDG uptake was measured using a gamma counter. [18F]FDS has been developed. The time-corrected radiochemical
Results: 18F-FDG in vitro accumulation of Gram-positive yield was 81 ± 6 % after 26 ± 2 min synthesis time, while our
bacteria was higher (mean = 5092 Bq/106 CFU) when compared old manual system took 41 ± 7 min and gave a 66 ± 14 % yield.
to Gram-negative (mean = 120 Bq/106 CFU). Among bacteria, S. TLC showed no traces of unreacted [18F]FDG. The pH for the
epidermidis clinical strain showed the highest uptake (7928 ± automatic systems product was always 6,5, while the manual
3305 Bq/106 CFU). Clinical and reference yeast cells (C. albicans) method needed 0,05-0,15 mL of additional NaOH. The produced
showed a thousand times higher 18F-FDG uptake in vitro than tracer has successfully been used for PET imaging in animal
any bacteria strain (mean clinical and reference strain = 1.2 ± 0.7 models of prosthetic infection. Conclusion: A system for the
MBq/106 CFU). Interestingly, P. aeruginosa incorporated virtually fully-automated production of [18F]FDS has been created. This
no 18F-FDG (mean clinical and reference strain = 4 ± 6 Bq/106 new system provides a 15% improvement in the radiochemical
CFU) and showed a decrease in the number of bacteria during yield and a 38% reduction of the time required for the synthesis.
the experiment that was not observed in the other species. The synthesis with the automatic module also showed an
Conclusion: Yeast cells (eukaryotic) presented unexpected increased reproducibility, with lower variability in the yield, time
higher uptake compared to bacteria. The lack of 18F-FDG uptake and final pH. Moreover, the system has also been used for the
both in the clinical isolate and the ATCC strain of P. aeruginosa synthesis of [18F]-2-fluoro-paraaminobenzoic acid ([18F]FPABA,
and the observed decrease in growth might be due to a higher other bacterial specific radiotracer) with minimal alteration of
radiosensibility of this specie. Since virtually all bacterial strains the configuration of the system. References: None.
associated with PJI showed 18F-FDG uptake in variable amounts
S317 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

EPS-033 411
Ga-citrate PET/CT findings in experimental acute
68

appendicitis induced rabbits: preliminary results


e-Poster Presentation Session 3 - Neuroimaging:
A. Gültekin, O. Uzunlu, A. Uğur, D. Yüksel;
Neurodegeneration, Amyloidosis and
Pamukkale University Medical Faculty, Denizli, TURKEY.
Neuroinflammation

Sunday, October 13, 2019, 14:30 - 16:00 Room 133/134


Aim/Introduction: Acute appendicitis (AA) is the most
common abdominal surgical emergency all around the world.
Lifetime risk of AA is about 7% to 8%. It is most commonly seen
in second and third decades of life. Preferred treatment for AA EPS-034
is surgery. Diagnosis of acute appendicitis is sometimes difficult. Clinical outcome of Amyloid PET: interim analysis of the
In addition to imaging methods such as ultrasonography and Spanish Registry of amyloid PET
computed tomography, infection imaging methods have J. Arbizu1, G. Marti1, C. Lorenzo-Bosquet2, C. Gamez3, M. Gomez-
been used for diagnosis in some limited cases. 67Ga-citrate is a Rio4, C. Marsal5, M. Balsa6, B. Rodriguez-Alfonso7, A. Garcia-Vicente8,
radiopharmaceutical that has traditionally been used in infection R. Larumbe9, E. Caballero10, A. Gomez-Grande11, P. Sopena12,
and inflammation imaging. However, due to its disadvantages, L. Dominguez-Gadea13, A. Rotger14, V. Camacho15, J. Boan16, P.
it is not used much now. 68Ga-citrate and 67Ga-citrate are an Tamayo17, A. Perissinotti18, I. Peñuelas1, C. Carnero4, P. Martinez-
analog molecule. Half-life of 68Ga is much shorter than 67Ga. It Lage19, I. Carrio15, on behalf of the Spanish Registry of Amyloid PET
is suitable for imaging in PET/CT devices and provides a good and PET ADDS Consortium;
image resolution. The aim of this study was to investigate the 1
Clinica Universidad de Navarra, Pamplona, SPAIN, 2Hospital
use of 68Ga-citrate in experimentally induced with AA rabbits. Universitario Vall d´Hebron, Barcelona, SPAIN, 3Hospital
Materials and Methods: Twelve rabbits from New Zeland Universitario de Bellvitge, Barcelona, SPAIN, 4Hospital Universitario
lineage (oryctogalus cuniculus) weigthing approximately 2750 Virgen de las Nieves, Granada, SPAIN, 5Complejo Hospitalario
grams each were included. The animals were divided into two de Toledo, Toledo, SPAIN, 6Hospital Universitario de Getafe,
groups. Appendicus of AA group rabbits was ligated from 10 cm Madrid, SPAIN, 7HospitalUniversitario Puerta de Hierro, Madrid,
distal. The abdomens of 6 rabbits in the sham group was opened. SPAIN, 8Complejo Hospitalario de Ciudad Real, Ciudad Real,
Their appendices were touched and their abdomens are closed SPAIN, 9Complejo Hospitalario de Navarra, Pamplona, SPAIN,
again. Both groups were imaged with 68Ga-citrate PET/CT for 12- 10
Hospital Universitario Dr. Peset, Valencia, SPAIN, 11Hospital
24-36 hours after the formation of AA model. For 68Ga-citrate Universitario 12 de Octubre, Madrid, SPAIN, 12Hospital 9 de
PET/CT imaging, the 68Ga citrate was synthesized as home Octubre, Valencia, SPAIN, 13Hospital Universitario La Paz,
made. Whole body scans were made after each 60 minutes of Madrid, SPAIN, 14Hospital Universitario Gregorio Marañon,
injection of about 37 mBq of 68Ga-citrate through the ear vein. Madrid, SPAIN, 15Hospital Universitario de la Santa Creu i
At the 36th hour, all rabbits were appendectomized. Appendices Sant Pau, Barcelona, SPAIN, 16Hospital Ruber Internacional,
were sent to the pathology laboratory for histopathological Madrid, SPAIN, 17Complejo Asistencial Universitario de
examination. Results: Macroscopically, 3 of 6 rabbits Salamanca, Salamanca, SPAIN, 18Hospital Clinic, Barcelona,
undergoing appendectomy had perforated appendicitis, 2 had SPAIN, 19CITA Alzheimer Foundation, San Sebastian, SPAIN.
suppurative appendicitis, and 1 had gangrenous appendicitis.
Appendices of the sham group rabbits were completely normal
in macroscopically. In all AA modeled rabbits, 68Ga citrate was Aim/Introduction: To evaluate the influence of amyloid PET
successfully visualized AA localisation after the 12th hour. The on planned prescription of Alzheimer´s disease (AD) drugs in
68
Ga citrate showed the increased uptake in the AA region subjects with progressive cognitive impairment of uncertain
within hours. Conclusion: 68Ga citrate has quite good uptake aetiology. Materials and Methods: A multicentric prospective
in the appendicitis region in the AA model created in rabbits. observational clinical study of patients with objective cognitive
However, high uptake of 68Ga-citrate in kidneys, liver, spleen and impairment evaluated for suspected AD and referred for an
very high blood pool activity are the most important limiting Amyloid-PET scan was conducted. The study consisted on a
factors. This study is ongoing. In AA, the relationship between monitored collection of clinical and image case record forms
histopathological signs of inflammation and 68Ga-citrate filled by neurologists and nuclear physicians of 18 centres
involvement will be shown. References: None. on a digital platform. Specifically, neurologists were asked
about therapeutic planning according to the suspected
aetiological diagnosis as well as diagnostic confidence pre-
and post-PET scan. A mixed effects logistic regression modelof
factors associated with change in AD drug therapy was fitted
considering age, gender, education level, dementia, AD
diagnosis, PET result, diagnostic confidence and controlled by
centre random effects. Results: 210 out of 369 patients with
complete pre- and post-PET data set were evaluated. Median
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S318

age was 68 years [IQR 63-73] and 55.6% were females. Subjects p=0.006), while the Aβ-negative patients showed lower QSM
were clinically evaluated by dementia specialists: 60.4% were values in the caudate nucleus (0.003±0.027vs. 0.051±0.039;
MCI and 39.6% were demented. Median age in MCI patients p=0.006). ROC analysis revealed the following threshold QSM
was 69 years [IQR 64-74], and 69 years [IQR 63-74] in dementia values: to differentiate between Aβ PET-positive patients and
patients (p=0.735). 50% of MCI cases and 64.5% of dementia HCs: putamen: -0.0014ppm (sensitivity: 0.88, specificity: 0.55,
patients were females (p=0.048). Median MMSE in MCI was 26 Youden’s index: 0.43); to differentiate between Aβ PET-negative
[IQR 24-28], and 20 [IQR 18-24] in dementia (p<0.001). Pre-PET patients and HCs: caudate nucleus: -0.0184ppm (sensitivity:
aetiological diagnoses were AD 86.3% (typical AD 50%, atypical 0.82, specificity: 0.60, Youden’s index: 0.42). Putaminal QSM
AD 36.3%), and non-AD 13.7%. The percentages of Amyloid-PET values showed a trend towards a significant correlation with the
positivity in typical AD were 71.6% in MCI and 82.8% in dementia MMSE scores (ρ=-0.340, p=0.053). Furthermore, in the Aβ PET-
patients; in atypical AD were 46.9% in MCI and 52.9% in dementia; positive patients, the putaminal QSM values were significantly
and in the non-AD were 38.5% in MCI and 60% in dementia. correlated with the composite neocortical SUVRs (ρ=-0.574,
Changes of planned AD drugs (start, stop and modification) p=0.020). Conclusion: Compared to the HCs, patients with
between pre- and post-PET was 42.2%. Multivariable analysis amyloid biomarker-supported AD showed significantly higher
of factors associated with AD treatment changes (Table 1) QSM values in the putamen, and non-AD patients significantly
showed significant interaction between PET scan results and lower QSM values in the caudate nucleus. These data indicate
pre-PET primary aetiological diagnosis (p=0.001). Conclusion: that QSM on hybrid 3T PET/MRI has potential in determining the
Amyloid PET result has a significant influence on the clinicians´ difference in iron content in deeper brain regions and in relation
planned management of patients with cognitive impairment to the pathophysiological process. The results encourage
of uncertain aetiology, including dementia syndrome. In our further investigations in well-defined patient cohorts to clarify
experience, the probability of changes in the prescription of the value of QSM/magnetic susceptibility in the course of
AD drugs increases when atypical AD or non-AD diagnoses are neurodegenerative diseases. References: None.
suspected References: None.

EPS-036
EPS-035 Validation of a pseudoreference region approach using
Simultaneous 3T Quantitative Susceptibility Mapping MRI [18F]DPA714 in ALS patients
and Amyloid PET in Dementia D. Van Weehaeghe1, N. Zürcher2, C. Tseng2, M. Koole1, M. Alshikho3,
M. Rullmann1,2, S. Tiepolt1, A. Schäfer2,3, T. H. Jochimsen1, M. L. J. Hooker2, J. De Vocht4, P. Van Damme4, K. Van Laere1, N. Atassi3;
Schroeter2, M. Patt1, O. Sabri1, H. Barthel1; 1
Department of nuclear medicine and biomedical imaging,
1
Department of Nuclear Medicine, University of Leipzig, University Hospital Leuven, Leuven, BELGIUM, 2Athinoula
Leipzig, GERMANY, 2Max-Planck-Institute for Human A. Martinos Center for Biomedical Imaging, Massachusetts
Cognitive and Brain Sciences, Leipzig, GERMANY, 3Siemens General Hospital, Harvard Medical School, Boston, MA, UNITED
Healthcare GmbH, Diagnostic Imaging, Magnetic Resonance, STATES OF AMERICA, 3Neurological Clinical Research Institute,
Research & Development, Erlangen, GERMANY. Massachusetts General Hospital, Harvard Medical School,
Boston, MA, UNITED STATES OF AMERICA, 4Department of
Neurology, University Hospital Leuven, Leuven, BELGIUM.
Aim/Introduction: It is known that, in Alzheimer’s disease
(AD), cerebral Aß plaques contain/are surrounded by excessive
iron. As iron is paramagnetic, it can be detected by certain MRI Aim/Introduction: Amyotrophic lateral sclerosis (ALS) is
methods, like Quantitative Susceptibility Mapping (QSM). So far, a devastating motor neuron disease. Neuroinflammation,
most QSM MRI studies in patients with the clinical diagnosis of reflected by glial activation, has been observed using [11C]
AD found an increase of iron-sensitive MR signals in the putamen PBR28,[11C]PK1195 and [18F]DPA714, mainly in the (pre)motor
and other deeper brain structures. The aim of this exploratory cortex and correlates with clinical parameters (1-7). Although full
study was to examine whether these results translate to dynamic modelling is the gold standard, genotype differences
simultaneous 3T amyloid PET/MRI. Materials and Methods: increase inter-subject variability and long dynamic scans are
We retrospectively analyzed the QSM MRI/C-11-PiB PET data of only feasible in early stage ALS due to fast progression and
11 healthy controls (HCs, 7 female; 65±3yrs) as well as 16 Aβ PET- bulbar symptoms. Studies using [11C]PBR28 in ALS have already
positive (12 female; 69±9yrs) and 10 Aβ PET-negative (6 female; successfully used pseudoreference regions (3-7). [18F]DPA714
73±8yrs) dementia patients. The data were analyzed regionally has a similar effect size as [11C]PBR28 however, the [18F]-labelling
using the AAL template (PMOD). A ROC analysis combined with facilitates distribution and enables multiple scans using one
the calculation of Youden’s index was performed to determine single production. In this work, we aim to validate the use of
QSM cut-off values. Outcome measures for the MRI data were a pseudoreference region approach using [18F]DPA714 in ALS.
regional QSM values, and for the PET data regional SUV ratios Materials and Methods: 7 healthy volunteers (HV,51.9±17.3y, all
taking the cerebellar cortex as reference region. Results: mixed affinity binders (MAB), 4F) and 6 ALS patients (61.7±6.7y, 3
Compared to the HCs, the Aβ PET-positive patients showed high AB-3 MAB, 2F) underwent a 60-minute [18F]DPA714 (145±21
higher QSM values in putamen (0.049±0.033vs.0.002±0.031; MBq injected activity) PET-MR scan with full kinetic modelling. VT
S319 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

maps (Logan approach) were calculated in Pmod v3.9. SUVR40-60 far mainly studied post-mortem, and is subject of a controversial
using cerebellum (CBL), occipital cortex (OC) and whole brain debate. We aimed to answering this question in vivo using the
without ventricles (WB-ventricles) were created. After region- recently developed α4β2-nAChR-specific radioligand (-)-[18F]
based partial volume correction (Freesurfer v6.0), the ratios of Flubatine and PET. Materials and Methods: Non-smoking,
mean (pre)motor over mean OC, CBL and WB-ventricles were drug-naïve AD-APOE ε4+ (n=7; 76±6ys; 6 females; MMSE 24±3)
calculated for VT and SUVR40-60 to correct for genotype. Student and AD-APOE ε4- (n=9; 75±7ys; 7 females; MMSE 24±2, n. sign.
t-test was performed to compare ALS to HV and Pearson was vs. AD-APOE ε4+) were investigated using (-)-[18F]Flubatine
used to correlate VT maps and SUVR40-60 (SPSS v25). Additionally, (370 MBq, ECAT Exact HR+, 0-90min p.i.) and compared with
surface based comparisons between ALS and HV on SUVR40-60 non-smoking healthy controls (HC; n=13; 72±4ys; 7 females).
images were performed after Gaussian smoothing (1 and 6 mm) For quantification of the α4β2-nAChR availability, kinetic
(projection factor 0.5, puncorr<0.05, pcluster FWE-corr<0.05) (Freesurfer modeling (1TCM, Logan) was performed and the distribution
v6.0). Results: Increased [18F]DPA714 signal (10%) in the (pre) volume (VT) was calculated. VOI analyses of a-priori selected
motor cortex was observed as measured by VT (gold standard) brain regions and exploratory SPM analyses were carried out
using OC(p=0.029) and by SUVR40-60 using OC (p=0.049) and (ANCOVA, significance at P<0.05 and T>3.0; P<0.003). Results:
WB-ventricles (p=0.025). A trend was observed for VT using Compared with HC, in AD-APOE ε4+, there was significantly
WB-ventricles (p=0.082). Surface-based comparisons showed lower VT within the basal forebrain, hippocampus, amygdala,
similar results. Highly significant correlations were observed and fronto-temporal cortices. Compared with HC, in AD-
between VT and SUVR40-60 for OCC (r=0.83, p<0.001), CBL (r=0.97, APOE ε4-, voxel-based analysis revealed significantly lower
p<0.001) and WB-ventricles (r=0.94, p<0.001)). Conclusion: VT in minor clusters within the fronto-temporo-parietal and
Reference region SUVR40-60 values provide similar and even more posterior cingulate cortices. In AD-APOE ε4+, directly compared
robust results as VT obtained by full quantification Additionally, with AD-APOE ε4-, there was significantly lower VT within the
SUVR40-60 correct for genotype, so no arterial sampling is needed basal forebrain, hippocampus, amygdala, fronto-temporal, and
and short static scans can be sufficient with highest sensitivity cingulate cortices. Conclusion: Using the recently developed
using WB-ventricles as pseudoreference region. In conclusion, (-)-[18F]Flubatine and PET, we demonstrated for the first time
these results indicate that instead of 60-minute full kinetic in-vivo the influence of APOE ε4 on α4β2-nAChR availability in
modelling with arterial sampling, a static 20-minute scan is mild AD. In contrast to earlier studies, we show that the APOE ε4
sufficient for [18F]DPA714 ALS analysis. References: 1.Turner. genotype modulates the α4β2-nAChR pathophysiology in AD.
et.al.Neurobiol Dis.2004 2.Corcia.et.al.PLoS ONE.2012 3.Zürcher. If replicated in larger cohorts, our findings encourage adjusting
et.al.Neuroim Clin.2015 4.Albrecht.et.al.JNM.2018 5.Ratai.et.al. cholinergic drug therapy to the APOE genotype in patients with
Neuroim Clin.2018 6.Alshikho.et.al.Neurology.2016 7.Alshikho. AD. References: None.
et.al.Ann Neurol.2018

EPS-038
EPS-037 Assessment of Centiloid [18F]flutemetamol values
Influence of APOE genotype on α4β2 nicotinic relative to CERAD-style pathology categories from a well
acetylcholine receptor binding in mild Alzheimer‘s characterised autopsy cohort
dementia as assessed by (-)-[18F]Flubatine PET C. J. Buckley1, M. Battle1, G. Farrar1, C. Foley1, A. Smith1, D. Thal2;
P. Meyer1, S. Wilke1, S. Hesse1,2, G. Becker1, M. Rullmann1, M. Patt1, J. 1
GE Healthcare Pharmaceutical Diagnostics,
Luthardt1, G. Wagenknecht3, A. Hoepping4, R. Smits4, B. Sattler1, S. Amersham, UNITED KINGDOM, 22.Department of
Tiepolt1, W. Deuther-Conrad5, H. Barthel1, P. Schönknecht6, P. Brust5, Neurosciences, KU Leuven, Leuven, BELGIUM.
O. Sabri1;
1
Department of Nuclear Medicine, University of Leipzig,
Leipzig, GERMANY, 2Integrated Research and Treatment Aim/Introduction: [18F]flutemetamol Centiloid (CL) values from
Centre (IFB) Adiposity Diseases, University of Leipzig, Leipzig, a PET-only SUVR analysis pipeline were compared to autopsy-
GERMANY, 3Electronic Systems (ZEA-2), Central Institute determined neuritic plaque densities assessed by a numeric
for Engineering, Electronics and Analytics, Research Centre CERAD-style method1 (mCERAD) with a view to determining the
Juelich, Juelich, GERMANY, 4ABX advanced biochemical band of CL values associated with the numerical equivalents of
compounds GmbH, Radeberg, GERMANY, 5Department of neuritic plaque mCERAD categories of none, sparse, moderate
Neuroradiopharmaceuticals, Institute of Radiopharmaceutical or frequent with a view to identifying the Centiloid band of
Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, values for those accumulating amyloid pathology in early stages
Research Site Leipzig, Leipzig, GERMANY, 6Department of Psychiatry Materials and Methods: [18F]flutemetamol PET images were
and Psychotherapy, University of Leipzig, Leipzig, GERMANY. made in 106 subjects in life and pathology CERAD scores of
neuritic plaque densities were measured post-mortem. The PET
images were analysed using an adaptive template-based PET-
Aim/Introduction: The question of whether the presence of only pipeline (AmyPype) to provide SUVR Centiloid values from
the APOE ε4 allele impacts α4β2 nicotinic acetylcholine receptor these subjects. Post-mortem histopathology assessments were
(α4β2-nAChR) availability in Alzheimer’s dementia (AD) was so from 8 regions. Neuritic plaque densities using Bielschowsky
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S320

silver-staining were made to obtain quantitative regional (SUVregion/SUVcerebellum) and compared in the two groups (based
pathology scores aligned with CERAD style scoring. Each on FDG PET/CT patterns) and with normal controls. Significance
subject’s pathology was considered abnormal if any region was evaluated statistically using Mann Whitney U test. Results:
had a numeric mCERAD score greater than the boundary Maximum 18F-ML-104 retention was noted in the medial
between sparse and moderate. Particular emphasis is given to temporal lobes in both the FDG hypometabolism group (mean
the Centiloid values in subjects whose levels of pathology are SUVR-1.63) and the no-hypometabolism group (mean SUVR-
positive, but below accepted autopsy thresholds. Results: CL 1.48), with a significant difference between groups (p=0.04).
values for the mCERAD bands are shown in Table 1. Conclusion: There was a significant difference in retention of the tracer in
The Centiloid values in the cases which had pathology but were the lateral temporal (p=0.02), precuneus (p=0.03) and posterior
below mCERAD positive thresholds had a median value of ~17 cingulate (p=0.03) cortex between the two groups. Compared
with most of the values lying below 28 Centiloids. The subjects to controls, tracer retention was significantly increased in all
in this band which had Centiloid values of greater than 28 had the regions evaluated in both groups (p <0.01). Conclusion:
Thal phases 3 to 5 indicating the likely role of diffuse plaques We could demonstrate a significant increase in tau deposition
in elevating the Centiloid scores. For those cases which had in amnestic MCI patients with a metabolic pattern consistant
border-line positive pathology, the majority had Centiloid values with early AD on FDG PET. This suggest the utility of tau PET as
above 50. However, there were 4 cases below 30 Centiloid. a biomarker for MCI patients who are likely to progress to AD
These cases typically had pathology scores that were regionally dementia. References: None.
variable which, though positive by mCERAD rules, the averaging
out the PET signal in the large Centiloid cortical VOI produced
a net lower value. In summary, subjects with Centiloid values EPS-040
between 15 and 30 are highly likely to be accumulating amyloid Sex Modulates the ApoE ε4 Effect on Tau Brain Deposition
pathology which may not have reached the density required to measured by18F-AV-1451 PET in Individuals with Normal
show as visually abnormal by PET. References: 1. Ikonomovic Aging and Mild Cognitive Impairment
et. al. Acta Neuropathologica CommunicationsNeuroscience of R. Wang1,2, M. Liu1, X. Chen1, Y. Zhou3;
Disease2016 4:130 1
Peking University First Hospital, Beijing, CHINA, 2Peking University
International Hospital, Beijing, CHINA, 3Johns Hopkins University
School of Medicine, Baltimore, MD, UNITED STATES OF AMERICA.
EPS-039
18F-ML-104 Tau Positron Emission Tomography/Computed
Tomography: a potential biomarker for mild cognitive Aim/Introduction: To evaluate sex differences in the association
impairment due to Alzheimer’s disease between apolipoprotein E type 4 allele (ApoE ε4) carrier status
J. Jaleel, M. Tripathi, V. Baghel, S. T. Arunraj, P. Kumar, A. Dey, C. Bal; and brain tau deposition measured using 18F-AV-1451 positron
All India Institute of Medical Sciences, New Delhi, INDIA. emission tomographic (PET) imaging among mild cognitive
impairment (MCI) participants. Materials and Methods:
Preprocessed 18F-AV-1451 tau and 18F-AV-45 amyloid PET
Aim/Introduction: Tau positron emission tomography/ images, T1-weighted structural magnetic resonance imaging
computed tomography (PET/CT) enables invivo imaging of (MRI) scans, demographic information, and cerebrospinal
the spatial distribution pattern of neurofibrillary tau tangles fluid (CSF) total tau (t-tau) and phosphorylated tau (p-tau)
in the brain. We have previously demonstrated increased tau measurements from 108 MCI subjects (mean age 78.3 (7.4)
deposition in temporo-parietal regions in Alzheimer’s dementia years) in the Alzheimer’s Disease Neuroimaging Initiative (ADNI)
(AD) and early AD in comparison to normal controls (paper database were included.After downloading pre-processed
in communication). This study was undertaken to evaluate images from ADNI, an iterative reblurred Van Cittertiteration
the tau distribution pattern in patients with amnestic mild partial volume correction (PVC) method was applied to all PET
cognitive impairment (MCI). Materials and Methods: Twenty images. MRIs were used for PET spatial normalization. Regions of
eight patients, who were diagnosed clinically as amnestic MCI interest (ROIs) were defined in standard space, and standardized
(MMSE ≥ 24) in the geriatric memory clinic, were included in uptake value ratio (SUVR) images relative to cerebellum were
the study. Ten normal controls, were also recruited. Each MCI computed. ApoE ε4 by sex interaction analyses on 18F-AV-1451
patient underwent 18F- Fluorodeoxyglucose (18F-FDG) PET/CT and CSF tau (t-tau, p-tau)were assessed using generalized linear
on the basis of which they were divided into two groups- those models. Correlation between 18F-AV-1451 SUVR and CSF tau
showing a metabolic pattern consistant with early AD (shown to (t-tau, p-tau) were calculated. Results: After applying PVC and
beat a greater risk of developing overt AD) and those who did controlling for age, education level and global cortical 18F-AV-45
not reveal any metabolic abnormality. All patients and controls SUVR, we found that the entorhinal cortex, amygdala, fusiform,
were taken up for the 18F-ML-104 Tau PET/CT (Neptis-ORA). The parahippocampal gyrus, posterior cingulate, and occipital ROIs
tau PET/CT images were independently evaluated using region exhibited a significant ApoE ε4 by sex interaction effect(FDR
of interest drawn over bilateral frontal, parietal, medial temporal, P<0.05) among MCI individuals. There were significant ApoE ε4
lateral temporal lobes, posterior cingulate, precuneus and by sex interaction effect in CSF t-tau and p-tau.18F-AV-1451 SUVR
cerebellum. The standardised uptake value ratios were calculated in all 6 ROIs with ApoE ε4 by sex interaction was significantly
S321 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

correlated with CSF p-tau and t-tau. Conclusion: Our findings differ. Assessment (B) decreased sensitivity (-7%, p=0.04)
suggest that women are more susceptible to ApoE ε4-associated while specificity increased (+10%, p=0.004). Assessment
accumulation of neurofibrillary tangles during preclinical stages (C) only decreased sensitivity (-6%, p=0.05). Assessment (D)
of AD compared to males, and may also be more cognitively decreased sensitivity (-14%, p=0.002) and increased specificity
resilient to higher loads of tauopathy. Both CSF tau (p-tau, (+15%, p=0.003). As compared to assessment (A), inter-reader
t-tau) and brain tau PET are robust quantitative biomarkers for agreement was higher for assessment (B) (0.80, p=5×10-211 vs.
studying ApoE ε4 by sex effects on tau brain deposition in MCI. 0.76, p=2×10-192). Intra-reader agreement did not relevantly differ
The strongest genetic risk factor for AD is the ApoE ε4. We report between the assessment types (85-90%). Conclusion: Standard
that sex modulates the relationship between ApoE ε4 carrier visual evaluation of [18F]Florbetaben PET images already has
status and brain tau deposition (a quantitative endophenotype high sensitivity, which cannot be further improved by the
in AD) in individuals with MCI. These new findings improve our approaches tested. Reliability and at the expense of sensitivity,
understanding of the role of sex and ApoE ε4 as risk factors in specificity can, however, be increased by superimposing
preclinical AD and help develop precision-medicine based WM/GM contrast and/or PVE correction of the PET data. A
therapeutics. References: None. prospective evaluation of this promising approach is warranted.
References: None.

EPS-041
At first sight - Can gray matter/white matter boundary EPS-042
delineation or partial volume effect correction improve Baseline Assessments of Striatal Amyloid Plaque
the visual read of [18F]Florbetaben PET images? Load, Hippocampal and Ventricular Volumes via [18F]
M. Rullmann1,2, S. Tiepolt1, K. Messerschmidt1, T. Gerhards1, flutemetamol PET and MRI Imaging Predicts Clinical
M. Schürer1, S. Hesse1,2, D. Saur3, C. Weise3,4, M. L. Schroeter4, J. Progression to pAD in a 3-year Observational aMCI Cohort
Classen3, O. Sabri1, H. Barthel1; Study
1
Department of Nuclear Medicine, University of Leipzig, L. Chedumbarum Pillay1, P. Wilkens2, C. J. Buckley3;
Leipzig, GERMANY, 2IFB AdiposityDiseases, Leipzig University 1
University of Oxford, Oxford, UNITED KINGDOM, 2GE
Medical Center, Leipzig, GERMANY, 3Department of Neurology, Healthcare, Marlborough, MA, UNITED STATES OF AMERICA,
University of Leipzig, Leipzig, GERMANY, 4Day Clinic of Cognitive 3
GE Healthcare, Amersham, UNITED KINGDOM.
Neurology, University of Leipzig, Leipzig, GERMANY.

Aim/Introduction: By clinicopathological diagnostic


Aim/Introduction: Beta-amyloid (Aß) PET tracers like [18F] requirements for Alzheimer Disease (AD), a minimum load of
Florbetaben are approved for clinical use via binary visual both Aß and neurofibrillary tau tangles (NFTs) should be present.
evaluation for the existing (Aß-negative) or missing (Aß-positive) Amyloid imaging is therefore critically limited in this regard.
contrast between specific gray matter (GM) and non-specific Post-mortem studies have indicated a stronger association,
white matter (WM) uptake. Consequently, a priori reader however, between striatal Aß deposition and advanced NFT
training focusses on evaluating the GM/WM contrast within Braak stages. Further to amyloid measures, structural MRI
the PET images. Of note, the influence of partial volume effects neurodegenerative biomarkers are a key consideration to be
(PVEs) is so far not considered in this clinical routine visual read. able to identify individuals with mild cognitive impairment
Thus, we tested the hypothesis that amyloid PET read can be (MCI) due to AD. In addition to assessments of striatal amyloid
improved by WM/GM boundary superimposition and/or PVE plaque burden, we investigate cortical thickness atrophy of
correction. Materials and Methods: Six nuclear medicine the medial temporal structures, hippocampal atrophy and
physicians (three experts, three novices after reader training) ventricular dilation in an aggregate measure of neuronal injury
blindly and independently evaluated 480 [18F]Florbetaben (N), with respect to their statistical predictive performance in
PET datasets (90-110min p.i.) including 20% duplicates and amnestic MCI (aMCI) to probable AD (pAD) progression and
four modalities: (A) Standard PET images, (B) PET images with survival rates over a three-year observation period. Materials
superimposed WM/GM boundaries (individual T1 MPRAGE and Methods: Facilitating our analysis were the baseline [18F]
MRI, segmentation in SPM12), (C) PVE-corrected (Van-Cittert flutemetamol PET and 3D T1 MRI scans of 231 aMCI subjects
deconvolution approach) PET images, (D) combined B and C. obtained in a three-year GE Healthcare led Phase-III clinical trial
Evaluation included binary diagnosis and diagnostic confidence comprising of cross-sectional PET/MR imaging and longitudinal
(five-point Likert scale). Results of the clinical consensus board clinical evaluation. Subjects’ baseline PET and MRI images were
served as standard of truth. Sensitivity, specificity, accuracy, pre-processed and co-registered in FSL v5.0. A striatal volume
multi-rater Fleiss’ kappa and percentage of agreement for of interest (VOI) based on an average pAD [18F]flutemetamol
duplicates were assessed for all four modalities. Differences in PET image was used to quantify striatal uptake by means of a
sensitivity, specificity, accuracy and confidence were tested by SUVr_pons ratio. Cortical thicknesses and hippocampal volume
paired t-tests. Results: Assessment (A) showed high sensitivity, were derived in FreeSurfer v6.0. Frontal-lateral ventricular
specificity, accuracy and confidence (97%, 82%, 90%, 81%, dilation was estimated in FSL. Results: Of the 95 Blinded
respectively). Here, experts and novices did not significantly Image Evaluated (BIE) Amyloid-Positive (A+) aMCI subjects,
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S322

those who progressed to pAD (N=51) had a mean(SD) bilateral composite SUVR of training and test sets were 0.031 and 0.064.
striatal SUVr_pons of 0.87(0.11), and those who remained aMCI The mean absolute error of florbetaben PET as an independent
(N=26, excl. 18 middle censored), 0.75(0.11). Striatal uptake was test set was 0.057. The correlation coefficients were 0.99, 0.93,
therefore significantly higher amongst BIE A+ subjects who had and 0.93 for the training set, test set of florbetapir PET, and
progressed to pAD (p=2.5e-05, Mann-Whitney U-test). Following florbetaben PET, respectively. Samples were divided into two
ROC analysis, also associated with striatal uptake was an AUC groups, amyloid-positive and negative, using a predefined
of 0.80. Cortical thickness measures of the entorhinal (ENT) cutoff value of the composite SUVR. The agreement measured
and parahippocampal (PHC) cortices over the full cohort had by Cohen’s kappa of two quantification methods, approaches
respective mean(SD)s of [Non-Converters: 3.2(0.42), Converters: of full-processing with MR and deep learning, was 0.84 and 0.78
2.9(0 .49)] and [Non-Converters: 2.6(0.3), Converters: 2.46(0.28)], for test sets of florbetapir PET, and florbetaben PET, respectively.
and respective AUCs of 0.30 and 0.30. We thus omit cortical The Bland-Altman plots showed the agreement without bias
thickness measures in our aggregate measure of neuronal for the quantification. Conclusion: We suggest a feasible
injury, and accounting for hippocampal atrophy and ventricular quantification method for amyloid PET with the end-to-end
dilation achieve sensitivity and specificity rates of 0.82 and 0.77, training of deep learning. For our approach, structural MR and
and improved hazard rates of up to 67% compared to (cortical) multiple preprocessing steps are not required. Furthermore, it
amyloid positivity status alone. Conclusion: Baseline striatal shows reliable quantification results of PET images obtained
amyloid load, hippocampal volume and ventricular dilation from multiple centers. References: None.
provide markedly improved statistical predictive performance
rates in aMCI progression to clinical pAD. References: None.
EPS-044
Comparison of Centiloid Scaling Values with Visual Read
EPS-043 Assessment in a Pathology Verified Autopsy Cohort
Direct quantification of native-space amyloid PET via end- M. Battle1, C. Buckley1, A. Smith1, G. Farrar1, D. R. Thal2, J.
to-end training of a deep learning Molineuvo3, O. Hansson4,5;
J. Kim, H. Choi, J. Paeng, G. Cheon, K. Kang, D. Lee; 1
GE Healthcare, Amersham, UNITED KINGDOM, 2Department
Department of Nuclear Medicine, Seoul National of Neurosciences, KU Leuven, Leuven, BELGIUM, 3Barcelona
University, Seoul, KOREA, REPUBLIC OF. Brain Research Centre, Barcelona, SPAIN, 4Clinical
Memory Research Unit, Department of Clinical Sciences
Malmö, Lund University, Lund, SWEDEN, 5Memory
Aim/Introduction: Accurate quantification of amyloid PET is Clinic, Skåne University Hospital, Malmö, SWEDEN.
crucial for the estimation of amyloid load in the gray matter as a
biomarker for Alzheimer’s disease. So far, the quantification has
required complicated preprocessing steps including structural Aim/Introduction: Centiloid scaling has been established
MR-based segmentation and normalization. It has been difficult as a method of standardising quantitative image analysis
to perform the quantification as a clinical routine because of for measuring the uptake of βamyloid imaging PET tracers
no unified method of multiple centers and time and effort for in Alzheimer’s disease (AD), with process pipeline equations
the processing. Here, we developed a deep learning model to reported by various groups 1,2,3. The “Standard” Centiloid
quantify amyloid PET via the end-to-end training using native- methods, described by Klunk et.al.4, utilise both PET and
space multiple center PET images. Materials and Methods: MR scans with defined regions of interest. Here the utility of
Amyloid PET data from the Alzheimer Disease Neuroimaging Centiloid scaling in a cohort of subjects with no MRI scans was
Initiative were used. 850 baseline florbetapir PET images investigated. AmyPype-derived Centiloid (AmyPCentiloid) values
were used as a training/validation set and 366 florbetapir PET for [18F]flutemetamol were calculated and compared against
images as 2-year follow-up were used as an independent visual read outcomes for the PET images. This is compared to
test set. We also validate the model using 89 florbetaben the pathology status. Materials and Methods: Using an in-
PET data. We designed a 3-d convolutional neural network house developed software platform (AmyPype) the Centiloid
model for the direct quantification. The end-to-end training of Volume of Interest (VOI) regions were applied to 104 [18F]
deep learning model was performed using native-space PET flutemetamol images obtained from subjects who were part
images as inputs and standardized uptake value ratios (SUVR) of a larger autopsy study. Images had been assessed as either
previously calculated by MR-based preprocessing as outputs. normal (n=34) or abnormal (n=70) by majority visual read. SUVR
SUVR of 4 cortical subregions (frontal, cingulate, parietal, and and AmyPCentiloid values for the VOI regions were calculated.
temporal) were estimated using the deep learning model. A comparison of the SUVR and AmyPCentiloid classifications
The composite SUVR was obtained by the mean value of the with the visual assessment reads were made. Results: SUVR
4 subregional SUVR. The model performance was estimated by and AmyPCentiloid values were ranked in ascending order and
mean absolute errors of the composite SUVR and correlation plotted for each subject. For the SUVR and Centiloid values, the
coefficients using a Pearson correlation. Bland-Altman plots threshold between normal and abnormal subjects as defined by
were drawn to evaluate bias and errors of the deep learning- visual reads were determined. A comparison of the AmyPCentiloid
based estimation. Results: The mean absolute error of the prediction, based on a threshold cut-off of 40 for an autopsy
S323 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

based normal/abnormal classification , gave an 89% (93/104) independent sample t-test in T+ vs T- sub-groups based on VA
agreement with the visual read assessment. Interestingly, in consensus. Results: Raters showed a substantial agreement in
the cases where there was disagreement between the visual visual classification, with a kappa ranging between 0.68 and
assessment and the AmyPCentiloid prediction, AmyPCentiloid 0.78 (percentage of agreement 87%-91%), and an average
predictions agreed with at least one reader in 45% (5/11) cases. confidence in the interval 3.4-4.5. Global SUVR was significantly
Conclusion: Centiloid values provide quantifiable information different in T+ vs T- subjects classified according to VA consensus
that can complement the visual read assessment. For the cases (t(118)=5.64, p<0.001). In the assessment of the T status based
where there was disagreement between readers, the availability on QA, the agreement between different methods ranged
of Centiloid values may have provided additional guidance from 0.33 to 0.66. The comparison of QA and VA showed the
in almost half (45%) of the cases. Centiloid scaling has some highest agreement between VA and a regional-based SUVR
limitations in sensitivity, based on the application global VOIs, cut-point (medial temporal regions: k=0.48, CI95% 0.32-0.64,
and these are discussed by Buckley et al. References: 1. Battle percentage of agreement 78%). Conclusion: This is the first
MR, et al. EJNMMI Res 2018. 2. Rowe C, et al. EJNMMI 2017. 3. study proposing and testing a standardized VA for flortaucipir
Navitsky M, et al. Alzheimer‘s & Dementia. 2016. 4. Klunk WE, et images. Readers performing VA obtained a substantial interrater
al. Alzheimer’s & Dementia 11, 2015. 5. Thurfjell L, et al. J Nucl agreement, higher than the agreement observed between
Med, 2014. different QA approaches. References: 1. A. J. Schwarz et al.,
Topographic staging of tau positron emission tomography
images. Alzheimers Dement 10, 221-231 (2018). 2. S. Mishra
EPS-045 et al., AV-1451 PET imaging of tau pathology in preclinical
Validation of a Visual Assessment Strategy for Alzheimer disease: Defining a summary measure. Neuroimage
18F-Flortaucipir PET 161, 171-178 (2017).
A. Dodich1, A. Rochat1, I. Mainta2, C. Noirot2, P. Andryszak3, B.
Rakotomiaramanana3, G. B. Frisoni3, V. Garibotto1,2;
1
NIMTlab, Neuroimaging and Innovative Molecular Tracers EPS-046
Laboratory, University of Geneva, Geneva, SWITZERLAND, AmyPype: an automated system to quantify AMYPAD’s
2
Nuclear Medicine and Molecular Imaging Division, Diagnostic [18F]flutemetamol and [18F]florbetaben images including
Department, Geneva University Hospitals, Geneva, SWITZERLAND, regional SUVR and Centiloid analysis
3
Memory Center and LANVIE - Laboratory of Neuroimaging C. J. Buckley1, C. Foley1, M. Battle1, E. Grecchi1, G. Farrar1, J. Gispert2,
of Aging, Department of Rehabilitation and Geriatrics, I. Lopes-Alves3, F. Barkhof3, A. A. Lammertsma3, S. Bullich4, D.
Geneva University Hospitals, Geneva, SWITZERLAND. Altomare5, G. B. Frisoni5, C. Moro5, V. Garibotto6, J. Cardoso7, M.
Modat8;
1
GE Healthcare Pharmaceutical Diagnostics, Amersham,
Aim/Introduction: The presence of pathological changes UNITED KINGDOM, 2BarcelonaBeta Brain Research Centre,
characterizing Alzheimer’s Disease can be assessed by amyloid Barcelona, SPAIN, 3Amsterdam UMC, Vrije Universiteit,
(A) and tau (T) imaging biomarkers, with important possible Amsterdam, NETHERLANDS, 4Life Molecular Imaging, Berlin,
implications in clinical practice. A key step is the reliable GERMANY, 5Laboratory of Neuroimaging of Aging (LANVIE),
assessment of the biomarker measure and threshold for University of Geneva, Geneva, SWITZERLAND, 6Division
positivity. We developed a visual assessment (VA) strategy for of Nuclear Medicine and Molecular Imaging, University
18F-flortaucipir PET and we tested its interrater agreement Hospitals of Geneva, Geneva, SWEDEN, 7Centre for Medical
as well as its consistency with quantitative (QA) assessment. Image Computing, UCL, London, UNITED KINGDOM,
Materials and Methods: 120 subjects with available 8
Dementia Research Centre, London, UNITED KINGDOM.
18F-flortaucipir PET and T1-weighted MRI images were
selected from the ADNI dataset. They were characterized by
heterogeneous clinical (55 cognitive normal, 65 cognitive Aim/Introduction: AMYPAD is a multi-centre pan European
impaired) and A status (53 A+ and 67 A-). Raters were instructed public-private partnership funded by Innovative-Medicines-
through a standard visual analysis procedure, including images Initiative aimed at understanding the added value of amyloid
synchronization and display on a continuous color map with PET imaging in the clinical workup of subjects with cognitive
the cerebellar crux set approximately at the 30% of the scale. complaints and for understanding the process of amyloid
Each reader provided as output an estimated Braak stage and deposition in the AD pathology continuum. In particular for
its level of confidence (5-level scale). Blinded visual reads were the clinical workup scenario, AmyPype was designed to allow
conducted by three raters. QA and definition of T positivity was the harmonized (including Centiloid1) quantitative assessment
based on two automated algorithms (Schwarz et al., 2018) and of [18F]flutemetamol and [18F]florbetaben amyloid PET without
literature-based global and regional cut-points for standardized the need for individual’s structural MRI images. Materials and
uptake value ratio (SUVR). Agreement between T positivity Methods: Amyloid PET images (static or dynamic) are co-
defined through VA (based on the classification performed registered with a pre-defined adaptive negative/positive PET
by the majority of readers) and QA was evaluated through template. Next, individual images are transformed into MNI152
Cohen’s kappa. Finally, we compared the global SUVR through space based on previously known transformation matrix these
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S324

templates. Next, a grey-matter parcellated cortical-volume and lateral temporal, medial and lateral parietal, frontal and
of interest (VOI) mask is applied to the images, together with occipital), and summing all individual ROI’s scores together; 2)
a Centiloid Cortical mask and whole cerebellum reference a FTP distribution pattern among one of four pre-determined
region. The application runs on a GE Advantage Workstation. distribution patterns: 1.negative scan 2.temporal binding
Centiloid GAAIN data were used to validate the process pipeline, only 3.AD-like 4.non-AD like binding patterns. The results of
as described in the methods by Klunk et al. (2015). In-house the visual interpretation were compared to global FTP SUVR,
data were used to validate the [18F]flutemetamol process and amyloid status and clinical diagnosis. Negative and positive
determine the Centiloid conversion equation (available on the predictive values of the distribution pattern based on clinical
GAAIN website). For [18F]florbetaben, data was also obtained diagnosis were calculated. Inter-rater reliability was calculated.
from the GAAIN website and used to validate the process Results: Average of the two readers’ global visual scores
Results: Amypype is able to receive PET-only amyloid scans were significantly associated with global FTP SUVR (r=0.69 for
in batch and output ascii tables of regional and composite ADNI, r=0.84 for UCSF/BACS). Mean visual scores within each
SUVR values together with Centiloid values for both [18F] diagnostic category were lower for amyloid negative subjects
flutemetamol and [18F]florbetaben PET images. Additionally, than for amyloid positive subjects. Visual scores were correlated
where a normal database was available (currently only for [18F] with diagnosis (tables 3 and 4): controls had the lowest scores,
flutemetamol), voxel wise Z-scores relative to the regional and MCIs intermediate, and AD the highest values. Patients with
voxel level normal database images are reported. Validation non-AD dementia had an average visual rating similar to
was achieved by comparing the output of AmyPype with the healthy controls. The low rate of false negative scans (clinically
Centiloids obtained through the GAAIN two step validation diagnosed AD described as having a visual FTP pattern different
approach. The difference between the Centiloid values from AD) determined a high NPV (80% and 89% for ADNI and
obtained with AmyPype compared to the standard MR-driven 97% and 98% for UCSF/BACS). PPV was 60% and 76% for ADNI
pipeline1 were substantially less than 1% on average for all and 84% and 94% for UCSF/BACS). Inter-rater agreement on
cohorts and both tracers. Conclusion: AmyPype provides a global visual scores was strong (linear weighted Kappa for
robust Centiloid amyloid quantification process platform that ADNI=.61, for UCSF/BACS=.83). Inter-rater agreement on the
allows quick and easy batch processing of PET-only images for definition of distribution pattern was also good with an overall
both [18F]flutemetamol and [18F]florbetaben. Centiloid scaling full agreement in 66% of cases (60% in ADNI and 71% in UCSF/
and the derived process reports, can complement visual reads BACS). Conclusion: Our data show that this purely visual rating
and provide additional quantitative information to better-aid scheme strongly correlates with FTP global quantification and
patient selection and management. References: 1. Klunk et. al. clinical diagnosis. Inter-rater reliability is strong. This visual
Alzheimers Dement. 2015 Jan; 11(1):1-15 method is a reliable, reproducible and promising alternative
approach to Tau measurement in clinical settings. References:
None.
EPS-047
Evaluation of a visual interpretation method for
Flortaucipir PET imaging EPS-048
I. Sonni1,2, O. H. Lesman-Segev3, S. L. Baker2, D. Korman4, G. D. A kinetics-based approach to amyloid PET semi-
Rabinovici3,2, W. J. Jagust4,2, S. M. Landau4; quantification
1
University of California, Los Angeles, CA, UNITED STATES OF S. Capitanio1, E. Peira2, M. Corosu2, S. Morbelli3, M. Bauckneht3, M.
AMERICA, 2Lawrence Berkeley National Lab, Berkeley, CA, Pardini4, D. Arnaldi4, C. Vellani5, D. D’ambrosio6, V. Garibotto7, F.
UNITED STATES OF AMERICA, 3University of California, San Assal8, B. Paghera9, G. Trifiro’5, U. Guerra10, F. Nobili4, G. Frisoni11, A.
Francisco, CA, UNITED STATES OF AMERICA, 4University of Chincarini2;
California, Berkeley, CA, UNITED STATES OF AMERICA. 1
IRCCS Ospedale Policlinico San Martino, Genova, ITALY, 2Istituto
Nazionale di Fisica Nucleare (INFN), Genova, ITALY, 3IRCCS
Ospedale Policlinico San Martino; Nuclear Medicine Unit
Aim/Introduction: We aimed to evaluate a visual interpretation (DISSAL), University of Genoa, Genova, ITALY, 4IRCCS Ospedale
method for the qualitative assessment of 18F-AV-1451 Policlinico San Martino; Dept of Neuroscience (DINOGMI),
(Flortaucipir - FTP) Tau PET scans in clinical settings. Materials University of Genoa, Genova, ITALY, 5Nuclear Medicine Unit,
and Methods: 274 subjects (137 ADNI, 137 UCSF/BACS, tables ICS Maugeri IRCCS, Pavia, ITALY, 6Medical Physics Unit, ICS
1 and 2) scanned with FTP-PET were selected. FTP-PET images Maugeri IRCCS, Pavia, ITALY, 7Nuclear Medicine and Molecular
(smoothed to 4mm, non-normalized, not co-registered to MRI Imaging Division, University Hospitals and University of Geneva,
to resemble a clinical scenario) were qualitatively interpreted Geneva, SWITZERLAND, 8Division of Neurology, Department of
independently by two readers. Readers were blinded to clinical Clinical Neurosciences, Geneva University Hospitals, Geneva,
information and to SUVR values. The rating scheme was purely SWITZERLAND, 9Nuclear Medicine Unit, ASST Spedali Civili,
visual and started with adjusting the color scale based on Brescia, ITALY, 10Nuclear Medicine, Fondazione Poliambulanza,
binding to inferior cerebellum. The rating provided 1) a global Istituto Ospedaliero, Brescia, ITALY, 11Laboratory of Neuroimaging
visual score (0-to-14 scale), obtained by assessing the binding of Aging (LANVIE), University of Geneva; Memory Clinic,
severity (0-to-2 ROI score) in 7 cortical regions (medial, inferior University Hospital of Geneva, Geneva, SWITZERLAND.
S325 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

Aim/Introduction: To date, amyloid-PET assessment consists in a der Isar, Technische Universität München, Neuro-Kopf-Zentrum,
visual binary evaluation of the scan (negative/positive) optionally Muenchen, GERMANY, 4Klinikum der Universität München, Institut
supported by semi-quantification techniques. Regional cerebral für Klinische Neuroimmunologie, Muenchen, GERMANY, 5Klinikum
blood flow (rCBF) changes between patients and intra-patient der Universität München, Klinik für Psychiatrie und Psychotherapie,
could hamper longitudinal evaluation. The aim of our work was Muenchen, GERMANY, 6Inselspital Bern, Universitätsklinik für
to develop and validate a semi-quantification method (TDr) for Nuklearmedizin, Bern, SWITZERLAND, 7Dept. of Nuclear Medicine,
amyloid-PET scans based on tracer kinetics information through University of Munich, LMU Munich, Muenchen, GERMANY.
a dual-time point acquisition and customized on the individual
patient anatomic and pathophysiological characteristics, which
does not need any template or MRI-coregistration. Materials Aim/Introduction: Corticobasal Syndrome (CBS) is a rare
and Methods: We retrospectively enrolled 143 subjects clinical condition with heterogeneous underlying diseases. The
(aged 54-87) with clinical suspicion of AD who underwent to most frequent neuropathological diagnoses of CBS patients are
18F-florbetapir PET/CT in 4 clinical italian centers. An early (E) either the 3R/4R tauopathy Alzheimer’s disease (AD) or the 4R
5 minutes PET/CT static acquisition was performed soon after tauopathies Corticobasal Degeneration (CBD) and Progressive
tracer injection as a proxy of brain perfusion, followed by a late (L) Supranuclear Palsy (PSP). Microglia, the cerebral innate immune
20 minutes static acquisition after 45 minutes. High rCBF regions cells, have been shown to be dysfunctional in AD, CBD and PSP.
were concentrated in the cortical gray matter and were used In our interdisciplinary study “Activity of Cerebral Networks,
to delineate the uptake regions of interest (ROIs). Time-delayed Amyloid and Microglia in Aging and Alzheimer’s Disease
ratio (TDr) was then calculated as the ratio between the average (ActiGliA)”, we generate multimodal prospective imaging and
intensities in the ROIs from E onto the reference ROI on L. TDr fluid biomarker data in CBS patients. Here we want to focus on
values were compared to the binary visual assessment and to 18kDa translocator protein (TSPO)-PET, which is a biomarker
two validated semi-quantification methods (cortical-cerebellar for microglial activity. Materials and Methods: Until now 30
SUVr and ELBA method, a SUVr-independent approach). TDr patients with suspected 4R tauopathy, 21 patients (66 ± 10; 15
area under the receiver operating characteristic curve (AUC) f/ 6 m) with probable CBS and 9 patients with probable PSP (67
was measured for negative versus positive scans. Results: TDr ± 7; 6 f/ 3 m), according to current diagnosis criteria underwent
showed excellent performance with respect to the binary visual 18
F-GE-180 TSPO-PET. All images (60-80 min time window)
assessment (AUC=0.99) with very good accuracy both on the were scaled by the temporal lobe and standardized uptake
whole dataset and on single center cohorts. It significantly value ratios (SUVR) were generated in cortical (central region)
correlated with both SUVr and ELBA although it related better and subcortical (putamen, globus pallidus, thalamus, nucleus
with ELBA as evidenced by the correlation coefficients on the subthalamicus, substantia nigra, nucleus dentatus) brain
negative and positive classes separately. Conclusion: TDr is regions known to be affected in 4R tauopathies. SUVR values
a highly accurate semi-quantification method that requires were compared between CBS and PSP and against ten healthy
minimal image processing, it is independent on predefined controls (HC). 18F-flutemetamol amyloid-PET served to confirm
ROI, does not require MR coregistration and implies a negligible a negative amyloid status in all patients. Results: We find
added patient discomfort. In clinical setting, the use of TDr significantly increased TSPO-PET SUVR values in the comparison
could lead to a very robust index of amyloid load particularly of CBS versus HC in the central region, putamen, thalamus,
suitable for measuring longitudinal changes in monitoring nucleus subthalamicus, substantia nigra and nucleus dentatus
disease progression or treatment response. References: (all p < 0.05). Significantly increased TSPO-PET SUVR values
Schmidt et al. The influence of biological and technical factors in PSP versus HC were observed in the central region, globus
on quantitative analysis of amyloid PET: Points to consider and pallidus and thalamus (all p < 0.05). In the direct comparison
recommendations for controlling variability in longitudinal of clinical CBS and PSP patients, there were higher TSPO-PET
data. Alzheimers Dement 2015;11:1050-68. Chincarini et al. SUVR values in the central region (+6% p < 0.05) but there were
Standardized Uptake Value Ratio-Independent Evaluation of no significant differences in subcortical areas. Conclusion: CBS
Brain Amyloidosis. J Alzheimers Dis 2016;54:1437-57.Cecchin and PSP patients show an elevated 18F-GE-180 signal in disease
et al. A new integrated dual time-point amyloid PET/MRI data associated brain regions, indicating a potential of TSPO-PET to
analysis method. Eur J Nucl Med Mol Imaging 2017;44:2060-72. serve as biomarker for microglial activation in 4R tauopathies.
Pronounced cortical TSPO activation in the central region of CBS
patients fits to the known predilection site of this phenotype.
EPS-049 Ongoing longitudinal measures of TSPO activation and clinical
Translocator Protein in 4R Tauopathies - Experience from severity in this prospective cohort will elucidate if microglial
the ActiGliA Study activation has a predictive potential on the clinical course in 4R
J. Sauerbeck1, L. Beyer1, S. Schönecker2, C. Palleis2, G. Höglinger3, E. tauopathies. References: None.
Schuh4, R. Boris5, G. Rohrer2, S. Sonnenfeld2, K. Bötzel2, A. Danek2, A.
Rominger6, J. Levin2, B. Matthias7;
1
Dept. of Nuclear Medicine, University of Munich, Muenchen,
GERMANY, 2Klinikum der Universität München, Klinik und
Poliklinik für Neurologie, Muenchen, GERMANY, 3Klinikum Rechts
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S326

EPS-050 511
[11C]PK11195 PET Quantification Analysis in Multiple
Sclerosis and Healthy Subjects: Preliminary Results
e-Poster Presentation Session 4 - Paediatrics &
P. N. Schuck1, A. S. Araújo1, C. M. Dartora1, L. D. Narciso2, M. A.
Other Clinical Studies: Joint Paediatrics & Other
Andrade1, C. S. Matushita1,3, M. Koole4, A. M. Marques da Silva1,3, J.
Clinical Studies
Becker1,3;
1
PUCRS, Porto Alegre, BRAZIL, 2Western University, Sunday, October 13, 2019, 16:30 - 18:00 Room 133/134
London, ON, CANADA, 3BraIns, Porto Alegre,
BRAZIL, 4KU Leuven, Leuven, BELGIUM.

EPS-051
Aim/Introduction: To investigate [11C]PK11195 PET Use of Iterative Reconstruction for Dose Optimisation of
quantification in brain white matter (WM) and gray matter (GM) Paediatric 99mTc MDP Bone SPECT
regions in relapsing-remitting multiple sclerosis (RRMS) subjects F. Fahey1,2, J. Ouyang3,2, X. Cao1, Z. Levin3, B. Sexton-Stallone1,
and healthy controls (HC). Materials and Methods: Eight HC A. Falone1, K. Zukotynski4, N. Kwatra1,2, R. Lim3,2, Z. Bar-Sever5, S.
(30±9 years, 75±10 kg) and eighteen RRMS subjects (29±9 years, Treves6, G. El Fakhri3,2;
67±15 kg) underwent [11C]PK11195 PET/CT and MRI. Dynamic 1
Boston Children’s Hospital, Boston, MA, UNITED STATES OF
60min post-injection list-mode PET/CT were acquired in a GE AMERICA, 2Harvard Medical School, Boston, MA, UNITED STATES
Discovery600, with (341±64) MBq. I Attenuation and motion OF AMERICA, 3Gordon Center of Medical Imaging, Massachusetts
correction images were reconstructed using VUE PointHD General Hospital, Boston, MA, UNITED STATES OF AMERICA,
algorithm, 32 subsets, 2 iterations, and smoothing filter 4.0 mm 4
McMaster University, Hamilton, ON, CANADA, 5Schneiders
FWHM. T1-weighted MR from each subject was co-registered Children’s Medical Center of Israel, Petah Tikva, ISRAEL, 6Brigham
to the first 10 min static PET. Thalamus, caudate, putamen, and Women’s Hospital, Boston, MA, UNITED STATES OF AMERICA.
pallidum, cerebellar cortex, cerebellar WM, hippocampus,
brainstem, apparently normal WM, whole GM and juxtacortical
and periventricular regions (JPV) binding were calculated Aim/Introduction: An observer study showed paediatric bone
using image-derived input function (IDIF) extracted from MR SPECTs using half the 99mTc MDP activity reconstructed using
segmented carotid in each subject. Two tissue compartment ordered subset expectation maximization with 3D resolution
model (2TCM) and Logan graphical method (LGM) were used recovery (OSEM3D) yielded similar/better image quality to
to calculate the total distribution volume (VT) with IDIF from filtered back-projection (FBP) with full activity [1]. That study
t*=20min and t*=40min. Group normality was tested using relied on subjective image-quality evaluation. This investigation
Shapiro-Wilk, and VT comparison between RRMS and healthy compares diagnostic performance for paediatric bone SPECTs
groups was evaluated with one-way ANOVA (p<0.05). Results: using localization receiver operating characteristic (LROC)
Using 2TCM, only JPV VT (RRMS=0.72±0.20; HC=0.92±0.28; analysis. Materials and Methods: Sixty-six normal bone
p=0.047) was significantly different between groups. LGM SPECTs (13 boys, 53 girls, 10-17 years, mean 14.9 years) using
(t*=20min) did not shown VT differences between groups. LGM administered activities consistent with the North American
(t*=40min) showed VT statistical differences between groups guidelines [2] were downloaded from the Boston Children’s
in caudate, GM, cerebellar GM, thalamus, putamen, brainstem, Hospital (BCH) database. These were acquired over 360o; thus,
and JPV (RRMS=0.70±0.19; HC=0.84±0.09; p=0.049). JPV VT was reconstructing data from one or both detectors simulated 2
different between RRMS and HC, both with 2TCM and LGM count/activity levels (half vs full). “Features” simulating focal stress
t*=40min. Although there was substantial heterogeneity in [11C] reactions/fractures were electronically inserted into posterior
PK11195 binding in RRMS subjects, caudate VT seems correlated elements of the lumbar spine (L3 - L5) and reconstructed twice
with the disease, considering lesions usually appear around (OSEM3D and FBP). A teaching (N=32) and study set (N=400)
this region [1]. Decreased GM and cerebellar GM suggests were generated. Five experienced nuclear medicine physician
demyelination in RRMS, in agreement with other studies [2,3]. observers were informed that a feature was present in L3, L4 or L5
Conclusion: [11C]PK11195 in RRMS cortical and JPV regions on the left or right in half of the cases with no feature in the other
seem related to the gradual vanishing of myelin fibres towards half. For each case, observers identified the most likely feature
the chronic degenerative phase, providing potential indicators location and ranked the likelihood of its presence on a 6-point
of disease progression. Further studies are required to determine scale (definitely, probably, possibly negative/possibly, probably,
the association between [11C]PK11195 binding and MS phase. definitely positive). Observers first reviewed the training set
References: [1] Thompson et al. The Lancet Neurology, 2018.[2] where they were informed if each case were negative or positive
Pitt et al. Arch Neurol 2010.[3] Debruyne et al. EJN, 2003. and its location for positive cases. The observers then evaluated
the 400 study cases. Using LROC analyses, the area under the
curve (AUC) and standard deviation were determined for the
pooled observer results. Differences were compared using one-
tailed Student’s t-test for dependent means. Results: OSEM3D
yielded slightly higher performance than FBP (AUC = 0.783 ±
S327 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

0.020 vs 0.749 ± 0.021). OSEM3D led to higher sensitivity but and 17% (muscle). Assuming that image noise levels below 20%
yielded contrast enhancement of small features leading to lower are acceptable for clinical work-up, VOI analysis of the liver and
specificity. For OSEM3D and FBP, the full-count performance mediastinum, indicated this level to be achieved at 50% counts,
was significantly higher than with half counts (OSEM3D: 0.783 or more when using OSEM. At this level of counts, noise levels
± 0.020 vs 0.678 ± 0.024; FBP: 0.749 ± 0.021 vs 0.671 ± 0.025, p in the lung and thigh muscle was slightly higher 22% and 24%
= 0.0021). OSEM3D did not perform considerably better than respectively. For PSF these noise levels could be reduced to 18%
FBP with half counts (0.678 ± 0.024 vs 0.671 ± 0.025, p = 0.22). (lung) and 21% (muscle). Conclusion: Ongoing evaluations of
Conclusion: Iterative reconstruction yielded slightly higher WB-[18F]FDG-PET/CT images of paediatric patients indicate a
performance than FBP (higher sensitivity/lower specificity). 50% dose reduction potential when using a 20% acceptable
Reducing dose by half yielded significantly lower performance. threshold on noise levels and iterative reconstruction with
References: 1. Stansfield EC, et al. Radiology. 2010;257:793-801. PSF. Adding TOF information is likely to promote further dose
2. Treves ST, et al. J Nucl Med. 2016;57:15N-18N. reduction. This quantitative analysis of reference regions in pilot
data will be complemented by qualitative grading of image
quality by clinical experts. Ethics approval 2019/ETH00138.
EPS-052 The financial support of the Austrian FWF Project I3451-N32 is
Reducing paediatic patient radiation exposure during gratefully acknowledged. References: None.
[18F]-PET/CT: The effect of reduced tracer dose and
reconstruction methods on image quality
H. Kertesz1, T. Beyer1, T. Traub-Weidinger2, J. Cal-Gonzalez1, M. EPS-053
Hacker2, T. Kitsos3, K. London3, P. L Kench4; Impact of 18F-FDG PET/CT in Therapy Management of
1
QIMP Team, Center for Medical Physics and Biomedical Pediatric Patients with Bone and Soft Tissue Sarcomas
Engineering, Vienna, AUSTRIA, 2Division of Nuclear Medicine, E. Riera1, S. Ortiz1, P. Bassa1, M. Soler1, P. Pérez2, M. Garraus2, E.
Department of Biomedical Imaging and Image-guided Inarejos2, I. Barber2, J. García1;
Therapy, Medical University of Vienna, Vienna, AUSTRIA, 1
CETIR-ASCIRES, Barcelona, SPAIN, 2Hospital Sant Joan
3
Nuclear Medicine Department, The Children’s Hospital de Déu, Esplugues de LLobregat, Barcelona, SPAIN.
at Westmead, Sydney, AUSTRALIA, 4Discipline of Medical
Radiation Sciences and Brain and Mind Centre, Faculty of
Health Sciences, The University of Sydney, Sydney, AUSTRALIA. Aim/Introduction: We have evaluated the impact of
18F-FDG PET/CT on the early therapy follow-up of a group of
pediatric patients with primary bone tumors and soft-tissue
Aim/Introduction: To assess image quality, by quantification of sarcomas. Materials and Methods: From 2007 through
noise, at reduced count levels for whole-body [18F]FDG-PET/CT 2018, 12 children with Bone Sarcomas and 11 children with
studies of paediatric oncology patients in relation to different Soft Tissue Sarcomas were evaluated by 18F-FDG PET/CT for
image reconstruction algorithms. Materials and Methods: This early post-therapy study and follow-up treatment response.
study is ongoing. To date, nine paediatric oncology patients Primary Bone Tumors: 1 Osteosarcoma (7 y-o) and
were included (4F/5M, (13±4)-y/o, 16.2≤BMI≤24.0). Subjects 11 Ewing Sarcoma (x̄: 8.5 y-o; range: 2-12 y-o).
were injected with a mean activity concentration of (3.8±08) Soft Tissue Sarcomas: 4 embrionary Rhabdomyosarcoma (x̄: 6.7
MBq/kg, and underwent routine [18F]FDG-PET/CT whole-body y-o; range: 2-13 y-o) and 5 Alveolar Rhabdomyosarcoma (x̄: 10
examinations on a Siemens Biograph mCT system with TOF y-o; range: 2-14 y-o) and 2 Synovial Sarcoma (x̄: 9.5 y-o). A total
capability (500ps). Emission data was collected in list mode (LM) of 82 PET/CT studies, with normal blood glucose levels, were
format and preprocessed to simulate a reduction of the injected acquired with a PET/CT Philips Gemini-GXL 1 hour +/- 10 min.
[18F]FDG activity by randomly removing counts from the after intravenous injection of 4.6 mBq/Kg of 18F-FDG. mA and
original LM (100%) to achieve activity levels of 75%, 50%, 35%, KV CT acquisition parameters were set to pediatric procedure. All
20% and 10%. Following attenuation and scatter correction, PET relevant findings and SUVmax were assessed and correlated
all emission data was reconstructed using the vendor e7-tools with CT and MRI findings and histology results whenever
with OSEM and OSEM plus resolution recovery (PSF), and PSF available. Results: Primary Bone Tumors: - Two out of 12 patients
plus time-of-flight (TOF) information. A 5mm FWHM Gaussian with negative PET in the early post-therapy study remained
post-filter was applied during all reconstructions. Four spherical negative in the follow-up PET studies. None of them died over
volumes-of-interests (VOIs) were defined in the right-lung, liver, the time of analysis. - Two out of 12 patients with negative PET
left-thigh muscle and in the mediastinum. We report, noise in the early post-therapy study became positive in the follow-up
and the signal-to-noise ratio (SNR) for each VOI and image PET studies. One patient died over the time of analysis. - Eight
reconstruction. Results: When using OSEM, the mean noise out of 12 patients with positive PET in the early post-therapy
levels were on the order of (17-44)% in the lung, (10-28)% liver, became positive in the follow-up PET studies. Four patients
(14-31)% mediastinum and (17-51)% thigh muscle for 100% died over the time of analysis. Soft tissue Sarcomas: - Nine out
counts. For PSF, the noise levels were reduced by 18% (lung), of 11 patients with negative PET in the early post-therapy study
16% (liver), 14% (mediastinum) and 13% (muscle), while the SNR remained negative in the follow-up PET studies. None of them
was increased by 24% (lung), 21% (liver), 17% (mediastinum.) died over the time of analysis. - Two out of 11 patients with
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S328

positive PET in the early post-therapy reduced SUVmax uptake EPS-055


on primitive lesions and no new lesions appeared in the follow- Risk stratification using 18 FDG PET/CT in high
up PET studies. None of them died over the time of analysis. risk neuroblastomas :Is it comparable with
Conclusion: 18F-FDG PET/CT is a useful imaging procedure for 131
I-metaiodobenzylguanidine (MIBG)-??
post-therapy follow-up of primary bone tumors and soft tissue C. V. Bongulwar1, S. Shah2, N. Purandare2, A. Agrawal2, V.
sarcomas in pediatric patients. Moreover, the early post-therapy Rangarajan2;
study showed prognostic value. References: None. 1
National Cancer Institute, Nagpur, INDIA, 2Tata
Memorial Hospital, Mumbai, INDIA.

EPS-054
Normal [11C]-metionine PET uptake in the brain in Aim/Introduction: Radio iodinated metaiodobenzylguanidine
children before and after treatment (mIBG) is an established imaging modality in neuroblastoma.
D. Susin, T. Skvortsova; Semiquantiative scoring -SIOPEN [International Society of
N.P. Bechtereva Institute of human brain, Saint- Pediatric Oncology Europe Neuroblastoma Group] and Modified
Petersburg, RUSSIAN FEDERATION. Curie using radiolabelled MIBG are used for prognostication in
high risk neuroblastomas. The present study aims to use 18F
-fluorodeoxyglucose (FDG) for semiquantitative scoring and
Aim/Introduction: Tumors of the central nervous system are compares it with mIBG scores thereby validating it for risk
the most common form of solid tumors in children age 0-14 stratification. Materials and Methods: Data of 90 patients
years. Subtentorial location and the midline of the brain are were retrospectively analyzed diagnosed to have stage IV high
the most frequent localization of embryonic and glial tumors risk neuroblastoma. MIBG scans were assessed according to
in children. Normally increased [11C]-methionine uptake in the SIOPEN and the modified Curie scoring method. Similarly
some brain structures makes it difficult to distinguish healthy 18 F FDG PET/CT scans were also scored using these semi
brain tissue from the tumor process and to find an appropriate quantitative systems. The paired scans were compared at initial
reference region to determine the metabolic activity of the staging and end of induction therapy. A Curie score of </=2 and
lesion. The purpose of our study was determine distribution > 2 and a SIOPEN score </=4 and >4 (best cutoff ) described in
of [11C]-methionine (Met) in the structures of posterior cranial previous studies was used to classify these scans into low and
fossa on PET/CT imaging of pediatric brain in control and after high risk and subsequently correlated with the clinical course
treatment. Materials and Methods: The children between of the disease. Results: At initial staging there was a statistically
2 and 15 years old were divided in two group. In the first significant difference between the Curie-FDG scores of (10.94 ±
group (n=30) we included children examined with suspicion 10.0)as compared to mIBG score of (7.99 ± 9.00)with an increase
on brain tumor that has not been confirmed. Second group of 2.94 with p=0.001.Also for SIOPEN -FDG scores of (20.00 ±
consisted of 17 children after combined treatment of tumors 26.00) against mIBG (11.72 ± 20.00) with a difference of 8.27 and
in the posterior cranial fossa without any residual tumor tissue. p=0.12.At end of induction therapy there was no statistically
A PET studies were performed on a GE Discovery 710 PET/CT significant difference (p >0.01)between the Curie FDG and MIBG
scanner according to the standard protocol. Different ROIs scores. Using the standard cut off values for Curie and SIOPEN
were drawn on PET-Met images including pons, cerebellum, scores 18 patients show discordance out of which 6 patients
thalamus and frontal cortex. A circle ROI of 10 mm in diameter (33%) showed disease progression or death. Conclusion:
was placed in the site of maximum Met uptake in the structure Modified CURIE score and SIOPEN score using 18F FDG shows an
of interest. Different uptake indexes (UI) were calculated: pons incremental value over MIBG score and can be correlated with the
to cerebellum ratio (PCR), pons to thalamus ratio (PThR), pons clinical outcome of the disease. The Modified Curie and SIOPEN
to brain cortex ratio (PBR). The differences between control UI score can be validated using 18 F FDG PET/CT establishing their
measurements and post-treatment UI values were tested using role in risk stratification . References: Borris decoralis et al Boris
M-W test. Results: In the control group PCR, PThR and PBR were Decarolis, Christina Schneider, Barbara Hero, Thorsten Simon,
1.11 ± 0.16, 1.21 ± 0.17, 1.38 ± 0.17 (mean ± SD), respectively. Ruth Volland, Frederick Roels,Markus Dietlein, Frank Berthold,
After the combined treatment of tumors in the posterior cranial and Matthias Schmidt Iodine-123 Metaiodobenzylguanidine
fossa PCR, PThR and PBR were 1.19 ± 0.13, 1.27 ± 0.17, 1.58 ± 0.21 Scintigraphy Scoring allows Prediction of Outcome in
(mean ± SD), respectively. Significant differences was found in Patients With Stage 4 Neuroblastoma:Results of the Cologne
PBR between two groups. There were no differences was fond Interscore Comparison Study2013 -JCO Matthay KK, Edeline
in PThR and PCR. Conclusion: The results should be taken into V, Lombroso J, et al: Correlation of early metastatic response
account in the diagnosis of childhood tumors in the posterior by123Imetaiodobenzylguanidinescintigraphy with overall
cranial fossa and in monitoring of their treatment. References: response and event-free survivalin stage IV neuroblastoma. J
None. Clin Oncol 21:2486-2491, 2003.
S329 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

EPS-056 EPS-057
Role of Large bowel transit scintigraphy in children with Hepatobiliary scintigraphy for pediatric biliary atresia: a
chronic constipation single-institution experience
K. Tigapuram, K. Seetharaman, A. Bhattacharya, S. Lal, B. R. Mittal, W. Wong, K. Chu, B. Kung, T. Au Yong;
R. Bolia; Nuclear Medicine and Clinical PET Centre, Queen
PGIMER, Chandigarh, INDIA. Elizabeth Hospital, Hong Kong, HONG KONG.

Aim/Introduction: To evaluate usefulness of large bowel Aim/Introduction: The purpose of this study was to evaluate
transit scintigraphy in management of children with chronic the diagnostic accuracy of hepatobiliary scintigraphy for biliary
constipation Materials and Methods: We retrospectively atresia. Materials and Methods: A retrospective analysis of 186
analysed data of 53 patients (36 M, 17 F) aged 2-15 (median infants (122 males and 64 females, median age of 52 days) at
7) years who presented with complaints of constipation, over Queen Elizabeth Hospital between January 2008 and February
a period of 3 years (January 2016-January 2019). The mean 2019 was performed. Demographic details, laboratory data,
duration of symptoms was 2 years and 9 months (range 1 results of ultrasonography are also evaluated. Results: Among
month - 9 years). Twenty-four of the 53 patients also had the 186 infants, 18 patients (9.7%) were diagnosed to have
pallor on clinical examination and 24 had history of retentive biliary atresia. Sensitivity, specificity, positive predictive value
measures being taken. Whole bowel transit scintigraphy was and negative predictive value of hepatobiliary scan were found
performed after oral administration of 5 mCi of Tc-99m sulphur to be 100% , 95%, 69%, and 100% respectively. For full-term
colloid (SC) labelled solid meal. Sequential static images were infant subgroup, positive predictive value is even higher (83%).
acquired hourly from 1 to 4 hours and delayed images at 6hr, There is greater proportion of false-positive cases in preterm
8hr, 24hr, 28hr and 36hrs (if required), in simultaneous anterior infants than full-term infants, and repeated hepatobiliary
and posterior projections using a dual-head gamma camera. scintigraphy was found to be able to pick up 38% of false
Gastric emptying time (GET) was also assessed in 26 patients. positive cases. Conclusion: This study shows that hepatobiliary
The scan findings were interpreted visually, based on intestinal scintigraphy is highly sensitive and specific, particularly among
transit of activity. Tracer transit to the sigmoid colon / rectum by full-term infants. Low positive predictive value among preterm
24 hours was regarded as normal, while persistent retention of infants can be improved by repeating follow-up scintigraphy.
activity upto the ascending / transverse colon till 28-36 hours References: 1. Kwatra N et al. (2013) Phenobarbital-enhanced
was interpreted as delayed colonic transit. All patients were hepatobiliary scintigraphy in the diagnosis of biliary atresia:
started on standard medical treatment after the scan. Clinical two decades of experience at a tertiary center. Pediatr Radiol.
response to treatment was assessed in 37 patients till April 43:1365-1375. 2. Zeissman HA (2014) Hepatobiliary scintigraphy
2019. Results: Of the 53 patients, 24 patients had a delayed in 2014. JNM. 55:1-9.
large bowel transit time and one had rapid transit time. Of the
26 patients who had also undergone GET evaluation, 1 patient
had delayed gastric emptying with normal whole bowel transit EPS-058
time and one had rapid GET. On follow-up, the patients were Age & puberty are major determinants of response
divided into two groups, one in which symptoms persisted to radioiodine in children and adolescents with
and the other in which constipation was relieved or controlled differentiated thyroid cancer
with medication. In patients with persisting symptoms (n=18), S. S. Singh, A. Sood, A. Bhattacharya, B. R. Mittal, G. Kumar, A. S.
delayed large bowel transit was seen in 14 and normal transit Shekhawat;
in 4. In the group in which symptoms were either relieved or Post graduate institute of medical education and
controlled with medication (n=19), delayed large bowel transit research (PGIMER), Chandigarh, INDIA.
was seen in 1 and normal transit in 18. On applying Fisher exact
test, the differences in large bowel transit time results were
significantly different between the two groups (p=0.0001). Aim/Introduction: Age and pubertal status have been
Conclusion: Large bowel transit scintigraphy is a useful non- speculated to affect the disease course and response to
invasive investigation to evaluate children with constipation. radioiodine therapy in children with differentiated thyroid cancer
Patients with normal large bowel transit times are more likely (DTC). Factors influencing post-operative risk stratification and
to respond to standard medical treatment than patients with applicability of response to initial treatment (RTT) classification
delayed transit times. References: None. have barely been explored in children. We aimed to assess
the effect of age and number of surgically-excised metastatic
lymph nodes on recurrence risk stratification and RTT (at 1.5
years follow-up) in children and adolescents. Materials and
Methods: Clinical, surgical & radioiodine treatment and follow-
up (minimum 1.5 years) data of 47 DTC patients (between
years 2010-2018), ≤ 20 years of age was retrospectively
analyzed. Mean age at symptom presentation was 15±3.8
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S330

years (range 5.5-20) and median follow-up duration was 3.6 months (37.8 ± 8.3), in some cases thyrotoxicosis recurred during
years (range 1.5 -8.5 years). Patients were stratified into three ATD reduction. Calculation of 131I activity was based on 131I kinetic
age-groups, namely, pre-pubertal (≤10 years; n=7), pubertal investigation. Prescribed 131I activities, specific 131I activity and
(11-15years,n=12) and post-pubertal (16-20years, n=28). All absorbed doses rates at maximum 131I uptake varied from 534
patients underwent total/near-total thyroidectomy; 46 patients to 1396MBq (889 ± 58MBq), 4.1 to 27.0MBq/ml (14.4 ± 1.4MBq/
received radioiodine therapy. More than 5 surgically-resected ml), and 0.44 to 2.9Gy/h (1.6 ± 0.2Gy/h). TSH, fT3, fT4 levels were
metastatic lymph nodes was used as cut-off to determine checked every month after the treatment. After 6 months were
minimal and extensive nodal disease (in central and/or lateral assessed; TSH, fT4, fT3, TSH receptor Ab ,thyroid ultrasound.
nodal stations) while applying postoperative pediatric ATA Results: The first week after radioiodine therapy (RIT) 11 (20%)
recurrence risk stratification. RTT reclassification, (ATA guidelines children complained of moderate pain when swallowing, which
for adult DTC 2015) was used to assess response to therapy at lasted 7-10 days. Hypothyroidism, euhyroidism, thyrotoxicosis
1.5 years under which patients with excellent & indeterminate developed within 6 months after the treatment in 46 (82.1%), 1
responses deemed as responders and biochemical & structurally (1.8%) and 9 (16.1%) patients, respectively. Four children received
incomplete responses as having persistent disease. Results: the second RIT: hypothyroidism developed in 3 cases, in one
Overall, resolution of radioiodine avid disease was significantly case it was euthyroidism. Fourteen (78%) children with GO signs
more in post-pubertal age group (p<0.00001) than pubertal had no worsening, 3 (16.7%) children showed a progression of
(p=0.004) and pre-pubertal age groups. There was a significantly exophthalmos with a subsequent improvement, only 1 (5.6%)
larger percentage of responders among post-pubertal patients child showed significant deterioration. The thyroid volume
than in pubertal age-group (60% vs 42%, p= 0.04). None of the decrease ranged from 12.2 to 94.3% (average 70.0 ± 4.7%). Thus,
pre-pubertal patients were rendered radioiodine negative at the predictors of hypothyroidism development are the thyroid
the 1.5-year follow-up. At the end of median follow-up of 3.5 volume (P <0.001); TRAb (P = 0.009); specific 131I activity (MBq/g),
years, 23/47 patients (49%) were deemed as responders. Using (P = 0.009); thyrotoxicosis recurrence during ATD reduction
>5 metastatic lymph nodes chosen as cut-off for recurrence (P = 0.017). Age, gender, GO, prescribed activity of 131I did not
risk estimation, 45% (n=19), 43% (n=18) and 14% (n=5) patients significantly affect the treatment outcome. Conclusion: RIT is
were categorized under high, intermediate and low risk groups an effective and safe method of GD management in children
of recurrence, respectively. At the end of median follow-up of and adolescents. The main predictors of RIT effectiveness in
3.5 years, all patients (100%) in low risk group were rendered children and adolescents with GD are the thyroid volume,
as responders whereas responders in intermediate and high- and specific131I activity. Further clinical investigation and
risk groups were 67% and 26%, respectively. Conclusion: Age advancement of individual dosimetry-based methodology
and pubertal status are major determinants of response to are required to improve treatment outcome and safety of RIT.
initial therapy in children & adolescents with DTC. Incorporation References: None.
of number of metastatic lymph nodes into recurrence risk
classification systems help in predicting response to radioiodine
in this age-group. References: None. EPS-060
Will pulmonary embolism diagnosis still be made with
ventilation/perfusion imaging?
EPS-059 P. Bonnefoy1, N. Prevot1, G. Mehdipoor2, A. Sanchez1, B. Bikdeli3, J.
Predictors Of Radioiodine Therapy Effectiveness In Lima4, L. Font5, A. Gil-Díaz6, P. Llamas7, J. Aibar8, L. Bertoletti9, M.
Children And Adolescents With Graves’ Disease Monreal10, RIETE investigators;
P. O. Rumyantsev, D. Dzeytova, A. Trukhin, M. Sheremeta, V. 1
CHU Saint-Etienne, Saint-Etienne, FRANCE, 2Cardiovascular
Yasuchenya, K. Slaschuck, M. Degtyarev, S. Serzhenko, Y. Sirota, V. Research Fondation, New York, NY, UNITED STATES OF AMERICA,
Nikitaev; 3
Division of Cardiology, Department of Medicine, New York-
Endocrinology Research Center, Moscow, RUSSIAN FEDERATION. Presbyterian Hospital, Columbia University Medical Center/ New
York-Presbyterian Hospital, New York, NY, UNITED STATES OF
AMERICA, 4Department of Pneumonology, Hospital Universitario
Aim/Introduction: Graves’ disease (GD) - common cause of de Valme, Sevilla, SPAIN, 5Department of Haematology,
hyperthyroidism in different age groups, including children and Hospital de Tortosa Verge de la Cinta, Tarragona, SPAIN,
adolescents. Treatment with 131I requires individual dosimetry- 6
Department of Internal Medicine, Hospital Universitario de
based justification of therapeutic activities to improve effective Gran Canaria Dr. Negrín, Las Palmas, SPAIN, 7Department of
outcome and acceptable safety. Materials and Methods: The Haematology, Hospital Universitario Fundación Jiménez Díaz,
article describes 56 children and adolescents (f - 50, m - 6) aged Madrid, SPAIN, 8Department of Internal Medicine, Hospital
from 8 to 17 years (14.2 ± 0.7 years) with GD. Follow-up ranged Clínic, Barcelona, SPAIN, 9Service de Médecine Vasculaire et
6 - 36 months (18.8 ± 2.8). Thyroid volume varied from 7.1 to Thérapeutique, CHU Saint-Etienne, Saint-Etienne, FRANCE,
94.5ml (34.7 ± 5.3ml), 99mTc-pertechnetate uptake met 1.8 to 10
Universitari Germans Trias i Pujol, Badalona, Barcelona, SPAIN.
41.2% range (15.1 ± 3.0%), 131I maximum uptake was observed
between 10 and 60% (42.5 ± 2.7%). The severity of Graves’
orbitopathy (GO) was assessed. ATD medication ranged 3 - 144
S331 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

Aim/Introduction: Ventilation/perfusion (V/Q) lung scan was and PISAPED criteria for LPS.We also reviewed the history of left
the first noninvasive imaging test validated to replace invasive heart disease, pulmonary disease, previous thromboembolisms,
pulmonary angiography in the diagnosis of acute pulmonary scleroderma and right - left SHUNT as possible cause of PH.
embolism (PE). Although there is no precise numerical data The frequency of PE is calculated, and it is related to the basic
about quantitative evolution, it appears as a second line test pathology of the patients and to the background of previous PE.
after computed tomography pulmonary angiography (CTPA). Results: 36 lung perfusion scintigraphy and 15 V/Q scintigraphy
We aim to report contemporary data about the relative of 50 patients, aged between 37 and 87 years, 25 female and
utilization and the patient characteristics associated with use 25 male, were selected. 30/50 of the patients (60%) had lung
of V/Q scanning. Materials and Methods: From the data of disease (chronic obstructive pulmonary disease, obstructive
RIETE (Registro Informatizado Enfermedad ThromboEmbolica) sleep apnea and interstitial lung disease), 20/50 (40%) had left
registry, including patients diagnosed with acute symptomatic heart disease (cardiomyopathy and valvulopathies) and 12/50
PE, we evaluate the number of patients per year diagnosed with (24%) had history of PE. Seven patients (12%), had diagnosis
V/Q or CTPA from 2007 to 2017. Characteristics of these patients of PE in the scintigraphy. Of these, 3/7 (43%) had history of
were also studied. Results: Over the entire 11-year period, 26,540 lung disease and 1/7 (14%) of left heart disease. We highlight
patients with acute PE were included. CTPA was performed in that 6/7 patients (85%) had history of PE, of which 50% (3/6)
87.7% of patients compared to 7.8% for V/Q scan. The number of had associated lung and/or heart disease simultaneously. On
PEs diagnosed by V/Q scan decrease from 288 in 2007 to 107 in the other hand, among the 12 patients with previous history
2017 (compared to 1,635 and 1,760 respectively for CTPA), a V/Q of PE, 6 (50%) had scintigraphic signs of residual pulmonary
scan reduction about 62,8% (p<0.001). In multivariate analysis, embolism, while among the 38 patients without previous PE,
patients diagnosed with V/Q scan were older (72.7 vs. 66.7 years, only 1 patient had signs of embolism on the scan (2.6%). Thus,
p <0.001) and more likely to present severe renal insufficiency the risk of probable CTEPH is 19 times higher among patients
(odds ratio [OR]: 10.6; 95% confidence interval [CI]: 7.49-15.0), with documented prior PE. One patient with right-left SHUNT
chronic lung disease (OR: 1.50; 95%CI: 1.07-2.11), diabetes (OR: and 4 patients with scleroderma, showed a normal scintigraphy
2.04; 95%CI: 1.50-2.77) or chronic heart failure (OR: 1.87; 95%CI: Conclusion: 1. Lung scintigraphy is capable to identify CTEPH,
1.25-2.80) than patients diagnosed with CTPA. Conclusion: The in patients with history of documented previous PE, even in a
rate of V/Q scan in diagnosed PE is relatively low but stabilized population with high prevalence of lung and cardiac disease,
in recent years. Patients diagnosed with V/Q scanning are older, therefore, allowing an adequate treatment for those patients
and more frequently have renal insufficiency, diabetes, chronic with CTEPH. 2. In those patients without previous PE, lung
lung disease or chronic heart failure than those diagnosed scintigraphy shows less benefit. References: None.
by CTPA. Pulmonary embolism diagnosis still be made with
ventilation/perfusion imaging, which appears as an essential
tool in some frail patients. References: None. EPS-062
Differences in Pulmonary Ventilation / Perfusion
Scintigrahpic in Patients with Chronic Thromboembolic
EPS-061 Disease with or without Pulmonary Hypertension
Findings in Lung Perfusion and Ventilation-Perfusion J. C. Cañadas Salazar, F. Gomez-Caminero Lopez, S. Cadenas
Scintigraphy in patients with suspicion of Chronic Menéndez, P. Álvarez Vega, P. Garcia-Talavera San Miguel, A. C.
Thromboembolic Pulmonary Hypertension Peñaherrera Cepeda, M. Martin Lopez, J. Villanueva Curto, C. Riola
G. Guzmán, M. Calderón, L. Nieto, M. Falgás, P. Navarro, M. Parada, M. Tamayo Alonso;
Sangrós, S. Álvarez, L. De la Cueva, D. Abós; Sacyl, Salamanca, SPAIN.
Hospital Universitario Miguel Servet, Zaragoza, SPAIN.

Aim/Introduction: To compare the scintigraphic findings


Aim/Introduction: To study the findings in 99mTc- and the possible differences observed after ventilation /
macroaggregated albumin lung perfusion scintigraphy (LPS) and perfusion scintigraphy (V/Q) in patients diagnosed with
99mTc- pertechnetate lung ventilation - perfusion scintigraphy chronic pulmonary thromboembolism (CTEP) with confirmed
(V/Q), in patients with clinical and echocardiographic suspicion pulmonary hypertension (PH) and patients with CTEP without
for pulmonary hypertension (PH), and in those who are not HP. Materials and Methods: We reviewed 387 lung ventilation
confirmed left heart or lung disease as single causes of PH, by and perfusion scans of patients with suspected chronic PE from
the treating doctor. Materials and Methods: We collected July 2015 to April 2019, of which 33 cases of CTEP were confirmed.
all consecutives lung scintigraphies of patients with suspect 470MBq 99mTc-DTPA was administered as an aerosol for the
of pulmonary embolism (PE) chronic/residual, as a cause of ventilation study and 185MBq of 99mTc-MAA was administered
PH, attended between January of 2017 and April of 2019.We intravenously for the perfusion study. Planar images were
performed a review of the scintigraphic findings, observing acquired in anterior, posterior and oblique posterior and right
whether they have been compatible with a diagnosis of suspected projections. Visual analysis of each of the studies was carried out.
chronic thromboembolic pulmonary hypertension (CTEPH). We The number of defects visualized, distribution according to lobes
used modified PIOPED diagnostic criteria for V/P scintigraphy and the existence of cardiomegaly were defined. Results: Of
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S332

the 33 patients who presented scintigraphic criteria suggestive 3 (G3) a 2D image obtained by sum of all coronal slices of the
of CTEP, 15 were males (45,5%) and 18 females (54,5%) with tomographic reconstruction. Relative perfusion was calculated
a total mean age of 76 years (range 34-86). Of these, 15 were in G1 and G2 using the geometric mean of counts and in G3
clinically and radiologically diagnosed of PH. In this group of using the counts obtained in the 2D image. The Wilcoxon
patients, the distribution of most defects was subsegmental signed rank test, a non-parametric test for related samples, was
and predominantly superior and right, observing defects in used to evaluate the statistical significance of the differences.
almost all patients (67%) and indirect signs of cardiomegaly Results: We found no statistically significant difference
(73%). without HP the distribution of the defects was similar. between G1 and G2, regarding relative perfusion of the: entire
Regarding the number of segments and subsegments affected right lung (p=0.057), right superior third (p=0.607), entire left
according to the criterion of both Nnuclear Physicians, greater lung (p=0.057), left superior third (p=0.404), left middle third
number of defects were observed in patients with TEPC + HP (p=0.262) and left inferior third (p=0.759); however, there
(51) than in those with only TEPC (36) and greater subsegmental was a statistically significant difference between the values
involvement (45). Although there were obvious differences regarding the middle right third (p=0.05) and the inferior right
visually, the statistical significance was not reached due, third (p=0.011). Comparing G1 and G3, we found no statistically
probably, to the small number of the sample. There were no significant difference regarding the: right superior third
differences in the existence or not of cardiomegaly. Conclusion: (p=0.081), right inferior third (p=0.146) and left middle third
Pulmonary V/Q scintigraphy demonstrated a greater number of (p=0.337); statistically significant difference was found for the:
perfusion defects in patients who were diagnosed with CTEP entire right lung (p=0.000), right middle third (p=0.000), entire
+ PH, despite the small sample size of patients included in left lung (p=0.000), superior left third (p=0.000) and inferior left
the study. The greater number of perfusion defects and their third (p=0.000). Conclusion: According to our results, for the
distribution help confirm the diagnosis of suspected CTEP purpose of pulmonary scintigraphy quantification, tomographic
with HP. References: 1. Fedullo, P.F. Clinical manifestations and acquisition data might be compared with the planar one,
diagnosis of chronic thromboembolic pulmonary hypertension. when using the sum of two anterior and two posterior frames
[Online]. Available from: {{configCtrl2.info.canonicahttps:// of the tomographic study, and only for the ratio between the
uptodate.publicaciones.saludcastillayleon.es/contents/clinical- two lungs. This should still be confirmed with larger series and
manifestations-and-diagnosis-of-chronic-thromboembolic- reproducibility evaluation. References: None.
pulmonar y-hyper tension?search=Pulmonar y%20
embolism&topicRef=8253&source=related_
link#referenceslUrl}} [Accessed 25 April 2019]. EPS-064
Lung Aerosol Scintigraphy in Diabetic Patients Without
Pulmonary Symptoms
EPS-063 K. Kota, N. Pandit;
Scintigraphic quantification of pulmonary perfusion - JIPMER, Pondicherry, INDIA.
comparison between planar and tomographic acquisition
M. Victor, S. Carmona, S. Chin, A. I. Santos;
Hospital Garcia de Orta, E.P.E., Almada, PORTUGAL. Aim/Introduction: Diabetes mellitus is one of the most common
chronic diseases in nearly all countries, and continues to increase
in numbers. Retinopathy, neuropathy, nephropathy, and
Aim/Introduction: Pulmonary perfusion quantification, being cardiovascular dysfunction are common diabetic complications
of major importance for pulmonary surgery or transplantation, and are basically caused by vascular damage. Pulmonary
has been performed in planar images. However, this mode of complications of diabetes are frequently disregarded. This is
acquisition is being replaced by tomography, and there is no mainly because the alveolar-capillary system is characterized by
established equivalence between these two types of acquisition a great micro vascular reserve, and pulmonary abnormalities are
for the quantification of pulmonary perfusion. Our aim was commonly subclinical in Diabetic patients. Aerosol clearance
to evaluate this equivalence, to facilitate follow-up evaluation from the lung is an indirect evaluation of capillary permeability.
of each patient. Materials and Methods: We retrospectively In this study we aim to compare the Aerosol clearance in
analysed all 47 patients (14 males and 33 females, median Diabetic patients who have Diabetic complications and who
age=62[P25:47;P75:75]years) that performed both planar and do not have complications and both are without pulmonary
tomographic pulmonary scintigraphies in our department. To symptoms. Materials and Methods: The inclusion criteria
evaluate the quality of the perfusion images, we calculated include Diagnosed cases of Diabetes on follow up and without
the ratio of counts/sec between the perfusion and ventilation any pulmonary Symptoms at the time of study with Age more
images, in both anterior (median=4.23[P25:3.08;P75:6.45]) and than 18 years and up to 60 years. The exclusion criteria include
posterior (median=4.25[P25:3.22;P75:6.24]) planar projections. History of smoking; with any other known pulmonary or cardiac
To calculate the percentage of counts obtained for each lung disorders; Respiratory tract infections within 6 weeks; Pregnancy
or thirds of each lung, three image data were used: Group 1 and breastfeeding. In this study we divided Diabetic patients
(G1) - Planar acquisition; Group 2 (G2) - the sum of two anterior into two groups. One with known Diabetic complications
and two posterior projections of the tomographic study; Group (Group 1) and the other without complications (Group 2).
S333 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

Lung aerosol Scintigraphy was performed using Tc-99m DTPA followed by scrotal edema. A reduction of ultrafiltration was
Aerosols. After aerosol inhalation for 3 minutes, we acquired a 30 also observed in all patients.Regarding peritoneal scintigraphy
minutes dynamic scan using Siemens Symbia T6 gamma camera result, DFL was detected in 100% of cases. Foci detected in
using 64x64 matrix. We calculated the T1/2 for DTPA clearance after drainage images, presented moderate uptake in 2 cases
by drawing a standard ROI on lung fields excluding the central and high in 6. Periumbilical region was the most frequent
area. Results: Total 58 patients are evaluated, in which 26 (M: F leak location (50%), followed by inguinal region (37.5%) and
= 4:22) are in Group 1 and 32 (M: F=13:19) are in group 2. Mean pelvis (12.5%) in the planar images. When evaluating leakage
(Standard deviation) T1/2 in Group 1 is 51.031 (15.1498) and in location by SPECT/CT was observed that the foci detected in
Group 2 is 62.115 (14.4895). Mean difference is compared using periumbilical region were located in the subcutaneous cellular
simple unpaired T test with 95% confidence interval, which is tissue. Inguinal foci were located in the left inguinal canal and
statistically significant (p<0.05). Conclusion: The significant both scrotal sacs. Pelvic focus was placed in right paravesical
difference in clearance pattern in both the groups suggests area. Conclusion: Peritoneal leakage is a possible complication
there is impaired permeability in Group 2 patients. With this of peritoneal dialysis that can be easily confirmed by 99mTc-
study we can assume that Lung Aerosol scintigraphy can detect MAA scintigraphy. The inclusion of SPECT/CT images increase
the changes in vascular permeability even before the patients confidency in the results obtained. References: None.
are symptomatic. So Lung Aerosol Scintigraphy can be used as
a baseline evaluation in diabetic patients, especially in those
who are planned for inhalational insulin therapy as vascular EPS-066
permeability is important for insulin to reach into circulation. Replacing the 3 hours imaging in 75Se-SehCAT bile acid
References: None. malabsorption investigations with a calculated value
L. Duchstein, C. Hædersdahl, J. Nielsen, A. Flensborg;
Bispebjerg and Frederiksberg Hospital, Dept. of Clinical Physiology
EPS-065 and Nuclear Medicine, Copenhagen NV, DENMARK.
Utility Of 99mTc-MAA Scintigraphy And SPECT/CT For The
Diagnosis Of Peritoneal Leakage In Dialyzed Patients with
End Stage Kidney Disease Aim/Introduction: We report a study carried out alongside
B. Pérez López, P. J. Turbay Eljach, J. Gómez Hidalgo, N. Álvarez our clinical routine aiming to replace the 3-hour imaging
Mena, S. Sanz Ballesteros, M. A. Ruíz Gómez, C. Gamazo Laherrán, investigation after administration of tauroselcholic (selenium-75)
M. Alonso Rodríguez, M. J. González Soto, A. Sainz Esteban, R. acid (75Se-SeHCAT) to patients referred for quantification of bile
Ruano Pérez; acid absorption. The current method used for carrying out a
Hospital Clínico Universitario de Valladolid, Valladolid, SPAIN. SeHCAT investigation in Denmark follows Williams et al. [1]: 1.
administration of a 75Se- SeHCAT capsule 2. gamma camera
imaging 3 hours after administration 3. repeated imaging 7
Aim/Introduction: Dialysis fluid leakage (DFL) represents a days after administration. The photon flux from the patient after
major noninfectious complication of peritoneal dialysis (PD). It 3 hours is essentially determined by attenuation of photons in
is a consequence of the loss of peritoneal membrane integrity. the patient’s body, since no redistribution has taken place yet.
When DFL occurs into subcutaneous tissues, it is sometimes It can therefore be estimated based on the patient’s weight
occult and difficult to diagnose. An early diagnosis in these and height. Smout et al. [2] proposed a logarithmic approach,
patients is important to prevent significant morbidity and but we could not fit that to our existing data. Instead, we
mortality. Our aim was to evaluate the utility of peritoneal propose: Cps=activity[kBq]·(a·height[m]/(b·weight[kg])2+c)
scintigraphy and SPECT/CT using macroaggregated albumin Where: Cps are the calculated counts per second, activity is the
tagged with 99mTc (99mTc-MAA) to assess the diagnosis of DFL. administered 75Se activity in kBq, height is the patients’ height
Materials and Methods: We reviewed patients from April 2014 in m, weight is the patients’ weight in kg and a, b and c are
to April 2019 referred to our Nuclear Medicine deparment with fitting parameters that are dependent on the setup and the
clinical suspicion of DFL.All patients underwent a peritoneal gamma camera Materials and Methods: In total 170 patients
scintigraphy with 99mTc-MAA. Planar images were obtained 15 were included (104 women, age 18-90 years, body-mass-index
minutes after the infusion of 99mTc-MAA in the peritoneal cavity (BMI) between 17.1kg/m2 and 47.2kg/m2). Administered dose
and 2 hours after the drainage. A SPECT/CT of the target region of 75Se-SeHCAT was between 222kBq and 450kBq. In addition
was also performed after the late images. We also recommended to our clinical routine we recorded the weight and height of
to patients to do exercises to increase intraabdominal pressure. our test patients. The data of the first 13 patients were used
As variables, we evaluated demographic data, PD duration, to establish the best fit of the parameters a, b and c specific to
scintigraphy detection capability, utility of SPECT/CT, grade our setup. These parameters were then used to predict count
of uptake (low, moderate and high) and leakage location. rates of the 3 hours investigation for the remaining patients and
Results: A total of 8 patients were reviewed (5 women and these were compared to the count rates actually measured.
3 men), average age 62.2 years old (range 49-76 years) and Results: According to our 3-hour imaging 80 patients showed
mean duration of the PD of 17 months.They presented edema a significantly reduced reabsorption of bile acid (below 15%),
as a clinical sign, being abdominal the most frequent location 90 patients were healthy. The calculated values showed as
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S334

well 80 with malabsorption and 90 healthy patients. Using prognostic factors in the univariate analysis. LVS invasion (p=
the measured counts after 3 hours as a gold standard, the 0.022, HR 3.403, 95 % CI 1.195-9.696) and CA 125 level (p= 0.006,
calculation produced 4 false positive and 4 false negatives. A HR 5.592, 95 % CI 1.657-18.866) were the significant prognostic
Bland-Altman plot shows a higher deviation with increased factors in the multivariate analysis. Conclusion: Preoperative
retention. Conclusion: Using the patient’s weight and height, TLG was the most significant factor for predicting recurrence
we can reliably estimate the number of counts measured by a in patients with uterine carcinosarcoma. For predicting OS in
gamma camera 3 hours after administration of 75Se- SeHCAT, uterine carcinosarcoma, LVS invasion and CA 125 level were
thereby sparing the patient for one investigation and 3 hours the more significant prognostic factors than F-18 FDG PET
waiting time. References: [1] Williams et al. Gut 1991; 32:1004-6 parameters. References: None.
[2] Smout et al, EANM 2016 EP723.

EPS-068
611 The use of the updated EARL harmonization of 18F-FDG
PET-CT in patients with lymphoma yields significant
e-Poster Presentation Session 5 - Oncology: differences in Deauville score compared with previous
Oncology - e-Poster All Stars EARL recommendations
J. Ly1,2, D. Minarik3, L. Edenbrandt4, P. Wollmer2, E. Trägårdh2,5,6;
Monday, October 14, 2019, 8:00 - 9:30 Room 133/134 1
Department of Radiology, Kristianstad Hospital, Kristianstad,
SWEDEN, 2Department of Translational Medicine, Lund University,
Malmö, SWEDEN, 3Radiation Physics, Skåne University Hospital
and Lund University, Malmö, SWEDEN, 4Department of Clinical
EPS-067 Physiology and Nuclear Medicine, Sahlgrenska University
Prognostic value of volumetric parameters of on F-18 Hospital, Region Västra Götaland, Gothenburg, SWEDEN,
FDG PET/CT in patients with uterine carcinosarcoma in 5
Department of Clinical Physiology and Nuclear Medicine,
predicting progression free survival and overall survival Skåne University Hospital, Malmö, SWEDEN, 6Wallenberg Centre
S. Kim, W. Kang; for Molecular Medicine, Lund University, Lund, SWEDEN.
Severance Hospital, Yonsei University College of
Medicine, Seoul, KOREA, REPUBLIC OF.
Aim/Introduction: The Deauville score (DS) is a classification
system which distinguishes treatment response in patients
Aim/Introduction: This study was aimed to analysis the with lymphoma. The standardized uptake value (SUV) of
prognostic value of volumetric parameters on preoperative F-18 a lesion in positron emission tomography with computed
fluorodeoxyglucose positron emission tomography/computed tomography (PET-CT) is compared to the SUV in reference
tomography (FDG PET/CT) in patients diagnosed with uterine organs which results in five numerical categories, 1-5. The rapid
carcinosarcoma for predicting progression free survival (PFS) development in PET-CT software algorithms and hardware
and overall survival (OS). Materials and Methods: Fifty eight affects SUV and consequently DS, which may lead to different
women (median age : 60 (range 30-81 years old)) were included medical decisions and treatment. Local preferences in scanner
who pathologically confirmed uterine carcinosarcoma and settings vary widely, therefore the EANM Research Ltd. (EARL)
underwent F-18 PET/CT before surgery from June 2006 to harmonization program from the European Association of
November 2016. Maximum standardized uptake value (SUVmax) Nuclear Medicine (EANM) makes it possible to unify scanning
of primary tumor was obtained. Also, we estimated metabolic results and produce multicentre studies. This program was
tumor volume (MTV) and total lesion glycolysis (TLG) of primary recently updated to accommodate modern PET-CT technology.
tumor using fixed SUV of 2.5 as the threshold for determining the We have investigated the discordance in DS calculated from
contouring margins around the tumor. Optimal cut-off values patients with lymphoma referred for 18F-fluorodeoxyglucose
of continuous variables were determined by receiver operating (FDG) PET-CT reconstructed with three different algorithms: the
characteristic (ROC) curve. PFS and OS were evaluated using Log- newly introduced block-sequential regularization expectation
rank test and Cox regression test. Results: The median duration maximization algorithm commercially sold as Q.Clear (QC,
of PFS was 24.7 months (range 1.4-123.1 months). Twenty six GE Healthcare, Milwaukee, WI, USA), compliant with the
patients (44.8 %) experienced recurrences. The median duration updated EARL recommendations, and two settings compliant
of OS was 62.4 months (range 3.1-127.5 months), and 21 (36.2 with the previous EARL recommendations (EARLlower and
%) patients died. In the univariate analysis, age, size, CA 125 EARLupper, representing the lower and upper limit of the EARL
level, SUVmax, MTV, and TLG were significant prognostic factors recommendations). Materials and Methods: 52 patients with
for predicting PFS. In the multivariate analysis, TLG was the only non-Hodgkin and Hodgkin lymphoma were included (18 females
significant prognostic factor for PFS. (p= 0.006, hazard ratio (HR) and 34 males). The patients were scanned on a Si-photomultiplier
4.131, 95 % confidence interval (CI) 1.508-11.313) For predicting based PET-CT system (Discovery MI, GE Healthcare, Milwaukee,
OS, age, size, myometrial involvement, lymphovascular space WI, USA) after being injected with 4 MBq/kg 18F-FDG and an
(LVS) invasion, CA 125 level , SUVmax, and TLG were significant accumulation time of 60 min. Segmentation of mediastinal
S335 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

blood pool and liver were semi-automatically performed, ALND was indicated in 15% of the patients, and application of
whereas segmentation of lesions was done manually. From that of the SESPM indicated in 75%. The sensitivity to perform
these segmentations, SUVmax and SUVpeak were obtained and ALND obtained in our sample with the ACOSOGZ0011 criteria
DS calculated for the three different reconstructions described was 25%, while the sensitivity with that of the SESPM was
above. Results: There was a significant difference in DS between 80%. Conclusion: The application of the SESPM criteria, using
the QC algorithm and EARLlower / EARLupper (p<0.0001 for both) a tumor burden greater than 25,000 copies, gives us a higher
but not between EARLlower and EARLupper (p=0.102) when SUVmax sensitivity to perform ALND in our patients, obtaining better
was used. For SUVpeak, there was a significant difference between results than with the ACOSOGZ0011 criteria, however, these
QC and EARLlower (p=0.001), but not for QC vs EARLupper (p=0.071) discordant results are probably related to the low number of
or EARLlower vs EARLupper (p=0.102). Five non-responders (DS 4-5) patients in our study. On the other hand, the ACOSOGZ0011
for QC were classified as responders (DS 1-3) when EARLlower criteria provided a higher specificity. Therefore, it could be useful
/ EARLupper was used, both when SUVmax and SUVpeak were to include some of their criteria in that of the SESPM in order
investigated. Conclusion: DS classification is significantly to create a single guide and achieve a greater sensitivity and
changed when comparing the updated with the previous EARL specificity. References: None.
recommendation. In select cases, the discordance in DS would
affect choice of medical treatment. Specifically, the previous
EARL recommendations were more often prone to classify EPS-070
patients as responders. References: None. Impact of 18F-FDG PET/CT comparing to MRI in primary
staging and treatment approach of anal cancer
M. Beheshti1,2, R. Manafi-Farid3, A. Beheshti4, H. Wundsam5, F. M.
EPS-069 Mottaghy1, H. Geinitz6, W. Langsteger7;
Comparison of criteria for the indication of axillary 1
Nuclear Medicine, University Hospital, RWTH University,
lymph node dissection in patients with breast cancer and Aachen, GERMANY, 2Nuclear Medicine, Paracelsus Medical
positive sentinel lymph node biopsy University, Salzburg, AUSTRIA, 3Research Center for Nuclear
D. Vega Perez, M. Tabuenca Mateo, M. Martin Ferrer, E. Martinez Medicine, Tehran University of Medical Sciences, Tehran, IRAN,
Albero, V. Godigna Guilloteau, A. Galiana Moron, S. Ruiz Solis, J. ISLAMIC REPUBLIC OF, 4Ludwig Maximilian University, Munich,
Estenoz Alfaro; GERMANY, 5Visceral Surgery, Ordensklinikum, Linz, AUSTRIA,
Hospital 12 de Octubre, Madrid, SPAIN. 6
Radiation Oncology, Ordensklinikum, Linz, AUSTRIA, 7PET-CT
Center, St. Vincent’s Hospital, Ordensklinikum, Linz, AUSTRIA.

Aim/Introduction: Our objective is to compare the criteria


for the indication of axillary lymph node dissection (ALND) Aim/Introduction: Accurate staging is imperative to preserve
in patients with breast cancer and positive sentinel lymph anal sphincter and enhance the quality of life. In this study,
node biopsy (SLNB), according to the Sociedad Española de we evaluated the additive value of 18F-FDG-PET/CT in the
Senología y Patología Mamaria (SESPM) guidelines and to those initial staging and management of Anal Carcinoma. Also, we
of the ACOSOG Z0011 study, to determine which method assessed the prognostic significance of pre-treatment intensity
is superior in the indication of ALND in our clinical practice. of 18F-FDG uptake. Materials and Methods: Fifty-four patients
Materials and Methods: A retrospective study of 124 women with anal carcinoma who underwent both semi-whole body
with breast cancer (32 excluded due to lack of information) 18F-FDG-PET/CT and MRI of pelvis for primary staging and
selected consecutively between 2013-2019, with positive SLNB treatment planning were included in this study. The interval
(analyzed using the OSNA method), and to whom a posterior between 2 imaging modalities had to be no longer than 4 weeks.
ALND was performed. The patients had an average age of 56.5 Data regarding primary tumor, lymph-nodes (anorectal, iliac, and
years (between 34 and 87 years) with tumor T stage, 5% T1b, inguinal regions), and metastatic lesions were compared. The
37% T1c, 44% T2 and 11% T3. Of these, 69% had a histology of additional relevant information provided by 18F-FDG-PET/CT
infiltrating ductal carcinoma, 18% infiltrating lobular carcinoma impacting the management was assessed. Also, patients were
and 13% others. Regarding the histochemical type, 49% luminal followed (mean of 41.5±29.3 months) to determine true/false
A, 44% Luminal B, 5% HER2 + and 2% triple negative. A total of findings, as well as find a correlation between SUVmax of the
222 sentinel lymph nodes were analyzed, with a mean of 2.4 lesions and disease-free-survival. Results: Discordant findings
(between 1 and 6) per patient.We reviewed the ALND indication were found in 46.30% (25/54) of patients (5 in T; 1 in T and N;
in all patients according to ACOSOGZ0011 criteria (tumor of> 18 in N; and 1 in M stage). T-stage appeared higher in 3.70%
3 cm, with histological grade II-III, negative hormone receptors, of patients and lower in 7.40% on 18FDG-PET/CT. Discordant
HER2 +, triple negative, with lymphovascular invasion or more findings regarding the region of involved lymph-nodes were
than 2 positive sentinel nodes) and that of SESPM (tumor burden observed in 35.18% of patients in a total number of 30 regions.
greater than 25,000 copies of sentinel node mRNA with OSNA There were20 more involved regions on 18FDG-PET/CT and 7
analysis, modified according to our clinical experience). Results: more on MRI;threeregionswere positive on MRI and negative
Of the total of 92 patients, 35% had ALND positive and 65% on 18FDG-PET/CT. N-stage was incongruent in 22.22% (higher
negative. With the application of the ACOSOGZ0011 criteria, in 14.82% on 18F-FDG-PET/CT and in 7.40% higher on MRI).
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S336

18FDG-PET/CT resulted in true up-staging in 9.26% and down- cases at least for one site, by either biopsy (n=31), or matched
staging in 3.70% of patients. 18F-FDG-PET/CT was negative in multiparametric MRI (n=16); 2 patients had negative biopsy
12.96% of patients with perirectal lymph-node involvement and 21 patients had lesions not amenable for biopsy or
leading to erroneous down-staging in only 3.7%. Moreover, refused biopsy. Conclusion: 18F-DCFPyL-PET imaging is helpful
18F-FDG-PET/CT resulted in management change in 24.08% of in identifying suspicious lesions in 77.8% of patients with
patients (18.52% received more radiation, 3.70% received less, biochemical recurrence prostate cancer; and importantly, it
and one patient (1.86%) underwent palliative therapy). Finally, an reveals a high number of positive imaging findings in the range
adverse relation was observed between metabolic lymph-node of low PSA values (<0.5 ng/mL), which might substantially
involvement and complete response to treatment (p=0.006). No impact further clinical management. References: 1) Giesel FL,
significant correlation was demonstrated between disease-free- Will L, Kesch C, Freitag M, Kremer C, Merkle J, Neels OC, Cardinale
survival and metabolic activity of the primary tumor (p=0.127) J, Hadaschik B, Hohenfellner M, Kopka K, Haberkorn U, Kratochwil
or lymph-nodes (p=0.478) by means of SUVmax. Conclusion: C. Biochemical Recurrence of Prostate Cancer: Initial Results
18F-FDG-PET/CT provided more accurate staging in about with [18F]PSMA-1007 PET/CT. J Nucl Med. 2018 Apr;59(4):632-
13% of patients and led to change in treatment management 635. 2) Caroli P, Sandler I, Matteucci F, De Giorgi U, Uccelli L, Celli
in 24% of cases. However, MRI was superior in the detection of M, Foca F, Barone D, Romeo A, Sarnelli A, Paganelli G. 68Ga-PSMA
anorectal lymph-nodes. No significant prognostic advantage PET/CT in patients with recurrent prostate cancer after radical
was demonstrated using semi-quantitative parameters of treatment: prospective results in 314 patients. Eur J Nucl Med
18F-FDG-PET/CT. Nevertheless, 18F-FDG-PET/CT seems to Mol Imaging. 2018 Nov;45(12):2035-2044.
play a pivotal role in treatment planning of Anal Carcinoma.
References: None.
EPS-072
Usefulness of combined analysis by both FDG-PET and
EPS-071 diffusion MRI in predicting overall survival in biliary cancer
The value of PSMA-based 18F-DCFPyL PET/CT imaging in S. Nagamachi1, M. Nonokuma1, Y. Mizutani2, T. Terada2, K.
patients with biochemical recurrence prostate cancer after Yoshimitsu1;
primary local therapy 1
Fukuoka University, Fukuoka Prefecture, JAPAN,
E. Mena1, B. Turkbey1, L. Lindenberg1, S. A. Harmon2, I. Lim1, S. 2
Miyazaki University, Miyazaki Prefecture, JAPAN.
Adler2, A. Ton1, A. N. Forest2, P. Eclarinal1, Y. L. Mckinney1, J. Weaver2,
D. Citrin3, W. Dahut3, J. F. Eary3, P. L. Choyke1;
1
Molecular Imaging Program. NCI. NIH, Bethesda, MD, Aim/Introduction: Both Total lesion glycolysis (TLG) calculated
UNITED STATES OF AMERICA, 2Clinical Research Directorate, by FDG-PET and apparent diffusion coefficient (ADC) calculated
Frederick National Laboratory of Cancer Research sponsored by diffusion MRI are useful for predicting overall survival (OS) in
by the NCI, Bethesda, MD, UNITED STATES OF AMERICA, biliary cancer. However, few researches predicting OS of biliary
3
NCI. NIH, Bethesda, MD, UNITED STATES OF AMERICA. cancer by the combined analysis with FDG-PET and diffusion
MRI have been reported. We investigated the usefulness of
combined analysis by both FDG-PET and diffusion MRI in
Aim/Introduction: To investigate lesion detection rate of predicting OS of biliary cancer. Materials and Methods: Forty-
18
F-DCFPyL PET/CT, a PSMA targeted PET agent, in patients with two biliary cancer patients (27 females and 15 males, mean age
biochemical relapse prostate cancer after primary local therapy. 67.7) were analyzed retrospectively. Although tumor location
Materials and Methods: This is a prospective IRB-approved (Extra-hepatic19, Intra-hepatic 9, Papilla of Vater14) and stages
study including 90 patients with documented biochemical were various (I 4, II 9 III19, IV10), all cases were undertaken
recurrence (average PSA of 4.2 ng/mL, range 0.21-35.5 ng/mL) surgical resection and given post-operative chemotherapy
after primary local therapy, either with radical prostatectomy (gemcitabine /cisplatin). Both pre-operative FDG-PET and MRI
(n= 38), radiation (n=27) or combination therapy (n=25), with diffusion images were analyzed retrospectively. The values of
negative conventional anatomical imaging. Patients underwent TLG (g) were calculated by multiplication of total volumes more
whole-body 18F-DCFPyL-PET/CT at 2 h p.i (299.9±15.5 MBq). than 40% of SUVmax and SUV mean value on FDG-PET/CT. ADC
PSMA-PET lesion detection rate was correlated with pre-scan mean values were measured within the tumor ROI on the ADC
PSA levels. Results: Seventy patients (77.8%) showed a positive map imaged by 3T MRI with b value 1000.We divided all patients
PSMA-PET scan, identifying a total of 287 suspicious lesions: in the four subgroups according to the value of TLG and ADC
37 in the prostate bed, 210 lymph nodes, and 40 bone/organ mean obtained in pre-therapy examinations. The cut-off values
distant sites; 11 patients had a negative scan and 9 patients of each examination were 30g and 1300 s/mm2 respectively.
showed indeterminate lesions, which were also considered We compared OS (days) among the four groups, namely the
as having a negative scan. The detection rates were 47.6% group with high TLG and low ADC mean (n=12), the group with
(n=10/21), 50% (n=5/10), 88.9% (n=8/9), and 94.0% (n=47/50) high TLG and high ADC mean (n=11), the group with low TLG
for PSA levels of >0.2 to <0.5, >0.5 to 1.0, >1 to 2.0, and ≥ 2.0 and low ADC mean (n=11) , the group with low TLG and high
ng/mL, respectively. Out of 70 patients with positive PSMA- ADC mean group (n=8). We also compared various parameters,
PET scan, tumor recurrence was confirmed in 67.1% of the including tumor locations and stages, among four subgroups.
S337 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

Results: The mean value of each OS was 481, 557, 941 and protocol from the skull to mid thighs would be suitable in most
959 days respectively. The OS of high TLG and low ADC mean cases, in addition it has the benefit of a shorter acquisition time
was significantly shorter compared with those of each low TLG and less radiation exposure. References: None.
groups (481 vs. 941 days, 481 vs. 959 days). Although there was
no statistical significance, each low ADC mean group showed
shorter OS compared with those of each high ADC mean EPS-074
groups (481 vs. 557 days, 941, vs. 959 days). Regarding other Assessment Of Abdominal Resectability With FDG-PET/CT
clinical parameters including pathological stages, there was no In Locally Advanced Ovarian Cancer
statistical significance among four subgroups. Conclusion: The A. Caresia Aróztegui1, J. Del Riego Ferrari2, Y. García García3, L.
patients group with both high TLG and low ADCmean had poor Ribot Luna4, B. Morillas Oliveras4, I. Costa Tranchsel5, J. Martín
prognoses compared to other groups.In planning treatment Miramon1, A. Rodríguez Revuelto1, M. Moragas Solanes1, Z. Bravo
of biliary cancer, combined analyses of TLG by FDG-PET and Ferrer1, J. Antoni Vives4, L. Bernà Roqueta1;
ADC mean by MRI is useful in order to stratify and predict OS. 1
Nuclear Medicine Department, Parc Taulí Hospital Universitari,
References: None. Sabadell, SPAIN, 2Radiology Department, Parc Taulí Hospital
Universitari, Sabadell, SPAIN, 3Oncology Department, Parc Taulí
Hospital Universitari, Sabadell, SPAIN, 4Gynecology Department,
EPS-073 Parc Taulí Hospital Universitari, Sabadell, SPAIN, 5Pathology
“Complete” whole-body 18F-FDG PET-CT scan in Department, Parc Taulí Hospital Universitari, Sabadell, SPAIN.
malignant supradiafragmatic cutaneous melanoma. Does
it have any added value?
N. Bustos, G. Bruno, C. Gonzalez, S. Traverso, M. Arceluz, P. Corona, Aim/Introduction: In locally advanced ovarian cancer
M. Namias; the primary treatment is debulking surgery followed by
Fundación Centro Diagnostico Nuclear, Buenos Aires, ARGENTINA. chemotherapy. Surgery is recommended in patients who can
be debulked upfront to no residual tumour. Therefore, there are
some specific criteria against primary surgical approach (Diffuse
Aim/Introduction: The aim of this study was to determinate deep infiltration of the root of small bowel mesentery; large and
if “complete” whole body (head-to-toe) PET/CT acquisition diffuse carcinomatosis of the small bowel, extensive involvement
protocol has a added value in the assessment of patients with of superior abdomen or multiple visceral metastases). In case of
supradiaphragmatic primary malignant cutaneous melanoma: inoperable disease, neoadjuvant chemotherapy with interval
Our experience in 212 patients. Materials and Methods: surgery should be planned. The aim of this study is to evaluate
We retrospectively evaluated 389 patients with cutaneous the capability of FDG-PET/CT to assess abdominal resectability
melanoma who underwent staging or restaging PET/CT in advanced ovarian cancer, before surgery (primary or interval
between 2008 and 2014, and selected those whose primary surgery). Materials and Methods: Unicenter, restrospective,
lesion was supradiaphragmatic located (212/389). All abnormal observational study included 35 patients (age 63.11, range
hypermetabolic areas and morphologic lesions related to the 40-82 years) with clinical and radiological suspicion of primary
primary disease were recorded, focusing mainly on findings in advanced ovarian cancer. All patients underwent contrast
lower extremities. Results: A total of 3.3% (7/212) of patients had enhanced PET/CT before surgery. Based on criteria against
lesions in lower limbs using whole body scan PET/CT. Most of surgical approach, patients were classified as resectable or non
the patients had primary melanoma lesions on trunk (128/212), resectable. Sensitivity, specificity, NPV, PPV and accuracy for PET/
while upper extremities (49/212) and head and neck (39/212) CT to predict complete surgical resectability were calculated
were the following locations per frequency. The percentage of (R0). Results: Thirty-one patients were concordant (18
patients with potentially suspicious metastases on lower limbs patients were considered resectables by PET/CT and surgery,
where 1.8% for trunk primary lesions and 1.4% for those situated 13 patients were considered non resectables by PET/CT and
at head and neck. Only two patients (0.9%) with primary lesions surgery). Only 4 patients were discordant: 1 patient presented
at external ear and trunk had lower limb metastases as unique inoperable milliary carcinomatosis, not visible by PET/CT. The
finding, changing the staging thus the treatment; whereas the other 3 patients were finally resectables but it seems not by
rest of the patients (5/212) had already more extensive disease PET/CT (large and diffuse carcinomatosis of the small bowel
with secondary involvement in lungs and distant lymph nodes. or extense involvement of superior abdomen). For detection
No CNS (central nervous system) metastases where found. of abdominal resectability, PET/CT presented a sensitivity of
It is emphasized that no patients with primary melanoma on 85.7% (95% CI:64-97), specificity 92.8%(95% CI:66-100), NPV
upper limb had secondary involvement at lower extremities 81.2%(95% CI:54-96), PPV 94.7%(95% CI:74-100) and accuracy
in our study. Conclusion: Primary cutaneous melanoma with of 88.57%(95% CI:73-96). PET/CT also revealed extrabdominal
supradiaphragmatic location had low incidence of lower limbs distant metastases in 9/35 patients (29%), mainly represented
metastases. Whole body (head-to-toe) acquisition protocol by supradiaphragmatic lymph nodes (8/9 patients), associated
in these cases has no added value in the assessment of the with additional metastases in pleura and/or liver. Conclusion:
disease, so it might not be necessary to routinely include lower In locally advanced ovarian cancer, PET/CT had good results
extremities beyond the mid thighs. Standard PET / CT scanning in assessment of surgical abdominal resectability, especially in
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S338

terms of specificity, PPV and accuracy. PET/CT could be helpful EPS-076


in patients with questionable initial terapeutic decision, due 18
F-FDG PET/CT based BRAFV600 prediction in melanoma
to its ability to detect additional unsuspected extraabdominal H. Saadani1, B. van der Hiel1, E. A. Aalbersberg1, I. Zavrakidis1, J. B. A.
disease. References: None. G. Haanen1, O. S. Hoekstra2, R. Boellaard2, M. P. M. Stokkel1;
1
Netherlands Cancer Institute, Amsterdam, NETHERLANDS,
2
Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer
EPS-075 Center Amsterdam, Amsterdam, NETHERLANDS.
TNF alfa therapy and radiosynoviorthesis in patients with
rheumatoid arthritis Aim/Introduction: Approximately 50% of melanomas contain
M. Szentesi1, Z. Mangel1, Z. Nagy2, G. Csőre3, P. Géher1; a BRAF mutation, which causes tumor growth, cell proliferation
1
Department of Rheumatology, Polyclinic of the Hospitaller and metastasis. BRAF mutation determination is the decisive
Brothers of St. John of God, Budapest, HUNGARY, 2Polyclinic of factor for commencing first line BRAF inhibition in metastatic
the Hospitaller Brothers of St. John of God, Budapest, HUNGARY, melanoma. The potential of PET/CT based prediction in
3
St. Andrew Hospital for Rheumatic Diseases, Hévíz, HUNGARY. melanoma has been mainly explored in conventional PET
features and visual assessments whereas current developments
Aim/Introduction: The treatment of patients with rheumatoid in precision medicine increase the need for in-depth tumor
arthritis (RA) has been spectaculary changed since the characterization, which can be enabled by radiomics analysis.
1950’s. Introduction of the steroid compounds and their local The aim of this study was to predict BRAFV600 mutation
application, the chemical and radionuclide synovectomy, surgical status with both conventional- and radiomics 18F-FDG PET/
synovectomy, use of non steroid drugs, the basic treatment and CT features, while exploring several methods of feature
the spread of biological therapy are the most important steps. selection in melanoma radiomics. Materials and Methods:
Introduction of the biological therapy has changed the quality Seventy unresectable stage III/IV melanoma patients who
of life for these patients. During biological therapy sometimes underwent a baseline 18F-FDG PET/CT scan were identified.
1 or 2 joints could be affected by inflammation. In this cases Patients were assigned to the BRAFV600 group or BRAF wild-
always the question is how to solve the problem. Change of type group according to mutational status. 18F-FDG uptake
the biological or basic therapy, use surgical synovectomy or quantification was performed on the three lesions with the
radiosynovectomy (RSO)? Materials and Methods: In our highest FDG uptake per organ region, diameter ≥2 cm or
reumatological department 2100 patients with RA were treated MATV ≥4.2 cm3 by SUVmax50% based semi-automatic lesion
with biological therapy between 2002 and 2018. In 100 patients delineation. Four hundred eighty radiomics features and four
we applied RSO because of the inflammation of the knee joint conventional PET features (SUVmax, SUVmean, SUVpeak and
during biological therapy. We made a long term follow-up in total lesion glycolysis) were extracted per lesion. Six different
82 patient. All participants provided written informed consent. feature selection methods (a correlation matrix of all radiomics
82 participants inflammatory knee joint disease was diagnosed features, a correlation matrix of all radiomics features with the
on the basis of the American College of Rheumatology. 70 of conventional PET features SUVpeak, MATV, and TLG; a principle
82 patients with rheumatoid arthritis were seropositive, 12 component analysis, selecting features from prior studies, a
seronegative. Steinbrocker functional stadium II was observed penalized binary logistic regression analysis of all radiomics
in 72, stadium III in 10. Mean age of 18 male and 76 female features, and a random forest model of all radiomics features)
patients was 51.4 years (range 24-79) years. In 42 patients the were implemented and ten-fold cross validated predictive
right knee, in 40 the left knee was treated by radiosynovectomy. models were built for each. Model performances were evaluated
Mean duration of disease was 8.3 years (range 0.5-25), of with Area Under the Curves (AUC) of the Receiver Operating
synovitis (6.3month (range 3-8) Mean number of punctions of Characteristic (ROC) curves. Results: Thirty-five BRAFV600
the treated joint prior to radiosynovectomy was 4,2 per patient mutated patients (100 lesions) and thirty-five BRAF wild-
and of steroid administrations prior to radiosynovectomy 3,0. type patients (79 lesions) were analyzed. AUCs predicting the
In 15 patients a systemic steroid therapy has been performed. BRAFV600 mutation varied from 0.54-0.62 and were susceptible
Results: During the study period, inflammation decreased. In to feature selection method. The best AUCs were achieved by
the first 3 years excellent and good results were recorded in feature selection based on literature, a penalized binary logistic
81,2%. 3 years after radiosynoviorthesis 82.2% of patients did regression model and random forest model. No significant
not need another punction. Before the knee inflammation difference was found between the BRAFV600 and BRAF wild-
patients were in complete remission which status has been type group in conventional PET features, nor predictive value.
achieved after RSO as well. DAS: 2,4+-0,4. Conclusion: 1. RSO Conclusion: BRAFV600 mutation status is not associated with-
is an effective method to treat the inflammation of the knees. nor can be predicted with conventional PET features, while
2. RSO performed during biological tehrapy is as effective as in radiomics features were of low predictive value (AUC=0.62). We
the case of patients without biological therapy. 3. In case of a showed feature selection methods influence predictive model
successful RSO there is no need for biological or basic therapy performance, describing and evaluating six unique methods.
neither for surgical synovectomy. 4. However an intraarticular Detecting BRAFV600 status in melanoma based on 18F-FDG PET/
injection has a low risk for infection it is recommended to avoid CT alone does not yet provide clinically relevant knowledge.
the biological therapy during the RSO. References: None. References: None.
S339 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

EPS-077 and dosimetry data demonstrated CP04 as a promising targeting


Phase I clinical trial using a novel CCK2 receptor-localizing vector also for radionuclide with therapeutic properties (177Lu).
radiolabelled peptide probe for personalized diagnosis Gelofusine co-injection unambiguously showed a reduction of
and therapy of patients with progressive or metastatic tracer retention in the kidneys, which can be crucial for planning
medullary thyroid carcinoma - final results future treatment. Conclusion: The project has provided a novel,
A. Hubalewska-Dydejczyk1, R. Mikolajczak2, C. Decristoforo3, promising diagnostic tool for MTC patients. 111In-CP04 has
P. Kolenc-Peitl4, P. A. Erba5, K. Zaletel4, H. Maecke6, T. Maina7, M. been proven as a safe, sensitive and highly specific imaging
Konijnenberg8, P. Garnuszek2, M. Trofimiuk-Müldner1, E. Przybylik- biomarker. The favorable dosimetry results justify action to
Mazurek1, I. Virgolini3, M. de Jong8, A. C. Froberg8, C. Rangger3, G. initiate clinical trials of therapeutic efficacy assessment with the
Goebel3, L. Scarpa3, B. Glowa9, K. Skórkiewicz9, L. Lezaic4, B. Solnica1, CP04 labelled with a beta emitting therapeutic radionuclide
D. Fedak1, P. Gawęda1, A. Sowa-Staszczak1, B. A. Nock7, D. Bergant4, (177Lu). References: None.
S. Rep4, V. Lenda-Tracz9;
1
Jagiellonian University, Krakow, POLAND, 2NCBJ POLATOM,
Otwock-Swierk, POLAND, 3Medical University, Innsbruck, EPS-078
AUSTRIA, 4University Medical Center, Ljubljana, SLOVENIA, Comparison of 68Ga-PSMA and 18F-FDG PET/CT in Multiple
5
University of Pisa, Pisa, ITALY, 6University Medical Center, Mieloma: Preliminary Results
Freiburg, GERMANY, 7National Center for Scientific Research C. D. Ramos1, F. C. Frasson1, S. P. M. Souza1, G. B. Oliveira1, V. P.
Demokritos, Athens, GREECE, 8Erasmus MC, Rotterdam, Castro1, F. V. Pericole1, E. C. S. C. Etchebehere1, M. C. L. Lima1, E. M. R.
NETHERLANDS, 9University Hospital, Krakow, POLAND. Brunetto1, J. Mengatti2, E. B. Araujo2, C. A. Souza1, I. Lorand-Metze1,
A. O. Santos1;
1
University of Campinas, Campinas, BRAZIL, 2Nuclear and
Aim/Introduction: We aim to present the final results of the Energy Research Institute (IPEN), Sao Paulo, BRAZIL.
translational study: GRAN-T-MTC in the innovative field of
targeted radionuclide therapy in advanced medullary thyroid
cancer (MTC). In this phase I study held within the multinational Aim/Introduction: 18F-FDG PET/CT has been used to
cooperation (ERA-NET,TRANSCAN), the 111In-labelled CCK2 detect active lesions of multiple myeloma (MM), but image
receptor (CCK2R)-seeking ligand (DOTA-(DGlu)6-Ala-Tyr-Gly- interpretation may be challenging in patients with mild lesion
Trp-Met-Asp-Phe-NH2 (CP04) was tested. The justification for uptake because of physiological FDG accumulation in the bone
the project was the limited efficacy of available imaging and marrow. Recent case reports (1,2) have suggested the use of
treatment options (including tyrosine kinaseinhibitors) and 68
Ga-labeled prostate-specific membrane antigen (PSMA) as a
a high expression of CCK2Rs on MTC lesions. Materials and possible tracer for MM evaluation. This study aimed to compare
Methods: The study consisted of a preclinical (WP1) and clinical these two imaging modalities in the MM. Materials and
(WP2) part. WP1 aimed to establish a clinically useful formulation Methods: Ten consecutive patients with biopsy proven MM
for radiolabelled peptide CP04. The primary objectives of (6 female, mean age 67.7 ±8.1 years) were submitted to whole
WP2 were to determine: i) the safety of CP04 intravenous body 18F-FDG and 68Ga-PSMA PET/CT with a time interval of
administration, ii) the biodistribution and dosimetry of [111In] 1-7 days between procedures. Two patients were under initial
CP04 in cancer and normal tissues, iii) the critical organs, and staging, 3 with disease relapse and 5 under follow-up after
iv) the ability of the biomarker to visualize MTC lesions. In phase treatment. ISS score was 1, 2 and 3 for respectively 4, 2 and 4
1A (4 patients) two peptide amounts, both radiolabelled with patients. Two experienced nuclear physicians analyzed images
[111In] (200 ± 10% MBq), were administered: 10 μg as a safety by consensus. All lesions were counted and had their maximum
step in the first applications of CP04 and 50 μg as the amount SUVs measured in both procedures. Results: A total of 90 lesions
representative of potential therapy with [177Lu]CP04. After were detected in 9/10 patients. FDG detected 50/90 lesions in 8
safety assurance, only 50 μg of 111InCP04 was applied (phase patients and PSMA 83/90 lesions in 9 patients. Both procedures
1B). Patients were randomized into two arms: with and without did not identify any active lesion in 1 patient. Forty lesions
the co-administration of gelofusine (a renoprotective agent). were detected only by PSMA and 7 only by FDG. Both tracers
Overall, sixteen patients were enrolled in the study. During identified 43 lesions, but with intra-lesion mismatch pattern
[111In]CP04 administration, blood samples were taken forthe in 6 lesions, found in 4 different patients. Different lesions with
purpose of dosimetry, pharmacokinetics and measurement of uptake of only FDG or PSMA in the same patient were found
the calcitonin and procalcitonin concentration in the blood. in 3 patients. The 50 FDG and the 83 PSMA avid lesions had a
www.clinicaltrials.gov: ID:NCT03246659; EudraCTnumber: median SUV of 3.8 (1.3-37.8) and 6.8 (1.3-51.3), respectively
2015000 80538 Results: The positive results of [111In]CP04 (p<0.0001). The median SUVs of the 43 lesions with uptake of
stability, radiolabelling, and toxicity studies (WP1) enabled the both tracers were respectively 4.0 (1.3-37.8) and 9.1 (1.3-51.3)
development of a clinically useful formulation for radiolabelled for FDG and PSMA (p<0.0001). FDG and PSMA respectively
CP04. The Investigator’s Brochure and IMPD were prepared.All identified 8 and 11 soft tissue lesions. Benign lesions with FDG
the study goals of the clinical trial were achieved. The safety of uptake had minimal or no uptake of PSMA. The absence of
[111In]CP04 intravenous injection was confirmed. The biomarker physiological uptake in the brain or in normal bone marrow
was able to detect even unknown MTC lesions. Biodistribution made it easier to identify MM lesions in PSMA than in FDG
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S340

images. Conclusion: Our preliminary results suggest that 68Ga- EPS-080


PSMA PET/CT may be a good alternative for detecting active Meet 99mTc-tilmanocept as next generation radiotracer
lesions in patients with MM. Neoangiogenesis is the supposed with the requirements for improved sentinel node
mechanism of PSMA uptake in MM. 18F-FDG and 68Ga-PSMA imaging?
might have a complementary role in these patients, due to the D. Rietbergen, L. Pereira Arias-Bouda, J. vd Hage, R. Valdes Olmos;
marked genomic heterogeneity of the disease. References: Leids Universitair Medisch Centrum (LUMC), Leiden, NETHERLANDS.
(1)Baerentzen S, et al. Clin Nucl Med 2017;42(10):790-792. (2)
Rauscher I, et al. Clin Nucl Med 2017;42(7):547-548. Aim/Introduction: Radiotracers with small particle size
have been associated with a successful sentinel node (SN)
visualisation; however, in many cases concomitant non-SN
EPS-079 lymph node uptake may difficult image interpretation and
Diagnosis of Pelvic Insufficiency Fractures in Oncology radioguided procedures at the operating room. Recently,
Patients: Radiological Findings and Role of Tc99m MDP 99mTc-tilmanocept, with an average molecular size of 7 nm,
SPECT/CT imaging has become available in Europe; due to the improved receptor
V. Sabaliauskas, S. Tiškevičius; affinity of its mannose component in surface macrophages this
National Cancer Institution, Vilnius, LITHUANIA. tracer is aimed to combine increased uptake in SN with a rapid
clearance from injection site. We evaluated 99mTc-tilmanocept
Aim/Introduction: Diagnosing pelvic insufficiency fractures for SN imaging in patients with breast cancer and melanoma
(PIFs) in oncology patients is a challenge to radiologists and scheduled for SN biopsy after interstitial tracer administration.
recognition of imaging features is essential in order to avoid Materials and Methods: In 25 patients scheduled for SN
misdiagnosis of bone metastases and prevent patients from biopsy (mean age: 63y, range: 45-81y) planar images were
inaccurate treatment. The aim of this study is to assess risk acquired 10 and 120 min after administration of 74Mbq 99mTc-
factors, clinical and imaging findings of PIFs and evaluate tilmanocept in order to evaluate lymphatic drainage as well as
a diagnostic role of single-photon emission computed uptake ratios between injection site (IS), SN and non-SN. SPECT/
tomography/computed tomography (SPECT/CT) in diagnosing CT was performed immediately after delayed planar images to
PIFs in oncology patients. Materials and Methods: This study enable anatomical lymph node localisation. Results: SNs were
is based on a retrospective analysis of 42 oncology patients visualized in all patients (100%), in 13 of them (52%) without
(from August 2006 till March 2019) with PIFs who underwent visible non-SN uptake on both planar images and SPECT/CT.
computed tomography (CT), magnetic resonance imaging Number of SNs was concordant between early and delayed
(MRI) of pelvis and radionuclide whole body scan (WBS) images in all patients excepting two (92%). In 21 patients tracer
followed by pelvic SPECT/CT. The analysis included radiological migrated to one lymph node basin (LNB), in three to 2 and in
findings, clinical information, time-to-onset, follow-up time, risk one to 4. When IS was included (N=21) on image IS/SN ratio per
factors and complications associated with radiation therapy. LNB at 2h decreased with an average of 69.3% (range:15-98%)
Results: Median age at onset of PIF was 68.5 years (range: 52-87 in comparison with 15-min ratio. SN/non-SN 2h ratio in 12 LNB
years). 34 of patients (81%) were postmenopausal women. The with visible non-SNs averaged 6.8 (range:2.3-15.6). In 7 patients
median follow-up time was 12 months (range: 8-48 months). 32 with two SNs SN1/SN2 ratio averaged 1.6 on early images
patients (76.2%) presented with clinical symptoms. 35 patients and 1.7 on delayed. Conclusion: Despite its small particle size
(83.3%) received pelvic radiotherapy (RT). The median time 99mTc-tilmanocept appears to amply meet the requirements
for the development of PIFs after the completion of RT was for improved SN imaging in breast cancer and melanoma on the
13 months (range: 2-36 months). PIFs were most frequently basis of early and persistent SN visualisation frequently without
observed in the sacrum (80.1%). Fracture lines or sclerotic lines non-SN lymph nodes. This is accompanied by rapid migration
were seen on CT and/or MRI scans in 25 of 40 patients, and from the injection site together with increasing SN uptake as
osteosclerosis with no visible fracture lines was observed in 17 expressed by decreasing IS/SN ratios, and, in the case of visible
of 42 patients. On CT and/or MRI scans 16 radiological changes non-SNs, an adequate delayed SN/non-SN ratio. Further head-
were interpreted as benign, 9 as malignant, and 17 abnormalities to-head comparison of 99mTc-tilmanocept with standard SN
were undetermined. All of the lesions were observed on SPECT/ radiotracers in larger series of patients is necessary to establish
CT; only 5 (11.9%) of 42 lesions were undetermined and needed its role as first choice option in SN procedures. References:
further follow-up. Postmenopausal state and prior RT were None.
concluded as the main risk factors for the development of PIFs.
Conclusion: SPECT/CT should be included in the differential
diagnostics when radiological features of pelvic bone pathology
on CT or MRI are undetermined or PIFs are suspected. PIFs must
always be considered in oncology patients with pelvic pain,
especially in postmenopausal state and after RT. For patients
with risk factors of PIFs, bone density screening and precise
review of the most common fracture sites are recommended.
References: None.
S341 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

EPS-081 Aim/Introduction: Sorafenib is an inhibitor of multiple


Integrating Clinical Experience Into Radiomics For small molecules involved in hepatocyte proliferation and
Reducing The False Positive Rate Of 18F-FDG PET/CT neoangiogenesis used in the last decade to treat advanced
Diagnosis In Patients With Suspected Lung Cancer hepatocellular carcinoma (HCC). Recently, a preclinical trial has
F. Kang1, W. Mu2, J. Gong3, W. Qin3, J. Tian2, J. Wang1; shown that response to sorafenib is associated to a metabolic
1
Department of Nuclear Medicine, Xijing Hospital, Xi’an, CHINA, shift towards aerobic glycolysis, with increased glucose
2
Key Laboratory of Molecular Imaging of Chinese Academy of consumption and lactate production, as early as 12 hours
Sciences, Institute of Automation, Chinese Academy of Sciences, following sorafenib administration. To text this observation
Beijing, CHINA, 3Life Sciences Research Center, School of Life in humans, we decided to conduct a proof-of-concept trial
Sciences and Technology, Xidian University, Xi’an, CHINA. investigating the role of metabolic shift detected on FDG PET
in predicting survival and tumor response in patients with
advanced HCC during treatment with sorafenib. Materials
Aim/Introduction: The high false positive rate (FPR) of 18F-FDG and Methods: For this study, we prospectively enrolled
PET/CT in lung cancer screening represents a severe challenge advanced HCC patients candidate to therapy with sorafenib
for clinical decision-making. This study aimed to develop a and undergoing FDG PET/CT before treatment, after 24 hours,
clinical-translatable radiomics nomogram for reducing the and at day 7. Response evaluation was performed after 8
FPR of PET/CT in lung cancer diagnosis, and to determine the weeks according to the modified Response Evaluation Criteria
impact of integrating manual diagnosis to the performance in Solid Tumors (mRECIST). All clinical variables, including
of the nomogram. Materials and Methods: Among 3947 alpha-fetoprotein, and metabolic parameters (i.e. SUVmax;
lung cancer patients diagnosed with 18F-FDG PET/CT, 157 metabolic tumor volume, MTV; total lesion glycolysis, TLG;
malignant and 111 benign patients were enrolled and divided and their variations) were compared to treatment response
into training and test cohorts. The data of manual diagnosis and correlated to PFS and OS, based on a median follow-up
were retrospectively recorded. A total of 4338 features were of 5.3 months. The trial was registered: www.clinicaltrials.gov
extracted from CT, thin-section CT, PET and PET/CT, and the (NCT02977754). Results: Overall, thirteen patients (10 male, 3
four radiomics signatures (RS) were then generated by LASSO female, median age 69) were enrolled for this proof-of-concept
method. A hybrid nomogram integrating PET/CT RS and trial between August 2016 and August 2018. According to
manual diagnosis was developed using multivariable logistic mRECIST, among the 10 patients who were evaluated after
regression. The performances of RS and hybrid nomogram 8 weeks, six (60%) patients obtained SD, four (40%) PD, and
were validated through key discrimination index and clinical no objective responses were reported. As expected, median
benefit. Results: The FPR of manual diagnosis was found to SUVmax, MTV, and TLG resulted lower in patients with stable
be 30.63%. Among the four RS, PET/CT RS exhibited the best disease than progressive disease according mRECIST (p=0.019).
performance. By integrating manual diagnosis, the hybrid Considering the overall cohort, we demonstrated a significant
nomogram demonstrated lowest FPR and highest C-index and negative correlation between ΔSUVmax at 24 hours and at 1
Youden index (YI) in both training and test cohorts (FPR: 5.36% week (rho= -0.733, p=0.016). Metabolic parameters and ECOG
and 9.09%, C-index: 0.982 and 0.924, YI: 85.78% and 75.53%, Performance Status (PS) resulted significantly correlated to PFS
respectively). The hybrid nomogram respectively corrected and OS at univariate analysis, while on multivariate analysis,
78.57% and 37.50% among FPR cases produced by PET/CT RS, only median MTV at 1 week was found as independent
without significantly sacrificing its sensitivity. The net benefit prognostic factor for PFS (p=0.033). Conclusion: Our study
of hybrid nomogram appeared highest at < 85% threshold indicates that FDG PET/is able to evaluate metabolic shift at 24
probability. Conclusion: The established hybrid nomogram hours and early treatment response as early as after 1 week of
integrating PET/CT RS and manual diagnosis can significantly treatment in patients with advanced HCC undergoing sorafenib
reduce FPR, improve diagnostic accuracy and enhance clinical therapy. Moreover, metabolic parameters and ECOG PS result
benefit compared to manual diagnosis. The performance of predictive and prognostic factors to PFS and OS, with MTV at
this hybrid nomogram is superior to PET/CT RS without manual 1 week appearing as an independent prognostic factor for PFS.
diagnosis integration, indicating the importance of clinicians’ References: Llovet JM, et al. NEJM 2008; 359:378-390. Tesori V, et
judgement as an essential information source for improving al. Sci Rep (2015) 5:9149.
radiomics diagnostic approaches. References: None.

EPS-083
EPS-082 Incidental finding of 68Ga-prostate-specific membrane
Impact of Metabolic Switch in HCC Patients Treated with antigen (PSMA) uptake in the thyroid gland in patients
Sorafenib - A Proof-of-concept Trial with prostate cancer: A single-center cross sectional study
E. Lopci, A. Castello, N. Personeni, T. Pressiani, V. Smiroldo, E. L. Petersen, F. Gossili, H. D. Zacho;
Mazziotti, L. Rimassa; Department of Nuclear Medicine, Aalborg
Humanitas Clinical and Research Hospital - IRCCS, Milano, ITALY. University Hospital, Aalborg, DENMARK.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S342

Aim/Introduction: 68Ga-prostate-specific membrane antigen Aim/Introduction: Dedicated CZT cardiac cameras have
(PSMA) PET/CT has become a well established imaging method been shown to provide accurate measurements of absolute
for evaluation of patients with prostate cancer. However, myocardial blood flow (MBF) and flow reserve (MFR). PET MBF
numerous cases have revealed PSMA uptake in a large variety studies using either Rb-82 or N-13-ammonia have shown
of other conditions than prostate cancer. Such findings often that MFR was predictive of major adverse cardiovascular (CV)
represent other malignancies, but also a wide range of benign events. In this study we evaluate the correlation between
conditions may show PSMA uptake. PSMA uptake in thyroid SPECT global MFR measurement and clinical cardiovascular
cancer has been reported. The aim of present study was to risk (CVR). Materials and Methods: Patients referred for
describe the frequency of focal, pathologic PSMA uptake in the Myocardial Perfusion Imaging (MPI) for Coronary Artery Disease
thyroid gland leading to further investigations, and to assess the (CAD) screening between June 2018 and March 2019 were
frequency of malignant findings in a large patient cohort with included. Clinical symptoms and CVR factors were collected
prostate cancer. Materials and Methods: We retrospectively to classify patients in 3 groups: moderate, high and very high
identified all patients referred for a 68Ga-PSMA PET/CT at the risk. HeartScore (SCORE) according to the European Society of
department of Nuclear Medicine, Aalborg University Hospital, Cardiology was calculated. SPECT data were acquired on a CZT-
Denmark between 11th of May, 2015 and 12th of February, 2019. based pinhole cardiac camera in listmode using a stress (249
Patients with focal, pathologic PSMA uptake in the thyroid gland ± 17 MBq) / rest (508 ± 29 MBq) one-day Tc-99m-tetrofosmin
were retrieved and follow up was conducted based on medical protocol. Kinetic analysis was done with FlowQuantTMsoftware
charts, blood samples, additional imaging and histology when using a 1-tissue-compartment model and converted to MBF
available. Results: A total of 321 68Ga-PSMA PET/CT were using a previously determined extraction fraction correction.
performed in patients with prostate cancer (mean age 68, range Statistical analysis was performed using Prism 8TM. Results: 87
47-83 years). 68Ga-PSMA avid lesions in the thyroid gland were patients (39 male, 48 female) were included and classified in
observed in 9 patients (2.8 %) (mean age 70 years, range 52- 3 clinical CVR groups: 31 moderate, 13 high and 43 very high
78 years). Further investigations were conducted in all of the risk. Mean SCORE was 3.9%. Mean global MFR was 2.50 ±0.91.
patients, and seven patients underwent biopsy of the thyroid 25 patients (29%) had impaired CFR (using a threshold of 2),
gland. The biopsy was without malignancy in four patients, one whereas only 7 patients had pathological MPI. MFR wasn’t
biopsy was intermediate and two biopsies were suspicious of significantly different between the three groups of CVR (p=0.08),
malignancy. Based on the results of the biopsy and other clinical nor according to patient symptomatology (p=0.31). There was a
indication, five men underwent hemi-thyroidectomy, which significant correlation with the SCORE (p=0.03) and the number
revealed a synchronous primary papillary thyroid cancer in one of CVR factors (p=0.02). Excepting dyslipidemia (p=0.011) and
patient, metastases from a renal cell carcinoma in the second family history of coronary artery disease (p<0.05), we did not
patient and finally, in three patients no malignancy was present notice any significant correlation between impaired MFR and
in the thyroid. Thus, malignancy was verified in two of nine (22 %) other CVR factors (p=0.07 for smoking, p=0.17 for hypertension
PSMA avid lesion in the thyroid gland. Conclusion: Pathologic, and p=0.29 for diabetes). Impaired MFR was significantly
focal PSMA uptake in the thyroid tissue in prostate cancer associated to microalbuminuria (p<0.05), using a urinary
patients is a rare condition. However, such findings should be albumin to creatinine ratio threshold of 20mg/g. Conclusion:
further investigated as these findings may represent metastatic MFR measured during MPI for CAD screening on CZT camera
or primary malignancy of the thyroid gland. References: None. is significantly correlated with the SCORE and the number of
CVR factors. Impaired MFR was also significantly associated
with microalbuminuria, reflecting microvascular dysfunction.
911 Adding MFR to MPI could dramatically increase CAD diagnostic
confidence and provide prognostic information. References:
e-Poster Presentation Session 6 - None.
Cardiovascular: Searching for Myocardial
Ischemia
EPS-085
Monday, October 14, 2019, 14:30 - 16:00 Room 133/134 Correlation Of Coronary Calcium Burden And Myocardial
Perfusion Assessed By Myocardial Perfusion SPECT/CT
S. Cho1, J. Kim1, S. Yoo2, S. Kang2, S. Kwon2, J. Min2, H. Song1, H.
Bom2;
EPS-084 1
Chonnam National University Hospital, Gwang-ju,
SPECT Myocardial Blood Flow measurement with a KOREA, REPUBLIC OF, 2Chonnam National University
dedicated cardiac CZT camera for Coronary Artery Disease Hwasun Hospital, Jeollanam-do, KOREA, REPUBLIC OF.
screening: correlation with cardiovascular risk
M. Bailly1, F. Thibault1, M. Courtehoux2, G. Metrard1, M. Ribeiro2;
1
CHR Orléans, Orleans, FRANCE, 2CHRU Tours, Tours, FRANCE. Aim/Introduction: We assessed the correlation between
coronary calcium scoring performed by low-dose attenuation
correction CT (AC-CT) and myocardial perfusion on myocardial
S343 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

perfusion SPECT/CT. Materials and Methods: We retrospectively male Sprague-Dawley rats were equally divided into control
included 225 patients with low-to-intermediate (≤ 90%) pretest (CTL), diabetic (T2D) and liraglutide-treated (T2D-LIR) groups.
probability, who underwent myocardial perfusion SPECT/CT T2D and T2D-LIR animals were fed a high-fat diet and received an
equipped with low-dose attenuation correction CT (AC-CT) for intraperitoneal injection of streptozotocin (35 mg/kg) to induce
evaluation of coronary artery disease. Patients with previous diabetes. T2D-LIR rats were treated with Liraglutide (4 weeks, 300
coronary artery disease, clinically suspected heart failure or left μg/kg/day subcutaneously). Heart structure and function were
ventricular ejection fraction < 45% or wall motion abnormality assessed with transthoracic doppler echocardiography. CMD
on echocardiography, heart rate > 75/min, other valvular or was assessed through MPE quantification from thallium-201
myocardial diseases were excluded. Agatston calcium score stress (dobutamine) SPECT MPI using an original and patented
(ACS) was calculated for each patient’s resting AC-CT images. algorithm. Results: T2D rats were hyperglycemic as compared
Total perfusion deficit (TPD) was calculated for stress and resting with CTL animals (5.5 ± 0.5 g/L vs 1.1 ± 0.3 g/L, P<0.001) and
SPECT images, and ischemic TPD was also calculated (stress had a significantly lower left ventricular (LV) ejection fraction
TPD - resting TPD). Abnormal SPECT was defined as stress TPD (LVEF) (65 ± 4% vs 74 ± 9%, P<0.01), decreased LV shortening
≥ 5% or ischemic TPD ≥ 3%. Clinical implications of ACS by fraction (LVSF, 37 ± 3.% vs 46 ± 10%, P<0.05), higher indexed
AC-CT were analyzed in terms of its correlation with TPD and LV mass (5.5 ± 1 g/m² vs 3.8 ± 0.7 g/m², P<0.001) and increased
its relationship with myocardial perfusion status against other LV end diastolic diameter (8.7 ± 0.4 mm vs 7.5 ± 0.6 mm,
coronary risk factors. Results: Total ACS by AC-CT showed P<0.001). Liraglutide partially restored glycemia (3.9 ± 0.6 g/L,
positive correlations with both stress TPD (r = 0.360, p < 0.001) P<0.05 vs CTL and T2D) and totally restored LVEF and LVSF
and resting TPD (r = 0.369, p < 0.001), but not with ischemic TPD (72 ± 7% and 43 ± 4%, P=NS vs CTL). MPE was significantly
(r = 0.065, p = 0.335). SPECT was abnormal in 52 (23%) patients increased in T2D rats (7.6 ± 0.5 vs 7.1 ± 0.5, P<0.05), but was
and total ACS by AC-CT was significantly higher in patients with not significantly improved in T2D-LIR rats despite being not
abnormal SPECT, as compared to those with normal SPECT significantly different from that of CTL animals (7.4 ± 0.4, P=NS
(319.3 ± 681.5 vs 121.2 ± 319.3, p = 0.049). Multivariate analysis vs CTL & T2D). Conclusion: T2D induced by a high-fat diet and
revealed that total ACS ≥ 100 was the only clinical factor related a moderate dose of streptozotocin resulted in increased MPE,
to abnormal SPECT result. Conclusion: Higher coronary calcium likely reflecting CMD. Liraglutide did not affect MPE, suggesting
burden on SPECT/CT was predictive of abnormal myocardial that CMD may not be a major target of liraglutide in the present
perfusion. References: Ghadri JR et al. Coronary Calcium Score experimental model. The relevance of MPE for the assessment of
as an Adjunct to NuclearMyocardial Perfusion Imaging for Risk CMD warrants further clinical investigation. References: None.
StratificationBefore Noncardiac Surgery. J Nucl Med 2012; 53:1-
6.
EPS-087
Prognostic value of myocardial perfusion entropy
EPS-086 quantified from SPECT myocardial perfusion images
SPECT Myocardial Perfusion Imaging Reveals Increased L. Djaileb1,2, A. Seiller1,3, A. Fraguas-Rubio1, J. Leenhardt1,2, A.
Myocardial Perfusion Entropy in a Rodent Model of Type 2 Martin4, J. Poujol1, A. Broisat1, J. Miranda1,3, G. Vanzetto1,4, D.
Diabetes Prone to Coronary Microvascular Dysfunction Fagret1,2, M. Desvignes3, C. Ghezzi1, L. Riou1, G. Barone-Rochette1,4;
A. Carabelli1,2, M. Canu2, A. Fraguas-Rubio2, J. Leenhardt3, A. 1
INSERM U1039 Radiopharmaceutiques Biocliniques,
Broisat2, J. Miranda2,4, G. Vanzetto1,2, D. Fagret3,2, M. Desvignes4, L. Grenoble, FRANCE, 2Grenoble - Alpes University Hospital
Djaileb3,2, C. Ghezzi2, G. Barone-Rochette1,2, L. Riou2; - Nuclear Medicine Dpt, Grenoble, FRANCE, 3GIPSA-lab,
1
Grenoble - Alpes University Hospital - Cardiology Dpt, UMR CNRS 5216, Grenoble, FRANCE, 4Grenoble - Alpes
Grenoble, FRANCE, 2INSERM U1039 Radiopharmaceutiques University Hospital - Cardiology Dpt, Grenoble, FRANCE.
Biocliniques, Grenoble, FRANCE, 3Grenoble - Alpes University
Hospital - Nuclear Medicine Dpt, Grenoble, FRANCE,
4
GIPSA-lab, UMR CNRS 5216, Grenoble, FRANCE. Aim/Introduction: Single-photon emission computed
tomography (SPECT) myocardial perfusion imaging (MPI)
for the assessment of myocardial ischemia provides valuable
Aim/Introduction: Type 2 diabetes (T2D) is a major risk factor prognostic value. However, the risk stratification of patients
for coronary microvascular dysfunction (CMD). The role of CMD with type 2 diabetes mellitus (T2D) remains suboptimal. Recent
in the occurrence of cardiovascular events (CVE) is increasingly studies have highlighted the role of coronary microvascular
being recognized. However, no noninvasive method is currently disease in the occurrence of coronary symptoms in this
available for the routine evaluation of CMD. The anti-diabetic, population. We hypothesized that enhanced signal analysis
glucagon-like peptide-1 analog Liraglutide decreases CVE. We from SPECT myocardial perfusion images may allow insights
hypothesized that enhanced, pixel-by-pixel signal analysis from into the coronary microvascular status. More specifically,
thallium-201 SPECT myocardial perfusion images (MPI) allowing we hypothesized that myocardial perfusion entropy (MPE)
the quantification of myocardial perfusion entropy (MPE) would as a surrogate marker of microvascular disease quantified
allow the assessment of MPE variations related to CMD in a from SPECT myocardial perfusion images may provide an
preclinical model of T2D. Materials and Methods: Thirty-nine incremental prognostic value in T2D patients independently
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S344

from the routinely performed assessment of myocardial that were stratified into two groups based on presence/
ischemia. Materials and Methods: T2D patients with very high absence of microalbuminuria. All participants underwent CAD
cardiovascular risk were studied (n=166, 65±12 years). Ischemia evaluation using MPS gated SPECT imaging. Other clinical
was assessed by SPECT myocardial perfusion imaging (MPI). In and laboratory indices were also recorded. Results: Studied
addition, SPECT MPI was used for the quantification of rest and population consisted of 120 patients ( 84 male 70%; 36 female
stress MPE using an original algorithm providing a global value 30%) with mean age of 9.90± 58.61). In total, asymptomatic
of MPE from reconstructed rest and stress SPECT images. The ischemia was detected in 78 (65% of the included diabetic
primary end point was major adverse cardiac events (MACEs) patients. Stress induced ischemia was found in 56 patients
defined as cardiac death, Q-wave myocardial infarction (MI) and (87.5%) of Alb+ group and in 22 patients(39.3%) of Alb- group.
myocardial revascularization >3 months after SPECT. Results: The frequency of stress induced ischemia was 10.81 times
46 patients underwent MACEs over a median follow-up of higher in the patients with micro albuminuria compared to
4.6 years. Significant differences in stress MPE were observed Alb- ones(p<0.001 , OR:10.81, 95% CI:4.33-26.99). Likewise , no
between patients with and without MACEs (4.19±0.46 vs. correlation was found between the presence of stress induced
3.93±0.39; p≤.01). By Kaplan-Meier analysis, the risk of MACEs ischemia and therapy type, diabetes duration , history of evident
was significantly higher in patients with higher stress MPE (log- retinopathy , history of hypertension and serum levels of HbA1C
rank p≤.01). Stress MPE was significantly associated with the risk (p > 0.05). Conclusion: The current study showed that abnormal
of MACEs (hazard ratio: 2.80, p≤.01) after adjustment for clinical MPI findings are significantly more common in diabetic patients
and imaging risk factors as identified from preliminary, univariate with microalbuminuria. With respect to low cost and availability
analysis and including age, hypertension and ischemia. The risk of urine albumin detection tests, it might be as a biomarker for
of overfitting was controlled by internal validation procedures prediction of silent myocardial ischemia in diabetic population.
such as LASSO, stepwise and random forests selections on References: None.
time-to-MACEs Cox models. A competing risk event (“other
deaths”) slightly overestimated Cox estimates. However, the
impact of informative censorship as assessed by Fine-Gray EPS-089
subdistribution hazard estimates proved to be marginal. The Prognostic value of coronary artery calcium and
incremental prognostic value of MPE over clinical risk factors myocardial perfusion reserve in patients with and without
was quantified using nested models showing improved AIC, diabetes mellitus
improved reclassification (global continuous Net Reclassification R. Assante1, W. Acampa1, E. Zampella1, C. Nappi1, T. Mannarino1,
Improvement [NRI]: 70.1, global Integrated Discrimination V. Gaudieri1, M. Panico2, V. Cantoni1, R. Green1, M. Petretta3, M.
Improvement [IDI]: 6.6%), improved discrimination (change in Memmott4, P. Arumugam4, A. Cuocolo1;
c-statistic : 0.69 vs 0.74), and improved time-dependent AUC 1
Department of Advanced Biomedical Sciences, University
(0.71 vs 0.77 at 4 years of follow-up). Conclusion: Stress MPE Federico II, Naples, ITALY, 2Institute of Biostructure and Bioimaging,
provided independent and incremental prognostic information National Council of Research, Naples, ITALY, 3Department of
for the prediction of MACEs in diabetic patients. References: Translational Medical Sciences, University Federico II, Naples,
None. ITALY, 4Nuclear Medicine Centre, Manchester University
NHS Foundation Trust, Manchester, UNITED KINGDOM.

EPS-088
Significance of microalbuminuria in predicting silent Aim/Introduction: We assessed the prognostic value of
myocardial ischemia (SMI) in patients with type 2 diabetes combined measures of structural abnormalities and coronary
using myocardial perfusion imaging vasodilator function by 82Rb PET/CT in diabetic and nondiabetic
M. Assadi1, T. Emami1, Z. Naeimei1, A. Salehifard1, D. Iranpour1, M. patients with suspected coronary artery disease (CAD). Materials
Kalantarhormozi1, Z. Azizmohammadi2, E. Jafari1; and Methods: A total of 985 patients (251 with and 734 without
1
Bushehr University of Medical Sciences (BUMS), Bushehr, IRAN, diabetes mellitus) without overt CAD, referred to 82Rb PET/CT
ISLAMIC REPUBLIC OF, 2Shahid Beheshti University of Medical as part of their diagnostic program were studied. CAC score
Sciences (BUMS), Tehran, IRAN, ISLAMIC REPUBLIC OF. was categorized into two groups (<400 and ≥400). Myocardial
perfusion reserve (MPR) was considered reduced when <2. The
outcome was a composite end-point of cardiac death, nonfatal
Aim/Introduction: In light of increased risk of cardiovascular myocardial infarction and unstable angina requiring coronary
events and the poor prognosis of coronary artery disease (CAD) revascularization. Results: Follow-up was 93% complete during
in diabetic versus non-diabetic patients and with respect to the a mean period of 41±16 months. During follow-up, 59 events
importance of early diagnosis of CAD in this status, the study occurred (6% cumulative event rate). Event rate was significantly
was aimed to assess the importance of microalbuminuria in higher in diabetic patients as compared to nondiabetic subjects
predicting silent myocardial ischemia (SMI) in patients with type (P<0.001). In both diabetic and nondiabetic patients event rate
2 diabetes using myocardial perfusion imaging . Materials and significantly increased with increasing of CAC score categories
Methods: This study included 120 patients with diabetes type (P<0.05). Similarly, event rate was significantly higher in the
2, but without previously known CAD or any cardiac symptoms presence of impaired MPR in both groups of patients with
S345 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

and without diabetes (both P<0.05). At multivariable Cox perfusion as pathological when a myocardial segment with a
analysis, CAC score ≥400 and impaired MPR were independent SSS≥2 also presented with a WT abnormality. Significant CAD
predictors of events in both diabetic and nondiabetic patients was defined by the presence of ≥90% stenosis/occlusion or
(both P<0.05). Event free survival was not significantly different fractional flow reserve ≤ 0.80 in the presence of a ≥50% coronary
between diabetic and nondiabetic patients with impaired MPR stenosis. Results: Upon per patient analysis, the occurrence of
and CAC <400 (P=0.26). Differently, event free survival was false positives was significantly higher in supine NG images
lower in diabetic patients with impaired MPR and CAC score (36.6%) than in both prone & supine NG and supine NG+WT
≥400 compared to nondiabetic patients (P<0.05). Conclusion: image sets (9.8% and 7.8%, respectively, p<0.05 vs supine NG)
In patients with suspected CAD atherosclerosis burden and (see Figure). Consequently, specificity decreased from prone &
coronary vascular function were independent predictors of supine NG to supine NG images (86.2% vs. 48.3%, p=0.003) and
cardiac events in both diabetic and nondiabetic patients. was restored when using supine NG+WT images (88.5%, p=NS
However, in patients with impaired MPR and CAC score ≥400, vs prone & supine NG), with no compromise in sensitivity (91.7%,
the presence of diabetes was associated with lower event free 91.7%, 83.3%, respectively, p=NS for all comparisons). Similar
survival. References: None. results were observed upon per vessel analysis. Conclusion:
The diagnostic performances of supine stress SPECT MPI are
restored compared with combined prone & supine acquisitions
EPS-090 when WT assessment in the ischemic segments is used as an
Prospective diagnostic performance of semi-conductor additional diagnostic criterion. References: None.
SPECT myocardial perfusion imaging: wall thickening
analysis overcomes the lack of prone acquisition
L. Djaileb1,2, B. Dubois3, N. de Leiris1, A. Seiller1, J. Leenhardt1, M. EPS-091
Canu1, A. Broisat1, G. Vanzetto1,4, D. Fagret1,2, M. Desvignes5, C. Comparison of the prognostic value of PET and SPECT in
Ghezzi1, L. Riou1, G. Barone-Rochette1,4; patients with coronary artery disease: A meta-analysis
1
INSERM U1039 Radiopharmaceutiques Biocliniques, Grenoble, H. Chen, R. Wang, J. Wei, C. Fan;
FRANCE, 2Grenoble - Alpes University Hospital - Nuclear Medicine West China Hospital of Sichuan University, Chengdu, CHINA.
Dpt, Grenoble, FRANCE, 3CH Métropole Savoie, Chambéry, FRANCE,
4
Grenoble - Alpes University Hospital - Cardiology Dpt, Grenoble,
FRANCE, 5GIPSA-lab, UMR CNRS 5216, Grenoble, FRANCE. Aim/Introduction: The prognostic value of single-photon
emission computed tomography (SPECT) myocardial perfusion
imaging (MPI) has been fully evaluated in the past few decades.
Aim/Introduction: The routine acquisition of combined For now, the positron emission tomography (PET) is widely
prone and supine SPECT myocardial perfusion images remains used clinically. However, whether the prognostic value of
limited despite the associated improvement in diagnostic and PET MPI superior to SPECT MPI is still unknow. We performed
prognostic accuracies. Our aim was to determine whether a meta-analysis to compare the negative predictive value
the assessment of regional wall thickening (WT) in addition (NPV) of normal PET MPI and SPECT MPI in patients with
to myocardial perfusion from stress supine acquisitions could known or suspected coronary artery disease (CAD). Materials
overcome the lack of prone acquisition and the corresponding and Methods: Studies published between January 2000 to
decrease in the diagnostic performances of SPECT myocardial June 2018 were identified by database search. We included
perfusion imaging (MPI) in patients with known or suspected studies using PET or SPECT to evaluate patients with known or
coronary artery disease (CAD). Materials and Methods: 41 suspected CAD and providing data on clinical outcomes with
patients (123 vessels) with known or suspected CAD were a follow-up time ≥1 year. Results: A total of 20 eligible articles
prospectively recruited for systematic prone and supine (9 PET MPI and 11 SPECT MPI) were finally included, recruiting
thallium-201 stress SPECT myocardial perfusion imaging 16,387 patients in PET and 21,936 patients in SPECT. The
using a semi-conductor, cardiac dedicated SPECT camera. The negative predictive value (NPV) for hard events (cardiac death
diagnostic performances of SPECT MPI were determined for and nonfatal myocardial) was 97.53% (95% confidence interval,
various image sets including non-gated, supine images (supine CI 95.67-98.88) in PET and 97.22% (95% CI 96.14-98.13) in SPECT,
NG), non-gated, combined prone and supine acquisitions resulting in estimated event rate after negative test (ERNT)
(prone & supine NG), and gated supine acquisition allowing equal to 2.47% (95% CI 1.12-4.33) and 2.78% (95% CI 1.87-3.86)
the evaluation of WT in addition to that of perfusion from NG respectively. The corresponding annualized event rate (AER)
images (supine NG+WT). Invasive coronary angiography (ICA) after a negative test was 0.73% and 0.63%. Conclusion: The
and fractional flow reserve (FFR) as the gold standard. Myocardial negative prognostic value of PET MPI and SPECT MPI for hard
perfusion was scored using a 5-point scale (0 = normal, 1 = events in patients with known or suspected CAD are similar and
equivocal, 2 = moderate, 3 = severely reduced radiotracer comparable. Further studies of prognostic value of PET MPI are
uptake, 4 = no detectable uptake) and a 17-segment model of still needed. References: None.
the left ventricle leading to summed stress score values (SSS).
Patients were classified as positive for the presence of ischemia
if SSS≥2. Additional WT analysis was used to classify myocardial
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S346

EPS-092 reserve (CFR) assessed by positron emission tomography (PET)


Predictability of Coronary Flow Reserve and Geriatric in predicting adverse cardiovascular events in patients with
Nutrition Risk Index for poor prognosis in the Patients suspected or known CAD. Materials and Methods: A search
with Dialysis dependent End-stage Renal Disease in electronic databases was conducted including PubMed and
S. Ohshima1, N. Umemoto2, R. Ito1, T. Sakakibara1, H. Hori1, T. Embase for studies published in English language until April
Murohara3; 2019. The studies were included in the analysis if they evaluated
1
Nagoya Kyoritsu Hospital, Nagoya, JAPAN, 2Ichinomiya CFR by PET in patients with suspected or known CAD, providing
Municipal Hospital, Ichinomiya, JAPAN, 3Nagoya University data on adjusted hazard ratio for the occurrence of adverse
Graduate School of Medicine, Nagoya, JAPAN. events. Because of the large heterogeneity experienced and to
minimize the effect of confounding, we considered separately
the hazard ratio derived from multivariate regression analyses
Aim/Introduction: Ischemic heart disease (IHD) is an important for the occurrence of both hard events, defined as cardiac
issue to be resolved in the patients with dialysis dependent death and nonfatal myocardial infarction, and all adverse
end-stage renal disease (dd-ESRD). Coronary flow reserve (CFR) events. Summary risk estimates for impaired CFR by PET were
measured using 13N-ammonia positron emission tomography derived in random effect regression analysis and causes of
(13N-NH3-PET) myocardial perfusion imaging (MPI) is an heterogeneity were determined in meta-regression analysis.
established and reliable parameter for detecting coronary artery Results: We identified 13 eligible articles including 9,090
disease and prediction for cardiovascular event and mortality. patients with suspected or known CAD with a mean follow-
On the other hand, it is shown that dd-ESRD patients with up of 3.17±0.55 years. All studies reported the hazard ratio
malnutrition status have poor prognosis. In previous studies, we for the occurrence of all adverse events. The pooled hazard
reported the relationship between low geriatric nutrition risk ratio was 1.57 (95% confidence interval 1.16-2.11). Among the
index (GNRI) and poor prognosis in the patients with dd-ESRD. included publications, five studies reported the hazard ratio
In this study, we investigated the predictability of CFR and GNRI for the occurrence of hard events. The pooled hazard ratio was
in dd-ESRD population. Materials and Methods: Consecutive 2.51 (95% confidence interval 1.73-3.64). At meta-regression
306 dd-ESRD patients, who were performed 13N-NH3-PET analysis we found an association between the hazard ratio for
MPI for suspected IHD, were studied. Patients undergone any all adverse events and clinical variables (family history of CAD
revascularization within 60 days after 13NH3-PET MPI were and prior myocardial infarction) and between the hazard ratio
excluded in this analysis. Patients were classified into 4 groups for hard events and demographic (male gender) and clinical
according the median value of CFR (1.99) and GNRI (97.73); variables (diabetes mellitus, arterial hypertension, and prior
Low CFR-Low GNRI group (n=77), High CFR-Low GNRI group coronary revascularization). Conclusion: The results of this
(n=76), Low CFR-High GNRI group (n=78) and High CFR-High meta-analysis suggest that in patients with suspected or known
GNRI group (n=75). We followed up to 1,544 days (median 833 CAD an impaired CFR is associated with adverse cardiovascular
days) about all-cause mortality, cardiovascular (CV) mortality events. However, the large heterogeneity in study population
and major adverse cardiovascular and cerebrovascular event underlines the need for further investigations to maximize the
(MACCE). Results: There was no mortality event in High CFR- prognostic role of CFR. References: None.
High GNRI group. Kaplan-Meyer analysis showed that there
were statistically differences in each group (all-cause mortality;
log rank p<0.01, CV mortality; log rank p=0.02, MACCE; log EPS-094
rank p<0.01). Conclusion: Dd-ESRD patients with low CFR Diagnostic Performance of Attenuation Corrected
and malnutrition status would have poorer prognosis than the Myocardial Perfusion Imaging for Coronary Artery
patients without them. References: None. Disease: A Meta-analysis of Vessel-based Data
J. Huang1,2, C. Huang3,2, R. Yen1, K. Ko1, C. Lu1,2, K. Chien3,2, Y. Wu4;
1
Department of Nuclear Medicine, National Taiwan University
EPS-093 Hospital and National Taiwan University College of Medicine,
Prognostic value of coronary flow reserve in patients with Taipei, TAIWAN, 2Institute of Epidemiology and Preventive
suspected or known coronary artery disease referred Medicine, College of Public Health, National Taiwan University,
to myocardial perfusion imaging by positron emission Taipei, TAIWAN, 3Department of Internal Medicine, National
tomography: a meta-analysis Taiwan University Hospital and National Taiwan University
V. Cantoni, R. Green, T. Mannarino, R. Assante, V. Gaudieri, E. College of Medicine, Taipei, TAIWAN, 4Department of Nuclear
Zampella, C. Nappi, G. Agliata, M. Petretta, W. Acampa, A. Cuocolo; Medicine, and Cardiology Division of Cardiovascular Medical
University Federico II, Naples, ITALY. Center, Far Eastern Memorial Hospital, New Taipei City, TAIWAN.

Aim/Introduction: Coronary vascular dysfunction is related Aim/Introduction: Myocardial perfusion imaging (MPI) with
to poor cardiovascular prognosis in patients with suspected or single photon emission computer tomography (SPECT) is a
known coronary artery disease (CAD). We conducted a meta- well-established tool for the diagnosis of coronary artery disease
analysis to evaluate the prognostic value of coronary flow (CAD). Soft tissue attenuation is a common artifact which limits
S347 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

the diagnostic accuracy of MPI. Attenuation artifacts showed of the vessel lumen >50% (and/or fractional flow reserve
different patterns in the three territories supplied by coronary ≤0.80) was considered haemodynamically significant, while
arteries. The aim of this study was to determine whether and how the presence of a stenosis in the left mainstem was considered
attenuation correction (AC) improved diagnostic performance equivalent to a two-vessel disease (angiographic score: 0-3). The
of MPI in different coronary artery supplied territories, using concordance of the software packages with the expert reading
coronary angiography as reference standard. Materials and (mean values) and the angiographic score, was evaluated with
Methods: Pubmed and EMBASE were searched until April 2019 the computation of intraclass correlation coefficients (ICCs) and
for studies evaluating AC MPI for the diagnosis of CAD with Bland-Altman 95% confidence intervals for limits of agreement.
vessel-base data. Methodological quality was assessed using Wilcoxon signed rank test were used to evaluate median
the Quality Assessment of Diagnostic Accuracy Studies tool. For differences, and agreement was further analyzed by comparing
each study, the sensitivity, specificity, diagnostic odds ratio and the categorized by percentiles measures of SSS, SRS and SDS with
area under summary receiver operating characteristic curve, weighted Kappa coefficients. Results: The agreement between
along with 95% confidence intervals (CIs), were calculated to the two observers evaluating MPI studies was very good (ICC
determine the diagnostic accuracy of AC vs. non-attenuation for interrater agreement >0.8 ). ICCs between the three software
corrected (NAC) MPI. A bivariate mixed-effect model was packages and the expert scoring were mainly moderate
applied for pooling the data. Results: Out of 332 articles, 21 to good (ICCs range: 0.41-0.8), but poor for SDS (ICCs<0.4).
studies (2,417 patients) were identified including 18 studies Paired comparisons for SSS, SRS and SDS showed significantly
with data of CAD at patient-level, 20 studies with data of LAD different values for the expert scoring, as compared to the three
and RCA ischemia and 19 studies with data of LCX ischemia. packages (p<0.001). Weighted Kappa coefficients were used to
Significant improvement of specificity (0.77 versus 0.56 in overall compare the agreement of expert scoring with the packages,
CAD, 0.87 versus 0.59 in RCA) and diagnostic odds ratios (16 after categorizing SSS, SRS and SDS in specific intervals defined
versus 8 in overall CAD, 18 versus in RCA) after AC were shown by percentiles. For all comparisons Kappa coefficients were low
in overall CAD and RCA stenosis. Improvement of area under (<0.4), indicating a not acceptable agreement. Furthermore,
summary receiver operating characteristic curve were also Bland-Altman 95% confidence intervals for limits of agreement
noted. MPI showed similar diagnostic performance in detecting were widely indicating that the average discrepancy between
LAD and LCX stenosis with or without AC. There was a trend of the expert scoring and software was large enough. Correlation
decreased sensitivity after AC, but none were significant. Details coefficients of expert SSS, SRS and SDS with angiographic score
of pooled estimates for detecting RCA stenosis were shown in were significant and high (r=0.65 for SSS, r=0.68 for SDS and
the table. Conclusion: The results from this study suggested r=0.42 for SRS, p<0.001), while the correspondence correlation
that attenuation correction should be applied to myocardial between the three packages estimates for SSS, SRS and SDS
perfusion imaging to improve the diagnosis of CAD, especially with angiographic score were low (r<0.3) Conclusion: Expert
in detecting RCA stenosis for better specificity. References: reading correlated significantly better with angiographic results,
None. in comparison to software packages. References: None.

EPS-095 EPS-096
Comparison between computer-based analysis and expert Causative factors of prolonged myocardial ischemic
reading in the interpretation of MPI studies damage shown on hybrid cardiac fatty-acid metabolism
G. Angelidis, V. Valotassiou, S. Alexiou, I. Tsougos, D. Psimadas, C. SPECT/CT in patients with coronary artery disease after
Tzavara, A. Ziaka, E. Baniora, E. Theodorou, C. Ziangas, A. Tzitzani, coronary artery bypass grafting
M. Kournouti, M. Asproudi, P. Georgoulias; Y. Fukushima, Y. Ishii, T. Kiriyama, T. Nitta, S. Kumita;
University Hospital of Larissa, Larissa, GREECE. Nippon Medical School, Tokyo, JAPAN.

Aim/Introduction: Quantitative parameters are widely used Aim/Introduction: Patients with coronary artery disease
in the interpretation of myocardial perfusion imaging (MPI) (CAD) undergoing coronary artery bypass grafting (CABG)
studies. We aim to compare the automated measurements occasionally have prolonged myocardial ischemic damage,
of SSS (summed stress score), SRS (summed rest score), and shown on cardiac fatty-acid metabolism SPECT using 123I-BMIPP.
SDS (summed difference score) using Emory Cardiac Toolbox, However, causes of persistent myocardial ischemic damage
Myovation, and Quantitative Gated SPECT software, with in this population are unknown. Despite their severe CAD
the expert scoring in patients who underwent coronary and complicated hemodynamics, hybrid cardiac SPECT/CT
angiography. Materials and Methods: The sample consisted can provide comprehensive diagnoses, including myocardial
of 143 patients with mean age 63.9 years, who underwent ischemic damage distribution, coronary artery lesion
99mTc-tetrofosmin gated SPECT studies. Each study was blindly distribution, and their relationship. This study aimed to examine
evaluated by two independent observers, and the mean SSS, the causative factors of persistent ischemic myocardial damage
SRS, and SDS values were recorded. One experienced observer using hybrid cardiac fatty-acid metabolism SPECT in patients
blindly interpreted the coronary angiography studies; a stenosis with CAD after CABG. Materials and Methods: A total of 192
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S348

consecutive patients between April 2016 and March 2019, who image resolution and thereby small lesion detection [1]. The use
underwent cardiac rest-stress perfusion SPECT and fatty-acid of 1x1x1 mm3 voxel reconstructions may even further improve
metabolism SPECT using Discovery NM 530c after CABG, were small lesion detection. Our aim was to evaluate the value of
included in this study. Among them, 125 patients who received these ultra-high-resolution (uHR) reconstructions, compared
cardiac CT (CCT) using Revolution CT and hybrid cardiac SPECT/ to high-resolution (HR) 2x2x2 mm3 reconstructions, to improve
CT imaging using CardIQ Fusion were analyzed. On cardiac small lesion detection in patients with cancer. Materials and
SPECT, the myocardial accumulation defect diagnoses were Methods: We included 31 consecutive cancer patients who
determined, and SSS, SRS, SDS, summed BMIPP defect score underwent FDG-PET/CT (Vereos, Philips Healthcare) that revealed
(SBS), and summed perfusion-metabolism mismatch score at least one FDG-avid lesion <6mL. For each FDG-positive
(SMS) were quantified using a 17-segment model with a 5-point- lesion SUVmax, SUVmean and lesion volume were determined,
grading system. Coronary artery segments, including coronary up to a maximum of 5 lesions per patient, in both HR and uHR
artery bypass grafts, were assessed on CCT. With hybrid cardiac images. Furthermore, we determined the noise level in each PET
SPECT/CT images, coronary artery territories were confirmed. image, defined by the ratio of the standard deviation and mean
Furthermore, the regional difference score (RDS) and regional pixel value in healthy liver tissue. In a qualitative analysis two
mismatch score (RMS) in each coronary territory were calculated. expert readers performed a blinded side-by-side comparison
Causative factors for myocardial residual perfusion-metabolism between HR and uHR images. Based on image contrast, noise,
mismatch (RPMM) were examined comparing with patients’ and diagnostic confidence, they stated their preference. In case
clinical and imaging findings. Moreover, the relationships of disagreement, a third expert reader was consulted to reach
between regional coronary artery stenosis, RDS, and RMS were consensus per image. Results: In total 112 FDG-positive lesions
assessed. Results: The interval between CABG and cardiac (volumes: 0.1-5.2mL) were included. Using uHR reconstructions,
SPECT was 17 ± 44 months. The myocardial segment number mean lesion volume decreased from 0.70 to 0.47 mL (33%±26%,
with ischemic myocardial damage was 4 ± 3, and SMS was p<0.001) while both the average SUVmax and SUVmean increased
significantly higher than SDS (6 ± 5 vs. 3 ± 3, p < 0.001). There with 12%±8% (p<0.001). The mean noise level increased with
was no correlation between SMS and the duration from CABG 11%±7% (p<0.001). Visually, there was no significant preference
to cardiac SPECT (p = 1.000). The significant causes of RPMM for either uHR or HR: readers had no preference (4 patients) or
were SDS (p = 0.007), previous myocardial infarction (p = 0.003), only a minor preference for either uHR (15 patients) of HR (12
LVEF (p = 0.023), and concomitant ischemic cardiomyopathy (p patients). Conclusion: With uHR reconstructions, small lesion
= 0.049). RMS was correlated with RDS (p < 0.001) but showed detection is less hampered by the partial-volume effect, resulting
no correlation with regional coronary artery stenosis (p = 1.000). in higher SUVs and decreased lesion volumes as compared
Conclusion: Ischemic myocardial damage, shown by hybrid to HR reconstructions. However, noise levels increased as
cardiac fatty-acid metabolism SPECT/CT, is likely to persist for a well, cancelling out the effect of enhanced uptake values, as
long period due to several causes, such as residual myocardial confirmed by a visual analysis by experts. Hence, we expect that
ischemia, low LVEF, and comorbid ischemic cardiomyopathy in the value of uHR image reconstruction in small lesion detection
patients with CAD undergoing CABG. References: None. with FDG-PET is limited. References: 1. D. Koopman, J. A. Van
Dalen, M. C. M. Lagerweij, H. Arkies, J. De Boer, A. H. J. Oostdijk,
C. H. Slump, and P. L. Jager, “Improving the Detection of Small
1011 Lesions Using a State-of-the-Art Time-of-Flight PET/CT System
and Small-Voxel Reconstructions,” J. Nucl. Med. Technol., vol. 43,
e-Poster Presentation Session 7 - Do.MoRe: no. 1, pp. 21-27, 2015.
Image Reconstruction & Data Analysis

Monday, October 14, 2019, 16:30 - 18:00 Room 133/134 EPS-098


Optimizing Image Reconstruction on Digital PET
E. G. Simons-Winters1,2, D. Koopman1,2, P. L. Jager1, C. H. Slump2, J.
A. van Dalen1;
EPS-097 1
Isala, Department of Nuclear Medicine, Zwolle,
Value of ultra-high resolution reconstructions in small- NETHERLANDS, 2Technical Medicine Centre, University
lesion detection with FDG-PET of Twente, Enschede, NETHERLANDS.
T. J. Gerritse1,2, D. Koopman1,2, A. H. J. Oostdijk1, H. Arkies1, P. L.
Jager1, C. H. Slump2, J. A. van Dalen3;
1
Isala, Department of Nuclear Medicine, Zwolle, NETHERLANDS, Aim/Introduction: PET imaging with digital photon counting
2
Technical Medicine Centre, Enschede, NETHERLANDS, 3Isala, technology is associated with better spatial resolution,
Department of Medical Physics, Zwolle, NETHERLANDS. however, at the expense of increased noise-levels. We aimed
to determine an image reconstruction that provides the best
small lesion detectability without unnecessary noise for FDG-
Aim/Introduction: We know that decreasing the image voxel- PET using a digital PET system. Materials and Methods: We
size to 2x2x2mm3 in FDG-PET reconstructions improves the performed a phantom study with the NEMA image quality
S349 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

phantom and micro-phantom (sphere diameters: 4-37 mm) staging in comparison to OSEM. Materials and Methods:
using a digital PET system (Vereos PET/CT, Philips Healthcare). We retrospectively analyzed 70 18F-FDG PET/CT studies of
We used 2x2x2 mm3 voxels and compared six different OSEM 33 females and 37 males with the diagnosis of lymphoma,
reconstruction settings (51, 45, 39, 34, 26 and 21 updates performed between the years 2015-2018. Our group included
(=iterations x subsets)). For every setting, the effect of applying 34 patients with Hodgkin lymphoma and 36 patients with non-
no filter and post-smoothing Gaussian filters of 2 and 4 mm was Hodgkin lymphoma. The median age was 46.5 and (range: 6 to
determined as well. Noise-levels were calculated by dividing the 84 years). The routine 18F-FDG PET/CT images were obtained
standard deviation to mean pixel value in a background area using Discovery IQ scanner (GE Healthcare). The PET scans were
of the NEMA-phantom. Furthermore, we determined contrast reconstructed using two different algorithms with the same
recovery coefficients based on the mean activity (RCmean) and normalisation correction factors and with CT-based attenuation
maximum activity (RCmax) in all spheres in both phantoms. In correction. Penalisation factor (beta) of 350 was used for Q.Clear
the patient study, the reconstruction settings providing the reconstruction algorithm. For both algorithms lymphoma
lowest noise-levels without impairing RCs, were tested on FDG- staging was performed using modified Ann Arbor 4-stage
PET scans of patients with breast cancer (n=5) and lung cancer system. Additionally SUVmax values of mediastinal blood pool
(n=19). We measured SUVmax and SUVmean of 81 FDG-avid lesions (MBPS), liver and lesion with the highest metabolic activity -
and noise-levels in the liver. Results: In the phantom study, the target lesion were measured and compared. Results: Of total
highest noise was found for 51 updates without filtering. Noise 70 PET/CT initial studies, 69 were concordant with regard to the
decreased with 14% for 45 updates and 22% for 39 updates stage. Only in 1 study, the Q.Clear algorithm increased the stage
(p<0.01). RCmean and RCmax were similar for those reconstructions from 1 to 2. The staging difference was not statistically significant
(p>0.12). By further reducing the number of updates, both (p=0.31). In all 70 studies, SUVmax values measured in the target
noise and RCs decreased, especially for the smaller spheres. For lymphoma lesions were higher when measure with Q.Clear.
all updates, applying a 2 mm filter resulted in decreasing noise SUVmax values of MBPS measured with Q.Clear where higher
levels (9-19%, p≤0.03) and decreasing RCs (3-4%, p<0.01). A 4 than measured with OSEM in 20/70 and lower - in 26/70 cases.
mm filter led to a noise reduction of 14-39% (p≤0.03) and a RC In the remaining 24/70 cases SUVmax values were equal with
decrease of 10-12% (p<0.01). Consequently, on patient data both algorithms. The SUVmax values of the liver were higher
we applied 51, 45 and 39 updates without filtering. Noise-level with Q.Clear in 21/70 cases, lower - in 32/70 and equal - in 17/70
decreased with 6% for 45 updates and with 13% for 39 updates cases. Conclusion: In spite of the influence of Q.Clear on the
when compared to 51 updates (p<0.01). For all lesions (size: SUVmax values of target lesions and reference regions, the use
0.1-8.1 mL), SUVmean and SUVmax were similar between updates. of this reconstruction algorithm has no impact on lymphoma
Conclusion: Adequate image quality for a digital PET system staging. References: None.
using the OSEM reconstruction algorithm requires a limited
number of updates. The lowest noise-level without impairing
small lesion detectability can be obtained using 2x2x2 mm3 EPS-100
voxels with 3 iterations x 13 subsets (39 updates) without Feasibility of Ra-224 SPECT/CT imaging in a therapeutic
post-smoothing filter. Post-smoothing filtering only results in a setting —a phantom study
reversed effect. References: None. C. Stokke1,2, L. Mikalsen1, T. Bønsdorff3, Ø. Bruland1,4,3;
1
Oslo University Hospital, Oslo, NORWAY, 2Oslo
Metropolitan University, Oslo, NORWAY, 3Oncoinvent AS,
EPS-099 Oslo, NORWAY, 4University of Oslo, Oslo, NORWAY.
The impact of Q.Clear reconstruction algorithm of 18F-FDG
PET on the staging of lymphoma
M. Wyrzykowski1, R. Czepczyński1,2, M. Ruchała3; Aim/Introduction: In preparation for an upcoming clinical trial
1
Dept. of Nuclear Medicine Affidea, Poznan, POLAND, using Ra-224 in dosages from 1 to 7 MBq, we have evaluated the
2
Poznan University of Medical Sciences, Poznań, POLAND, possibility for direct SPECT/CT imaging of the agent’s distribution.
3
Poznan University of Medical Sciences, Poznan, POLAND. The principle emitter of imageable gamma is Pb-212, but other
nuclides, including Ra-224 itself, also contribute. There are also
high and very high energy photons up to 2615 keV from Tl-208,
Aim/Introduction: Q.Clear is a Bayesian penalized-likelihood which scatter in the collimator and patient bed and decrease
reconstruction algorithm for PET that was implemented by GE contrast, making an optimized protocol important. Materials
Healthcare on their new scanners. Q.Clear allows to achieve and Methods: Using the NEMA IEC PET Body Phantom without
more effective convergence in images that results in more the lung insert, the phantom spheres were filled with Ra-224-
accurate standardized uptake value (SUV) measurement. RaCl dissolved in an EDTA solution. 28 kBq/ml at the time of
Previously Q.Clear has been shown to be superior to ordered scan (total activity 1.36 MBq) and no background activity was
subset expectation maximization algorithm (OSEM) in used. Imaging was performed on a Siemens Symbia Intevo Bold
phantom studies, as well as in liver metastates, lung nodules SPECT/CT system using high energy (HE) and medium energy
and mediastinal lymph nodes in lung cancer. The aim of the (ME) collimators and a 20 % energy window at 240 keV, with
study was to determine whether Q.Clear influences lymphoma dual 5 % scatter windows, 60 views and a 30 min acquisition
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S350

time. Reconstructions were performed using the Flash3d and scattering, PET, and others).The uncertainty of the reconstructed
the Tomo Reconstruction workflow, with 16mm Gaussian post PET image was improved by applying an analytic correction in
filters and CT-based attenuation correction. Datasets were the reconstruction of each line of response (LOR) based on the
reconstructed with and without scatter, using 20 mm Gaussian time-of-flight (TOF) information, along with attenuation and
filter on the scatter windows. Reconstructions were performed scattering probabilities.The PET scanner geometry used in this
at 25 different levels; from 5 to 900 iterations x subsets. The study resembled the PET component of the Whole Gamma
visibility of a lesion was defined as having a local maximum. Imaging (WGI) detector from NIRS-QST (16x16x4-DOI array
Results: The image quality obtained indicate that we can detect of 2.8x2.8x7.5mm3GSO, in four rings with 66cm diameter). A
accumulations of the agent as low as 14 kBq (activity of smallest spherical PMMA phantom with 5cm radius was used in this
sphere). Imaging is possible using both collimators; however, work. The performance of the MEGAlib in the reconstruction
ME was preferable due to a higher degree of visibility of the two of PET events was investigated by considering the accuracy
smallest spheres. Still, the HE collimator did have greater contrast of the TMVA machine-learning algorithm and performance
for the two largest spheres. Scatter correction was found to of TOF and attenuation-scattering corrections. Results: The
increase the contrast of the four largest spheres relative to their accuracy of the TMVA machine learning has been found to be
immediate surroundings, but reduce the visibility of the two 90%. Implementation of the TOF information into the PET image
smallest spheres. In general, the reconstructions benefited from reconstruction could improve the signal-to-noise ratio (SNR) of
relatively high numbers of updates, approximately 30 to 100. the PET images up to 88% for a coincidence time resolution of
With the employed level of post filtering, artefacts in the sphere 500ps. Comparing the detected PET photons of a point positron
shapes were not observed. Conclusion: Imaging of relatively source positioned inside a PMMA phantom and air at the
low activities of Ra-224 is feasible. Overall, we recommend center of the PET scanner revealed that using the attenuation-
the use of the ME collimator on this system. For small uptakes scattering corrections could significantly improve the signal lost
nearby high activity regions, attenuation correction only may inside the PMMA phantom by up to 64%. Conclusion: This study
be preferable, but in general the combination of attenuation showed that the upgraded MEGAlib software could be used as a
and scatter correction seems to provide higher contrast. promising simulation and image reconstruction framework for
(Mikalsen LTG, Bønsdorff T, Bruland ØS, Stokke C.) References: PET imaging, which in combination with its proven capabilities
None. in the context of Compton imaging makes it a valuable toolkit to
facilitate research projects for PET, PG imaging, and novel hybrid
detection schemes in ion therapy monitoring. References:
EPS-101 None.
Development of a Novel Simulation and Image
Reconstruction Toolkit for PET and PG Imaging
M. Safari1, A. Zoglauer2, G. Lovatti1, V. Anagnostatou1, M. Nitta1, H. EPS-102
Tashima3, P. Thirolf1, T. Yamaya3, K. Parodi1; Impact of reconstruction settings and respiratory motion
1
Ludwig-Maximilians-Universität München, Munich, GERMANY, correction strategies on image quality and quantitation
2
Space Sciences Laboratory, University of California, Berkeley, with 68Ga in phantom studies
CA, UNITED STATES OF AMERICA, 3National Institute of T. Q. Christensen1, P. Braad2;
Radiological Science, National Institutes for Quantum and 1
Department of Clinical Engineering, Region of Southern
Radiological Science and Technology (QST), Chiba, JAPAN. Denmark, Esbjerg, DENMARK, 2Department of Nuclear
Medicine, Odense University Hospital, Odense, DENMARK.

Aim/Introduction: Positron emission tomography (PET)


imaging of the beta+-activity induced during ion beam therapy Aim/Introduction: Respiratory motion causes blurring in PET/
is one of the most clinically investigated methods for 3D in-vivo CT and inaccurate quantitative values. Neuroendocrine tumors
ion range verification. Along with the rapid improvements in the (NETs) are often detected in the lung and liver, areas with a high
capabilities of detectors and in-beam PET systems, the necessity degree of respiratory motion. Diagnosis of NETs are frequently
of using more reliable simulation software with dedicated done with 68Ga-radiopharmaceuticals. We designed a phantom
analysis tools for spatial reconstruction of the PET-like positron- study to study the impact of reconstruction settings and
annihilation radiation and prompt gamma-ray (PG) emission is respiratory motion correction strategies on image quality and
becoming more important. In this study the Medium-Energy quantification in lung and liver lesions in 68Ga-PET. Materials
Gamma-ray Astronomy library (MEGAlib) has been further and Methods: A NEMA/IEC torso phantom with six fillable
developed in order to use this toolkit as a standard simulation spherical inserts with diameters ranging between 10 and
and image reconstruction framework for PET imaging in 37 mm was filled with a homogeneous aqueous solution of
addition to its established features for PG imaging. Materials 68
Ga and scanned on a GE Discovery MI (GE Healthcare) PET/
and Methods: The MEGAlib software was equipped with the CT scanner at lesion-to-background ratios (LBRs) of 2.5:1, 5:1
Toolkit for Multivariate Analysis (TMVA), which provides a ROOT- and 10:1. Acquisition times and background concentrations
integrated machine-learning environment for a better and corresponded to typical liver concentrations in clinical 68Ga-
more accurate classification of various event types (Compton DOTATOC PET-scans. Reconstructions were done using block
S351 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

sequential regularized expectation maximization (BSREM) at filter. Two expert readers visually evaluated the image quality
penalization values (β) of 300-1000. Contrast recovery (CR), of the 80 reconstructions by ranking the 4 reconstructions per
background variability (BV) and contrast-to-noise ratios (CNR) scan. For quantitative assessment, we measured SUVmax of the
were compared. The impact of respiratory motion correction thyroid remnants and signal-to-noise ratio (SNR=SUVmax/σ),
was studied in the CIRS Dynamic Thorax Phantom with movable where σ was defined by the standard deviation in a background
spheres of 0.5, 2.5 and 8 ml. PET scans were performed without area above the lungs. Results: The smooth standard-voxel
background activity in lung equivalent tissue and at LBRs of reconstruction was preferred above the other reconstructions
2.5:1, 5:1, and 10:1 of aqueous 68Ga solutions while spheres for both the 24h and 96h scans. The quantitative analysis (24h
were moved with patient-like respiratory motion patterns at scans) showed that the average SUVmax increased from 5.4
amplitudes of 0, 5, and 10 mm respectively. The impact of GE’s (smooth standard-voxel) to 5.8 (non-smooth standard-voxel)
motion correction methods Q.Static and Q.Freeze on lesion to 10.8 (smooth small-voxel) to 11.6 (non-smooth small-voxel)
detectability, lesion size, and lesion activity quantification was (p<0.01). However due to increased noise levels, the average
analyzed. Results: With increasing β values a small decrease in SNR decreased from 76 on smooth small-voxel images to 47,
CR was seen with an average relative difference from β=300 to 52 and 46 for the other three reconstructions respectively
β=1000 of -8.1% (-19.2 to -1.9) and a bigger decrease in BV of (p<0.01). For the 96h scans we found similar quantitative trends.
-32.8% (-46.9 to -18.9) which lead to an improved CNR of 37.5% Conclusion: Smooth standard-voxel reconstructions provide
(19.1 to 69.9). The results were confirmed qualitatively although the best visual and quantitative assessment of lesions with
differences in the images were not apparent at values of 700 I-124 PET. For each radiopharmaceutical, evaluation of different
and above. The image quality and quantitative accuracy were reconstruction settings is required for optimized PET imaging.
greatly improved with Q.Freeze at all motion displacements References: Koopman D. et al. Improving the detection of small
and LBRs. Q.Static showed improvements at the highest motion lesions using a state-of-the-art time-of-flight PET/CT system
displacement amplitudes but not significantly at 5 mm and and small-voxel reconstructions. J Nucl Med Technol 2015.
below. Conclusion: Optimization of the reconstruction and
the use of respiratory motion strategies can improve the image
quality and quantitative accuracy of 68Ga PET/CT scans. A high EPS-104
BSREM β value increases image quality at a small expense of Value of Non-TOF Reconstruction from TOF Compressed
quantitative accuracy. Q.Freeze seems favorable in all situations Data for High Resolution TOF Scanner
and Q.Static in most. References: None. V. Panin;
Siemens Medical Solutions USA, Knoxville,
TN, UNITED STATES OF AMERICA.
EPS-103
Optimizing image reconstruction for lesion assessment
with I-124 PET Aim/Introduction: The new Siemens Biograph Vision PET/
D. Koopman1,2, I. M. Spenkelink1,2, P. L. Jager1, H. Arkies1, C. H. CT scanner provides both improved spatial resolution and
Slump2, J. A. van Dalen3; improved TOF resolution by about 210 ps. Although raw Vision
1
Isala, Department of Nuclear Medicine, Zwolle, NETHERLANDS, data are significantly increased in size, good TOF resolution
2
Technical Medicine Centre, Enschede, NETHERLANDS, 3Isala, allows their substantial compression in the azimuthal and
Department of Medical Physics, Zwolle, NETHERLANDS. polar angle dimensions without a loss of spatial resolution.
While the so-called histo-projection format was developed
solely for TOF reconstruction, pseudo non-TOF reconstruction
Aim/Introduction: Iodine-124 (I-124) PET/CT scans are from these data is still possible. TOF reconstructions are very
performed in follow-up of patients treated for differentiated sensitive to the time calibration errors. We developed a non-TOF
thyroid carcinoma. For FDG-PET, it has been shown that reconstruction, which is unaffected by the time calibrations, as
decreasing the image reconstruction voxel-size from 4x4x4 mm3 a tool used in the object-based timing calibration approach
to 2x2x2 mm3 improves the image resolution and thereby small to obtain accurate time alignment in high performance, high
lesion detection [1]. It is unknown if small voxel reconstructions time resolution PET scanners. Materials and Methods: TOF
are beneficial for I-124 PET as well. Different reconstruction compressed data are additionally compressed over the TOF
settings may be preferred due to the low-count statistics of dimension to generate pseudo non-TOF data. Since correction
I-124 PET. Our aim was to optimize the image reconstruction for factors are TOF dependent, non-TOF reconstruction will require
lesion assessment with I-124 PET. Materials and Methods: We modification of the update equation in the commonly-used
included 10 patients who were treated for thyroid cancer and OSEM algorithm, which stays TOF intrinsically. In the analytical
underwent PET/CT imaging (Ingenuity TF, Philips Healthcare) 3D DIFT algorithm, convergence into the non-TOF format
24h and 96h after administration of 74 MBq I-124. All patients is performed in the Fourier domain by using only part of the
had thyroid remnants and/or metastases visible on PET. Images available data. The NEMA IQ phantom and its various degree,
were reconstructed 4 times using two voxel-sizes (standard post-smoothed reconstructions were used in construction of
4x4x4 mm3 and small 2x2x2 mm3) and two relaxation settings the smallest sphere (10 mm diameter)-to-background value
(0.5 and 1.0), indicating a smoothing and a non-smoothing ratio versus background variability trade-off curve. Additionally,
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S352

uniform cylinder data were produced with detector timing were found for BPLR compared to HDAC OSEM for active lesions.
residual offsets of about 40ps when an approximate time The significant improvements in CNR with BPLR over OSEM
calibration procedure was used and with the most exact time did not consistently accompany improvements in detection.
alignment procedure. Results: At the same noise level, small Conclusion: BPLR was found to provide superior small ‘hot’
sphere recovery was reduced by more than 10% in non-TOF lesion detection when compared to a more conventional
analytical reconstruction. A relatively small misalignment HDAC OSEM approach. No advantages were found for the
produces detectable bias in the TOF uniform cylinder detection of ‘cold’ lesions. Collectively these results indicate a
reconstructed image, in the form of image non-uniformity of superior performance of BPLR over HDAC OSEM. These gains,
more than five percent. Both iterative and analytical algorithm however, do not appear to be universal for all simple detection
non-TOF reconstructions from the same cylinder data do not tasks. Furthermore, in this case more conventional measures of
reproduce this TOF image non-uniformity. This property can be estimating quality gains, such as CNR, were shown to not directly
used to correct time offsets during the scanner time calibration, map onto the performance of these visual tasks. References:
and allows for accurate time calibration. Conclusion: Pseudo None.
non-TOF reconstruction from TOF compressed data is inferior to
TOF reconstruction in bias noise trade-off, but it is insensitive to
the time alignment imperfections. References: None. EPS-106
NEMA NU 2-2007 Measurements and GATE Monte Carlo
Simulations of GE Signa integrated PET/MR for Pure and
EPS-105 Non-Pure Positron Emitters
Detectability of small objects in positron emission P. R. R. V. Caribe1, M. Koole2, A. Diogo3, Y. D’Asseler1, T. Deller4, S.
tomography/ computed tomography images with Vandenberghe1;
Bayesian penalized likelihood reconstruction 1
Medical Imaging and Signal Processing – MEDISIP Ghent
M. Macnab1, T. J. Biggans2, F. I. Mckiddie1, M. I. Pether1, J. B. University, Ghent, BELGIUM, 2Division of Nuclear Medicine and
Straiton1, R. T. Staff1; Molecular Imaging – UZ/KU Leuven, Leuven, BELGIUM, 3Faculty
1
NHS Grampian, Aberdeen, UNITED KINGDOM, of Sciences of the University of Lisbon, Lisbon, PORTUGAL, 4GE
2
NHS Tayside, Dundee, UNITED KINGDOM. Healthcare, Waukesha, WI, UNITED STATES OF AMERICA.

Aim/Introduction: This study investigated the small lesion Aim/Introduction: NEMA characterization of PET systems
(3mm-7mm) visual detection gains brought about by is generally done with 18F. However, other PET isotopes such
Bayesian penalized likelihood reconstruction (BPLR) (Q.Clear, as 68Ga and 90Y are gaining clinical importance as they are of
GE Healthcare) in positron emission tomography/ computed specific interest for oncological applications and for follow up
tomography (PET/CT) phantom images when compared to of radionuclide therapy. However, the physical properties of
a more conventional high definition attenuation corrected these PET isotopes are quite different and there may be a larger
ordered subset maximisation (HDAC OSEM) reconstruction interference with the magnetic field of the MR compared to 18F.
(Vue Point HD, GE Healthcare). Materials and Methods: Therefore, it is relevant to determine the performance of PET/
Lesions within a phantom were constructed using insoluble MR for those clinically relevant and commercially isotopes.
putty, removing the requirement for Perspex walls usually used Materials and Methods: The aim was divided into two parts:
to separate different compartments. This design eliminated the (1) NEMA NU 2-2007 tests were performed for characterizing
partial volume effects brought about by these compartmental the spatial resolution (SR), sensitivity, image quality (IQ) and
walls in conventional phantoms. 70 inactive and 93 (18F) active NECR for 18F, 68Ga, and 90Y. NECR was performed using 18F and
lesions, with diameters of 3mm, 5mm or 7mm were suspended 68
Ga. (2) Modelling of a realistic GATE Monte-Carlo model of
in active backgrounds at varying contrast ratios (2:1 to 32:1) the GE Signa PET/MR to investigate the Sensitivity, NECR and
within a NEMA 2012 phantom. PET/CT images were acquired the effect of the 3T MR field on positron range using 18F, 11C,15O,
with a GE Discovery 710 and reconstructed using both BPLR 13
N, 68Ga and 82Rb. These simulated results were compared
with a penalization coefficient of 400 and HDAC OSEM (2 with the NEMA measurements. Results: NEMA tests for 18F, 68Ga
iterations, 24 subsets). Images were presented to three blinded and 90Y resulted in substantially different system characteristics.
experienced observers, who were asked to identify lesions and The SR is about 1mm larger in the axial direction (compared
assign confidence ratings. These responses were used to create to18F). The impact of this lower resolution is also visible in the
free receiver operator characteristic (FROC) and alternative FROC recovery coefficients of the smallest spheres of 68Ga in IQ tests,
curves. Image contrast to noise ratio (CNR) for lesions with each where clearly lower values are obtained compared to 18F. The
reconstruction was found for comparison. Results: Moderate differences in sensitivity are due to the scale factor from the
visual detection gains were seen for active, ‘hot’, lesions with positron emission fraction of the isotopes. The peak NECR was
BPLR over OSEM. When split by subset, these improvements lower than for 18F and appears at higher activities. The peak
were significant for 5mm and a lesion to background ratio of NECR were: 216.8, 217.6, 212.0, 216.4, 207.1 and 173.5 kcps for
8:1. No significant differences were seen for the identification of F, C, 15O, 13N, 68Ga and 82Rb respectively. The positron range is
18 11

inactive, ‘cold’, lesions of any size. Significantly higher CNR values a tissue-dependent and reduces in the x/y-direction by a factor
S353 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

3-4 when compared to z-direction for the higher positron energy for efficient training of CNN. Our work shows that by relying on a
emitters. Comparing to the measurements, the detectability of two-step approach these requirements can be in part alleviated.
this transversal reduction was affected by the spatial resolution Further experiments are ongoing to improve the accuracy of
of the system. Conclusion: The system performance of GE the prediction as well the tumor detection with the addition of
Signa integrated PET/MR was substantially different, in terms the PET component in case of PET/CT scans. References: None.
of NEMA SR, IQ and NECR for 68Ga compared to 18F. For 90Y
the resolution is comparable to 68Ga and the low number of
counts leads to a large variability in the IQ measurements. The EPS-108
transversal direction is significantly affected by the 3T MR field Fuzzy Radiomics: A novel approach to minimizing the
and the spatial resolution of the system is limited to detect this effects of target delineation on radiomic models for PET
reduction. References: None. L. Papp1, I. Rausch1, M. Hacker2, T. Beyer1;
1
QIMP team, Center for Medical Physics and Biomedical
Engineering, Medical University of Vienna, Vienna,
EPS-107 AUSTRIA, 2Division of Nuclear Medicine, Medical
Relying on deep convolutional neural networks on PET/ University of Vienna, Vienna, AUSTRIA.
CT images for stage II and III non-small cell lung cancer
outcome prediction
M. Ibrahim1, D. Visvikis1, C. Cheze Le Rest2, M. Hatt1; Aim/Introduction: In-vivo characterization of tumours with
1
Laboratory of Medical Information Processing, Brest, radiomic features from Positron Emission Tomography (PET)
FRANCE, 2CHU MIlitaire, Poitiers, FRANCE. imaging is currently of great interest to clinical researchers.
However, the different lesion delineation approaches
significantly affect radiomic models. Here, we seek to integrate
Aim/Introduction: To design a deep convolutional neural fuzzy logics into the process of radiomics feature extraction in
network based workflow for non-small cell lung cancer (NSCLC) order to address uncertainties arising from variations in lesion
outcome fully automated prediction, i.e. without the need delineation. Materials and Methods: PET images from NEMA
for tumor segmentation, as is usually required for radiomic IQ studies performed on 13 PET/CT systems [1] were included.
analyses. Materials and Methods: Several modified versions In each PET the largest sphere (d=37mm) was delineated with
of 3D deep convolutional neural networks (CNN, e.g., C3D and two automated approaches to generate 3-dimensional binary
Inception) were evaluated using computed tomography (CT) volumes-of-interest (VOI) masks: the first method built on
images as input. The proposed workflow is divided into two dichotomized fuzzy clustering (DFC), while the second method
modules. The first consists of a primary tumor detector relying employed gradient maximization (GM) to identify optimal
on a 3D CNN trained on two publicly available datasets of CT boundaries of lesions. In addition, a third approach, a fuzzy
scans (1397 and 888 patients) with or without lung nodules/ delineation (FD) was executed, which provided a non-binary
tumors (not necessarily NSCLC). This CNN was also trained to probability VOI mask over the largest sphere. Thirteen radiomic
classify the detected lesion as normal or cancerous. This trained features with <20% multi-centric variations [2] were extracted
tumor detector was then evaluated in 3 different cohorts of from the DFC, GM and FD VOI masks in each of the 13 PET
patients with NSCLC (110, 422 and 61 patients). The goal is to images. The binary VOI masks were used for classic radiomics
feed only the image region containing the primary tumor to calculations that considered binary membership of voxels, while
a second CNN trained specifically for outcome prediction. We the fuzzy VOI mask was used for modified radiomics calculations,
assumed that training would be more efficient if the CNN can handling non-binary probability membership voxel values.
focus on the primary tumor only instead of the whole image. Coefficients-of-variation (CoV) were calculated for each feature
Two different methods were compared to design this second and delineation method across the 13 PET. Finally, the mean
module: first, a modified version of the 3D CNN used in the of the feature CoVs across features was calculated to describe
first module (detector) with transfer learning using the tumor the average multi-centric variation of each delineation method.
region as input. Second, we created 8×8 tiles where each tile Results: The mean CoV across all features of the fuzzy mask (FD)
has the size of 64×64 pixels as 2D input representing the entire was 21%, compared to 37% (DFC) and 63% (GM). Conclusion:
3D region containing the tumor as a training data and ability to Fuzzy radiomics appears to be a promising approach to minimize
classify patients below or above the median overall survival in variations of radiomic features in a multi-centric environment
the three NSCLC cohorts was evaluated. Results: The accuracy compared to the selected binary delineation methods, thus,
of the trained CNN for differentiating normal from cancerous supporting efforts towards reproducible quantitative radiomics
nodule in the two lung CT scans datasets was 86%. It was in large data cohorts. References: 1. Rausch I., et al; Variation of
able to correctly detect the primary tumor in 70% of patients, system performance, quality control standards and adherence
detected only partial areas of the tumor in 30% of patients and to international FDG-PET/CT imaging guidelines. A national
failed for the remaining 10% patients. The best accuracy for survey of PET/CT operations in Austria. Nuklearmedizin
outcome prediction for patients with tumor correctly detected 2014;53(6):242-248 2. Papp L., et al: Optimized feature extraction
by the first module was 70% using 2D networks. Conclusion: for radiomics analysis of 18F-FDG-PET imaging. JNM 2018,
The availability of large datasets is usually a crucial requirement 10.2967/jnumed.118.217612.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S354

EPS-109 EPS-110
Towards automated whole-body MTV/TLG calculation A Deep Learning Model to Predict a Classification of Tc-
using artificial intelligence uptake classification 99m ECD SPECT of the Brain by Using Different Pre-trained
C. Von Gall, D. Thomas, L. Sibille, V. Shah, B. Spottiswoode; Models
Siemens Medical Solutions USA Inc, Knoxville, Z. Lin1, F. P. Tseng1, Y. C. Ni1, P. Y. Chiu2, G. U. Hung3, M. C. Pai4;
TN, UNITED STATES OF AMERICA. 1
Institute of Nuclear Energy Research, Taoyuan, TAIWAN,
2
Show Chwan Memorial Hospital, Changhua, TAIWAN,
3
Chang Bing Show Chwan Memorial Hospital, Changhua,
Aim/Introduction: Whole-body Total Lesion Glycolysis TAIWAN, 4National Cheng Kung University, Tainan, TAIWAN.
[TLG] and metabolic tumor volume [MTV]-based therapy
assessments using Fluorodeoxyglucose [18F-FDG] are gaining
clinical interest. However, such measurements are tedious to Aim/Introduction: To develop an aggregation algorithm
perform in cases with a large number of findings. The aim of that predicts the classification of Alzheimer disease (AD) and
this work was to investigate workflow improvements offered normal cognition at Tc-99m ECD SPECT of the brain by using
by an Artificial Intelligence (AI) algorithm which classifies small dataset and different pre-trained models. Materials and
uptake in 18F-FDG PET/CT scans. Materials and Methods: An Methods: In Taiwan, dementia population was about 270,000
existing convolutional neural network [CNN] trained to classify people at the end of 2017, with a prevalence of about 8 percent.
uptake in PET/CT as physiological or non-physiological [1] was There is an ongoing program to collect Tc-99m ECD SPECT
augmented with ~120,000 physiological findings generated images from AD, DLB, VaD and age-various control subjects.
by applying multiple SUV thresholds. The training data was First in order to neglect the deviation between different centers,
limited to lung cancer and lymphoma patients scanned the images in this study were chosen from one hospital. The
with 18F-FDG on two scanner types. This study evaluates the images of 53 AD patients and 32 healthy people (from 2014
refined CNN on 181 independent PET/CT datasets (not used to 2019) were collected. Final clinical diagnosis was recorded.
for training or testing the AI algorithm) consisting of lung The pre-trained models including InceptionV3, Xception,
cancer, lymphoma, melanoma, colorectal and other cancer DenseNet121, ResNet50 and VGG16 and were fine-trained on
types [27.1%, 26%, 9.4%, 4%, 24.3%]. In 9.4% the underlying 93 % of the dataset and tested on the remaining 7%. After each
disease was not available. Data was acquired on Biograph model has been fine-trained, final predictions were based on
TruePoint, mCT, Horizon and Vision PET/CT scanner generations the aggregated testing results of the fine-trained models and
(4%, 19%, 57%, 20%)(Siemens Medical Solutions USA, Inc.) analyzed with F1 score for performance evaluation. Results:
Findings were identified using PERCIST recommendations The F1 scores were 0.67, 0.57, 0.86, 0.86 and 0.8 for InceptionV3,
(SUVpeak>1.5*liverSUVmean+2SDs) and segmented using 42% Xception, DenseNet121, ResNet50 and VGG16 respectively. And
of SUVmax. All findings were reviewed by two experienced the F1 score of the aggregation algorithm is 0.86. The F1 score of
nuclear medicine physicians [CvG, DT], who were blinded to the aggregation algorithm was highest as the one of ResNet50
the disease type and patient history. If required, additional seed- and VGG16. Conclusion: By using limited data from Tc-99m
point-based segmentations were added manually. All findings ECD SPECT of the brain, different models of architecture with
were classified by the CNN, and manually corrected if necessary. fine-training achieved various performance results. However,
Analysis was performed for findings where both readers agreed, the aggregation algorithm achieved better results and avoided
and workflow improvements were assessed by the number of worse performance from choosing a model improperly.
manually added findings and classification corrections. Results: References: None.
A total of 5744 findings were identified resulting in an average
of 31.7±27.5 (mean±stdev) total findings per patient of which
5.7±11.8 were non-physiological. Manually added findings and EPS-111
characterization changes per patient were 0.4±1.2 and 0.4±1.0, Integrating respiratory gating into PET/CT and PET/MR:
respectively. Conclusion: AI assisted PET/CT analysis can evaluating an improved clinical workflow
optimize complex workflows to facilitate whole-body MTV/TLG E. Solari, C. Kruschke, S. Schachoff, B. Bogdanovic, A. Winter, M.
measurements. This approach enables whole body MTV/TLG to Mustafa, W. Weber, S. G. Nekolla;
be calculated with an average of 0.8 clicks per patient compared Klinik der Nuklearmedizin, Klinikum rechts
to creating 5.7 manual segmentations, an 86% reduction in der Isar, TUM, München, GERMANY.
manual clicks.However, interobserver disagreement may bias
the workflow impact and additional sub-analysis is warranted
to confirm the overall improvements. References: 1.Sibille et Aim/Introduction: Respiratory motion correction (RMC) is
al. PET Uptake Classification in Lymphoma and Lung Cancer available on PET/CT and PET/MR systems to improve diagnostic
using Deep Learning, Proc. SNMMI, Philadelphia, (2018)2. Wahl, accuracy by reducing motion blurring. However, increased
R. et al. From RECIST to PERCIST: Evolving Considerations for PET scan times and logistical overhead hinder its widespread
Response Criteria in Solid Tumors. J Nucl Med 50, 122S-150S clinical use. Therefore, we investigated whether an integration
(2009). with continuous bed motion (CBM) scanning addresses
these limitations for PET/CT, and if similar results could be
S355 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

achieved with PET/MR that does not allow CBM. Materials among all packages, were extracted: 4 conventional: Metabolic
and Methods: Patients undergoing [18F]-FDG (n=20) and Tumor Volume, SUVmax, SUVmean, SUVstd; 3 histogram-based
[18F]-PSMA (n=8) PET/CT examinations were scanned with features: Skewness, Kurtosis, Entropy; 6 grey level co-occurrence
CBM and a respiration monitor belt (RMB). As reference, [18F]- matrix (CM) features: HomogeneityCM, EnergyCM, CorrelationCM,
PSMA PET/MR examinations (n=9) were acquired with a long ContrastCM, EntropyCM, DissimilarityCM; 11 grey level run-length
(15 min) single-bed-position pelvis acquisition protocol with matrix (RLM) features: SRERLM, LRERLM, LGRERLM, HGRERLM, SRLGERLM,
RMB. CBM PET scan speed was reduced from 1.1 mm/sec to 0.5 SRHGERLM, LRLGERLM, LRHGERLM, GLNURLM, RLNURLM, RPRLM; 11
mm/sec during half of the scan area, with 40% duty cycle. For grey level size-zone matrix (SZM) features: SZESZM, LZESZM,
PET/MR, 40% and 50% duty cycle corrections were compared. LGZESZM, HGZESZM, SZLGESZM, SZHGESZM, LZLGESZM, LZHGESZM,
Complete and expiration phase images were compared using GLNUSZM, SZNUSZM, ZPSZM, and 3 neighbourhood grey level
a three-point score (poor, sufficient, good) for signal to noise difference matrix (NDM) features: CoarsenessNDM, ContrastNDM,
ratio (SNR) and definition of kidney and lesions. Quantitative BusynessNDM. Finally, the texture features collected by the three
comparisons included liver and bladder ROI (5cm radius sphere) software packages were analysed and compared. To evaluate
SNR, as well as lesion statistics: mean, standard deviation (SD), the agreement among texture features across packages a non-
lesion volume (40% iso-contour VOI). Results: We observed parametric Kruskal-Wallis test was used. Differences in radiomic
reduced scores in overall background SNR (2.4 vs 2.9) but features between each couple of software packages were
increased visual definition of lesions (2.6 vs 2.1) and kidneys assessed using a subsequent Dunn test. Correlation between
(3.0 vs 2.3). The quantitative analysis confirmed a reduced SNR texture features was assessed via Spearman coefficient (r).
in liver on RMC images (4.8±2.6 vs 7.8±1.3 for FDG, 5.0±1.2 vs The Bonferroni correction for multiple comparisons and a
8.8±1.5 for PSMA). An overall reduction in tumor volume was significance level of .05 were used for all the tests. Results:
achieved (ΔVmean[%]= -9.85 ±18.39), most significantly in Metabolic Tumor Volume, SUVmax, SUVmean, and SUVstd showed a
liver (-26.8±19.7) and lung (-15.8±18.7) lesions, and smaller in good agreement across the three software. For the histogram-
abdominal (-6.2±9.8) and prostate (-2.0±4.1) lesions. For PSMA based features, the agreement was good for Skewness and
PET/MR studies, most lesions were located in the prostate. The Kurtosis. For high-order features, a good agreement was
SNR in bladder was smaller on RMC images (40% RMC: 4.5±0.7; found for: HomogeneityCM, ContrastCM, and DissimilarityCM;
50% RMC: 5.1±0.8; NO RMC: 6.9±1.0), whereas lesion size [%] in HGRERLM, SRHGERLM, LRLGERLM, GLNURLM, and RLNURLM; SZESZM,
prostate was slightly reduced (-0.7±8.7 for 40% RMC, -4.4±11.8 LZESZM, HGZESZM, SZHGESZM, LZHGESZM, GLNUSZM, and SZNUSZM;
for 50% RMC), similar to the results for PET/CT. Conclusion: The CoarsenessNDM and BusynessNDM features. The agreement was
combination of respiratory gating and CBM (PET/CT) showed better between LIFEx vs. Metavol (95%, 36 features of 38) and
improved lesion definition and significantly altered uptake worse between CGITA vs. Metavol (63%, 24 features of 38) and
statistics, especially for thorax lesions. For prostate lesions, both CGITA vs. LIFEx (60%, 23 features of 38). All features resulted highly
PET/CT and PET/MR protocols showed a small reduction in correlated (r>=0.7, p<.001) in comparing LIFEx vs. Metavol, while
tumor sizes, with significant SNR loss. Enhanced preparation and 5 of 38 features (13%) were found not in agreement and slightly
examination times need to be put into consideration depending or not correlated (r<0.7, p<.001) in comparing CGITA vs. LIFEx,
on the scan area, especially for high throughput settings.(This and CGITA vs. Metavol. Conclusion: Some texture discrepancies
project is funded by European Union’s Horizon 2020 research across software packages exist. It could be interesting to further
and innovation programme under the Marie Sklodowska-Curie investigate the origin of these differences and how these can
grant agreement No 764458) References: None. affect radiomic analyses conducted using different software
packages. References: None.

EPS-112
Quantitative Characterization Of Tumors In PET: A EPS-113
Comparison Of Three Texture Analysis Software Packages Accuracy of 18F-FDG brain activity quantification on the
M. Larobina, R. Solla, R. Megna; GE SIGNA PET/MR system with MR derived attenuation
Institute of Biostructure and Bioimaging, correction
National Research Council, Naples, ITALY. P. Braad1,2, T. L. Andersen1,2, P. Grupe1;
1
Department of Nuclear Medicine, Odense C,
DENMARK, 2Department of Clinical Research, University
Aim/Introduction: To compare differences in texture feature of Southern Denmark, Odense, DENMARK.
values computed by three different software packages on
18
F-FDG-PET images. Materials and Methods: PET images
from 15 patients with head and neck cancer were processed Aim/Introduction: Combined 18F-FDG PET/MR has potentially
with three different freeware software: CGITA version 1.4, LIFEx a large clinical value for the diagnostic work-up of dementia
version 4.6, and Metavol/Ptexture version 20181009. First, for and other neurodegenerative diseases. However, the lack
each of the three software, patient’s lesions were segmented of MR signal from bony structures challenges stable activity
using the 40% of the SUVmax. Second, for each lesion a total of quantification and thus, until recently, attenuation correction
38 textural features representing the common group of features in clinical studies could only be performed without bone
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S356

segmentation. GE Healthcare has recently introduced the Zero foot and ankle in evaluation of heel pain (HP) for diagnosis of
Echo Time MR-sequence (ZTE) to extract signals from bones plantar fasciitis (PF) and Achilles tendinopathy (AT). Materials
in head scans. Before routine implementation of PET/MR for and Methods: A total of 47 patients with HP were enrolled.
18F-FDG brain scans we wanted to compare the quantitative Orthopedic clinician made preliminary clinical diagnosis
performance of the ZTE attenuation method to conventional (CD) of HP according to physical examinations and patient’s
PET/CT (CTAC) attenuation correction and the standard PET/ symptom. Provisionally, typical plantar HP was regarded as PF
MR method without bone segmentation (MRAC). Materials and posterior HP was diagnosed as AT. Patients with atypical
and Methods: 10 dementia patients referred for 18F-FDG pain were categorized into inconclusive group. Radiographs
PET/CT were scanned on PET/CT and subsequently on the GE and SPECT/CT of foot and ankle were acquired. On SPECT/CT,
SIGNA PET/MR system (GE Healthcare) using the same activity plantar uptake of calcaneus in relation to the attachment point
injection. PET/MR attenuation correction was performed using of plantar fascia was diagnosed as PF and posterior uptake of the
MRAC, ZTE and with CT attenuation maps extracted from calcaneus in relation to the Achilles tendon was regarded as AT.
the PET/CT. PET/MR images were reconstructed with and The results of preliminary CD were compared with visualization
without time-of-flight (TOF). T1 weighted MR images were of bony activity on SPECT/CT. The radiographic findings of ankle
registered to a NURBS-based HUman Brain (NHUB) Phantom spurs including plantar spur, Haglund’s deformity, and Achilles
containing 98 segmented brain regions using the ITK based spurs were also compared with presence of bony activity.
Elastix toolbox. Calculated transformations were applied on Additional findings on SPECT/CT were also evaluated. Results:
reconstructed PET images. Average 18F-FDG radionuclide Among 47 patients, 26 patients were clinically diagnosed PF
activities were calculated in all segmented brain regions for all in 18 and AT in 8 patients by well-localized typical HP. In these
patients and reconstruction methods. Median patient activities 26 patients with typical HP, preliminary CD matched SPECT/CT
in brain regions were compared to activities in PET/MR images in 88% (23/26) of patients. The prevalence of ankle spurs with
reconstructed with the CTAC method. Results: Average 18F-FDG bony activity was 48% (16/33) of lesions. SPECT/CT showed
brain activities were 2% lower on images reconstructed with additional information related to coexistent pathologies in 12%
MR-derived attenuation maps compared to the reference (3/26) of patients (metatarsal bone fracture: 1, osteoarthritis: 1
images reconstructed with CTAC. With MRAC and ZTE, activity and idiopathic neuropathy: 1). In 21 patients with atypical HP,
quantification inaccuracy was <5% in the majority of brain SPECT/CT made the diagnosis of PF and AT in 67% (14/21) of
regions but as large as 10% in some outer parts of the brain. patients by visualization of bony uptake in plantar or posterior
With ZTE based attenuation correction images appeared more calcaneus. The prevalence of ankle spurs with bony activity was
homogenous and the uniformity of activity quantification 35% (6/17) of lesions. SPECT/CT provides additional information
accuracy in bone-near brain regions and lower parts of the brain related to coexistent pathologies in 33% (7/21) of patients
was improved. TOF reduced the maximum median brain region (arthritis: 3, chondrosarcoma: 1, delayed union of fibular fracture:
activity quantification inaccuracy by 5% and further enhanced 1, symptomatic accessory navicular bone: 1 and simple bone
image quality, particularly in regions with a high scatter cyst: 1). Conclusion: In typical and atypical heel pain. bony
content. Conclusion: With ZTE attenuation correction and TOF activity of SPECT/CT showed good outcome for diagnosis of
reconstruction methods, clinical 18F-FDG PET/MR brain studies PF and AT. Also, it gives information for hidden pathologies of
can be performed with activity quantification inaccuracies of foot and ankle not suspected by clinicians. Therefore, SPECT/
<5%. References: None. CT imaging can improve diagnostic accuracy of PF and AT
in patients with HP, and it will enable confident therapeutic
planning by showing hidden pathologies with HP, especially in
1111 atypical HP. References: None.
e-Poster Presentation Session 8 - Bone & Joint:
Bone SPECT/CT - Clinical Imaging Pattern and EPS-115
Quantification Tools Bilateral Osteochondritis Dissecans Of The Ankle Joints In
A Young Female
Tuesday, October 15, 2019, 8:00 - 9:30 Room 133/134 I. El Bez, R. Tulbah, I. Munir, F. Alghamlas, M. Alharbi;
KFMC, nuclear medicine department, Riyadh, SAUDI ARABIA.

EPS-114 Aim/Introduction: Osteochondritis dissecans (OCD) of bilateral


The role of SPECT/CT for diagnosis of planatar fascitis and ankles is very rare, with few reported cases of bilateral OCD of
Achilles tendinopathy both medial part of the talus. We report a case of 25 year old
I. Hyun, B. Kim, Y. Kim, M. Lee; lady, medical student, with bilateral osteochondritis dissecans
Inha University Hospital, Incheon, KOREA, REPUBLIC OF. in ankles; who was diagnosed with plain radiographs, magnetic
resonance imaging and triphase bone scan with SPECT-CT.
Materials and Methods: The patient was a 25 year-old women.
Aim/Introduction: We evaluated the role of SPECT/CT of She came to the orthopedic clinic of orthopedics Department
S357 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

in king Fahad Medical City Riyadh, with a complaint of pain of SPECT and MRI was performed in the program RView 9.06
and swelling in both ankles for around three months.The pain (Colin Studholme). Results: All patients were divided into two
began insidiously in both ankles, without any history of trauma. groups: the first group (n = 42) for developing the scoring
It’s not improved with non-steroidal anti-inflammatory drugs system, the second group (n = 38) for testing the scoring system.
and worsened after exercise practice. The patient underwent In the first group diagnostic indicators of typical symptoms of
radiographs of the bilateral foot and of the bilateral ankle on osteomyelitis were calculated. Тhe scoring system was based
anterior, posterior and lateral view radiographs, as well as MRI on the positive predictive value. Each symptom has received
of the wright foot. Triphase bone scan was performed. The a certain amount of scores: radiopharmaceutical differential
patient received approximately 814 MBq of Technetium-99m accumulation iqual 1,56 - 4, fistula - 4, bone marrow edema - 3,
MDP intravenously. Limited Flow and blood pool images of the radiopharmaceutical hyperfixation in one or two foot bones - 3,
bilateral ankle and foot were immediately performed, as well as bone destruction - 2, soft tissue disorganization - 2, soft tissue
delayed spots views and SPECT-CT of the same area. Results: The swelling - 1, tenosynovitis - 1. According to the results of the ROC
patient underwent radiographs of the bilateral foot and of the analysis, the threshold value of the presence of osteomyelitis
bilateral ankle on anterior, posterior and lateral view radiographs, was obtained with a score of more than 12. This quantitative
and bilateral osteochondral lesions are noted in the medial talar criterion was extremely highly specific and sensitive (Se = 95.5%
domes with no radiographic evidence of displaced fragment. Sp = 100.0%). Conclusion: The study shows a high diagnostic
MRI of the right foot was requested, which revealed moderate efficiency of the SPECT / MRI-based scoring system in detection
to severe chondropathy involving the medial talar dome of osteomyelitis in patients with diabetic foot syndrome
articular cartilage suggesting OCD.Limited Flow and blood (sensitivity 95.5% and specificity 100.0%). References: None.
pool images of the bilateral ankle and foot were immediately
performed, as well as delayed spots views and SPECT-CT of
the same area. The flow and the blood pool images involving EPS-117
the bilateral ankle and foot demonstrate bilateral symmetrical Irradiated sciatic pain as an unusual presentation of
increased uptake within the ankles. The delayed planar and osteoid osteoma in distal limb bone
SPECT-CT images demonstrate significant symmetrical increase J. Uña, C. Alvarez Gonzalez, C. Cardenas Negro, A. Allende Riera, F.
activity involving the bilateral medial talar domes. Conclusion: de Leon Garcia;
In conclusion, we propose that the diagnosis of OCD of bilateral Servicio Canario Salud, Santa Cruz de Tenerife, SPAIN.
ankles should be kept in mind in young adults with a history
of trauma or repetitive microtrauma. For imaging, MRI is usually
sufficient. The tri-phase bone scintigraphy is sensitive and Aim/Introduction: We present an atypical case of an adult
specific in determining the mechanical stability of OCD lesions. with classic irradiated right sciatic pain with affectation of L3-
The addition of SPECT-CT increases the clinical accuracy due S1 roots. It was initially treated as lumbar pain with imaging
to increased contrast resolution and anatomical localization. and neurophysiological evidence that guided it. Materials and
References: None. Methods: After multiple ineffective conservative treatments
and two year of evolution, even with worsening of the
involvement of the right S1 root, it was decided to track the
EPS-116 pelvis with an MRI and later the body with a 99mTc-HMDP
Diabetic patients with suspected foot osteomyelitis: new bone scintigraphy. An osteoid osteoma was detected on the
method for evaluating hybrid images SPECT-WBC/MRI right tibia on the scan, later confirmed with SPECT-CT and a
based on a score system simple Rx. It was treated by radiofrequency ablation of the nidus
V. Udodov1, M. Zorkaltsev1, V. Zavadovskaia1, M. Zamyshevskaia1, and irradiated pain disappeared without further analgesia.
A. Kurazhov1, E. Grigoriev2, N. Vegerin1; Results: After reviewing the available scientific literature in
1
Siberian State Medical University, Tomsk, RUSSIAN FEDERATION, Pubmed with the search terms “osteoid osteoma and radicular
2
Cancer Research Institute, Tomsk, RUSSIAN FEDERATION. pain” and “osteoid osteoma and irradiated” we have found
articles that refer to the presence of osteomas with irradiated
radicular pain in the proximal bones of both extremities. None
Aim/Introduction: The abstract presents the possibilities of the articles that we found referred pain like our patient’s
of the software combined SPECT-WBC/MRI in the detection with osteoma in distal limb. Osteoid osteomas with pathologic
of osteomyelitis in patients with diabetic foot syndrome. electromiography are described in femur or humerus. Thus to
Materials and Methods: 80 patients with diabetes type I and the best of our knowledge this is the first patient described in
II, suspected osteomyelitis were studied (35 (43.7%) males and the literature with osteoid osteoma in distal limb and sciatic
45 (56.3%) females, mean age 58.4 ± 12.3 years). The study type irradiated pain with positive tests describing neural lesions.
included patients with neuropathic (n = 27), ischemic (n = 3) Conclusion: Bone scintigraphy with phosphonates remains a
and neuroischemic (n = 50) DFS forms. All patients underwent useful test to determine the presence of unsuspected lesions
scintigraphy with 99mTc-HMPAO labeled leukocytes (370 MBq; in patients with clinical conditions that do not respond to usual
SPECT Philips Brightview) and magnetic resonance imaging therapy. In addition, the possibility offered by modern gamma
(Siemens Magnetom Essenza 1.5T; T1WI, T2WI, PD-FSat). Fusion cameras to perform hybrid studies facilitates the diagnosis and
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S358

location of injuries, making patient management faster and intramuscular myxomas in the Mazaraud’s syndrome, should
more efficient. References: Stoffelen D, Martens M, Renson L, be known and recognized as a benign differential diagnosis of
Fabry G. Osteoid osteoma as a cause of knee pain. A review of bone metastases to not misguide the clinicians and the patient
10 cases.Acta Orthop Belg. 1992;58(4):395-9. L Kiers, L K Shield, for further therapeutics and explorations. References: None.
W G Col. Neurological manifestations of osteoid osteoma.
Archives of Disease in Childhood 1990; 65: 851-855. Bea Muñoz
M, Jiménez Álvarez M., Pérez Vallina J.R., Medina Sánchez M. EPS-119
Osteoid osteoma of the proximal femur preenting as knee pain: Hypertrophic Osteoarthropathy as a warning in bone
A well-known problem difficult to diagnose. Doi: 10.1016/j. scintigraphy
anpedi.2009.04.16. Saqtas E, Gokkus K, Aydin AT. Intra-Articular L. S. Torres, V. Alves, A. Oliveira, J. Pereira;
Osteoid Osteoma as a Cause of Anteromedial Knee Pain. Case Centro Hospitalar Universitário S. João, Porto, PORTUGAL.
Rep Orthop. 2017;2017:5846368. doi: 10.1155/2017/5846368.
Epub 2017 May 2. Ebrahimzadeh M.H., Ahmadzadeh-Chabock
H.,Ebrahimzadeh A.R. Osteoid Osteoma: A Diagnosis for Aim/Introduction: Hypertrophic osteoarthropathy (HO) is a
Radicular Pain of Extremities. Orthopedics. November 2009 syndrome characterized by abnormal proliferation of the skin
-Volume 32 · Issue 11.DOI: 10.3928/01477447-20090922-23. and periosteum mainly at the extremities. Clinical and imaging
features include digital clubbing, periostosis of tubular bones,
and synovial effusions. Secondary HO is associated with lung
EPS-118 cancer, other pulmonary disorders, and several other conditions.
Mazabraud’s syndrome a new case report In this study, we aim to review the findings and value of
Z. Jemni1,2, A. Ezzine1,2, H. Chekir3, H. Boudrigua1, M. Ben Fredj1,2, S. bone scintigraphy for this syndrome, while also assessing its
Mensi1, T. Dardouri1, H. Charfi1, R. Sfar1, M. Nouira1,2, K. Chatti1; possible causes. Materials and Methods: After retrospective
1
Nuclear medicine department, Sahloul university review of our patient database from April 2009 to April 2019,
hospital, Sousse, TUNISIA, 2LR12ES02, University of Sousse, bone scintigraphies reported as demonstrating or possibly
Faculty of medicine of Sousse, Sousse, TUNISIA, 3Imaging demonstrating HO were selected. A diagnosis of HO was
Department, Sahloul university hospital, Sousse, TUNISIA. considered in patients with a scintigraphic pattern of diffusely
increased uptake along the cortical margins of long bones.
Every bone scintigraphy was performed with an acquisition of
Aim/Introduction: Polyostotic fibrous dysplasia (FD) in anterior and posterior static images, taken 3-4h after i.v. injection
association with intramuscular myxomas is a rare condition. of approximately 925 MBq of 99mTc-HDP. Results: 51 patients
Only few case reports are mentioned in the literature and this met the inclusion criteria for HO on bone scan. All 51 patients
is known as Mazabraud’s syndrome. We present this case report showed higher activity of 99mTc-HDP in the lower limbs (3 only
to enlighten the value of radionuclide bone scintigraphy and in the femur and 1 only in the tibia), 21 (41%) also in the upper
SPECT/CT in the diagnosis of FD and subsequently in referring limbs (9 only in the humerus, 2 only in the radio/ulna) and 1
to other clinical syndromes. Materials and Methods: A 50-year- (2%) in the clavicles. In 7 (14%) of the patients, 99mTc-HDP uptake
old female patient was referred to our department in order to in the affected bones was asymmetrical. 40 patients (78%) had
underwent a whole-body bone scan for suspicion of skeletal diagnosed lung carcinoma, and 7 (14%) others had known
metastases on the basis of osteolytic bone lesions incidentally conditions associated with HO, namely lung metastasis (n=3),
discovered on a CT-scan. The patient then proceeded directly other pulmonary disorders (n=3; COPD, tuberculosis, interstitial
for SPECT/CT for anatomic location and further evaluation. pulmonary disease) and colorectal cancer (n=1). Of the 4
Results: Tc-99m MDP whole body scan showed multiple sites patients with no apparent cause for HO at the time of the bone
of increased tracer uptake, including the skull and the right scan, 1 patient was afterwards diagnosed with lung metastasis
facial bones, multiple ribs, pelvis and bones of both lower limbs. due to breast cancer, 1 patient is still in staging for breast cancer,
The SPECT/CT findings showed expanding, cystic lesions with and only 2 remain with no likely cause for HO (breast and
ground glass density, corresponding to bone scan abnormalities prostate carcinomas with no known metastasis). Conclusion:
.Overall, it was interpreted as consistent with polymelic subtype As described in previous literature, HO affects mainly the
of a fibrous dysplasia of the bone. On further examination, the lower limbs, is usually, though not always, symmetrical in its
patient was found to have a large sessile tumor of right arm with presentation, and remains highly linked to malignancy. Due
a separate soft tissue swelling within the biceps muscle, notably to its easily recognizable pattern, bone scintigraphy remains a
asymptomatic, painless on palpation.Blood samples were simple and powerful tool to help in the detection of HO, and
requested revealing that alkaline phosphatase were greater than can serve as a warning sign for an underlying causal condition,
four times the upper limit of normal and hormonal tests were be it malignant or benign, pulmonary or otherwise. References:
correct. The soft tissue tumor on excision and histopathological None.
examination was found to be intramuscular myxoma. The
combination of the above two, called Mazabraud’s syndrome is
being reported. Conclusion: Polyostotic (FD) may closely mimic
the appearance of bony metastatic disease. Its association with
S359 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

EPS-120 EPS-121
Comparison of conventional MDP bone scan and Assessment of instablity in thoracolumbar burst fractures
Somatostatin Receptor PET CT in detection of active using bone scintigraphy
Rheumatoid Arthritis M. Seo1, J. Choi2, J. Kim3, S. Park3;
S. Shamim, A. Behra, R. Gupta, G. Arora, S. Datta Gupta, C. Bal; 1
Ulsan University Hospital, Ulsan, KOREA, REPUBLIC OF,
All India Institute of Medical Sciences, Delhi, INDIA. 2
Dongkang Medical Center, Ulsan, KOREA, REPUBLIC
OF, 3Ulsan University Hospital, University of Ulsan
College of Medicine, Ulsan, KOREA, REPUBLIC OF.
Aim/Introduction: Rheumatoid arthritis (RA) despite various
available treatment options is considered an incurable
disease. The treatment is predominantly composed of drugs Aim/Introduction: Unstable thoracolumbar burst fractures
for symptomatic relief and a class of drugs known as disease (TLBF) require surgical management because they may result
modifying anti-rheumatic drugs (DMARDs). Despite these in varying degrees of neurologic deficit, especially when the
available treatment options, some patients are not able to Thoracolumbar Injury Classification and Severity (TLICS) score
achieve satisfactory clinical results and some patients are is over 4. The aim of this study was to evaluate whether a bone
outright refractory to all available treatment options. Such scintigraphy using a proposed scoring system can accurately
patients may require modification of treatment protocols and assess instability in TLBF. Materials and Methods: Among TLBF
new treatment options. Recently, few studies have reported patients who underwent bone scintigraphy between January
radiotracer uptake of somatostatin receptor (SSR) analogues 2015 and August 2017, 52 patients who underwent imaging
in chronic inflammatory sites including active RA [1,2]. work-up {bone scintigraphy and magnetic resonance imaging
SSR targeted imaging may provide a novel method for RA (MRI)} before operation were chosen for analysis. Instability of
evaluation. This study thus aims to investigate the potential TLBF was determined by clinical and imaging assessments. The
utility of SSR PET imaging in RA as compared to 99mTc-MDP bone TLICS score was also determined. Bone scintigraphy was visually
scan, which is already an established modality for detection of evaluated with a proposed scoring system {ST (total score) = SB
active joint inflammation. Materials and Methods: Nineteen (body score, 5 points) + SP (spinous process score, 2 points)}.
patients (>18years) with clinical diagnosis of RA were included Diagnostic performance of the scoring system in assessing
in the study. The patients underwent skeletal scintigraphy and instability of TLBF was assessed. Results: Among 52 TLBF,
68
Ga-DOTANOC PET/CT. 3-phase bone scan was done post- 34 (65.4%) were unstable fractures and 31 (59.6%) had TLICS
intravenous (i.v.) injection of 20mCi 99mTc-MDP. 68Ga-DOTANOC score > 4. ST ≥ 4 was an optimal cut-off for assessing instability
PET/CT was acquired from head to toe, 30 min post-i.v. injection after receiver operating characteristic curve analysis. The
of 2mCi 68Ga-DOTANOC. Both bone and PET/CT scan images diagnostic performance of the proposed scoring system (ST ≥
were visually assessed independently by two experienced 4) for assessing unstable TLBF were as follows; sensitivity 61.8%,
nuclear medicine physicians. Results: Nineteen patients (16 specificity 94.4%, positive predictive value (PPV) 95.5%, and
female; 3 male) of clinically proven RA, with mean age of 41.9 negative predictive value (NPV) 56.7%. Diagnostic performance
± 12 years were included in the study. In 19 patients, 196 joints of ST ≥ 4 for assessing lesions with TLICS score > 4 were as follows;
were clinically positive. Of these 196 joints, 157 joints (80%) sensitivity 58.1%, specificity 81.0%, PPV 81.8%, and NPV 56.7%.
were positive on Tc-99m MDP scan and 151 joints (77%) were Conclusion: Bone scintigraphy using the proposed scoring
positive on 68Ga-DOTANOC scan. The difference in the detection system shows high specificity and PPV for detecting TLBF that
efficiency between 99mTc-MDP and 68Ga-DOTANOC scan was are unstable or have TLICS score > 4. This scoring system may be
found to be insignificant (p <0.7). Conclusion: From this study of use in deciding surgical management of TLBF. References:
of comparative evaluation of conventional 99mTc-MDP bone scan None.
and SSR PET/CT in articular manifestation of RA, we conclude
that 68Ga-DOTANOC and MDP bone scan are equally efficient
in the detection of RA with an added advantage of therapeutic EPS-122
potential with 68Ga-DOTANOC. However, further evaluation Tc-99m-DPD xSPECT Bone Scan Quantification of
with larger sample size is warranted. References: 1. Vanhagen Subchondral Bone Uptake: An Updated Analysis in
PM, Markusse HM, Lamberts SW, Kwekkeboom DJ, Reubi JC, Osteoarthritic Knee Assessment
Krenning EP. Somatostatin receptor imaging. The presence of M. Jreige, N. Schaefer, P. Omoumi, J. O. Prior, M. Nicod-Lalonde;
somatostatin receptors in rheumatoid arthritis. Arthritis Rheum. Lausanne University Hospital, Lausanne, SWITZERLAND.
1994; 37(10):1521-1527 2. Anzola-Fuentes LK, Chianelli M, Galli F,
Glaudemans AWJM, Martin Martin L, Todino V, et al. Somatostatin
receptor scintigraphy in patients with rheumatoid arthritis and Aim/Introduction: Bone scintigraphy with Tc-99m labeled
secondary Sjögren’s syndrome treated with Infliximab: a pilot DPD can identify osteoblastic reactions within the spectrum
study. EJNMMI Res. 2016; 6(1):49. of osteoarthritic (OA) bone changes with a high sensitivity,
especially at the knee level. The aim of this study was to
investigate the emerging role of Tc-99m DPD absolute uptake
quantification with xSPECT/CT in normal and osteoarthritic
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S360

tibial and patellar subchondral bone and to correlate obtained


SUV to CT density using Hounsfield units (HU). Materials and Aim/Introduction: The purpose of this study was to
Methods: We retrospectively assessed 14 patients (mean determine whether quantitative three-phase 99mTc-MDP
age 50±15 years) with no/minimal knee OA and 18 patients bone scintigraphy can provide accurate thresholds for
(aged 62±11y) with advanced knee OA and contralateral total predicting loosening in symptomatic patients with knee total
knee replacement. Quantitative xSPECT/CT (Symbia Intevo, endoprostheses. Materials and Methods: A total of 125 patients
Siemens Healthineers, Erlangen, Germany) was acquired and of knee total endoprostheses (TEP) (126 K - TEP) suffering pain
SUV quantified on post-processed images using SUVmax, symptoms were retrospectively included in this study. For the
SUVmean (g/mL) in tibial and patellar subchondral bone. HU of quantification of the 3-phase skeletal scintigraphy, the ratio of
the same regions of interest were measured on CT. Results: A pathological peri-prosthetic tracer uptake to normal bone was
total number of 18 osteoarthritic knees were analyzed showing evaluated. In case of visually equivocal findings, the change in
a mean tibial and patellar SUVmax, SUVmean (g/mL) and CT ratios was analyzed between 2 examinations at the 6-month
density (HU) of 6.6 ±2.9, 4.1±1.6 and 263±80 and 8.1±4, 5.4±2.8 interval whether cut-off point could be found to predict
and 374±86, respectively. In 14 knees with no/minimal OA loosening. The imaging interpretations were validated by the 6
mean corresponding tibial and patellar SUVmax, SUVmean (g/ months clinical course or the revision operation. Results: The
mL) and CT density (HU) were 3.5±1.2, 2.2±0.8 and 261±36 quantitative analysis enhances the predictive value of loosening
and 3.8±1.8, 3.8±1.8, and 306±69 respectively. Comparison of in the region of the “tibial plateau” in equivocal cases at a cut-off
both SUVmax and SUVmean between the OA and no/minimal of 1.55 (AUC = 0.52) with a sensitivity of 50% and specificity of
OA groups showed a statistically significant difference for tibial 57% in early images. Six months follow up images of equivocal
and patellar SUVmax and SUV mean (all p<0.0008). CT density cases reveal a cut off of 1.53 (AUC79%) with 71% sensitivity
was statistically different between the OA and no/minimal OA and 79% specificity. The percentage of the ratio changes in
groups only in patellar region (p=0.02). We found a positive the follow-up control for the detection of a loosening process
correlation between SUVmax and SUVmean with CT density rises at a cut-off of 3.88% in the “tibial plateau” (sensitivity 87%,
(HU) in tibial subchondral bone in the group with no/minimal specificity 89%, AUC = 0.94, p = 0.056). Conclusion: Exclusive
OA (rho=0.839, p<0.0005 and rho=0.672, p=0.0001), but not in uptake ratios are not sufficient to predict loosening in equivocal
the OA group (both p<0.81). Conclusion: This study showed cases. While increased uptake ratios with time in quantitative
significant differences in Tc-99m-DPD uptake on bone scan three-phase bone scintigraphy improves the predictive value
between OA and no/minimal OA in the subchondral tibial for the recognition of a loosening process in cases with ​​K-TEP
and patellar bone based on quantitative data analysis. There equivocal imaging findings. References: None.
were significantly higher SUVmax and SUVmean in OA group
but no difference in CT density (HU) of the subchondral tibial
bone. Thus, integrating quantitative analysis of bone scan EPS-124
might be valuable in increasing sensitivity for initial detection, Bone SPECT/CT in patients with persistent low back pain
stratification and evolution assessment of knee OA. References: after lumbar spine stabilization
[1]McCrae , Shouls J, Dieppe P,et al. Scintigraphic assessment of R. García Jiménez, Y. Herrera-Martinez, E. López Rodríguez, P.
osteoarthritis of the knee joint. Ann Rheum Dis. 1992 Aug; 51(8): Fernandez-Rodríguez, J. Jiménez-Hoyuela García;
938-942.[2]Kraus VB, Worrell TW, Renner JB,et al. High prevalence Hospital Universitario Virgen del Rocio, Sevilla, SPAIN.
of contralateral ankle abnormalities in association with knee
osteoarthritis and malalignment. Osteoarthritis Cartilage. 2013
Nov;21(11):1693-9. Aim/Introduction: The incidence of low back pain after lumbar
stabilization surgery (LSS) is observed in 10-20% of cases. There
are limitations in the sensitivity and specificity of conventional
EPS-123 imaging techniques (radiography, CT and MRI), conditioning
Quantitative three-phase 99mTc-MDP scintigraphy in the the presence of errors in the diagnosis in 20% of cases. The aim
assessmenmt of loosening of total knee endoprostheses of this study was to determine the sensibility of bone SPECT/
in patients with equivocal imaging findings CT as a diagnostic method in patients with low back pain after
M. Beheshti1,2, Z. Paymani3, R. Ortmaier4, C. Schiller5, F. Fitz5, F. LSS Materials and Methods: Descriptive, cross-sectional,
Masoumi6, J. Hochreiter7, W. Langsteger5; retrospective study was performed. A total of 96 consecutive
1
Nuclear Medicine, University Hospital, RWTH University, patients with lumbar pain after LSS, who underwent 99mTc-HDP
Aachen, GERMANY, 2Nuclear Medicine, Paracelsus Medical bone SPECT/CT from January 2010 to December 2018 were
University, Salzburg, AUSTRIA, 3Research Center for Nuclear included in this study. The sensitivity, specificity and accuracy
Medicine, Tehran University of Medical Sciences, Tehran, IRAN, of 99mTc-HDP bone SPEC/CT were determined. Results were
ISLAMIC REPUBLIC OF, 4Orthopedics surgery, Ordensklinikum, confirmed with surgery results or with clinical variables. Results:
Linz, AUSTRIA, 5Nuclear Medicine, St. Vincent’s Hospital, 96 patients were included (41,7% men, 58,3% women) with an
Ordensklinikum, Linz, AUSTRIA, 6Orthopaedics Surgery, Tabriz average age of 52,9 ± 12,3 years. In 92,7% the LSS was initially
University of Medical Sciences, Tabriz, IRAN, ISLAMIC REPUBLIC indicated by degenerative causes, while the 7, 3% by traumatic
OF, 7Orthopaedics surgery, Ordensklinikum, Linz, AUSTRIA. causes. In 47,8% of patients the arthrodesis of more than two
S361 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

joints were performed. Image study was performed on average both observers of 80%. The asymmetry index obtained for
52,2 months after the first surgery (range 4-360 months). The symptomatic patients was 1.8 while for asymptomatic patients
most frequent diagnosis by bone SPECT/CT was “Insufficient it was 1.6. There was no difference between the group of
stabilizing function”, followed by “mobilization of the material” symptomatic patients with surgically confirmed pseudoarthrosis
and “Insufficient stabilizing function with mobilization of the and in those who discarded this disease. In 2 symptomatic
material”. The SPECT/CT was negative in 12,5% of the cases. The patients without pseudoarthrosis (2/6), facet and intervertebral
sensitivity of the test was 94% with a specificity of 53,8% (PPV: osteodegenerative activity was associated at different levels.
92%; NPV 58%). Diagnostic accuracy was 88,5%. Subsequently, Conclusion: Our preliminary results suggest a probable causal
25,5% of the cases required surgery, 43.7% were managed in relationship between the increase in osteoblastic activity in the
the unit of pain, and 31,6% were treated by medical treatment. arthrodesis and the biomechanical characteristics of the fixation
Conclusion: Bone SPECT/CT has high sensitivity for diagnosis material. We propose a simple and reproducible quantification
of the etiology of low back pain in patients with previous LSS. method that contributes to the diagnosis of pseudoarthrosis.
Its systematic use may improve the precocity and efficiency However, more patients and standardization of the follow-up
of treatment in these cases, especially in those cases with criteria are needed to clarify its usefulness. References: None.
inconclusive conventional imaging. References: None.

EPS-126
EPS-125 Usefulness of bone SPECT/CT for the prediction of bone
Utility of SPECT-CT in the follow-up of patients graft viability after maxillofacial reconstruction with
undergoing cervical intersomatic arthrodesis vascularized bone grafts
M. Moreno-Caballero1, A. Moreno-Flores2, A. Martínez-Esteve1, P. H. Kim1, S. Ha1, E. Shin1, J. Lee2,3, K. Ahn2,3, J. Ryu1,3;
Jiménez-Granero1, A. Cobo-Rodríguez1, J. Infante-de la Torre1, J. 1
Department of Nuclear Medicine, Asan Medical
Serrano-Vicente1, J. Rayo-Madrid1; Center, Seoul, KOREA, REPUBLIC OF, 2Department of
1
Departamento de Medicina Nuclear. Hospital Universitario oral and maxillofacial surgery, Asan Medical Center,
de Badajoz, Badajoz, SPAIN, 2Departamento de Neurocirugía. Seoul, KOREA, REPUBLIC OF, 3University of Ulsan
Hospital Universitario de Badajoz, Badajoz, SPAIN. College of Medicine, Seoul, KOREA, REPUBLIC OF.

Aim/Introduction: To evaluate the usefulness of SPECT- Aim/Introduction: The accurate assessment of bone graft
CT 99mTc-HDP in patients undergoing cervical spinal fixation viability is important in patients who had maxillofacial
with intersomatic cage system (Cervios®) and its possible reconstructive surgery with vascularized bone graft after
contribution to the diagnosis of pseudoarthrosis. Materials resection of mandible or maxilla. Bone scintigraphy has
and Methods: A retrospective pilot study including 13 proved to be of value for non-invasive, simple and effective
subjects, 8 women and 5 men, average age: 52.1 years [32- in postoperative assessment of bone graft. Hybrid imaging of
72]. Of these, 4 were asymptomatic, 9 with persistent cervical single photon emission computed tomography (SPECT) and
pain or signs of myelopathy. All of them underwent SPECT- computed tomography (CT) has more advantages by providing
CT study (Symbia T2®, GE Healthcare). Median of 39 months complex anatomical information of maxillofacial region
[9-132] between surgery and scintigraphy. The images were and attenuation correction of SPECT images. We performed
visually interpreted independently by 2 nuclear physicians, with this study to evaluate the performance of bone SPECT/CT
clinical blinding. A scale of 3 degrees was used according to the in the prediction of bone graft viability after maxillofacial
intensity of uptake (mild, moderate or intense). Subsequently, a reconstruction with vascularized bone grafts. Materials and
quantitative analysis was carried out using rectangular 35 mm Methods: We retrospectively reviewed the medical record and
ROIs in summative slices of the tomographic image. The ratio of images of 34 consecutive patients (M:F=23:11, age 26 - 89 years)
counts per pixel in the arthrodesed area to the one measured who underwent bone SPECT/CT with 99mTc-DPD or 99mTc-HDP
on adjacent healthy vertebra was calculated, obtaining an index at about one week (5 - 8 days) after reconstructive surgery of
of asymmetry. The results were finally compared with the Gold mandible (n=28) or maxilla (n= 6) with vascularized bone graft
standard established: clinical evolution for 7 individuals and between February 2014 and March 2019. Fibular free flap (n=21)
surgical reintervention in 6. Results: Five patients presented or iliac crest free flap (n= 13) were used, and 11 patients had
arthrodesis in 2 levels, being the most frequently intervened reconstructive surgery with 2 segments of bone graft. Patients
C5-C6 (53.8%). Of the 9 symptomatic patients, only 3 confirmed were clinically followed for at least one month (range 5 - 61,
the presence of pseudoarthrosis due to surgical reoperation median 13 months), and the final diagnosis of non-viable graft
(3/9). In the remaining 6 (6/9), 3 did not show graft mobility was surgically confirmed. For visual analysis of bone SPECT/CT
during reoperation and in 3 others surgery was ruled out, 2 due images, two readers who blind to clinical information scored
to radiological imaging and 1 for mild symptomatology. The the uptake degrees of each bone graft segment in comparison
4 asymptomatic patients remained stable during the period with those of calvarium as follows; 0 = absence of tracer uptake,
considered. All showed increased uptake of the radiotracer in the 1 = decreased uptake, 2 = same degree of uptake, and 3 =
arthrodesed area, with a degree of visual agreement between increased uptake. Results: In the visual analysis of bone graft
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S362

uptake on SPECT, the anatomical CT information from hybrid EPS-128


images was helpful for discriminating bone graft uptake on A Novel Sn-117m Colloid for Human Radiosynoviorthesis
SPECT from adjacent stump end of maxilla or mandible, or Clinical Trials
soft tissue uptake of surgical bed. Forty-one of all 45 bone N. R. Stevenson1, C. A. Doerr1, G. R. Gonzales1, J. Simon2, A.
graft segments were scored more than 1, and all of them Bendele3;
were viable graft and uneventful during follow-up. Four bone 1
Serene, LLC, Buford, GA, UNITED STATES OF
grafts had score 0 (absence of tracer uptake), and all of them AMERICA, 2IsoTherapeutics Group, LLC, Angleton,
were surgically removed and confirmed as nonviable bone TX, UNITED STATES OF AMERICA, 3Bolder BioPATH,
graft with osteonecrosis. Conclusion: Absent tracer uptake in Inc., Boulder, CO, UNITED STATES OF AMERICA.
the vascularized bone graft on bone SPECT/CT at one week
after reconstructive surgery could be used to predict the graft
failure. Bone SPECT/CT would be useful for the assessment of Aim/Introduction: In patients with advanced arthritis,
vascularized bone graft at risk after maxillofacial reconstruction. direct injections of a radio-colloid into affected joints
References: None. (radiosynoviorthesis a.k.a. radiosynovectomy) is used
therapeutically to relieve pain and increase mobility. Isotopes
such as Y-90, Re-186 and Er-169 are in routine clinical use.
EPS-127 Recently, a Sn-117m (γ 159 keV, 86% ; e- ~140 keV, 112% ; t½ 14d)
Bone SPECT/CT in the early diagnosis of calciphylaxis homogeneous colloid (HTC) has become available for treating
Y. Herrera-Martinez, J. Martín-Marcuartu, P. Fernández-Rodríguez, canine osteoarthritis (OA) [1]. This product was modified
J. Jiménez-Hoyuela García, R. García Jiménez; with ascorbic acid (causing a color change) to differentiate
Hospital Universitario Virgen del Rocío, Seville, SPAIN. it for human use. Studies were undertaken to demonstrate
comparable physical and safety characteristics so that the
product can be used in human trials. Materials and Methods:
Aim/Introduction: Calciphylaxis is an uncommon understood The addition of a small quantity of ascorbic acid to commercially
vascular calcification disorder with the subsequent necrosis of available HTC results in a color change from yellow/orange to
skin and soft tissues, affecting patients with end-stage renal white. We anticipated that all other characteristics would remain
disease (ESRD). Two-year mortality rates from sepsis ranges from unchanged as determined by measurements of particle size
50% to 80%. In this context, early diagnosis and subsequent distributions, pH, endotoxicity, sterility, stability and free tin in
treatment are necessary. The aim of this study is to determine solution performed in accordance with the established cGMP
the sensibility of the bone SPECT/CT as a diagnostic method in manufacturing procedures. Additionally, a study was undertaken
patients with skin lesions suggestive of calciphylaxis. Materials to demonstrate that there were no in-vivo differences between
and Methods: Descriptive, cross-sectional, retrospective study the two products. Fourteen Sprague-Dawley rats (~ 120 g)
was performed. A total of 46 consecutive patients with skin were placed in 2 groups based on sex, totaling 7 male and 7
lesions suggestive of calciphylaxis, who underwent 99mTc-HDP female rats in this study. All rats received HTC injected in the left
bone SPECT/CT from July 2011 to January 2019 were included in knee, and the ascorbic acid homogeneous Sn-117m hydroxide
this study. The sensitivity, specificity and accuracy of 99mTc-HDP colloid (AHTC) injection in the right knee. The planned dose
bone SPEC/CT were determined. Results were confirmed with administration was nominally 20 μCi (740 kBq) per injection for
the histological analysis and the response to treatment with every rat, which scales in humans to about 12 mCi (444 MBq) or
sodium thiosulfate. Results: Forty-six patients (71,7% women, double the highest anticipated human knee dose. All rats were
28,3% men) were included in this study with an average of 65,5 sacrificed at 42 days and both knees of each rat were harvested
± 11,4 years. The 91,3% of the patients had ESRD and were in and fixed in formalin. The knees were sent for histopathological
hemodialysis, 8,7% of them had not renal disease. Lesions were examination and a comparison of the left and right tissues.
localized in the lowers limbs in the 73,9% of the cases (34 of Results: There were no significant differences observed
46). Hybrid image was performed on average 147 days after in the physical characteristics between the two colloidal
the appearance of the lesions (range 14-700 days). Histological preparations other than the desired color change. No significant
analysis was performed in 54,4% of the cases (25 of 46). The histopathological differences were observed between the HTC
sensibility of the test was 100% with a specificity of 31,25% (PPV: and AHTC treated joints. Conclusion: An ascorbic Sn-117m
73%; NPV 100%). Diagnostic accuracy was 76%. Histopathology homogeneous colloid has been developed specifically for
was positive in 48% of the cases (12 of 25). Conclusion: Bone human use. Other than the appearance (color) the physical and
SPECT/CT is a non-invasive tool with a high sensibility for in-vivo characteristics are identical to the well-studied canine
the diagnosis of calciphylaxis. Its indication in early stages HTC product. The AHTC will now be used in upcoming human
of the disease could improve the early diagnosis and specific clinical trials in Canada. References: 1. “Intraarticular Injection of
treatment. It also avoids performing skin biopsy, which can have a Tin-117m Radiosynoviorthesis Agent In Normal Canine Elbows
serious complications such as septicemia. References: None. Causes No Adverse Effects”, Journal of Veterinary Radiology &
Ultrasound, DOI: 10.1111/vru.12757 (2019).
S363 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

1311 EPS-130
Radiation Dosimetry for 99mTc-labeled PSMA-I&S
e-Poster Presentation Session 9 - Do.MoRe: S. Urbán, I. Farkas, Z. Besenyi, L. Pávics;
Dosimetry University of Szeged, Szeged, HUNGARY.

Tuesday, October 15, 2019, 11:30 - 114:30 Room 133/134


Aim/Introduction: Prostate-specific membrane antigen (PSMA)
is a metallopeptidase expressed predominantly in prostate
EPS-129 cancer (PCa) cells. Recently, PSMA has shown promising results
Predictive value of99mTc-MAA SPECT-CTbased dosimetry in patients with PCa. The aim of this study was to estimate the
before radioembolization of liver tumors radiation dosimetry of 99mTc-PSMA-I&S in healthy volunteers.
P. D’abadie, R. Lhommel, S. Walrand, M. Hesse, N. Amini, P. Goffette, Materials and Methods: 4 healthy man volunteers (mean age
I. Borbath, F. Jamar; 65.2 ± 5.6 y) were injected with 561-828 MBq of 99mTc-PSMA-I&S.
Cliniques Universitaires Saint Luc, Brussels, BELGIUM. Whole-body anterior and posterior PSMA scintigraphies (WB)
was performed at 1, 2, 3, 6 and 24 h after radiopharmaceutical
administration using a triple head gamma camera (AnyScan Trio
Aim/Introduction: 99mTc- macroaggregated albumin SPECT/ SPECT/CT, Mediso Medical Imaging Systems Ltd.), equipped
CT(99Tc-MAA) is performed before 90Y liver radioembolization with low energy, high-resolution collimators (LEHR). Additionally,
(RE) for evaluating lung shunt, ruling out extrahepatic SPECT/CT images were acquired at 6 h after p. i. with the same
deposition and sometimes for calculating the delivered activity device. Regions of interest were drawn on WB and SPECT/CT
for treatment using the partition model1,2. 99mTc-MAA is then images for source organs (salivary glands, kidneys, liver, spleen,
considered as a surrogate to 90Y-microspheres to predict tumor small intestine, urinary bladder) and the whole body. Dose
and liver absorbed doses. The aim of this study is to assess factors from the OLINDA/EXM software was used to determine
the value of the dosimetry based on 99mTc-MAA SPECT-CT organ absorbed dose and equivalent doses using the RADAR
compared to the real distribution of 0Y-microspheresobserved method. Results: Physiological uptake in salivary glands,
with 90Y PET-CT. Materials and Methods: Patients treated by kidneys, liver, spleen, small intestine and urinary bladder was
RE in our institution between 2011 and 2018 for hepatocellular seen. Salivary glands with highest mean organ absorbed dose
carcinoma and cholangiocarcinoma were studied. 53 treatments (0.0207 mSv/MBq) were the critical organs followed by liver
and 136 lesions were analyzed. Tumor volumes of interest (VOIs) (0.0117 mSv/MBq), spleen (0.0086 mSv/MBq), small intestine
were delineated using the baseline imaging (arterial contrast (0.0084 mSv/Mbq), kidneys (0.0049 mSv/Mbq) and urinary
enhanced MRI ou CT scan). VOIs were fused with 99mTc-MAA bladder wall (0.0039 mSv/MBq). The mean effective dose was
SPECT and 90Y PET using PMOD 3.7 for calculation of a tumor found to be 0.0044 mSv/Mbq, which means 3.29 ± 0.51 mSv
to total liver ratio (T/L). Mean doses (DY90 and DMAA) and Dose effective dose using 740 MBq PSMA I&S. Measured absorbed
Volume histogram (DVH) were calculated using the MIRD doses and effective doses are similar to previously reported
formula with input of the delivered activity of 90Y microspheres 99m
Tc-EDDA/HYNIC-iPSMA (3.42 ± 0.78 mSv/740 MBq) [1] and
and of the ratio T/L (MAA or 90Y). Using DVH, the minimal dose much lower than the 99mTc-MIP-1404 (6.5 mSv/740 MBq) and the
deposited in 66% of the tumor volume (D66) was calculated. 99m
Tc-MIP-1405 (5.82 mSv/740 MBq) [2]. Conclusion: To the best
Patients were categorized as a function of the catheter’s of our knowledge, this is the first report on radiation dosimetry
position during the 99Tc-MAA and 90Ymicrospheres injections. of 99mTc-labeled PSMA-I&S in healthy volunteers. PSMA-I&S is
Correlations were analyzed using the Spearman’s coefficient found to be a safe diagnostic agent with similar effective dose to
(R) and the accuracy of the prediction was studied using the 99m
Tc-EDDA/HYNIC-iPSMA. References: [1] C. Santos-Cuevaset
standard error of the estimate (SEE). Results: Regarding only al. 99mTc-labeled psma inhibitor: Biokinetics and radiation
treatments realized in the same angiographic conditions (25 dosimetry in healthy subjects and imaging of prostate cancer
treatments, 58 treatments), the correlation was strong (R=0,78) tumors in patients. Nuclear Medicine and Biology, 52:1 - 6, 2017.
but the linear regression demonstrates a significant risk of error [2] S. Vallabhajosula et al. 99mTc-labeled small-molecule inhibitors
(SEE=76 Gy). A better correlation was found after exclusion of of prostate-specific membrane antigen: Pharmacokinetics
angiographies with injections in the proximity of an arterial and biodistribution studies in healthy subjects and patients
bifurcation (R=0,88, SEE=56 Gy). Using DVH and D66, results were with metastatic prostate cancer. Journal of Nuclear Medicine,
quite similar in both conditions (R=0,71, SEE=57 Gy and R=0,82, 55(11):1791-1798, 2014.
SEE= 51 Gy). Conclusion: Despite good catheter positioning,
our study failed to confirm an accuracy in 99Tc-MAA dosimetry.
In clinical practice, this dose estimation would not guarantee EPS-131
to avoid liver toxicity in case of dose escalation based on the Correlation between lesion absorbed dose and relative
partition model. Moreover, DVH applied to 99Tc-MAA SPECT/CT variation of the 99mTc-HDP lesion uptake before the first
is not predictive in many cases. References: 1- Padia SA et al. J cycle and after the sixth cycle in patients treated for
Vasc Interv Radiol 28:1-15, 2017.2- Garin E et al. Eur J Nucl Med metastatic castration resistant prostate cancer with 223Ra
Mol Imaging 43:559-75, 2016. P. Minguez Gabiña, A. Gomez de Iturriaga Piña, A. Esteban
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S364

Figueruelo, M. Nevares Herrero, R. Valverde Jorge, I. Fernandez up about 25% of the per capita medical effective dose in the
Tercero, E. Rodeño Ortiz de Zarate; United States1. Thorough investigation of health risks associated
Osakidetza, Barakaldo, SPAIN. with NM procedures relies on the accuracy of the radiation dose
assessment and hence on the human anatomy models in use.
Existing organ dose estimation tools are limited to simplified
Aim/Introduction: We looked for a possible correlation anatomy models or fixed body morphometry. To fill the research
between relative variation of the 99mTc-HDP uptake in bone gaps, we developed a new dose calculation tool using advanced
lesions and lesion absorbed dose in patients with metastatic human anatomy models. Materials and Methods: We adopted
castration resistant prostate cancer (mCRPC) treated with 223Ra. the twelve National Cancer Institute (NCI) pediatric and adult
Materials and Methods: Ten patients were included in the phantoms2 developed from patient computed tomography
study. Absorbed doses of the lesions with the higher 99mTc-HDP images as well as the two adult reference computational
uptake were determined for the first cycle of the 223Ra therapy. phantoms3 from the International Commission on Radiological
The 223Ra activity in the lesions was obtained from planar Protection (ICRP). Specific Absorbed Fractions (SAFs) were
imaging at 3d and 7d after 223Ra administration, and the time- calculated for photon and electron on the NCI phantoms for
integrated activity from a mono-exponential curve determined 68 source and 55 target regions using the MCNPX Monte Carlo
by those two time-points. The lesion volume was obtained from radiation transport code4. SAFs for the two adult ICRP reference
99m
Tc-HDP SPECT/CT imaging and the S-value calculated for phantoms were adopted from the ICRP Publication 1335. S
unit-density spheres of that volume. A correction for the bone values were then derived from the SAFs for 299 radionuclides
mass density was applied to the calculated lesion absorbed commonly used in nuclear medicine6. A graphical user
dose. For the lesions for which dosimetry had been performed, interface-based computer program, named National Cancer
in the 99mTc-HDP WBSs performed before the first cycle and Institute dosimetry system for Nuclear Medicine (NCINM), was
after the sixth cycle were administered, the mean value of the finally developed to facilitate data input and output. Results:
counts in the ROIs encompassing them, CROI, was determined. The ratios of the iodine-131 S values from the NCI phantoms
As the time between the 99mTc-HDP injection and the WBS was to those from the ICRP ones were on average 0.96±0.10σ and
not the same for all patients, CROI was made relative to the femur 0.92±0.59σ for eight major organs in the adult male and female
uptake. The relative variation of CROI between the two WBSs, phantoms in case of self-absorption and cross-irradiation,
ΔCROI, was obtained. In order to analyse the effect on ΔCROI of respectively. The ratios of the iodine-131 S values from the NCI
other variables, a multivariate analysis was performed including phantoms to those from OLINDA/EXM 1.07(based on the ORNL
the lesion absorbed doses, the received concomitant therapies stylized phantoms) were on average 0.91±0.15σ and 1.34±0.62σ
(abiraterone, enzalutamide, external beam radiotherapy) and for eight major organs in the adult and pediatric phantoms
the total number of lesions. Results: The absorbed dose of 29 in case of self-absorption and cross-irradiation, respectively.
lesions was determined. Values of ΔCROI and of the absorbed Conclusion: A good agreement was overall observed between
doses followed a normal distribution, with mean±1SD values iodine-131 S values from the NCI phantoms series vs. the ICRP
of 46±32% of 1.4±0.Gy, respectively. A logarithmic correlation 110 reference phantoms, both of which have realistic anatomy
was obtained between ΔCROI and the lesion absorbed dose compared to the ORNL stylized phantoms. Greater differences
(Pearson’s correlation coefficient of 0.86). The multivariate were, however, revealed in S values between the NCI phantoms
analysis concluded that the effect of other variables on ΔCROI and the stylized phantoms (OLINDA), especially for cross-
was no significant in relation to that of the lesion absorbed irradiation, which emphasizes the importance of realistic human
dose. Conclusion: We found a strong correlation between the anatomy models in S value calculations. The NCINM program
relative variation of the mean value of the counts in the ROIs will be useful for epidemiologic studies of risk and patient dose
encompassing lesions in the 99mTc-HDP WBSs performed before monitoring in NM procedures. References: 1NCRP Report 160
the first cycle and after the sixth cycle and the lesion absorbed (2009) 2Lee et al (2010)3ICRP Publication 110 (2009) 4Briesmeister
dose determined for the first cycle of the 223Ra therapy. These JF (2000) 5ICRP Publication 133 (2016) 6ICRP Publication 107
results show that determining lesion absorbed doses may be (2008) 7Stabin et al (2005).
useful in order to evaluate the evolution of those lesions in the
treatment of mCRPC with 223Ra. References: None.
EPS-133
Validation of a voxel based MRT dosimetry software
EPS-132 module for 3D slicer
NCINM: an internal dosimetry software using ICRP and NCI D. P. Rushforth, J. Jear, I. Murray, G. Flux;
pediatric and adult computational phantoms The Royal Marsden NHS Foundation Trust,
D. Villoing, C. Lee; Sutton, UNITED KINGDOM.
National Cancer Institute at the National Institutes of
Health, Rockville, MD, UNITED STATES OF AMERICA.
Aim/Introduction: Dosimetry for Molecular Radiotherapy
can be complex and time consuming. An in-house dosimetry
Aim/Introduction: Nuclear medicine (NM) procedures make module, was designed to speed up and simplify this process.
S365 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

Voxelised calculations were used to enable 3D visualisation and and Methods: We tested two ways of modelling a radioactive
analysis. The aim of this project was to validate this approach source within GATE (version 8.2): manual spectrum input (from
against conventional region based dosimetry, particularly to [2]) and explicit radioactive decay process modelling (ion
evaluate those factors relevant to voxel dosimetry including source). To implement the comparison, simulations in cubes
higher noise to signal ratios. Materials and Methods: Written of various materials (15) were set up. Cubes were made large
in python for the open-source platform, 3D Slicer, the module enough to account for the deposition of most emitted energy
calculates absorbed doses at both voxel and region levels. (>99%).We considered 12 radioactive isotopes relevant in a
Time activity curves are fitted using least squares minimisation, context of nuclear medicine: 32P, 51Cr, 89Sr, 90Y, 131I, 153Sm, 177Lu,
with constraints to compensate for voxel noise. Final absorbed 186
Re, 188Re, 192Ir, 212Pb, 223Ra. Absorbed doses per decay (S factors)
doses can be determined using either local deposition (LD) or were calculated for 107 primaries (manual spectrum input) or
fast convolution (FC). Validation was performed using a SPECT 107 Bq.s (ion source). Results: The comparison between manual
scan of a 3D-printed anthropomorphic phantom with known spectrum input and ion source yield little differences (<1%)
activities of Y90 in liver, spleen, kidney and lesion compartments. for simple decay. In complex decay chains, more important
The acquired image was used to replicate a set of time-activity differences (>10%, 160% for 223Ra) were observed. This was
images with voxel half-lives of 24 hours. Absorbed doses explained by the presence within the chain of semi-stable
calculated using LD and FC were compared to results obtained daughters (mainly alpha) with very long half-lives. These are fully
using region based calculations and Olinda Dose Factors. To accounted for in ion source decay process, even though the
determine the effect of image noise on voxel based calculations, secular equilibrium is never achieved in practice. Geant4 handles
simulated datasets were created comprising three uniform this with a pre-equilibrium decay models that are not currently
images containing 1283 voxels with effective half-lives ranging implemented in GATE. Using ion source requires less user input
from 1/3 to 1 times the physical half-life. A random Gaussian since it explicitly models nucleus decay (all emitted particles);
number generator was used to add noise and produce a range the input should be given in Bq.s, whereas for manual spectrum
of datasets with coefficients of variation (CoV) ranging from 0 to input, the total number of simulated particles and type should
100%. Results: LD and FC gave absorbed organ doses for the be entered. Furthermore, the ion source implementation uses a
phantom dataset that were on average within 3.4% (SD=0.01%) variance reduction technique to model all decay chains [1]. As
and 1.6% (SD=0.02%) of the conventional methodology a consequence, the simulation time to get the same statistics is
respectively. Data were unaffected by the presence of image lower for complex emission spectra (average 3 times for 51Cr, 5
noise when doses were calculated using average VOI activities. times for 131I, 2.55 for 177Lu and 17.8 times for 223Ra). Conclusion:
When fitting at the voxel level a 0.017% difference was observed The validation results show that ion source is an accurate yet
for noise levels up to a CoV of 10%. For the dataset used, noise efficient way to model isotope decay for nuclear medicine
in the dose map was 40% less than that present in the original dosimetry. Yet we recommend caution when using it in GATE
images. Conclusion: The module provides a simple and simulations involving radioactive nuclides who contain decay
efficient solution for performing dosimetry reducing the time chains. References: 1 Steffen Hauf et al. IEEE Trans Nuclear
required from 5 hours to 20 minutes. The results derived are Science 60.4 (2013); 2 K.F. Eckerman and A. Endo. J. Nucl Med
in good agreement with our previous methodology and the 50.12 (2008).
constraints used for the voxel calculations have a negligible
effect on the resulting doses. Further work will investigate the
quantitative impact of different registration methods (rigid and EPS-135
deformable) and explore alternate methods for reporting voxel Customisation of Internal Dosimetry Phantoms by Using
dose information. References: None. the OpenDose SAFs Generated for the ICRP Voxel Phantom
A. Malaroda1, E. McKay2;
1
St Vincent’s Hospital Sydney, Sydney, AUSTRALIA,
EPS-134 2
St George Hospital, Sydney, AUSTRALIA.
Geant4/GATE ion source implementation for internal
dosimetry applications
A. Vergara Gil1, M. Chauvin1, G. Kayal1,2, J. Ocampo1, M. Bardies1; Aim/Introduction: The OpenDose project [1] is generating
1
CRCT, UMR 1037, INSERM, Université Toulouse III, a database of Specific Absorbed Fractions (SAFs) for the 140
Paul Sabatier, Toulouse, FRANCE, 2SCK.CEN, Belgian regions of the ICRP Publication 110 voxel phantoms. One
Nuclear Research Centre, Boeretang, BELGIUM. major application of this data is the computation of internal
dosimetry for arbitrary radio-pharmaceuticals. Existing software
such as OLINDA/EXM or IDAC provide a hard-coded set of
Aim/Introduction: In Geant4, the ion source implementation source and target regions which do not necessarily match,
allows the full integration of isotope decay within simulations for example, the sources for which residence time data might
[1]. This feature has not been tested for internal dosimetry of be available. There is a need for software which enables the
complex decay chains in GATE. The aim of this work is to study construction of customised dosimetric phantoms where
the dosimetric implications of the use of ion source for several source and target regions are comprised of arbitrary sets of
radionuclides currently used in Nuclear Medicine. Materials composable parts from the OpenDose database or other SAF
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S366

collections. Materials and Methods: A packaging module no effect on the process of NCT. Measurements of changes
was implemented for the OpenDose calculator [2]; this allows in electrical resistivity are carried out by the four point probe
subsets of the SAFs generated by the OpenDose project to be method, manually or automatically. Results: In the framework
combined, as mass-fraction weighted sums, to form SAFs for of this work, the conditions for using monocrystalline silicon
composite source and target regions. The module was validated plates to determine dose during the NCT were determined.
by estimating dose depositions for the radio-iodide model The relationships between the determined conductivity of
described by the ICRP Publication 128. The model comprised 12 plates with distribution of thermal neutrons over the volume of
sources (blood, thyroid, salivary glands, liver, kidneys, bladder, a biological object for ionizing radiation beams with different
stomach wall, stomach contents, small, upper-large and lower- spectral characteristics have been developed. Conclusion: The
large intestine contents) and 22 targets (as in OLINDA/EXM, advantages of the proposed method are that P-32 formed is
except for bone surfaces which can not be simulated in voxel a stable isotope and its inclusion in the silicon crystal ensures
models) constructed from 26 and 53 components of the ICRP that information on the accumulated dose is preserved for
voxel phantom respectively. The phantom’s composite SAFs an extremely long period of time. In this way, it is possible
were compared against SAFs generated by direct Monte Carlo to restore information about modes of irradiation after any
simulation using a previously validated GATE macro [3]. Results: arbitrary period of time. In this case, the sample is not subject
Excellent agreement was observed between the composite SAFs to aging, ultraviolet radiation, oxidation, or exposure to high
and the SAFs estimated by the GATE Monte Carlo simulation, temperatures. At the same time, measurement accuracy in
with differences of less than 5% in more than 90% of the source- therapeutic range (10^11-10^13) of thermal neutron fluence is
target combinations. In general, percentage differences were measured with high accuracy, since in this fluence range that a
less than 10% except for the combinations: thyroid <-- bladder sharp drop in electrical resistivity is observed.The disadvantage
(~18%), skin <-- salivary glands (~18%), testes <-- salivary glands of this method is the need to pre-calibrate silicon samples on
(~14%) and skin <-- thyroid (~14%). Conclusion: Composition each neutron beam, since in the general case the nature of
of SAFs from separate sources and targets provides a viable and the change in the conductivity of silicon will depend on the
flexible alternative to hard-coding SAFs into internal dosimetry spectrum of neutron radiation. References: None.
software. References: 1. Chauvin M, et al; Physica Medica, 42(1):
32-33 (2017) 2. Mckay E, Malaroda, A; Australas Phys Eng Sci Med
(2019) 42: 285 3. Mckay E, Chatrie F, Malaroda, A; Australas Phys EPS-137
Eng Sci Med (2018) 41: 245. Effects of timing and number of SPECT acquisition on
biodistribution and dose evaluation in hepatocellular
carcinoma patients treated with 188Re SSS Lipiodol
EPS-136 radioembolization
Feasibility study of using monocrystalline silicon as a K. Delaunay1,2, E. Garin3,4,5, Y. Rolland6, N. Lepareur3,5, S. Laffont3, V.
dosimeter for neutron capture therapy Ardisson3, J. Edeline7,4,5;
M. Anikin, I. Lebedev, N. Smolnikov, A. Naymushin; 1
Paris Diderot University, Paris, FRANCE, 2Bichat Claude
National Research Tomsk Polytechnic University, Bernard University Hospital, Department of Nuclear Medicine,
Tomsk, RUSSIAN FEDERATION. Paris, FRANCE, 3Comprehensive Cancer Institute Eugene
Marquis, Department of Nuclear Medicine, Rennes, FRANCE,
4
University of Rennes 1, Rennes, FRANCE, 5INSERM INRA UMR
Aim/Introduction: During preclinical studies of interaction of 1241 NuMeCan, Rennes, FRANCE, 6Comprehensive Cancer
ionizing radiation with biological objects exact experimental Institute Eugene Marquis, Department of Radiology, Rennes,
determination of dosimetric fields is necessary. In this paper, FRANCE, 7Comprehensive Cancer Institute Eugene Marquis,
aspects of using nuclear purity monocrystalline silicon plates Department of Medical Oncology, Rennes, FRANCE.
as accumulative dosimeters during NCT are considered.
Materials and Methods: The essence of the method for
determining thermal neutrons fluence using monocrystalline Aim/Introduction: Phase one trial Lip Re 1 (NCT 01126463)
silicon is transmutation of Si-31 nuclei into P-32 after interaction results are promising concerning 188Re-SSS Lipiodol
with thermal neutron. Since electrical conductivity of silicon radioembolization in hepatocellular carcinoma [1]. In order to
depends, inter alia, on presence of impurities, it is possible to develop a simple dosimetry protocol that could reduce the
unambiguously determine the relationship between specific number of imaging time points, we evaluated the impact of
electrical resistance of silicon and amount of P-32 formed. The the number of SPECT acquisition on the biodistribution and
method of dose measuring involves installation of a thin (less dose evaluation. Materials and Methods: Quantification of
than 1 mm) silicon plate with a diameter of more than 15 mm in tumor and target organs uptake (in % of detected activity, DA)
front of the irradiated sample. The location of the plate is chosen of 188Re-SSS Lipiodol evaluated on SPECT/CT studies performed
so that the surface of plate is perpendicular to radiation beam at 1, 6, 24, 48- and 72-hours post-administration with biological
and located as close as possible to surface of the biological elimination corrected. Evaluation of tumor and target organs
object. Silicon monocrystalline plate has small cross-section of absorbed doses using MIRD formalism. Relative quantification
interaction with neutrons of all energies, so there is practically and the dose estimation in each organ derived from each of
S367 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

these 5 subsets and derived from one, two- or three-time subsets with neoadjuvant chemotherapy were enrolled in this study.
were compared to those obtained using all five data points. The diagnosis was performed: breast and axillary ultrasound,
Variability of the relative quantification and the dose evaluation breast MRI and mammography. During the treatment, MRI
were calculated as percent difference. Results: Between May was performed in the middle and at the end of treatment. The
19, 2010 and September 1, 2017, six patients were administered response at the end of the treatment by MRI was classified as:
1645±361MBq of 188Re-SSS Lipiodol. Based on 5 data points of Complete Response (RC): Disappearance of the enhancement,
SPECT studies (reference quantification): 90.96±1.15% of activity Subtotal Response (SR): Punctate uptake <4mm and Partial
was detected in the liver, with 65.96±1.12% of DA in the tumor. Response (PR): Tumor Remains > 4 mm. To evaluate the
25.0±1.29% of DA was in the healthy liver and 9.03±0.55% in pathological histological response we used The Miller and Payne
the lungs, with 5.48±0.55% in the right and 3.65±0.61% in system. The day before surgery an intralesional dose of 99mTc-
the left lungs. Using one, two and three time SPECT subset, nanocolloid (activity of 4 mCi and 0.2 ml volume) was injected
biodistribution quantification ranged from (compared to the guided with MRI using a titanium needle. The site of injection
reference value): -3,13 to 1.71% in whole liver, -3.84 to 1.27% in and lymphatic drainage were confirmed by scintigraphy image.
the tumor, -14.73 to 5.56% in healthy liver, -21.61 to 32.87% in Intraoperative lesion and sentinel lymph node were localized
right lung and -10.63 to 29.41% in left lung. Based on 5 times and excised during surgery using a gamma probe. In some cases
SPECT studies (reference dose), mean absorbed doses were were necessary to administer blue day. Results: The 100% of
as follows: 7.9±3.7Gy to whole liver, 42.7±34.0Gy to tumour, the patients got a complete surgical excision of primary breast
10.2±3.7Gy to healthy liver, and 1.5±1.2Gy to lungs. Using one, tumour with free margins. Lymphoscintigraphy showed drainage
two- and three-time SPECT subset, dose calculation ranged in 89% patients. When we analyzed the correlation between
from (compared to the reference value): -8.74 to 1.56% in whole MRI-response and the pathological histological response: 82.2%
liver, -17.56 to 1.24% in the tumor, -18.75 to 6.57% in healthy patients with CR corresponded G5 and 15.5% G4. 50% patients
liver, -16.49 to 29.97% in lungs. Conclusion: Biodistribution with SR corresponded G5 and 41.7% G4. 50% patients with RP
quantification and dose evaluation based on one, two- or three- corresponded G3, 17% G2 and 33.3% G4 and G5. 5-years Follow-
time subsets are reliable for whole liver, tumor and healthy liver. up Media, 94.4 % patients were free disease. Conclusion: Our
References: [1] Delaunay K, Edeline J, Rolland Y, Lepareur N, results demonstrate MRI radioguided surgery after neoadjuvant
Laffont S, Palard X, et al. Preliminary results of the Phase 1 Lip- chemotherapy is a reliable technique for complete excision
Re I clinical trial: biodistribution and dosimetry assessments nonpalpable breast lesions and to avoid recurrences. We found
in hepatocellular carcinoma patients treated with 188Re-SSS a good correlation between MRI-response and the pathological
Lipiodol radioembolization. Eur J Nucl Med Mol Imaging. 2019. histological response. References: None.

1411 EPS-139
PSMA Expression according to different Prostate Cancer
e-Poster Presentation Session 10 - Oncology: Bone Metastases subtypes
Oncology - Mixed Pickles P. I. d. P. Soeiro1, R. Silva1,2, G. Costa1,3, J. Pedroso de Lima1,2,3;
1
Centro Hospitalar e Universitário de Coimbra, Coimbra,
Tuesday, October 15, 2019, 14:30 - 16:00 Room 133/134 PORTUGAL, 2Instituto de Ciências Nucleares Aplicadas
à Saúde, Coimbra, PORTUGAL, 3Faculdade de Medicina
da Universidade de Coimbra, Coimbra, PORTUGAL.
EPS-138
Is it reliable to perform radioguided surgery with Magnetic
Resonance Imaging after neoadjuvant chemotherapy in Aim/Introduction: Prostate cancer (PCa) has historically been
patients with breast cancer? associated with blastic bone metastases, but hybrid imaging and,
S. Fuertes Cabero, V. Martinez de Vega, S. Linares, U. Vera more recently, [68Ga]Ga-PSMA PET/CT have shown that other
Schmülling, G. Hernandez Cortes, R. Sainz De La Cuesta, R. Murillo, types, although less frequent, are also present. Furthermore,
L. Gonzalez Cortijo, A. Maldonado Suarez; the scientific literature implies that lytic lesions are associated
H. Universitario Quironsalud Madrid, Pozuelo with aggressive PCa phenotypes.The aim of this study was to
de Alarcón (Madrid), SPAIN. evaluate PSMA expression of different PCa bone metastasis
subtypes, as assessed by [68Ga]Ga-PSMA PET/CT uptake.
Materials and Methods: All PCa patients referred to our center,
Aim/Introduction: To evaluate if it is reliable to perform between October 2015 and March 2019, for [68Ga]Ga-PSMA
radioguided surgery with breast Magnetic Resonance Imaging PET/CT with bone metastasis were included. Only staging and
(MRI) after neoadjuvant chemotherapy in patients with breast restaging scans performed in a first biochemical relapse setting
cancer. The study evaluated the correlation with the pathological were accepted. Castration resistant PCa and patients submitted
histological response and follow-up of the disease. Materials to palliative systemic therapies (as chemotherapy or ADT) were
and Methods: This is a retrospective study performed from also rejected. All bone metastasis of significant size (above
October-2011 to April-2015. 71 breast cancer patients treated 15mm) were classified according to morphology as blastic,
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S368

lytic, mixed or undetectable. Size, SUVmax and Hounsfield units nature, we found subtle differences between the use of FLUC
were also recorded. Results: A total of 725 [68Ga]Ga-PSMA PET/ and PSMA. Both scans were more useful in the high risk group,
CT scans were performed during the designated time window. and FLUC scans were more likely to be abnormal in the 65 to 70
One hundred and eighty seven patients presented with bone age group while PSMA scans were more likely to be abnormal
metastasis, of which only 43 (70±9.2 46-87 years) fulfilled the in the 70 to 75 age group. Further analysis across a bigger
inclusion criteria. We analysed 216 lesions: 100 blastic, 42 mixed, comparative cohort involving multiple centres may be helpful
38 lytic and 36 undetectable by CT. The pelvis was the most to identify specific roles for each tracer. References: None.
frequent location (77), followed by the spine (65), costal grid (34)
and lower limbs (13). The average SUVmax for all subtypes was
9.0 g/ml (±9.0, 1.1-68.0). SUVmax was not statistically different EPS-141
between the different bone metastasis subtypes (Kruskal-Wallis, Risk-stratification of significant prostate cancer by
p: 0,065). Conclusion: PSMA expression, as assessed by [68Ga] 18F-choline PET/MRI is more accurate and cost-effective
Ga-PSMA PET/CT uptake, was not statistically different between than multi-parameter MRI alone
the diverse bone metastasis subtypes. References: None. M. R. Piert1, M. S. Davenport1, C. Barnett1,2, J. S. Montgomery1, E.
Lee1,3, X. Shao1, L. P. Kunju1, B. Denton1;
1
University of Michigan, Ann Arbor, MI, UNITED STATES OF
EPS-140 AMERICA, 2RTI Health Solutions, Research Triangle Park, NJ, UNITED
Ga68 PSMA or F18-Fluciclovine: When & Why - A STATES OF AMERICA, 3Department of Information and Statistics,
Comparative Review of early clinical experience in a UK Chungnam National University, Daejeon, KOREA, REPUBLIC OF.
centre
M. Didier, S. Vinjamuri;
The Royal Liverpool and Broadgreen University Aim/Introduction: A prospective single-arm clinical trial
Hospitals NHS, Liverpool, UNITED KINGDOM. (NCT01751737) was conducted to determine the diagnostic
efficacy and cost-effectiveness of 18F-choline PET/MRI to detect
Gleason ≥3+4 prostate cancer. Materials and Methods: Before
Aim/Introduction: Due to various regulatory and targeted and systematic prostate biopsy, multi-parametric MRI
commissioning restrictions, Centres across the world are and 18F-choline PET/CT were performed in 56 subjects with 90
allowed to use different tracers to characterize the prostate, Likert score 3-5 MRI target lesions, using a 18F-choline target-to-
pelvis and bones in patients with possible recurrent prostate background ratio (TBR) >1.58 to indicate a positive 18F-choline
cancers. Temporary suspension of our Ga68 PSMA (PSMA) result. MRI-targeted- and standard prostate biopsies were
scanning service enabled us to attain approval and use a performed after registration of real-time transrectal ultrasound
relatively newer tracer F18-Fluciclovine (FLUC). Given this with T2-weighted MRI. A mixed-effects logistic regression was
opportunity we sought to make some comparison of the applied to measure the performance of MRI vs. 18F-choline
clinical usefulness of these two tracers. In the absence of direct PET/MRI (based on prospective Likert and retrospective PI-
comparison of usage of the two tracers in the same patient, we RADS version 2 scores). Health and economic consequences of
decided to have a “real-world experience” comparison between 18F-choline PET/MRI for detection of Gleason ≥3+4 cancer were
the two tracers in cohorts matched for age and risk status. assessed using a Markov model of prostate cancer onset and
Materials and Methods: 31 patients scanned (age range 57 to progression. The cost-effectiveness of PET/MRI strategies was
80) with FLUC since March 2019 were therefore matched with compared to universal standard biopsy, MRI alone with biopsy
31 matched patients from our cohort of 370 patients scanned only for PI-RADS=3-5 lesions, and MRI alone with biopsy only
with PSMA between 2016 -19 . We then analysed the patterns for Likert=4-5 lesions. For each MRI strategy, either no biopsy
of avidity (ie prostate, pelvic nodes or bones/distant metastases or standard biopsy could be performed after a negative MRI.
or combinations of these). Results: The largest proportion Deaths averted, quality-adjusted life years (QALYs), cost, and
of the patients were found within the age ranges 65 to 70 ( incremental cost-effectiveness ratios (ICERs) were estimated.
n=13) and 70 to 75 (n=9) and there were more high risk group Results: The per-patient accuracy of systematic and targeted
patients (n=20). The net overall positivity rate for FLUC was 74% biopsy based on MRI alone was 69.6% for Likert=4-5 scores. The
(23) compared to 84% (26) for PSMA. The FLUC scan identified best-performing PET/MRI strategy that selected all high-risk
more local prostatic avidity (13/23 vs 8/26 for PSMA), while the (Likert=5) plus any Likert=4 lesion with elevated 18F-choline
PSMA scan identified more extra-prostatic sites of avidity (21/26 TBR>1.58 improved the accuracy to 92.9% (p=0.002). Also,
vs 14/23 for FLUC). In the more common ages of presentation selecting all PI-RADS=5 lesions plus any PI-RADS=3-4 lesion with
to us, PSMA identified more disease in both groups of 65 to 70 18F-choline TBR>1.58 was significantly more accurate (91.1%)
(FLUC 50% vs PSMA 70%) and 70 to 75 (FLUC 50% vs PSMA 89%). than MRI alone (accuracy=75%;p=0.016). When 18F-choline
When these results were interpreted in the clinical context, the PET/MRI was negative, standard biopsy was more expensive
comparative detection rates were for High Risk (FLUC 60%; and had lower QALYs than performing no biopsy. The screening
PSMA 76%); Intermediate risk (FLUC 0%; PSMA 75%;] and Low strategy that performed 18F-choline PET/MRI with Likert scoring
Risk (FLUC 0%; PSMA 100%) (2 cases had unknown risk status). ($22,706/QALY gained relative to MRI alone) recommended
Conclusion: In this small study limited due to its retrospective standard and targeted biopsy for men with positive imaging
S369 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

and no biopsy for men with negative imaging, and reduced and 18F-DCFPyL in the setting of biochemical recurrence of PCa
the number of biopsies by 35% compared to MRI alone. When post-prostatectomy is comparable. References: None.
comparing the same policies using PI-RADS, hybrid 18F-choline
PET/MRI cost $46,867/QALY gained relative to MRI alone. In
threshold analysis, the best strategy among those considered EPS-143
remained cost-effective when sensitivity and specificity of PET/ Prognostic role of the Total Metabolic Tumor Volume
MRI and combined biopsy were simultaneously reduced by 20 (TMTV) and the Total Lesion Glycolysis (TLG) in the
percentage points, indicating robustness of the conclusions to definition of clinical outcome and response to therapy in
model parameter estimates. Conclusion: 18F-choline PET/MRI Hodgkin’s Lymphoma
for detection of Gleason ≥3+4 primary prostate cancer is more M. Spallino1,2, M. Cuzzocrea1, E. De Ponti3, S. Bolis4, I. Casaroli4, C.
accurate and cost-effective than MRI alone, mainly by reducing Landoni1,5, L. Guerra5;
the number of unneeded biopsies and therapies. References: 1
Nuclear Medicine Department, University Milan Bicocca,
None. Milan, ITALY, 2ASST Grande Ospedale Metropolitano Niguarda,
Milan, ITALY, 3Medical Physics Department, San Gerardo
Hospital ASST, Milan, ITALY, 4Hematology Department, San
EPS-142 Gerardo Hospital ASST, Monza, ITALY, 5Nuclear Medicine
Comparison of 68Ga-PSMA-11 and 18F-DCFPyL in prostate Department, San Gerardo Hospital ASST, Monza, ITALY.
cancer patients with biochemical recurrence after
prostatectomy
L. van Kalmthout1, M. Wondergem2, B. Jansen3, H. van Melick4, D. Aim/Introduction: Recent papers showed that the TMTV and
Oprea-Lager3, A. Vis3, J. de Klerk5, F. van der Zant2, M. Lam1; TLG assessed in baseline-PET are correlated to prognosis and
1
Academic hospital, Utrecht, NETHERLANDS, 2Noordwest consequently could be used to optimize the treatment strategy,
Ziekenhuisgroep, Alkmaar, NETHERLANDS, 3Academic but published results are sometimes discordant. In this work
hospital, Amsterdam, NETHERLANDS, 4St. Antonius we evaluate whether quantitative parameters in baseline-PET
Ziekenhuis, Nieuwegein, NETHERLANDS, 5Meander are correlated to overall-survival (OS), disease-free-survival
Medisch Centrum, Amersfoort, NETHERLANDS. (DFS) and treatment response in patients with Hodgkin’s
Lymphoma (HL) treated at our Hematology Division. Materials
and Methods: 163 patients (94men; mean age: 38y(18-81)
Aim/Introduction: 68Gallium (68Ga)-labeled PET tracers, e.g. with newly diagnosed HL, stage I-IV (11stage I, 49stage IIA,
68
Ga-PSMA-11, targeting the prostate-specific membrane 34stage IIB, 33stage III, 36stage IV) referred to our Hospital were
antigen (PSMA) receptor are increasingly used to localize the retrospectively evaluated. We calculated the semiquantitative
site of recurrence in patients with a biochemical recurrence parameters at baseline-PET using PET viewer add-on of FIJI
(BCR) of prostate cancer (PCa). Labeling of PSMA tracers with software with a fixed threshold of 41% of the maximum. Sum
fluor-18 (18F), e.g. 18F-DCFPyL, leads to improved image quality rank test was performed to evaluate statistical differences
and may enhance the detection of metastases. The present between the semiquantitative parameters in patients with
study aims to assess the detection performance of 18F-DCFPyL different outcome. Receiver operating characteristics (ROC)
PET/CT compared to 68Ga-PSMA PET/CT in patients with a analysis was performed to evaluate the best threshold to
BCR after prostatectomy. Materials and Methods: From 2015 discriminate patients’ prognosis. Results: Overall, baseline-
up to 2018, 160 consecutive patients, scanned with either PET of 158/163 HL patients were evaluated for quantitative
68
Ga- PSMA or 18F-DCFPyL for BCR (PSA-level: 0.5-3.5 ng/ml) parameters. Median follow up duration was 40 months, 5
after prostatectomy in four hospitals in the Netherlands, were patients died and 11 relapsed.In dead and alive patients, median
retrospectively analyzed. Imaging was performed according MTV values were 269.5 (87.3-546.5) vs 84.6 (3.5-590.9) (p=0.036)
to standard acquisition protocols using 68Ga-PSMA-11 (n = 80; respectively and median TLG values were 2772.1 (341.7-3724.1)
1.5-2.0 MBq/kg, PET 60 min post-injection) or 18F-DCFPyL (n = vs 492.4 (15.5-4596.8) respectively (p=0.029). According to ROC
80, 3.0 MBq/kg, PET 120 min post-injection). Both tracers were analysis, a TMTV cut-off value of 269.5 mL showed a sensitivity,
compared on basis of site of tumor recurrence, number of specificity and accuracy respectively of 60%, 88.2% and 87.3%
detected lesions and PSA-stratified detection rates. Statistical to identify patients with good vs worse prognosis; the same
analyses were performed using SPSS Statistics version 24. figure for TLG were 60%, 96.7% and 95.6% with a cut-off value
Results: The overall detection rate of 68Ga-PSMA PET/CT of 2772.1. Kaplan Meier curves showed an OS significantly
and 18F-DCFPyL PET/CT was 71.3% and 74.4% (p = 0.795), different in patients with low and high TMTV (p=0.05) and TLG
respectively. For PSA-levels of 0.5-1.0, 1.0-1.5, 1.5-2.0, 2.0-2.5, 2.5- (p<0.05). We classified patients with Deauville Score (DS) 1-2-3
3.0 and 3.0-3.5 ng/ml, PSA-stratified detection rate of 68Ga-PSMA at interim-PET as responders and patients with DS 4-5 as non-
was 63.6%, 75.0%, 83.3%, 84.6%, 66.7% and 100%. Detection responders. TMTV and TLG were good to discriminate responder
rate of 68F-DCFPyL in these PSA-categories was 62.1%, 73.7%, vs non-responder patients with the sum rank test (p=0.07 and
90%, 100.0%, 80.0%, 100.0%. Differences in detection rate were 0.05 respectively).No statistically significant difference was
not found to be statistically significant. Conclusion: Our data found comparing metabolic parameters relative to relapsed
suggest that the diagnostic performance of both 68Ga-PSMA-11 and non-relapsed patients. Conclusion: We demonstrated
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S370

the correlation between baseline-PET metabolic parameters with negative PET/CT and BMB results(58%). Discordant results
and clinical outcome in terms of prognosis and response to were obtained in 16 cases(17%), 10 of them with positive PET/
therapy defined by interim-PET. These results are promising CT and negative BMB(2 diffuse BMU>L, 1 diffuse BMU=L+E,
but confirmation in a larger series is requested, particularly and 7 uni/multifocal pattern), and 6 with negative PET/CT and
to increase patients with worse prognosis. If these results will positive BMB. A, S, Sp, PPV and NPV were 83%,84%,81%,76%
be validated in a larger population, TMTV and TLG, in addition and 88%, respectively, for visual analysis; 75%,56%,88%,77%
to other imaging parameters (interim-PET), can be useful and 74%, respectively for semiquantitative analysis using the
benchmark to stratify patient prognosis and modulate the ratio SUVmaxBMU/liver; and 73%,43%,94%,84% and 70%,
treatment strategy. References: None. respectively, using the ratio SUVmeanBMU/liver. Conclusion:
PET/CT detects more BMI in FL compared to BMB. Concordance
between both techniques is high. Around 30% of patients with
EPS-144 a focal uptake at the PET/CT had a negative BMB, while more
Bone Marrow Evaluation In Initial Staging Of Follicular than 80% with a diffuse pattern had a positive BMB. References:
Lymphoma. 18F-FDG PET/CT Versus Bone Marrow Biopsy None.
M. Cortes Romera1, S. Mercadal-Vilchez2, A. Palomar-Muñoz1, A.
Sabaté-Llobera1, F. Climent-Esteller3, E. Llinares-Tello1, E. Gonzalez-
Barca2, C. Gámez-Cenzano1; EPS-145
1
Unit PET/CT (IDI)- Department of Nuclear Medicine. Hospital Impact of interim FDG PET/CT on Hodgkin Lymphoma
U. de Bellvitge-IDIBELL., L’Hospitalet De Llobregat (Barcelona), adult patients at King Hussein Cancer Center (KHCC),
SPAIN, 2Department of Hematology. ICO. Hospital Duran Jordan
i Reynals-IDIBELL., L’Hospitalet De Llobregat (Barcelona), A. N. K. Al-Ibraheem, F. Anwer, A. Khalaf;
SPAIN, 3Department of Pathology. Hospital U. de Bellvitge- King Hussein Cancer Center, Amman, JORDAN.
IDIBELL, L’Hospitalet De Llobregat (Barcelona), SPAIN.

Aim/Introduction: The aim of this study was to assess the value


Aim/Introduction: Bone or bone marrow focal FDG of interim FDG PET/CT in predicting response to treatment of HL
uptake in PET/CT is highly sensitive to detect bone marrow patients at KHCC. Materials and Methods: We retrospectively
involvement(BMI) in HL and in aggressive NHL, obviating reviewed the records of HL patients who underwent FDG PET/
the need of a bone marrow biopsy(BMB). However, there are CT between January 2014 and December 2017. 254 patients
limited data to support this procedure in other histologies, were included in this study whose records comprised initial
such as follicular lymphoma(FL). The aim of this study is to PET, interim PET after cycle 2 or cycle 4 of ABVD and end of
assess the utility of PET/CT and its concordance with BMB in therapy PET. All had their PET scans in KHCC.The Deauville
the detection of BMI in FL. Materials and Methods: Ninety- 5-point scoring (5-ps) was considered for the classification of
two patients(45 women, mean age 60.8 years) diagnosed with patients as complete metabolic responders (CMR) if patients
FL(de novo or relapsed) underwent an FDG-PET/CT. Patients achieved 5-ps 1-3 in interim PET or as non-complete metabolic
with transformed or grade 3B FL, as well as those without a BMB responders (nCMR) if patients achieved 5-ps 4 and 5. The
or with non-valuable BMB findings were excluded. BMB was decision of the multidisciplinary team based on the results of
used as reference standard. PET images were evaluated visually the end of treatment PET were adopted to classify patients as
and semiquantitatively. PET was considered positive for BMI at having complete response (CR) or residual active disease (RAD).
the visual assessment when there was diffuse bone marrow Results: Our patient cohort are illustrated in the table below.
uptake(BMU) over liver(BMU>L), when it was equal to liver and Interim FDG-PET scan (either after cycle 2 or cycle 4 of ABVD
there was also BMU in the limbs(BMU=L+E), or when there was a therapy) was classified as CMR in 188/254 (74%) with their final
focal/multifocal/heterogeneous BMU pattern. Semiquantitative FDG-PET showed CR in 185/188 (98.4%) of cases and 3 (1.6%)
assessment was performed using the ratio between SUV(max patients with RAD within the first 6 months follow up. In the
and mean) of the left iliac crest and the liver. Concordance and remaining 66 (26%) patients, interim FDG-PET was nCMR with
agreement between PET(using visual analysis) and BMB were Score 4 in 60 patients (23.6%) and Score 5 in 6 patients (2.4%).
analyzed. Accuracy(A), sensitivity(S), specificity(Sp), and positive In the aforementioned 60 patients with 5-ps 4 who continued
and negative predictive values(PPV and NPV, respectively) the ABVD protocol, end of treatment FDG- PET imaging showed
between visual and semiquantitative analysis were calculated. RAD in 25 patients (41.6%) of patients, CR in 30 patients (50%)
Results: Histological grading based on WHO classification and indeterminate response in 5 patients (8.4%).Statistical
showed: grade 1-2 in 59, 3A in 28, and “non-gradable” in 5 analysis revealed that interim FDG- PET after 2 or 4 cycle of ABVD
patients. PET/CT detected BMI in 42 cases(45%), and BMB in had a negative predictive value of 98.4% and positive predictive
38(41%). A substantial agreement was obtained between value of 45.4%. Significant percent of patients with nCMR,
both techniques(Cohen’s kappa 0.647). Concordant results particularly Deauville score 5, didn’t achieve further response on
between PET/CT and BMB were obtained in 76 patients(83%): this ABVD regimen at the end of treatment. Conclusion: This
32 with positive PET/CT(13 uni-/multifocal, 3 heterogeneous, 13 study showed that interim FDG-PET/CT scan after cycle 2 or 4
diffuse(BMU>L) and 3(BMU=L+E) and BMB results(42%) and 44 has a valuable role in predicting response to ABVD treatment
S371 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

in HL. Patients with nCMR Deauville score 5 in interim PET departments. PET/CT is used both to differentiate between
commonly would have RAD at the end of treatment. Escalating malignant and benign pulmonary nodules and to assess
of treatment in this group should be advocated. References: mediastinal lymph nodes and distant metastases. Our aim
None. is to develop a completely automated method based on
artificial intelligence (AI) for the analysis of FDG-PET/CT in
patients with known or suspected lung cancer. In this project
EPS-146 we take the first step and focus on the detection of abnormal
Usefulness of gradient tree boosting for predicting lung lesions. Materials and Methods: A total of 81 patients,
histological subtype and EGFRmutation status of non- who underwent FDG-PET/CT due to suspected lung cancer
small cell lung cancer on 18F FDG-PET/CT or for the management of known lung cancer were studied.
S. Koyasu, M. Nishio, H. Isoda, Y. Nakamoto, K. Togashi; The patient group was divided into a training (80%) and a
Graduate School of Medicine, Kyoto University, Kyoto, JAPAN. validation (20%) group. A nuclear medicine specialist manually
marked abnormal lung lesions in all FDG-PET/CT studies.A
convolutional neural network (CNN) was trained to classify each
Aim/Introduction: To develop and evaluate a radiomics image voxel as either background or lung lesion. The input to
approach for classifying histological subtypes and epidermal the network was the PET and CT images along with an organ
growth factor receptor (EGFR) mutation status in lung mask, marking the lungs, vertebrae and the heart. The organ
cancer. Materials and Methods: PET/CT images of NSCLC mask was automatically generated from the CT image using
Radiogenomics were obtained from public databases and used a different CNN [1]. To focus on detection rather than exact
to establish two datasets, respectively to classify histological delineation, the boundaries of each annotated lesion were
subtypes (156 adenocarcinomas and 32 squamous cell marked as don’t-care in the training.The output of the CNN
carcinomas) and EGFR mutation status (38 mutant and 100 was processed by removing spurious voxels far away from the
wild-type samples). Seven types of imaging features were lungs as well as components smaller than 0.1 ml. The remaining
obtained from PET/CT images of lung cancer. Two types of connected components are then treated as detected lesions.
machine learning algorithms were used to predict histological Results: A total of 26 abnormal lesions were detected in 16 of
subtypes and EGFR mutation status: random forest (RF) and the 17 patients of the validation group. The lesion sensitivity
gradient tree boosting (XGB). The classifiers used either a single was 91% and the positive predictive value was 85%. One of
type or multiple types of imaging features. In the latter case, the the 17 patients did not have any abnormal lesions and the AI-
optimal combination of the seven types of imaging features method correctly marked no lesions in this case. Conclusion:
was selected by Bayesian optimization. Receiver operating A completely automated AI-based method can be used to
characteristic analysis, area under the curve (AUC), and 10-fold detect lung lesions with high accuracy. In future studies we
cross-validation were used to assess the performance of the will apply AI-methods for the assessment of lymph nodes and
approach. Results: In the classification of histological subtypes, distant metastases. These type of clinical decision support tools
the AUC values of the various classifiers were as follows: RF, appears to have significant clinical potential. References: [1].
single type: 0.759; XGB, single type: 0.760; RF, multiple types: Lindgren Belal S, Sadik M, Kaboteh R, Enqvist O, Ulén J, Poulsen
0.720; XGB, multiple types: 0.843. In the classification of EGFR MH, Simonsen J, Høilund-Carlsen PF, Edenbrandt L, Trägårdh
mutation status, the AUC values were: RF, single type: 0.625; E. Deep learning for segmentation of 49 selected bones in CT
XGB, single type: 0.617; RF, multiple types: 0.577; XGB, multiple scans: First step in automated PET/CT-based 3D quantification
types: 0.659. Conclusion: The radiomics approach to PET/CT of skeletal metastases. Eur J Radiol. 2019 Apr;113:89-95.
images, together with XGB and Bayesian optimization, is useful
for classifying histological subtypes and EGFR mutation status in
lung cancer. References: None. EPS-148
Efficacy and toxicity profile of low dose 177 Lutetium-
Ethylenediamine tetra methylene phosphonate (177Lu-
EPS-147 EDTMP) for bone pain palliation in patients with skeletal
AI-based Detection of Lung Lesions in FDG-PET/CT from metastases
Lung Cancer Patients A. S A, D. Halanaik, N. Pandit, M. Ponnusamy;
L. Edenbrandt1, R. Kaboteh1, S. Salehian1, J. Ulen2, O. Enqvist2,3, P. JIPMER, Pondicherry, INDIA.
Borrelli1;
1
Sahlgenska University Hospital, Gothenburg,
SWEDEN, 2Eigenvision, Malmö, SWEDEN, 3Department Aim/Introduction: Radionuclide therapy has the advantage in
of Electrical Engineering, Chalmers University comparison to other modalities for pain palliation in targeting
of Technology, Gothenburg, SWEDEN. all the involved skeletal metastasis sites simultaneously. It is
associated with fewer side effects. The only side effect is dose
limiting transient myelosuppression. There is paucity of data
Aim/Introduction: Staging lung cancer is one of the most on therapeutic efficacy and safety profile of low dose 177Lu-
common indications for FDG-PET/CT in nuclear medicine EDTMP in terms of the degree of pain relief, performance status
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S372

and toxicity profile for bone pain palliation. We conducted the accuracy of tumor resection. An interesting target involved
a prospective observational study to assess the efficacy and in the proliferation and progression of pancreatic cancer is the
toxicity profile of low dose 177Lu-EDTMP for bone pain palliation neurotensin receptor 1 (NTSR1). In this study, we describe the
in patients with skeletal metastases. Materials and Methods: development and in vivo evaluation of PET/fluorescent imaging
Patients with multiple painful bone metastasis documented agents targeting NTSR1. Materials and Methods: Five bimodal
on 99mTc-MDP bone scan within last 8 weeks were being imaging agents were synthesized, based on the structure of
included for 177Lu-EDTMP therapy. Pain and performance the NTSR1 peptide agonist NT20.3. The radiometal chelator,
were assessed using visual analog scale, Karnofsky performance (R)-NODAGA, and three cyanine 5 derivatives were conjugated
scale and mobility score. Pre-therapy haemogram was in the to the N-terminal lysine residue. Several spacers were
range as in inclusion criteria. Patients were given 0.37 MBq/ introduced. The affinity of ligands for NTSR1 was determined
kg body weight of 177Lu-EDTMP intravenously on out-patient in vitro after natGa labeling. The compounds were radiolabeled
basis. Whole body scan was done after 2 hours to document with 68Ga and their biodistribution was evaluated on nude
radiopharmaceutical distribution. All patients were followed up mice bearing a subcutaneous xenograft of AsPC1 (human
at 4, 8 and 12 weeks post-therapy. Blood hemogram is advised pancreatic adenocarcinoma) cells. PET images were acquired 1
following therapy every fortnightly up to 12 weeks. The VAS h post injection. Mice were sacrificed and the uptake of tracers
pain score, mobility score and Karnofsky performance scores (KF into different organs was measured by gamma-counting.
score) were recorded at 4, 8 and 12 weeks. Results: 20 patients Fluorescence images were recorded at different times and
who completed the follow up of 3 months were included in tumors were removed through fluorescence-guided surgery.
the analysis. The VAS Pain, KF score, mobility score and blood Results: Bimodal imaging agents were obtained with an overall
parameters were expressed as mean and standard deviation. yield of 10 to 33%. In vitro studies confirmed the high affinity of
The changes in continuous variables at different time point all compounds for NTSR1 with Ki values in the nanomolar range.
were assessed by using one-way repeated measure of ANOVA. It Spacers did not have a significant impact on affinity for the
was observed that the pain response assessed by VAS score has receptor. In contrast, the addition of sulfonate groups resulted in
significantly decreased (p<0.05). KF score showed statistically a decrease in affinity. The radiolabeling with 68Ga was achieved
significant change (p<0.05). Mobility score improved but was with good radiochemical yields (95%) and purity (>99%). PET
not statistically significant (p>0.05). The blood parameters imaging studies allowed us to identify the compound [68Ga]-
were in the normal range during the entries period of follow NODAGA-Lys(Cy5**)-PEG2-[Me-Arg8, Tle12]-NT(7-13), as the
up. But there was statistically significant decrease in WBC count one showing the most promising pharmacokinetic profile.
(p<0.05). Conclusion: Low dose 177Lu-EDTMP was effective Biodistribution data showed a high tumor uptake (2.6%ID/g
in reducing pain in patients with skeletal metastasis. The 90 min p.i.) with a high tumor-to-normal tissues ratio. Similar
performance of the patient was improved. The only observed results were obtained by fluorescence imaging and confirmed
toxicity was myelosuppression mostly affecting the WBC count. during the fluorescence-guided resection of tumor masses.
But the WBC count came to normal by the end of the 3 month Conclusion: A novel peptide-based bimodal imaging agent for
follow up. So 177 Lu-EDTMP in low dose is definitely a promising NTSR1-positive tumors was developed. This compound showed
radionuclide in bone pain palliation. References: None. high tumor uptake and fast clearance from non-targeted organs,
leading to high contrast in PET and fluorescence imaging. These
results highlight the potential of this agent for the diagnosis
EPS-149 and the fluorescence-guided surgery of pancreatic cancer.
Design of a Bimodal Ligand of Neurotensin Receptor 1 for References: None.
68
Ga-PET Imaging and Fluorescence-Guided Surgery of
Pancreatic Cancer
E. Renard1, P. A. Dancer2, C. Portal3, F. Denat1, A. Prignon4, V. EPS-150
Goncalves1; PSMA-targeting hybrid tracers based on
1
Institut de Chimie Moleculaire de l’Université de Bourgogne, heterobifunctional cyanine spacer moieties - tuning the
Université Bourgogne Franche-Comté, Dijon, FRANCE, 2Kaer pharmacokinetic properties and exploring dye interaction
Labs, Nantes, FRANCE, 3Edinburgh Molecular Imaging, with PSMA
Edinburgh, UNITED KINGDOM, 4Laboratoire d’Imagerie A. Hensbergen1, T. Buckle1, D. M. van Willigen1, M. Schottelius2, M.
Moleculaire Positonique, Sorbonne Université, Paris, FRANCE. M. Welling1, F. A. van der Wijk1, H. G. van der Poel3, T. Maurer4, H.
Wester2, F. W. B. van Leeuwen1;
1
Leiden University Medical Center, Leiden, NETHERLANDS,
Aim/Introduction: Pancreatic cancer is the 4th leading cause of 2
Technische Universität München, Garching, GERMANY,
death by cancer in Europe. This cancer has a poor prognosis, 3
The Netherlands Cancer Institute, Amsterdam,
which is due to late clinical presentation, rapid progression and NETHERLANDS, 4Martini Klinik, Hamburg, GERMANY.
limited effect of chemotherapy. Moreover, 30 to 50% of patients
who have had surgery, relapse because of the difficulty to
accurately delineate tumor margins. Therefore, there is real need Aim/Introduction: Precision surgery provides means to
to develop new methods that improve both the diagnosis and improve patient outcome after prostate cancer surgery. Herein
S373 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

radical resection can be promoted via visualisation of tumour Sadi Konuk Research and Training Hospital, Pathology
margins and (local) metastases. The prostate-specific membrane Department, Istanbul, TURKEY, 4Istanbul Bahcelievler
antigen (PSMA) has been shown to support staging of the Memorial Hospital, Urology Department, Istanbul, TURKEY.
disease via preoperative nuclear imaging and has helped realize
radioguided tumour resections. Ideally, the latter approach is
complemented with the ability to optically detect lesions. As Aim/Introduction: Prostate-specific membrane antigen
the chemical composition of the linker moiety has been critical (PSMA)-targeted positron emission tomography / computed
in PSMA radiotracer development, the same should be true for tomography (PET/CT) is successful imaging modality in prostate
the development of hybrid (radioactive and fluorescent) tracer cancer (PC). But many centers do not have Germanium/Gallium
analogues. Here, the relationship between the linker moiety (Ga)-68 generator and/or PET/CT. Also, reliable identification of
and overall hybrid tracer performance was structurally studied small and/or atypically localized lymph nodes (Ln) during robotic
by exploring the use of heterobifunctional Cy5 molecules that surgery is challenging. In this prospective multicenteric study,
act as a linker between an EuK moiety and a MAS3 chelate. feasibility of tracer production using 99mTechnetium (Tc)-based
Materials and Methods: A panel of five EuK-(X)Cy5(X)-MAS3 PSMA-11 sterile cold kit, imaging procedure and accuracy with
(X = SO3- or Ar) PSMA-specific hybrid tracers was synthesized. single photon emission tomography/computed tomography
The effect of the C- or N- terminal dye functionalisation was (SPECT/CT), technique and feasibility of 99mTc-based PSMA-
evaluated through assessment of the lipophilicity, (photo) radioguided robot-assisted laparoscopic radical prostatectomy
physical properties, serum interactions, chemical stability, (99mTc-PSMA-RG-RALRP) for Ln dissection of primary PC patients
ability to target PSMA in vitro (confocal microscopy) and were evaluated. Materials and Methods: 9 primary PC patients
PSMA receptor affinity (IC50 with ([125I]I-BA)KuE)). Following (Mean age 65,7 years) with intermediate (n:2) or high (n:7)
radiolabelling with 99mTc (40 MBq), in vivo SPECT imaging, risk score who had PSMA receptor affinity according to Ga-68
quantitative biodistribution analysis (%ID/g; 1 nmol) and ex PSMA-11 PET/CT were enrolled. 99mTc-labelled PSMA-ligand
vivo fluorescence imaging was conducted in BALB/c nude (99mTc-PSMA-I&S) was injected iv. (Mean 630 MBq; range 555-
mice (n = 6/tracer) with orthotopically transplanted PSMA- 770 MBq). 61.6±7.8 min. after the injection, whole body planar
positive PC346C tumours. Results: Synthesis yielded EuK-Cy5- scintigraphy and abdominopelvic SPECT/CT were performed.
MAS3, EuK-(SO3-)Cy5-MAS3, EuK-Cy5(SO3-)-MAS3, EuK-(Ar)Cy5- Mean time to start 99mTc-PSMA-RG-RALRP with DaVinci XI robotic
MAS3, EuK-Cy5-(Ar)-MAS3. Presence of a SO3- moiety resulted platform and laparoscopic gamma probe was 18±1.7 h after
in preferable photophysical properties (higher brightness) and injection. Radioactive rating (positive vs negative; according
serum interactions (binding and chemical stability). All tracers to background activity) of resected tissue was compared with
allowed tumour visualization with SPECT and fluorescence the findings of postoperative histopathology. Physiological and
imaging. C- or N-terminal dye functionalisation was shown pathological uptakes of organs and tissues for both imaging
to directly influence in vitro and in vivo tracer performance; modalities were compared visually and quantitatively with
clear differences were seen in tracer affinity (IC50 range: 19.2 ± maximum and mean standard uptake values vs. region of
5.8-175.3 ± 61.1 nM) and in vivo characteristics (e.g., tumour- interest and volume of interest counts. Results: 99mTc-PSMA-
to-prostate and tumour-to-muscle ratio: respectively 5.4-31.7 I&S was prepared in 2 hours with > %96 purity. Physiological
and 9.3-465.8). [99mTc]EuK-(SO3)Cy5-MAS3 showed the highest radiotracer distribution were similar for both imaging modalities
affinity and most favourable in vivo characteristics, i.e., highest visually but PC lesions were much more visible on PET/CT. Late
tumour-to-background and low renal (18.4 ± 8.5 %ID/g), splenic imaging with SPECT/CT could able to visualize lesions better.
(1.0 ± 1.2 %ID/g), and salivary gland (0.02 ± 0.01 %ID/g) uptake. Mean operation time and mean console time were 6 h and 4.6
Conclusion: Incorporation of bifunctional Cy5 bridging dyes h, respectively. No patient suffered from complication related
between an EuK moiety and a MAS3 chelate in PSMA-targeting to surgery. Post-operative Gleason score were 7 (n:6), 8 (n:1)
tracers was shown to be feasible. Next to influencing the receptor and 9 (n:2). Dissected locoregional Ln number were 23,3 ± 7,8
affinity, systematic variation in C- and N-terminal substitution of ( Range: 12 - 39) .Total dissected lymph nodes were 210 with
the cyanine backbone of the EuK-(X)Cy5(X)-MAS3 hybrid tracers only 2 of them were metastatic. These results were exactly the
was shown to exert influence on the optical properties and in same with per-operative probe counts. Conclusion: According
vivo performance. References: None. to preliminary findings of this ongoing study, 99mTc-PSMA-RG-
RALRP seems to be of high value in patients with localized
PC and loco-regional Ln metastases which may shorten the
EPS-151 operation time and make surgeon feel more comfortable. If
PSMA Targeted Nuclear Robotic Surgery: Preliminary Tc-99m PSMA-I&S SPECT/CT is used for only imaging purpose,
Results late imaging up to 20 hours is recommended. For operation
B. Yilmaz Gunes1, S. Sahin2, N. Ergul1, H. F. Baytekin3, Y. Colakoglu2, patient selection based on 68Ga-PSMA PET imaging is crucial.
D. Sokmen4, V. Tugcu4, A. I. Tasci2, T. F. Cermik1; References: None.
1
Istanbul Research and Training Hospital, Nuclear Medicine
Department, Istanbul, TURKEY, 2Istanbul Bakirkoy Dr.
Sadi Konuk Research and Training Hospital, Urology
Department, Istanbul, TURKEY, 3Istanbul Bakirkoy Dr.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S374

EPS-152 EPS-153
Impact of Ga-68 PSMA PET/CT on diagnosis and staging of Texture analysis of 18F-choline uptake in prostate gland of
hepatocellular carcinoma patients with untreated cancer: relationship with the Risk
C. Gundogan1, N. Ergul1, M. S. Cakir2, T. Aksoy1, N. O. Kilickesmez2, T. Assessment Score, additional prostate biopsy findings and
F. Cermik1; patient’s outcome
1
University of Health Sciences, Istanbul Training and M. Cuzzocrea1, L. Florimonte1, V. Longari1, G. Santaguida1,2, E.
Research Hospital, Clinic of Nuclear Medicine, Istanbul, Orunesu1, M. Castellani1;
TURKEY, 2University of Health Sciences, Istanbul Training and 1
Nuclear Medicine Department, Fondazione IRCCS Cà
Research Hospital, Clinic of Radiology, Istanbul, TURKEY. Granda Ospedale Maggiore Policlinico, Milan, ITALY,
2
Università degli Studi di Milano, Milan, ITALY.

Aim/Introduction: In this study, we investigated the diagnostic


impact of staging Ga-68 Prostate Specific Membrane Antigen Aim/Introduction: PET/CT imaging with 18F-choline for staging
(PSMA) PET/CT on patients with Hepatocellular Carcinoma prostate cancer patients is currently used in selected cases
(HCC). Materials and Methods: Twelve Child Pugh (CP)-A and when there is a high risk of local or distant metastases on the
2 CP-B HCC patients (13 M, 1 F; mean age 68.3±5.9 [range 58- basis of PSA levels, Gleason Score and T grade (Risk Assessment
76] years) were enrolled in this prospective study. All patients Score: RAS). Radiomics features of PET/CT prostate images could
underwent PSMA-PET/CT scan and F-18 fluorodeoxyglucose provide additional information to predict the outcome of these
(FDG) PET/CT scan which performed within 30 days of each high-risk patients. Aim of the study was to assess the relationship
other. Magnetic resonance imaging (MRI) was performed between texture analysis of 18F-choline prostate gland uptake
to all patients before included in the study. The maximum and patient’s outcome. Materials and Methods: PET/CT images
standardized uptake value (SUVmax) was measured for primary of 42 males (mean age: 67.6; range: 49-84 yrs) with increased
tumors, lymph nodes and distant metastases in PSMA-PET/ PSA levels (median value 9.3; range: 2.4-329) and histological
CT and FDG-PET/CT. In addition to SUVmax, tumor-to-liver diagnosis of prostate cancer, were retrospectively evaluated. The
(T/L) and tumor-to-background (T/B [gluteus medius muscle]) radiomics features and metabolic parameters of prostate gland
taken into consideration Liver tumors defined on PET/CT were calculated for each patient along with RAS. Univariate
scans compared with MRI. Histopathology confirmed only in 6 analysis was performed to assess the relationship of the single
patients. Results: In PET/CT imaging, increased PSMA uptake parameters with the patient’s outcome expressed in terms of
was observed in11 patients, mild uptake was observed in two stable disease or biochemical progression at follow-up (median:
patinets and no uptake was observed in one patient. (mean±SD 19.8 months; range 3-47). The performance of continuous
SUVmax 20.9±11.7). Five patients tumors were non-FDG avid, variables was assessed by comparing area under curves (AUC)
three patients showed mild FDG uptake and six patients at ROC analysis. Independent predictors of outcome were also
showed increased FDG uptake (mean±SD SUVmax 9±5.3). PSMA assessed with Cox model multivariate analysis. Results: Among
uptake mean ratio for T/B was significantly higher in primary 38 texture features derivable from PET images analysis, 19 were
tumors compared with FDG (p = 0.001). However, PSMA uptake statistically different (p≤0.03) in patients with stable disease and
mean ratio for T/L in primary tumors was higher than FDG, no biochemical progression. Significant differences (p<0.01) were
significant difference was found (p=0.16). In our study group, also observed in RAS and SUV values. At ROC analysis of radiomic
61 (98%) lesions were detected with PSMA-PET/CT, while FDG- and metabolic features, the best performance for predicting
PET/CT detected only 30 (48%) lesions. Seven (50%) patients patients outcome was observed when grey level co-occurrence
had high-AFP-secreting tumors (>200 ng/mL) and 5 (35%) matrix contrast (GLCM_contrast; AUC 0.828; p< 0.001) and
had low-AFP-secreting (<20 ng/mL) tumors. We did not find a grey-level zone length matrix High Gray-level Zone Emphasis
relationship between AFP levels and PSMA or FDG uptake. Three (GLZLM_HGZE; AUC=0.858; p<0.001) were used. In particular,
patients had abdominal metastatic lymph nodes in PSMA-PET/ a sensitivity (Se), specificity (Sp), positive predictive value (PPV)
CT and one of them was non-FDG avid. Abdominal metastatic and negative predictive value (NPV) of 77.8, 87.9, 63.6 and 93.5
lymph nodes uptake in PSMA-PET/CT was higher than FDG- respectively, was calculated for GLZLM_HGZE (cut-off = 151.4)
PET/CT in 2 of 3 patients. On the other hand, three patients had in the prediction of the different outcome. Similar results was
mediastinal lymph nodes and these lesions had higher SUVmax reported for GLCM_contrast (Se 77.8; Sp 84.8; PPV 58.3; NPV
values in FDG-PET/CT than PSMA-PET/CT. Biopsy results from 93.3; cut-off= 9.9). At Cox regression, both radiomic parameters
subcarinal and right lower paratracheal lymph nodes of one were found to be independent variables in the prediction of a
of these patients were reported as anthracosis. Conclusion: In different outcome. Conclusion: These preliminary data suggest
patients with HCC, PSMA-PET/CT is superior to FDG-PET/CT as that texture analysis of prostate 18F-choline uptake is feasible
a molecular imaging modality, and we think PSMA-PET/CT may and some radiomic features are related to the prognosis.
be a potential new method in the diagnosis of primary tumors However, the creation of prognostic/predictive models able to
and metastatic lesions. References: None. consider the multiplicity of texture features and an increase of
the sample size of patents are mandatory. References: None.
S375 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

EPS-154 1511
Feasibility of Intra Arterial LU-177 DOTA TATE Therapy in
Metastatic Neuroendocrine Tumors with Liver Dominant
e-Poster Presentation Session 11 -
Disease - “A Novel Theragostic Approach to Augment
Cardiovascular: Imaging Cardiomyopathies
Therapeutic Potential”
A. A. Rajan, S. Sumati; Tuesday, October 15, 2019, 16:30 - 18:00 Room 133/134
Gleneagles Global Hospitals, Chennai, INDIA.

Aim/Introduction: Few recent preclinical and clinical studies EPS-155


have demonstrated a higher first pass effect with a higher tumoral Spect Imaging Of Tspo Expression In Rat Myocardial-
uptake in the early phases of intra-arterial administration of Ga- Infarction- Reperfusion Models With 99TcM -labeled Tspo
68 DOTANOC and In-111 DOTANOC imaging of liver metastasis Ligand Cb86
in neuroendocrine tumors 1,2. It has been hypothesized that this X. Su, F. Su, W. Dong, J. Li, Z. Guo;
novel approach could be translated into theragnostics. The aim Zhongshan Hospital Xiamen University, Xiamen, CHINA.
of this study was to assess the safety, tolerability and efficacy
of intra arterial Lu-177 DOTA TATE therapy in patients with liver
dominant metastasis in well differentiated NETs. Materials Aim/Introduction: Objective The purpose of this study is
and Methods: Four patients with well differentiated NET liver to develop a specific TSPO-targeting 99Tcm -labeled agent
dominant metastasis were given 4 cycles of 200 mCi of Lu-177 (99Tcm-DTPA-CB86) for single-photon-emission- computed-
DOTATATE therapy intra arterially at interval of 8 weeks through tomography (SPECT) imaging of TSPO expression in myocardial-
selective hepatic arterial cathrterization. All patients received infarction-reperfusion rat models. Materials and Methods:
bilobar hepatic arterial infusions. All patients were administered After SPECT/CT imaging with 99Tcm-DTPA-CB86 at 1, 2, 4, 12,
aminoacid infusions for 4-6 hours starting pretherapy and and 36 h after myocardial- infarction-reperfusion, the models
continued post therapy infusions. Their complete blood were validated by ex vivo autoradiography, TTC staining, and
counts, liver function, renal function and coagulation profiles immunohistochemistry and in vivo echocardiography and
were assessed within 2 weeks prior to each treatment cycle, in classical 18F-FDG PET metabolic imaging. Results: The 99Tcm-
the immediate post therapy period and within 6 weeks post DTPA-CB86 SPECT/CT showed that the infarcted myocardium
treatment. Radiological assessment and tumor markers were (Fig.1) could be visualized with high quality as early as 1 h
also assessed pre and post treatment. Results: Significant and still clearly identified at 36 h after myocardial-infarction-
reduction in serum chromogranin A levels with partial reperfusion and that TSPO up-regulation was still visible at 36
reduction in size and tracer uptake in all patients were noted. h after myocardial-infarction-reperfusion. In the biodistribution
None of the patients experienced any acute side effects or study, high uptakes in the infarcted myocardium (0.39 ± 0.03,
unexpected complication during therapy or in the immediate 0.46 ± 0.06, 0.52 ± 0.07, and 1.97 ± 0.12% ID/g at 1, 2, 4, 12,
post therapy period. No RILD or renal toxicity seen during the and 36 h after myocardial-infarction-reperfusion, respectively)
course of therapy and even after the last cycle. Liver functions were observed that were much higher than that of normal
remained stable with improved quality of life. Conclusion: myocardium. The highest uptake was reached at 36 h after
Our initial experience of intra-arterial administration of Lu-177 myocardial-infarction-reperfusion, which agreed well with the
DOTA TATE therapy in patients with liver dominant metastasis SPECT/CT imaging results. In addition, the radioactivity uptakes
is promising, feasible, safe and tolerable treatment. Survival of the infarcted myocardium in both the biodistribution and
benefits evaluation is ongoing and will be evaluated on SPECT imaging could be blocked effectively by excess amounts
subsequent follow up. References: 1. Kratochwil C, et al. Hepatic of unlabeled DTPA-CB86, indicating the high specificity of 99Tcm-
arterial infusion enhances DOTATOC radiopeptide therapy DTPA-CB86 to TSPO (Fig.2,3). Conclusion: 99Tcm-DTPA-CB86
in patients with neuroendocrine liver metastases. Endocr may serve as a powerful TSPO-expression diagnostic probe for
Relat Cancer. 2011;18(5):595-602. doi: 10.1530/ERC-11-0144. evaluating lesions and monitoring therapy responses in patients
2. Pool SE, Kam B, Breeman WAP. Increasing intrahepatic with cardiovascular diseases. References: None.
tumour uptake of 111 In-DTPA-octreotide by loco regional
administration. Eur J Nucl Med Mol Imaging. 2009;36:S427. NETs
- Neuroendocrine Tumors. RILD - Radiation induced liver disease. EPS-156
Comparison between 99mTc-sestamibi/123I-BMIPP
mismatch and reverse redistribution of 99mTc-sestamibi
using cadmium-zinc-telluride SPECT system in patients
with acute myocardial infarction
S. Hida, Y. Fujita, Y. Igarashi, T. Hatano, T. Morishima, C. Shiba, T.
Chikamori;
Tokyo Medical University Hospital, Tokyo, JAPAN.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S376

Aim/Introduction: Although both 99mTc-sestamibi/123I- compared the predictability of functional recovery between FDG
BMIPP mismatch and reverse redistribution of 99mTc-sestamibi PET and MRI, based on the regional wall motion abnormality
in patients with acute myocardial infarction (AMI) are significant (RWMA) improvement. Materials and Methods: Eleven patients
markers for predicting functional recovery in the infarcted (mean age 60.5 y-o, 9 males) with AMI (4 NSTEMI and 7 STEMI)
territory in chronic phase, few studies compare them by underwent simultaneous PET/MRI. Myocardium was defined
simultaneous dual-isotope imaging with 99mTc-sestamibi/123I- ‘PET viable(PET-V)’ of ≥50% FDG uptake or as ‘MRI viable(MR-V)’
BMIPP using cadmium-zinc-telluride (CZT)SPECT system. when LGE transmurality of ≤50% was present. Eight patients
Materials and Methods: We evaluated 63 consecutive patients also underwent myocardial perfusion SPECT. We compared the
with AMI who had undergone simultaneous dual-isotope viability between FDG and LGE including the perfusion. Clinical
99mTc-sestamibi:370MBq/123I-BMIPP:111MBq SPECT using follow-up with echocardiography were reviewed. Results: Nine
Discovery NM530c within 8±4 days after PCI. Simultaneous patients received successful PCI, 1 patient was failed to PCI and
dual-isotope imaging time ware 8 min for both 1 hour (early) 1 patient was performed PCI after PET/MR scan. No patient met
and 4 hours (delayed) after administration of isotopes. The cardiac event during follow period (8-42 months). Five patients
estimated radiation exposure was 5.1 mSv. Each SPECT image showed PET-V and 4 of them showed also MR-V. Another 5
was assessed with a 17-segment model using a 5-point scoring patients showed PET-non-viable (PET-NV) and all of them also
system, and regional scores related to each coronary territory showed MR-NV. One patient showed reverse FDG uptake:
was calculated. When 123I-BMIPP defect scores were higher infarcted myocardium showed increased FDG uptake, he
than those of the 99mTc-sestamibi defect scores in infarcted showed MR-NV. 8/9 with concordant PET/MRI results showed
territory, it was considered as 99mTc-sestamibi/123I-BMIPP similar lesion size, only one patient showed diffuse FDG defect
mismatch. And when 99mTc-sestamibi defect scores in the with focal LGE at LAD territory. Via echocardiography, 3 patients
delayed image were greater than those in the early image in had no RWMA, 2 patients had improvement RWMA, 5 patients
infarcted territory, it was considered as a reverse redistribution showed no improvement and one patient showed worsening of
of 99mTc-sestamibi. We assessed the frequency of respective RWMA. No RWMA or improvement RWMA group (viable group)
findings and compared defect scores in the infarcted territory. was consisted of 2 PET-V/MR-V, 2 PET-NV/MR-NV and 1 PET-V/
Results: The number of each infarcted related coronary arteries MR-NV. The worsening RWMA or no change RWMA group (non-
was 29 in LAD, 26 in RCA and 8 in LCX. Of 63 patients, 99mTc- viable group) was consisted of 2 PET-V/MR-V, 2 PET-NV/MR-NV
sestamibi/123I-BMIPP mismatch were more frequent than and 1 reverse PET/MR-NV. Two patients without RWMA showed
reverse redistribution of 99mTc-sestamibi (71% vs 43%; p=0.036). normal perfusion SPECT. Two patients with improvement of
And the scores of 99mTc-sestamibi/123I-BMIPP mismatch were RWMA showed larger perfusion defects than metabolic defects.
greater than those of reverse redistribution of 99mTc-sestamibi Four patients of non-viable group showed matched perfusion-
in the infarcted territory (4.0±3.3 vs 0.8±1.7; p=0.0001). And metabolism defect. Conclusion: The simultaneous assessment
similar results were observed with respect to each infarcted of FDG uptake and LGE is feasible. However, the predictability of
related coronary arteries. Conclusion: In the simultaneous viability is not satisfactory. Perfusion could improve to predict
99mTc-sestamibi/123I-BMIPP dual-isotope imaging at rest with viability. In case of discordant between PET and MRI findings,
low radiation exposure using CZT SPECT system, the presence FDG uptake was a better predictor for functional recovery.
of 99mTc-sestamibi/123I-BMIPP mismatch was more frequently References: None.
observed than that of reverse redistribution of 99mTc-sestamibi
in the infarcted territory. The further examination is needed
for their prediction of functional recovery in chronic phase. EPS-158
References: None. A Comparison Between Ora Glucose Load And Acipimox/
Asa/Insulin Administration Efficiency In Stimulating
Myocardial Uptake Of Fdg
EPS-157 I. Schiorlin, S. Casagrande, C. Gobbo, S. Scotti, D. De Palma;
Integrated FDG PET/MR imaging for the evaluation of ASST Sette Laghi, Varese, ITALY.
myocardial viability in patient with acute myocardial
infarction
E. Kong1, I. Cho1, C. Lee1, D. Shin1, B. Ahn2; Aim/Introduction: 18-FDG PET/CT is a well established tool
1
Yeungnam university hospital, Daegu, KOREA, for evaluating the presence of viable myocardium into necrotic
REPUBLIC OF, 2School of Medicine, Kyungpook post-infarction cardiac walls. The main technical problem is to
National University, Daegu, KOREA, REPUBLIC OF. address myocardial metabolism toward glucose consumption.
In non-diabetic patients, this is normally obtained by oral
glucose load (OGL). Diabetic patients represent a challenging
Aim/Introduction: The gold standard to identify viable group. The (2005) EANM/ESC procedural guidelines for
myocardium is FDG PET imaging. An alternative method is Late myocardial perfusion imaging in nuclear cardiology suggests,
Gd enhancement technique (LGE) by cardiac MRI. Although in diabetic patients, the use of an hypolipemic drug, Acipimox,
both approaches are valuable to predict functional recovery, coupled with ASA and insulin (AAI). Nevertheless, literature
the studies for acute myocardial infarction (AMI) are limited. We search found less than 10 papers published on this topic in the
S377 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

last 10 years, including some in animals. We began to use this Results: In study group after 12-month follow-up the summed
protocol in diabetic patients five years ago. Now we reviewed stress score in a typical RCA supply area (SSSRCA) improved
our experience, assessing semiquantitatively the AAI protocol from 7.0 [5.5; 10.5] to 4.0 [1.0; 5.5] (p <0.01), summed rest score
efficiency in comparison to the established OGL protocol (SRSRCA) improved from 3.0 [0.0; 7.0] to 1.0 [0.0; 3.5] (p <0.01), and
Materials and Methods: we select 44 (37 males and 7 females summed different score (SDSRCA) improved from 3.0 [1.0; 4.0] to
) patients in which 18-FDG PET/CT was requested in search of 1.0 [0.0; 2.0] (p = 0.03). Control group patients after 12-month
viable myocardium. 29 underwent to OGL, 15 to AAI protocol. In follow-up showed the significant improvement of SSSRCA only
the first group, FDG was administered when glycemia fell about - from 8.0 [6.0; 12.0] to 5.0 [4.0; 7.0] (p <0.01). Conclusion: After
20-30 mg% after the peak, whilst the AAI protocol followed 12-month follow-up in patients with diffuse and (or) distal
strictly the EANM GL published schedule, with no more than RCA disease, the procedure of intramyocardial implantation of
2 hours between patient arrival and FDG administration. FDG the erythropoietin preconditioned ABMC in laser channels is
PET was always performed 75 min after FDG administration safety and induces the improvement of myocardial perfusion.
(2.5 MBq/kg) with a single-bed 10-min acquisition with a four References: None.
ring PET/CT scanner (Siemens Biograph MCi). The scans were
evaluated semiquantively. Semi-quantitative evaluation was
made tracing two identical VOIs into the cardiac blood pool and EPS-160
into the myocardial portion with the highest uptake. We than Relationship between myocardial cardiac fibrosis and
took into account the myocardial and blood pool SUVmax and myocardial denervation in non-ischemic idiopathic dilated
the ratio between for comparing the capability of both protocols cardiomyopathy
to stimulate myocardial glucose consumption. Results: The F. Heurtebize, N. Deleval, E. Gayat, A. Benada, A. Cescau, J. Laissy, L.
OGL group had a mean myocardial SUVmax of 6.61 +2.71, a Sarda, A. Cohen-Solal;
mean cardiac blood pool SUVmax of 2.15 +0.52 and a mean Lariboisière, Paris, FRANCE.
myocardial/blood ratio of 3.2. The AAI group has 8.76 +5.01,
2.58 +0.91, 3.43 respectively. These values show no statistical
difference at the Wilcoxon test. Conclusion: Although in a small Aim/Introduction: Myocardial 123I-MIBG scintigraphy (MIBG)
group of patients, our data support the hypothesis that the and cardiac magnetic resonance (CMR) are used to evaluate
AAI protocol in diabetics is at least as effective as OGL (in non- cardiac sympathetic denervation and myocardial fibrosis
diabetics) in stimulating myocardial FDG uptake. This protocol respectively, in patients with reduced left ventricular ejection
seems then more effective in respect to literature reported fraction (LVEF) heart failure. We evaluated potential concordance
results for OGL in diabetics, and with the practical advantage of between denervation and fibrosis for pathophysiological
a fixed maximum duration time. References: None. purpose in non-ischemic idiopathic dilated cardiomyopathy
(DCM). Materials and Methods: Thirty-eight symptomatic
DCM patients, referred for MIBG and CMR within 3 months, were
EPS-159 included retrospectively between 2011 and 2018 at Lariboisière
Effect of intramyocardial injection of erytropetin University Hospital. Myocardial innervation was quantified
stimulated autologus bone marrow cells on myocardial using heart-to-mediastinum ratio (H/M) determined on 4hours
perfusion in patients with chronic myocardial ischemia - (late)-post injection thoracic planar anterior images. Myocardial
SPECT 99mTc-MIBI study fibrosis was quoted as present (late gadolinium enhancement
S. Minin, A. Fomichev, N. Nikitin, A. Chernyavskiy; LGE+) or absent (LGE-) on CMR. Results: Mean age was 52 ±
Meshalkin National Medical Research Center, 15 years (28 men). Mean LVEF and BNP level were respectively
Novosibirsk, RUSSIAN FEDERATION. reduced to 30 ± 9% and increased to 211 (77-642) ng/L. Mean
late H/M ratio was decreased to 1.51 ± 0.21 (normal ≥ 1.8). Sixteen
patients (42%) had CMR LGE. The concordance score between
Aim/Introduction: To evaluate the changes of myocardial severe denervation (H/M<1.6) and presence of fibrosis (LGE +)
perfusion using 99mТс-MIBI single-photon emission computed was 0.52. Eleven patients (46%) with severe denervation were
tomography (SPECT) after the intramyocardial implantation of LGE +, versus 36% (n=5) of patients with no or mild denervation
erythropoietin preconditioned autologous bone marrow cells (H/M ≥ 1.6) (NS). BNP appeared higher in the severe denervation
(ABMC) in laser channels during coronary artery disease surgery. group with fibrosis, than in the no or mild denervation group
Materials and Methods: Randomized study of 40 patients without fibrosis. The anteriority of the disease didn’t seem
(mean age 58 ± 6.9 лет, 9 females) with diffuse and (or) distal to be different between these groups. Conclusion: In non-
right coronary artery disease (RCA). Patients of the study group ischemic idiopathic dilated cardiomyopathy, concordance
(n = 23) underwent coronary artery bypass grafting (CABG) between myocardial denervation assessed by cardiac 123I- MIBG
of the left coronary artery (LCA) system and intramyocardial scintigraphy and the presence of myocardial fibrosis assessed by
implantation of erythropoietin preconditioned ABMC in the LGE on CMR was low. This suggests that denervation does not
left ventricular inferior wall. Patients of the control group (n reflect presence of myocardial fibrosis in DCM, and may be only
= 17) underwent CABG of the LCA system only. 99mТс-MIBI related to sympathetic increased tone. The rate of fibrosis was
SPECT performed 1-2 days before and 12 months after surgery. comparable in patients with severe myocardial denervation and
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S378

in patients with no or mild denervation. References: Jacobson Results: LogBNP was significantly correlated with Delayed H/M
AF, Senior R, Cerqueira MD, Wong ND, Thomas GS, Lopez VA, et ( r= 0.688 p<0.0001) and with WR ( r= 0.585 p<0.0001 ). LogBNP
al.Myocardial iodine-123 meta-iodobenzylguanidine imaging was significantly correlated with LV mechanical dyssynchrony
and cardiac events in heart failure.Results of the prospective (with PhaseSD r=0.618 p<0.0001, with Bandwidth r=0.618
ADMIRE-HF study. J Am Coll Cardiol. 18 mai 2010;55(20):2212- p<0.001). Conclusion: It was significantly relationship between
21. Assomull RG, Prasad SK, Lyne J, Smith G, Burman ED, Khan LV mechanical dyssynchrony and BNP concentrations, between
M, et al.Cardiovascular magnetic resonance, fibrosis, and uptake of MIBG and BNP concentrations. These results suggest
prognosis in dilated cardiomyopathy. J AmColl Cardiol. 21 nov that LV mechanical dyssynchrony in pediatric heart disease
2006;48(10):1977-85. patients can serve as a novel diagnostic tool to evaluate the
severity of HF. References: None.

EPS-161
Correlation Between Left Ventricular Mechanical EPS-162
Dyssynchrony And 123I-metaiodobenzylguanidine Uptake Cardiac sympathetic activity and dyssynchrony in
In Pediatric Heart Disease Patients prediction of cardiac resynchronization therapy response
M. Ota1, S. Kasama2, K. Omoya3, T. Yamamoto1; in heart failure patients
1
Gifu Prefectural General Medical Center, Gifu, A. Mishkina, K. Zavadovsky, V. Saushkin, M. Gulya, D. Lebedev, Y.
JAPAN, 2Nara Medical University Hospital, Kashihara, Lishmanov;
JAPAN, 3Awano Children’s Clinic, Gifu, JAPAN. Cardiology Research Institute, Tomsk National
Research Medical Centre, Russian Academy of
Sciences, Tomsk, RUSSIAN FEDERATION.
Aim/Introduction: In general, neuronal uptake of
norepinephrine is impaired in the failing myocardium.
123
I-Metaiodobenzylguanidine (MIBG) has become known as Aim/Introduction: Cardiac resynchronization therapy (CRT)
a reliable indicator of cardiac sympathetic activity. MIBG has is considered an effective treatment method in improving
been used to assess myocardial sympathetic nervous activity outcomes on HF patients. But 25-30% of CRT patients do not
and severity of heart failure (HF). On the other hand, Gated show significant response despite following current guidelines.
Myocardial Perfusion SPECT (GMPS) tended to be used for The aim of this study is to evaluate the prognostic significance
estimation of only ischemia in pediatric cardiology. Recently, a of cardiac sympathetic activity and dyssynchrony in cardiac
newly developed program, EXINI heart (ExH) software, enabled resynchronization therapy efficacy. Materials and Methods:
the evaluation of Left Ventricular (LV) mechanical dyssynchrony This study included 28 chronic heart failure patients (mean age
using GMPS in adult heart disease. We could observe that small of 56.5±10.2 years; 17 male). Before CRT all patients underwent
heart effect on end systolic volume and ejection fraction were 123
I-metaiodobenzylguanidine (123I-MIBG) scintigraphy for
significantly improved by using ExH with magnified GMPS. cardiac sympathetic activity evaluation. Early and delayed heart
Moreover Plasma Brain Natriuretic Peptide (BNP) concentrations to mediastinum ratios (eH/M and dH/M) as well as 123I-MIBG
has been studied in emergency department to establish the washout rate (WR) were calculated. Before CRT and six months
severity of acute HF. Many studies had shown that decreased after all patients underwent gated blood-pool SPECT (GBPS) for
uptake of MIBG is associated with LV dyssynchrony. However, to left and right ventricular end-systolic (ESV) and end-diastolic
our knowledge, it is no data on childhood HF about relationship (EDV) volumes, ejection fraction (EF) and dyssynchrony (intra-
between LV mechanical dyssynchrony and uptake of MIBG. and interventricular) evaluation. All scintigraphic images were
The aim of this study was assessed in pediatric heart disease acquired on Discovery NM/CT 570c, equipped with CZT gamma-
patients to relationship between the cardiac neuronal function camera. Results: Six months after CRT all patients were divided
using MIBG and severity of HF using BNP concentrations, and to into two groups: (1) responders (n=15) - LV ESV decreased by
relationship phase analysis using GMPS and severity of HF using ≥15% or LV EF increased by ≥5%; (2) non-responders (n=13) -
BNP concentrations . Materials and Methods: The population LV ESV decreased by <15% and LV EF increased by <5%. Prior
is consecutive 34 pediatric heart disease patients (aged 2.5±2.2 to CRT, significant differences in the following preoperative
year-old <15year old) including complex Congenital Heart scintigraphic parameters between responders and non-
Disease (CHD) of suspect HF . The subjects were received 99mTc- responders were found: eH/M (2.42 and 1.87; p<0.05), dH/M
Sestamibi (MIBI) GMPS at rest and MIBG scintigraphy. MIBI (1.89 and 1.78; p<0.05), LV EDV (271 and 299; p<0.05); LV ESV
GMPS was performed before and 1 month after performed (206 and 227; p<0.05) and interventricular dyssynchrony (109 ms
MIBG scintigraphy and measured BNP concentrations. Cardiac and 62 ms; p<0.05). According to univariate logistic regression
sympathetic activity was assessed by MIBG scintigraphy as analysis dH/M per 0.1 unit increase (odds ratio=1.87; 95%
the delayed Heart-to-Mediastinum ratio (H/M ratio) and the confidence interval 1.03-3.38, p=0.0002) and interventricular
Washout Ratio (WR). LV mechanical dyssynchrony as the dyssynchrony (odds ratio=1.027; 95% confidence interval
PhaseSD and the Bandwidth was determined by ExH software 1.008-1.046, p=0.005) were the only independent predictors of
using MIBI GMPS. It was assessed to relationship delayed response to CRT. The ROC-analysis showed that dH/M (cut of
H/M ratio, WR, PhaseSD, Bandwidth with BNP concentrations. point - 1.49; sensitivity - 89%, specificity - 100%), WR (cut of point
S379 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

- 36%; sensitivity - 67%, specificity - 100%) and interventricular EPS-164


dyssynchrony (cut of point - 61.9 ms; sensitivity - 92%, specificity Detection of left ventricular dyssynchrony in hypertensive
- 64%) had the greatest prognostic significance. Conclusion: patients using phase dyssynchrony analysis in gated
In chronic heart failure patients preoperative values of delayed myocardial perfusion SPECT
H/M and interventricular dyssynchrony are independent S. Fatima1, S. T. Butt1, M. A. Saeed1, A. Ammar1, K. B. Mir1, N.
predictors of response to CRT. 123I-MIBG scintigraphy and GBPS Ahmed1, Z. Chiragh2;
can be used as additional criteria for predicting the effectiveness 1
Nuclear Medicine, Oncology & Radiotherapy
of CRT. Acknowledgment: Grant of the President of the Russia Institute (NORI), Islamabad, PAKISTAN, 2Gurayat
Federation (No. MK-3947.2018.7) References: None. General Hospital, Al-Qurayyat, SAUDI ARABIA.

EPS-163 Aim/Introduction: LV systolic and diastolic dysfunction and


The value of gated blood-pool SPECT-derived cardiac dys-synchrony are not uncommon in patients with treatment
dyssynchrony in the cardiac resynchronization therapy naive hypertension. Diastolic dys-synchrony has been associated
response prediction with increasing incidence of heart failure, cardiovascular
V. Saushkin, A. Mishkina, V. Shipulin, A. Mochula, D. Lebedev, K. morbidity, and mortality. The objective of our study was to
Zavadovsky; assess left ventricular (LV) dys-synchrony in hypertensive
Cardiology Research Institute, Tomsk National patients with normal systolic function using GATED myocardial
Research Medical Center of the Russian Academy perfusion imaging (GMPS) in comparison with Two dimensional
of Sciences, Tomsk, RUSSIAN FEDERATION. echocardiographic (2DE) evaluations. Materials and Methods:
73 enrolled individuals were divided into two groups. Group A
included 42 hypertensive patients with good LV systolic function
Aim/Introduction: To evaluate the cardiac mechanical (ejection fraction more than 50%) and narrow QRS on the ECG
dyssynchrony (based on the GBPS results) for the selection of less than120 ms).Group B included 31 age-matched and sex-
patients with non-ischemic CHF for cardiac resynchronization matched healthy volunteers and represented the control
therapy. Materials and Methods: We examined 22 patients group. All participants underwent GMPS and 2DE . GMPS with
with non-ischemic CHF, 12 of them were observed six months 99mTc tetrofosmin was performed to assess LV dyssynchrony
after CRT. All patients underwent gated blood-pool SPECT using phase analysis. Acquired images were then submitted
(GBPS). Phase images using the first harmonic Fourier transform to the Emory Cardiac Toolbox for phase analysis. Summed Two
were computed. The phase standard deviation (PSD), histogram quantitative indices were calculated from the phase arrays of all
bandwidth (HBW) and phase entropy (E) were used as an patients: (i) histogram bandwidth, which includes 95% of the
indicator of mechanical dyssynchrony for the both ventricles. elements of the phase distribution, and (ii) phase SD, which is the
Results: Mechanical dyssynchrony of both ventricles before SD of the phase distribution. 2DE was performed and standard
CRT was increased. Median value PSD LV was 48°(35-55°), PSD 2D and color Doppler data, triggered to the QRS complex, were
RV 33°(23-43°), HBW LV 192°(126-216°), HBW RV 78°(54-210°), E saved in cine-loop format. LV end-systolic volume (LVESV) and
LV 69%(66-75%), E RV 58%(56-71%). Six months after CRT 7(58%) LV end-diastolic volume were derived from the conventional
respondents were identified. We divided the patients into two apical 2- and 4-chamber views, and LVEF was calculated.
groups and compared phase parameters. It was found that the Results: The hypertensive group had no significant perfusion
PSD (LV=38,6°, RV=26,1°) and HBW (LV=147,6°, RV=87,0°) in the abnormalities (SDS <2) as compared to control group (p<0.05).
responders group were significantly lower than in the non- In addition, treatment naïve hypertensive (57.6%) and normal
responders group (PSD (LV=56,8°, RV=61,2°); HBW (LV=234,0°, controls(42.4%) had comparable baseline characteristics, except
RV=175,2°). The value of phase entropy between both groups for histogram bandwidth (166°±6.7° vs. 109°± 6.32° (P<0.05)
is statistically not different (Responders: E LV=68%; E RV=57,5%. and phase SD (54.9°±18.7° vs. 33.1±13.9° (P<0.05), which were
Non-responders: E LV=75%; E RV=64%). Receiver operating significantly larger in hypertensives compared with controls
characteristic curve analysis demonstrated that the cutoff value (P <0.05). There was no correlation between dys-synchrony
of PSD LV ≤ 47,8° (sensitivity 74%, specificity 80%), PSD RV ≤ 33° and perfusion abnormalities in both groups. The severity of
(sensitivity 75%, specificity 80%), HBW LV ≤ 192° (sensitivity 87,5%, dys-synchrony is significantly related to the LV mass, septal
specificity 90%) and HBW RV ≤ 78° (sensitivity 75%, specificity wall thickness, posterior wall thickness, and left ventricular
80%) for predicting a good response to CRT. Conclusion: end-diastolic dimension. Conclusion: Patients with systemic
Radionuclide evaluation of mechanical dyssynchrony of the hypertension and normal systolic function demonstrate LV
left and right ventricles allow assessing the prognosis of CRT dys-synchrony by GMPS. Systolic dys-synchrony may identify
in patients with non-ischemic CHF. Acknowledgment: Grant hypertensive patients at risk for the development of further
of the President of the Russia Federation (No. MK-3947.2018.7) complications, and who may benefit from more intensive
References: None. hypertension control at an earlier stage in their disease process.
References: Folks RD, Rt N, Cooke CD, Garcia E V. Optimizing
gated myocardial perfusion imaging processing for phase
analysis. J Nucl Cardiol. 2016;23:1348-54. Peix, A., Karthikeyan, G.,
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S380

Massardo, T. et al. J. Nucl. Cardiol. (2019). https://doi.org/10.1007/ EPS-166


s12350-018-01589-5. Assessment of chemotherapy-induced systolic and
diastolic myocardial impairments using gated perfusion
SPECT
EPS-165 A. A. Ansheles, Y. A. Prus, E. I. Vasilenko, I. V. Sergienko, V. B.
The value of stress gated blood pool SPECT in prognosis Sergienko;
of early postoperative period course in patients with National Medical Research Center of Cardiology,
ischemic cardiomyopathy Moscow, RUSSIAN FEDERATION.
V. Shipulin, K. Zavadovsky, S. Andreev, A. Pryakhin, V. Shipulin;
Cardiology Research Institute, Tomsk National
Research Medical Centre, Russian Academy of Aim/Introduction: Currently, advances in treatment led
Sciences, Tomsk, RUSSIAN FEDERATION. to improved survival of patients with cancer, but have also
increased morbidity and mortality due to treatment side
effects. Cardiotoxicity is the most common complication of
Aim/Introduction: To assess the course of early postoperative chemotherapy, which must be evaluated at certain points.
status in patients with ischemic cardiomyopathy (ICM) based The aim of current research was to evaluate the effect of
on preoperative stress gated blood pool SPECT (GBPS) results. anthracyclines on the contractile (systolic and diastolic) function
Materials and Methods: The total of 44 patients with ICM were of myocardial left ventricle (LV) by using myocardial perfusion
enrolled. Prior to surgery all patients underwent GBPS at rest SPECT with 99mTc-MIBI. Materials and Methods: 52 patients
and at stress (increasing doses of dopamine according to the (19 men, 33 women) referred to chemotherapy (substantially
protocol 5/10/15 µg/kg /min). The duration of each step was with anthracyclines), underwent gated myocardial perfusion
5 minutes. Patients were divided into 2 groups: 1)n=12, with a SPECT/CT at rest before the onset of therapy and after 4 courses.
complicated course of the early postoperative period (death, Regarding functional assessment of LV, we evaluated the
the usage of intra-aortic balloon pump, inotropic support for following parameters: ejection fraction (EF) and peak ejection
more than 5 days with the need to stay in the UAR); 2)n=32, with rate (PER) as systolic indicators, peak filling rate (PFR), mean
uncomplicated postoperative course. The following parameters filling rate at first third of diastole (MFR/3), and time to peak filling
were calculated: left and right ventricular end-systolic (ESV) (TTPF) as markers of diastolic function, as well as end systolic
and end-diastolic (EDV) volumes, ejection fraction (EF), ejection and diastolic volumes (ESV, EDV, ml) as markers of probable LV
and filling rates (PER,RFR,TTPF,MFR/3) as well as dyssynchrony dilation. Results: LV systolic and diastolic function parameters
indices. Results: According to univariate U-test mots GBPS in patients after 4 courses of chemotherapy worsened in a
indexes had statistically significant differences between two parallel manner. Rest LVEF before and after 4 courses was 64±14
groups. Univariate logistic regression analysis showed that the and 59±12%, respectively, p=0.053, mostly due to systolic
following GBPS parameters allow predicting the severity of early ejection function impairment (PER decreased from 3.26±0.96
postoperative period, measured at rest: LV EF OR 0,888 (CI 0,815 to 2.81±0.74 EDV/s, p<0.01) and mild LV dilation (EDV increased
- 0,965, p=0,001); LV ESVI OR 1,033 (Cl 1,012 - 1,054, p<0,001); from 78.2±25.4 to 87.6±26.6 ml, p=0.07, and ESV increased from
LV SD OR 1,0052 (Cl 1,013 - 1,092, p=0,003); LV Bandwidth 32.2±19.8 to 38.6±20.6 ml, p=0.11). Overall peak filling rate was
OR 1,012 (Cl 1,002 - 1,023, p=0,008); RV EF OR 0,945 (Cl 0,909 decreased from 2.94±0.93 to 2.57±0.83 EDV/s, p=0.03, while
- 0,985, p=0,022); RV PFR OR 0,291 (Cl 0,111 - 0,764, p=0,006). MFR/3 and TTPF changes were not statistically reliable: MFR/3
Parameters measured at stress: LV EF OR 0,933 (Cl 0,877 - 0,993, decreased from 1.58±0.44 to 1.46±0.37 EDV/s, p=0.14, that
p=0,01); LV EDVI OR 1,018 (Cl 1,003 - 1,045, p=0,034); LV ESVI led to TTPF prolongation from 154±34 to 163±36 ms, p=0.19.
1,035 (Cl 1,014 - 1,056, p<0,001); RV EDV OR 1,014 (Cl 1,005 - Conclusion: Our findings suggest that patients pass through
1,022, p<0,001); LV SVI OR 0,248 (Cl 0,071 - 0,854, p=0,02). In systolic and diastolic myocardial function impairments during
multivariate logistic regression LV EF at rest (OR 0,866 (Cl 0,795 anthracyclines chemotherapy. While diastolic dysfunction is
- 0,956, p=0,004) and RV EDV at stress (OR 1,016 (Cl 1,007 - 1,025, known to be the first phase of doxorubicin cardiomyopathy
p<0,001) were significantly associated with complicated course and chronic heart failure development, we observed parallel
of early postoperative period. According to the ROC analysis, the decrease of LV systolic function. We assume those impairments
area under the curve (AUC 0,810; CI 0,712 - 0,886, p<0,0001) for to be reversible, but not immediately after therapy completion.
multivariate logistic regression model [LV EF at rest and RV EDV Gated myocardial perfusion SPECT enables additional evaluation
at stress] was significantly (p<0.05) higher than that for each of LV systolic and diastolic function and is reliable for dynamic
factor separately (0,717 and 0,694 respectively). Conclusion: assessment of chemotherapy cardiotoxic effects. References:
Left and right ventricular volumes and contractility parameters None.
obtained from stress GBPS are associated with the course of an
early postoperative period in patients with ICM. Stress GBPS
could be useful in the preoperative evaluation of such patients.
References: None.
S381 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

EPS-167 biopsy (EMB). Amyloid specific PET-tracers may propose high


Potential of imaging modalities as gatekeeper prior to potential for non-invasive diagnosis of CA and some tracers
endomyocardial biopsy in patients suspected of cardiac already showed promising results. Aim of this study was to
sarcoidosis: Ga-67 SPECT vs F-18 FDG PET evaluate F-18-Flutemetamol as PET-tracer for PET/MRI and
K. Takanami, K. Takase; PET/CT imaging of CA. Materials and Methods: Hybrid F-18-
Tohoku University Hospital, Sendai, JAPAN. Flutemetamol-PET imaging was performed in 22 subjects
with suspected cardiac amyloidosis (17 PET/MRI and 5 PET/
CT). 13 of those 22 patients had a verified CA by EMB, imaging,
Aim/Introduction: Endomyocardial biopsy may be required or lab results. Mean injected activity was 183.7 ± 22.6 MBq
to confirm the diagnosis of cardiac sarcoidosis (CS) in cases of and imaging was performed 68.7 ± 24.7 min p.i.. Myocardial
negative extracardiac biopsy. However, endomyocardial biopsy SUVmean and SUVmax were measured and a background VOI
has low sensitivity due to the focal nature of the disease. We was placed in the thoracic aorta for calculation of tracer-to-
examined whether low-invasive imaging modalities including background ratios (TBRmean and TBRmax). Additionally, MR-
Ga-67 SPECT and F-18 FDG PET could enhance appropriate based parameters such as late gadolinium enhancement (LGE),
endomyocardial biopsy indication in patients suspected of CS. T1 mapping and extracellular volume (ECV) were evaluated.
Materials and Methods: This study included 39 patients with Results are reported as mean±SEM. Results: Mean patient
clinically suspected CS, who underwent F-18 FDG PET, Ga-67 age was 72.7±8.8 years. TBRmax and TBRmean were higher
SPECT and myocardial biopsy. A nuclear medicine specialist in patients with CA but did not reach statistical significance
classified the myocardium F-18 FDG uptake as positive when (TBRmax 1.3±0.2 vs. 0.95 ±0.03; TBRmean 1.3±0.2 vs. 1.0±0.07).
nonuniform or diffuse high F-18 FDG uptake were observed, On visual analysis, only 3 patients had positive PET scans
and classified the myocardial Ga-67 uptake as positive when with proven amyloidosis. There was no significant difference
faint or high Ga-67 uptake were observed. The correlation between TBRmax and TBRmean in patients with AL or ATTR
between the presence of CS positive pathology and each image subtypes. MR-based parameters showed a prolonged T1-time
examination was examined using Fisher’s exact test. P < 0.05 was native in all patients (CA 1448±16ms vs. no CA 1364±30ms).
set as statistically significant. Results: Positive endomyocardial Interestingly, the measured ECV showed significantly different
pathology rate was as low as 15% (6/39). In the 6 positive-biopsy results in CA and no CA patients CA 58.9±4.7 vs. no CA 35.1±2.5).
patients, 83%(5/6) and 100%(6/6) patients were positive at Ga- Conclusion: Hybrid F-18 Flutemetamol PET/MRI is a novel tool
67 SPECT and F-18 FDG PET, respectively. Meanwhile, in the 33 for the assessment of cardiac amyloidosis. Our preliminary data
negative-biopsy patients, 91% (30/33) and 24% (8/33) patients shows a strong trend towards higher tracer-uptake in patients
were negative at Ga-67 SPECT and F-18 FDG PET, respectively. with cardiac amyloidosis. The combination with MR imaging
There was a significant association between the positive beneficially adds morphological information and MR-based
pathology and Ga-67 positive findings (p < 0.05). Meanwhile, parameters, which can substantiate the diagnosis. Despite that
no significant difference was observed between the positive only a small proportion of the verified patients had a visually
pathology and FDG positive findings. Conclusion: Ga-67 SPECT enhanced tracer-uptake leading to the question if this tracer
has a clinical potential as gatekeeper prior to endomyocardial is feasible for the evaluation of CA. Further studies in a larger
biopsy in patients suspected of CS, although further studies are cohort of patients are warranted. References: None.
needed. References: None.
Scientific e-Posters
EPS-168 EP-01
Evaluation of F-18-Flutemetamol in hybrid PET-imaging of
cardiac amyloidosis: A pilot study
Neuroimaging: Neurology
L. Kessler1, M. Papathanasiou2, A. Brainman1, D. Kersting1, P.
Lüdike2, M. Weber1, A. Carpinteiro3, T. Hagenacker4, T. Rassaf2, K. October 12 - 16, 2019 e-Poster Area
Herrmann1, C. Rischpler1;
1
Department of Nuclear medicine, University-hospital Essen,
Essen, GERMANY, 2Department of Cardiology, University-
hospital Essen, Essen, GERMANY, 3Department of Hematology, EP-0001
University-hospital Essen, Essen, GERMANY, 4Department of Disorders of Consciousness and visual fixation: a
Neurology, University-hospital Essen, Essen, GERMANY. combined analysis with flash visual evoked potentials, MRI
and PET/CT
G. Marotta1, D. Sattin2, L. D’Incerti2, D. Rossi Sebastiano2, D. Guido2,
Aim/Introduction: Cardiac amyloidosis (CA) is a rising diagnosis S. Tirelli2, A. Bersano2, D. Duran2, S. Ferrraro2, L. Minati2, A. Nigri2, C.
in patients with severe heart failure. AL (light-chain) and ATTR Rosazza2, M. Leonardi2, R. Benti1;
(transthyretin) amyloidosis are mainly responsible for cardiac 1
Fondazione IRCCS Ca’ Granda Ospedale Maggiore
involvement of amyloidosis. However, diagnosing CA can be Policlinico, Milano, ITALY, 2Fondazione IRCCS Istituto
challenging and the gold standard still is endomyocardial Neurologico Carlo Besta, Milano, ITALY.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S382

Aim/Introduction: Recent studies showed as visual responses Aim/Introduction: To assess the combined effects of reducing
to tailored stimuli seem to be one of the first evidence revealing injected [18F]FDG activity levels and applying novel image
that one patient is changing from Vegetative State (VS) to reconstruction techniques on clinical readings in patients with
minimal consciousness (MCS). The aim of this cross-sectional non-lesional epilepsy (NLE). Materials and Methods: Nine
study is to analyze the visual system in a selected group of patients with NLE underwent a 60-minute dynamic [18F]FDG-
patients in order to find useful markers for clinical classification PET/MRI examination on a fully-integrated Siemens Biograph
of participants showing visual fixation ability. Materials and mMR system. The mean injected activity was (305±95)MBq. Raw
Methods: Flash visual evoked potentials (fVEPs), structural 3T data was stored in list mode (LM) format and the last 10-minutes
magnetic resonance imaging (sMRI) and FDG-PET were analyzed of the LM data was used for static image reconstructions. To
in 58 inpatients. Forty-two (72%) patients out of 58 showed evaluate the effect of decreased dose, four LM data sets were
only visual blink reflex in the Coma Recovery Scale-Revised generated for each patient: LM data with 50%, 35%, 20% and
visual function subscale, twelve (21%) visual pursuit and four 10% of the original counts by randomly removing counts from
(7%) fixation scores. For FDG-PET, SUV maps were coregistered the original LM data. The data was reconstructed with two
using SPM12 to individual volumetric T1 series, which were different image reconstruction techniques. First, the standard
segmented to generate the normalization deformation field OSEM algorithm with resolution recovery (PSF) available from
to be applied to the coregistered FDG-PET scan. The general the vendor tools and, second with the Asymmetrical Bowsher
linear model was used to perform a voxel-by- voxel univariate (AsymBowsher) algorithm. The AsymBowsher algorithm takes
statistical test for groups comparison: a two-sample t-test was advantage of the simultaneously acquired T1-MPRAGE MR
conducted between patients with the visual blink response information for the PET image reconstruction. Additionally,
only and patients with visual pursuit. The voxel-based statistical a 3mm FHWM Gaussian post-filter was applied to all
analysis was performed by applying a threshold of p<0.001 reconstructions. The diagnostic quality of the PET images was
and considering clusters of at least 100 voxels. Results: A evaluated visually by an experienced Nuclear Medicine specialist
significant difference was also found between the two groups using a 5-point image quality scale: 5-(very good) to 1-(poor).
(voxel threshold= p<0.001 FDR-corrected) considering FDG- The clinical readings were repeated after 4-months to assess the
PET data. The cluster was composed of 389 voxels and it was intra-reader agreement. Absolute differences between readings
localized in the right calcarine cortex (Broadmann area 17) and that did not exceed a score difference of ±1 were considered
in the neighboring right lingual gyrus cortex (areas 18/19). The acceptable, higher deviations were reported. Results: For full
relationships between instrumental data (fVEPs, sMRI, PET) and count statistics, PSF image reconstruction was graded highest in
sociodemographic variables and presence of visual blink to both readings (mean value of 3.9 and 3.7 for the first reading and
threat or visual pursuit responses were fitted in univariate and second reading respectively), while the filtered AsymBowsher
multivariable logistic regression models to predict visual pursuit received a score of (2.6 and 3.0). The results of the first reading
behavior finding specific cut-off values. An AUC=0.902 was were significantly lower than the second reading, especially at
found using tailored cut-off values. Finally, a qualitative test of low count levels (35%-50%). The PSF reconstructions at 35% of
the best predictive model was made on four patients with visual the original counts received a mean grading of good (3). The
fixation revealed in 3/4 patients a good probability to predict if intra-reader accuracy of the scores was 87% for PSF and 80% for
fixation data could support/correlate to visual pursuit behavior AsymBowsher reconstructions. Conclusion: Our results indicate
or not, reducing diagnostic error using standard assessment that [18F]FDG injected activity could be potentially reduced
scale only (25% in our small sample). Conclusion: The role of down to 35% of the original counts without loss of diagnostic
primary visual cortex area for the differentiation between blink value. Moreover, although PSF reconstructed images were
and pursuit visual behavior seems to be important and our initially preferred by the clinical reader, acceptance of images
model could help clinicians to evaluate if visual fixation response created using the AsymBowsher reconstruction increased after
supports or not the diagnosis of MCS. References: None. training. Thus, the full potential of AsymBowsher reconstruction
might only be appreciated following extensive training with this
type of images. The financial support of the Austrian FWF Project
EP-0002 I3451-N32 is gratefully acknowledged. References: None.
Evaluation of reducing the [18F]FDG activity levels for
clinical readings of PET/MRI scans of patients with non-
lesional epilepsy EP-0003
H. Kertesz1, T. Traub-Weidinger2, J. Cal-Gonzalez1, I. Rausch1, O. Brain regions involved in cochlear implant user’s speech
Muzik3, L. Shiyam Sundar1, T. Beyer1; comprehension: Insights from brain-perfusion-SPECT and
1
QIMP Team, Center for Medical Physics and Biomedical EEG during a sentence discrimination task
Engineering, Vienna, AUSTRIA, 2Division of Nuclear Medicine, M. L. Kessler1,2, I. Schierholz3,2, M. Mamach4,2, F. Wilke4, A. Hahne5, L.
Department of Biomedical Imaging and Image-guided Geworski4, F. M. Bengel1, P. Sandmann6, G. Berding1,2;
Therapy, Medical University of Vienna, Vienna, AUSTRIA, 1
Department of Nuclear Medicine, Hannover Medical School,
3
Department of Radiology, Wayne State University School Hannover, GERMANY, 2Cluster of Excellence Hearing4all,
of Medicine, The Detroit Medical Center, Children’s Hospital Hannover Medical School, Hannover, GERMANY, 3Department
of Michigan, Detroit, MI, UNITED STATES OF AMERICA. of Otolaryngology, Hannover Medical School, Hannover,
S383 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

GERMANY, 4Department of Medical Physics and Radiation could be used to predict seizure outcome in patients
Protection, Hannover Medical School, Hannover, GERMANY, with drug-resistant temporal lobe epilepsy (TLE).
5
Saxon Cochlear Implant Center, University Hospital, Materials and Methods: We analyzed metabolic data with
Dresden, GERMANY, 6Department of Otorhinolaryngology, FDG-PET in 82 patients with unilateral intractable TLE (25.6 ±
University of Cologne, Cologne, GERMANY. 10.6 years old at the time of surgery, 48 female participants, 37
left). Thirty age-matched controls were included. Patients were
classified either as having seizure recurrence (Engel class II or
Aim/Introduction: The current study examines the underlying greater, SZR) or becoming seizure-free (Engel class I, SZF) at least
mechanisms of speech processing in CI patients using a 1 year after temporal lobectomy. Pearson χ2 tests were used to
multimodal approach. Data are collected by single photon compare categorical variables including clinical, pathological,
emission tomography (SPECT) and electroencephalography magnetic resonance imaging and FDG PET visual findings
(EEG). Materials and Methods: 21 post-lingually deafened between two postoperative seizure outcomes. We compared
CI patients (62±11y, 18 right-handed, 10 f ) participated in the regional abnormal glucose metabolism in inside and outside
study with two sessions. One session includes a task in which epileptogenic foci between each outcome group (SZR and
sentences are classified as semantically correct or incorrect. SZF) and control group in each TLE side. Imaging processing
During the task, a 96-channel EEG is being recorded. Two minutes was performed with statistical parametric mapping (SPM12).
after the start of the task, 740 MBq of 99mTc-HMPAO are injected The volume, intensity and special brain areas of abnormal
intravenously. A SPECT scan 1.5 hours after injection shows metabolism in temporal and extratemporal region visualized or
the cortical activity during the task. A second session includes quantified using xjView Matlab toolbox. Results: With a median
a SPECT scan after injection at rest. Image-based analysis was follow-up 1.5 years (IQR 1.2-2.3), 60% of patients achieved SZF.
carried out with SPM8. Results: A larger N400 wave in the EEG Multivariate analyses demonstrated three predictors of seizure
was associated with enhanced activity in the middle temporal recurrence: left TLE (P =0.006), nonlesional pathology results
area revealed by the SPECT scan (task vs. rest). A higher working (P=0.007) and extensive hypometabolism on FDG-PET (P =
memory capacity was associated with increased activity in left- 0.03). All patients had hypometabolism in the temporal cortex
sided inferior, middle and superior temporal areas, as well as ipsilateral to the epileptogenic region, but the surgical outcomes
bilateral occipital and parietal areas. Contrasting CI users with were not associated with the volume and intensity of ipsilateral
higher and lower performance, using a median-split of scores temporal hypometabolism (P˃0.05), whereas SZR correlated
in the Göttinger sentence test (speech reception threshold with extratemporal metabolic changes that differed according
for 50% speech understanding in noise), a higher increase in to the lateralization: In right TLE, compared with SZF patients,
perfusion in the bilateral high (pre)frontal lobe, Broca’s area, patients with SZR had larger volume of metabolic changes in
as well as right-sided superior temporal, inferior temporal and extratemporal areas (P<0.05), the critical value of the volume of
temporopolar regions was observed in the group of lower CI metabolic changes outside the right TLE foci calculated by ROC
performers considering difference images (stimulation-rest). curve was 12580 mm3, regional abnormal negative predictors
The group of higher performers, in contrast, showed a higher were in the Cingulum_Ant_R/L, Frontal_Inf_Orb_R and
increase in perfusion in occipital, left-sided middle and inferior Supp_Motor_Area_R(aal). In left TLE, SZR presented a volume
temporal regions, as well as in the right-sided motor cortex. of metabolic changes in extratemporal areas similar to right
Conclusion: Combined SPECT/EEG measurements in the TLE, but the difference was not significant (P˃0.05), whereas
context of a speech processing task show the recruitment of Cingulum_Ant_R, Precuneus_R and Frontal_Sup_Orb_L(aal)
a temporo-frontal network with differential activation patterns involvement metabolic changes correlated to a less favorable
according to speech recognition abilities. The correct detection outcome. Conclusion: Extratemporal metabolic profile outside
of semantic violations, as indicated by an enhanced N400 in the the seizure foci on FDG-PET may represent a prominent cause
EEG, was related to higher perfusion in the middle temporal of temporal lobe surgery failure. Seizure control after epilepsy
region, which is in line with findings in normal hearing subjects, surgery might be improved by investigating areas of abnormal
providing further evidence that this region is the generator of metabolism extratemporal as candidates for resection or
the N400. References: None. neuromodulation. References: None.

EP-0004 EP-0005
Extratemporal metabolic profile on FDG-PET in temporal FDG-PET in theevaluation of patients with drug-resistant
lobe epilepsy as a predictor of surgical failure focal epilepsy
Y. Tang, G. Liao, J. Li, T. Long, Y. Li, S. Hu; G. Capriotti1, P. Pizzichini1, L. Carideo1, G. Franchi1, L. De Palma2, D.
Department of PET Center, XiangYa Hospital Prosperi1, A. Signore1;
Central South University, Changsha, CHINA. 1
Sapienza University, Rome, ITALY, 2Ospedale
Pediatrico Bambino Gesù, Rome, ITALY.

Aim/Introduction: To evaluate whether the profile


of extratemporal metabolic changes on FDG-PET Aim/Introduction: Interictal [18F]fluorodeoxyglucose-positron
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S384

emission tomography (FDG-PET) is useful in the presurgical metabolism from that to the energy consumption to manage
evaluation of patients with drug-resistant focal epilepsy. cognitive tasks. The aim of the present study, therefore, was
Hypometabolism overlies the seizure-onset zone (SOZ) with a to clarify the mechanism of this phenomenon. Materials and
sensitivity of 86-90% in temporal lobe epilepsy (TLE) and of 45- Methods: In this double-blind, placebo-controlled study-
60% in extra-TLE. We aimed at clarifying its relationship with ictal design, 18 healthy young Japanese men received single
high-frequency oscillation (iHFOs), arterial spin labeling (ASL - an doses of non-sedative antihistamine (levocetirizine 5 mg) and
emerging non-invasive magnetic resonance imaging perfusion sedative antihistamine (diphenhydramine 50 mg) at intervals
technique), and PET/CT. Materials and Methods: Twelve of at least six days (Task group). Task performances and brain
consecutive patients with cortical epilepsy for pre-surgical activity were evaluated during three cognitive tests (word
evaluation underwent a standardized assessment including fluency, two-back, and Stroop). Additional 6 healthy young
video-electroencephalography (EEG) monitoring, structural MRI Japanese men received the antihistamines and were tested in
with ASL sequences and FDG-PET. We studied the correlation the same manner as Task group but without cognitive studies
between epileptogenicity maps and FDG-PET and ASL. Results: (Rest group). Regional cerebral glucose consumption changes
we studied 12 patients [7 women and 5 man; mean age 23] for were measured using positron emission tomography (PET) with
12 total lesions. Of these 12 patients: 9 were affected by TLE and [18F]fluorodeoxyglucose, by scanning these subjects before and
3 by extra-TLE (2 patients with orbital epilepsy and 1 with cortical after antihistamine treatments. Then, brain energy consumption
displasia). The frequency band of iHFOs was on average 81-139 was examined in terms of standardized uptake value (SUV).
Hz (lowest,30-60 Hz; highest, 160-210 Hz) and locolized the Results: Energy consumption (SUV) in the prefrontal regions
epilettogenic zone.PET scan identifies interictal hypometabolism of Task group was significantly higher after antihistamines
in all patients with TLE and cortical displasia, whereas the scan treatments (with levocetirizine and diphenhydramine) than that
were negative in the remains extra-TLE (orbital epilepsy). ASL- after placebo treatment. In Rest group, however, brain energy
MRI identified abnormalities (hypoperfusion) were seen in consumption in the prefrontal regions showed no-significant
7 of 9 patients vith TLE and in 2 of 3 patients with extra-TLE. change before and after both antihistamines treatments and
Conclusion: Conclusion: This finding suggests that interictal placebo treatment. As for the results of cognitive studyin
FDG-PET and ictal HFOs may share common underlying Task group, Stroop test accuracy was significantly impaired
pathophysiologic mechanisms of ictogenesis in temporal lobe by diphenhydramine although the performance after
epilepsy.Interictal ASL is a non-invasive method that may help levocetirizine treatment was not impaired. Conclusion: These
to localize the epileptogenic in extra-TLE zone showing hypo- results suggested that the increased brain energy consumption
perfusion in FCD. References: None. observed in our previous study(1) was more associated with the
increased energy demand to manage cognitive tasks during
coginitive tests than with the increased energy consumption in
EP-0006 the baseline state of the brain of subjects/patients. References:
Effects of different antihistamine drugs on energy 1) Kikuchi A, et al. Effects of levocetirizine and diphenhydramine
consumption in the brain of healthy volunteers during on regional glucose metabolic changes and hemodynamic
cognitive study responses in the human prefrontal cortex during cognitive
M. Tashiro1, N. Suzuki1, E. Chen1, A. Kikuchi1, A. Inami1, A. Mohsen2,1, tasks. Hum Psychopharmacol. 2018;33(2):e2655.
S. Watanuki1, M. Miyake1, K. Takeda1, K. Hiraoka1, M. Maurer3, K.
Yanai4, H. Watabe1;
1
Cyclotron and Radioisotope Center, Tohoku University, EP-0007
Sendai, JAPAN, 2National Institutes of Biomedical Innovation, The Different Metabolic Patterns Of Brain 18f-FDG PET In
Health, and Nutrition, Osaka, JAPAN, 3Department of Anti-nmda,anti-lgi1 And Anti-gabab Encephalitis
Dermatology and Allergy, Charité—Universitätsmedizin Berlin, X. Zhao, X. Li, Z. Qiao, K. Wang, Q. Chen, L. Ai;
Berlin, GERMANY, 4Department of Pharmacology, Tohoku Beijing Tiantan hospital, Beijing, CHINA.
University Graduate School of Medicine, Sendai, JAPAN.

Aim/Introduction: Pathogenic auto-antibodies targeting


Aim/Introduction: Antihistamines often have sedating side the recently identified LGi-1, NMDA and GABAb induce
effects on the brain of allergic patients. This side effect has autoimmune encephalitis. The comparison of brain metabolic
been associated with certain accidents during car-driving or patterns in 18F-FDG PET of anti-NMDA,anti-LGi-1,and anti-GABAb
operating dangerous machinery. That is why this topic has encephalitis patients has not been performed yet in a larger
been of social importance. In our previous study using positron sample and shall be helpful in differentiating these autoimmune
emission tomography (PET) and [18F]fluorodeoxyglucose, encephalitis. Materials and Methods: The brain 18F-FDG
we observed that the brain energy consumption increased uptake of eleven anti-NMDA , twenty-eight anti-LGi-1 and seven
significantly after cognitive loads following antihistamine anti-GABAb encephalitis patients admitted to Beijing Tiantan
treatments in comparison to the results after the same hospital between 2014 and 2018 was retrospectively analyzed.
cognitive studies following placebo treatment (1). But we could Group analysis by statistical parametrical mapping of 18F-FDG
not separate the effect of antihismines to the baseline brain shows significant (p < 0.05, two sample t-test uncorrected for
S385 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

multiple comparisons and an extent threshold of 30 voxels ) PET/CT scan of the brain. The patterns of FDG uptake were
hypermetabolism and hypometabolism in different brain regions recorded and comparison with normalized data was attempted.
of these three types of encephalitis patients compared to forty- The areas of hypo/hypermetabolism that were two standard
seven age and sex matched controls. Results: In general , the deviations from the mean were considered as abnormal. The
hypermetabolism brain regions of three types of encephalitis patients were also analyzed based on the Z score surface maps
were observed in the cerebellum and basal ganglia. Group of the 3D stereotactic surface projections (SSP) image and
analysis of anti-NMDA encephalitis patients demonstrated regional Z scores were evaluated. Post treatment follow-up
regionally limited hypermetabolism in cerebellum contrasting scans, when available were compared with the pre-treatment
hypometabolism in occipital and frontal lobes. The anti- scans. The FDG PET CT scans were compared with the diffusion
LGi-1 was characterized by hypermetabolism in cerebellum weighted MRI scans and the areas of concordance recorded.
and basal ganglia as well as an extensive frontal and parietal Results: All patients had an abnormal pattern of FDG uptake,
hypometabolism. The GABAb encephalitis patients showed both on visual inspection and semiquantitative analysis. Variable
hepermetabolism in medial temporal lobe and basal ganglia. degrees of focal hypermetabolism was noted in the pons,
Conclusion: This retrospective 18F-FDG PET study provides novel mid brain, thalami, basal ganglia, cerebellum, brain stem and
evidence for distinct brain metabolic patterns in patients with bilateral medial temporal regions with or without associated
anti-NMDA,anti-LGi-1 and anti- GABAb encephalitis. References: cortical hypometabolism. Out of the 6 subjects, 3 patients had
[1] Graus F, Titulaer M J, Balu R, et al. A clinical approach to normal MRI at the time of clinical and scintigraphic diagnosis
diagnosis of autoimmune encephalitis.[J].The Lancet Neurology, and 3 showed mildly restricted diffusion in the pons. All the
2016:S1474442215004019.[2] Solnes L B, Jones K M, Rowe S P, et subjects were positive for ODS on delayed MRI scans. On follow
al. Diagnostic Value of18 F-FDG PET/CT Versus MRI in the Setting up, 2 out 6 showed improvement in the cerebral glucose
of Antibody-Specific Autoimmune Encephalitis[J]. Journal of metabolic pattern. Conclusion: FDG PET is a sensitive non
Nuclear Medicine,2017,58(8):1307-1313.[3] Baumgartner A, invasive imaging modality which may contribute to the early
Rauer S, Mader I, et al. Cerebral FDG-PET and MRI findings in diagnosis and management of patients with clinical suspicion
autoimmune limbic encephalitis: correlation with autoantibody of ODS, especially in the setting of non contributory/normal
types[J]. 2013,260(11):2744-2753. MRI. References: None.

EP-0008 EP-0009
Early diagnosis of Osmotic Demyelination syndrome with FDG-PET assessment and metabolic patterns in Lafora
18-FDG PET CT disease: a multicenter retrospective study
N. K. Seniaray1, R. Verma1, R. Ranjan2, E. Belho1, D. Malik1, H. A. Paccagnella1, A. Farolfi1, F. Pondrelli2, L. Muccioli2, G. D’Orsi3, R.
Mahajan1; Michelucci4, E. Freri5, L. Canafoglia6, L. Licchetta2, G. Marotta7, F.
1
Mahajan Imaging Center, Sir Ganga Ram Hospital, Toni4, T. Martino3, P. Tinuper2, F. Bisulli2, C. Pettinato8, S. Civollani8, R.
New Delhi, INDIA, 2Department of neurology, Sir Bonfiglioli1, V. Allegri1, S. Fanti1;
Ganga Ram Hospital, New Delhi, INDIA. 1
S.Orsola Hospital, University of Bologna, Bologna, ITALY,
2
Department of Biomedical and Neuromotor Sciences, University
of Bologna, Bologna, ITALY, 3Epilepsy Centre, Clinic of Nervous
Aim/Introduction: Osmotic Demyelination Syndrome (ODS) System Diseases, University of Foggia, Ospedali Riuniti, Foggia,
which compasses both Central Pontine Myelinolysis (CPM) ITALY, 4IRCCS Istituto delle Scienze Neurologiche di Bologna,
and Extrapontine Myelinolysis (EPM) is a rare neurological Bologna, ITALY, 5Pediatric Neurology, Fondazione IRCCS
complication attributed to rapid correction of hyponatremia or Istituto Neurologico Carlo Besta, Milano, ITALY, 6Department of
rapid shifts of osmolality in certain metabolic and toxic states. Neurophysiology and Diagnostic Epileptology, Fondazione IRCCS
It is characterized by destruction of the myelin sheath and Istituto Neurologico Carlo Besta, Milano, ITALY, 7IRCCS Ca’ Granda
oligodendrocytes in pons, cerebellum, hippocampus, basal Ospedale Maggiore Policlinico di Milano, Milano, ITALY, 8Medical
ganglia, brain stem and thalamus without any inflammation Physics Unit, Radiology Unit, S.Orsola Hospital, Bologna, ITALY.
and with relative preservation of the axons. Early diagnosis is
imperative for adequate management of patients with Osmotic
Demyelination Syndrome. MRI with its special sequences is Aim/Introduction: Lafora disease (LD) is a rare, lethal,
the investigation of choice for the detection of the osmotic autosomal recessive progressive myoclonus epilepsy.
changes in the brain but sometimes is non contributory very 18
F-fluorodeoxyglucose positron emission tomography (FDG-
early in the course of disease. 18-FDG PET shows areas of PET) reports in LD patients are anecdotal, showing heterogeneous
focal hypermetabolism in the pons, cerebellum, brain stem findings. Here we describe cerebral glucose metabolism pattern
and bilateral medial temporal regions as early as within 24 as assessed by FDG-PET in eight patients with LD. Materials and
hours of the disease and may be useful for establishing the Methods: We included patients referred to three Italian epilepsy
diagnosis in clinically suspected ODS. Materials and Methods: centers with genetically confirmed LD who underwent FDG-PET
7 consecutive patients (3 males and 4 females) with suspected scan between April 2014 and January 2019. FDG-PET images
Osmotic Demyelination Syndrome, were evaluated with FDG were coregistered with MRI and evaluated by two independent
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S386

nuclear medicine physicians, with at least 3 years of experience progressive increase in brain glucose metabolism Conclusion:
in neuroimaging and unaware of clinical history. Furthermore, Diffuse progressive increase in brain FDG activity may be
paired t-tests were performed for subgroups analysis on the related to the cell therapy and his clinical benefit. References:
basis of genetic (EPM2A vs. NHLRC1 mutations) and clinical VaqueroJ,ZuritaM,RicoMA,BonillaC,AguayoC,Montilla J, et al.
features (presence of visual symptoms, stage of disease) An approach to personalized cell therapy in chronic complete
employing SPM8 software. When possible, the examination was paraplegia: the Puerta de Hierro phase I/II clinical trial.
repeated during follow-up assessment. Results: Eight Italian Cytotherapy 2016;18:1024-35.Vaquero J, Zurita M. Functional
patients (3M/5F) underwent FDG-PET examination after a mean recovery after severe central nervous system trauma: current
of 6.6 years from disease onset (range: 1-9). Visually assessed perspectives for cell therapy with bone marrow stromal cells.
FDG-PET was abnormal in 8/8 patients, with a substantial Progr Neurobiol 2011;93: 341-9.
agreement (Cohen’κ 0.63) between two readers in the region-
based visual analysis. Seven out of eight patients (88%) showed
diffuse bilateral cerebral hypometabolism, more pronounced in EP-0011
advanced stages of disease. Most severely (moderate to severe) 18F-FDG-PET in Focal, Drug-Resistent Epilepsy: An
hypometabolic areas were parietal lobe (6/8 patients), temporal Important Tool for the Pre-Surgical Evaluation
lobe (5/8), frontal lobe (5/8) and thalamus (4/8). Severe thalamic F. Mattana1, A. Farolfi1, A. Paccagnella1, G. M. Lima1, A. Lambertini1,
hypometabolism was a recurrent finding in our cohort. The SPM V. Barone2, V. Allegri1, S. Fanti1;
subgroup analysis found no significant differences between 1
Metropolitan Nuclear Medicine, S. Orsola-Malpighi Hospital,
patients with EPM2A and NHLRC1 mutations, whereas a different University of Bologna, Bologna, ITALY, 2IRCCS Bologna Institute
pattern was found in patients with visual symptoms (bilateral of Neurological Sciences, University of Bologna, Bologna, ITALY.
hypometabolism in the parietal and temporal lobe) compared
to those without. Moreover, higher stage of LD progression
scale was positively associated with a more compromised and Aim/Introduction: Interictal [18F]fluorodeoxyglucose-positron
diffuse hypometabolism. In 3/8 patients (38%) the exam was emission tomography (FDG-PET) is used in the presurgical
repeated after a mean of 17 months (range: 8-36) showing a evaluation of patients with drug-resistant focal epilepsy. We
more pronounced hypometabolism compared to the baseline aimed to understand the role of FDG-PET in individualizing the
FDG-PET. Conclusion: FDG-PET seems highly sensitive to epileptogenic zone (EZ) and if it should be useful to guide the
evaluate LD at any stage. Our findings may speculatively be placement of electrodes in SEEG. Materials and Methods: We
related with LD pathogenesis (impairment of normal glycogen studied the correlation between FDG-PET and epileptogenicity
metabolism with consequent diffuse destruction of neurons maps in an unselected series of 25 consecutive patients. All
and LBs accumulation). FDG-PET may also correlate with disease patients underwent SEEG, as part of their pre-surgical evaluation.
stage and be therefore useful to evaluate response to upcoming Period of reference was 2013-2015 with a minimum follow up
therapeutic strategies for LD. Further prospective studies would of two years after surgery. Results: 16/25 (64%) had TLE: 9 with
be useful to confirm the relation between FDG-PET findings and only temporal lobe involved, 6 with temporal and another extra
disease stage. References: None. temporal area involved, 9/25 (36%) patients had extra-TLE. The
extra TLE was determined by a combined analysis of the ictal
clinical semiology, EEG, MRI, SEEG, and FDG-PET. 13/25 (52%)
EP-0010 patients were MRI positive and 12/25 (48%) patients were MRI
Brain Metabolism changes in patients with diffuse axonal negative for brain anomalies, while 23/25 (92%) were PET positive
injure after intrathecal cell therapy (defined from a presence of focal area of hypometabolism) and
J. Mucientes, J. Vaquero, M. Zurita, C. Fernandez, M. Mitjavila; 2/25 (8%) where PET negative. Surgical resection was performed
Hospital Universitario Puerta de Hierro, in all of these patients, and after a mean postoperative follow-up
Majadahonda, Madrid, SPAIN. of 28 months (range 24-50 months), seizure outcome, according
to Engel’s classification, showed that 19 patients were in class I
(76%), 3 in class II (12%), 1 in class III (4%), and 2 in class IV (8%).
Aim/Introduction: Neuroimaging in cell therapy in In 19 cases FDG-PET was concordant whit the SEEG (showing
neurological disability is in its initial clinical stage. We describe the presence of an hypometabolic area in the EZ was detected),
our preliminary clinical experience with neurological FDG whereas in 2 cases the hypo area was close to the EZ; in 2cases
PET-CT before and after treatment in patients with defuse PET was negative in the EZ and in other 2 cases showed an
axonal injury (DAI) treated with cell therapy. Materials and hypo area without a corresponding EZ in SEEG. Conclusion:
Methods: Three patients with established neurological This study aimed to compare the localization of EZ on SEEG at
sequelae due to DAI received intrathecally autologous seizure onset, with the interictal patterns of metabolism for each
mesenchymal stromal cells MSCs. We performed a brain FDG patient. We showed that hypometabolic regions correlate with
PET before and a month after treatment. Results: All the the SEEG, not only in TLE as described in the previous literature,
three patients showed improvement after cell therapy, and but also in the extra-TLE. This data could confirm the value of
subsequent studies with 18F-fluorodeoxyglucose (18F-FDG) FDG-PET in the diagnostic process for focal, drug-resistent,
positron emission tomography (PET) showed a diffuse and complex cases of epilepsy. The power of these data is the very
S387 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

good post-surgical outcame for most of enrolled patients, while Medica Sur, Ciudad de México, MEXICO, 2Rodrigo
1

the main limitations are the heterogeneity of the epileptogenic Hernandez, Ciudad de México, MEXICO.
zone and the few number of the patients. References: None.

Aim/Introduction: Assess the utility of PET/CT with 18F-FDG,


EP-0012 for the investigation of patients with suspected autoimmune
Multimodal imaging approach in epilepsy: PET-MRI encephalitis Materials and Methods: A retrospective study
software coregistration in the assessment of localization was conducted from June 2009 to February 2019. We reviewed
the potential epileptogenic focus 18
F-FDG PET/CT scans of patients with clinical diagnosis of acute
A. Mestre Fusco1, S. González-Ortiz2, S. Medrano2, M. Suárez- encephalitis,18 cases were selected to be further reviewed
Piñera1, M. Ley3, A. Principe3, J. Capellades2, R. Rocamora3; for antibodies laboratory, historical information, diagnostic
1
Nuclear Medicine, Hospital del Mar - Parc de Salut Mar, workup, medications administered, and neuroimaging findings
Barcelona, SPAIN, 2Radiology, Hospital del Mar - Parc de Results: 18 patients (14 women, 4 men; mean age, 63 y) with
Salut Mar, Barcelona, SPAIN, 3Epilepsy Unit - Neurology, clinical diagnosis of autoimmune encephalitis presented with
Hospital del Mar - Parc de Salut Mar, Barcelona, SPAIN. acute altered mental status, with seizures, depression, visual
hallucinations the most common neurological symptoms.
All 18 patients had abnormal uptake with 18F-FDG PET/CT
Aim/Introduction: Our aim is to evaluate the usefulness of the showing hypermetabolism most commonly in the superior
cerebral positron emission tomography (PET) and magnetic frontal, orbitofrontal, dorsolateral prefrontal, and parietal cortex,
resonance imaging (MRI) images coregistration in order to mesial temporal structures, cingulate, caudate and putamen.
identify the potential epileptogenic areas preoperatively in 6 patients had an abnormal radiopharmaceutical uptake as
patients with drug-resistant epilepsy (DRE). Materials and a suspicion of a primary tumor, which were subsequently
Methods: We prospectively included 40 consecutive patients confirmed as having malignancy. The rest of the patients were
(January 2016-March 2018, mean 38 years-old, 19 male) with evaluated with EEG and CSF samples for the study of infections
DRE both, PET and MRI, as part of the presurgical study. The and paraneoplastic antibodies. CSF was positive in 1 patient for
18F-FDG PET (Siemens Biograph 6 PET-CT) and MRI (Philips Borrelia burgdorferi infection. CSF was significant in 7 patients
Achieva 3-Tesla), acquired separately, are coregistered with with elevation of white cell count in 5 patients and mild
“integrated registration” application of the AW-server 2.0 elevation of protein in 2 patients. 7 patients had paraneoplastic
software. FDG-PET and MRI are evaluated separately by a panel results available with 6 being negative for NMDA, anti-
nuclear medicine and neuroradiologist and then the PET-MRI Hu, VGK antibodies, and 1 being positive for GAD65. All seven
fusion is evaluated together in a second-look. We compare patients that had hypermetabolism with PET/CT were treated
the localization of epileptogenic lesions by the three methods. with immunoglobulin, which all improved clinically. MRI were
The potential epileptogenic area determined by neuroimaging available in 8 of the patients. 2 patients had hyperintensity on
is compared with the electroclinical hypothesis and in some FLAIR weighted MRI, one located in bilateral internal frontal
cases with the invasive EEG studies in patients who were convolution cortex and the second at the bilateral mesial
implanted. Results: In 26 out of 40 patients (65%) the PET-MRI temporal lobe. The rest of MRIs were all unremarkable except
fusion second-look has changed the suspicious area either by a development of isolated gliosis areas Conclusion: PET/CT is a
reduction in the spread of hypometabolism or by the detection useful tool in the diagnostic workup of patients with clinically
of a new hypometabolic focus. Structural MRI showed no suspected autoimmune encephalitis, to rule out neoplastic
lesions in 16 patients. In these patients, PET-MRI fusion images and infectious origin and to those who do not test positive for
showed a hypometabolic area in 13 (81%) patients that was paraneoplastic antibodies. PET/CT should be performed in such
concordant with clinical hypothesis or seizure onset zone on patients, FDG-PET can be positive despite a normal brain MRI
EEG. Localization of hypometabolism areas include temporal References: None.
lobe (hippocampus, amydala or temporo-polar region), insula,
frontal operculum, parietal lobe and parieto-occipital areas.
Structural findings on MRI include focal cortical dysplasia, EP-0014
sclerosis, heterotopia and cortical asymmetries. Conclusion: 18F-DOPA positron emission tomography features in brain
The fusion of 18F-FDG PET-RMI is a useful method to detect or tumefactive demyelinating lesions
to delimit the potential epileptogenic zone and can be useful S. Raffa1, M. Bauckneht2, L. Roccatagliata1,3, S. Capitanio2, E.
for planning invasive EEG studies or surgery. References: None. Sbragia4, M. Pardini4,5, C. Lapucci4, M. I. Donegani1, A. A. Miceli1, A.
Uccelli4,5, M. Inglese4,5, F. M. Nobili4,5, G. Sambuceti1,2, S. Morbelli1,2;
1
Department of health sciences (DISSAL), University of Genoa,
EP-0013 Genoa, ITALY, 2Nuclear Medicine Unit, IRCCS Policlinico San
Autoimmune encephalitis: utility of PET/CT with18F-FDG Martino, Largo R. Benzi 10, Genoa, ITALY, 3Neuroradiology, IRCCS
as the first diagnostic step Ospedale Policlinico San Martino, Largo R. Benzi 10, Genoa, ITALY,
E. Fajardo Ordoñez1, R. Hernandez2, J. Chavez Torres1, D. Pachuca 4
Clinical Neurology, Department of neuroscience (DINOGMI),
Gonzalez1;
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S388

University of Genoa, Genoa, ITALY, 5Clinica neurologica, IRCCS Aim/Introduction: Regional cerebral perfusion (rCBF) may be
Ospedale Policlinico San Martino, Largo R. Benzi 10, Genoa, ITALY. modified during exposure to microgravity. Microgravity induces
a rapid thoraco-cephalic fluid shift and generates a possible
increase of intra-cranial pressure [1]. Dry immersion (DI) is a
Aim/Introduction: Tumefactive Demyelinating Lesions (TDLs), simulated microgravity model that reproduces the effects of
are defined as acute, large (>2 cm), tumor-like lesions in the microgravity on human fluids [2]. However, consequences on
central nervous system. These lesions are often associated with rCBF have never been directly assessed in real or simulated
ring enhancement ad a T2 Hypointense rim, peripheral restriction microgravity. Materials and Methods: Cerebral perfusion was
on diffusion-weighted imaging ad venular enhancement, and measured 4 days before and at the end of a 5-day DI in 18 healthy
presence of surrounding edema that causing mass effect. For male subjects (34.0 +/- 5.5 years old, 16 right dominant hand)
these radiological characteristics, TDLs may mimic space- using a single photon emission computed tomography (SPECT)
occupying lesions (SOLs). It has been suggested that positron with the radiopharmaceutical 99mTc-hexamethylpropylene
emission tomography (PET), particularly with labelled amino amine oxime (HMPAO). SPECT-HMPAO were compared between
acid tracers, could be useful in the differential diagnosis (d.d.) of the two groups using SPM 12, by paired t test statistical analysis
TDLs, especially with primary brain tumors (PBTs), in particular with a threshold of p < 0.005. Results: DI induced a significant
with low-grade gliomas (LGGs) or primary brain lymphomas. hypoperfusion in the cortex, mainly in the two temporal regions
Based on these considerations, we aimed to individuate specific (right temporal peak level : Z = 3,61, p uncorr <0,001;left temporal
18F-DOPA-PET and MRIs features of TDLs in a retrospective peak level : Z = 3,40, puncorr <0,001))and induced an increase
case series including TDLs, LGGs and lymphomas. Materials in perfusion in subcortical regions (including left thalamus
and Methods: We retrospectively evaluated brain MRI and (peak level: Z = 3,07, p uncorr <0,001)). Conclusion: After 5 days
18F-DOPA-PET performed between February 2018 and March of DI, subjects presented significant hypoperfusion mainly in
2019 in patients with SOLs whose d.d. included TDLs. MRIs were the bilateral temporal regions and hyperperfusion in the left
visually coregistered to 18-DOPA-PET images, and maximum thalamus region, measured by SPECT-HMPAO. Hyperperfusion
standardized uptake (SUVmax) values within lesions and their in the left thalamus may be related to a muscular biopsy in
mutual ratios with striatum were calculated. The final diagnosis the right vastus lateralis performedthe day before the SPECT
was established based on histology or clinical/radiological the end of DI. Hypoperfusion in the cortical regions might be
follow-up at six months. Results: A total 8 patients were due to the thoraco-cephalic fluid shift and/or to the unloading
identified. In 3 patients the final diagnosis was TDLs. In the other support induced by the DI model. To test these assumptions, we
5 patients 4 were diagnose with LLGs (1 with gliomatosis cerebri need to conduct analysis of other parameters such as indirect
pattern) and 1 primary brain B-cell Lymphoma (PBBCL). Mean assessment of intracranial pressure and psychological tests.
SUVmax was 2,02 for TDLs (standard deviation s.d.- 0,48; range References: [1] Heer M, et al. Space motion sickness: incidence,
1,31-2,42) and 4,48 (s.d. 0,86; range 3,19-5,53) for PBTs, with etiology, and countermeasures. Auton Neurosci 2006; 129(1-
lowest value recorded in PBBCL (3,19). Mean ratios with striatum 2):77-9.[2] Navasiolava et al. 2011). Long-term dry immersion:
in TDLs were 0,7 (s.d. 0,17; range 0,6-0,9) and 1,5 (s.d. 0,44; range review and prospects. Eur J Appl Physiol 2011;111(7):1235-60.
0,9-2,1) for PBTs, with the lowest value recorded in PBBCL,
overlapping with values of TDLs (0,9). Conclusion: The present
case series support the potential usefulness of 18F-DOPA-PET EP-0016
in the differential diagnosis of TDL. For instance, there was no Brain perfusion SPECT imaging in comparison to brain MRI
overlap in SUVratio in patients with TDLs with respect to LLGs. imaging and their correlation with clinical condition in
However, a gray-zone between TDLs and lymphomas was patients with multiple sclerosis
highlighted. Coregistration of PET and MRI data and more deep M. Assadi1, H. Shooli1, R. Nemati1, N. Chabi1, E. Jafari1, H. Dadgar2;
integration of 18F-DOPA-PET and MRI features might be of 1
Bushehr University of Medical Sciences (BUMS), Bushehr,
interest to better disclose the potential role of 18F-DOPA-PET in IRAN, ISLAMIC REPUBLIC OF, 2Imam Reza International
the differential diagnosis of TDLs. References: None. University, Mashhad, IRAN, ISLAMIC REPUBLIC OF.

EP-0015 Aim/Introduction: Multiple sclerosis (MS) is an inflammatory,


Cerebral perfusion measured by 99mTc-HMPAO SPECT disabling, and unpredictable disorder that involves the central
in a simulated microgravity model using a 5-day dry nervous system (CNS) and results in the progressive neurological
immersion disturbance. The role of gray matter in Multiple sclerosis (MS) is
L. Guillon1, M. P. Bareille2, E. Cassol1, A. Beck2, M. Beaurain1, P. increasingly evident. Both gray matter perfusion and volume
Peran3, J. A. Lotterie1,3, A. Pavy - Le Traon4,5, P. Payoux1,3; reduction are correlated with cognition and ambulation
1
Nuclear Medicine Department of University Hospital of Toulouse, impairment and other clinical disturbance. We aimed to compare
Toulouse, FRANCE, 2MEDES, Toulouse, FRANCE, 3TONIC, Toulouse quantitative brain perfusion SPECT with brain MRI imaging and
NeuroImaging Center, University of Toulouse, Inserm, UPS, their correlation with clinical tests. Materials and Methods: In
Toulouse, FRANCE, 4Neurological Department of University Hospital this cross-sectional descriptive study, 19 patients with RRMS
of Toulouse, Toulouse, FRANCE, 5I2MC - INSERM, Toulouse, FRANCE. were recruited. They underwent brain perfusion SPECT imaging
S389 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

and brain MRI imaging along with several clinical examinations images were blindly analyzed both visually and with SISCOM
including EDSS, MMSE, SPPB, rapid smell test, Wechsler memory by two experienced nuclear medicine physicians. The reference
test, word-color complex Stroop (software version). The intima standard of EF location was defined by pathology and follow-
layer thickness of the carotid artery measured by external up in operated patients. In non-operated patients the reference
ultrasound. The brain SPECT and brain MRI images quantitatively standard was determined by the set of patient’s exams (seizure
analyzed (grouped and individual) by SPM software employing semiology, serial EEG, long-term-video-EEG, and MRI). Visual and
VBM technique to identify abnormal areas in the brain. the SISCOM analyses were compared to reference standard and
location of areas with significantly reduced grey matter density classified as concordant, discordant and partially concordant.
or perfusion was detected by using AAL (Automated Anatomical Results: Ictal and interictal SPECT images were analyzed both
Labeling) software. Data analysis was performed using SPSS visually and by SISCOM in twenty-four patients (13 women;
version 22 software. Results: All of RRMS patients were 30.8 ± 13.3 years). In relation to the reference standard, SISCOM
cognitively unimpaired. Quantitative images analysis revealed was concordant in 18 cases (75.0%), while visual analysis was
SPECT imaging can detect broad abnormal areas on the brain concordant in 13 cases (54.2%). SISCOM increased by 20.8% the
better than MRI imaging except for areas deep in the brain correct location of the EF. SISCOM was discordant in 5 (20,8%)
(insula and basal ganglia) in which MRI imaging is better than and partially concordant in one patient. Conclusion: SISCOM
SPECT imaging. Although both imaging modality correlated with SPM is feasible in the clinical practice routine, and it can
with clinical tests in cognitively unimpaired patients with RRMS, be a powerful tool in EF precise location, aiding in the surgical
MRI imaging correlated with cognitive and ambulatory tests treatment of patients that are refractory to clinical treatment.
better than SPECT imaging but SPECT correlated with a more References: 1.Chen T, Guo L. The role of SISCOM in preoperative
diverse spectrum of clinical tests. Conclusion: Quantitative evaluation for patients with epilepsy surgery: A meta-analysis.
brain perfusion SPECT imaging can be a complementary Seizure.2016;41:43-50. 2.Tamber MS, Mountz JM. Advances in
modality along with quantitative brain MRI imaging to either the Diagnosis and Treatment of Epilepsy. Seminars in Nuclear
larger coverage of abnormality detection and early detection of Medicine.2012;42(6):371-86.
cognition decline in cognitively unimpaired patients with RRMS
before becoming clinically impaired. References: None.
EP-0018
Syndrome of the Trephined: evaluating brain perfusion
EP-0017 before and after cranioplasty using 99m-Tc HMPAO and
Feasibility and Effectiveness of SISCOM With SPM To SPECT-CT
Locate Epileptogenic Focus in Clinical Practice Á. Galiana, S. Ruiz, I. Paredes, E. Gutiérrez, M. Tabuenca, M. Marín,
C. Oliveira, E. M. Souza, S. Brunetto, M. Alvim, F. Cendes, C. D. E. Martínez, V. Godigna, D. Vega, J. Estenoz;
Ramos, B. J. Amorim, E. Etchebehere; Hospital Universitario 12 de Octubre, Madrid, SPAIN.
Unicamp, Campinas, BRAZIL.

Aim/Introduction: The Syndrome of the Trephined (SoT)


Aim/Introduction: Epilepsy is one of the most common is a complication of craniectomy, responsible for multiple
neurological disorders and patients with drug-refractory seizures neurological symptoms in a period comprised between
can be treated with surgical removal of the epileptogenic focus days and years after the surgery. The pathophysiology is still
(EF). Visual comparison of ictal and interictal Single Photon in discussion, although changes in brain perfusion are one
Emission Computed Tomography (SPECT) images to locate EF of the principal hypothesis. Main symptoms include motor
can be difficult. To overcome the difficulties, softwares such as weakness (56,9%) as well as cognitive and language deficits
SISCOM that are capable of subtracting these ictal and interictal (41,4% and 27,6%). Treatment of SoT is cranioplasty, which has
SPECT images and also combining the images to an MRI, can demonstrated symptomatic improvement. This ongoing study
improve the localization of the EF. This study aim to demonstrate aims to evaluate the changes in brain perfusion before and
the feasibility of performing SISCOM using the free software after cranioplasty using 99mTc-HMPAO and SPECT-CT imaging.
Statistical Parametric Mapping (SPM), as an initial experience at Materials and Methods: The study involves 18 patients, aged
an epilepsy reference center. Materials and Methods: Patients 16 to 81, who had a craniectomy performed due to cranial
with refractory epilepsy were submitted to ictal and interictal traumas, and intracranial hemorrhages amongst other causes.
SPECT images. All patients received 1110MBq of 99mTc-ECD The patients were diagnosed with SoT in our hospital, and
prior to SPECT images. Images were acquired using the same were all eligible for cranioplasty. The cerebral perfusion of the
acquisition parameters. Electroencephalogram (EEG) monitoring patients was studied in three moments: before surgery, after
was performed during both ictal and interictal injections. Inter- one week and at least three months after the cranioplasty. Brain
ictal injection was performed with the patient resting in a dark, perfusion was evaluated both visually and quantitatively using
quiet room. Ictal injection was undertaken at the beginning QBrain© software, taking special attention to the non-surgically
of a seizure while undergoing telemetry monitoring. SISCOM affected hemisphere, where automated analysis is less prone
reconstruction was performed by a trained physician or physicist to errors caused by surgical alterations of brain parenchyma.
using the Statistical Parametric Mapping (SPM) software. The Quantification was evaluated in 12 areas on each hemisphere.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S390

Results were analyzed using multivariate analysis considering with significantly lower values in experimental animals (P<0.05).
the changes in perfusion regarding the timeline of the study as Pathological data demonstrated reduced neuronal damage
well as the brain hemisphere (surgically affected hemisphere or in the experimental group compared with controls at 72h.
not). The variables studied were the ratio comparing the region Conclusion: FDG-PET/CT could be used to monitor early
of interest with the pons (as the reference area) and Z-score cerebral damage and demonstrate the protective effects of
(using QBrain© database of non-pathological brain as controls). hydrogen in brain after cardiac arrest. References: None.
Results: First results show a statistically significant increase in
ratio of perfusion on both hemispheres (surgical and no-surgical)
between the pre-surgical evaluation and the study obtained at EP-0020
least three months afterwards (ratios 1,11 and 1,14 respectively Effects of bariatric surgery on brain glucose metabolism
in non-surgical hemisphere). Same significance was obtained for and cognitive function: insight from dynamic FDG PET/CT
Z-score (0,36 and 0,77 respectively in non-surgical hemisphere). study
Therefore, preliminary results show changes in 6 out of 12 D. Volterrani, G. Daniele, S. Mazzarri, F. Guidoccio, A. Dardano,
areas, 2 of which were only significant in z-score values while L. Giusti, L. Fantechi, G. Manca, C. Morrone, S. Del Prato, G.
the rest were significant in both z-score and ratio. Conclusion: Aghakhanyan;
According to our results, brain perfusion significantly changes University of Pisa, Pisa, ITALY.
in SoT patients before and after cranioplasty. This findings may
be related to the pathophysiology of SoT. The increase in brain
perfusion can also have implications in the clinical outcome of Aim/Introduction: We aimed to evaluate the impact of
SoT after cranioplasty. The clinical relevancy of these findings bariatric surgery (RYGB) on the brain glucose metabolism and
needs to be furtherly evaluated in long term clinical studies. the interplay between gut hormones/metabolomics, cerebral
References: None. metabolic rate of glucose (CMRGlu) and cognitive function.
Materials and Methods: Thirteen morbidly obese subjects with
normal glucose tolerance (BMI 46±4.9 kg/m2; HbA1c 40.1±5.9
EP-0019 mmol/mol; age 42.4±9.8 years) planned for RYGB surgery were
FDG-PET/CT for Assessing The Cerebral Protective Effects recruited. Theoral glucose tolerance test (OGTT) was performed,
of Hydrogen in Rabbits with Cardiac Arrest followed by 60 minutes FDG dynamic PET study.Continuous
Y. Tang1, G. Huang2, J. Li1, T. Long1, Y. Li1, S. Hu1; blood samples were drawn before and at 30, 60, 90, and 120 min
1
Department of PET Center, XiangYa Hospital Central South for glucose, insulin, GLP, VIP, GIP and C-peptide measurements.
University, Changsha, CHINA, 2Department of Emergency, The same venous blood samples were used for calculating
XiangYa Hospital Central South University, Changsha, CHINA. radioactivity concentration in plasma. Fasting blood samples for
metabolomics (leptin, brain derived neurotrophic factor, BDNF)
were also collected and the homeostasis model assessment
Aim/Introduction: To assess fluorodeoxyglucose (FDG)- of insulin resistance (HOMA-IR) was calculated as an index of
positron emission tomography (PET) / computed tomography insulin resistance. The influx constant (Ki) and MRGlu were then
(CT) for evaluating the cerebral protective effects of hydrogen quantified using the two tissue compartment Patlak approach
in rabbits with cardiac arrest. Materials and Methods: Male with an imaged-derived input function (PMOD). Subsequently,
rabbits were divided into the hydrogen (n=6), control (n=6), and the parametric CMRGlu images were created and spatially
sham (n=3) groups. Cardiac arrest was induced by intravenous normalized in MNI space. The paired t-test and Spearman rank
potassium chloride. During resuscitation, hydrogen/oxygen correlation were applied to assess changes and associations of
(1:24 v/v) and pure oxygen were inhaled by the hydrogen and voxel-wise CMRGlu and metabolomics. All patients underwent
control groups, respectively. Maximum standardized uptake a battery of neuropsychiatric tests (MMSE, MoCA, Token test,
values (SUVmax) measured by FDG-PET/CT at baseline and at TMT, etc) to assess cognitive function in several domains, before
2 and 24h post-resuscitation. Blood samples were collected for and 6 months after RYGB. Results: Six months after RYGB a
UCH-L1 level measurements preoperatively, and at 24, 48, and significant BMI reduction (p<0.001) was achieved. Post-OGTT
72h post-operation. After euthanasia (72h post-operation), brain GLP1 was increased (p<0.01) as well as GIP (p<0.01). The HOMA-
tissues were extracted for Nissl’s staining. Results: SUVmax values IR dropped significantly 6m after RYGB (p=0.02). Either whole
were first decreased before rising at 2 and 24h of resuscitation brain and region-selective CMRGlu decreased 6m after surgery
in hydrogen treated and control animals. SUVmax values in the (15.9±4.6 to 10.5±5.1 µmol/min/100ml; p<0.01). Voxel-wise
frontal, occipital, and left temporal lobes as well as the whole paired analysis displayed clusters of decreased CMRGlu 6m after
brain were significantly different between the hydrogen and RYGB in the widespread brain regions. In addition, we found a
control groups, at 2 and 24h after resuscitation (P<0.05); NDS significant positive relationship between CMRGlu and HOMA-IR.
scores at 24 and 48h were lower in hydrogen treated animals All patients at baseline presented MMSE and MoCA scores in
(P<0.05). At 24h, serum UCH-L1 levels were increased in the the normal range. However, 6 months after RYGB, the cognitive
hydrogen and control groups, but less pronounced in the domains examined showed a trend of global improvement.
hydrogen group (P<0.05). At 48 and 72h, UCH-L1 levels in the MMSE score increased statistically significantly (p 0.002) as well
experimental and control groups were gradually decreased, as MoCA score (p <0.005). Conclusion: After bariatric surgery,
S391 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

there are several modifications of multiple factors that play a EP-0022


role in the so-called “intestinal-brain cross-talk”, in CMRGluand The Evaluation of Brain FDG PET Images in Temporal
in cognitive function. CMRGluof morbidly obese subjects is Lobe Epilepsy by Data Mining Methods in Terms of
abnormally enhanced in response to insulin. Bariatric surgery Lateralization of Epileptogenic Focus
seems to reverse this insulin-mediated signal dysfunction and Ü. Akdemir1, I. Yildirim2, U. Aydos1, S. Gulbahar Ates1, G. Kurt3, L.
could produce significant CNS effects decreasing brain glucose Atay1;
over-consumption and promoting potential neuroprotective 1
Gazi University Medical Faculty Department of Nuclear
effects References: None. Medicine, Ankara, TURKEY, 2Gazi University Medical Faculty
Department of Neurology, Ankara, TURKEY, 3Gazi University
Medical Faculty Department of Neurosurgery, Ankara, TURKEY.
EP-0021
Studying Rat Model of Herpes Simplex Virus type-
1 Infection by [18F]FHBG in Accompanied by Aim/Introduction: The aims of this study were to evaluate
Neuroinflammation and Glucose Metabolism the relative metabolism values ​​ obtained from different
N. Ghazanfari, E. E. F. J. de Vries, R. A. J. O. Dierckx, J. Doorduin; brain regions by using data mining methods and to make a
UMCG, Groningen, NETHERLANDS. classification model for lateralization of epileptogenic focus
in resistant temporal lobe epilepsy (TLE). Materials and
Methods: Interictal brain FDG PET images of 53 patients with
Aim/Introduction: Herpes simplex virus type 1 (HSV-1) is the resistant TLE (mean age ± standard deviation = 27.1 ± 7.0) who
most common cause of the Herpes simplex encephalitis (HSE) had seizure control after surgical treatment at our hospital
in humans. Animal studies have shown that HSV-1 enters the were evaluated retrospectively. The numerical analysis of PET
brain via the olfactory nerves, which are the only neurons with images were done with SPM8 (“Wellcome Center for Human
direct discloser to the environment. HSV-1 was found to affect Neuroimaging”) and WFU_PickAtlas (“ANSIR Laboratory, Wake
the same brain regions as the ones affected in Alzheimer’s and Forest University School of Medicine”) softwares. The AAL
schizophrenia pathology. The aim of this study was to evaluate (“Automated Anatomical Labeling”) atlas was used to obtain
the feasibility of [18F]FHBG PET for studying HSV-1 infection of the regional count values ​​from spatially normalized PET images.
brain and to monitor the accompanying inflammatory response The regional asymmetry indices [AI = (left hemisphere-right
and changes in glucose consumption with [11C]PK11195 and hemisphere) / (left hemisphere + right hemisphere) x 200] were
[18F]FDG PET. Materials and Methods: Male Wistar rats (n= calculated to eliminate the need for reference region and the
45) were inoculated with HSV-1 by the application of the virus need for count normalization of PET images. The patient group
on the nostrils, a similar approach with PBS was performed for was randomized and divided into learning (n = 20) and test (n =
controls (n=16). The onset of clinical symptoms of infection 33) sets. A lateralization model was created with learning set in
varied between animals. The presence and spread of active R software by using RWeka classification tool, definitive clinical
HSV-1 were analyzed by scanning animals (n=11) with [18F] lateralization information and asymmetry values ​​of 13 different
FHBG at day 6 or 7. The occurrence of neuroinflammation due regions in which significant differences were observed in terms of
to infection was examined [11C]PK11195 PET (n=24) at day 5 lateralization. This model was then evaluated for the lateralization
or 7. [18F]FDG scans were performed longitudinally on infected accuracy using the test data. The findings of this lateralization
animals (n=26) to evaluate glucose metabolism consumption model was compared with the clinical outcome. Results: The
on day 1, 3, 4, 5 and 6. 60-min dynamic PET acquisition was clinical diagnoses (with regard to surgical procedures and
performed for all tracers. The statistical differences between clinical follow-up findings) were right TLE in 21 patients and left
control and HSV-infected groups for [18F]FHBG were analyzed TLE in 32 patients. The asymmetry values ​​of the 13 regions with
using either the independent sample t-test (single measures) significant asymmetry between regional metabolism values
or the generalized linear model (repeated measures). The final (mesial temporal lobe and functionally associated regions) were
values are considered to be significant at P<0.05 for all studies. included in the classification analysis. When the classification
Results: PET showed significant differences in [18F]FHBG model determined by RWeka (for Rolandic operculum, if AI>
uptake (SUV) in accumbens, cingulate cortex, prefrontal cortex, 2.06, right TLE; if AI ≤2.06, left TLE) was used on the test data for
hippocampus, septum, striatum, thalamus, and midbrain. prediction, the results of the classification were found to be 90%
Differences in [11C]PK11195 uptake between day 5 and 7 were consistent with definitive clinical lateralization (Cohen’s kappa
significant for all brain regions, except for cortical regions. [18F] was 0.800; %95 CI 0.474 - 1.000; p < 0.001). Conclusion: In our
FDG uptake on day 5 was significantly different from days 1, patient group, the success rate of the metabolic asymmetry
3 and 4 in all the brain regions, while tracer uptake on day 4 associated with rolandic operculum was found to be 90% in
was significantly different from days 1 and 3 only in the insula the lateralization of epileptogenic foci. The numerical analysis
cortex. Conclusion: Scanning with [18F]FHBG showed mainly based on regional asymmetry of brain FDG PET findings in TLE
the virus path through the trigeminal nerve after inoculation via can be used as an objective evaluation method with a very high
the nostrils. [11C]PK11195 and [18F]FDG showed the secondary diagnostic accuracy. References: None.
effects accompanying an HSV-1 infection. References: None.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S392

EP-0023 EP-02
Target Volume Definition With 68GA-DOTATOC-PET/CT And Neuroimaging: Movement Disorders
MRI For Patients With Meningiomas
M. Colandrea1, C. Garibaldi1, M. E. Ferrari1, A. Iannalfi2, S. Pesente3, October 12 - 16, 2019
e-Poster Area
S. L. Fracassi1, L. Gilardi1, A. P. Rocca1, L. L. Travaini1, D. Militano1, S.
Papi1, A. S. Cascio1, M. Cremonesi1, C. M. Grana1;
1
Istituto Europeo di Oncologia, Milano, ITALY, 2CNAO,
Pavia, ITALY, 3Tecnologie Avanzate, Udine, ITALY. EP-0024
Reliability of Dopamine Transporter PET Measurements
with [18F]FE-PE2I in Early Stage Parkinson´s Disease: A
Aim/Introduction: To investigate the potential impact of Preliminary Test-Retest Evaluation
68
Ga-DOTATOC PET/CT in addition to standard morphological V. Kerstens1, P. Fazio1, M. Sundgren2,3, G. J. Matheson1, E. Franzén4,5,
imaging (MRI and CT ) in gross tumour volume (GTV) delineation C. Halldin1, S. Cervenka1, P. Svenningsson2, A. Varrone1;
in patients affected by skull base meningiomas and treated with 1
Department of Clinical Neuroscience, Centre for Psychiatry
particle therapy. Materials and Methods: Sixteen patients Research, Karolinska Institutet and Stockholm County
(median age 51.4 y) with skull base meningiomas underwent Council, Stockholm, SWEDEN, 2Department of Clinical
68
Ga-DOTATOC PET/CT for target tumor delineation followed by Neuroscience, Neuro Section, Karolinska Institutet, Stockholm,
constract-enhanced (CE) MRI and CT for treatment planning with SWEDEN, 3Neuro Department, Karolinska University Hospital,
particle therapy. GTV for treatment was defined on the CE-MRI Stockholm, SWEDEN, 4Department of Neurobiology, Care
fused to the simulation CT (CTsim) integrating information from Sciences and Society, Division of Physiotherapy, Karolinska
the PET/CT. Three methods to delineate the PET volume were Institutet, Stockholm, SWEDEN, 5Function Area Occupational
evaluated: manual (PETman), semiautomatic (42% threshold of Therapy & Physiotherapy, Allied Health Professionals Function,
SUVmax, PETSUV42%) and an automatic adaptive thresholding Karolinska University Hospital, Stockholm, SWEDEN.
method incorporating PET reconstruction parameters (PETauto)
(iTA, TA, Udine). PETman volumes were delineated by the same
nuclear medicine physician, while PETSUV42% and PETauto Aim/Introduction: The reliable quantification of dopamine
volumes were determined by medical physicists. The PET/CT, transporter (DAT) imaging in Parkinson’s disease (PD) is
CE-RMI and CTsim were coregistered with a deformable image important for diagnostic purposes as well as for potential
registration algorithm using the MIM Software (v. 6.1) and tumor evaluation of disease modifying treatment. [18F]FE-PE2I is a
volumes and positions were determined. The overlapping suitable radioligand for imaging the nigrostriatal DAT in patients
region of MRI and PETman resulted in GTVcommon. Results: with PD (1). A test-retest study in young healthy subjects has
The brain lesions had a median SUVmax of 12.1 ± 6.8 (range: shown that [18F]FE-PE2I has a favourable low variability and
3.2-32.6). Overall, the GTV-MRI was larger than GTVPETman in 7 good reliability of the measurements (2). However, the test-
patients (43.8%), smaller in 6 (37.5%) and almost the same in 3 retest properties of [18F]FE-PE2I in PD patients remains to be
(18.8%). The median value of the different volumes were: GTV- examined. Due to degeneration of dopaminergic neurons
MRI = 14.3 ± 37.2 cc, GTV-PETman = 14.4 ± 47.0 cc, GTVcommon and thus loss of specific binding to DAT, higher measurement
= 12.2 ± 33.6 cc, GTV-PETSUV42% = 8.3 ± 18.3 cc, GTV-PETauto variability in PD might be expected. Therefore, the aim of this
= 11.3 ± 26.2 cc. As expected, volumes determined by the fixed study was to examine the test-retest reliability of [18F]FE-PE2I
threshold technique were always smaller than GTV-PETman (∆ = PET measurements in patients with early stage PD. Materials
- 51.0 ± 32.7%) and GTV-PETauto (∆ = - 21.5 ± 12.7%) since they and Methods: Seven patients with early stage PD (5 men, 2
do not take into account variations in tumor heterogeneity. The women; mean age 65.6±7.6 y; disease duration 8±3 y; Hoehn
largest differences were observed for lesion showing a high SD and Yahr 1-2; UPDRS 17.8±7.4) have so far been included. For
of SUV. The median difference between GTV-PETman and GTV- each patient, two 93-minute PET-measurements with [18F]FE-
PETauto was 39.6 ± 29.5 %. Conclusion: 68Ga-DOTATOC-PET/CT PE2I were performed within an interval between 7 and 28 days
seems to improve the target volume delineation in skull base using a high resolution PET system (HRRT). On the day of PET,
meningiomas, often leading to a reduction of GTV compared patients were examined in “off” with the MDS-UPDRS-III and for
with results from MRI. The automatic adaptive thresholding one week prior to each PET visit they wore a physical activity
delineation method may provide robust and reliable tool to monitor (Actigraph GT3X+), to ascertain clinical stability within
help physician in segmenting PET images, reducing inter- and the study period. Parametric images of binding potential (BPND)
intra-observer variability. References: None. were obtained with the wavelet-aided parametric imaging
software using Logan graphical analysis and cerebellum as
reference region (1). Regions of interest were caudate, putamen,
ventral striatum, and substantia nigra. Test-retest reproducibility
was determined with calculation of repeatability (absolute
variability) and reliability (intraclass correlation coefficient, ICC).
Results: The intrasubject variability was 6.1±4.4% for caudate,
8.6±9.8% for putamen, 8.1±6.6% for ventral striatum, and
S393 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

10.7±14.7% for substantia nigra. The ICC for caudate, putamen, between DAT bindings and PDRP expressions was only showed
ventral striatum and substantia nigra were 0.97, 0.92, 0.87, and in LOPD group (P<0.05). Conclusion: In this dual-tracer PET
0.79 respectively. Conclusion: These preliminary results show study we demonstrated the unique dopaminergic dysfunction
good reliability of DAT-PET measurements with [18F]FE-PE2I in and cerebral glucose metabolic characteristics of Parkin EOPD
early stage PD patients. The results are in agreement with the patients at voxel, regional and network levels. This was the first
results previously reported in younger, healthy subjects (2), FDG and CFT dual-tracer study in Parkin EOPD patients. Our
indicating that [18F]FE-PE2I-PET provides reliable estimates of DAT findings might promote the understanding in further studies
availability also in patients with PD. After completing the study, of pathophysiological and compensatory mechanisms in
power-calculations can be made to estimate the sample size for Parkin EOPD as well as non-Parkin EOPD, and demonstrated
future clinical trials using [18F]FE-PE2I as DAT imaging marker. a brand-new idea for other kinds of studies in genetics of PD.
References: 1. Fazio et al. Mov Disord. 2018;33(4):592-599. References: [1] Liu FT, Ge JJ, Wu JJ, et al. Clinical, Dopaminergic,
2. Suzuki et al. Nucl Med Commun.2014;35(3):231-7. and Metabolic Correlations in Parkinson Disease: A Dual-Tracer
PET Study. Clin Nucl Med. 2018;43(8):562-571.

EP-0025
Dopaminergic and Metabolic Characteristics of Parkin EP-0026
Early Onset Parkinson’s Disease: a Dual-tracer PET Study Tc-99m TRODAT-1 SPECT Images in Diagnosis and Severity
J. Lu1, F. Liu2, J. Ge1, P. Wu1, J. Wang2, C. Zuo1; Evaluation of Parkinson’s Disease using Deep Learning
1
PET Center, Huashan Hospital, Fudan University, Model
Shanghai, CHINA, 2Department of Neurology, Huashan P. Chuang1, C. Ko1, C. Lin2, R. Yen1;
Hospital, Fudan University, Shanghai, CHINA. 1
Department of Nuclear Medicine, National Taiwan University
Hospital, Taipei City, TAIWAN, 2Department of Neurology,
National Taiwan University Hospital, Taipei City, TAIWAN.
Aim/Introduction: Mutation in Parkin is the most common
cause of autosomal recessive Parkinson’s disease(PD). Early onset
PD (EOPD) is considered to have special disease progression. Aim/Introduction: Dopaminergic transporter imaging using
Dopaminergic and metabolic PET could provide nigrostriatal 99m
Tc-TRODAT-1 SPECT is known to reflect neurodegeneration
dopaminergic dysfunction and abnormal metabolic changes in Parkinson’s disease (PD) and served as clinical routine in
effectively. We aimed to investigate dopaminergic dysfunction differentiating PD from non-PD patients. Nevertheless, challenge
and metabolic characteristics of Parkin EOPD and their is often encountered with inevitable interobserver variability.
associations with clinical ratings. Materials and Methods: We Semiquantitative analysis such as striatal-to-background uptake
analyzed dopaminergic dysfunction (11C-CFT) and metabolism ratio and asymmetric index shows adequate performance
(18F-FDG) of 17 Parkin EOPD, 16 non-Parkin EOPD, 30 late onset however time and manpower consuming, especially in cases
PD (LOPD) patients and 18 normal controls at voxel, regional with variable anatomy or poor uptake activity. The aim of our
and network levels after age correction. Patient groups were study is to build suitable deep learning model aid in diagnosis
matched for UPDRS motor ratings and H&Y scales. We analyzed and evaluate severity of PD. Materials and Methods: From
relationships of dopaminergic, metabolic PET and clinical January 2016 to December 2017, 313 consecutive patients
ratings in levels mentioned above. All analyzes were conducted diagnosed with idiopathic PD (iPD) or non-parkinsonism
in SPM 8 and ScanVP 7.1 implemented in Matlab8.4. Results: tremor referred for 99mTc-TRODAT-1 SPECT images were
Three patient groups showed abnormal dopamine transporter included retrospectively, all of which was closely followed at
(DAT) bindings and metabolic activities compared to normal neurology department for at least 1 year to confirm diagnosis.
controls. Parkin EOPD had lower DAT bindings than non-Parkin Disease severity was categorized into early and late stage using
EOPD (P<0.05, post hoc: LSD) and similar DAT bindings with Hoehn and Yahr scale with cutoff of 3. Every image was visual
LOPD (P>0.05, post hoc: LSD) in striatum. Some of the abnormal interpreted using 6-point score (with 0 stands for normal uptake
metabolic regions were different among patient groups. and 5 for background activity) [1]. Patients were randomized
Compared to non-Parkin EOPD group, Parkin EOPD group into training (50%), validation (20%), and testing (30%) groups.
decreased glucose metabolism in superior and medial frontal The original SPECT were resampled into 128x128x64 matrix
gyrus, middle temporal gyrus, while increased in cerebellum, without any registration. We introduced random shift and
lingual gyrus and fusiform (P<0.01, uncorrected). However, rotation into training group to balance case number of each
three patient groups didn’t show significant difference in visual score. We built a convolutional neural network (CNN)
network expressions (P=0.569, one-way ANOVA). It was with three convolution layers and two fully-connected layers to
noteworthy that Parkin EOPD had the lowest DAT binding and predict the score. Training was terminated when the validation
network expression among three patient groups which was group got the best performance. The comparisons were made
in conflict with former impression of PD[1]. For correlations, on the testing group. Results: Characteristics including age,
DAT bindings had significant correlations with clinical ratings gender, diagnosis of iPD, disease severity, and visual score of
in whole PD, non-Parkin EOPD and LOPD groups (P<0.05), but training, validation, and testing groups were without significant
none survived in Parkin EOPD group. Significant correlation difference using ANOVA. Using Kendall’s tau correlation test,
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S394

the CNN-derived score showed fair correlation with visual provides a good diagnostic concordance with results from
score (r=0.6784, p<0.01). Diagnostic performance of CNN- conventional gamma camera, both for visual and quantitative
derived score was non-inferior to visual score using receiver- analyses. Furthermore, the high-count sensitivity of this camera
operating-characteristic curve analysis by margin of 0.1, with gives the possibility of significantly reducing acquisition time
area-under-curve 0.9163 and 0.9113 respectively (p=0.02), as and/or injected activity. References: None.
well as indifferent correlation with clinical staging, r=0.6074 and
r=0.5489 respectively (p=0.19). Conclusion: Our CNN model
showed good diagnostic performance and fair clinical stage EP-0028
correlation which were comparable to routinely used visual Corticobasal syndrome: is [18F]FDG-PET a feasible tool to
interpretation of 99mTc-TRODAT-1 SPECT images. References: predict underlying Alzheimer’s pathology?
1. Huang WS et al. Usefulness of brain 99mTc-TRODAT-1 SPECT A. M. N. Coutinho, J. B. Parmera, M. R. Aranha, A. Studart Neto, C. R.
for the evaluation of Parkinson’s disease. Eur J Nucl Med Mol Ono, E. R. Barbosa, R. Nitrini, C. A. Buchpiguel, S. M. D. Bucki;
Imaging. (2004)31:155. University of São Paulo, São Paulo, BRAZIL.

EP-0027 Aim/Introduction: Corticobasal Syndrome (CBS) is an atypical


Comparison of 123I-ioflupane SPECT imaging between the parkinsonian syndrome first considered a motor disorder but
VeritonTM 360° CZT camera with striatum focusing and a now also recognized as a cognitive disorder. The term CBS
conventional gamma-camera denotes the phenotype of multiple pathologies, including
M. B. Chawki, M. Bordonné, T. Zaragori, G. Karcher, P. Marie, L. Alzheimer’s disease (AD) and 4-repeat Tauopathies found
Imbert, A. Verger; on corticobasal degeneration (CBD). Accurate antemortem
CHRU de Nancy, Nuclear Medicine Department, diagnosis is challenging, and diagnostic methods are being
Vandoeuvre-Lès-Nancy, FRANCE. developed to predict the underlying pathology. Previous
works with post-mortem analysis established [18F]FDG-PET
patterns closely related to AD underlying pathology and those
Aim/Introduction: The Veriton 360° CZT-camera (Spectrum commonly seen on CBD. The present study aimed to investigate
Dynamics Medical) provides better performances in comparison the capacity of [18F]FDG-PET to predict cortical amyloid
to conventional gamma cameras owing to the properties of CZT deposition and cognitive features of AD in patients with CBS.
detectors, and also to an original 360° geometry of detection Materials and Methods: Thirteen patients meeting criteria for
allowing to focus the acquisition on striatum which could be probable CBS were prospectively evaluated and underwent
particularly advantageous for 123I-ioflupane SPECT imaging. both [18F]FDG-PET and [11C]PiB-PET scans to assess their brain
This study aimed to compare the 123I-ioflupane SPECT imaging amyloid status. According to their brain [18F]FDG-PET metabolic
with striatum focusing provided by the Veriton CZT-camera to patterns, patients were distributed in two groups: CBS likely
imaging from a conventional gamma camera. Materials and related to AD (AD group) and CBS likely unrelated to AD (non-
Methods: 123I-ioflupane SPECT acquisitions of 30 minutes, AD group). Participants were evaluated concerning their
obtained with a conventional camera (Symbia T2, Siemens movement disorders and cognitive symptoms and underwent
Healthineers) in clinical routine in 30 patients, were immediately a complete neuropsychological evaluation. Clinical evaluation
followed by an additional 15 minutes acquisition focalized on was performed blinded to the PET images. [18F]FDG-PET and
striatum with the Veriton 360° CZT-camera. Tomographic count [11C]PiB-PET scans were evaluated blindly to each other results
sensitivity was measured from projection images in counts/ and also to the clinical data. Results: Five patients with CBS had
MBq/s after correction for the radioactive decay. SPECT images an AD pattern on [18F]FDG-PET scans, and all of them (100%)
were reconstructed with previously optimized parameters tested positive for brain amyloid deposition. The remaining
and a comparison was planned between the 2 cameras for a eight patients had a non-AD metabolic pattern, and 6 of them
visual classification as normal or pathological exam obtained (75%) had negative [11C]PiB-PET scans, all with typical features
by consensus of 3 experiences observers and for an automatic of CBD on [18F]FDG-PET. Two patients had non-AD brain
quantification of binding potentials of striatum structures on metabolic patterns and positive [11C]PiB-PET examinations.
parametric images. Results: Tomographic count sensitivity from All cases of negative amyloid scans were blindly classified as
the Veriton camera was 50% higher than that of the conventional having a non-AD-pattern. There were significant differences on
camera (397.3 ± 89.5 vs. 260.5 ± 54.1 counts/MBq/s, p&lt;0.001). the [18F]FDG-PET AD and non AD subgroups on MMSE score,
The visual classification as normal or abnormal was concordant Clinical Dementia Rating (CDR), and Addenbrooke’s Cognitive
between the 2 cameras in 87% of patients (26/30 patients, kappa Examination-Revised (ACE-R) scales, with worst scores on the
coefficient of 0.73). Spearman correlation coefficients between AD group (p<0.05). We also observed significant differences
the 2 cameras for the quantitative binding potentials of the in MMSE and ACE-R according to the amyloid status (lower
right and left caudate and of the right and left putamen were scores in individuals with positive [11C]PiB-PET examinations).
respectively: 0.89, 0.84, 0.85 and 0.91 (p&lt;0.001). Conclusion: Conclusion: Patients with an AD pattern on [18F]FDG-PET were
123
I-ioflupane SPECT images, obtained through a focused striatal predominantly positive on amyloid scans and had lower scores
recording of only 15 min with the Veriton 360° CZT-camera, in cognitive scales despite age, gender, symptom duration, and
S395 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

motor features, suggesting a higher functional decline related bilateral precuneus, and after DBS preserved parieto-occipital
to AD pathology in CBS. Functional molecular imaging with brain metabolism seemed to predict better motor response
[18F]FDG-PET might be a potential factor to predict CBS variants and improvement in ADL. In MCI-SD PD preserved presurgical
depicting their specific degeneration patterns. References: brain metabolism in bilateral precuneus and parieto-occipital
None. regions could be useful to identify patients who could benefit
most from DBS. References: None.

EP-0029
Presurgical cognitive phenotype and its relation to EP-0030
brain metabolic pattern in the evaluation of the clinical Utility of 18FDG-brainPET for parkinsonisms diagnosis in
outcome of Deep Brain Stimulation in Parkinson’s Disease: daily clinical practice: our experience in a non-dedicated
an FDG-PET study hospital
C. Polito, V. Berti, S. Ramat, F. Terenzi, G. Puccini, M. De Cristofaro, S. P. Santos-Holgueras, P. Garrastachu-Zumaran, C. Albornoz, X.
Sorbi, R. Sciagrà; Boulvard, L. Romero, A. Cabrera, F. Cañete, R. Delgado, R. Ramirez;
Università di Firenze, Firenze, ITALY. Nuclear Medicine and Molecular Imaging Division,
San Pedro Hospital-CIBIR, Logroño, SPAIN.

Aim/Introduction: Deep Brain Stimulation (DBS) is not Aim/Introduction: Establishing the diagnosis in patients with
currently indicated for Parkinson’s Disease (PD) patients with parkinsonian syndromes is based on clinical diagnostic criteria,
dementia. Several studies have addressed the cognitive and and many times is difficult at the early onset of the disease.
brain metabolic outcomes of DBS, but whether the presurgical To improve this, the use of different support biomarkers is
cognitive phenotype and its relation to brain metabolism could proposed and beyond them appears 18FDG-brainPET. This study
affect the clinical outcome of DBS has been less explored. The aims to evaluate the validity of 18FDG-brainPET in our daily
aim of the present study is to identify the cognitive-metabolic clinical practice and its modulatory role in relation to the initial
profile of PD patients who could benefit the most from DBS. diagnostic suspicion. Materials and Methods: We selected
Materials and Methods: 36 consecutive PD patients (10F/26M patients with parkinsonian symptoms sent for 18FDG-brainPET
mean age 59±7years), treated with DBS between 2008 and between 2012-2017. A visual analysis of 18FDG-brainPET was
2017 were selected. Clinical and neuropsychological profiles performed by two independent observers, classifying images as
were collected before and one year after surgery. All patients atypical parkinsonism (AP), non-atypical parkinsonism (non-AP),
underwent FDG-PET within a month before surgery. Patients and different atypical parkinsonisms subtypes, according to the
were divided into three groups according to the cognitive accepted metabolic patterns. We analysed the validity of PET
phenotype: non-Mild Cognitive Impairment (non-MCI-PD, n=7, against clinical diagnosis in the follow-up, only in patients who
MMSE=29.29±0.9), MCI single non-amnestic domain (MCI-SD, had an established diagnosis by PET and by clinical assessment.
n=12, MMSE=27.33±1.49), MCI multiple domain (MCI-MD, n=17, Logistic regression models were used to estimate the probability
MMSE=26.76±2.30). Chi-Square and ANOVA were performed in of diagnosing parkinsonism according to the PET result adjusted
order to explore presurgical clinical-demographic differences for clinical suspicion of parkinsonism. A positive probability
between groups, and paired t-test to assess DBS clinical ratio was used to transform the previous probability of having
outcome in each group. SPM12 ANOVA design was performed parkinsonism only with clinical suspicion into the a posteriori
to investigate presurgical brain metabolic differences between probability once PET was done. Results: 68 patients (37 female,
groups, and multiple regression design to explore the relation age 70, range 38-87) had undergone 18FDG-brainPET. We finally
between presurgical brain metabolism and the clinical variable analysed 54 patients with established diagnosis by PET and by
showing the best response to DBS at follow-up in each group clinical assessment. Validity of PET showed: sensitivity (S) 83,3%,
distinctively. Results: There were no differences between non- specificity (E) 80%, positive predictive value 76,9%, negative
MCI, MCI-SD and MCI-MD in clinical and demographic variables. predictive value 85,7% and accuracy 81,5%. Also high values
The motor part of the Unified Parkinson’s Disease Rating Scale were found when we analysed atypical parkinsonism subtypes:
(UPDRSIII) and the Schwab And England Activities Of Daily Living multiple system atrophy (S 85,7%, E 95,7%, accuracy 94,4%)
Scale (SE-ADL) showed significant improvement after DBS in the and progressive supranuclear palsy (S 88,9%, E 97,8%, accuracy
Off-Therapy condition in MCI-SD and MCI-MD. At voxel-based 96,3%). A logistic regression model showed that positive result
analysis MCI-MD showed grater hypometabolism in bilateral in PET for AP is 2,7 times more likely to be an AP than PET with
Precuneus with respect to MCI-SD. UPDRSIII-Off-Therapy-post- non-AP result, regardless of diagnostic suspicion. Probability
DBS negatively correlated with presurgical brain metabolism of AP diagnosis with clinical suspicion was 60,7%, that rised to
in bilateral superior parietal gyrus in MCI-SD. The SE-ADL-Off- 86,6% if the PET is positive for AP, decreasing to 24,4% if the result
Therapy-post-DBS positively correlated with presurgical brain was non-AP. Conclusion: Our results show that 18FDG-brainPET
metabolism in bilateral parieto-occipital regions in MCI-SD. No accurately classifies patients with atypical parkinsonisms. This
significant correlation was found in MCI-MD neither for UPDRSIII tool is useful in daily clinical practice, helping neurologists in
nor for SE-ADL. Conclusion: In the present study MCI-SD PD clinical diagnosis. References: None.
patients showed presurgical preserved brain metabolism in
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S396

EP-0031 speculate that the decreased frontal CDR might be attributed


Does aggregated tau moderate functional and structural to neurodegeneration, whereas increased FC and temporal SC
connectivity profiles of the globus pallidus externus in might represent a potential adaptive mechanism. Conditional
progressive supranuclear palsy? Preliminary results of a on replication in a larger PSP cohort, these hybrid tau PET/MRI
[18F]PI-2620 PET/MRI study results might lead to an improved understanding of tau-related
G. Aghakhanyan1,2, M. Rullmann1, J. Rumpf3, M. Schroeter4, M. connectivity dysfunction and adaptive mechanisms in PSP.
Patt1, J. Classen3, O. Sabri1, H. Barthel1; References: None.
1
Department of Nuclear Medicine, University of Leipzig,
Leipzig, GERMANY, 2Regional Center of Nuclear Medicine,
University Hospital of Pisa and Department of Translational EP-0032
Research on New Technologies in Medicine and Surgery, Preliminary Exploration of PET/MR Radiomics Features for
University of Pisa, Pisa, ITALY, 3Department of Neurology, Differential Diagnosis of Parkinson’s Disease and Multiple
University of Leipzig, Leipzig, GERMANY, 4Max Planck Institute System Atrophy
for Human Cognitive and Brain Sciences, Leipzig, GERMANY. X. Hu1,2, X. Sun1,2, J. Guo3, X. Lan1,2, R. An1,2;
1
Department of Nuclear Medicine, Union Hospital, Tongji Medical
College, Huazhong University of Science and Technology,
Aim/Introduction: Progressive supranuclear palsy (PSP) Wuhan, CHINA, 2Hubei Key Laboratory of Molecular Imaging,
is a primary 4R tauopathy predominantly affecting globus Wuhan, CHINA, 3GE Healthcare (CHINA), Shanghai, CHINA.
pallidus (GP), subthalamic nucleus and substantia nigra. The
globus pallidus externus (GPe), the lateral component of the
GP, is considered as a subcortical relay structure: Evidence Aim/Introduction: The study aims to preliminarily explore the
suggests that GPe exhibits direct connections with associative, value of 18F-FDG and multi-MR sequence imaging from the
sensorimotor and limbic cortical areas (corticopallidal network). integrated Time of Flight PET/MR system for differential diagnosis
[18F]PI-2620 is a second-generation tau PET tracer with high of Parkinson’s disease (PD) and multiple system atrophy (MSA) by
binding affinity for aggregated tau in Alzheimer’s disease (AD) using radiomics analysis. Materials and Methods: 69 patients
and non-AD tauopathies. We aimed to assess the relationship were included with 46 Parkinson’s disease (PD) and 23 Multiple
between [18F]PI-2620 uptake and functional/structural system atrophy (MSA). The final diagnosis was made according
connectivity (FC/SC) of the GPe. Materials and Methods: Six to the assessment of imaging findings, clinical symptoms, and
PSP patients with the predominant parkinsonian/cortico-basal follow-up with more than 1 year. Patients were performed
phenotype (4 female, age 72±6 years) underwent 60 minutes 18
F-FDG PET/MR (GE SIGNA), and 3D-T1BRAVO, SWAN, T2FLAIR,
dynamic PET imaging following 300 MBq bolus injection T2PROPELLER were acquired at the same time. 18F-FDG PET
of [18F]PI-2620 with hybrid 3T PET/MRI. Ten age-matched images were transformed to SUV images by normalized with
controls were included for comparison of MRI data consisting dose/kg. Regions of interest (ROIs) of the bilateral putamen and
of 3D T1, diffusion-tensor imaging (DTI) and resting-state fMRI. caudate nucleus were drawn on each 3D-T1BRAVO image and
Regional [18F]PI-2620 standardized uptake value ratios (SUVr) mapped to other image sequences, which were then confirmed
were calculated using the cerebellum as a reference region by experienced clinician. From 46 ROIs of PD patients’ (first
by averaging 40 to 60 min p.i. dynamic frames. For FC analysis, affected side) and 46 ROIs of MSA patients (bilateral sides), the
the hypothesis-guided GPe-seed-based approach was applied. radiomics features (396/side) were extracted with A.K. (Analysis-
SC was estimated using probabilistic tractography calculating Kinetics, GE), and then feature selection was applied with
connection probability to frontal, temporal, parietal and occipital spearman correlation and support vector machine-recursive
cortical targets for each GPe voxel. Hard segmentation of the feature elimination (SVM-RFE). Extremely randomized trees were
GPe was performed by classifying seed voxels with the highest applied to do modeling with each image and combinations of
connectivity to each cortical target resulting in connectivity- 18
F-FDG and MR images (train: test = 7:3, 5-fold cross-validation).
defined regions (CDR). Results: PSP patients demonstrated focal The ability of PET/MR images to differentiate the diseases was
[18F]PI-2620 uptake in the GPe (SUVr = 1.4±0.12). Compared evaluated with receiver operating characteristic curves, area
to controls, the GPe displayed increased FC within the frontal under the curve (AUC), sensitivity, specificity and accuracy (ACC).
network (right precentral/inferior frontal and left orbitofrontal Results: In the monomodal radiomics analysis, 36 features are
cortices). The SC analysis depicted a trend towards decreased selected for 18F-FDG, which has the highest AUC (0.852) and
frontal and increased temporal CDR in the left GPe (p=0.08). ACC (0.75) as well as ideal sensitivity (0.714) and specificity
Although frontal and temporal CDR in each hemisphere (0.786). Besides, 3D-T1BRAVO and SWAN perform best sensitivity
showed significant influence on the unilateral connectivity (0.857, AUC=0.827, ACC=0.75) and specificity (0.857, AUC=0.811,
strength (p < 0.05), ANCOVA analysis did not reveal significant ACC=0.714), respectively. Combined 18F-FDG with one of the MR
strength difference between groups. Interestingly, the SUVr sequences, the AUC, ACC, sensitivity and specificity are improved
in the GPe showed an inverse relationship with left frontal (r= in different aspects, where 18F-FDG combined 3D-T1BRAVO
- 0.83, p=0.05) and a direct relationship with temporal CDR shows the higher sensitivity (0.857, AUC=0.847, ACC=0.786)
(r=0.82, p=0.058). Conclusion: GPe-related [18F]PI-2620 uptake and 18F-FDG combined SWAN shows the better specificity
in PSP is associated with altered corticopallidal connectivity. We (0.857, AUC=0.857, ACC=0.714). Conclusion: Radiomics
S397 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

features of putamen and caudate nucleus from 18F-FDG and MR 2


Nuclear Medicine, University of Brescia and Spedali Civili
3D-T1BRAVO, SWAN, T2FLAIR and T2PROPELLER images could Brescia, Brescia, ITALY, 3University of Brescia, Brescia, ITALY.
provide helpful information for differentiating PD and MSA.
18
F-FDG combined 3D-T1BRAVO showed better sensitivity, while
18
F-FDG combined SWAN demonstrated better specificity. More Aim/Introduction: Brain SPECT is the most common
cases should be included for further identification.Funding: This used technique to differentiate degenerative parkinsonian
study was supported by NSFC (81701759) and Key Project of syndromes from non-degenerative parkinsonism. The aim of
Hubei Technological Innovation (2017ACA182). References: our study was to directly compare, in the same population, the
None. different performances of two methods of semiquantitative
analysis data: one based on 2D ROI analysis (DaTSCAN 3-2
software; GE Xeleris workstation) and the other one based on
EP-0033 3D VOI method (the basal ganglia V2 software). Materials and
Assessment of dopamine transporter imaging and Methods: 250 patients (146 male; 104 female) median age 65
olfactory testing in patients with Parkinson’s disease: a who underwent a 123I-Ioflupane SPECT in our Department for an
semi-quantities analysis as yet unclassified parkinsonian syndrome were retrospectively
M. Assadi, A. Moradi, E. Moradi, S. Farrokhi, H. Salimipour, N. Chabi, evaluated. At least after 2 year follow up a new clinical revaluation
E. Jafari; was made. SPECT were processed using two commercial
Bushehr University of Medical Sciences (BUMS), programs to determine the relative uptake in the striatum. 1)
Bushehr, IRAN, ISLAMIC REPUBLIC OF. DaTSCAN 3-2 software, an 2D operator depending software 2)
the free software Basal-Ganglia Matching-Tool v.2 operator free
3D automatically software. A comparison of the results from
Aim/Introduction: Parkinson’s disease (PD) is a chronic the softwares was performed, together with a comparison
progressive and degenerative disorder affecting about 1% of with the visual assessment. Results: 123I-Ioflupane striatal
people over 65 years old. Olfactory disorder is one of the early uptake was normal in 63/250 patients (25%) and abnormal in
non-motor symptoms in patients with Parkinson’s disease. In 187/250 patients (75%) with a mild, medium or severe unilateral
this study, we investigate olfactory dysfunction in patients with or bilateral decreased uptake. In the cohort visual assessment
Parkinson’s disease with 99mTc-TRODAT, olfactory test and MRI. showed a Sensitivity of 96.9%, Specificity of 100%, PPV of 98,5%,
Materials and Methods: Patients with confirmed Parkinson’s NPV of 89,4% for degenerative parkinsonism. The quantitative
disease were enrolled in this study. Patients underwent the 40- analysis was not obtained in 3 patients for the manual method
item Smell Identification olfactory test and SPECT scans with and in 12 patient for the BasGan method. The mean caudate-
99m
Tc-TRODAT and MRI for measuring olfactory bulb. Results: 30 occipital uptake ratio with 2D manual method was 3.21±0.65
patients (19 (63%) males and 11 (37%) females) with Parkinson’s for the right caudate and 3.22±0.64 for the left; with the BasGan
disease were included in this study. 99mTc-TRODAT SPECT scan respectively 3,18±0.97 for the right and 3.15±0.96 for the left.
showed severe uptake reduction in 15 (78.9%) of males and Putamen/occipital mean uptake ratio with the 2D manual ROI
8 (72.7%) of females in left putamen and left caudate and 16 was 2.62±0.69 for the right and 2.6±0.72 for the left putamen;
(84.2%) of males and 9 (81.8%) of females had a mild uptake BasGan method was respectively 2.07±1.01 for the right and
reduction in right putamen and caudate. In the olfactory test 2.09±1.00 for the left side. The ROC curve showed a sensitivity
of patients, 13 (68.4%) of males and 7 (63.7%) of females had of 80,6% and specificity of 71.9 % with the Basal ganglia method
severe hyposmia to anosmia. Comparison of olfactory bulb and a sensitivity of 78,1% and specifity of 69.8% with the manual
in patients with Parkinson’s disease and healthy people didn’t method. AUC for Basal Ganglia method was 0.827 for the
show any significant difference (P>0.05). There was significant caudate and 0.915 for the putamen. AUC for the manual method
relationship between 99mTc-TRODAT uptake reduction in right was 0.805 for caudate and 0.894 for putamen. No statistical
putamen and caudate with hyposmia (p<0.05). Conclusion: difference between the two method was found (p=0.081 for
This study showed that a high percentage of patients with the caudate and p=0.1 for the putamen). Conclusion: The
Parkinson’s disease had olfactory dysfunction. And the uptake two semiquantitative methods provide very robust results for
of 99mTc-TRODAT was decreased in these patients. Also, the routine evaluation of 123I-Ioflupane scans and they are both
olfactory test showed a decrease in odor identification in most remarkably accurate. References: None.
people with Parkinson’s disease. References: None.

EP-0035
EP-0034 Characterization of the FDOPA Uptake of the Brainstem
Comparison of semiquantitative analysis of dopaminergic and Diencephalon in Parkinsonian Syndromes by PET /
brain imaging MRI
R. Durmo1, B. Paghera1, D. Albano1, M. Bonacina1, M. Gazzilli1, E. G. Demonceau1,2, A. Tebbani1, Q. Demonceau1, V. Lebon1,3;
Cerudelli1, F. Dondi1, A. Mazzoletti1, F. Bertagna2, R. Giubbini2, P. 1
CEA-SHFJ Orsay, Paris, FRANCE, 2Bois de l’Abbaye, Liège,
Bellini3; BELGIUM, 3University Paris Sud, Paris, FRANCE.
1
Nuclear Medicine, Spedali Civili Brescia, Brescia, ITALY,
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S398

Aim/Introduction: FDOPA PET / CT is commonly used for DBS between 2008 and 2017. Clinical and neuropsychological
the investigation of dopaminergic denervation, the diagnosis profiles were collected before and after surgery. All patients had
being based on striatal uptake. But other brain structures, undergone FDG-PET within a month before surgery. We divided
including monoaminergic neurons of the brainstem and the patients into two groups depending on the Schwab And
diencephalon, metabolize FDOPA and are likely to be affected. England Activities Of Daily Living Scale (SE-ADL) results during
Using the values ​​automatically generated by a homemade clinical follow-up of at least 1 year after surgery. The first group
PET / MRI atlas, we looked for alterations in the FDOPA uptake consist of 26 patients with a score of SE-ADL ≥ 90%, the second
in parkinsonian syndromes. We retrospectively selected 120 group include 9 patients with SE-ADL<90%. A SPM12 two-
patients who underwent FDOPA PET / MRI examination, 49 with sample t-test (age and SE-ADL at baseline as nuisance variables)
Parkinson’s syndrome according to clinical and scintigraphic was performed comparing the two groups. Results: At voxel-
data, 71 others considered very unlikely to have this condition based analysis subjects with SE-ADL <90% at follow-up showed
(the control group). Materials and Methods: the T1 images significant hypometabolism in right occipital lobe (inferior and
of each patient were registered on the T1 images of a model middle gyri) and left temporal lobe (middle gyrus), as compared
where 28 anatomical regions had been previously identified. to subjects with SE-ADL ≥ 90% at follow-up Conclusion: DBS
The adjustment parameters were then applied to FDOPA has been an effective treatment for the majority of selected
images acquired 90 min after injection. In each region VOIs of patients, but not for all. FGD-PET demonstrated a greater cortical
different sizes were then generated: 1 voxel (1mm3), 27 voxels hypometabolism in SE-ADL<90-group involving occipital
or a volume adapted to the size of the region to be studied. The and temporal lobe. This could suggest that an extensive
mean SUV, alone or compared to that of the other regions, was impairment in these areas, assessed by pre-DBS FDG-PET, might
used to distinguish the 2 groups, by the way of a Student’s test. be useful in identifying patients who could benefit less from
Results: the results were similar, using different sizes of VOIS. the procedure. Instead patients with preserved metabolism in
In the parkinsonian group, a significant reduction in SUV was these areas seem to more likely benefit from surgery. Greater
observed in the substantia nigra (p = 0.002), amygdala (p = sample size is needed in order to confirm the pattern of the
0.01) and pulvinar (p = 0.03). We did not observe any significant distribution of hypometabolism. References: - Walker Z et al.
difference in the A8 zone, the reticular or the raphe nuclei. In Clinical utility of FDG PET in Parkinson’s disease and atypical
the supratentorial area, the occipital region was unaffected too, parkinsonism associated with dementia. Eur J Nucl Med Mol
in contrast to the striatum. The best discriminations between Imaging. 2018; - Brajkovic L et al.The utility of FDG-PET in the
parkinsonian and control groups, obtained by combining the differential diagnosis of Parkinsonism. Neurol Res. 2017;- Welter
activities of the whole regions, were provided by the difference ML et al. Clinical predictive factors of subthalamic stimulation
between the SUV of, on the one hand, the putamen and, on in Parkinson’s disease. Brain 2002;- Rossi M et al. Challenges in
the other hand, the A8 area, the hypothalamus, the pulvinar, PD Patient Management After DBS: A Pragmatic Review. Mov
the substantia nigra and the caudate nucleus, all with p less Disord Clin Pract. 2018.
than 10-20. Conclusion: for the first time in nuclear medicine,
we think we have been able to automatically demonstrate the EP-03
involvement of nuclei of the brainstem and diencephalon in
Parkinson’s syndrome. This opens perspectives in terms of early
Neuroimaging: Psychiatry and
detection, staging and differential diagnosis of this disease.
Neurotransmission
References: None.
October 12 - 16, 2019 e-Poster Area

EP-0036
Prognostic Role Of FDG PET Before Deep Brain Stimulation EP-0037
In PD Patients: A Voxel-Based Study Brain Dysfunction in Active and Abstinent Smoked
G. Puccini1, V. Berti1, S. Ramat2, F. Terenzi2, C. Polito2, M. De Cocaine Addicts from Brazil and Uruguay
Cristofaro2, S. Sorbi2, R. Sciagrà1; R. Ferrando1, C. Pascovich1, S. Parra1, M. Langhain1, A. Silveira1, P.
1
Nuclear Medicine Unit - University of Florence, Florence, ITALY, Fielitz1, A. Negrin1, V. Esmoris2, V. Martin1, C. Rodríguez1, F. Cadenas1,
2
Neurology Unit - University of Florence, Florence, ITALY. E. Moreno3, M. Bidegain3, R. Ponde de León3, L. Hopner4, L. Mendes4,
F. Ornell4, Y. Moreschi4, N. Fares5, M. Carballo3, F. Kessler4;
1
Clinics Hospital, University of the Republic, Montevideo, URUGUAY,
Aim/Introduction: Deep Brain Stimulation (DBS) is a 2
Maciel Hospital, Montevideo, URUGUAY, 3Catholic University,
neurosurgical procedure that could be a reliable tool for Montevideo, URUGUAY, 4Clinics Hospital of Porto Alegre, Porto
selected Parkinson’s Disease (PD) advanced patients. Our aim Alegre, BRAZIL, 5University of Zurich, Zurich, SWITZERLAND.
is to identify the specific brain metabolic profile of PD patients
who could benefit the most from this therapeutic option, in
order to correctly select PD patients to treat with DBS. Materials Aim/Introduction: Smoked cocaine (SC) has been linked to
and Methods: We selected a group of 35 consecutive PD severe dependence, serious bio-psycho-social deterioration
patients (10F/25M mean age 59±7years) who were treated with and criminal behavior, representing a big challenge for health,
S399 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

education and public security. The drug is widely available in hallucinations) are common and prominent features in
Latin America and impure forms are highly prevalent in the Alzheimer’s disease (AD) and their prevalence ranges from 30%
deprived population. The aim of the study was to evaluate brain to 50%. Delusions appear more frequently than hallucinations
dysfunction produced by chronic use of SC and its changes and the main forms are paranoid ideation and misidentification,
with abstinence in patients from two countries of our region. while hallucinations are usually visual. Clinical evidence supports
Materials and Methods: This prospective study recruited the hypothesis that degeneration of frontal cortex is responsible
166 subjects (127 from Uruguay and 39 from Brazil) divided in for the appearance of psychotic symptoms. The aim of this
four groups: active SC users (G1, n=64), abstinent SC users (G2, study was to evaluate perfusion in Brodmann areas (BAs) in
n=34), active intranasal cocaine hydrochloride (CH) users (G3, AD patients with psychotic symptoms compared with healthy
n=33) and normal controls (NC) (G4, n=35). 91% of the users controls in order to detect areas implicated in the manifestation
were male and ages ranged 17-37 years (27.0 ± 5.8, mean ± SD) of these symptoms. Materials and Methods: We studied 65
without differences between groups or with NC. Mean dose of consecutive patients (20 men, 45 women, age±SD 69.9±8.1
SC (3.1±3.3 g/day) did not differ from CH (2.2±1.7, p=0.11). Time years, duration of disease±SD 3.4±2.4 years, education±SD
of use was higher for CH (9.8±5.3 years) than SC (6.7±4.4, p=0.01). 9.4±4.7 years) from an outpatient Memory Clinic. We used
Mean time of abstinence in G2 was 4.5 months (range 1.0-22.3). the established DSM-IV criteria for the diagnosis of dementia
Associated use of alcohol and cannabis without criteria for and the specific established criteria (NINCDS-ADRDA) for the
dependence was present in groups 1-3 in similar proportions. diagnosis of AD. All the patients had a neuropsychological
All subjects underwent resting 99mTc-ECD SPECT. Analysis evaluation with a battery of tests including the mini-mental state
was performed in SPM8. Country of origin was entered as a examination (MMSE, mean 19.6±5.5) and the Neuropsychiatric
nuisance variable when necessary. Uncorrected voxel p-values Inventory (NPI). All the patients underwent a brain SPECT
lower than 0.001 and clusters > 100 voxels were reported. scan 20 min after the intravenous administration of 740MBq
Results: G1 showed mesial frontal, anterior cingulate and of 99mTc-HMPAO. We applied the NeuroGamTM software on the
ventromedial frontal hypoperfusion, and occipital and cerebellar reconstructed data, for the comparison of brain perfusion in
hyperperfusion relative to NC. Hypoperfusion in G3 was more BAs in the right (R) and left (L) hemispheres with the software’s
limited. G1 showed lower mesial prefrontal perfusion than normal data base consisted of healthy subjects of the same age.
G3. Brazilian SC users showed more prefrontal hypoperfusion Results: Compared with normal subjects, psychotic symptoms
than Uruguayan ones. The differences markedly reduced when in AD patients were correlated (p=0.05) with hypoperfusion
controlling for time of substance use, which was longer in in anterior and dorsolateral prefrontal cortices (BAs 8LR, 9LR,
Brazilians. Mesial and dorsal prefrontal and posterior cingulate 10 LR, 46LR), left ventral and right dorsal posterior cingulate
perfusion increased in G2 relative to G1, and occipital, cerebellar cortex (BA 23L, 31R), dorsal anterior cingulate cortex (BA
and anterior temporal perfusion decreased. Conclusion: SC 32LR), left anterior temporal gyrus (BA 22L), inferior frontal gyri,
abuse was characterized by greater dysfunction than CH in mainly on the left (BAs 44LR, 45L, 47LR), right supplementary
paralimbic prefrontal cortex comprising the reward system that somatosensory cortex (BAs 5R, 7R), left supramarginal gyrus (BA
play a major role in emotional control and adapted behaviour, 40L) and right secondary visual cortex (BA 18R). Conclusion:
providing a neural basis for the clinical profile described in Our findings support the hypothesis that impairment of frontal
addicts. Findings were similar in both countries despite possible lobe is the underlying cause of psychotic symptoms in AD.
regional differences in SC composition. Although some grade Moreover, other connected regions in parietal, temporal and
of brain dysfunction still persisted during abstinence, prefrontal visual cortices, as well as cingulate cortex may be parts of a
activity increased, probably reflecting an improve in limbic broader neural network underpinning the psychotic symptoms
balance, self-control and executive function, enhancing the in AD. References: 1. Rosenberg PB, Nowrangi MA, Lyketsos
probability of staying away from the drug. References: None. CG. Neuropsychiatric symptoms in Alzheimer’s disease: What
might be associated brain circuits? Mol Aspects Med. 2015;43-
44:25-37.2. Murray PS, Kumar S, Demichele-Sweet MA, Sweet
EP-0038 RA. Psychosis in Alzheimer’s disease. Biol Psychiatry. 2014 Apr
Brain SPECT Perfusion Imaging With Brodmann Areas 1;75(7):542-52.
Mapping Of Psychotic Symptoms (Delusions And
Hallucinations) In Patients With Alzheimer’s Disease
V. Valotassiou1, N. Sifakis2, C. Tzavara1, E. Lykou3, G. Angelidis1, EP-0039
N. Tsinia4, V. Kamtsadeli3, I. Tsougos1, D. Psimadas1, S. Alexiou1, S. Examinantion of brain perfusion and metabolism in
Papageorgiou5, P. Georgoulias1, J. Papatriantafyllou3; metabolic diseases (focusing on diabetes and obesity)
1
Dpt of Nuclear Medicine, University Hospital of Larissa, K. Zita1, J. Varga2, F. Nagy3, M. Emri2, M. Kaplar4, C. Aranyi2, I. Garai3;
Larissa, GREECE, 2Dpt of Nuclear Medicine, “Alexandra” 1
University of Debrecen, Debrecen, HUNGARY, 2Division
University Hospital, Athens, GREECE, 3IASIS Third Age of Nuclear Medicine and Translational Imaging, Medical
Center, Athens, GREECE, 4Aeginition Hosp., 1st University Imaging Department, Faculty of Medicine, University of
Psychiatric Clinic of Athens, Athens, GREECE, 52nd University Debrecen, Debrecen, HUNGARY, 3Scanomed Ltd., Debrecen,
Neurological Dpt., Attikon Hospital, Athens, GREECE. HUNGARY, 4Department of Internal Medicine, Faculty of
Aim/Introduction: Psychotic symptoms (delusions and Medicine, University of Debrecen, Debrecen, HUNGARY.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S400

Aim/Introduction: Microcircular alterations that could already on SPECT studies. Abnormal areas were designated below 2
be observed in prediabetic state (obesity and insulin resistance) standard deviations of the normal mean uptake in area >50%
are supposed to have significant role in the developement of pixels. Evaluation of the affected cerebral lobes was performed
the consequences of diabetes mellitus. The main aim of our independently and according to the number of affected lobes.
study was to compare the cerebrovascular microcirculation and Thus, group 1 - G1 were patients with affected CBF in only
metabolism of obese patients and patients suffering from type one lobe, group 2 - G2 patients with low CBF in two lobes
2 diabetes mellitus. Materials and Methods: In our prospective and group 3 - G3 patients with three or more affected lobes.
study 57 patients with controlled type 2 diabetes mellitus (52±9,6 Results: Reduced CBF was found in the limbic lobes in all
years) and 46 obese patients (50,6±7,9 years) were enrolled. patients. Participation of temporal, parietal and frontal lobes
BMI proved to be 34,06±5,94 in the diabetic group while it was were noted in 8/15 (53%), 5/15 (33%) and 2/15 (13%) patients
38,14±6,06 among the obese patients. Dynamic Tc99m-HMPAO respectively. In G1 there were 7/15 (20%) patients with low CBF
study (AnyScanFlex, Mediso) was performed for evaluation of in limbic system. In G2 there was noted 3/15 (20%) patients with
hemispheral perfusion using Patlak analysis. Then tomographic at least two hypoperfused CBF lobes and in G3 in 5/15 (33%)
imaging was carried out at rest condition. Brain metabolism patients. Conclusion: Patients with first episode of psychosis,
was estimated applying 18F-FDG PET/CT (AnyScan PC, Mediso). have low CBF, especially in the limbic system. This finding
FDG and HMPAO scans were transformed to MNI152 brain map is of importance, since hypoperfusion may be a precursor
after T1 registration and used for SPM (Statistical Parametric of structural changes later in the course of the illness. The
Mapping) analysis. NeuroQ application (Syntermed) was used to heterogeneity of the affected brain areas may be related to the
evaluate regional differences. Statistical analysis (Shapiro-Wilk, duration of untreated psychosis (DUP or to other characteristics
Wilcoxon, Spearman correlation) was applied for assessment of of the disease. The small study sample preclude us from drawing
group differences. Results: Hemispheral perfusion calculated general conclusions. References: None.
with Patlak analysis showed positive correlation with BMI
(rho=0.35, p=0.016). There were no significant differences in
hemispheral and regional perfusion in T2DM and the obese EP-0041
group. However, we found hypometabolism in right and left From metabolic connectivity to molecular connectivity:
cuneus (Br17) in T2DM with SPM analysis. NeuroQ analysis did application to dopaminergic pathways
not reveal significant regional perfusion or metabolic defects A. Verger1, T. Horowitz2, M. Chawki1, N. Girard2, E. Guedj2;
in either groups. Conclusion: Based on current literature 1
CHRU Nancy, Nancy, FRANCE, 2Timone, APHM, Marseille, FRANCE.
hypometabolism in the region of the cuneus is a characteristic
feature of neurodegenerative diseases. The reason why no
significant perfusion defects were found could be explained Aim/Introduction: This study aims to reveal the feasibility and
by the fact that the enrolled diabetics were therapeutically potential of molecular connectivity based on neurotransmission
well managed. Unexpected significant correlation with BMI is in comparison to the metabolic reference with an application
unclear, further investigation is required. References: None. to dopaminergic pathways. For this purpose, we propose to
compare the midbrain’s connectivity and related dopaminergic
pathways through a metabolic connectivity analysis using
EP-0040 18
F-FDG PET and neurotransmission connectivity analyses using
Scintigraphic low cerebral blood flow in first episode 123
I-FP-CIT SPECT and 18F-FDOPA PET. Materials and Methods:
psychosis Images of 47 subjects for 18F-FDG PET and 123I-FP-CIT SPECT, and
C. Sioka, G. Georgiou, A. Karampas, P. Petrikis, A. Papadopoulos, S. of 177 subjects for 18F-FDopa PET, with absence of neurological
Tsiouris, A. Fotopoulos; or psychiatric disorder, were selected. Interregional correlation
University Hospital of Ioannina, Ioannina, GREECE. analysis was performed at the group-level to determine
midbrain’s connectivity with metabolic rate of glucose for
18
F-FDG PET imaging, and binding potential parametric images
Aim/Introduction: To evaluate brain perfusion abnormalities for 123I-FP-CIT SPECT and 18F-FDopa PET imaging. SPM-T maps of
in antipsychotic-naive, first episode patients with psychosis. each radiotracer were generated, also with the use of masks to
Materials and Methods: Cerebral blood flow (CBF) with highlight the significant different findings obtained with each
99m
Technetium-hexamethylpropyle (99mTc-HMPAO)-single imaging modality and target. Results: 18F-FDG PET, 123I-FP-CIT
photon emission computer tomography (SPECT) is an imaging SPECT and 18F-FDopa PET imaging allowed revealing the nigro-
method that may be useful to evaluate changes of regional striatal pathway (52.70, 14.36 and 55.16 cm3, with respective
cerebral perfusion (RCP). Fifteen patients (10 men, five women) T-voxel max of 14.96, 5.28 and 17.69), the meso-limbic pathway
were included in the study. They were experiencing their first (8.36, 12.07, and 17.79 cm3 with respective T-voxel max of 13.44,
psychotic episode, they were in the acute phase of the illness 5.12 and 16.41) and the meso-cortical pathway (3.59, 2.49 and
with prominent positive symptoms (delusions, hallucinations). 26.47 cm3 with respective T-voxel max of 6.83, 2.49 and 7.05),
All of them were antipsychotic naive, they received only at T-voxel threshold of 5.10, 2.80 and 5.10, respectively. Using
benzodiazepines for less than a week. They were subjected a same T-voxel threshold of 5.10, SPM-T maps of 18F-FDopa
to 99mTc-HMPAO-SPECT RCP. NeuroGam software was applied PET showed larger extended areas within the dopaminergic
S401 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

pathways than 18F-FDG PET and 123I-FP-CIT SPECT (+38.25 and normal patients, chiefly for the analysis of the trunk, where the
+99.42 cm3 respectively), and less unspecific findings outside differences between pathology and normality are more subtle
these pathways than 18F-FDG PET (-46.85 cm3). Conclusion: than in the striatum References: None.
The present study illustrates the feasibility and interest to
use molecular connectivity with 18F-FDopa PET imaging for
dopaminergic pathways. Such analysis can be applied to EP-04
specific diseases involving the meso-telencephalic dopamine
system, and potentially with other molecular SPECT/PET targets
Neuroimaging: Dementia and
to other systems. References: None.
Neurodegeneration

October 12 - 16, 2019 e-Poster Area


EP-0042
Factors influencing the cerebral 18F-DOPA uptake
A. Tebbani1,2, Q. Demonceau1, V. Lebon1,2, G. Demonceau1,3;
1
CEA-SHFJ, Orsay, FRANCE, 2Université Paris Sud, Paris, EP-0043
FRANCE, 3Bois de l’Abbaye, Seraing, BELGIUM. A Direct Comparison Between 18F-FDG PET and Arterial
Spin Labelling Perfusion MRI in Patients Referred for
Differential Diagnosis of Dementia Using Simultaneous
Aim/Introduction: besides the neurological diseases, PET/MR
others factors could influence the uptake of 18F-DOPA in J. Ceccarini1, S. Bourgeois1, K. Goffin1, S. Sunaert2, K. Van Laere1;
the brain. Knowing their impact could ultimately lead to 1
Department of Imaging and Pathology, KU Leuven; Nuclear
identify by quantitative measurements the neurological Medicine and Molecular Imaging, University Hospitals
disorders. Therefore the impact of some of the most Leuven, Leuven, BELGIUM, 2Department of Radiology,
current physiological and pharmacological parameters University Hospitals Leuven, Leuven, BELGIUM.
has been evaluated in an almost normal population.
Materials and Methods: 70 consecutive patients, referred for
suspicion of Parkinson disease but by which the striatal F-DOPA Aim/Introduction: [18F]FDG-PET is an established tool to assist
uptake was normal on a PET/NMR examination, were included the clinical diagnosis and differentiation in the main forms
in the study. Age, gender, right- or left-handed, hypertension, of dementia syndromes, namely Alzheimer’s disease (AD),
diabetes and chronic intake of levodopa were retrospectively frontotemporal dementia (FTD), Lewy body dementia (LBD), and
collected. For each patient, the SUV of 28 regions of interest vascular dementia. Arterial spin labelling (ASL) perfusion MRI
of the trunk, the diencephalon and the cortex was measured has been proposed as a proxy marker for measuring neuronal
from an automatic atlas based on the PET/NMR imaging. dysfunction. The aim of the current study is to directly compare
Briefly, the T1 images of each patient were registered on the simultaneously acquired [18F]FDG-PET with enhanced ASL
T1 images of a reference model where several anatomical (eASL)-MRI in the accuracy for differential diagnosis of dementia
regions had been previously identified. The registration was in a clinical prospective set of patients referred for differentiation
carried out in a progressive way, in non-deformable and then of a dementing disorder. Materials and Methods: Twenty-
deformable mode, after creation of a mask including the seven patients with suspected neurodegenerative dementia
brainstem, the diencephalon and the striatum. The registration disorder (age 64.3 ± 11.2 years, 14 M/13 F, MMSE 11-30) first
parameters were then applied to the 18F-DOPA images underwent clinical routine 30-min brain [18F]FDG-PET-CT scan
acquired 90 min after injection. The SUV of the 28 regions (150.5 ± 11.5 MBq), and subsequently received a 20-min PET/MR
were finally related to the reticular SUV and the influence of scan, simultaneously acquired with an eASL-MRI acquisition on
the factors on them was statistically assessed by Student t-test. a 3T GE Signa PET-MR system. Thirty carefully screened age- and
Results: influence of hypertension was the most prominent gender-matched healthy subjects served as controls (CON; age
factor, increasing the ratio to reticular nuclei of the amygdala 63.9 ± 10.6 years; 14 M/16 F; MMSE 28-30; 40-60 min p.i static scan,
(+38%) and hypothalamus (+14%; p=0.009). The asymmetrical 152.2 ± 11.1 MBq). [18F]FDG-PET and eASL-MRI were compared
SUV of pulvinars decreased (-50%; p=0.004). Difference by a standardized visual qualitative and semiquantitative
between SUV of substantia nigra and reticular nuclei increased regional analysis by two experienced nuclear medicine
(+36%; p= 0.002). The chronic intake of levodopa reduced the physicians, scoring activity/flow abnormalities using a 4-point
amygdala to reticular ratio (19%; p=5.10-4). In male, the SUV scale. To determine group differences in glucose metabolism
ratio to reticular nuclei was higher in amygdala (+10%; p=0.01) and blood flow, and to investigate the differences in statistical
and A8 region (+10%; p=0.005). Age, right-or left-handed sensitivity and pattern deduction for both methodologies, voxel-
and diabetes had no statistical influence in our population. based (t-test and 2nd level) analyses were performed in SPM12
Conclusion: Hypertension gender and the intake of levodopa (pFWE<0.05 at cluster level). Results: The working diagnosis for
are factors influencing the SUV to reticular ratio in different the patient group consisted of 8 AD, 2 FTD, 1 LBD, 1 multiple
brain areas. These factors should be taken into consideration system atrophy of the cerebellar type, 1 motor neuron disorder,
for quantitative discrimination between pathological and 1 traumatic brain injury and 13 patients with no clear pre-PET
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S402

arguments for a neurodegenerative cause for the cognitive false-positive in 3/76 (4%) and false-negative in 8/76 (11%). In
complaints. The visual analysis resulted in equal specificity (0.70) terms of accuracy, FBB-PET/CT showed values of sensitivity,
for differentiating normal and abnormal images between the specificity, Negative predictive value, positive predictive
two modalities, but in a higher sensitivity and confidence rating value and global accuracy of 83%, 88%, 75%, 93% and 84%,
of the readers for FDG-PET (0.87) compared to ASL (0.60). Both respectively. At the semi-quantitative evaluation of FBB-PET/CT
VOI- and voxel-based analyses revealed reduced regional and using our new processing imaging algorithm, a value of 1.006 in
quantitative hypometabolism and hypoperfusion between the inferior-frontal-cortex and of 1.03 in the precuneus-region,
CON and AD, mainly in the mid-cingulate, posterior cingulate- previously proposed in other study by our group (1), resulted
precuneus cortices and parietotemporal areas as angular gyrus, the best cut-off SUVR-value, showing a good correlation with
although the pattern was more pronounced with FDG-PET and the diagnosis of AD. Based on FBB-PET/CT positivity (followed
assessable on each individual patient. Conclusion: Overall, in a by other necessary features for inclusion criteria), 13/44 patients
direct head-to-head comparison, FDG-PET has higher accuracy have been successfully enrolled in clinical trials using innovative
and confidence compared to eASL when differentiating patients monoclonal-antibodies therapy. Conclusion: SPM-normalized
referred for potential neurodegenerative causes, both visually as SUVR-analysis on FBB-PET/CT may allow better differential
well as semiquantitatively (larger effect size). References: None. diagnosis of neurodegenerative disease in the clinical scenario.
This new method could represent a valuable tool for the final
diagnosis of AD and to correctly select patients into clinical trials
EP-0044 using new target monoclonal-antibodies therapy. References:
SPM MRI-less 18F-Florbetaben PET for amyloid burden 1):Alongi P, Sardina DS, Coppola R, Scalisi S, Puglisi V, Arnone A,
quantification and potential AD patients selection in Raimondo GD, Munerati E, Alaimo V, Midiri F, Russo G, Stefano
clinical trials A, Giugno R, Piccoli T, Midiri M, Grimaldi LME. 18F-Florbetaben
P. Alongi1,2, R. Laudicella3,4, D. Sardina5, S. Giliberto2, G. Russo5, A. PET/CT to Assess Alzheimer’s Disease: A new Analysis Method
Stefano5, R. Coppola6, M. Midiri2, L. Grimaldi6; for Regional Amyloid Quantification. J Neuroimaging. 2019 Feb
1
Nuclear Medicine Unit, Fondazione Istituto G.Giglio, Cefalù 3. doi: 10.1111/jon.12601.
PA, ITALY, 2University of Palermo, Palermo, ITALY, 3Department
of Biomedical and Dental Sciences and of Morphofunctional
Imaging, University of Messina, Messina, ITALY, 4Nuclear EP-0045
Medicine Unit, Fondazione Istituto G.Giglio, Cefalù, ITALY, Unveiling the Amyloid PET Patterns that Promote
5
Institute of Molecular Bioimaging and Physiology, National Cognitive Impairment among Amyloid-positive Subjects
Research Council (IBFM-CNR), Cefalù PA, ITALY, 6U.O.C. A. Moscoso Rial1, J. Silva-Rodríguez2, J. Aldrey3, J. Cortés3, Á.
Neurologia, Fondazione Istituto G. Giglio, Cefalù PA, ITALY. Ruibal3, P. Aguiar1;
1
University of Santiago de Compostela, Santiago de Compostela,
SPAIN, 2Fundacion Instituto de Investigación Sanitaria de Santiago
Aim/Introduction: To assess the impact of 18F-Florbetaben (FIDIS), Santiago de Compostela, SPAIN, 3University Hospital of
(FBB)-PET/CT using a new processing-imaging-algorithm in Santiago de Compostela, Santiago de Compostela, SPAIN.
correlation with clinical-data, neuropsychological-assessment
and cerebrospinal-fluid (CSF) analysis to diagnose Alzheimer-
disease (AD) in dementia’s patients to be potentially included Aim/Introduction: Amyloid PET allows the detection of amyloid
in clinical trials. Materials and Methods: Seventy-six patients plaques in the neocortex, one of the defining neuropathological
with clinical evidence of dementia according to ENS-EFNS- features of Alzheimer’s Disease (AD). However, cortical plaques
criteria, underwent diagnostic FBB-PET/CT were retrospectively are also commonly found in cognitively normal elderly and
evaluated by a multidisciplinary-team (MDT). FBB-PET/CT results therefore the clinical utility of amyloid PET is limited to exclude
were correlated with clinical, cognitive-status, CSF-analysis and AD as the cause of cognitive impairment [1]. This study is
other imaging-technique. FBB-PET/CT images were processed aimed at (1) identifying the amyloid PET patterns that promote
with SPM-MRI-less and converted in standard-space (MNI-space) clinical symptoms among amyloid-positive (A+) subjects, and
by normalizing them with tissue-probability-map as a template. (2) implementing a new index from these patterns (Amy-Cog)
Automated-anatomical-labeling atlas was used to mask each to stratify A+ subjects into low/high cognitive impairment
regional-VOI followed by extraction of SUVR, normalized on profiles. Materials and Methods: The Amy-Cog score was built
the cerebellar-grey-matter. The regional SUVR and scores from using the amyloid PET uptake patterns that best discriminate
clinical and cognitive tests were used to create ROC-curves, between A+ cognitively normal (CN) subjects and A+ patients
obtaining the best thresholds for the clinical diagnosis. Leave- with mild AD. For this, we aggregated Florbetapir and PiB
one-out cross-validation was carried out to validate the results. PET data from 3 observational studies (Alzheimer’s Disease
Results: At the qualitative-assessment, 48/76 patients (63%) Neuroimaging Initiative, Australian Imaging Biomakers and
showed an elevated amyloid burden at FBB-PET/CT scan,. In AD- Lifestyle Study of Ageing, and Open Access Series of Imaging
detection and in comparison with conventional imaging (MR/ Studies-3). Florbetapir scans from 131 A+ CN and 129 A+ mild
CT), MDT evaluation and follow-up analysis, FBB-PET/CT resulted AD subjects were used for optimal selection of uptake regions
as true-positive in 40/76 (53%), true-negative in 23/76 (30%), of interest (ROI) and model training. The model was then
S403 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

evaluated in an independent sample of 235 A+ CN and 109 A+ for these older subjects is highlighted. This may be of particular
mild AD individuals, and associations with the Amy-Cog status relevance in DLB referrals where a balanced loss of dopamine
and longitudinal cognition were assessed in the A+ CN sample transporters is prevalent, and can be more challenging to detect
and in 322 A+ mild cognitive impairment (MCI) subjects. All the visually. References: European multicentre Database of Healthy
associations were adjusted by potential confounders, as well as Controls for 123I FP-CIT SPECT (ENC-DAT): Age-related Effects,
by cortical amyloid burden and striatal uptake [2]. Results: The Gender Differences and Evaluation of Different Methods of
optimal set of amyloid PET uptake ROIs included allocortical, Analysis. Varrone A et al. Eur J Nucl Med Mol Imaging (2013) 40:
striatal, and white matter regions. Classification accuracy 213-227.
between A+ CN and A+ AD in the test set was high (AUC = 0.94),
and superior to cortical amyloid burden and striatal uptake (p
< 0.001). Among A+ CN subjects, the 14% Amy-Cog+ showed EP-0047
faster longitudinal cognitive decline (-0.36 MMSE points/year, p Individual brain metabolic connectome indictors predict
< 0.001) than Amy-Cog-. MCI Amy-Cog+ patients also showed the development of Alzheimer’s dementia in mild
faster cognitive decline and progression to AD dementia than cognitive impairment
Amy-Cog-. Both in A+ CN and MCI, longitudinal cognition was I. L. Alberts1, M. Wang2, J. Jiang3, Z. Yan4, J. Jiang4, J. Ge5, H. Zhang5,
better predicted after including the Amy-Cog score in a model C. Zuo5, J. Yu6, P. Cumming1, A. Rominger1, K. Shi1;
with cortical and striatal uptake alone (p < 0.001). Conclusion: 1
University clinic for Nuclear Medicine, Bern, SWITZERLAND,
The Amy-Cog score increases the value of a positive amyloid 2
Shanghai Institute for Advances Communication and Data
PET, providing a closer association between amyloidosis and Science, Shanghai University, CHINA, 3Key laboratory of
clinical symptoms, and predicts cognitive decline in A+ CN specialty fibre optics, Shanghai University, Shanghai, CHINA,
and MCI subjects. References: [1] Johnson KA, et al. Alzheimers 4
Shanghai University, Shanghai, CHINA, 5Fudan University,
Dement. 2013 Jan; 9(1):e-1-16. [2] Hanseeuw BJ, et al. Alzheimers Fudan, CHINA, 6Huashan Hospital, Shanghai, CHINA.
Dement. 2018 Oct;14(10):1281-1292.

Aim/Introduction: The value of metabolic connectome


EP-0046 approaches based on 18F-fluorodeoxyglucose (FDG) positron
123
I FP CIT Quantification in Older Subjects emission tomography (PET) has been demonstrated by
A. Nicol; numerous previous studies in neurodegenerative diseases.
Queen Elizabeth University Hospital, Glasgow, UNITED KINGDOM. However, such metabolic networks are typically derived from
groups of patients, with a resultant lack of individuality. We now
present an individualised connectome approach to characterise
Aim/Introduction: 123I FP-CIT imaging of striatal dopaminergic brain-wide metabolic networks and explore the application in
neuron terminals is used in the diagnostic pathway of Parkinson’s predicting the conversion of individuals with mild cognitive
Disease (PD) and Lewy Body dementia (DLB). Quantification is impairment (MCI) to Alzheimer’s dementia (AD). Materials and
performed as an adjunct to visual assessment of images, using a Methods: We obtained FDG-PET data from the ADNI database
normal database derived from healthy control subjects. Specific consisting of 50 individuals without cognitive disturbance,
striatal binding is known to have a non-linear age dependency 332 patients with stable MCI during 36 months’ follow-up,
and corrections for age are applied. Databases are commonly 178 MCI patients who did develop AD within the follow-up
produced using subjects up to age approx. 80 with interpolation interval, and 50 AD patients. The metabolic network for each
for older subjects. This study aims to assess the accuracy of individual was ascertained using connectome methodology
quantification for older subjects. Materials and Methods: based on Kullback-Leibler similarity. Furthermore, 457 network
Subjects referred for a 123I FP-CIT scan which was subsequently properties were derived from the individual metabolic network.
reported as normal were collated. Fifteen consecutive subjects We analyzed the metabolic network properties along with other
aged 80-90 (10F, 5M, mean age 85.0, SD 2.5) and fifteen subjects clinical characteristics by the multivariate Cox proportional
aged > 90 (11F, 4M, 92.5 (2.2)) were included. For reference, hazards technique. We also established four different Cox
twenty subjects aged 60 - 80 were also assessed (14F, 6M, 67.4 models, i.e. clinical characteristics, imaging pattern, imaging
(5.7)). Quantification was performed using age matched striatal connectome and the combined model. Our proposed approach
Z scores from the European EARL database (Hermes BRASS). was compared with the spatial covariance mapping analysis.
Results: The average striatal Z-scores for the groups of subjects Results: The individual connectome analysis revealed brain
aged 80-90 and > 90 were significantly different to zero (p<0.05, metabolic network abnormalities, confirming a disruption of
80-90: mean 0.7, SD 1.4; >90: mean 0.7, SD 1.5). The average the network modular structure in the progression from MCI to
striatal Z-scores for the group aged 60-80 was not significantly AD. We found significant between-group differences in network
different to zero (mean 0.1, SD 1.0). Conclusion: Quantification properties across clinical groups in the precuneus, lingual,
of 123I FP-CIT scans may provide a useful adjunct to visual and temporoparietal cortices, precentral gyrus, and putamen.
assessment. This uses databases which were developed with a Metabolic connectome expression was a superior predictor
focus on movement disorders and did not include many subjects of conversion than were other clinical or imaging pattern (HR,
older than age 80. The requirement for accurate reference data 3.80; 95% CI, 2.99-4.82; P < 0.001). The predictive performance
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S404

improved further when clinical and metabolic pattern variables MCI subgroup, only MCIP showed lower rCMglc in the right
were combined in the Cox model. The C-index scores in the superior frontal gyrus. In activation PET between NC and each
test dataset were as follows: 0.728 (clinical), 0.749 (imaging MCI groups, only MCIP showed lower rCMglc in the right mid
pattern), 0.807 (connectome), and 0.827 (the combined model). frontal gyrus, right anterior cingulate gyrus, right inferior frontal
Conclusion: Our individual brain connectome analysis identifies gyrus, left inferior parietal gyrus and right superior parietal gyrus.
abnormal brain networks associated with conversion from Conclusion: During memory and attention tasks, cerebral
MCI to AD, thus potentially constituting a clinically applicable metabolism changes compared with that in resting state. The
imaging biomarker. References: None. patterns of this changes are different according to amyloid
deposition in MCI patients. References: None.

EP-0048
Task-specific regional cerebral metabolic pattern EP-0049
according to amyloid deposition in MCI patients: SPM Comparison of MR-based and PET-only quantification of
analysis with paired FDG PET images tau load using [11C]PBB3
E. Lee1, H. Youn2, S. Lee3, H. Jeong2,4, J. Eo1; E. Yousefzadeh-Nowshahr1,2, G. Winter2, P. Bohn3, K. Kneer2, C.
1
Department of Nuclear Medicine, Korea University Guro Hospital, von Arnim4, M. Otto4, C. Solbach2, S. Anderl-Straub4, D. Polivka4,
Korea University College of Medicine, Seoul, KOREA, REPUBLIC P. Fissler4, V. Prasad2, P. Kletting1,2, M. W. Riepe5, H. Braak4, K. Del
OF, 2Department of Psychiatry, Korea University Guro Hospital, Tredici4, M. Higuchi6, A. Ludolph4, A. J. Beer2, G. Glatting1,2;
Korea University College of Medicine, Seoul, KOREA, REPUBLIC 1
Medical Radiation Physics, Department of Nuclear
OF, 3Department of Biomedical Sciences, Korea University Medicine, Ulm University, Ulm, GERMANY, 2Department of
Graduate School, Seoul, KOREA, REPUBLIC OF, 4Korea University Nuclear Medicine, Ulm University Hospital, Ulm, GERMANY,
Research Institute of Mental Health, Seoul, KOREA, REPUBLIC OF. 3
Department of Nuclear Medicine, University Hospital
Cologne, Köln, GERMANY, 4Department of Neurology, Ulm
University, Ulm, GERMANY, 5Department of Psychiatry and
Aim/Introduction: We investigated whether changes of the Psychotherapy II, Ulm University, Ulm, GERMANY, 6National
regional cerebral glucose metabolism (rCMglc) in resting and Institute of Radiological Sciences, Chiba, JAPAN.
memory and attention task conditions are different according
to amyloid deposition in MCI patients. Materials and Methods:
Cognitively normal elderly peoples (NC) and MCI patients were Aim/Introduction: [11C]pyridinyl-butadienyl-benzothiazole3
prospectively enrolled and performed F-18 fluorodeoxyglucose ([11C]PBB3) is a promising tracer developed for tau imaging in
(FDG) PET scanning in two different conditions, which were neurodegenerative diseases. Although MR-based quantification
paired FDG PET image data. First basal FDG PET imaging was of tau load is commonly used as reference method, not all
performed in the resting state with FDG injection in the lying subjects necessarily have current MR images available in
position to minimize motor cortex activation. Second activation clinical routine. Here the ability of PET-only method for the
FDG PET imaging was performed after FDG injection during quantification of [11C]PBB3 tau tracer was evaluated and
memory and attention tasks while lying on the PET bed. compared to the MR-based quantification. Materials and
The tasks were continued until the end of the scanning to Methods: Eleven patients with suspected neurodegenerative
fully activate related cerebral regions during scanning. F-18 disease were examined with [11C]PBB3-PET and structural MRI.
florbetaben (FBB) PET were also performed. MCI patients were In the MR-based method, the MR images were normalized
classified into amyloid negative (MCIN) and amyloid positive into the standard Montreal Neurological Institute (MNI) space
(MCIP) groups based on FBB PET. FDG PET images were using standard MRI templates. The estimated transformation
preprocessed using SPM12 with T1 MR images and estimated matrix was then applied to the corresponding PET images. For
on a voxel-by-voxel basis. Basal and activation FDG PET images the PET-only method, a [11C]PBB3-PET template was created by
were compared within the subgroups and between subgroups averaging these PET images previously normalized to the MNI
(NC vs. MCIN, NC vs. MCIP and MCIN vs. MCIP) with statistical space. Then the PET images were registered into the [11C]PBB3-
threshold of uncorrected P value <0.001 and extent threshold PET template. The automated anatomical labelling (AAL) brain
>100 continuous voxel size. Results: Ten normal control, 9 atlas was used to define masks for the frontal, temporal, parietal
MCIN and 11 MCIP were recruited in this study. In activation and occipital lobes in both methods. All regions of interest
PET compared with basal PET within the group, NC showed were masked for gray matter with a 30 % probability threshold.
significantly increased rCMglc in the left precentral gyrus, right Standardized uptake value ratios (SUVRs) were calculated using
precentral gyrus, left lingual gyrus, left thalamus and left mid the cerebellum as a reference region. Bland-Altman analysis
frontal gyrus, MCIN showed significantly increased rCMglc in was applied for comparison SUVRs from both methods. The
the left mid temporal gyrus, right superior medial frontal gyrus, correlations between SUVRs and mini-mental state examination
right superior temporal gyrus, right superior temporal pole, left (MMSE) were evaluated by Pearson’s correlation analysis. A
precentral and right caudate, and MCIP showed significantly value of p<0.05 was assumed significant. Results: There was
increased rCMglc in the right superior temporal gyrus and no significant difference between PET-only and MR-based
left superior frontal gyrus. In basal PET between NC and each quantification. In agreement with the MR-based method, the
S405 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

[11C]PBB3 uptakes obtained using the PET-only method were The PET based A(N) staging system unveiled significant A(N)
the highest in the temporal lobe and then followed by the differences between AD and the other groups, whereas aMCI
occipital, parietal and frontal regions. For both methods, the and controls had similar A profiles and minor differences in
significant correlations between SUVRs and mini-mental state the (N) staging. [18F]FDG-PET could be used beyond simple
examination (MMSE) were comparable in frontal (rMRI=-0.81 vs. (N) staging, since it provided alternative hypotheses to cases
rPET=-0.85); temporal ( rMRI=-0.76 vs. rPET=-0.74); parietal (rMRI=- with clinical-biomarker “mismatches” and its AD hypometabolic
0.84 vs. rPET=-0.84); and occipital regions ( rMRI=-0.78 vs. rPET=- pattern correlated with amyloid positivity. Low education was
0.85 ). Bland-Altman analysis showed lower and upper limits related to dementia in the absence of biomarker changes.
of agreement of -0.06 to +0.12 between global SUVRs of the References: None.
MR-based versus the PET-only method. Conclusion: The PET-
only approach provides accurate and precise [11C]PBB3 load
quantification without the need of MR images and it can be EP-0051
used for clinical diagnosis purposes, which might be of special Agreement between amyloid-PET early phase images and
relevance in a routine clinical setting. However, the MR-based FDG-PET: a single subject validation in amyloid positive
method is more suitable for definition of the reference and gray and amyloid negative subjects
matter regions. References: None. P. Santos-Holgueras1,2, A. Dodich3, P. Andryszak4, B.
Rakotomiaramanana4, M. Scheffler5, K. Lövblad6, G. B. Frisoni4, V.
Garibotto2,3;
EP-0050 1
Nuclear Medicine and Molecular Imaging Division, San Pedro
A Brain PET staging system using Amyloid and Hospital-CIBIR, Logroño, SPAIN, 2Nuclear Medicine and Molecular
Neurodegeneration Biomarkers for Individual Assessment Imaging Division, Diagnostic Department, Geneva University
in the Context of the 2018 NIA-AA Research Framework: Hospitals, Geneva, SWITZERLAND, 3NIMTlab, Neuroimaging and
an approach exploring clinical-biomarker mismatches and Innovative Molecular Tracers Laboratory, University of Geneva,
socio-demographic parameters Geneva, SWITZERLAND, 4Memory Center and LANVIE - Laboratory
A. M. N. Coutinho, F. Porto, D. de Paula Faria, C. R. Ono, A. T. Garcez, of Neuroimaging of Aging, Department of Rehabilitation and
P. Squarzoni, F. L. S. Duran, M. O. Oliveira, E. S. Tres, S. M. D. Bucki, O. Geriatrics, Geneva University Hospitals, Geneva, SWITZERLAND,
V. Forlenza, R. Nitrini, G. Busatto Filho, C. A. Buchpiguel; 5
Radiology Division, Diagnostic Department, Geneva
University of São Paulo, São Paulo, BRAZIL. University Hospitals, Geneva, SWITZERLAND, 6Neurodiagnostic
and Neurointerventional Division, Diagnostic Department,
Geneva University Hospitals, Geneva, SWITZERLAND.
Aim/Introduction: [18F]FDG-PET and [11C]PIB-PET are
validated as neurodegeneration and amyloid biomarkers of
Alzheimer´s disease (AD). We used a PET staging system based Aim/Introduction: FDG-PET and amyloid-PET are validated
on the 2018 NIA-AA research framework to compare the biomarkers of neurodegeneration and of Alzheimer disease
proportion of amyloid positivity (A+) and hypometabolism (N+) (AD) pathology. The acquisition of images immediately after
in AD, amnestic mild cognitive impairment (aMCI) and healthy injection for amyloid-PET (amy-PETep) offers the opportunity
control groups in the specific context of a Latin-American to measure cerebral blood flow, possibly representing an
Megacity. We also incorporated an additional classification of alternative to the evaluation of brain metabolism through FDG-
abnormal [18F]FDG-PET patterns and their co-occurrence with PET. This study aims to evaluate the concordance of amy-PETep
A+, exploring [18F]FDG-PET to generate hypotheses in cases and FDG-PET in a large sample of amyloid positive and negative
presenting with clinical-biomarker “mismatches”. Materials individuals using two different amyloid tracers. Materials and
and Methods: Elderly individuals (N = 119) clinically classified Methods: We selected 126 subjects (68 female, age: 71±7) from
as controls (N = 38), aMCI (N= 43) or early AD (N= 38) were two ongoing studies at Geneva University Hospitals. All subjects
included. We assessed their A(N) profiles and [18F]FDG-PET performed both FDG-PET and amy-PETep (interval in months:
neurodegenerative patterns (classified as typical or atypical of 3±4.9; 18F-florbetapir: 76, 18Fflutemetamol: 50), spanning across
AD), performing re-assessments of images whenever clinical the whole cognitive spectrum (6 unimpaired, 89 mild cognitive
classification was in disagreement with the staging (clinical- impairment, 31 dementia). 85 subjects were amyloid positive.
biomarker “mismatches”). We also investigated associations All subjects had T1-weighted MRI images, used to normalize
between “mismatches” and socio-demographic characteristics. PET images. We computed standardize uptake value ratio
Results: AD presented with higher rates of A+ and (N)+. aMCI (SUVR) images using cerebellum and pons/vermis as reference
and controls had similar “A” profiles, with a tendency of more region for amyloid and FDG images, respectively. SUVR values
individuals with neurodegeneration (N+) in aMCI. Amyloid were extracted from atlas-based regions of interests (ROIs)
positivity and typical (N)+ AD hypometabolic patterns were (bilateral frontal, temporal and parietal, anterior and posterior
statistically associated. A non-AD pattern of hypometabolism cingulate cortex). Correlation analyses between SUVR obtained
was seen in all cases of neurodegeneration without amyloid (A- from each region and from the mean SUVR across all regions
(N)+) in the clinically-defined AD group. All A-(N)- cases in the AD between the early-phase (SUVRepA) and FDG images (SUVRFDG)
group had less than four years of formal education. Conclusion: through Pearson r index in the overall sample. Correlation
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S406

coefficients according to amyloid status and tracer were validation (not detailed). Statistics were computed using
compared using the Fisher r-to-z transformation. FDG-PET PRISM8.0 and the Percentile 90 (PC90) of the control group
and amy-PETep was evaluated visually as negative/non-AD/ defined as the cutoff reference for a «positive scan». Results:
AD pattern by 2 independent readers, using statistical maps HC SUVr3.5 and SUVrcentiloid. (mean±SD/median/PC90) were
of single-subject comparison with a reference database of 30 respectively 1.30±0.16/1.25/1.49 and 1.08±0.18/1.03/1.37 ,
FDG or 18 amy-PETep normal subjects, respectively. Results: both significantly different from the MCI group (1.55±0.34/1.45;
We found significant correlations (p<0.005) in the overall group p=0.0001***) and (1.34±0.37/1.30; p=0.008***). SUVrcentiloid. were
between SUVRepA and SUVRFDG in all the ROIs investigated, with r significatively lower than SUVr3.5 values (P<0.0001**** ; bias:
values ranging from 0.52 (left frontal) to 0.73 (right angular). The -18.8%, SD of bias: 5.1). However, a good correlation was found
correlation was significant and did not differ between amyloid between SUV3.5 and SUVrcentiloid (R2:0.94 ; Y=1.0037*X-0.2665). A
positive and negative subjects (r 0.68 and 0.52, respectively, excellent correlation was found between SUVr 3.5 cutoff and
p=0.2), nor between tracers (r 0.66 with florbetapir and 0.52 the visual reading (only 4/161 visually borderline scans). The
with flutemetamol, p=0.3). The agreement between raters best fit of the Flut SUVr centiloid values in the centiloid scale
in classifying patients according to the single-subject maps was obtained using the equation (CSV= 116.0 x SUVrcentiloid
was good (Cohen’s kappa: 0.69, SE: 0.056 CI95%: 0.58-0.80) -113.9) derived from previous calibration steps (not detailed).
Conclusion: Our results show that amy-PETep values are highly The derived cutoff values (PC90 of the HC) were 1.374 for
correlated with FDG-PET, in all ROIs analysed, for both tracers and SUVrcentiloid and 45.98 for the CSV. Conclusion: Despite lower
also for both amyloid statuses. The good agreement observed in values, Flutemetamol SUVrcentiloid favorably compared with
single subject analysis, comparable to the agreement reported previous SUVr 3.5 but present the main advantage to be directly
for the interpretation of FDG-PET, supports the routine use of transposable in the centiloid scale for direct comparison with
amy-PETep in clinical practice. References: None. other study results. References: Klunk et al. Alzheimer Dement,
2015. http://www.gaain.org/centiloid-project

EP-0052
In vivo Amyloid Plaques quantification using F18- EP-0053
Flutemetamol PET/CT in 31 healthy controls and 130 MCI: Multimodal Imaging of X-linked Adrenoleukodystrophies
SUVr methods’s comparison and transposition in the with [18F]Florbetaben PET/MRI
centiloid scale T. Gerhards, M. Rullmann, H. Roicke, D. Lobsien, K. Hoffmann, J.
R. Lhommel1, B. Hanseeuw1, V. Malotaux2, L. Dricot2, A. Ivanoiu1; Classen, M. Patt, O. Sabri, W. Koehler, H. Barthel;
1
Cliniques Universitaires St-Luc, UCLouvain, Brussels, BELGIUM, University Hospital Leipzig, Leipzig, GERMANY.
2
Institute of NeuroScience (IONS), UCLouvain, Brussels, BELGIUM.

Aim/Introduction: Leukodystrophies are a group of rare


Aim/Introduction: F18-Flutemetamol PET is now a well hereditary diseases characterized by impaired myelination
validated surrogate biomarker to non invasively estimate the or demyelination. In the case of X-linked adulthood cerebral
brain amyloid load of patient suspected of (pre-clinical) AD adrenoleukodystrophy (X-ACALD), cerebral white matter (WM)
disease, either by visual or semi-quantitative SUVr analysis, changes are considered to be triggered by a gene defect that
approach less dependent of the operator’s expertise and causes an insufficient degradation of very long chain fatty acids
more appropriate to follow the amyloid variations under (VLVFA) with subsequent neurotoxic effects. Recently, we were
targeted investigational drugs. By proposing the centiloid able to show that the beta-amyloid PET Tracer 18F Florbetaben
scale approach in 2015, Klunk has pointed the importance to which in addition to the actual target also binds to myelin has
harmonize quantitative reports of Amyloid PET series. Therefore, a great potential for improved imaging of WM diseases. The
we have planned to retreat our MCI patient’s database to obtain aim of this current pilot study was to evaluate for the first time
individual centiloid SUVr and centiloid scale values (CSV) for the suitability of hybrid 18F Florbetaben PET/MRI for imaging
each patient. The results of this centiloid analysis is reported here of X-ACALD. Materials and Methods: So far, we examined 4
and compared to our previous SUVr computation methodology patients with X-ACALD (mean age 43+/-7yrs, Loes score=9,8
(still used for data consistency and comparison with our ±2,6). 0-10min p.i. (perfusion equivalent) and 90-110min p.i.
previous reports). Materials and Methods: Since 2011, 31 (myelin equivalent in WM) after application of about 300MBq
healthy controls (HC) and 130 MCI were imaged at baseline with 18
F Florbetaben, PET (SUVRs, global brain as reference), structural
Flutemetamol (target I.D 185 MBq; dyn 6X5min; 90min pi). Visual MR as well as DTI MR (FA values) images were simultaneously
analysis (Sokoloff scale) and SUVr computation were performed acquired on a 3T Siemens mMR hybrid PET/MR system. The
using different evolution of the PNEURO workflows (PMOD, WM signals were regionally analysed using the Johns Hopkins
Zurich) from 3.2 to 3.9/4.0 version, natively implementing University WM tractography atlas (48 VOIs). Furthermore, we
now the centiloid vois atlas. Historical SUVr3.5 (=SUVneocortex/ analysed a cross-sectional area of the outer lesion-rim and
grey_cerebellum in PET space) were compared to SUVrcentiloid created profiles for the above imaging data. Results: Structural
values (= centiloid composite voi/GM+WM_cerebellum in MNI MRI revealed findings typical for X-ACALD with inflammatory
atlas space) and converted to CSV after PNEURO3.9 workflow demyelinating lesions in parieto-occipital, frontal or cerebellar
S407 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

WM. In comparison with an age matched healthy control group, patients had MRI evaluation. Among them, only 37.5% of the
28% of the DTI WM VOIs and 20% of the myelin PET WM VOIs patients presented a narrowing of the callosal angle, and 60%
showed pathologic values (more than 2STDEV). Regional myelin showed alterations in CSF flow, findings associated with NPH.
PET WM SUVRs were correlated with the regional WM FA values Regarding the confirmed CSF fistulas scenario, 70% of the
(r̄ = 0.43). The cross-sectional profiles showed a clear increase patients had positive results on RC-SPECT/CT versus 50% on
of the FA levels in the transition zone from the lesion to the MRI. RC-SPECT/CT did not confirm only one CSF fistula detected
adjacent normal-appearing WM (NAWM). Here, perfusion PET by MRI. Conclusion: The present study suggests a high rate of
showed a broader transition zone, while myelin PET revealed prediction of response to VPS therapy by RC-SPECT/CT in NPH,
a steady increase from the centre of the lesion towards the apparently superior to the measurement of callosal angle and
adjacent NAWM. Conclusion: From these initial results it is CSF dynamics by MRI, despite the low number of individuals
concluded that multimodal 18F Florbetaben WM PET/MRI could with all the studies in the present sample. RC-SPECT/CT also
lead to a more specific characterization of the extent of the identified a more significant percentage of patients with CSF
lesional burden and disease stage in X-ACALD as compared to fistula than MRI, in addition to more accurately detecting the
MRI. This novel imaging approach would, thus, also be of great level of extravasation of the CSF due to the use of SPECT-CT.
interest for monitoring re-myelination therapies. To confirm this References: None.
assumption, however, larger case numbers and longitudinal
imaging are required. References: None.
EP-0055
Clinical progression over one-year in mild cognitive
EP-0054 impairment subjects with low ß-amyloid neocortical
Radionuclide Cisternography revisited in the SPECT/CT retention levels
era: applications in Normal Pressure Hydrocefalus and in E. Giovannini1, G. Giovacchini1, M. Riondato1, S. Pastorino1, O.
the detection of Cerebrospinal Fistulas in comparison with Ferrando1, V. Duce1, M. De Biasi2, C. Passera2, E. Carabelli1, A.
Magnetic Resonance Imaging techniques Mannironi1, L. Mansi3, A. Tartaglione2, A. Ciarmiello1;
M. Waitman, A. M. N. Coutinho, R. F. Nunes, M. Trindade, E. C. 1
Asl5, La Spezia, ITALY, 2Memory Center, La
Zaniboni, L. Bastos, M. Scaff, C. A. Buchpiguel; Spezia, ITALY, 3University, Napoli, ITALY.
Sírio Libanês Hospital, São Paulo, BRAZIL.

Aim/Introduction: The rate of clinical progression of cognitive


Aim/Introduction: Radionuclide cisternography continues impairment in amyloid positive subjects with moderate retention
being an important exam for the evaluation of both Normal levels is unknown. The primary aim of the study was to perform
Pressure Hydrocephalus (NPH) and cerebrospinal fluid (CSF) a 1-year follow-up on rate of cognitive decline in patients
fistulas. NPH is characterized by the classic clinical triad of with mild cognitive impairment (aMCI) featuring moderate
ataxia, urinary incontinence, and dementia, resulting from a amyloid retention level with standardized uptake value ratio
change in the flow dynamics of CSF. The improvement of the (SUVr) ranging from 1.3 to 1.5. The secondary objective was to
symptoms tends to occur with a ventriculoperitoneal shunt compare the rate of cognitive decline in subjects with moderate
(VPS). CSF fistulas result from multiple factors, including trauma, amyloid positivity and negative ones. Materials and Methods:
post-lumbar puncture or even spontaneously. However, most In this prospective phase III trial (EudraCT 2015-001184-39), 38
diagnostic techniques have limited sensitivity to investigate participants with aMCI underwent clinical, neuropsychological
both conditions. The present study investigated the role of and PET amyloid imaging tests. Study participants were
Radionuclide Cisternography with SPECT/CT (RC-SPECT/CT) in followed for 1 year to assess changes in global cognition and
two scenarios: (1) prediction of VPS response in patients with amyloid burden. PET images were scored as positive (Aß+) for
suspected NPH; (2) in the detection of CSF fistulas. In both amyloid retention using a standardized uptake value ratio ≥ 1.3,
situations, we compared RC-SPECT/CT results with state-of-the- measured in grey matter, at baseline scan. The Mattis Dementia
art MRI examinations. Materials and Methods: In scenario 1 we Rating Scale (MDRS) was used to assess clinical longitudinal
retrospectively included all patients with positive RC-SPECT/CT changes of cognitive impairment. Results: Thirty-eight aMCI
for NPH between the years 2006 and 2019 (N = 17). When at subjects completed the assessment according to study
disposal, we also evaluated the MR results (callosal angle in 16 protocol. Amyloid positive subjects showed greater clinical
individuals and CSF dynamics in six). Patients had their charts worsening on MDRS score (p=0.006). Aß- showed no significant
reviewed to characterize the clinical response to VPS. In scenario changes on MDRS scores over 1 year. We found significant MDRS
(2), patients ate with a confirmed diagnosis and effective score decrease in 37% of aMCI cohort (MDRS+), whereas in the
treatment of CSF fistulas (N = 10) had their results of RC-SPECT/ remaining 63% MDRS were stable (MDRS-). Among subjects
CT and MRI retrospectively assessed to evaluate both the with cognitive deterioration 86% had positive amyloid scan and
sensivity and the agreement between the methods. Results: In 14% were classified as amyloid negative while in MDRS- group
the NPH scenario, 88.2% of the patients with positive RC-SPECT/ 25% were Aß+ and 75% were Aß- (χ2=13; P=0.0003). Aß SUVr
CT presented clinical improvement, and only two (11.8%) had above 1.3 identified individuals with significant progression
no improvement in the symptoms after VPS placement. Sixteen over one-year with a SS of 86% and a SP of 75%, as compared to
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S408

Aß- subjects. The PPV was 67% and NPV was 90%. Conclusion: EP-0057
This study demonstrates that, aMCI cognitive decline can be Quantification of tau load using [11C]PBB3: a voxel-wise
predicted at low retention amyloid level and above the threshold statistical analysis
of SUVr=1.3 the rate of decline is increased. Detection of low E. Yousefzadeh-Nowshahr1,2, G. Winter2, P. Bohn3, K. Kneer2, C.
amyloid deposition may help in selecting target population for von Arnim4, M. Otto4, C. Solbach2, S. Anderl-Straub4, D. Polivka4,
preventive therapeutic interventions and to design treatment P. Fissler4, P. Kletting1,2, V. Prasad2, M. W. Riepe5, H. Braak4, K. Del
trial. References: None. Tredici4, M. Higuchi6, A. Ludolph4, A. J. Beer2, G. Glatting1,2;
1
Medical Radiation Physics, Department of Nuclear
Medicine, Ulm University, Ulm, GERMANY, 2Department of
EP-0056 Nuclear Medicine, Ulm University Hospital, Ulm, GERMANY,
Evaluation of different methods for spatial normalization 3
Department of Nuclear Medicine, University Hospital
of PIB-PET brain images Cologne, Köln, GERMANY, 4Department of Neurology, Ulm
F. Xie1, Q. Huang1, D. Jiang1, F. Hua1, Y. Guan1, Q. Guo2; University, Ulm, GERMANY, 5Department of Psychiatry and
1
Huashan Hospital, Fudan university, Shanghai, CHINA, Psychotherapy II, Ulm University, Ulm, GERMANY, 6National
2
Department of gerontology, Shanghai Jiaotong university Institute of Radiological Sciences, Chiba, JAPAN.
affiliated sixth people’s hospital, Shanghai, CHINA.

Aim/Introduction: PIB-PET can be used for detecting and Aim/Introduction: [11C]pyridinyl-butadienyl-benzothiazole3


quantitative measurement of the Aβ plaques. The precise positron emission tomography ([11C]PBB3-PET) has the potential
of spatial normalization of PIB-PET images is important in to visualize and quantify accumulation and distribution of tau
quantitative measurements. So we evaluated the precise of deposits in neurodegenerative diseases. Here we evaluated the
spatial normalization methods regularly used PIB-PET images ability of using [11C]PBB3-PET in a routine clinical environment
analysis, and try to recommend a more precise method for to detect and measure regional tau burden. Materials and
the quantitative measurements of PIB-PET. Materials and Methods: 17 patients were examined with [11C]PBB3-PET, 5 of
Methods: 21 AD patients ascertained by neurological physician them with advanced neurodegenerative diseases (ND) from the
were enrolled in this study. All subjects underwent FDG-PET, frontotemporal lobar degeneration (FTLD) or Alzheimers Disease
PIB-PET and MRI T1-weighted scanning. The PIB-PET images (AD) spectrum (age: 64.0±8.1 y; mini-mental state examination
were normalized into MNI space by the following methods: (MMSE): 10-21) and 12 patients with mild cognitive impairment
(A) normalized to H2O-PET template by SPM8; (B) FDG-based (MCI) (age: 63.8±7.1 y; MMSE: 23-30). The cerebrospinal fluid
normalization by SPM8: co-registration of FDG-PET images levels of tau (CSF_tau) and amyloid-β42 (CSF_Aβ) were assessed
of each subject to their corresponding PIB-PET images, then using a lumbar puncture. An automated PET-only method
nonlinear normalization parameters were calculated between was developed to quantify tau pathology. To achieve this, all
the co-registered FDG-PET images and the H2O-PET template images were registered to a [11C]PBB3-PET template, generated
by SPM8 to transform the PIB-PET images to the MNI space; (C) by averaging PET scans previously normalized to the standard
MRI-based normalization by SPM8: co-registration of MRI to their Montreal Neurological Institute space. Statistical parametric
corresponding PIB-PET images, then nonlinear normalization mapping was used to perform a voxel-wise two-sample t-test
parameters were calculated between the co-registered MRI analysis across groups. To compute target-to-cerebellum
images and the MRI template by SPM8 to transform the PIB-PET standardized uptake value ratios (SUVr) within 90 volume of
images to the MNI space; (D) normalization to the dementia interests (VOIs), the automated anatomical labelling brain
template[1]by SPM8; (E) FDG-based normalization to dementia atlas was used. All VOIs were masked for gray matter with a 30
template by SPM8; (F) normalization by SPM12; (G) FDG- % probability threshold. The correlation between SUVr values,
based normalization by SPM12; (H) MRI-based normalization MMSE, CSF_tau and CSF_Aβ were investigated by Pearson’s
by SPM12. After normalization, the standard deviation (s.t.d) correlation analysis. Results: Significantly higher [11C]PBB3
images were calculated, and the coefficient of variation (CV = binding was observed in patients with advanced ND compared to
s.t.d/mean) of the brain regions were calculated, including basal MCI patients in the inferior and middle temporal lobe (1.25±0.07
ganglia, frontal lobe, lateral parietal lobe, lateral temporal lobe, vs. 0.91±0.05, p = 0.02), and middle frontal lobe (1.23±0.07 vs.
medial temporal lobe, occipital lobe, posterior cingulate gyrus 0.88±0.05, p = 0.04). Although there was a substantial difference
and precuneus,. Results: The accuracy of normalization to H2O between groups in the left posterior cingulate (1.33±0.07 vs.
and dementia template by SPM8 was 80.95% and 95.33%, no 0.95±0.05), the results did not reach significance (p = 0.08). The
mismatches were found in other methods by visual inspection. regional analysis revealed that CSF_tau values were associated
Quantitative analysis showed the s.t.d and CV value of FDG-based with occipital tau pathology (r = 0.64, p = 0.02), whereas CSF_Aβ
normalization by SPM8 was minimum . Conclusion: FDG-based values were related inversely to the increased tau burden in the
normalization of PIB-PET images by SPM8 was recommend for parietal (r = -0.62, p = 0.03) and precuneus regions (r = -0.67, p
the measurements of PIB-PET image in AD studies. References: = 0.02). MMSE showed significant inverse correlations in many
1. Rosa, P.A.D., et al., A Standardized [18F]-FDG-PET Template regions with the strongest correlations in prefrontal, temporal,
for Spatial Normalization in Statistical Parametric Mapping of parietal, occipital and precuneus regions (r = -0.49 to -0.59, p
Dementia.Neuroinformatics, 2014. 12(4): p. 575-593. < 0.05). Conclusion: Statistical voxel-wise analysis effectively
S409 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

showed group differences in [11C]PBB3-PET tau signal. Both emission computed tomography. Mov Disord. 2011;26:416-23.
MMSE and CSF values had significant correlations with tau 5. Helmich RC, Hallett M, Deuschl G, Toni I, Bloem BR. Cerebral
uptake in several brain regions, suggesting that [11C]PBB3-PET causes and consequences of parkinsonian resting tremor: a tale
indeed is an effective surrogate parameter for tau load and of two circuits? Brain. 2012;135:3206-26.
disease severity. References: None.

EP-0059
EP-0058 Imaging of tau deposition in neurodegenerative diseases
Tremor and non-tremor Parkinson’s disease show different of the FTLD/AD spectrum in a clinical setting using [11C]
patterns of 11C-CFT and 18F-FDG PET/CT imaging PBB3 PET/CT
M. Xin, C. Wang, J. Liu, G. Huang; G. Winter1, P. Bohn2, E. Yousefzadeh-Nowshahr3, K. Kneer1, C. A. F.
Renji Hospital, School of Medicine, Shanghai von Arnim4, M. Otto4, C. Solbach1, G. Glatting3, S. Anderl-Straub4, D.
Jiao Tong University, Shanghai, CHINA. Polivka4, P. Fissler4, V. Prasad1, M. W. Riepe5, H. Braak4, K. Del Tredici4,
M. Higuchi6, A. Ludolph4, A. J. Beer1;
1
Department of Nuclear Medicine, Ulm University, Ulm, GERMANY,
Aim/Introduction: Parkinson’s disease (PD) is a heterogeneous 2
Department of Nuclear Medicine, University Hospital Cologne,
neurodegenerative disorder, including a tremor-dominant and Köln, GERMANY, 3Medical Radiation Physics, Department of
a non-tremor (bradykinesia or rigid) subtypes. Tremor-dominant Nuclear Medicine, Ulm University, Ulm, GERMANY, 4Department
PD is generally prone to follow a benign disease course. To of Neurology, Ulm University, Ulm, GERMANY, 5Department of
explore the relationship between the metabolic patterns and Psychiatry and Psychotherapy II, Ulm University, Ulm, GERMANY,
different PD clinical phenotypes, and whether the metabolic 6
National Institute of Radiological Sciences, Chiba, JAPAN.
characteristics can reflect the PD disease progression, we
investigated the dopamine transporter (DAT) and glucose
metabolic PET imaging in patients with or without tremor. Aim/Introduction: The accumulation of tau protein in the brain
Materials and Methods: 11C-CFT together with 18F-FDG PET/ is a pathological hallmark of many neurodegenerative diseases.
CT scans of 33 consecutive patients with a clinical diagnosis For positron emission tomography (PET) diagnostics, several tau-
of PD and abnormal DAT binding (24 with tremor, 9 without specific radiotracers have been developed in recent years, with
tremor) were analyzed both visually and semiquantitatively. [11C]PBB3 as one of the promising compounds. In this study, we
Results: Caudate dopamine depletion in patients with tremor retrospectively evaluated the first clinical experiences with PBB3
was milder than patients without tremor (P<0.05). Sorted by the in a patient population with suspected neurodegenerative
modified Hoehn-Yahr (H-Y) stage, tremor-dominant PD patients diseases, mostly from the AD and FTLD spectrum. Materials
with an early stage (H-Y: 1-2) showed less caudate dopamine and Methods: The standardized uptake value ratio (SUVr) of
depletion than non-tremor patients (P<0.05); while there were [11C]PBB3 binding was determined for 27 patients based on a
both severer dopamine depletions of anterior and posterior PET/CT examination in the region of individual lobes (frontal,
putamen in tremor-dominant PD patients with a late stage (H- temporal, parietal, occipital) and basal ganglia with cerebellar
Y: 2.5-5) than patients without tremor (P<0.01, respectively). In cortex as reference. Correlations between the SUVr and other
the 18F-FDG PET/CT imaging, the thalamus glucose uptake of clinical tests (mini-mental state examination - MMSE) and
patients with tremor showed more active than non-tremor PD cerebrospinal fluid (CSF) parameters (CSF-Abeta; CSF-tau) were
patients (P<0.001). Conclusion: The dopamine and glucose determined using the Pearson correlation. In addition, in 14
metabolic phenotypes is associated with different clinical PD cases a [11C]PIB PET/CT and in 17 cases a [18F]FDG PET/CT were
subtypes, as caudate dopamine function is less affected in the available for correlation analysis. The final diagnosis was based
early stage of tremor-dominant patient. Multimode imaging on the integration of all clinical and imaging data as well as the
may contribute to elucidate the mechanism of PD motor pattern follow-up of the patients. Results: In 13 patients, no or only a
and provide information of the disease prognosis. References: weak accumulation of [11C]PBB3 was detected (PBB3-negative),
1. Neudorfer C, Hinzke M, Hunsche S, El Majdoub F, Lozano A, while in 14 patients a moderate to pronounced uptake was
Maarouf M. Combined Deep Brain Stimulation of Subthalamic found (PBB3-positive). Based on the visual assessment of tracer
Nucleus and Ventral Intermediate Thalamic Nucleus in Tremor- accumulation, the strongest PBB3 uptake occurred in the
Dominant Parkinson’s Disease Using a Parietal Approach. temporal lobe, followed by the occipital, frontal, and parietal
Neuromodulation. 2019. 2. Zeng Q, Guan X, Guo T, Law Yan lobes. In addition, basal ganglia uptake was observed in all
Lun JCF, Zhou C, Luo X, et al. The Ventral Intermediate Nucleus patients. The determination of the Pearson correlation resulted
Differently Modulates Subtype-Related Networks in Parkinson’s in significant moderate correlations of SUVr for the respective
Disease. Front Neurosci. 2019;13:202. 3. Akakin A, Yilmaz B, lobes with MMSE (frontal: r = -0.54*; occipital r = -0.46*; parietal
Kilic T, Rhoton AL, Jr. Anatomy of the subthalamic nucleus, r = -0.57**) and CSF-tau (occipital r = 0.68*) (*p≤0.05; **p≤0.01).
with correlation of deep brain stimulation [RETRACTED]. J No correlation was found for basal ganglia. All PBB3-negative
Neurosurg. 2015. 4. Eggers C, Kahraman D, Fink GR, Schmidt M, scans were also PIB-negative, while PBB3-positive scans were
Timmermann L. Akinetic-rigid and tremor-dominant Parkinson’s both PIB-positive and -negative. Most PBB3 scans were also
disease patients show different patterns of FP-CIT single photon FDG-positive. Conclusion: Uptake of [11C]PBB3 was most
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S410

pronounced in amyloidogenic neurodegenerative diseases,


such as Alzheimer’s disease, and correlated with CSF-tau. In these Aim/Introduction: Our aims were to test inter-rater agreement
cases, typical uptake patterns were observed corresponding to and concordance between visual and semiquantitative
the neurofibrillary tangle (NFT) stages III-VI. The uptake of [11C] scoring at different amyloid retention levels in Mild Cognitive
PBB3 correlated significantly with MMSE , suggesting that PBB3- Impairment (MCI) patients. Materials and Methods: A sample
PET might be a good parameter for disease severity. However, of 71 amnestic MCI patients (AGE 73.96 ± 7.35 years, MMSE
owing to the generally only moderate intensity of [11C]PBB3 24.23 ± 5.33, CDR-SOB 2.16 ± 2.14) underwent 18F-florbetaben
uptake, the clinical benefit at the individual patient level is still PET/CT and clinical assessment. Amyloid positivity was
unclear and needs to be assessed in further prospective studies. assessed by semiquantitative approach by means of previously
References: None. published threshold (SUV ≥ 1.3). Images were visually scored
as positive or negative by three independent, certified readers
blinded to neuropsychological result. Fleiss kappa coefficient
EP-0060 was used to test inter-reader concordance on the whole
[18F] FBB Cortical Uptake Is Not Related To The Age Of population and on 3 subgroups with low (SUVr <1.1), medium
Onset Of Alzheimer’s Disease (SUVr >1.1 <=1.5) and high (SUVr> 1.5) Aß burden. Results:
A. Chiaravalloti1, A. E. Castellano2, A. Martorana1, M. Ricci3, O. Fleiss’s kappa statistic was k=0.86,P <0.00001 on the whole
Schillaci1; sample. By evaluating the groups with different Aß burden
1
Department of biomedicine and prevention, University separately, the inter-raters agreement changed according to
Tor Vergata, Rome, ITALY, 2IRCCS Neuromed, Pozzilli, ITALY, tracer retention levels:k=0.85,P=0.0001; low Aß burden (SUVr
3
Department of Radiological, Oncological and Pathological <1.1)k=0.48,P=0.0001; medium Aß burden(1.1 <SUVr<=1.5)
Sciences, Sapienza University of Rome, Rome, ITALY. k=0.98,P=0.00001; high Aß burden (SUVr> 1.5) Moreover we
found the lower reliability between visual and unsupervised
evaluation of Aß positivity in the group with moderate retention
Aim/Introduction: To investigate the relationships between levels ranging between SUVr =1.1 and 1.5. Conclusion: Inter-
amyloid burden in brain and the age of onset of Alzheimer’s raters agreement of visual detection of amyloid positivity is
disease (AD), exploring the differences between patients with high in low and high retention levels group but reduces in the
early onset of Alzheimer’s disease (EOAD, aged ≤ 65 years) and range of 1.1<SUVr <=1.5, in these cases the support of semi-
patients with late onset of Alzheimer’s disease (LOAD, aged > quantitative analysis would be necessary to reduce the risk of
65 years). Materials and Methods: We examined 60 patients amyloid positivity misclassification. References: None.
with clinical diagnosis of Alzheimer’s disease according to
NINCDS-ADRDA criteria. Of them 22 were EOAD, and 38
were LOAD. All of them underwent a brain Positron Emission EP-0062
Tomography (PET) scan 90 minutes after the injection of 4-[(E)- Impact of MR-based head motion correction on amyloid
2-[4-[2[2-(2-fluoranylethoxy)ethoxy]ethoxy]phenyl]ethenyl]-N- PET diagnosis - A simultaneous PET/MRI study
methylaniline ([18F] FBB); 300 ± 10 MBq). Qualitative analysis of M. Schürer1, T. Jochimsen1, M. Rullmann1, M. Patt1, S. Tiepolt1, M.
PET data was positive for increased amyloid burden in the brain Schroeter2, C. Weise3, D. Saur3, K. Hoffmann4, O. Sabri1, H. Barthel1;
in all the AD subjects. Relationships between amyloid burden 1
Department of Nuclear Medicine, University of Leipzig
in brain and age of onset of AD were assessed by means of Medical Center, Leipzig, GERMANY, 2Max Planck Institute
Statistical Parametric Mapping (SPM) version 12, with the use of for Human Cognitive and Brain Sciences Leipzig & Clinic
age as regression factor and sex, MiniMental State Examination for Cognitive Neurology, Leipzig, GERMANY, 3Department
(MMSE) as covariates in the regression analysis. Moreover, a of Neurology, University of Leipzig Medical Center, Leipzig,
two-sample t-test was used for comparison between EOAD and GERMANY, 4Department of Neuroradiology, University
LOAD subjects. Results: There were no significant differences of Leipzig Medical Center, Leipzig, GERMANY.
[18F] FBB uptake between EOAD and LOAD patients. Multiple
regression analysis did not show any significant correlation
between age of onset and brain amyloid deposition in AD Aim/Introduction: [18F]Florbetaben amyloid PET/MRI is a
subjects. Conclusion: In our study population, age of onset is useful tool for early and differential dementia diagnosis. It is able
not related to brain amyloid burden in AD patients. Other factors to deliver, in a convenient way, dual amyloid pathology and
may be involved in explaining the clinical differences between neurodegeneration biomarker information [1]. One potential
EOAD and LOAD patients. References: None. additional advantage of simultaneous PET/MR imaging is related
to MR-based movement correction (MoCo) of the PET data
[2]. As head movement can be a relevant problem in imaging
EP-0061 cognitively impaired patients, we initiated the present study to
Impact of tracer retention level on visual classification of evaluate the diagnostic relevance of MoCo in F18-florbetaben
amyloid PET images brain PET/MRI. Materials and Methods: We so far acquired
E. Giovannini, P. Lazzeri, E. Borsò, M. Riondato, A. Ciarmiello; simultaneous [18F]Florbetaben PET/MRI data (300MBq, 90-
Asl5, La Spezia, ITALY. 110min p.i., 3T Siemens mMR) of 13 cognitively impaired patients
S411 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

(5 female, age=64±15yrs). In parallel to the PET acquisition, the acquisition on Symbia T6 dual head gamma camera (Siemens).
vendor-provided BrainCompass MoCo (Biograph mMR E11P, Brain PET images, 3D emission scans of 15 minutes, were
Siemens Healthcare, Germany) was carried out. The MoCo PET acquired 60 min after injection of 5 mCi of FDOPA intravenously
vs. non-MoCo PET data were analyzed visually (standard BAPL on a Biograph mCT (Siemens) PET/CT scanner. Both scans were
scores for amyloid state and 5-point image quality scores) and visually interpreted, SPECT scans before the PET scans and
semi-quantitatively (SUVRs, reference: cerebellar cortex, AAL each independent of the other. Consensus was sought where
template in SPM12). Results: 5/13 patients scored positive in interpretations differed. All the patients were telephonically
the blinded read of the non-MoCo PET images. For the MoCo interviewed to assess clinical outcome and treatment at a
PET images, the BAPL scores were lower in our study population follow up that ranged from 6 months to four years. Results:
as compared to the non-MoCo PET images (1.62±0.96 vs. A concordant result between TTDS and FDOPA PET/CT was
1.77±1.01, p<0.001). In 1/13 patients, binary visual diagnosis obtained in 27/32 patients (84%). 24 of these patients (89%) with
changed from amyloid-positive to -negative via MoCo. MoCo concordance on both modalities concurred with the clinical
led to an increase of image quality as compared to that of the diagnosis and this included 17 patients with PD and 7 with
non-MoCo data (4.38±0.51 vs. 4.00±0.82, p<0.05). The Cohen’s non-neurodegenerative parkinsonism. In the remaining three
d effect sizes for the regional SUVRs between the patients patients (11%) the imaging diagnosis did not concur with the
visually score amyloid-positive vs. -negative were higher for clinical follow-up. Discordant results were seen in 5/32 patients
the MoCo images as compared to the non-MoCo images in (16%). Of these in 2 cases (6.3%), the SPECT results concurred
52/90 VOIs. Analyses of a potential association between the with the clinical follow-up while in the other 3 cases (9.3%),
individual degree of head movement and the individual degree PET correlated better with the clinical follow up. Conclusion:
of PET signal/diagnosis change are ongoing. Conclusion: Concordance of TTDS and FDOPA PET/CT with each other and
These preliminary results might point to a diagnostic benefit the clinical diagnosis is good so TTDS as a single investigation
of MoCo in hybrid amyloid PET/MR imaging. This might be the is useful to evaluate PSDD that characterises PD. When the two
case for both visual (special relevance for primary diagnosis) modalities are discordant FDOPA PET correlates better with the
and semi-quantitative (special relevance for longitudinal clinical outcome. References: None.
assessments) [18F]Florbetaben PET data. Regardless, these
early data encourage investigating more patients employing
this technique. References: [1] Schütz, Lobsien, Fritzsch et al. EP-0064
Feasibility and acceptance of simultaneous amyloid PET/MRI. Diagnostic and prognostic value of FDG-PET in AD
Eur J Nucl Med Mol Imaging 2016;43:2236-2243; [2] Catana, patients with behavioural and psychological symptoms: is
Benner, van der Kouwe et al. MRI-assisted PET motion correction there a specific hypometabolic pattern?
for neurologic studies in an integrated MR-PET scanner. J Nucl V. Berti, C. Ferrari, P. Cappelletto, G. Puccini, C. Polito, G. Lombardi,
Med 2011;52:154-161. G. Lucidi, M. De Cristofaro, A. Passeri, S. Sorbi, R. Sciagrà;
University of Florence, Florence, ITALY.

EP-0063
(99m)Tc-TRODAT-1 SPECT and (18)F-FDOPA PET in Aim/Introduction: Behavioural and psychological symptoms
clinically suspected Parkinson’s disease in dementia (BPSD) represent a heterogeneous group of
V. Baghel, M. Tripathi, N. Damle, H. Goyal, P. Kumar, A. Sharma, C. non-cognitive symptoms and behaviours that could occur in
Bal; patients with Alzheimer’s disease (AD), reducing the quality
All India Institute of Medical Sciences, New Delhi, INDIA. of life. This cross-sectional study investigated the relationships
between BPSD in AD patients and cerebral metabolic activity
as measured by FDG-PET. Our aim is to find a specific pattern
Aim/Introduction: The current study aimed to assess the of hypometabolism in AD patients with BPSD and in patients at
correlation between dopamine transporter imaging (DAT) risk of developing them, in order to use it as a prognostic factor.
using Tc-99m-TRODAT-1 SPECT/CT (TTDS) and FDOPA PET/CT Materials and Methods: Sixty patients with AD diagnosis and
in patients with clinically suspected Parkinson’s disease (PD). brain FDG-PET were included in this study. Among them, 29
The usual protocol followed in our department is to do TTDS subjects were not affected by BPSD (AD-noBPSD), 17 presented
to confirm presynaptic dopaminergic dysfunction (PSDD) in BPSD (in the form of phsycosis, AD-BPSD) and 14 did not present
patients referred with parkinsonism. This is followed by FDOPA BPSD but developed them (psychosis) after 1 year or more (AD-
PET/CT in those cases where the reporting physician was developer).FDG-PET scans of the 3 groups were compared with
not confident in reporting the TTDS and further correlation FDG-PET of 50 controls, and with each other using SPM software
was felt useful. Materials and Methods: We undertook this and multivariate ANOVA routine. Nuisance variables were age
retrospective review in 32 patients with clinical suspicion of in the first analysis, and age and MMSE in the second analysis.
PD who underwent both 99m Tc-TRODAT-1 SPECT/CT scan Results: As compared to controls, all AD patients showed the
and (18)F-FDOPA PET/CT scan in our department between typical AD pattern, with significant hypometabolism in bilateral
2014-2018. SPECT images were acquired 4hrs after intravenous posterior cingulate cortex (PCC) and precuneus, bilateral medial
injection of 20-25 mCi of Tc-99m TRODAT, followed by CT temporal and parieto-temporal cortices. The hypometabolic
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S412

pattern in AD-noBPSD involved mostly PCC and precuneus resulted in 22,6±8,6 for RAVLT, immediate; 71,4±5,9 for RAVLT,
bilaterally, and left inferior parietal lobule and hippocampus. delayed;18,2±10,4 for RCFT, copy; 7,6±6 for RCFT, delayed;
In AD-BPSD, the hypometabolic pattern involved also superior, 18,8±9 (RCPM); 22,2±10,1 for PWF and 44,6±36,2 for Stroop test.
middle and inferior temporal gyri bilaterally, in addition to We found a significant relationship between [18F]FDG uptake
bilateral PCC/precuneus. In AD-developer, the hypometabolic and performance in RAVLT immediate in a large portion of the
pattern involved PCC bilaterally, left parahippocampal gyrus left temporal lobe [positive correlation, Brodmann Area (BA)37
and superior temporal gyrus bilaterally. AD-BPSD showed and BA22) and with RCFT, copy (positive correlation in left and
significant hypometabolism in right middle and superior right BA40 and left and right BA7). We did not find any significant
temporal gyri as compared to AD-noBPSD, and only in middle relationships with other tests. Conclusion: The results of our
temporal gyrus as compared to AD-developer. AD-developer study show that cortical and subcortical glucose consumption
showed significant hypometabolism in bilateral superior is moderately related to the neuropsychological assessment
temporal gyrus as compared to AD-noBPSD. No other clusters in patients with AD thus suggesting a limited impact on data
of significant hypometabolism were found. Conclusion: analysis of brain metabolism in these subjects. References:
Our results suggest a possible role of lateral temporal cortex, None.
especially of the right hemisphere, in the development of BPSD
in AD.The hypometabolic pattern specific of AD-BPSD patients
is characterized by a widespread lateral temporal involvement. EP-0066
Besides, our results could suggest a possible role of superior 123I FP-CIT Image Characteristics in Parkinson’s Disease
temporal hypometabolism as a prognostic signature of future and Lewy Body Dementia
BPSD development, and an association of the progression of A. Nicol1, A. Spratt2, R. Jampana3, D. Grosset3, E. Jackson2, M.
hypometabolism to more anterior temporal regions of the right Sheridan2;
hemisphere with the development of BPSD. References: None. 1
Queen Elizabeth University Hospital, Glasgow, UNITED
KINGDOM, 2NHSGGC, Glasgow, UNITED KINGDOM, 3INS, Queen
Elizabeth University Hospital, Glasgow, UNITED KINGDOM.
EP-0065
Relationships between neuropsychological assessment
and cortical/subcortical [18F] FDG uptake in patients with Aim/Introduction: 123I FP-CIT imaging of striatal dopaminergic
Alzheimer’s disease neuron terminals is used in the diagnostic pathway of
A. Chiaravalloti, D. Di Biagio, A. Martorana, O. Schillaci; Parkinson’s Disease (PD) and Lewy Body dementia (DLB). 123I
Department of Biomedicine and Prevention, FP-CIT scans of a series of consecutive patients with PD or DLB
University Tor Vergata, Rome, ITALY. who had 123I FP-CIT imaging in their diagnostic phase were
assessed. The frequency and characteristics of the patterns of
123
I FP-CIT uptake were determined. Materials and Methods:
Aim/Introduction: The aim of the present study was to Patients were followed up clinically and PD or DLB subsequently
investigate the relationships between cortical and subcortical confirmed. Clinical follow up was also performed on a group
[18]F FDG uptake and neuropschological assessment in a of subjects subsequently determined to have neither PD nor
cohort of subjects with Alzheimer’s disease (AD). Materials and DLB. The 123I FP-CIT scan appearances were assessed visually
Methods: We evaluated 116 subjects with clinical diagnosis of (normal, anterior-posterior gradient or balanced loss) and
AD (males=66;females=50) with a newly diagnosed with AD frequencies compared for the PD and DLB groups. Putamen-
according to the NINCDS-ADRDA criteria. Mean age was 71,4±6 caudate ratios were calculated for the scans classified as normal,
years old. All the subjects underwent a brain PET/CT scan using anterior-posterior gradient and balanced loss. Results: Subjects
[18F]FDG, a complete neuropsychological assessment that with PD (n=19, 14 M, 5 F, mean age 69 (SD 9.3)) had an anterior-
included Mini Mental State Examination (MMSE); Rey Auditory posterior gradient pattern in 95% of cases, with the remaining
Verbal Learning Test, immediate recall (RAVLT immediate); Rey scan a balanced loss. Subjects with DLB (n=13, 9 M, 4 F, mean
Auditory Verbal Learning Test, delayed recall (RAVLT,delayed); age 77 (5.5)) had an anterior-posterior gradient in 46% of cases
Rey Complex Figure Test, copy (RCFT, copy); Rey Complex Figure and a balanced loss in 54% of cases. The frequency of scan
Test, delayed recall (RCFT, delayed); Raven’s Colored Progressive patterns was different for the PD and DLB groups (chi squared
Matrices (RCPM); Phonological Word Fluency Test (PWF) and test of homogeneity, p<0.01). All the subjects subsequently
Stroop test. All the subjects were subjected to a cerebro spinal determined to have neither PD nor DLB (n=22) had a normal
fluid (CSF) assay for amyloid, total tau and phopshorylated tau. 123
I FP-CIT scan. The putamen-caudate ratios of the striata in the
The relationship between brain uptake of [18F] FDG and CSF normal (n=44, mean 0.94, SD 0.07), anterior-posterior gradient
biomarkers was analysed using statistical parametric mapping (n=48, mean 0.75, SD 0.10) and balanced loss (n=16, mean 0.87,
(SPM12; Wellcome Department of Cognitive Neurology, London, SD 0.08) groups were significantly different (ANOVA, p<0.01).
UK) implemented in Matlab R2018a using sex and age and CSF Conclusion: The frequency of 123I FP-CIT scan patterns differs
biomarkers as covariates. Results: The values of CSF amyloid, between PD and DLB. Knowledge of the prevalence of patterns
total tau and phosphorylated tau were respectively 363,6±162, of dopaminergic loss is critically important when clinically
689±338,1 and 92,4±70,7. Neuropsychological assessment evaluating scans. References: None.
S413 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

EP-0067 EP-0068
Usefulness Of Both 18F-FDG And Amyloid PET/CT In Regional brain metabolism assessed by 18F-FDG PET/
Patients With Cognitive Impairment: Is It Always Necessary CT in patients with amnestic mild cognitive impairment:
To Perform Both Of Them? evolutive changes and comparison with11C-PIB PET/CT
M. Martínez de Bourio Allona1, L. Rodriguez-Bel1, J. Mora- J. F. Jimenez-Bonilla1, M. De Arcocha-Torres2, R. Quirce2, I.
Salvadó1, R. Reñé-Ramírez2, J. Gascón-Bayarri2, J. Campdelacreu- Martínez-Rodríguez2, A. Pozueta3, E. Rodríguez-Rodríguez3, P.
Fumado2, J. Robles-Barba1, L. Gràcia-Sánchez1, C. Gámez- Sánchez-Juan3, A. Sánchez-Salmón2, F. Gómez-de la Fuente2, I.
Cenzano1; Banzo2;
1
Department of Nuclear Medicine-PET (IDI). Hospital Universitari 1
Nuclear Medicine Service, Marqués de Valdecilla Universitary
de Bellvitge-IDIBELL, L´Hospitalet de Llobregat (Barcelona), Hospital, Molecular Imaging Group-IDIVAL, University of Cantabria,
SPAIN, 2Department of Neurology. Hospital Universitari de Santander, SPAIN, 2Nuclear Medicine Service, Marqués de
Bellvitge-IDIBELL, L´Hospitalet de Llobregat (Barcelona), SPAIN. Valdecilla Universitary Hospital, Molecular Imaging Group-IDIVAL,
University of Cantabria, Santander, SPAIN, 3Neurology Service,
Marqués de Valdecilla Universitary Hospital, Santander, SPAIN.
Aim/Introduction: The aim of our study was to analyze the
utility of performing both 18F-FDG and amyloid positron
emission tomography (PET/CT) in patients with cognitive Aim/Introduction: The purpose of this work was the evaluation
impairment in order to contribute to the final diagnosis. of the regional brain metabolic pattern in patients with amnestic
Materials and Methods: We performed a retrospective study mild cognitive impairment (a-MCI) assessed by 18F-FDG PET/CT
of 43 patients with cognitive impairment (mean age: 70 years at initial diagnosis and at 5-year outcome, and its correlation
old; 21 men) who had undergone both 18F-FDG and amyloid with clinical evolution and 11C-PIB PET/CT scan. Materials and
PET/CT. 18F-FDG PET/CT was considered abnormal when Methods: The study included 17 a-MCI patients (7 men; mean
pathological cortical and/or subcortical hypometabolism was age: 67 years) who had 18F-FDG and 11C-PIB PET/CT scans at
seen supported by the semiquantitative analysis. The amyloid initial diagnosis and 5 years later. All patients were clinically re-
PET was considered positive or negative using the visual and evaluated at five years. A visual analysis of scans was performed
quantitative analysis (Z-scores). Results: Out of the total patients by 2 experienced nuclear medicine specialists. The following
studied, 70% (30/43) had an abnormal FDG-PET/CT. In 30% cerebral areas were evaluated: cerebellum, temporo-parietal
(9/30) of these, the FDG-PET/CT results were Alzheimer’s disease (TP), occipital, frontal, anterior and posterior cingulated, and
(AD) versus Dementia with Lewy Bodies (DLB). Amyloid PET/CT basal ganglia. Brain 18F-FDG PET/CT distribution was reported as
was positive, with a diffuse pattern, in all of them, confirming AD normal or abnormal. Degrees of glucose hypometabolism were
in most of them. In 27% (8/30) of the cases, the FDG pattern was mild, moderate or severe. 11C-PIB PET/CT cerebral retention
suggestive of frontotemporal dementia (FTD) versus atypical was considered positive or negative. Sensitivity, specificity,
AD. Amyloid PET/CT was positive, confirming atypical AD, in 6 positive predictive value (PPV) and negative predictive
of them and negative in the remaining cases suggesting FTD value (NPV) for Alzheimer’s disease dementia (AD-D) were
and other causes (multifactorial, vascular...). In 7% (2/30) of the calculated considering TP hypometabolism as the key finding
patients, the FDG-PET/CT differential diagnosis was corticobasal for 18F-FDG PET/CT exam. Results: Thirteen out of 17 a-MCI
degeneration (CBD) versus AD: one had a positive amyloid patients evolved to AD-D and 4 out of 17 a-MCI patients did
PET/CT and was finally diagnosed of CBD related to AD. In the not. In the group of 13 patients who developed AD-D, visual
remaining 11 cases (36%) the FDG pattern was non-specific: analysis showed abnormal glucose distribution in 8 (unilateral
one with findings suggestive of vascular disease supported TP hypometabolism in 6 and bilateral TP hypometabolism in 2).
by a negative amyloid study and the others (10/11) with low Two patients had also frontal hypometabolism. All 13 patients
intensity FDG hipometabolism, 6 of them with a negative had positive 11C-PIB PET/CT scans. In the group of 4 patients
amyloid PET/CT and the others with a positive amyloid scan who did not evolved to AD-D, 18F-FDG PET/CT was abnormal
(diagnosed of early stage AD and mixed diseases). FDG-PET/CT in 2 and normal in 2. In these 4 patients, PIB scan was positive
was considered normal in 30% of the patients (13/43). Amyloid in 1 and negative in 3. At 5-year, 18F-FDG PET/CT showed more
PET/CT was positive in 54% of these (7/13) and negative in the extensive glucose hypometabolism in all patients with initial
remaining cases, excluding AD. In the positive cases: 4 were abnormal scan. Moreover, 18F-FDG PET/CT showed severe TP
finally diagnosed of early stage AD, 1 of mixed dementia and hypometabolism in 3 patients with initial normal scan. From
2 had uncertain results. Conclusion: The use of amyloid PET/ these results, 18F-FDG PET/CT has a sensitivity 66.6%, specificity
CT could be avoided if the symptoms, cognitive functioning 50%, PPV 90% and NPV 16.6% for diagnosing AD-D. On the other
examination and FDG-PET/CT are very suggestive of Alzheimer’s side, 11C-PIB PET/CT had a sensitivity 100%, specificity 66%, PPV
disease. Nevertheless, in patients with similar or uncertain FDG 92.8% and NPV 100%. Conclusion: 18F-FDG PET/CT correctly
pattern, it could be useful for making the differential diagnosis predicted the type of dementia being TP hypometabolism the
between AD and other diseases. In the negative FDG cases, most frequent abnormality at initial diagnosis and linked to
more than 50% had a positive amyloid scan which means the evolutive changes of the brain glucose metabolism pattern.
importance of performing the amyloid study in these patients. The association of 18F-FDG with amyloid 11C-PIB PET/CT may
References: None. improve the diagnostic yield for AD-D. References: None.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S414

EP-0069 GREECE, 2Dpt of Nuclear Medicine, “Alexandra” University Hospital,


Imaging and CSF biomarkers for cognitive impairment Athens, GREECE, 3IASIS Third Age Center, Athens, GREECE, 42nd
M. Agudelo, J. Bernal, B. Martinez-Sanchis, P. Sopena-Novales, A. University Neurological Dpt., Attikon Hospital, Athens, GREECE.
Yepes-Agudelo, A. Utrera-Costero, P. Bello-Arques;
Hospital Universitario y Politecnico La Fe, Valencia, SPAIN.
Aim/Introduction: Apathy is one of the most common
neuropsychiatric symptoms in patients with Alzheimer’s disease
Aim/Introduction: The diagnosis of Alzheimer’s disease (AD) affecting up to 80% of patients with moderate cognitive
(AD) is based on postmortem anatomopathological findings. impairment. It is characterized by decreased motivation,
Currently a probable diagnosis of AD in vivo could be suggested initiative and interest, resulting in impaired functioning in daily
based on biomarkers and clinical findings (IWG-2 criteria). living, early institutionalization and poor outcome of patients,
Our aim is to assess the sensitivity and specificity of two as well as in great caregiver distress. Nevertheless, there is great
biomarkers (Amyloid-PET and cerebrospinal fluid (CSF) controversy about its neural underpinnings in the literature
biomarkers) for the detection of AD, taking as a gold standard and its neurobiological basis remains unclear. The aim of this
the final clinical diagnosis in the follow-up by Neurology. Also to study was to evaluate perfusion in Brodmann areas (BAs) in
estimate the concordance and relationship between the findings AD patients with apathy compared with healthy controls in
on Amyloid-PET and CSF biomarkers Materials and Methods: A order to reveal areas associated with this neuropsychiatric
descriptive, retrospective study was carried out on patients with symptom. Materials and Methods: We studied 65 consecutive
cognitive impairment referred to our center, who were evaluated patients (20 men, 45 women, age±SD 69.9±8.1 years, duration
with a brain amyloid-PET (18F-florbetapir, 18F-florbetaben of disease±SD 3.4±2.4 years, education±SD 9.4±4.7 years)
or 18F-flutemetamol) and had a lumbar puncture for CSF from an outpatient Memory Clinic. We used the established
biomarkers between 01/01/2016 and 03/31/2019. The results DSM-IV criteria for the diagnosis of dementia and the specific
of the tests were compared with the final clinical diagnosis established criteria (NINCDS-ADRDA) for the diagnosis of AD. All
in the last available follow-up by Neurology (gold standard), the patients had a neuropsychological evaluation with a battery
standardized for our analysis as AD or not AD (NAD). We found of tests including the mini-mental state examination (MMSE,
61 patients, who were evaluated with brain amyloid-PET. Only 34 mean±SD 19.6±5.5) and the Neuropsychiatric Inventory (NPI,
patients had CSF analysis and clinical follow-up. The mean age apathy mean±SD score 4±4.2). All the patients underwent a
was 68,26 years, 45% of the patients were women. In order to brain SPECT scan 20 min after the intravenous administration
calculate the Kappa coefficient of concordance, sensitivity and of 740MBq of 99mTc-HMPAO. We applied the NeuroGamTM
specificity, the findings of amyloid-PET were classified as positive software on the reconstructed data, for the comparison of brain
or negative for cortical amyloid deposit by visual assessment perfusion in BAs in the right (R) and left (L) hemispheres with
performed by a nuclear medicine specialist and the CSF markers the software’s normal data base consisted of healthy subjects of
were classified as positive if Aβ1-42 was decreased and at least the same age. Results: Compared with normal subjects, apathy
one Tau marker was elevated according to reference values​​ in AD patients was correlated (p=0.05) with hypoperfusion in
of our laboratory (otherwise negative). Results: The amyloid- right anterior prefrontal cortex (BA 10R), dorsolateral prefrontal
PET showed a sensitivity of 100%, specificity of 83,3%, with 2 cortices (BAs 8L, 9LR, 46R), ventral posterior cingulate cortices
false positives. The CSF analysis had a sensitivity of 27,3% and (BA 23LR), left dorsal anterior cingulate cortex (BA 32L), right
specificity of 100%. The weighted Kappa coefficient between entorhinal and perirhinal cortices (BAs 28R, 36R). Conclusion:
amyloid-PET and CSF biomarkers was 0.164 (95% CI). The level Hypoperfusion of frontal and temporal cortices, as well as
of concordance between amyloid-PET and CSF biomarkers was cingulated cortex may be the underlying neural correlates
poor, indicating their complementary value in diagnosing AD. of apathy in AD patients. Functional nuclear imaging may
Conclusion: We found that amyloid-PET has high sensitivity. CSF contribute significantly to the understanding of the causative
biomarkers presented high specificity, but lower sensitivity. Low mechanisms and the improvement of patients’ management.
concordance between both biomarkers was found, supporting References: 1. Theleritis C, Politis A, Siarkos K, Lyketsos CG. A
their combined use as mutually complementary tests in the in review of neuroimaging findings of apathy in Alzheimer’s
vivo diagnostic workup of AD to ensure a better sensitivity and disease. Int Psychogeriatr. 2014;26(2):195-207 2. Rosenberg
specificity. References: None. PB, Nowrangi MA, Lyketsos CG. Neuropsychiatric symptoms in
Alzheimer’s disease: What might be associated brain circuits?
Mol Aspects Med. 2015;43-44:25-37.
EP-0070
Perfusion Correlates Of Apathy In Patients With
Alzheimer’s Disease. A Brain SPECT Study With Brodmann
Areas Mapping
V. Valotassiou1, N. Sifakis2, C. Tzavara1, V. Kamtsadeli3, G.
Angelidis1, E. Lykou3, N. Tsinia3, I. Tsougos1, D. Psimadas1, S.
Papageorgiou4, P. Georgoulias1, J. Papatriantafyllou3;
1
Dpt of Nuclear Medicine, University Hospital of Larissa, Larissa,
S415 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

EP-0071 EP-0072
Assessing the Effect of Noise on the Semi-Quantitative Semi-Quantitation in DaTSCAN SPECT: Preliminary Results
Analysis of Striatal Dopamine Transporter Imaging of a Prospective Comparison of Cadmium Zinc Telluride
E. Hesketh, P. Hillel, S. Redgate, J. Taylor; (CZT) and Sodium Iodide (NaI) Detectors
Medical Imaging and Medical Physics, Sheffield, UNITED KINGDOM. F. Thiele1, J. M. Rogasch1, C. Lange1, W. Schäfer2, J. Eßer2, O. S.
Großer3, H. Amthauer1;
Aim/Introduction: There is conflicting guidance on the 1
Charité – Universitätsmedizin Berlin, Klinik für Nuklearmedizin,
minimum required total counts for optimal SPECT imaging Berlin, GERMANY, 2Kliniken Maria Hilf Mönchengladbach,
of 123I-Ioflupane. The DaTSCAN (GE Healthcare) summary of Klinik für Nuklearmedizin, Mönchengladbach, GERMANY,
product characteristics states 0.5million, SNM guidelines (SNM, 3
Universitätsklinikum Magdeburg A.ö.R., Klinik für Radiologie
2012) recommend >1.5million, and EANM guidelines (EANM, und Nuklearmedizin, Magdeburg, GERMANY.
2009) state >3million. The local average is 1.7±0.54million. A
combination of phantom and patient images were utilised
to determine the required minimum total counts in order to Aim/Introduction: Cadmium zinc telluride (CZT) detectors
avoid noise artefacts adversely affecting semi-quantitative offer improved sensitivity and noise characteristics over NaI
results. Materials and Methods: A novel anthropomorphic detectors with a potential to reduce activity or acquisition
3D-printed phantom (J Taylor et al, 2018) was assembled time. This preliminary analysis of a prospective intraindividual
with layers of radioactive ink patterns on paper, representing comparison of CZT and NaI in dopamine transporter (DaT)
a realistic normal DaTSCAN.The phantom was scanned 8 SPECT with DaTSCANTM focused on the potential for acquisition
times on a standard gamma camera (Discovery 670, GE time reduction. Materials and Methods: Prospective analysis
Healthcare) using the clinical protocol but with 15seconds of 30 patients (20 males; age, 68 [range, 35-83] a) undergoing
per projection. Images were summed together to simulate subsequent SPECT with a CZT and NaI system in a randomized
scans with 30, 45, 60, and 120seconds per projection. order (GE Discovery NM/CT 670 CZT / Pro). SPECT was acquired
A normal patient scan with 3.4million counts was resampled for 30s per angular step (3°) after a median of 3.4 (2.6-4.5) h and
using Poisson resampling software on an Xeleris workstation 4.2 (3.6-4.9) h after injection of 180 (171-191) MBq DaTSCAN.
(GE Healthcare) to simulate images with 3, 2, 1.5, 1, and CZT data were reconstructed (100% acquisition time, CZT100).
0.5million total counts. Three resampled scans were produced CZT list mode data were used to simulate a shortened scan time
with 3, 2, and 1.5million counts each. Ten resampled scans (reduction of 25%, 50%, and 75%, CZT75, CZT50, CZT25). Signal-
were produced with 1 and 0.5million counts. All scans were to-background ratios (SBR) and z-scores were automatically
processed using in-house semi-quantitative software to calculated for 4 regions (left/right caudate nucleus and
calculate specific binding ratios, caudate-putamen ratios, and putamen) using dedicated software (GE DaTQUANT), including
left/right symmetry parameters. Results were compared against a normal database from the Parkinson’s Progression Markers
locally-derived normal ranges. Results: Phantom Acquisitions: Initiative. NaI represented standard of reference. Results: 11/30
Total counts per scan for the 15 seconds per projection datasets patients had reduced putaminal DaT density (NaI z-score < -2).
were ~0.64 million counts per scan; 30 seconds- 1.27 million, 45 SBR and z-scores were each significantly lower with CZT100
seconds- 1.9 million, 60 seconds- 2.56 million, and 120 seconds- than NaI in 4/4 regions (median SBR / z-score difference, -0.22 /
5.1 million. Of the eight 15seconds per projection scans, five -0.51), CZT75 vs. NaI in 2/4 regions (median, -0.23 / -0.53), CZT50
(62.5%) had one or more quantitative parameters outside the vs. NaI in 0/4 regions (median, -0.08 / -0.2), and CZT25 vs. NaI
normal range. Of the four 30seconds per projection scans, one in 3/4 regions (median, +0.17 / +0.43; each p<0.05). The effect
(25%) had an abnormal semi-quantitative parameter. Patient on clinical assessment was evaluated for each region defining a
scan: 60% of the 0.5million and 30% of the 1million counts pathologic z-score < -2. Regardless of the CZT acquisition time,
scans had one or more abnormal semi-quantitative parameters, CZT and NaI results were discordant in ≥1/4 regions in up to
consistent with the rate of abnormality seen in the phantom 6 patients. CZT100 determined pathologic putaminal z-scores
acquisitions. For phantom scans reconstructed to ≥45seconds discordantly to CZT75 and CZT50 in 1/30 patients each. CZT100
per projection (≥1.9million counts) and patient resampled and CZT25 were discordant in 3/30 patients. Conclusion: In this
scans with ≥1.5million counts, all results were within normal preliminary study of patients undergoing DaTSCAN SPECT, CZT
ranges. Conclusion: This study has demonstrated that there resulted in systematically lower SBR than NaI which necessitates
is the potential for misdiagnosis of 123I-Ioflupane studies due separate normal databases. Among different CZT acquisition
to noise artefacts where the total counts acquired are below times, high concordance in determination of pathologic
1.5-2million. In order to achieve a consistent level of counts putaminal activity may allow for acquisition time reduction of at
above this minimum, it may be advisable to implement patient- least 25%. References: None.
specific projection times based on the count-rate from a short
pre-scan acquisition. References: None.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S416

EP-0073 concordance between the results obtained in AP and the FDG-


Periodontal disease and PET amyloid imaging study PET scans positive or dubious for AD and the AP and the NPA
E. Triviño Ibáñez1, M. Gerez-Muñoz2, M. Rashki1, T. Rudolphi- with amnesic cognitive impairment with hippocampal pattern.
Solero1, A. González-Jiménez1, J. Gil-Montoya2, M. Gómez-Río1; Results: 92 amyloid PET imaging were performed (50 men, mean
1
Department of Nuclear Medicine, University Hospital age 67(8sd). Of these, 75% had primary studies, 46% previous
Virgen de las Nieves, Granada, SPAIN, 2School of Dentistry, neurological or psyquiatric disordes, 64% cardiovascular risk
Granada Biohealth Research Institute, Granada, SPAIN. factors, 30% family neurodegenerative background and 56%
changes in RM/TAC . Amyloid PET imaging was positive in 60
patients (65,22%), confirming the suspected diagnosis of AD. Of
Aim/Introduction: Scientific evidence has shown an association these 60, 30 had also undergone FDG PET, and of those 30, 13(
between periodontal disease, a peripheral chronic infectious/ 14%) had a metabolic pattern compatible with AD, 6 a dubious
inflammatory disease, and cognitive impairment, although a pattern, 2 a non-EA but neurodegenerative pattern and 3 had
causative relationship between dementia and periodontitis has no significant hypometabolism. The kappa index between AP
yet to be confirmed. The aim of this study is to determine whether and the group of patients with definitive and dubious FDG-
clinical periodontitis is associated with the neuronal amyloid-β PET was 0,05 CI (-0,38- 0,5). The 92% of the patients with AP
accumulation. Materials and Methods: We have designed positive who were studied with NPA had a amnesic cognitive
a case-control study with cognitive impairment patients who impairment with hippocampal pattern. Kappa index (0,14 ci
meets appropriate use criteria (AUC) to perform PET-amyloid -0.1-0.4).The 13% of the AP positive patients were included in
scan. Periodontitis disease it has been evaluated by measuring pharmacological assays. PET amiloid imaging helped to decide
tooth loss, plaque and bleeding indexes, probing depths, and to initiate pharmacological and cognitive stimulation in 52 and
clinical attachment loss (CAL). Results: At this moment, the 43.7% respectively. Of the 32 AP negative patients, 17 had clinical
study includes 38 dentate adults (mean age: 62.95±7.2 years, and NPA suspition of AD. Follow up will confirm final diagnosis.
52.5% men). Amyloid-PET was positive in 22 patients (57.9%) and Conclusion: PET amyloid was a useful biomarker to confirm
negative in 16 patients (42.1%). According with CAL, the 60.5% the suspected diagnosis of AD in our daily clinical practice and
of patients had periodontitis. The percentage of patients with allowed the prompt instauration of pharmacological treatment
periodontitis who presented a positive result of amyloid PET and cognitive stimulation. References: None.
was higher in comparison with the group of patients without
periodontitis (72.7% vs 27.3% respectively), although there is not
a significant association. Conclusion: Our preliminary results EP-0075
suggest that clinical periodontitis appears to be associated with A pilot study to assess the feasibility of utilising a
positive result of amyloid PET, although results are not at the dedicated cardiac gamma camera based on pin-hole
moment statistically significant. References: None. collimated solid state detectors for Striatal Dopamine
transporter imaging of the brain (DaTscan)
P. Hillel, S. Redgate, E. Lorenz, G. Armitage, J. Taylor, C.
EP-0074 Romanowski, J. Himsworth, S. Wiles;
Implementation of amyloid brain PET imaging biomarker Sheffield Teaching Hospitals NHS Foundation
in the diagnosis of Alzheimer’s disease: our experience in a Trust, Sheffield, UNITED KINGDOM.
non-dedicated dementia clinic
P. Garrastachu Zumaran, P. Santos Holgueras, B. Matute Tobias,
S. Lopez Álava, C. Albornoz Almada, X. Boulvard Chollet, L. Romero Aim/Introduction: The GE Discovery NM 530c (D530c) is a
Robles, F. Cañete Sánchez, A. Cabrera Villegas, R. Delgado-Bolton, dedicated cardiac camera utilising Cadmium-zinc-telluride
R. Ramirez Lasanta; (CZT) detectors to achieve high sensitivity, high spatial
Fundacion Riojasalud. CIBIR, Logroño, Rioja, SPAIN. resolution SPECT images in a 19cm field of view. The study
assesses its use for 123I-Ioflupane imaging. Materials and
Methods: Imaging of an anthropomorphic head phantom
Aim/Introduction: Amyloid PET imaging has been established with fillable striatal inserts was employed to assess feasibility
as a biomarker for Alzheimer disease (AD). We analyse our first and determine the optimal head/scanner orientation and
22 months experience using amyloid brain PET imaging (AP) acquisition/reconstruction parameters. A pilot study was then
in our hospital in patients with mild cognitive impairment performed on 20 patients being investigated for Parkinson’s
(MCI) Materials and Methods: We studied patients with MCI disease or Lewy Body Dementia (17 PD, 3 LBD; Age range 37 -
and suspicion of AD sent to our Department to undergone 90y). Following administration of 185MBq 123I-Ioflupane, patients
AP imaging. Patients underwent an extensive demographic, were scanned on a standard dual-headed gamma camera
neurological, neuropsychological assessment (NPA) and directly before the D530c with acquisition times of 33min and
brain MRI or CT scans. Some of them had also undergone 10min respectively. Patients completed a questionnaire to score
FDG brain PET scan. AP was categorized as positive or for comfort/claustrophobia (1-5) following each scan and all
negative by visual analysis using the rules proposed in each images were blindly reported by four experienced reporters.
of the radiopharmaceutical leaflet.Besides, we analyze the Results: Optimal head orientation was found with the patient
S417 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

positioned erect with the detector arc just above their head. group. The normal range values of brain metabolism for each
This required the patients to be seated on a specially-designed region was considered as the mean SUVr + 2 SD obtained in the
chair with supporting headrest. The shorter acquisition time, control group. For semiquantitative analysis, the SUVr of each
lack of camera movement and unobstructed view meant region in each a-MCI patient was compared to the normal range
patients generally preferred being scanned on the D530. Half values previously established in the control group. Sensitivity,
scored this significantly better for comfort/claustrophobia than specificity and predictive positive value for Alzheimer’s disease
the standard camera whilst the other half found no significant dementia (AD-D) were calculated considering temporo-parietal
difference (significance based on the score differing by 2 or hypometabolism as key finding for visual and semiquantitative
more). The D530c generated mostly high quality scans. Blinded analysis and then, both were compared. Results: Thirteen
reporting revealed diagnostic agreement between scanners a-MCI patients evolved to AD-D and 3 a-MCI patients did not
in 34/40 striata (85%). In 2/6 discordant cases the diagnosis (1 remained as A-MCI, 1 was diagnosed as normal pressure
changed from normal on the standard camera to abnormal on hydrocephallus and 1 as vascular a-MCI). All controls remained
the D530c. In the other 4 cases, reports were equivocal from healthy after 5-year evolution. In the a-MCI who evolved to AD-D
one of the scanners (the D530c in 3/4 of these cases). In 4/6 (n=13), visual analysis showed abnormalities in 8/13 (unilateral
discordant cases, patients had a head tremor that resulted in TP hypometabolism in 6 and bilateral TP hypometabolism in
greater head movement during the D530c scan where their 2; moreover 2 patients associated a frontal hypometabolism).
head was less supported. Conclusion: Using a bespoke chair, The semiquantitative analysis in those patients showed TP
patients could be scanned on the GE Discovery NM 530c cardiac hypometabolism in 10/13 (unilateral TP hypometabolism
camera to obtain high quality 123I-Ioflupane brain scans. Overall, in 5, bilateral TP hypometabolism in 5; moreover, frontal
patients found this camera less claustrophobic compared with hypometabolism in 12/13; posterior cingulate hypometabolism
a traditional camera. Images showed good agreement with in 4 and occipital hypometabolism in 5). In the a-MCI who did
those obtained from the standard camera. Discordant cases are not evolved to AD-D (n=3), visual analysis did not show any
thought to be mainly due to greater head movement during abnormality and semiquantitative analysis showed unilateral
the D530c scan as well as possible noise artefacts. Further TP hypometabolism in 1, and frontal hypometabolism in 2/3.
investigation is warranted using a slightly longer imaging time Sensitivity, specificity and PPV of 18F-FDG PET/CT to diagnose
and a re-designed imaging chair affording greater head stability. AD-D were 61.5%, 66% and 88% for visual analysis and 76.9%,
References: None. 33.3% and 83% for semiquantitative analysis. Conclusion:
18
F-FDG PET/CT showed a limited prognostic value for AD-D in
a-MCI patients. Visual and semiquantitative analysis provided
EP-0076 similar PPV. The meaning of frontal, posterior cingulate and
Visual and semiquantitative analysis of regional brain occipital abnormalities deserves deeper studies. A combination
metabolism in patients with amnestic mild cognitive with amyloid PET/CT may be desirable for this purpose.
impairment assessed by 18F-FDG PET/CT: prognostic value References: None.
after 5 years of evolution
J. F. Jimenez-Bonilla1, R. Quirce1, M. De Arcocha-Torres1, I.
Martínez-Rodríguez1, S. López-García2, E. Rodríguez-Rodríguez2, EP-0077
P. Sánchez-Juan2, N. Martínez-Amador1, A. Sánchez-Salmón1, F. Changes of Cerebral Glucose Metabolism in Semantic
Gómez-de la Fuente1, I. Banzo1; Dementia: a 18F-FDG PET Study
1
Nuclear Medicine Service, Marqués de Valdecilla University J. Lu1, K. Chen2, J. Ge1, Y. Zhu1, J. Xiao1, C. Zuo1, Q. Guo3, P. Wu1;
Hospital, Molecular Imaging Group-IDIVAL, University of 1
PET Center, Huashan Hospital, Fudan University, Shanghai,
Cantabria, Santander, SPAIN, 2Neurology Service, Marqués CHINA, 2Department of Neurology, Huashan Hospital, Fudan
de Valdecilla University Hospital, Santander, SPAIN. University, Shanghai, CHINA, 3Department of Geriatrics, Sixth
People’s Hospital, Shanghai Jiao Tong University, Shanghai, CHINA.

Aim/Introduction: To evaluate the regional brain metabolic


pattern in patients with amnestic mild cognitive impairment Aim/Introduction: Semantic dementia (SD), characterized
(a-MCI) assessed by 18F-FDG PET/CT and to correlate it with by progressive loss of semantic knowledge and relative
clinical evolution. Materials and Methods: Sixteen a-MCI preservation of grammatical aspects of language and episodic
patients (7 men; mean age: 67 years) and six healthy controls memory, is part of the disease spectrum of frontotemporal
(3 men; mean age: 62 years) underwent 18F-FDG PET/CT after lobar degeneration (FTLD). MRI is the most widely used method
30 minutes of i.v. injection of 185 MBq 18F-FDG and clinically to detect the characteristic anterior temporal lobe atrophy.
re-evaluated five years later. Cerebellum, temporo-parietal, Glucose metabolism of SD was seldom explored. This study
occipital, frontal, anterior and posterior cingulate areas and aimed to investigate whether there were distinctive metabolic
basal ganglia were visual and semi-quantitatively analyzed. changes in SD patients using 18F-FDG PET imaging. Materials
Using the cerebellum as reference region, SUV ratios (SUVr) and Methods: 15 SD (5 with predominance of right and 10 with
for each region were calculated in patients and controls. Mean predominance of left temporal atrophy) and 15 age-/gender-
of SUVr (mean SUVr) in regions was obtained in the control matched normal controls were enrolled. All subjects underwent
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S418

18
F-FDG PET and structural T1 MRI within 3 months in Huashan period. 16 Diabetic patients were identified. Of these 16, 6
hospital, Shanghai, China. SPM 8 software implemented in had an abnormal study and 10 were considered negative for
Matlab8.4 was used for analysis. Scans with atrophy mainly the presence of a neurodegenerative dementia. Of the 152
located in the right hemisphere were flipped so that all patients patients, global hypometabolism was reported in 7 patients,
had the left hemisphere of the brain as the major affected side. 5 of which were diabetic. Conclusion: There is an increased
Each PET image was co-registered to individual structural T1 prevalence of global hypometabolism in diabetic patients,
MRI and anatomically normalized into MNI152 standard space despite a normal blood glucose at the time of scanning. This can
using DARTEL, and then smoothed. FDG Two-sample t test prove to be challenging and mask the characteristic patterns
model was used to explore the regional metabolic differences of hypometabolism that support the presence of an intrinsic
between two groups. Voxel threshold was set at P < 0.001 neurodegenerative dementia. References: None.
(uncorrected). Clusters were also searched at FWE-corrected
P < 0.05 level. A 4-mm radius spherical value of interest (VOI)
was used to calculated the regional cerebral metabolic rate EP-0079
of glucose (rCMRglc) with ScanVP 7.1software. Results: Amyloid PET/CT for the diagnosis of Alzheimer’s disease
Compared to normal controls, SD patients showed decreased dementia and other dementias in patients with cognitive
glucose metabolism in left temporal lobe (BA 21) and bilateral impairment and its relationship with cognitive functioning
parahippocampal gyrus while increased in bilateral frontal lobe L. Rodriguez-Bel1,2, M. Martínez de Bourio-Allona1,3, J. Mora-
(BA 4,6,9), bilateral parietal lobe (BA 3), bilateral occipital lobe (BA Salvadó1,2, I. Rico-Pons4,2, R. Reñé-Ramírez5,2, J. Gascón-Bayarri5,2,
18) and right cerebellum(P<0.001, uncorrected). Left temporal E. Llinares-Tello1,2, I. Sánchez-Rodríguez1,2, J. Vercher-Conejero1,2, C.
lobe (BA 21), left parahippocampal gyrus, right frontal lobe (BA Gámez-Cenzano1,2;
6), right parietal lobe (BA 3), bilateral occipital lobe (BA18) and 1
PET-Unit. Department of Nuclear Medicine, L’Hospitalet
right cerebellum were survived at FWE P<0.05. As for rCMRgIc, De Llobregat. Barcelona, SPAIN, 2Hospital Universitari de
right parahippocampal gyrus and the regions survived at FEW Bellvitge-IDIBELL, Barcelona, SPAIN, 3Hospital Univertario de
P<0.05 except right occipital lobe (BA 18) showed significant Bellvitge-IDIBELL, Barcelona, SPAIN, 4Department of Neurology,
differences (P<0.05, student t-test) between two groups, while L’Hospitalet De Llobregat. Barcelona, SPAIN, 5Department of
differences in the rest regions were insignificant(P>0.05, student Neurology, L’Hospitalet De Llobregat. Barcelona, SPAIN.
t-test). Conclusion: Our study showed that SD patients had
distinctive metabolic characteristics. 18F-FDG PET might offer
help in differential diagnosis of SD and other variants of FTLD, Aim/Introduction: Diagnosis of Alzheimer’s disease (AD)
and even probable Alzheimer’s disease. It may provide a new combines clinical criteria with biological markers. This study
perspective for understanding brain regions involved in lexical aimed to investigate the usefulness of amyloid positron emission
and semantic processing. Future studies were needed to verify tomography (PET) in the diagnosis of patients with cognitive
these observations. References: None. impairment and its relationship with cognitive functioning.
Materials and Methods: Eighty subjects were enrolled in the
study (mean age: 69 years; range: 54-79y), including 58 Mild
EP-0078 cognitive impairment (MCI), 11 dementia due to AD, 8 Atypical
Are there limitations in reporting brain PET for suspected AD versus frontotemporal Dementia (FTD) and 3 possible non-
neurodegenerative dementia in diabetic patients? AD dementia patients. They underwent 18F-Flutemetamol
K. Mullin; PET/CT and an extensive cognitive functioning (MMSE and
Belfast Health and Social Care Trust, Belfast, UNITED KINGDOM. the Neuropsychological examination). The amyloid PET were
dichotomized as positive or negative based on the visual PET
reading and using a quantitative analysis (Z-scores). Results:
Aim/Introduction: Interpretation of 18F FDG PET CT brain in Amyloid PET was positive in 50% of patients, mostly of them
patients with suspected neurodegenerative dementia relies on presenting a clinical MCI (amnestic subtype). The final clinical
the patterns of hypometabolism in the brain. In our institution diagnosis according positive amyloid PETand additional clinical
we noted patterns of global hypometabolism, many of which workup,was suggestive for dementia highly likely due to AD in
appeared to be associated with diabetic patients, therefore 67,5 %, MCI due to AD with high likelihood in 30%, and Lewy
we undertook a retrospective analysis to review these studies Body Dementia in 2,5% of patients. In the dementia AD group,
and identify any emerging trends. Materials and Methods: 63% of patients presented typical-AD, 22,2% atypical-AD and
We conducted a review of all 18F FDG PET CT brain performed 14,8% mixed forms. Atypical variants of AD included: aphasic
over a six month period. Diabetic patients and those patients variants of AD , posterior cortical atrophy (PCA) and corticobasal
reported with ‘global hypometabolism’ were evaluated further syndrome underlying AD (CBS-AD). Positive amyloid PET studies
and information was obtained, including diabetic treatment, showed a diffuse pattern and there were no differences in
blood glucose level at the time of scanning and any further the distribution and intensity of amyloid deposition between
relevant clinical history. We compared findings from visual different diagnostic groups. Mean MMSE was 21,8 (range 10-28)
interpretation alongside computer assisted diagnostic software. and the Neuropsychological examination showed a moderate
Results: 152 PET brain scans were performed over a 6 month or severe cognitive impairment in 67% of patients with a
S419 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

Global Deficit Score (GDS: 4-5). In the negative amyloid group, and temporo-mesial, temporo-lateral and cerebellum reduced
the exclusion of AD diagnosis as a possible cause of cognitive uptake in the other, thus confirming CBD clinical suspect. Group
impairment was made. Mean MMSE was 25,9 (range 14-30) and 3: frontal and prefrontal hypometabolism in one case and
the neuropsychological examination showed a mild cognitive temporo-parietal in the remaining one possibly attributable to
impairment in 66% of patients (GDS: 3). Conclusion: The use AD in discordance with clinical symptoms (balance disturbance,
of amyloid PET was associated with improved diagnostic ideomotor slowing with frontal aspects). Group 4: temporo-
confidence, change in diagnosis and change in patient occipital hypometabolism in accordance with initially suspected
management in a majority of patients with MCI and patients with LBD in one case and prefrontal reduced uptake compatible
dementia. The most frequent change in clinical management with CCS in the other case with suspected MSA. Conclusion:
involved the use of Alzheimer disease drugs. Amyloid PET was 18
F-FDG PET could be useful in correct CCS classification in APS
useful for discriminate AD dementia from non-AD dementia patients since, in our casuistry although modest, the procedure
such as frontotemporal dementia. Nevertheless, the pattern confirmed the cognitive disorder clinical suspect in 77.7%
of amyloid deposition was not useful for discriminate MCI due of patients, while it excluded the presence or suggested an
to AD from typical or atypical forms of AD. Neuropsychological alternative diagnosis in respect of initial clinical classification in
examination was closed related to amyloid PET results and was 22.3% of cases. According to these data an adequate cognitive
helpful in the final diagnosis. References: None. disorder treatment has been started and the follow up with
clinical and 18F-FDG PET evaluations is currently in progress.
References: None.
EP-0080
Brain 18F-FDG PET qualitative and quantitative analyses
in Atypical Parkinsonian Syndromes (APS) with Cognitive EP-0081
Clinical Symptoms (CCS) Assessing the Impact of Alternative 123I Ioflupane Imaging
S. F. Nuvoli1, M. R. Piras2, G. Tanda1, A. Lazzarato1, A. Spanu1, G. Protocols on Image Interpretation for Complex Patients
Madeddu1; E. Hesketh, J. Taylor;
1
University of Sassari, Unit of Nuclear Medicine, Sassari, ITALY, Medical Imaging and Medical Physics, Sheffield, UNITED KINGDOM.
2
University of Sassari, Unit of Neurology, Sassari, ITALY.

Aim/Introduction: The aim of this study was to identify


Aim/Introduction: APS diagnosis is generally based on alternative 123I Ioflupane (DaTSCAN, GE Healthcare) scanning
clinical criteria but often symptoms and signs may overlap in protocols that would be more tolerable for complex patients
the different forms and particularly when cognitive disorders including those with excessive spine curvature (kyphosis), and
are present. Recent data suggest that brain 18F-FDG PET could claustrophobia. Phantom scans were performed to establish a
support clinical diagnosis since specific metabolic patterns are suitable protocol that produces images of a similar diagnostic
described.We further evaluated 18F-FDG PET clinical usefulness quality to those from the standard protocol. Materials and
in the diagnosis of CCS in APS patients. Materials and Methods: Five alternative scanning protocols were identified;
Methods: We investigated 18 consecutive patients with clinical 180° L-mode and 180° extended-detector H (EDH)-mode (A.
symptoms attributable to APS already also ascertained with 123I Notghi et al, 2010), standard protocol with increased detector
Ioflupane SPECT; moreover, each of these also referred slight to separation (kyphosis protocol), single-detector planar at
severe CCS. In particular, according to clinical and SPECT data, vertex of skull, and a solid-state dedicated cardiac camera (CC)
patients were classified in different groups:12/18 with evident seated protocol (Hillel and Redgate, 2019). A novel 3D-printed
signs of extrapyramidal disorders (Group 1), 2 with suspected anthropomorphic phantom (J Taylor et al, 2018) was constructed
corticobasal degeneration (CBD) Group 2), 2 with movement twice to represent a normal and a subtly abnormal pattern of
disorders and suspected behavior disorders (Group 3), and one tracer uptake. The phantom uses alternating attenuation slabs
of the remaining 2 cases had a suspect Lewy bodies dementia and paper built up into a head shape. The paper is printed with
(LBD) with visual hallucinations and the other one a multisystem radioactive ink patterns that realistically represent striatal tracer
atrophy (MSA) with ideomotor slowdown (Group 4). All uptake. Each phantom was scanned on a standard gamma
patients underwent brain 18F-FDG PET/CT using GE Discovery camera (Discovery 670, GE Healthcare) using the standard
tomograph. Images were evaluated both qualitatively and 30-minute H-mode clinical protocol, alternative protocols, and
quantitatively with automated analysis program (Cortex Suite, on the cardiac camera. A group of 4 reporters scored the images
GE Healthcare); brain metabolic map and normal age matched on image quality, and diagnosis confidence where a score of 1 =
control group comparative analysis was produced. Results: “definitely abnormal”, 3 = “equivocal”, and 5 = “definitely normal”.
18
F-FDG PET showed different bilateral cortical hypometabolism These were compared to scores for the standard protocol,
patterns in the different groups. Group 1: 9/12 cases had and that which scored most closely was deemed the best
reduced 18FDG uptake in prefrontal and temporo-parietal areas alternative protocol. Results: Image quality was rated “good”
attributable to Alzheimer Disease (AD), while the remaining for the standard and CC protocols, “poor - satisfactory” for EDH-
3/12 cases had normal metabolism despite CCS. Group 2: mode, kyphosis, and L-mode protocols, and “unacceptable” for
prefrontal and superior parietal hypometabolism in one case the vertex protocol. Diagnosis confidence scores for the normal
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S420

phantom were: standard protocol= 4.6±0.5, CC= 5±0, kyphosis= one. In the other 11/18 (61%) had a previous complementary
3.4±0.9, EDH-mode= 3±1, L-mode= 2.8±1.3, vertex= 3±0. For imaging test not suggesting Alzheimer disease, and this one
the subtly abnormal phantom; standard protocol= 2.3±1.2, was ruled out in 10/11. Finally the amyloid PET was a helpful tool
CC= 2±1.1, kyphosis= 1.8±0.7, EDH-mode= 1.6±0.9, L-mode= in 15/46 (32,6%) to have a more certain diagnosis of Alzheimer
3±1.1. EDH-mode protocol acquired 50% fewer counts than disease. Conclusion: PET/CT amyloid is a valuable tool for the
the standard protocol. Conclusion: The CC protocol rated diagnosis of Alzheimer’s disease. It is capable of identifying a
most consistently with the standard protocol so is suggested suspicious diagnosis in 32,6% of the patients, having a potential
as a suitable comfortable alternative for patients with impact in therapeutic management. References: None.
claustrophobia and/or kyphosis. Both EDH-mode and L-mode
protocols rated poorly therefore further work is required to
determine a suitable alternative if no cardiac camera is available. EP-0083
References: A. Notghi et al, “Acquiring diagnostic DaTSCAN Prognostic Value Of Brain Perfusion Spect In Patients With
images in claustrophobic or difficult patients using a 180degree Atrial Fibrillation And Dementia
configuration,” NMC, vol.31, no.3, pp.217-226, 2010.J.Taylor et al, H. Hashimoto, R. Nakanishi, S. Mizumura, Y. Hashimoto, Y.
“The subresolution DaTSCAN phantom: a cost-effective, flexible Okamura, K. Yamanaka, T. Ikeda;
alternative to traditional phantom technology,” NMC, vol39, Toho University Faculty of Medicine, Tokyo, Japan,
pp268-275, 2018. Oomori-nishi/Ootaku/Tokyo, JAPAN.

EP-0082 Aim/Introduction: Atrial fibrillation (AF) is the most common


Contribution of the amyloid-PET to diagnosis Alzheimer cardiac arrhythmia, and those afflicted have reduced quality of
disease life, functional status, and cardiac performance. The patients with
S. Perez Quiros, B. Rodriguez Alfonso, S. Seijas Marcos, A. Sanfiel AF have a high risk of coronary heart disease and cardiovascular
Delgado, M. Mitjavila Casanovas; disease. Although the prevalence of AF is increasing, cognitive
Hospital Puerta de Hierro, Majadahonda, SPAIN. disorders are also on the rise in tandem with the aging of the
population. The patients with dementia have also experienced
lower the quality of life and have increased mortality.
Aim/Introduction: Alzheimer’s disease has a high social impact Technetium 99m ECD brain perfusion single photon emission
for patients and their environment. Due to this is very important computed tomography (99mTc-ECD brain perfusion SPECT) is
to have an early diagnosis in order to reduce its symptoms. The a useful modality for diagnosing dementia and identifying high
diagnosis is mainly made by clinical factors, although there are risk patients with mild cognitive impairment. However, there are
also available complementary imaging tests supporting the few reports about the relationship between the value of Z score
diagnosis for the neurology. The aim of our study is to analyze calculated by 99mTc-ECD brain perfusion SPECT and prognosis
the contribution of the amyloid-PET to finding a final diagnosis in of patients with AF and dementia. The aim of this study was
patients with possibility of having Alzheimer’s disease. Materials to evaluate the prognostic value of brain perfusion using
and Methods: This observational retrospective study includes 99mTc-ECD SPECT in patients with AF and dementia. Materials
all amyloid studies which could be an Alzheimer’s disease, and Methods: Among 405 consecutive patients who were
having a previous complementary imaging brain test (18F-FDG- diagnosed as AF in cardiac outpatients and as dementia using
PET/TC or 99mTc-HMPAO-SPECT) from December/2014 until Mini-Mental State Examination by neurologists or psychiatrists,
nowadays. Results from both diagnostic test was compared. we identified 170 patients (81±10 years) who underwent
A final diagnostic was established by the neurology, with a 99mTc-ECD brain perfusion SPECT. Of those, 73, 73, and 24 were
18 months follow-up. We analyze if the diagnosis accuracy diagnosed as Alzheimer’s dementia (AD), vascular dementia
percentage was influenced by the amyloid data. Results: (VD), and non-specified dementia respectively. Multivariate Cox
The inclusion criteria was in 46 studies. The average age of model was used to assess if higher Z score by 99mTc-ECD brain
the patients was 60 years old. 82,6% of the patients had a perfusion SPECT and clinical parameters were associated with
SPECT-HMPAO previous and 76% of the patients had a FDG- major adverse cardiovascular events (MACE) including cardiac
PET with or without SPECT. The amyloid PET was positive in death, myocardial infarction, hospitalization for heart failure,
28/46 of patients (61%). 18/28 of these patients had a previous and stroke. Sub-analyses of multivariate Cox models by AD or
complementary imaging test suggesting posterior neurological VD were also assessed. Results: During a mean follow-up of
disease (64%). All these patients were finally confirmed with 1258±1044 days, 62 MACE occurred. There was not significant
Alzheimer disease. The other 10 studies were not conclusive difference of MACE between AD and VD (33%, vs. 44%, p=0.153).
for posterior neurological disease (36%). 9/10 of patients were By multivariable Cox model, the higher Z score of temporal-
finally confirmed with Alzheimer disease, ando 1/10 of patients occipital-pariental lobe was associated with increased MACE
has “esclerosis mesial temporal”. The amyloid PET was negative compared to the lower group (HR 2.521, 95% CI 1.465-4.337, p
in 18/46 of patients (39%). 7/18 of these patients (39%) had a < 0.001). In a sub-analysis of patients with AD, Z score was the
previous complementary imaging test suggesting posterior most significant prognostic factor for MACE (HR 3.969, 95% CI
neurological disease, but confirming Alzheimer disease just in 1.374-11.468, p=0.011). The similar trend was observed in those
S421 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

with VD (HR 2.247, 95% CI 1.028-4.913, p=0.043). Conclusion: EP-0085


This study demonstrated that the Z score of temporal-occipital- A MRI-PET study between behavioral variant
pariental lobe could be a potential prognostic value among Frontotemporal Dementia and elderly Bipolar Disorder
patients with AF and dementia, regardless of type of dementia. G. Marotta, G. Delvecchio, G. M. Mandolini, A. Arighi, C. Prunas, M.
References: None. C. Mauri, A. M. Pietroboni, C. Cinnante, F. M. Triulzi, E. Scarpini, C.
Altamura, P. Brambilla;
Fondazione IRCCS Ca’ Granda Ospedale Maggiore
EP-0084 Policlinico, University of Milan, Milano, ITALY.
Application of the 2018 NIA-AA Research Framework to a
large cohort of patients with cognitive impairment
G. Marotta, T. Carandini, A. Arighi, G. G. Fumagalli, A. M. Pietroboni, Aim/Introduction: Elderly Bipolar Disorder (BD) and Behavioral
L. Ghezzi, A. Colombi, M. Scarioni, C. Fenoglio, M. A. De Riz, E. Variant of Frontotemporal Dementia (bvFTD) may exhibit similar
Scarpini, D. Galimberti; symptoms and both disorders are characterized by selective
Fondazione IRCCS Ca’ Granda Ospedale abnormalities in cortical and subcortical regions that are
Maggiore Policlinico, Milano, ITALY. associated with cognitive and emotional impairments.Aim of the
study is to investigate common and distinct neural substrates
of BD vs bvFTD by coupling, positron emission tomography
Aim/Introduction: The 2018 NIA-AA Research Framework (PET) and magnetic resonance imaging (MRI). Materials and
use biological biomarkers to define Alzheimer’s disease (AD) Methods: FDG-PET and MRI scans were acquired for 23 bvFTD
by its underlying pathologic process. Our aims were to assess patients with mild cognitive impairments, 16 elderly BD patients
the applicability of the 2018 NIA-AA Research Framework to and 68 healthy controls (48 for PET and 20 for MRI analyses).
a large cohort of patients with cognitive impairment (CI), and PET scans were obtained with a Biograph Truepoint 64 PET/
to evaluate correspondence between cerebrospinal fluid CT scanner. MR images were acquired using a 3-Tesla Philips
(CSF) and positron emission tomography (PET) biomarkers of Achieva MRI scanner. For PET analyses, all FDG-PET images
Aβ deposition. Materials and Methods: We retrospectively were subjected to affine and nonlinear spatial normalization
analysed all patients who underwent CSF analysis from 2011 into the MNI space with SPM12 using the dementia-optimized
to 2017 in our Centre, receiving a diagnosis of CI, according to brain FDG-PET template and smoothed with an 8-mm Gaussian
their clinical follow-up and neuroimaging. Patients were divided filter. For VBM analyses, all T1-weighted images were segmented
according to their CSF biomarkers, as defined by 2018-NIA-AA- and Dartel tools were then used to determine the nonlinear
RF. Prevalence of Normal, AD-continuum and Non-AD profiles deformations for registering the GM and white matter images of
in each clinical syndrome was calculated. When available, all subjects, and the resulting images were spatially normalized
Aβ pathology was evaluated also with florbetapir-PET and into the MNI space and smoothed with an 6-mm Gaussian
correlation between PET and CSF data was performed. Results: filter. Inference on the GM volumes and metabolic differences
CSF data were available from 628 patients. CSF analysis was between groups was made using double-sided t-tests with a
available from 628 patients, of whom 49 underwent florbetapir- threshold of p<0.0 01. Results: bvFTD and BD patients exhibit
PET within 12 months. MRI/PET co-registration was obtained different localization of gray matter (GM) reductions in the
in 39 patients. Almost all patients with a positive florbetapir- lateral prefrontal cortex (PFC), with the first group showing GM
PET 89% was classified as AD-continuum by their CSF data, decrease in the ventrolateral PFC and the latter group showing
8% as non-AD, and 3% as Normal. Conversely, 43% and 28.5% GM reduction in the dorsolateral PFC and unique alterations
of subjects with negative florbetapir-PET had Non-AD and within the orbitofrontal cortex. The bvFTD group also displayed
Normal CSF profiles, respectively, but 28.5% was AD-continuum. unique volumetric shrinkage in regions within the temporo-
Among patients diagnosed of AD, 87.3% were AD-continuum, parietal network together with greater metabolic impairments
whereas 11.3% were Non-AD. The AD-continuum profile was within the temporal cortex and more extensive volumetric and
found also in 12% of frontotemporal dementia, 40% of Lewy metabolic abnormalities within the limbic lobe. Finally, while
bodies dementia, 16% of atypical parkinsonism, and 32% of the BD group showed greater GM volumes in caudate nucleus,
vascular dementia. Amnesic MCI displayed a higher prevalence bvFTD subjects displayed lower metabolism. Conclusion: The
of AD-continuum compared to not amnesic (56.6% versus study explored structural and functional abnormalities in bvFTD
36.4%). 50% of patients with negative FBP-PET were classified and elderly BD patients, with the final aim of identifying the
as AD-continuum according to CSF analysis, and no correlation specific biological signature of these disorders, which might
between PET data and CSF Aβ levels was found. Conclusion: have important implications not only in prevention but also in
The AD continuum profile resulted a sensitive, but not specific, differentiating diagnosis and treatment. References: None.
biomarker in detecting AD pathology. The incomplete
agreement we found between CSF and PET Aβ biomarkers
suggests that they are not perfectly interchangeable to quantify
the Aβ burden, possibly because they assess different features
of AD pathology. References: None.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S422

EP-0086 EP-0087
A Comparative PET Study for Assessing Abnormal Retinal and brain tau deposition evaluated by
Metabolic Brain Network Activity in Dementia with Lewy 18
F-Flortaucipir and its correlation with AD biomarkers in
Bodies and Parkinson’s Disease CSF
P. Wu1, J. Ge1, L. Li1, Y. Zhu1, J. Xiao1, Q. Guo2, C. Zuo1; M. Meyer1, O. Rouaud1, G. Allenbach1, M. Nicod-Lalonde1, V.
1
PET center, Huashan Hospital, Fudan University, Shanghai, Garibotto2, A. Ampuero1, G. Frisoni2, N. Schaefer1, J. Demonet1, J. O.
CHINA, 2Department of Geriatrics, Sixth People’s Hospital, Prior1;
Shanghai Jiao Tong University, Shanghai, CHINA. 1
Lausanne University Hospital and University of Lausanne,
Lausanne, SWITZERLAND, 2University Hospitals of Geneva, Faculty
of Medicine and University of Geneva, Geneva, SWITZERLAND.
Aim/Introduction: It has been debated for decades whether
Dementia with Lewy bodies (DLB) and Parkinson’s Disease (PD)
are the same disorder. Previous studies with FDG PET have Aim/Introduction: The retina shares many common features
demonstrated PD is associated with a specific spatial covariance with brain tissue, and changes in retinal neurons might
pattern (PDRP) and its individual expression could be used mirror brain pathology. Previous studies have investigated
for differential diagnosis with atypical parkinsonism (multiple the presence of pathological changes in human retinas in
system atrophy and progressive supranuclear palsy) [1], In this Alzheimer disease (AD). However, the detection of these
study, we aimed to investigate whether an analogous pattern changes was not consistent across studies. The aim of our study
exists in DLB patients and how it characterizes the boundary was to quantify 18F-Flortaucipir in the retina and to investigate
issues between DLB and PD. Materials and Methods: We any correlation with brain tau deposition and AD biomarkers
prospectively recruited 20 DLB patients and 20 age-/gender- in Cerebro-Spinal Fluid (CSF). Materials and Methods: We
matched healthy subjects to perform FDG PET imaging. 33 prospectively analyzed 18F-Flortaucipir PET/CT examinations
PD patients and 33 age-/gender-matched healthy subjects from October 2018 to April 2019 (Siemens Biograph Vision 600).
used to identify the PDRP [2] were also enrolled. DLB-related We measured retinal SUVmax, SUVmean and SUVratio (SUVR)
pattern (DLBRP) was identified by using SSM/PCA toolbox in the using the cerebellar grey matter as a reference, on static images
DLB patients and corresponding control subjects. The DLBRP acquired 75 to 105 minutes after the injection of 180 MBq of
was determined from a linear combination of select principal 18
F-Flortaucipir. All brain regions of interest PET data were also
components (PCs) whose expression in individual scans gave the converted to SUVRs using the cerebellar grey as a reference. A
maximum separation between the patient and control groups. composite brain SUVR was calculated by averaging the SUVR of
For each pattern (DLBRP&PDRP), the individual expression was 6 cortical regions (frontal, occipital, parietal, lateral temporal and
computed and compared between groups. Results: For DLBRP posterior and anterior cingulate cortex regions). AD biomarkers
identification, the first 3 PCs accounted for 57% of the subject in CSF were collected for each patient (total-tau, phospho-
× voxel variance. A logistic regression model including PC1 and tau and αβ-42). Correlation used the Spearman ρ. Results: 12
PC3 yielded the lowest Akaike information criterion (AIC) value patients with cognitive impairment due to AD or suspected
and their linear combination was disease-related, i.e., subject non-Alzheimers’ pathology (SNAP) were included. 7 presented
scores for this pattern best discriminated the two subject groups pathological brain tau deposition and 5 patients presented
(P<0.001). DLBRP was characterized by metabolic increases normal brain tau deposition, on the basis of visual inspection
in the bilateral putamen, premotor cortex and cerebellum of PET images. Retinal SUVmax ranged from 1.41 to 4.99, retinal
accompanied by metabolic decreases in the bilateral caudate, SUVmean from 0.79 to 2.58 and retinal SUVR from 1.21 to 3.97.
thalamus, posterior cingulate and bilateral parietal-occipital There was no difference concerning retinal SUVmax, SUVmean
regions. The topographic characteristics of DLBRP were similar and SUVR between patients with normal and pathological brain
to that of PDRP, but with an overall wider range. For each pattern tau deposition (p=0.88, p=0.64 and p=0.11, respectively). Retinal
(DLBRP/PDRP), subject scores measured in all subjects showed SUVR presented negative correlation with occipital and lateral
an effect of group (ANOVA; DLBRP: F[3,102]=108.1, p<0.001; temporal SUVR (ρ=-0.598, p=0.040 and ρ=-0.665, p=0.018,
PDRP: F[3,102]=74.1, p<0.001) with elevation in the DLB/PD respectively), but no significant correlation with composite brain
patients (p<0.001, post-hoc tests) compared to the healthy SUVR (ρ=-0.531, p=0.076). Retinal SUVR presented negative
controls. Moreover, network scores were similarly greater in the correlation with total-tau in CSF (ρ=-0.601, p=0.039), but not
DLB patients than in the PD patients in both patterns (p<0.001). with αβ-42 or phospho-tau. Composite brain SUVR presented
Conclusion: This is the first study to demonstrate the specific negative correlation with αβ-42 in CSF (ρ=-0.616, p=0.033), but
metabolic brain network corresponding to DLB using FDG PET not with tau biomarkers. Conclusion: With this preliminary
imaging which presents a similar topography with PDRP but analysis, we have showed that 18F-Flortaucipir deposition in the
with wider range as well as higher quantitative expression. retina evolved a contrario to brain tau deposition, and to total-
These results indicate that PD/DLB maybe under the spectrum tau in CSF. Retinal signal with 18F-Flortaucipir could represent an
of the same disease. References: [1] Tang et al. Lancet Neurol early non-invasive biomarker for AD. These results have to be
2010 [2] Wu et al. Parkinsonism Relat Disord 2013. confirmed with a larger population. References: None.
S423 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

EP-0088 metabolic connectivity of the afflicted regions. References:


Metabolic Correlates of Dopaminergic Loss in Dementia None.
with Lewy bodies
L. Beyer1, M. Huber1, S. Morbelli2, M. Unterrainer1, A. Chincarini3,
R. Bruffaerts4, M. Kramberger5, M. Grmek5, V. Garibotto6, N. EP-0089
Nicastro6, G. Frisoni7, A. Pilotto8, S. Garcia-Ptacek9, I. Savitcheva9, M. PET/CT brain imaging using 18F-FDG in patients with
Pchoa-Figueroa10, V. Camacho11, D. Aarsland12, P. Bartenstein1, A. Creutzfeldt-Jakob disease
Rominger13, M. Brendel1; M. Grmek1, T. Rus2, M. Popović3, M. Trošt2;
1
LMU, Munich, GERMANY, 2University of Genoa, Genoa, ITALY, 1
Department for Nuclear Medicine, University Medical
3
National Institute of Nuclear Physics, Genoa, ITALY, 4University Centre Ljubljana, Ljubljana, SLOVENIA, 2Department
of Leuven, Leuven, BELGIUM, 5University of Ljubljana, Ljubljana, of Neurology, University Medical Centre Ljubljana,
SLOVENIA, 6University of Geneva, Geneva, SWITZERLAND, Ljubljana, SLOVENIA, 3Institute of Pathology, Medical
7
LANVIE, Geneva, SWITZERLAND, 8University of Brescia, Faculty, University of Ljubljana, Ljubljana, SLOVENIA.
Brescia, ITALY, 9Karolinska Institutet, Stockholm, SWEDEN,
10
University of Linköping, Linköping, SWEDEN, 11University
of Barcelona, Barcelona, SPAIN, 12University of Stavanger, Aim/Introduction: Creutzfeldt-Jakob disease (CJD) is a fatal
Stavanger, NORWAY, 13University of Bern, Bern, SWITZERLAND. rapidly progressing neurodegenerative disorder presenting
with cognitive decline and additional neurological signs
caused by deposition of misfolded prion protein. Our aim
Aim/Introduction: Striatal dopamine deficiency is a well- was to identify and validate a specific multivariate metabolic
known phenomenon in Dementia with Lewy Bodies (DLB) brain pattern of CJD and to test its biological significance.
and can be quantified in vivo by 123I-FP-CIT single photon Materials and Methods: 10 patients with rapidly progressing
emission computed tomography (DaT-SPECT). DLB is further dementia and additional neurological signs (group CJD1;
characterized by metabolic decline in distinct brain regions age 68.3 ± 12.4 years, survival from first symptoms 8.4 ± 10.6
as accessible by 18F-fluorodesoxyglucose positron emission months, Mini-Mental State Examination (MMSE) 19.9 ± 7.2)
tomography (FDG-PET). However, the linkage of dopamine underwent diagnostic PET/CT brain imaging using 18F-FDG.
deficiency to declining glucose metabolism and its role in the All of them were diagnosed pathologically with CJD. 10 age-
pathophysiological course of DLB are ill-understood. Hence, matched normal controls (NC) (group NC1; age 66.9 ± 5.4 years,
we made use of the hitherto largest dataset of combined DaT- MMSE 28.5 ± 1.2) were used as a control group. After spatial
SPECT and FDG-PET data in DLB to elucidate their associations normalization into MNI space and smoothing performed in
during disease progression and to study metabolic connectivity SPM5 (Wellcome Trust Centre for Neuroimaging), multivariate
as a function of degree of dopamine deficiency. Materials and Scaled Subprofile Modeling/Principal Component Analysis
Methods: We investigated 84 DLB patients of the European DLB (SSM/PCA) was performed using ScanVP software (http:// www.
consortium, all whom had undergone DaT-SPECT and FDG- feinsteinneuroscience.org; Center for Neuroscience, Feinstein
PET investigations, along with molecular imaging data from Institute for Medical Research, NY, USA) to identify a specific
historic healthy controls. After normalization of FDG-PET to the CJD related pattern (CJDRP). The stability of CJDRP was studied
global mean uptake, we tested the correlation between striatal with bootstrapping algorithm. The pattern was validated on
dopamine deficiency with relative glucose metabolism by another cohort of 7 CJD patients (group CJD2; 6 patients with
region-based and voxel-based methods. Metabolic connectivity definite CJD, 1 with probable CJD, age 67.6 ±7.8 years, disease
was analysed by inter-region coefficients at different stages duration 4.8 ± 6.7 months, MMSE 10.4 ± 6.6) and 10 age-
of dopamine deficiency and compared to that in healthy matched NC (group NC2). Expression of CJDRP was studied with
controls. Data were controlled for center, age, gender, and TPR algorithm (ScanVP software) and was correlated with age,
educational level. Results: There was an inverse relationship survival, disease duration, relative disease duration, cognitive
between striatal dopamine innervation and relative glucose (MMSE), clinical (CJD Neurological Status Scale), functional (MRC
hypermetabolism in striatum. Regional and voxel-based Prion Disease Rating Scale) scales and with cerebral-spinal fluid
methods revealed increasing relative glucose metabolism when (CSF) tau, p-tau and amyloid beta concentrations in both the
dopaminergic function decreased in the basal ganglia and in identification and validation groups. Results: The CJDRP was
limbic regions. With increasing dopamine deficiency, metabolic characterized by interconnected relative metabolic decreases
connectivity showed strong deteriorations in distinct brain in bilateral thalamus, caudate, cingulum, precuneus, frontal
regions implicated in DLB. However, the greatest disruptions of and parietal lobe. The CJDRP expression (z-scores) completely
metabolic connectivity involved the basal ganglia and limbic separated CJD patients in identification and validation cohorts
system, spatially coincident with relative hypermetabolism. from corresponding NC groups (p<0.0001). The pattern was
Conclusion: Combined analysis of dopamine-SPECT and FDG- stable on bootstrapping test (all but minimal areas of parietal
PET in patients with DLB indicate pronounced associations lobe hypometabolism). Its expression correlated with relative
of abnormality of the two biomarkers in the basal ganglia disease duration, MMSE, clinical and functional scales but not
and limbic system. Greater dopamine deficiency correlated with the CSF tau, p-tau nor amyloid beta. Conclusion: The
with increasing relative glucose metabolism, but decreasing CJDRP is a promising metabolic biomarker of CJD. It can help
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S424

clinician make a diagnosis in patients with suspected CJD. CJDRP newly-diagnosed gliomas with 18F-FDopa PET, and especially
expression correlates well with disease severity and progression of the presence or not of an IDH mutation, may be obtained
and has therefore a potential to become a biomarker of CJD with dynamic but not with current static uptake parameters.
progression in the possible disease modifying clinical trials. References: None.
References: None.

EP-0091
EP-05 The pentose phosphate pathway in glioma - a promising
target for nuclear medicine?
Neuroimaging: Brain Malignant E. Klebermass1, A. Woehrer2, G. Ricken2, S. Bucconi1, A. Haschemi3,
T. Balber1, M. Hacker1, H. Viernstein4, M. Mitterhauser1,5, T. Traub-
October 12 - 16, 2019 e-Poster Area Weidinger1;
1
Department of Biomedical Imaging and Image-guided
Therapy, Division of Nuclear Medicine, Medical University of
EP-0090 Vienna, Vienna, AUSTRIA, 2Institute of Neurology, Medical
Integration of dynamic parameters in the analysis of University of Vienna, Vienna, AUSTRIA, 3Department of
18
F-FDopa PET imaging improves the prediction of Laboratory Medicine, Medical University of Vienna, Vienna,
molecular features of gliomas AUSTRIA, 4Department of Pharmaceutical Technology and
T. Zaragori1,2, M. Ginet1, P. Marie1,3, V. Roch1, G. Gauchotte4,5, F. Biopharmaceutics, University of Vienna, Vienna, AUSTRIA, 5Ludwig
Rech6,7, M. Blonski6,7, Z. Lamiral3, L. Taillandier7,8, L. Imbert1,2, A. Boltzmann Institute Applied Diagnostics, Vienna, AUSTRIA.
Verger1,2;
1
Department of Nuclear Medicine & Nancyclotep Imaging
plateform, CHRU Nancy, Lorraine University, Nancy, FRANCE, Aim/Introduction: Gliomas account for 81% of malignant
2
IADI, INSERM U1254, Lorraine University, Nancy, FRANCE, brain tumors, with glioblastomas being the most lethal and
3
INSERM U1116, Lorraine University, Nancy, FRANCE, 4Department common ones (1). The pentose phosphate pathway (PPP)
of Pathology, CHRU-Nancy, Nancy, FRANCE, 5INSERM constitutes a major carbohydrate pathway in tumor metabolism
U1256, Lorraine University, Nancy, FRANCE, 6Department that is exploited by tumor cells for nucleic acid synthesis and
of Neurosurgery, CHRU-Nancy, Nancy, FRANCE, 7Centre de elimination of redox stress. Regarding glioma, most studies of
Recherche en Automatique de Nancy CRAN, CNRS UMR the PPP have focused on the evaluation of glucose-6-phosphate
7039, Université de Lorraine, Nancy, FRANCE, 8Department dehydrogenase, the rate-limiting enzyme in its oxidative arm,
of Neuro-Oncology, CHRU-Nancy, Nancy, FRANCE. and highlight a prognostic relevance (2). However, little is
known about the impact of the non-oxidative arm, although
its enzymes and the intermediate sedoheptulose-7-phosphate
Aim/Introduction: 18F-FDopa PET imaging of gliomas is seem to play an important role in other malignancies (3, 4).
routinely interpreted with standardized uptake value (SUV)- We therefore aim to evaluate the role of sedoheptulose kinase
derived indices. This study aimed to determine the added (SHPK), a key regulator of carbon flux making sedoheptulose
value of dynamic 18F-FDopa PET parameters for predicting the available for cells through phosphorylation. Materials and
molecular features of newly-diagnosed gliomas. Materials Methods: The anti-SHPK antibody (abcam, ab69920) was
and Methods: We retrospectively included 58 patients having tested and validated on formalin-fixed paraffin-embedded
undergone an 18F-FDopa PET for establishing the initial diagnosis healthy brain and glioma. Subsequently, immunohistochemical
of gliomas, whose molecular features were additionally staining in a 1:500 dilution was performed on tumor biopsies
characterized according to the WHO 2016 classification. of a heterogeneous cohort of 48 patients, having had [11C]
Dynamic parameters, involving time-to-peak (TTP) values and methionine and, in 21 cases, additional 2-[18F]FDG PET scans.
curve slopes, were tested for the prediction of glioma types in Hematoxylin was used as a counterstaining, colon and cervix
addition to current static parameters, i.e. tumor-to-normal brain FFPE tissues as positive- and negative controls, respectively.
or tumor-to-striatum SUV ratios and metabolic tumor volume Expression was semi-quantitatively assessed using the following
(MTV). Results: There were 21 IDH-mutant gliomas, 16 IDH- classification: positive cells 0-10%, 10-40%, and ≥ 50%. Staining
mutant and 1p/19q co-deleted gliomas and 21 IDH-wildtype intensity was rated from 1 to 4, 1 being the least intense.
gliomas; dynamic parameters enabled differentiating the Results: 38/48 glioma biopsies showed expression in >10%
gliomas according to these molecular features, whereas static of cells; 26 of them in ≥ 50% of cells. SHPK was detectable in
parameters did not. In particular, a longer TTP was the single tumor cells and microenvironmental cells such as microglia,
best independent predictor for differentiating: 1) IDH-mutant macrophages and rare astrocytes. The majority of positive cells
gliomas from IDH-wildtype gliomas (area under the curve displayed a variable cytoplasmic staining (intensity 1-4), whereas
(AUC) of 0.789, global accuracy of 74% for the criterion of a TTP tumor cells and macrophages occasionally exhibited a nuclear
> 5.4min) and 2) IDH-mutant from 1p/19q co-deleted gliomas staining of higher intensity (3-4). Significant expression was
(AUC of 0.679, global accuracy of 69% for the criterion of a TTP present in 14/14 glioblastomas, and 11/18 low-grade gliomas
> 6.9min). Conclusion: Prediction of the molecular features of (WHO grades I-II). Interestingly, 12/14 biopsies of completely
S425 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

2-[18F]FDG PET-negative gliomas showed SHPK staining in 0-8.13mL), resulting in a median spatial congruence of 4.15%
>10% of cells. Conclusion: Evaluation of SHPK in glioma shows (range, 0-59.7%). RGD positivity was mostly located in tumour
a significant expression in different tumor types across all grades portions showing contrast enhancement at MRI. In two patients
of malignancy involving both tumor and microenvironmental with high-grade tumours, there was RGD uptake extending to
cells. These encouraging results might open up new FET-negative tumour portions. One patient had a meningioma
possibilities for metabolic imaging and/or treatment in these showing increased RGD uptake and negative FET. Conclusion:
patients. References: (1) Ostrom QT., Bauchet L., Davis FG., et The information provided by FET and RGD PET are substantially
al. Neuro Oncol. 2014 Jul (2) Yang CA., Huang HY., Lin CL., et al. J different. FET PET identifies larger volumes than RGD. Some
Neurooncol 2018 (3) Ying H., Kimmelman AC., Lyssiotis CA., et al. volumetric mismatch exists, whose significance should be
Cell. 2012 Apr (4) Patra KC., Hay N. Trends Biochem Sci. 2014 Aug. further investigated in larger patient series with follow-up.
References: 1) Albert NL, et al. Neuro Oncol. 2016;18:1199-208.
2) Gnesin S, et al. EJNMMI Res. 2017;7:43. 3) Cicone F, et al. Eur J
EP-0092 Nucl Med Mol Imaging. 2015;42:905-15.
Volumetric assessment of gliomas: Comparison between
18
F-FET and 68Ga-NODAGA-RGDyK
N. Testart1, F. Cicone1, A. Hottinger2, M. Nicod Lalonde1, N. EP-0093
Schaefer1, S. Gnesin3, M. Meyer1, P. Mitsakis1, J. O. Prior1; Correlation of [11C]Methionine PET Uptake With Ki-67
1
Nuclear Medicine and Molecular Imaging, Lausanne Immunohistochemistry In Patients With Untreated
University Hospital and University of Lausanne, Lausanne, Gliomas
SWITZERLAND, 2Neuro-Oncology, Lausanne University T. Skvortsova, D. Zakhs, Z. Savintseva, A. Gurchin, A. Kholyavin;
Hospital and University of Lausanne, Lausanne, SWITZERLAND, N. P. Bechtereva Institute of the Human Brain of Russian
3
Institute of Radiation Physics, Lausanne University Hospital Academy of Sciences, Saint-Petersburg, RUSSIAN FEDERATION.
and University of Lausanne, Lausanne, SWITZERLAND.

Aim/Introduction: The aim of the study was to determine


Aim/Introduction: Amino acid PET with 18F-FET (FET) is correlation between [11C]methionine uptake measured by
becoming a standard functional imaging technique for the positron emission tomography (PET) in newly diagnosed
evaluation of glioma [1]. 68Ga-NODAGA-RGDyK (RGD) is a novel gliomas and tumor proliferative activity as measured by Ki-67
radiopharmaceutical targeting the integrin ανβ3 [2], which labeling index in tumor samples after surgery. Also analysis
might provide additional information for stratifying patient of matches between two biomarkers in each patient was
prognosis and response to anti-angiogenic treatments. Our aim performed. Materials and Methods: The glioma uptake of [11C]
was to compare the tumour volumes identified by FET and RGD methionine (Met) was assessed using PET/CT (or PET) scanner
in a series of patients with glioma. Materials and Methods: in 214 patients between 18 and 75years of age (100 males, 114
Seven patients with newly diagnosed or recurrent glioma were females) with untreated gliomas. The final diagnosis was based
referred for PET/CT examinations with both FET and RGD, less on both histology and immunohistochemistry using Ki-67
than one week apart. Images were registered with the software antibodies. Tumor samples were classified as grade II gliomas
PMOD version 3.903 (PMOD Technologies, Zurich, Switzerland). (n=129; 97 astrocytomas, 32 oligodendrogliomas), grade III
After image registration, automatic tumour segmentation gliomas (n=66; 49 astrocytomas, 17 oligodendrogliomas) and
of both sets of images was performed using the average glioblastomas (n=19). On PET-Met tumor-to normal brain
background signal in a large hemispheric VOI multiplied by uptake ratio (TBR) was calculated by dividing maximum Met
1.6 as a threshold for positivity. Tumour volumes identified by uptake in the tumor (hot spot 10 mm in diameter) to activity
both modalities were compared and their spatial congruence concentration in the contralateral cortex. The Spearmen rank
calculated [3]. Results: The study population consisted of 7 correlation test was used to analyze the relationships between
patients (1F/6 M, mean age: 56y). According to the WHO 2016 TBR and Ki-67 labeling index (LI). Results: PET-Met analysis
classification of brain tumors, there were two glioblastomas showed that TBR (mean±SD) of low-grade gliomas, anaplastic
(Grade IV, IDH wild-type), one ganglioglioma (Grade II IDH wild- gliomas and glioblastomas were 1,67±0,64, 2,41±1,05,
type), two oligodendrogliomas (Grade II, IDH mutant, 1p19q 3,45±1,03, respectively. The differences of TBR values between
co-deleted), one oligodendroglioma (Grade III, IDH mutant, gliomas grade II vs III and grade III vs IV were significant
1p19q co-deleted) and one newly diagnosed non-enhancing, (p<0,001). Among grades II-III gliomas Met uptake was higher
non-biopsied glioma. Magnetic resonance imaging showed in oligodendroglial tumors than in astrocytomas (p<0,01).
presence of contrast enhancement in 3 out of 7 patients. On The mean Ki-67 LI of low-grade and high-grade gliomas
visual inspection, 100% (7/7) FET studies and 57% (4/7) RGD were 5%±4%, 14%±9%, respectively. Correlation analysis
studies were positive. The tumour volume delineated using demonstrated weak correlation between Ki-67 LI and TBR values
FET (FETvol 1.6) largely exceeded that of RGD (RGDvol 1.6). (r =0,50, p<0.05). With analyzing glioma subgroups TBR values
Median FETvol 1.6 and RGDvol 1.6 were 29.0mL (range, 10.8- correlated with Ki-67 LI in diffuse astrocytomas (r=0,52, p<0,05),
207mL) and 2.95mL (range, 0-11.3mL), respectively (p=0.015). oligodendrogliomas (r=0,34, p<0,05) and in high-grade gliomas
Overall, median overlapping volume was 2.95 ml (range (r=0,44, p<0,05) but not in low-grade gliomas. Higher Met
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S426

uptake in oligodendrogliomas compared with astrocytomas prognostic factor in gliomas: evidence from a systematic review
did not depend on Ki-67 LI. Comparison between TBR value and and meta-analysis. Asian Pac J Cancer Prev. 2015;16(2):411-20.
Ki-67 LI in each glioma showed a lack of coincidence in 24% 2) I. Law, N.L. Albert, J. Arbizu, et al. EANM/EANO/RANO practice
of cases (high Met uptake but low Ki-67 LI and vice versa). The guidelines/SNMMI procedure standards for imaging of gliomas
main reasons for such discrepancies were tumor molecular using PET with radiolabelled amino acids and [18F]FDG: version
biology or incorrect biopsy target. Conclusion: The study 1.0. Eur J Nucl Med Mol Imaging. 2019 Mar;46(3):540-557.
showed that Met uptake in diffuse gliomas increases in parallel
with the increase in their proliferative activity which justifies the
use of PET-Met for glioma grading. In case of mismatch between EP-0095
two biomarkers one should rely on the indicator that implies a 18F-FAZA PET and MRI for hypoxia, perfusion and
higher aggressiveness of the glioma. References: None. diffusion assessment in high-grade glioma
P. Mapelli1,2, P. Scifo2, G. Conte1,3, F. Fallanca2, A. Castellano1,3, E.
Incerti2, V. Bettinardi2, A. Coliva2, V. Masiello2, A. Compierchio2, N.
EP-0094 Anzalone1,3, L. Gianolli2, M. Picchio1,2;
18
F-DOPA uptake ratio correlates with Ki67 in gliomas at 1
Vita-Salute San Raffaele University, Milan, ITALY, 2Nuclear
initial diagnosis, in a per-biopsy analysis Medicine Department, IRCCS San Raffaele Scientific
A. Girard1, X. Palard-Novello1, P. J. Le Reste2, A. Metais3, F. Le Jeune1; Institute, Milan, ITALY, 3Neuroradiology Unit and CERMAC,
1
Centre Eugène Marquis, Rennes, FRANCE, 2Neurosurgery IRCCS San Raffaele Scientific Institute, Milan, ITALY.
- Universitary Hospital, Rennes, FRANCE, 3Pathology
- Universitary Hospital, Rennes, FRANCE.
Aim/Introduction: 18F-FAZA PET/CT provides information on
tumour hypoxic status, perfusion and diffusion weighted MRI
Aim/Introduction: Ki67 has been reported as a predicative (pw-MRI, dMRI) can further improve tumour characterization.
factor for poor prognosis of glioma patients (1). At initial diagnosis, The aim of the present study is to evaluate the complementary/
diffuse gliomas are highly infiltrative and heterogeneous additive role of 18F-FAZA PET and MRI, in assessing the functional
tumors, and Ki67 expression varies spatially across each tumor. status of high-grade glioma (HGG). Materials and Methods:
18
F-DOPA PET might be a useful tool to target biopsies and Seventeen patients with brain MRI suggestive for HGG have
guide tumor resection, but does not appear in this indication in been included. All patients underwent 18F-FAZA PET/CT, MRI
the last EANM/EANO/RANO guidelines (2). We hypothesize that (3D-T1w, T2w, FLAIR w pre- and post-contrast), diffusion (DTI)
18
F-DOPA uptake correlates with Ki67 expression, in a per-biopsy and perfusion (PWI) images; 11 pts have been considered for
analysis. Materials and Methods: In these preliminary results of analysis in this preliminary work. PET-FAZA, pw-MRI and dMRI
the GLIROPA study (NCT03525080) we prospectively included images were firstly co-registered to 3D-T1 MR. Ktrans, Vp and
8 patients with suspicion of diffuse glioma. 18F-DOPA PET was CBV maps were derived from PW images. Mean Diffusivity (MD)
performed before surgery in accordance with the last EANM/ was obtained from DTI. 18F-FAZA SUV maps were calculated,
EANO/RANO guidelines (2). Based on 18F-DOPA PET images, one divided by muscle value and a threshold of tumour-to-blood
to three 1mL volumes of interest (VOI) were defined for each (T/B) >1.2 was used to define FAZA-based ROIs. Using these
patient, depending on the size and heterogeneity of the tumor. ROIs, Spearman correlations between FAZA SUV and PWI
During surgery, biopsies were performed in these targets under parameters were calculated. A second ROI was defined based
neuronavigational control. The per-biopsy statistical analysis on the Gd-enhanced regions on FLAIR images. Dice coefficient
included bilateral Spearman’s rank correlation coefficient between the two ROIs was calculated to assess overlapping
between Ki67 and VOI-SUVmax (VOImax), VOI-SUVmean between them. Gd-based ROI was used to mask PWI and DTI
(VOImean) and VOI-SUVmax/Striatum-SUVmax ratio (VOI/Smax), maps, centers-of-mass (CoM) of ROIs in each single parametric
respectively. Results: Six high grade gliomas (HGG) and two map (Ktrans, Vp, CBV, MD, FAZA) were found and the relative
low-grades gliomas (LGG) were found at pathological analysis distances were calculated. Results: No significant correlation
of tumors. There was 18F-DOPA uptake in 7/7 HGG and 1/2 LGG. between PET and PWI parameters (CBV, Ktrans and Vp) were
Sixteen biopsies were performed. In a per-biopsy analysis, Ki67 obtained. The mean value of Dice coefficient among patients
mean was 11% [range : 1% - 40%], VOImax 4.02 [range : 1.89 was 0.68±0.16. The CoMs of pw maps and MD in the ROIs
- 9.17], VOImean 2.51 [range : 1.26 - 4.79] , and VOI/Smax ratio defined by Gd-enhacement, were located slightly differently in
1.26 [range : 0.63 - 2.67]. Ki67 was significantly correlated with the group of patients. The analysis of the relative 3D-distances
the VOI/Smax ratio (rho 0.52 ; p =0.037), but neither with VOImax between FAZA CoM and CoM in the 4 MRI maps in the 11
(rho 0.48 ; p =0.058), nor with VOImean (rho 0.49 ; p =0.056). patients suggests that FAZA CoM is located in a position closer
Conclusion: In a per-biopsy analysis, Ki67 was significantly to the CoMs of DCE maps, but further away from CBV-CoM and
correlated with the VOI/Smax ratio. These results strengthen MD-CoM. Conclusion: In the present cohort, 18F-FAZA PET/
the idea that 18F-DOPA PET may be a useful tool to localize CT and MR parameters are not strongly related, suggesting the
the most proliferative part of gliomas, and thus might help to complementary role of these techniques in providing different
target biopsies and guide tumor resection at initial diagnosis. information on tumour status. Among MR maps, CBV seems to
References: 1) W.J. Chen , D.S. He , R.X. Tang, et al. Ki-67 is a valuable provide the “most different” information compared to FAZA. The
S427 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

limited number of patients might have hampered the statistical p=0.001 for PFS), multilesionality (HR:3.58, p=0.009 for OS and
power of the analysis. Further analysis on larger cohorts are HR: 2.67, p=0.012 for PFS) and sphericity (HR: 4.80, p=0.004 for
mandatory to deeply investigate these relevant aspects of HGG. OS). Conclusion: In patients with glioma, SUV-based variables,
References: None. obtained from 18F-fluorocholine PET/CT, showed association
with histological and molecular characteristics of tumors.Some
metabolic variables were stronger prognostic predictors than
EP-0096 biological ones, as patients with tumors with higher SUVmean,
18
F-Fluorocholine PET/CT in the prediction of molecular lower sphericity and multiple foci on 18F-fluorocholine PET/CT,
subtypes and prognosis for gliomas had shorter PFS and OS. References: None.
A. Garcia Vicente1, J. Perez-Beteta2, M. Amo-Salas2, G. A. Jimenez
Londoño1, F. J. Pena Pardo1, M. Villena Martin1, H. Sandoval
Valencia3, R. Barbella3, J. M. Borras Moreno1, E. Casillas Sagrado1, V. EP-0097
Perez-Garcia2, A. Soriano Castrejon1; MGMT methylation and IDH1 mutations do not affect [18F]
1
Hospital General Universitario de Ciudad Real, Ciudad Real, FDOPA uptake in primary brain tumors
SPAIN, 2Universidad de Castilla La Mancha, Ciudad Real, SPAIN, A. Chiaravalloti1, A. Cimini1, M. Zinzi2, M. Salzillo2, E. Di Giorgio2, V.
3
Hospital General Universitario de Albacete, Albacete, SPAIN. Villani3, O. Schillaci1;
1
Department of biomedicine and prevention,
University Tor Vergata, Rome, ITALY, 2IRCCS Neuromed,
Aim/Introduction: To study the association of metabolic Pozzilli, ITALY, 3Neuroncology Unit, IRCCS Regina
features of 18F-fluorocholine PET/CT in gliomas with Elena National Cancer Institute, Rome, ITALY.
histopathological and molecular parameters and prognosis.
Materials and Methods: Prospective multicenter and non-
randomized study (FuMeGA: Functional and Metabolic Glioma Aim/Introduction: The aim of our study was to investigate
Analysis). Patients underwent a basal 18F-fluorocholine PET/CT the effects of methylation of the promoter of methyl guanine
and were included after histological confirmation of glioma. methyl transferase (MGMT) and isocitrate dehydrogenase
Histological and molecular profile were assessed: grade, Ki-67, (IDH1) mutations on amino acid metabolism evaluated with
isocitrate dehydrogenase (IDH) status and 1p/19q codeletion. [18F]-L-dihydroxyphenylalanine [18F] FDOPA) Positron Emission
Patients underwent standard treatment after surgery/biopsy, Tomography/Computed Tomography (PET/CT uptake in
depending on their clinical situation. Overall survival (OS) primary brain tumors (PBT). Materials and Methods: 72
and progression free survival (PFS) were obtained.After tumor patients with PBT were enrolled in the study (33 women and 39
segmentation of PET images, maximum and mean standardized men; mean age 44±12 yo). All of them were subjected to PET/
uptake value (SUV based variables), metabolic tumor volume CT examination after surgical treatment. Of them, 29 (40,3%)
and total lesion activity (volume-based variables), sphericity, were affected by grade II glioma and 43 (59,7%) by grade III. PET/
surface, coefficient of variation and multilesionality were CT was scored as positive or negative and standardized uptake
obtained. Relations of metabolic variables with histological value ratio (SUVr) was calculated as the ratio between SUV max
and molecular profiles and prognosis were evaluated using of the lesion vs. that of the background. Statistical analysis was
Pearson’s chi-square and t-student tests. Receiver operator performed with the Mann Whitney U test. Results: Methylation
caracteristic (ROC) curves were used to obtain the cut-off of of MGMT was detectable in 61 out of the 72 patients examined.
PET variables and survival analysis was performed using Kaplan- Mean SUVr in patients without methylation of MGMT was
Meier and Cox regression analysis. Results: 45 patients were 1.44±0.38 vs. 1.35±0.48 of patients with methylation (p=0.15).
assessed, 38 were diagnosed as having high-grade gliomas Data on IDH1 mutations were available for 43 subjects; of them,
(HGG).Multilesionality was detected on PET in 11 cases (24.4%). 31 had a deletion of IDH. Mean SUVr was 1.38±0.51 in patients
Significant differences were found with respect to the IDH status with deletion and 1.46±0.56 in patients without deletion
and SUVmax and SUVmean, with higher values in IDH wild type (p=0.79). Conclusion: MGMT methylation and IDH1 mutations
as compared to IDH mutated tumors (SUVmax of 3.66±1.77; and do not affect [18F] FDOPA uptake in primary brain tumors;
1.61±1.84, respectively; p=0.025 and SUVmean of 1.22±0.48 and thus representing a biomarker independent from the genetic
0.67±0.51, respectively; p=0.033). No significant relation was patterns explored in our study. Analyses of quantitative uptake
found with the other metabolic variables.The overall median may not require adjustments for MGMT methylation and IDH1
PFS and OS were 5 and 14 months, respectively.Tumor grade, mutations. References: None.
Ki-67, SUVmax and SUVmean were related to progression.
SUVmax of 2.20 and 0.88 for SUVmean (AUC of 0.865, p=0.003
and AUC of 0.841, p=0.005, respectively) were the cut-off EP-0098
valid to predict progression.Kaplan-Meier analysis revealed PET- and MRI-derived [18F]FET PET parameters for the
significant association of SUVmax, SUVmean and multilesionaly discrimination of low- and high-grade gliomas
with OS and PFS. SUVmean, sphericity and multilesionality S. Donche1, M. Henrotte1, S. Bonte1,2, J. Verhoeven3,1, M. Acou4, C.
were independent predictors of OS and PFS in Cox regression Van den Broecke5, R. Van Holen6, I. Goethals1;
analysis.SUVmean (HR:4.61, p=0.002 for OS and HR: 3.64, 1
Department of Nuclear Medicine, Ghent University Hospital,
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S428

Ghent, BELGIUM, 2Department of Electronics and Information 4


Department of Pathology, Saitama Medical University
Systems, Ghent, BELGIUM, 3Department of Pharmaceutical International Medical Center, Hidaka, Saitama, JAPAN.
Analysis, Ghent University, Ghent, BELGIUM, 4Department
of Radiology, Ghent University Hospital, Ghent, BELGIUM,
5
Department of Pathology, Ghent University Hospital, Ghent, Aim/Introduction: Intracranial germ cell tumours (IGCT) are
BELGIUM, 6Department of Electronics and Information rare tumours occurring mostly in children and young adults. A
Systems, Ghent University Hospital, Ghent, BELGIUM. few systematic reviews have reported the use of 11C-methionine
(11C-MET) positron emission tomography/computed
tomography (PET/CT) in the detection and follow-up of IGCT
Aim/Introduction: Gliomas are the most frequent malignant [1-2]. We compared the diagnostic accuracies of 11C-MET and
primary brain tumours in adults and can be classified into either 18
F-fluorodeoxyglucose (FDG) PET/CT. Materials and Methods:
low-grade gliomas (LGG) or high-grade gliomas (HGG). There The subjects were 36 patients (age: 5-59 years) with IGCT (25 with
is an increasing interest in non-invasive diagnostic methods germinoma, 5 with mixed germ cell tumour, 3 with immature
to support preoperative treatment planning, due to the risks teratoma, and 3 with yolk sac tumour) who underwent 11C-MET
associated with performing biopsies and resections. In this PET/CT before therapy and/or at serial follow-ups. There were 65
retrospective study, the role of different positron-emission PET/CT scans showing 33 patients with tumours (TM+) and 32
tomography (PET)-based, and magnetic resonance imaging without (TM-). A volume of interest analysis was performed on
(MRI)-based O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET) PET- the tumours and on both intact contralateral brain and intact
parameters in discriminating HGG from LGG was investigated. cerebellum. Indices of maximum standardised uptake value
Materials and Methods: A pre-treatment [18F]FET PET-scan and (SUVmax), tumour-to-normal-brain ratio (TNR), and tumour-
an anatomical MRI were performed in 30 patients (14 LGG and 16 to-cerebellar ratio (TCeR) were obtained from the measured
HGG). Twenty-four PET-derived parameters were calculated using values on 11C-MET and 18F-FDG PET/CT. The tumour size, human
various SUV thresholds. Subsequently, an in-house developed chorionic gonadotropin beta (hCGβ), alpha-fetoprotein (AFP),
segmentation algorithm [1] was used to label different tissue and tumour-free survival (TFS) were correlated with the PET
categories on both contrast-enhanced T1-weighted and FLAIR indices. The PET indices in TM(+) and TM(-) were compared
MR images: necrosis (N), oedema (OE), non-enhancing tumour using receiver operating characteristic (ROC) curve analysis.
(NET) and contrast-enhancing tumour (CET). MR-derived Results: The areas under the ROC curve (AUCs) for SUVmax, TNR,
tumour masks were applied to the PET-images to calculate and TCeR were 0.917 (p<0.0001), 0.925 (p<0.0001), and 0.936
55 PET-parameters. PET- and MR-derived FET PET-parameters (p<0.0001), respectively, on 11C-MET PET/CT, while the AUCs
were compared between HGG and LGG. Significantly different were 0.732 (p=0.003), 0.684 (p=0.017), and 0.707 (p=0,007),
parameters were analysed by ROC analysis. Results: Significant respectively, on 18F-FDG PET/CT. Moreover, the AUC for tumour
differences between HGG and LGG were found for 13 out of 24 size was 0.779 (p<0.0001) and for hCGβ was 0.599 (p=0.197).
and 17 out of 55 parameters for respectively the PET- and MR- The AUC in both types of PET was higher for TNR than for TCeR.
derived PET-parameters. Conclusion: This study illustrates that Among all the indices, the 11C-MET-TCeR had the highest AUC.
various PET- and MRI tumour-derived [18F]FET PET-parameters All AUCs on 11C-MET PET/CT were higher than those on 18F-FDG.
are significantly different between HGG and LGG. Hence, these The optimal threshold for the discrimination of TM(+) from TM(-)
parameters may aid the pre-treatment diagnostic classification was 1.65 for SUVmax, 1.55 for TNR, and 1.05 for TCeR on 11C-MET
of gliomas. References: [1] Bonte, S., Goethals, I., & Van Holen, R. PET/CT. Conclusion: TCeRs on 11C-MET PET/CT demonstrated
(2018). Machine learning based brain tumour segmentation on the highest AUC (0.936) for the detection of intracranial germ
limited data using local texture and abnormality. Computers in cell tumours. The optimal threshold of TCeR was 1.05, with 77%
biology and medicine, 98, 39-47. sensitivity and 94% specificity on 11C-MET PET/CT. References:
[1]Fukuoka K, Yanagisawa T, Watanabe Y, Suzuki T, et al. Clinical
interpretation of residual uptake in 11C-methionine positron
EP-0099 emission tomography after treatment of basal ganglia germ
Comparison of the diagnostic accuracy for intracranial cell tumors: report of 3 cases. J Neurosurg Pediatr. 2015;16:367-
germ cell tumours between 11C-methionine and 71. [2]Okochi Y, Nihashi T, Fujii M, Kato K, et al. Clinical use of
18
F-fluorodeoxyglucose positron emission tomography/ 11
C-methionine and 18F-FDG-PET for germinoma in central
computed tomography nervous system. Ann of nucl med. 2014;28:94-102.
I. Kuji1, T. Suzuki2, T. Yamane1, A. Seto1, E. Uchida2, M. Shirahata2,
J. Adachi2, K. Fukushima1, K. Mishima2, A. Sasaki3, M. Yasuda4, R.
Nishikawa2; EP-0100
1
Department of Nuclear Medicine, Saitama Medical 99mTc-DMSA (V) SPECT/CT scanning in patients with brain
University International Medical Center, Hidaka, Saitama, gliomas: diagnostic and prognostic utility
JAPAN, 2Department of Neuro-Oncology/Neurosurgery, Y. G. Abdelhafez1,2, N. Ragab3, W. Diab3, W. Abd-El-Ghani3, M.
Saitama Medical University International Medical Center, ElNaggar3, M. Mekkawy3;
Hidaka, Saitama, JAPAN, 3Department of Pathology, 1
University of California Davis, Sacramento, CA, UNITED STATES OF
Saitama Medical University, Moroyama, Saitama, JAPAN,
S429 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

AMERICA, 2South Egypt cancer Institute, Assiut University, Assiut, Aim/Introduction: A retrospective study was done to explore
EGYPT, 3Faculty of Medicine, Assiut University, Assiut, EGYPT. the diagnosis value of PET/CT and integrated TOF PET/MR in
brain tumors and the differences of two systems were compared.
Materials and Methods: 32 patients with intracranial tumors
Aim/Introduction: Several PET and SPECT tracers are done sequentially 18F-FDG PET/CT imaging and PET/MR brain
available for the differentiation between radiation necrosis imaging on the same day were enrolled. Referring to the
and residual/recurrent glioma. PET with radio-labeled amino pathology and follow-up results, t test and χ2 test were used
acids, has several advantages; however, it is expensive and to compare the semi-quantitative value and the diagnostic
not widely available, especially in developing world. SPECT performance between PET/CT and PET/MR. Results: A total of
has the advantages of being more widely-available and less 78 lesions, including10 glioma, 11 lymphoma, 55 metastases,
expensive. Multiple SPECT tracers have been explored. The aim 1meningiomas, 1 pituitary. 31 additional lesions were found
of this work was to evaluate the utility of post-therapy 99mTc- in PET/MR while not in PET/CT, and there was a statistically
pentavalent dimercaptosuccinic acid (DMSA (V)) brain SPECT/ significant difference between the two (χ2 =38.69, P<0.01).
CT in patients with glioma. Materials and Methods: Patients The SUVmax-MR and SUVmax-CT of 50 lesions whose 18F-FDG
with pathologically or radiologically documented glioma were uptake were significantly higher than brain parenchyma were
prospectively recruited for this study. 99mTc-DMSA (V) brain in good agreement (r=0.799). The T/B values ​​of PET-MR were
SPECT/CT scanning was acquired after a mean interval of 10 slightly higher but no statistically difference (t=1.297, p<0.05)
weeks from therapy, 2-3 h. after i.v. injection of 555-740 MBq with PET-CT. For other 28 lesions with comparable or lower
of the tracer. Three nuclear medicine physicians (experience uptake of brain parenchymal, PET/MR detected 17 more lesions
was 10, 22 and 15 years for readers 1, 2, and 3; respectively) than PET/CT, and the detection rates were statistically significant
independently and blindly interpreted the images visually as (χ2 =28.76, P<0.01). There were 36 lesions with obvious edema
positive or negative for residual/recurrent disease. Agreement found in both examinations, though 3 in PET/CT only found
between two or more readers was considered a consensus. edema with no clear lesions. Among the 42 lesions with no
Reader 1 was asked to repeat the readings after 3 months edema, 28 more were found in PET/MR which is significant
interval to establish intra-reader agreement. All the readings different with PET/CT (χ2=42.00, P<0.01). For 62 lesions with
were compared against the reference standard which was Dmax <3.0 cm, 31 more were found in PET/MR, demonstrating
formulated based on subsequent clinical/neuroimaging follow significant difference with PET/CT. Conclusion: Compared with
up or pathology whenever performed. Overall survival was PET/CT, better detection rate of intracranial lesions was obtained
calculated from time of diagnosis till death or last follow-up. for lesions with mild uptake (comparative to brain parenchyma),
Results: Thirty-Four patients; (18 male,16 female; mean age with no obvious edema, and with Dmax <3.0 cm which benefit
37.7±16, 82% of them with high grade glioma) were enrolled from the higher SNR of PET and excellent MR soft-tissue contrast
in this study. According to the reference standard, residual/ in integrated PET/MR. References: None.
recurrent disease was documented in 16 patients, while 18
patients were disease free. Consensus reading of 99mTc-DMSA
(V) SPECT/CT successfully identified 13 true positive (sensitivity EP-0102
81%, 95% confidence interval [CI]:54-96%) and 17 true negative Value of quantitative Tc-99m Pentavalent (V) DMSA
cases (specificity 94%, 95% CI:73-100%). The overall accuracy brain SPECT in predicting prognosis in patients with
was 88% (95% CI: 72-96%). Inter-observer kappa agreement Glioblastoma Multiforme
between the three readers ranged from 0.71 to 0.82. Intra- A. Kandeel, A. Badawy, M. A. Abougabal, E. Abdelhady;
observer agreement for Reader 1 was 0.76 (95%CI: 0.50-0.94). Faculty of Medicine, Cairo University, Cairo, EGYPT.
After 2-year of follow-up, 4/20 patients with negative DMSA (V)
findings died compared to 7/14 with positive findings (overall
survival was 65% compared to 0%, respectively, p=0.004). Aim/Introduction: Introduction: Gliomas are the most
Conclusion: Post-therapy brain SPECT/CT with 99mTc- DMSA common primary brain tumours, representing 40-50% of
(V) is reliable and specific tool for assessment of patients with cases. GBM (WHO grade IV) is the most common type of
glioma after definitive therapy. Positive scans are linked to worse primary gliomas; and also the most aggressive and resistant to
overall survival. References: None. treatment. The median survival time for malignant glioma grade
IV by WHO is about 12 months. Aim: To evaluate the value of
qualitative and quantitative 99m Tc (V)-DMSA uptake by the
EP-0101 viable tumour tissue in patients with GBM before and after the
Comparison of diagnosis vaiue between PET/CT and PET/ end of therapy and correlating the SPECT results to the overall
MR in brain tumors: a preliminary study survival (OS) and progression-free survival (PFS). Materials and
Y. Xu, J. Wang, S. Wang, C. Li; Methods: This prospective study included 40 patients (16 males
Hangzhou Universal Imaging Diagnostic and 14 females; mean age 47.8 ± 12.9 years) with pathologically
Center, Hangzhou, CHINA. proven Glioblastoma Multiform (GBM). Patients were clinically
assessed for performance status to determine the treatment
protocol. Brain SPECT studies were acquired early at 30 min
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S430

and late after 120 min after I.V injection of 15-20 mCi of 99mTc glucose infusion, the tumor was delineated more clearly than
(V) DMSA at baseline as well as at least 4 weeks after the end the control in all high grade tumors. T/N ratio was 2.09 ± 0.55
of radiotherapy. SPECT images were interpreted qualitatively under glucose loading and 1.70 ± 0.54 at fasting (p < 0.05) in
by visual assessment and semi-quantitatively by calculation of high grade gliomas. In contrast, no remarkable FDG uptake was
lesion/non-lesion (L/NL) ratio and retention index (RI). SPECT noted in low grade gliomas (T/N ratio with glucose loading vs
results in baseline and in follow up studies were correlated fasting, 0.81 ± 0.03 vs 0.72 ± 0.07). Analysis of animal PET images
with the OS and PFS. The overall survival was calculated from also showed a significant positive correlation of T/N ratio over
the date of diagnosis (in the current study we considered it as the blood glucose levels (R2= 0.849). Similarly, at the cellular
the date of surgery) till the end of follow up period or death. level, tumor to neuron ratio was 2.89 ± 0.49 in high glucose level
The Progression-free survival was calculated from the date and 1.74 ± 0.25 in low glucose levels (P < 0.005). Conclusion:
of diagnosis to the date of documented disease progression In brain tumors, FDG PET/CT under glucose loading provided
(clinical deterioration of the patients or radiological evidence better tumor delineation compared with FDG PET/CT at fasting
of disease progression) or the date of death from any cause. due to the lower background uptake in the normal cerebral
Results: At baseline, enhanced 99mTc (V) DMSA uptake (either cortex. FDG PET/CT methodology of regulating blood glucose
positive or negative) was significantly correlated with PFS at can improve sensitivity for the characterization and volume
both early and late images (p 0.04 and 0.026, respectively) and delineation of brain tumor. References: None.
with OS only at late images (p 0.036). Quantitatively, L/NL ratios
at late images (mean 3.6±1.3) showed a statistically significant
correlation with PFS and OS (p 0.021 and 0.025, respectively). EP-0104
RI had a significant positive correlation with only PFS (p 0.01). 68
Ga-DOTANOC PET/CT in Meningioma
Conclusion: A a significant association between the degree of S. Shamim, G. Arora, J. Hussain, S. Somani, S. Datta Gupta, M.
tumour uptake in 99mTc (V) DMSA brain SPECT and the overall & Tripathy, N. A. Damle, R. Kumar, C. Bal;
progression-free survival in patients with brain GBM. In addition All India Institute of Medical Sciences, Delhi, INDIA.
99m
Tc (V) DMSA brain SPECT may predict the prognosis of patients
with brain GBM and can expect shorter progression-free survival
in tumours with increased retention index. References: None. Aim/Introduction: Meningioma are the most common non-
glial tumors and are mostly benign. Its incidence is higher in
females and increases with age. The expression of somatostatin
EP-0103 receptor in meningioma is well known that may be exploited
Incremental values of FDG PET/CT by glucose loading for for developing potent diagnostic and/or theranostic tool using
characterization and delineation of brain tumors 68
Ga-DOTANOC. Hence, we evaluated the diagnostic utility of
D. Kim, H. Ko, S. Lee, S. Kim, J. Chung, M. Yun; 68
Ga-DOTANOC PET/CT in patients with meningioma. Materials
Yonsei University, Seoul, KOREA, REPUBLIC OF. and Methods: Fourteen patients (7 male, 7 female) of suspected
or known meningioma, who underwent 68Ga-DOTANOC PET/
CT at our institute, were retrospectively evaluated. All patients
Aim/Introduction: F-18 fluorodeoxyglucose (FDG) PET/ were injected 3-5mCi of 68Ga-DOTANOC intravenously. Whole
CT has been used successfully for diagnosis in patients with body scan (vertex to mid-thigh) and an additional spot view of
malignancy. However, FDG may not be the suitable tracer for either brain or head and neckwas acquired for each patient on
detection of gliomas because of the high-rate of physiologic a dedicated PET/CT scanner (BiographmCT, Seimens, Germany
glucose metabolism in normal brain tissue. In this study, we or Discovery 710, GE, US) 60 minutes post-injection. PET/CT
aimed to enhance the value of FDG PET/CT for the detection diagnosis was later corroborated with histopathology, clinical
and delineation of brain tumors by regulating blood glucose follow-up or conventional imaging suggestive of meningioma,
level. Materials and Methods: Nine patients with a suspicion assuming them as reference standard.Semi-quantitative
of glioma underwent two FDG PET/CT scans; one with fasting analysis was done by estimating SUVmax of the lesion and the
and the other with glucose loading. For glucose loading, the contralateral background. Results: Mean age of the patients was
patient was given intravenous infusion of 10% Dextrose water 41.8±15.7 years. Twelve out of fourteen patients (~86%) were
(DW) to obtain approximately 200mg/dL of blood glucose positive for meningioma on PET/CT while two were negative.
level. On each patient, standardized uptake value (SUV) and PET/CT findings were equivocal for glomus jugulare in one of
tumor-to-normal cortex (T/N) ratio on FDG PET/CT images the negative cases and for calcified granuloma in the other
were analyzed. In addition, FDG PET/CT of mouse glioblastoma patient, with meningioma as the second differential in both
(GBM) models were obtained on an animal PET and the the cases. The 12 PET/CT positive patients were also positive on
correlation of T/N ratio with blood glucose level was assessed. the basis of reference standard. Amongst these 12 patients, 8
Finally, FDG uptake of GBM cells (U87MG) and human neuron were biopsy proven while 4 others were confirmed by clinical
cells (HNC2) was compared under a different concentration data and conventional imaging. Therefore, it shows a strong
of glucose in the media. Results: Based on the new 2016 correlation between PET/CT and other reference standard
World Health Organization (WHO) classification, there were 3 modalities in the detection of meningioma. Furthermore, the
low grade gliomas and 7 high grade gliomas included. With lesion to background ratio in these 12 patients was very high
S431 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

with a median value of 17.85 indicating high SSTR expression Dynamic [18F]FET-PET/CT and multiparametric MR imaging
in meningioma in contrast to normal brain parenchyma. have a very high sensibility to detect new tumoral lesions or
Conclusion: 68Ga-DOTANOC PET/CT can be an effective suspect glioma recurrence. Agreement between PET and MRI
tool for the diagnosis of meningioma, owing to its high SSTR is essential to improve diagnostic specificity. References: None.
expression. Further evaluation with larger patient population,
might be useful to study its theranostic application, especially in
unresectable lesions. References: None. EP-0106
18
F-FET PET/CT In The Management Of Patients With Brain
Tumor
EP-0105 M. Colandrea1, I. M. Milanesi2, E. Lamperti2, M. Schiariti2, S. Alessi1,
Comparison between dynamic [18F]Fluoroethyltyrosine M. E. Ferrari1, S. L. Fracassi1, L. L. Travaini1, A. Silvani2, L. Fariselli2, P.
PET/CT and advanced MRI in cerebral high and low grade Ferroli2, A. S. Cascio1, S. Papi1, M. Fiorenza1, C. M. Grana1;
gliomas 1
Istituto Europeo di Oncologia, Milano, ITALY,
L. Picori, U. Rozzanigo, D. Donner, M. Erini, P. Feraco, M. Recla, F. 2
Istituto Neurologico Besta, Milano, ITALY.
Chierichetti;
Santa Chiara Hospital, Trento, ITALY.
Aim/Introduction: The aim is to present our experience with
18
F-FET PET as diagnostic tool in the initial staging of suspected
Aim/Introduction: To investigate if dynamic [18F]fluoroethyl- glioma (for guiding biopsy or when biopsy is not feasible) or
L-tyrosine [18F]FET PET/CT improves the diagnosis in patients for differentiation of glioma recurrence from radionecrosis.
with suspected new or recurrent cerebral gliomas, respect Materials and Methods: We performed PET/CT with 18F-FET
to advanced MRI techniques. Materials and Methods: We in 30 patients with a doubtful MR imaging. Group A: 21/30
retrospectively evaluated 20 patients who performed [18F] patients affected by brain tumors (1 GI, 7 GII, 8 GIII, 5 GIV
FET by a PET/CT tomograph: 15 had an indeterminate brain according to WHO 2016) and already treated with surgery and
lesion, 5 a suspect glioma recurrence. All patients underwent radio-chemotherapy. These patients were evaluated by 18F-FET
a 40 minutes dynamic [18F]FET PET/CT acquisition and two PET in order to better define the nature of the lesions. Group
different sequences, between 5-15 minutes and 20-30 minutes. B: 9/30 patients received 18F-FET PET in the initial staging for
For dynamic studies time-activity and time to peak curves were guiding biopsy or when biopsy is not feasible. Manually drawn
extracted using different region-of-interest (ROIs) and volume of regions of interest over areas of maximal FET uptake were used
interest (VOIs) definitions. MRI was performed with a 1.5T scanner to calculate tumor to background ratios (TBRmax). Results: 23
just before [18F]FET-PET/CT using perfusion (PWI) and diffusion patients underwent 0-40 dynamic 18F-FET PET scans and 7pts
(DWI) weighted imaging: afterwards rCBV and ADC values were received a 20-40 min scan. TBRmax was assessed in the 20-40
calculated placing the VOIs on the solid components of the min summation images in all patients, as well as in summation
lesion. In case of doubt (13 cases) single-voxel MR spectroscopy images from 5-20 min in 23 patients: no differences between
was performed. Multimodality imaging by fusion of PET/CT and early and late images in terms of TBRmax was found. Group A:
different MRI sequences was performed for a joint assessment 17/21 patients had positive PET consistent with recurrent disease
(radiologist and nuclear physician). Results: Final diagnosis was (TBRmax > 1.6), 1 patient with suspected recurrence (TBR max
based on histology in 8 patients who underwent neurosurgery >1.52) and 3 had negative PET consistent with radiation necrosis
(5 HGG, 3 LGG) and on follow-up imaging in 12 patients (8 tumor (no focal uptake). Moreover in 1 patient with two MRI lesions,
progression, 4 stable benign lesion). On the basis of [18F]FET- PET discovered a third area of pathological uptake. 2/17 positive
PET, 7 cases were classified as high uptake (2 glioma recurrence patients are still in good clinical conditions (false positive
and 5 new diagnosis of HGG tumor), 8 as low uptake (4 glioma PET?), 3 in stable disease, 2 in progression disease, 4 died and
recurrence, 2 new diagnosis of LGG tumor, 1 tumor progression, 6 were lost at follow-up. The patient with doubdful PET is in
1 tumefactive demielinating lesion) and 5 as no uptake (1 new stable disease. 2/3 PET negative patients are still in follow-up
diagnosis of LGG tumor, 4 stable benign lesion). Sensibility while 1 died after seven months (false negative PET?). Group
for dynamic [18F]FET-PET was 93% and specificity was 80%. B: 6/9 patients had positive PET suspicious for glioma. To date,
Multiparametric MRI was in agreement with [18F]FET-PET in all 3 have died (1 GII, 1 GIV and 1 without histological data) and
7 cases of high uptake and in 5 cases of low uptake. [18F]FET- 3 are lost at follow-up (between them 1 GIII). 3/9 patients had
PET helped to classify 6 MRI indeterminate lesions (2 suspect negative PET, in 1 patient biopsy revealed gliosis and 2 were lost
radionecrosis with pathologic uptake, 4 benign lesions without at follow-up. Conclusion: 18F-FET PET/CT fused with functional
uptake). In 2 cases there was a discrepancy between MRI and and morphological images allows a better definition of areas
PET: 1 tumefactive demielinating lesion was classified by [18F] of uptake. 18F-FET PET/CT allows a conclusive recognition of
FET as low uptake lesion, 1 LGG confirmed at histology showed recurrence or radiation necrosis and is a useful tool for guiding
no uptake. Conclusion: In our experience, adding quantitative biopsy or helping in the diagnosis when biopsy isn’t possible.
data, such as dynamic acquisition in PET/CT by aminoacid tracer References: None.
like [18F]FET, to rCBV and ADC maps in advanced MRI is crucial for
a better comprehension of tumor lesions and to assess grading.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S432

EP-0107 complement the results obtained from mpMRI. References:


99mTc-MIBI SPECT/CT and multi-parametric MRI in None.
patients with brain gliomas after therapy: initial results
Y. G. Abdelhafez1,2, E. Roshdy2, H. Atta2, M. ElNaggar3, S. Gamal3, A.
Kandeel4, Y. Mohamed4, M. Abdel-Wanis2; EP-0108
1
University of California Davis, Sacramento, CA, UNITED STATES Comparison of diagnostic accuracy of aMRI, 201Tl-SPECT
OF AMERICA, 2South Egypt cancer Institute, Assiut University, and 18F-fluorocholine PET/CT in the follow-up of low-grade
Assiut, EGYPT, 3Faculty of Medicine, Assiut University, Assiut, gliomas
EGYPT, 4Faculty of Medicine, Cairo University, Cairo, EGYPT. N. Testart, E. Triviño Ibañez, M. Zurita Herrera, A. Jorques Infante,
R. Luque Caro, A. Gonzalez-Jiménez, M. Rashki, A. Rodriguez-
Fernandez, M. Gómez-Río;
Aim/Introduction: Several molecular imaging tracers and MRI Hospital Universitario Virgen de las Nieves, Granada, SPAIN.
techniques are investigated for differentiating radiation necrosis
from residual/recurrent glioma. We aimed to explore the utility
of post-therapy 99mTc-methoxy-isobutyl-isonitrile (MIBI) brain Aim/Introduction: The follow-up of treated low-grade
SPECT/CT and multiparametric MRI (mpMRI) in patients with glioma (LGG) requires the evaluation of subtle clinical changes
glioma. Materials and Methods: Patients with pathologically and MRI results. When the result is inconclusive, additional
or radiologically documented glioma were prospectively procedures are required to assist decision-making, such as the
recruited for this study. 99mTc-MIBI brain SPECT/CT scanning use of advanced MRI (aMRI) sequences and nuclear medicine
was acquired 1 h. after i.v. injection of 666-925 MBq of the tracer. scans such as SPECT and PET. The aim of this study was to
Lesion volume was quantified using isocontour threshold of 70% assess and compare the sensitivities and specificities of each
of the maximum pixel counts (volMIBI). mpMRI was performed imaging procedure and to determine whether incorporating
on a 1.5 Tesla MRI machine within a median of two weeks 18
F-fluorocholine PET/CT in the follow-up protocol for treated
from MIBI SPECT/CT study for a subset of patients. Techniques LGG improves diagnostic accuracy and if it has a clinical impact.
included perfusion, with calculation of relative mean transit time Materials and Methods: This was a retrospective analysis of a
and relative cerebral blood volume (rCBV), spectroscopy, with prospective cochort of consecutive patients with treated LGG
calculation of choline/NAA ratio, and diffusion, with calculation during standard follow-up with indeterminate clinical and/or
of mean apparent diffusion coefficient (ADC). Qualitatively, radiological findings of tumour activity. All patients underwent
the readings from both modalities were reported on a 5-point clinical evaluation, aMRI, 201Tl-SPECT and 18F-fluorocholine PET/
probability score as (1=definitely negative, 2=probably negative, CT. Images were interpreted by visual evaluation complemented
3=equivocal, 4=probably positive, and 5=definitely positive with semiquantitative analysis. To determine its sensitivity
for residual/recurrent disease malignant). For the purpose of and specificity, the imaging results were compared to a gold
analysis, scores≥3 were considered positive. Results: Thirty- standard, either a surgical resection or a biopsy or a consensus
five non-consecutive patients; (25 male, 10 female; mean age based on a follow-up > 6 months. Results: Between January
43.5±16.4 years, 86% of them with high-grade glioma) were 2012 and December 2017, 34 patients (20 men and 14 women,
enrolled in this study. 8/21 patients who were scored positive mean ± SD age 41 ± 11.6 years (range 19 - 61 years) were included
on MIBI SPECT/CT died by the time of analysis, compared to in this study. The final diagnosis was established by histology
only 1/14 scored negative (p=0.056). volMIBI was significantly (eight surgical specimens, one biopsie) or by consensus of the
higher in high-grade compared to low-grade tumors (1.0±1.4 Neuro-Oncology Group (25 patients) after a follow-up of >6
vs. 2.6±2.4;p=0.039), and in patients who died compared months (mean 16.7 ± 2.83 months). In our cohort, the sensitivity
to those who were still alive (1.9±1.9 vs. 3.8±3.2;p=0.038). and specificity respectively for each test were: aMRI 95% and
volMIBI was significantly predictive of mortality with AUC from 66% 201Tl-SPECT 62% and 80%; 18F-fluorocholine PET/CT 89%
ROC analysis of 0.76 (95%CI:0.56-0.97;p=0.02). 13/35 patients and 86%. The global diagnostic accuracies were 91% for aMRI
underwent mpMRI. volMIBI showed strong positive correlation (36% inconclusive), 65% for 201Tl-SPECT (28% inconclusive), and
with Choline/NAA ratio (r=0.872;p=0.054). Both MIBI SPECT/CT 88% for 18F-fluorocholine PET/CT with no inconclusive studies.
and mpMRI agreed on categorizing 4 benign and 7 malignant The performance of 18F-fluorocholine PET/CT had a clinical
lesions. Two patients showed positive findings only on MIBI. impact with changes in the pre-test intended management
Those two patients continued to demonstrate increasing uptake in 64.7% of patients. Preliminary results from this cohort have
on subsequent follow-up MIBI SPECT/CT scanning. One of them previously been published in this journal [1]. Conclusion: Our
progressed rapidly and died on disease. 19/35 patients had at results support the need to complement structural MRI with
least one additional follow-up MIBI SPECT/CT study. Among aMRI and nuclear medicine procedures in selected patients.
the 19, 3/8 patients with negative initial findings demonstrated 18
F-Fluorocholine PET/CT can be useful in the individualized
positive uptake on subsequent scans while the remaining 11, management of patients with treated LGG with uncertain
who were originally scored positive, continued to show uptake clinical and/or radiological evidence of tumour activity.
impressive of residual/recurrent disease. Conclusion: In patients References: [1] Gómez-Río et al. Eur J Nucl Med Mol Imaging.
with glioma, post-therapy brain SPECT/CT with 99mTc-MIBI can 2015 May;42(6):886-95.
provide useful diagnostic and prognostic information, that may
S433 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

EP-0109 important index for evaluating hearing functional preservation


Spatial relationship of 11C-Methionine PET and Gd- in Neurofibromatosis Type 2 (NF2) patients with bilateral
enhanced MRI in oncological brain lesions by using a fully vestibular schwannomas (VS) who underwent surgery resection.
hybrid PET/MRI system The aim of this study was to investigate the utility of SUVmax on
P. Mapelli1,2, P. Scifo2, F. Fallanca2, V. Bettinardi2, A. Castellano1,3, M. 11
C-MET PET/CT in patients with NF2 to predict the change of
Barbera1,3, A. Falini1,3, L. Gianolli2, N. Anzalone1,3, M. Picchio1,2; hearing. Materials and Methods: Thirty young NF2 patients
1
Vita-Salute San Raffaele University, Milan, ITALY, 2Nuclear in a prospective natural history (17 men, 13 women; median
Medicine Department, IRCCS San Raffaele Scientific age, 21.7 years) with 53 measurable hearing ears was minored
Institute, Milan, ITALY, 3Neuroradiology Unit and CERMAC, by brain 11C-MET PET/CT and MRI imaging from 2015 to 2018.
IRCCS San Raffaele Scientific Institute, Milan, ITALY. The hearing function was classified by the American Academy
of Otolaryngology-Head and Neck Surgery (AAO-HNS) criteria.
Tumor maximum standardized uptake (SUVmax) was obtained
Aim/Introduction: 11C-Methionine (MET) PET and Gd- from PET/CT images automatically . Cox regression were
enhanced MRI regions are known to be both related with used to assess the association between PET/CT markers with
malignancy of brain neoplasms. In the present study their mutual hearing. Results: Eighteen ears maintained effective hearing
relationship by using a fully hybrid PET/MRI system was explored (Class A and B) ears while 35 ears hearing significant loss (Class
in a group of patients with brain oncological lesions. Materials C and D) among 53 ears during follow-up. The SUVmax was
and Methods: Nine patients (13 lesions) with MRI suspicion correlated significantly with hearing grades (P=0.002, rs=0.324).
for recurrent oncological disease underwent fully hybrid PET/ In comparison with those patients with low metabolic activity in
MRI with MET. During the simultaneous acquisition of PET and 11
C-MET PET/CT findings (SUVmax<2.75), a significant decrease
MRI, the MRI protocol consisted of T2w, FLAIRw, 3D-T1w pre- of hearing was discovered in patients with high metabolic
and post-contrast, diffusion and Dynamic contrast enhanced activity in 11C-MET PET/CT findings ( SUVmax>2.75) . The higher
(DCE) perfusion sequences. MET PET and MR perfusion were SUVmax was associated with hearing decrease on a univariate
firstly co-registered to 3D-T1 MR. A volumetric region of interest Cox model (hazard ratio = 0.433, P=0.002). Conclusion: The
(VOI) was used to measure standardized uptake value (SUV) SUVmax was related to the patient’s hearing in NF2, as an
max, metabolic tumour volume (MTV) and SUVmean for each independent predictive factor of hearing loss in natural history.
lesion evident on MET images. A first analysis was performed by References: None.
defining a second VOI based on the Gd-enhanced regions. Dice
coefficient between the two VOIs was calculated to assess the
overlapping between them. Results: Ten/13 lesions detected EP-06
by MRI resulted positive (metabolically active) on MET PET
images (mean SUVmax: 4,5; range: 2,5-10,8; mean SUVmean:
Translational and Molecular Imaging Therapy:
2,7; range: 1,5-6,5; MTV: 21,7, range: 0,5-94,6). The mean value of
Optimisation of Tracer Kinetics
Dice coefficient among patients with both positive regions was
0.55±0.18. Conclusion: In patients affected by oncological brain October 12 - 16, 2019 e-Poster Area
lesions, MET PET is confirming its capability in differentiating
between tumour active lesions and post therapeutic effects.
From this preliminary spatial location analysis, it is evident that
the areas defined by MET PET SUV and Gd MRI characterize EP-0111
different aspects of the tumour lesions (active lesions within First Reported SPECT/CT to Investigate Pharmacokinetics
non enhancing areas and viceversa) even if there is a quite good of Host Defence Peptides
overlapping. Further analysis on the complete cohort of patients K. Saatchi1, T. V. F. Esposito1, D. Pletzer2, C. Blackadar1, C. Rodriguez-
evaluating the quantitative perfusion and diffusion maps will be Rodriguez1, R. E. W. Hancock2, U. O. Häfeli1;
useful to deeply investigate these potentially relevant aspects of 1
Faculty of Pharmaceutical Sciences, University of
recurrent brain lesions. References: None. British Columbia, Vancouver, BC, CANADA, 2Centre for
Microbial Disease and Immunity Research, Department
of Microbiology and Immunology, University of
EP-0110 British Columbia, Vancouver, BC, CANADA.
Relationship Of Hearing Preservation Of Patients
With Neurofibromatosis Type 2 With Tumor Maximum
Standardized Uptake From The 11c-met Pet/ct Images Aim/Introduction: Host defense peptides (HDPs) are short,
X. Zhao, Z. Chen, S. Li, S. Zhang, C. Zhao, J. Zhang, X. Wang, F. cationic, amphipathic peptides with antimicrobial and
Zhao, P. Liu, L. Ai; immunomodulatory activity. HDPs present a promising
Beijing Tiantan hospital, Beijing, CHINA. alternative to existing antibiotics, which is of significance
given the rise in antimicrobial resistance. Challenges, such
as the aggregation of HDPs in biological media and lack of
Aim/Introduction: Preoperative hearing test results was an comprehensive pharmacokinetic assessments, have delayed
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S434

their translation into the clinic. This study presents the first was observed in the spleen (55%, n=33), mediastinum (90%,
detailed look at the biodistribution of lead HDPs and novel n=54) and liver (100%, n=60). In the second group (15-min);
formulations using nuclear imaging techniques. Materials SUVmax increased in the lacrimal glands (90.8%, n=109), parotid
and Methods: HDPs (eg. IDR1002) and formulations thereof glands (100%, n=120), submandibular glands (85%, n=102) and
were radiolabeled with 67Ga and characterized by standard duodenum (82.5%, n=99) in 60-min scans while decrease of the
techniques. The tracer was administered to healthy mice at uptake was observed in the spleen (60.8%, n=73), mediastinal
different dose levels (2, 5 and 50 mg/kg) via subcutaneous, blood pool (75.8%, n=91) and liver (100%, n=120). DIFFave of the
intravenous, intraperitoneal, and intratracheal delivery. Each lacrimal, parotid and submandibular glands, mediastinal blood
mouse underwent serial SPECT/CT scans up to 48 hours to pool, liver, spleen and duodenum were 3.8, 5.1, 4, 1.3, 1.7, 1,6 and
quantitatively track the distribution of the HDP. An ex vivo 3.5 g/mL respectively for the first group and 3.5, 4.5, 3.9, 0.7, 1.3,
biodistribution was also conducted following the terminal scan. 3.7, 3.6 g/mL respectively for the second group. %DIFFave of the
Results: 67Ga- IDR1002 precipitated upon injection forming a lacrimal, parotid and submandibular glands, mediastinal blood
local depot in the peritoneal cavity, subcutaneous fat, and lung pool, liver, spleen and duodenum were 36.2%, 29.6%, 22.4%,
parenchyma. The peptide was slowly absorbed systemically (i.e., 48%, 43.2%, 21.9% and 28.9% respectively for the first group and
subcutaneous absorption half-life was ~6h) and predominantly 31.5%, 24.4%, 20.2%, 27.4%, 34%, 23.8%, 28.3% respectively for
excreted renally. The peptide also precipitated into micron- the second group. The correlation between early (5-min and
size particles in the blood, which embolized in the lung 15-min) and 60-min post-injection scans was good (P<0.01)
capillaries and was lethal at higher doses. From the lung, the in all evaluated physiological uptake areas. Conclusion: It
peptide cleared via the reticuloendothelial system and kidneys. is observed that 68Ga-PSMA uptake of lacrimal and salivary
Conclusion: This study is an important first step in examining glands and gastrointestinal tract increases in time while uptake
the behaviour of HDPs in vivo. The tendency of IDR1002 for of liver, spleen and mediastinal blood pool tends to decrease.
example to precipitate upon injection may be useful for some References: None.
treatments, by forming a local depot of the drug and slowly
releasing it thereafter. However, most indications and route of
administration will require novel formulations of the peptide to EP-0113
overcome uncontrolled aggregations. References: None. Monitoring early vascular disrupting agent (VDAs)
treatment response with 68Ga-DOTA-Heptap, an albumin
binding tracer, in vivo PET/CT imaging
EP-0112 C. Huang1, G. Chang1, J. Lin1, S. Hsu1, W. Chang1, F. Huang2;
Comparison of the Physiological Uptake of 68Ga-PSMA 1
Center for Advanced Molecular Imaging and Translation,
Between Early and 60-min Post-injection PET/CT Scans Taoyuan, TAIWAN, 2National Taiwan University, Taipei, TAIWAN.
T. Hekimsoy, S. Isgoren, G. Daglioz Gorur, H. Demir;
Kocaeli University School of Medicine, Department
of Nuclear Medicine, Kocaeli, TURKEY. Aim/Introduction: The dynamic tumor vasculature changes
may be associated with tumor staging, treatment responds
monitoring and prognostic evaluation. In this study, the
Aim/Introduction: The purpose in this study was to investigate feasibility of using novel blood pool tracer-68Ga-DOTA-Hepta
the change in the physiological uptake of 68Ga-PSMA between as a surrogate biomarker for early detection of the functional
early (5-min and 15-min) and 60-min post-injection PET/CT status of tumor vasculature and whether such a biomarker
scans. Materials and Methods: One hundred eighty male can be used to monitor the treatment response after vascular
patients (mean age: 68.3±8.2) who underwent 68Ga-PSMA disrupting agent treatment was evaluated in vivo. Materials
PET/CT were analyzed. Patients were divided into two groups. and Methods: A subcutaneous tumor model was established
PET/CT was performed at 5-min and 60-min in the first group by inoculation of 5 × 106 of U87MG tumor cells into the front
(n=60) and at 15-min and 60-min in the second group (n=120) flanks. The resultant tumors were allowed to grow for 3−5 weeks
after administration of 68Ga-PSMA. Physiological uptake was until they reached volumes of 200−500 mm3. Tumor-bearing
determined by calculating SUVmax for the lacrimal, parotid mice were treated with vascular disrupting agent CA4-P at
and submandibular glands, mediastinal blood pool, spleen, a dose of 40mg/kg by intraperitoneal injection once a week
duodenum and SUVmean for the liver and compared between for 2 weeks. As a control, saline (100uL) was injected into the
early and 60-min images. Any 10% change in the SUV values was control cohort of mice (n=5), repeating the same procedures. In
accepted as increase or decrease. The average SUV difference addition to the PET/CT imaging assessment, the tumor growth
(DIFFave) between two datasets was calculated. The average was monitored every three days by caliper measurement of the
percent differences (%DIFFave) were calculated by dividing perpendicular dimensions of each mass (0.5 × length × width2)
the SUV difference to the SUV value at 60-min post-injection. during the experimental period. Results: Extremely high vessel
Results: In the first group (5-min); SUVmax of the lacrimal, parotid density of glioblastoma U87MG tumor correlated with its high
and submandibular glands was increased in 100% (n=60) of the tumorigenic potential and blood pool volume justifies its role
patients and SUVmax of the duodenum was increased in 83.4% as a potential prognostic marker. The 68Ga-DOTA-Heptap PET
(n=50) of the patients in 60-min scans. Decrease of the uptake tracer longitudinally demonstrated prominent tumor uptake in
S435 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

subcutaneous U87MG xenografts along with the steady growth different fractions was confirmed using mass spectrometry.
of tumor size monitoring with the caliper. However, upon the SPR of HER2 specific Nbs showed a marginally decreasing (~5-
administration of CA4-P, the immediate vessel collapse was 9 nM) affinity with additional conjugated chelators, whereas
observed with minimal tracer accumulation in PET imaging SPR for MMR-specific Nbs is pending. In vivo biodistributions
(2.74 ± 0.26 %ID/g) but rapidly restore and had even higher revealed typical biodistribution patterns, with minor differences
tracer uptake (6.75 ± 0.43 %ID/g ) than the control group (5.1± between fractions. The MMR-specific fractions show similar
0.26 %ID/g) with the repeated PET imaging after 24 h post- tumor targeting (~2% IA/g) for increasing NOTA amounts,
treatment. These imaging analysis results correlated well with though decreased uptake can be seen in targeted organs such
the subsequent tumor growth profile in which CA4-P treated as spleen (4.9±0.8 to 1.7±0.01% IA/g), liver (6.2±1.9 to 3.6±1.5%
group has an elevated tumor growth rate than the control IA/g) and bone (2.2±0.4 to 0.9±0.3% IA/g). Uptake in the kidneys
group ( 2.5-fold ), indicating that to compensate for the VDAs appears to increase when going from 1 to 2 conjugated NOTA-
effects, tumor cells might recruit growth hormones or signals chelators, though the difference is not significant. For the HER2-
to revive the blood vessel growth and deteriorate the treatment specific compounds, no off-target uptake is observed. There is,
prognosis. Conclusion: These results suggest that the proposed however, a significant difference in the uptake of the fractions in
68
Ga-DOTA-Heptap tracer is a promising surveillance biomarker kidneys (40.2±5.4 to 24.0±1.7 % IA/g), with increasing C/Nb ratio
for early malignant tumor detection as well as subsequent corresponding to decreased uptake. Due to lacking growth of
treatment effect monitoring. Thus, the non-invasive detection the HER2+ tumor model no statistical analysis was performed
of tumor vascular leaking activity in vivo may permit a more on tumor targeting. This experiment will therefore be repeated.
precise definition of the roles of tumor vasculature status and Conclusion: Overall biodistribution of the different Nb-NOTA
yield insight regarding novel therapeutic strategies in the fractions matched the expected distribution for Nbs, with
molecular level. References: None. minor differences between fractions. Additional analyses will be
performed for further evaluation. References: None.

EP-0114
Influence of the degree of chelator conjugation on the EP-0115
physicochemical properties of Nanobody PET tracers Design and biodistribution of 64Cu_labelled liposomes
P. Debie1, H. Baudhuin1, J. Puttemans1, S. Hernot1, C. Xavier1, T. bearing anti-CD44 aptamer in triple negative breast
Lahoutte2; cancer murine model
1
Vrije Universiteit Brussel, Jette, BELGIUM, F. Antoni1, H. Hillaireau2, F. Hontonnou1, B. Hosten1, N. Vignal1, L.
2
UZ Brussel, Jette, BELGIUM. Durand3, S. Denis4, V. Parietti5, C. Chomienne6, L. Sarda-Mantel1, E.
Fattal7;
1
Unité Claude Kellershohn Institut Universitaire d’Hématologie,
Aim/Introduction: A first 68Ga-labeled nanobody (Nb) for Paris, FRANCE, 2Institut Galien Paris-Sud, UMR CNRS 8612,
PET/CT imaging, targeting human epidermal growth factor Châtenay-Malabry, FRANCE, 3UMR INSERM 1131 Institut
receptor-2 (HER2), was translated to clinic, with other Nbs to Universitaire d’Hématologie, Paris, FRANCE, 4Institut Galien Paris
follow. To date, these compounds are prepared by random Sud, UMR 8612, Paris, FRANCE, 5Département d’expérimentation
conjugation with NOTA-chelator on the primary amines of animale, Institut Universitaire d’Hématologie, Paris, FRANCE, 6UMR
their lysine residues, generating a heterogenous mixture with INSERM 1131, Institut Universitaire d’Hématologie, Paris, FRANCE,
different chelator to Nb ratios (C/Nb). Different fractions may 7
Institut Galien Paris-Sud, UMR CNRS 8612, Paris, FRANCE.
have differences in affinity and pharmacokinetics, which is
relevant for their use in the clinic. We therefore evaluated
different fractions of two clinically relevant Nbs, against HER2 Aim/Introduction: Liposomes bearing anti-CD44 aptamers
and Macrophage Mannose Receptor (MMR), bearing 1, 2 or 3 (anti-CD44 aptasomes) have recently demonstrated great
chelators. Both binding capacity and in vivo biodistribution potentialities for in vivo siRNA delivery to triple negative MDA-
were investigated. Materials and Methods: Nbs were MB 231 breast cancer cells. This report attempts to evidence the
conjugated using standard procedures, at pH ~8.5 with 30* whole biodistribution of such aptasomes by Positron Emission
molar excess of NOTA. Conjugates were separated using anion- Tomography (PET) upon intravenous (IV) administration to
exchange chromatography, made possible due to the negative mice xenografted with MDA-MB 231, in order to consider a
charge of the NOTA-chelator. Obtained fractions were assayed companion imaging for further theranostic applications in
through, mass spectrometry and Surface Plasmon Resonance patients. Materials and Methods: The strategy to obtain anti-
(SPR). Finally, the different fractions were radiolabelled with CD44-NOTA-64Cu fluorescent aptasomes was first to develop a
68
Ga and injected in HER2+ tumor-bearing athymic, or MMR+ liposomal formulation containing both the metal chelator NOTA
Macrophage-infiltrated tumor bearing C57Bl/6 mice. The and fluorescein, then to post-insert a DSPE-PEG phospholipid
anti-MMR nanobody is cross-reactive for murine and human coupled to an anti-CD44 aptamer (Apt1). Radiolabeling
MMR, whereas the anti-HER2 Nb has reactivity for the human with Cu-64 was optimized. Fluorescent Cu-aptasomes were
homologue only. Ex vivo biodistributions (n=3/group) were tested in-vitro for specific binding to CD44-expressing cells
determined 80 minutes post-injection. Results: Separation of and cytotoxicity evaluation. Their in-vivo biodistribution was
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S436

quantified in comparison to that of NOTA-64Cu liposomes, affinity. Binding to cells was rapid, but internalized fraction was
using iterative microPET/CT imaging (from time of injection low for all conjugates and cell lines. Clearance of [57Co]Co-(HE)3-
to 72h post-IV) in mice bearing MDA-MB 231 xenografts. ZHER3-X from blood was quick (<1%ID/g 3h pi). All conjugates
Then tissular distribution of aptasomes and liposomes was specifically accumulated in the tumors and in organs with
studied ex-vivo by fluorescent microscopy. Results: NOTA was mErbB3 expression. The composition and charge of the Co-
successfully attached to liposomes and demonstrated good chelator-complex influenced the tumor and normal tissue
chelatant properties without affecting aptamer attachment uptake. Tumor uptake of NODAGA- and DOTA-conjugates with a
to CD44-expressing cells. Radiolabelling was achieved in 30 single negative charge (-1) of the radiometal-chelator-complex
minutes without any purification step. Aptasomes’ uptake in was 2-3 fold higher than for Co-NOTA- (neutral charge) and Co-
tumors was higher (2-fold) than that of non-targeted liposomes, DOTAGA- (-2 charge) variants. [57Co]Co-(HE)3-ZHER3-DOTA had
and inhibited by the co-administration of CD44’s natural ligand the best tumor retention and significantly lower concentration
(hyaluronic acid). Histological studies evidenced the presence in blood than the other conjugates at both time points, leading
of liposomes and aptasomes inside tumor cells. Conclusion: to superior tumor-to-blood (18 ± 5) and tumor-to-liver ratios
Our anti-CD44 aptasomes showed higher tumor uptake than (1.6 ± 0.3) at 24h pi. No significant differences between [68Ga]Ga-
untargeted liposomes, related to specific interaction with CD44 NODAGA and[57Co]Co-DOTA-labeled variants were observed 3h
in-vivo, so are good candidates for targeted anti-cancer therapy pi, but tumor-to-organ ratios improved with time for [57Co]Co-
in patients with CD44-positive tumoral types. Also, antiCD44- (HE)3-ZHER3-DOTA suggesting [57Co]Co-(HE)3-ZHER3-DOTA might
Apt-Lip-NOTA-64Cu aptasomes can be used for companion be favorable for imaging of HER3 expression. Conclusion:
PET imaging in this setting. References: Développement d›un [57Co]Co-(HE)3-ZHER3-DOTA with a mononegative charge of the
agent théranostique liposomal anti-CD44 pour le traitement de cobalt-chelator-complex was the most favorable cobalt-labeled
cancer,Médecine Nucléaire, (2018) 42 (3) 154. variant. Further increase in negative charge had an adverse
effect on biodistribution. The use of longer-lived PET nuclides,
such as cobalt-55, might be a promising alternative to [68Ga]Ga-
EP-0116 labeled affibody molecules for imaging of HER3 expression with
Optimizing affibody-mediated PET imaging of HER3 affibody molecules. References: None.
expression using long-lived radiocobalt for the next day
PET image
S. Rinne1, C. Dahlsson Leitao2, B. Mitran1, V. Tolmachev1, S. Ståhl2, J. EP-0117
Löfblom2, A. Orlova1; Pretargeted Radioimmunotherapy and SPECT Imaging
1
Uppsala University, Uppsala, SWEDEN, 2KTH - Royal of Peritoneal Carcinomatosis Using Bioorthogonal Click
Institute of Technology, Stockholm, SWEDEN. Chemistry: Probe Selection and First Proof-of-Concept
F. Degoul1, A. Rondon1, S. Schmitt1, A. Briat1, N. Ty1, M. Quintana1,
R. Membreno2, B. Zeglis3,2, I. Navarro-Teulon4, J. Pouget4, J. Chezal1,
Aim/Introduction: Oncogenic signaling of human epidermal E. Miot-Noirault1, E. Moreau1;
growth factor receptor type 3 (HER3) is a common cause of 1
UMR1240, Clermont-ferrand, FRANCE, 2Department of
disease progression and therapy resistance in cancer. Imaging Chemistry, Hunter College, City University of New York, New
of HER3 expression could improve patient management. York, NY, UNITED STATES OF AMERICA, 3Department of
However, low target expression and endogenous expression, Radiology, Memorial Sloan Kettering Cancer Center, New York,
particularly in liver, limit the imaging contrast. We previously NY, UNITED STATES OF AMERICA, 4Institut de Recherche en
demonstrated feasibility of radiolabeled anti-HER3 affibody Cancérologie (IRCM), U1194 – Université Montpellier – ICM,
molecules for PET imaging in preclinical models. We observed Radiobiology and Targeted Radiotherapy, Montpellier, FRANCE.
that increased negative charge of the radiometal-chelator-
complex reduces hepatic uptake and improves tumor-to-liver
contrast. Aim of this study was to investigate the influence Aim/Introduction: Pretargeted radioimmunotherapy
of charge of radiocobalt-chelator-complexes and compare (PRIT) based upon bioorthogonal click chemistry has been
the best radiocobalt-labeled variant of anti-HER3 affibody investigated for the first time in the context of peritoneal
molecule (HE)3-ZHER3 with the most favorable, recently optimized carcinomatosis using a 35A7 mAb bearing trans-cyclooctene
gallium-labeled variant. Materials and Methods: (HE)3-ZHER3-X (TCO) moieties and several 177Lu-labeled tetrazine (Tz)
(X=NOTA,NODAGA,DOTA,DOTAGA) was labeled with [57Co]Co as radioligands. Starting from three Tz probes bearing PEG linkers
a surrogate for 55Co. Binding specificity and cellular processing of varying lengths between the DOTA and Tz groups (i.e. PEGn
were investigated in HER3-expressing cancer cell lines BxPC- = 4, 8, or 12, respectively, for Tz-1, Tz-2, and Tz-3), we selected
3 and DU145. Binding affinity was measured on BxPC3 cells [177Lu]Lu-Tz-2 as the most appropriate for pretargeted SPECT
in real time. Biodistribution and targeting specificity of [57Co] imaging and demonstrated its efficacy in tumor growth control.
Co-(HE)3-ZHER3-X was studied 3h and 24h pi in Balb/c nu/nu Materials and Methods: An orthotopic model of PC was
mice with BxPC-3 xenografts and compared to [68Ga]Ga-(HE)3- obtained following the intraperitoneal (i.p.) injection of A431-
ZHER3-NODAGA. Results: (HE)3-ZHER3-X was stably labeled with CEA-Luc cells in nude mice. Tumor growth was assessed using
radiocobalt and bound specifically to HER3 with subnanomolar bioluminescence imaging. Anti-CEA 35A7 mAb was grafted
S437 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

with 2-3 trans-cyclooctenes per molecule. Pretargeted SPECT and structure-activity relationship analysis will be performed.
imaging and biodistributions were performed to quantify the Results: We could prepare total 13 compounds in reasonable
activity concentration of [177Lu]Lu-Tz-1-3 in tumors and non- yields and now we’re working on the biological assay to confirm
target organs to determine the best Tz probe for the PRIT of PC. its binding affinity to alpha-synuclein fibrils. When we changed
Results: The pharmacokinetic profiles of radiolabeled [177Lu] indolinone ring to thiazolidine-2,4-dione system, (E,E)-diene
Lu-Tz-1-3 were determined using both SPECT imaging and isomer, which is relevant to (Z,E)-diene of indolinone system,
biodistributions and demonstrated renal and hepatic clearances was exclusively formed and isolable. Since compound 1 is prone
for [177Lu]Lu-Tz-1, while [177Lu]Lu-Tz-2 and [177Lu]Lu-Tz-3 were to Z/E isomerization in DMSO solution and (E,E) isomer is much
mainly excreted renally. In addition, the longer the PEG, the less effective than (Z,E) isomer, we expect thiazolidine-2,4-dione
more rapidly the Tz probe was cleared from the peritoneal cavity. system will show better activity and properties. Conclusion:
In our PRIT study, we showed that 24 hours after the systemic Thioflavin T assay is now underway to confirm binding affinities
injection of 35A7-TCO, the i.p. injection of 40 MBq of [177Lu]Lu- of newly synthesized compounds and soon will be completed.
Tz-2 significantly slowed tumor growth compared to control Once we get the biological assay data, we’ll analyze structure-
mice receiving only saline or 40 MBq of [177Lu]Lu-Tz-2 alone. activity relationship and propose possible binding mode via
Ex vivo measurement of the peritoneal carcinomatosis index molecular docking study. References: 1. J. Med. Chem. 2015,
(PCI) confirmed that PRIT significantly reduced tumor growth 58, 6002−6017.
(PCI = 15.5 ± 2.3 after PRIT vs 30.0 ± 2.3 and 30.8 ± 1.4 for the
NaCl and [177Lu]Lu-Tz-2 alone groups, respectively). Conclusion:
Our results clearly demonstrate the impact the length of the EP-0119
PEG linker exerts upon the biodistribution of the 177Lu-labeled Identification of Peptide Ligands from Peptide Mixtures by
Tz radioligands. Furthermore, we demonstrated for the first Quantitative Analyses of Differential Cell Uptake Patterns
time the possibility of using bioorthogonal chemistry for both M. Parzinger, H. Wester;
the pretargeted SPECT and PRIT of peritoneal carcinomatosis. Technical University of Munich, Garching bei München, GERMANY.
References: None.

Aim/Introduction: The classical wet-chemical selection of a new


EP-0118 peptidic lead structure for a given target is a time-consuming
Structural Modification of Indolinone-Diene Analogues process that requires extensive synthetical and analytical efforts
as Alpha-Synuclein Ligands and Its Structure-Activity and subsequent in vitro assessment. To accelerate the classical
Relationship Analysis selection process we investigated a screening method, based
J. Lee, J. Han, E. Nam, K. Chang, S. Lee; on the synthesis of a mixture of peptide ligands, followed by the
Neuroscience Research Institute, Gachon differential analysis of the cellular uptake profile upon incubation
University, Incheon, KOREA, REPUBLIC OF. of cells with the radiolabeled mixture of these peptide ligands.
For proof-of-concept, CXCR4 was chosen as a model system
in combination with a mixture of 25 peptides, including
Aim/Introduction: Development of novel radioligand for iodo-FC131 (IC50 = 2.07 ± 0.34 nM). Materials and Methods:
alpha-synuclein imaging is one of the most challenging A mixture of 25 cyclic pentapeptides with 5 variations at 2
topics in the diagnostic radiopharmaceutical research area. positions was synthesized, isolated by preparative RP-HPLC and
Although the early detection of neurodegenerative diseases finally labeled with 125I. Subsequently, CXCR4+ Jurkat cells were
is still not very practical, there are several promising agents incubated at room temperature with the peptide mixture (1 nM
for Alzheimer’s disease (AD) targeting beta-amyloid, tau, and plus 10 nM control). After removing the supernatant, the cells
neuroinflammation, but none for Parkinson’s disease (PD). Lewy were washed with PBS and treated with a citrate buffer to isolate
body (LB) is a specific hallmark for PD, and to detect LB via a cell bound peptides. Supernatant and cell bound fractions were
non-invasive method, a lot of research groups are striving to concentrated via StrataX SPE followed by RP-HPLC analysis.
develop an effective small compound as an alpha-synuclein The peptide ‘enrichment pattern’ in the cell bound fraction
ligand. Materials and Methods: Indolinone-diene analogue1 1 was corrected for unspecific binding obtained in the control
was recently reported, showed not only a good binding affinity experiment. After comparison with the ‘depletion pattern’ in
with synthetic alpha-synuclein fibrils but a high selectivity over the supernatant fraction, the differential uptake of each peak in
beta-amyloid and tau fibrils (Ki= 2.1, 142, 80 nM, respectively, the original HPLC profile was determined and thus, after HPLC-
Thioflavin T assay result). Based on this structure, we designed MS, the peptides with the highest affinity towards CXCR4 were
several derivatives to increase binding affinity and selectivity selected. Results: The selection process described above was
but decrease lipophilicity to ensure better bioavailability. To validated by the successful ‘selection’ of iodo-FC131. In addition,
keep the overall structural feature, we modified 1) indolinone the analytical data revealed a second peptide (peptide-B) with
core to other heterocyclic ring systems, 2) one double bond in a twofold higher enrichment on the 1 nM test level. Analyses
diene to aromatic heterocyclic ring system and introduced 3) of the supernatants did not result in interpretable data since
several indolinone N-substituents. Prepared compounds were insufficient peak separation and thus complex peak integration
tested its binding affinity using Thioflavin T as a competitive dye did not allow for quantitative analysis. Affinity studies of the
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S438

two selected peptides resulted in IC50’s of 79.3 ± 4.8 nM for to the excellent nuclear properties with a half-life of 6 hours and
the newly isolated peptide-B (cyclo(Gly-2-Nal-Dap-Arg-tyr)) a gamma energy of 140 keV this would be a valuable addition
and 2.07 ± 0.34 nM for the ‘selected’ iodo-FC131. Conclusion: to the growing toolbox of pretargeted imaging applications
The described cell-based screening method allowed to and could help improve image contrast and reduce radiation
successfully isolate the well-known CXCR4 ligand iodo-FC131 burden to patients. References: 1. J. Med. Chem. 2016, 59, 20,
and a newly described second peptide-B ligand from a mixture 9381-9389.
of 25 peptides. However, due to the limited sensitivity of the
radiodetector, cross-evaluation of the supernatant and cell-
bound fraction failed, making this method less valid and more EP-0121
complicated than initially expected. References: None. Al18F-NOTA-octreotide PET imaging of the somatostatin
receptor: preliminary results of a human biodistribution,
dosimetry and safety study
EP-0120 E. Pauwels1, F. Cleeren2, T. Tshibangu2, M. Koole1, K. Serdons1, K. Van
99m
Tc Labeled Tetrazines for In Vivo Pretargeted Imaging Laere1, G. Bormans2, C. M. Deroose1;
L. Bohrmann1, P. Biniecka1, S. Karagiozov1, C. Rodriguez- 1
Nuclear Medicine - UZ Leuven; Nuclear Medicine and
Rodriguez1, M. M. Herth2, K. Saatchi1, U. O. Häfeli1; Molecular Imaging - KU Leuven, Leuven, BELGIUM,
1
University of British Columbia, Vancouver, BC, CANADA, 2
Radiopharmaceutical Research - KU Leuven, Leuven, BELGIUM.
2
University of Copenhagen, Copenhagen, DENMARK.

Aim/Introduction: Implementation of 68Ga-DOTA-peptide


Aim/Introduction: Targeted nuclear imaging using antibodies PET for somatostatin receptor (SSTR) imaging, the current
or nanoparticles often suffers from the drawback of requiring gold standard, can be restricted due to the limited availability,
long-lived radionuclides owing to the slow pharmacokinetics high cost and relatively low throughput associated with 68Ga-
of these targeting vectors. Using pretargeted imaging the labeled PET tracers. Recent radiopharmaceutical developments
biodistribution of the targeting vector and the radionuclide is have allowed to replace gallium-68 by fluorine-18 bound to
separated in order to mitigate this shortcoming and to improve aluminium (Al18F). Promising preclinical results with the Al18F-
imaging contrast. In a first step, a tagged carrier is administered labelled somatostatin analogue NOTA-octreotide have been
and allowed to accumulate at the target site. In a second step, reported, with an affinity of 3.6 nM for the SSTR[1]. Our ongoing
a radiotracer is injected with the aim of specifically binding study aims to obtain preliminary human data supporting
to the tagged carrier. Here we evaluate a panel of four 99mTc the feasibility of Al18F-NOTA-octreotide PET in patients with
labeled tetrazines for use in pretargeted imaging with a trans- neuroendocrine tumours (NETs). Materials and Methods:
cyclooctene (TCO)-tagged bisphosphonate that accumulates Three healthy volunteers were included so far (2M/1F; age
at sites of active bone metabolism1. Materials and Methods: 41-52 years). An IV bolus of 4 MBq/kg Al18F-NOTA-octreotide
Two aromatic tetrazines linked to a novel chelator for labeling was administered after a low dose CT. Tracer injection was
with 99mTc either directly or through an octaethyleneglycol- followed by consecutive whole-body PET scans up to 90
linker were synthesized using standard Pinner-like synthesis. minutes post-injection (PI), with additional scans at 150 and
Radiolabeling was performed using the commercially available 300 minutes PI. Safety and tolerability were assessed through
IsoLink kit (Covidien, Petten, The Netherlands) to convert regular monitoring for adverse events, clinical evaluations and
generator-eluted 99mTcO4- into [99mTc(CO)3(H2O)3]+. Tetrazines serial biochemical analysis. Images were analysed using MIM
were incubated with 99mTc tricarbonyl under mild conditions (70 (MIM Software Inc, US). For dosimetry, all source organs with
°C, 30 min) to afford the labeled tracers in high radiochemical relevant activity were delineated on the PET images, with CT
purity. For preclinical in vivo evaluation, healthy Balb/c mice guidance. Time-activity curves were extracted and integrated
were injected TCO-functionalized alendronate followed one to compute time-integrated activity. Individual absorbed organ
hour later by the tetrazines. Mice were imaged 0, 2 and 6 doses and the effective dose were determined using OLINDA/
h p.i.of the radiotracer and a full biodistribution study was EXM. Results: No adverse events were observed. Mean SUVmax
performed after the last imaging time point. Control animals at 60 minutes PI in the spleen, kidneys, liver, gall bladder, adrenal
were injected saline prior to the tetrazines. Results: SUV analysis glands, pituitary gland, pancreas, bone marrow and muscle were
shows immediate accumulation of the tetrazines in knees and 26.2±5.2, 29.9±10.8, 7.7±1.7, 7.7±1.5, 12.1±4.3, 8.6±1.5, 4.6±1.0,
shoulders of mice that received TCO-tagged alendronate, which 1.2±0.4 and 0.8±0.4, respectively. Excretion was mainly renal.
remains constant during the duration of the imaging study. Overall, this biodistribution is similar to that of the 68Ga-DOTA-
These findings are confirmed by the biodistribution which peptides. The low bone uptake on the PET images indicates
shows up to 3.34 %ID/g of bone uptake, which is a factor of that free 18F-fluoride formation is not clinically relevant. In a
27.8 higher than in control animals. Surprisingly, tetrazines first analysed subject, the highest dose was received by the
containing an octaethyleneglycol performed worse than their spleen (0.184 mGy/MBq), followed by the urinary bladder wall
counterparts without the hydrophilic linker. Conclusion: An (0.104 mGy/mBq) and the kidneys (0.046 mGy/MBq), with
established preclinical screening model for pretargeted imaging an effective dose of 0.021 mSv/MBq, which is comparable to
was used to identify a potential new 99mTc-labeled tetrazine. Due 18
F-FDG. Biodistribution, dosimetry, safety in healthy volunteers
S439 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

and initial findings in up to six patients with at least five SSTR Conclusion: Replacing the 2-naphthylalanine in PSMA-617
positive lesions on routine 68Ga-DOTA-peptide PET are planned. had profound impact on PSMA binding affinity and tumor
Conclusion: Administration of Al18F-NOTA-octreotide was well uptake. 68Ga/177Lu-HTK03041 showed higher tumor uptake than
tolerated and biodistribution and dosimetry are in line with 68
Ga/177Lu-PSMA-617, and the tumor accumulation remained
the 68Ga-DOTA-peptides. These preliminary results indicate stable over time. 177Lu-HTK03041 warrants further investigation
that Al18F-NOTA-octreotide shows promise for further human as an endoradiotherapeutic agent to treat metastatic prostate
exploration in imaging SSTR. References: [1] Laverman J.Nucl. cancer. References: None.
Med.2010;51(3).

EP-0123
EP-0122 68
Ga-labled N-Carboxymethyl-substituted PSMA ligands
Linker optimization to improve tumor uptake of PSMA enhancing binding affinity
binding radiopharmaceuticals B. Lee1, S. Chu1, W. Jung1, H. Moon1, H. Jeong1, H. Kim1, M. Kim1, J.
H. Kuo, Z. Zhang, H. Merkens, C. Zhang, N. Colpo, K. Lin, F. Bénard; Kim1, M. Kim1, Y. Lee2, K. Lee2, S. Lim2, D. Chi1,3, K. Song2;
Department of Molecular Oncology, BC 1
FutureChem, Seoul, KOREA, REPUBLIC OF, 2Korea Instituted
Cancer, Vancouver, BC, CANADA. of Radiological & Medical Sciences, Seoul, KOREA, REPUBLIC
OF, 3Sogang University, Seoul, KOREA, REPUBLIC OF.

Aim/Introduction: Various radiolabeled prostate-specific


membrane antigen (PSMA)-targeting constructs have been Aim/Introduction: High uptake in tumor cells and low
designed and evaluated for endoradiotherapy of prostate non-specific binding to normal organs are all important for
cancer. 177Lu-PSMA-617 is currently being studied in clinical trials the diagnostic and therapeutic efficacy of PSMA-targeted
for its therapeutic efficacy. To date, in current published series, radioligand. However, it is not easy to find compounds that
the complete response rate was low. The goal of this study was satisfy both of these factors at the same time. We made many
to increase the tumor uptake to improve endoradiotherapeutic efforts to solve this question and finally found that N-substituted
efficacy. Toward this goal, we investigated if substitution of methyl carboxylic acid of the lysine of Glu-urea-Lys enhances
the 2-naphthylalanine in PSMA-617 with other lipophilic the binding affinity to PSMA protein. Materials and Methods:
amino acids could improve binding affinity and tumor uptake. 22RV1 and PC3 PIP cell lines were used in vitro and in vivo
Materials and Methods: Four new derivatives (HTK03026, experiments, respectively. Binding studies were performed by
HTK03027, HTK03029 and HTK03041) were synthesized on solid- competition with 125I-labeled MIP-1095. MicroPET images were
phase. The 2-naphthylalanine in PSMA-617 was replaced with acquired using an INVEON PET/CT scanner. Results: In order to
2-aminooctanoic acid, 3-(2-anthryl)-L-alanine, 3-(1-pyrenyl)- confirm the effect of the carboxylic acid on the binding to PSMA,
L-alanine and 3-(9-anthryl)-L-alanine to generate HTK03026, simple acetylated Glu-urea-Lys compounds were synthesized
HTK03027, HTK03029 and HTK03041, respectively. The binding and tested in vitro. As a result, N-carboxymethyl substituted
affinity of non-radioactive standards to PSMA was determined acetylated compound (Ki = 3.31±0.25 nM) was found to
by in vitro competition assays. 68Ga labeling was performed have 11.3-fold higher binding affinity than only acetylated
in HEPES buffer (2 M, pH 5.0) with microwave heating (1 min). compound (Ki = 37.3±2.31 nM). This is probably due to the salt
Imaging and biodistribution studies were performed in mice bridge interaction with the arginine patch region in PSMA. DOTA
bearing LNCap prostate cancer xenografts. The best candidate chelator was then introduced in place of the acetyl group with
was selected, radiolabeled with 177Lu, and compared with 177Lu- a spacer of the appropriate length in between (FC694). A series
PSMA-617. Results: The binding affinities (Ki) of Ga-PSMA-617, of albumin binding moieties (phenyl, tolyl, and 4-iodophenyl
Ga-HTK03026, Ga-HTK03027, Ga-HTK03029, Ga-HTK03041, Lu- butanoyl) groups were added to the FC694 compound using
PSMA-617 and Lu-HTK03041 to PSMA were 1.23, 12.5, 22.0, 16.6, lysine to make FC701, FC703, and FC705, respectively. Binding
0.63, 0.24 and 1.88 nM, respectively. All 68Ga-tracers enabled clear affinities (Ki value) of these cold Ga-labeled DOTA-PSMA ligands
visualization of tumors in PET images. Tumor uptake values at 1h were measured to be 12.9±0.49, 8.12±0.16, 5.82±0.11, and
post-injection (p.i.) were 16.7±2.3, 12.9±2.9, 13.3±5.4 13.9±5.7 3.00±0.11 nM for FC694, FC701, FC703, and FC705. 68Ga-FC694
and 23.1±6.11 %ID/g for 68Ga-PSMA-617, 68Ga-HTK03026, 68Ga- showed moderate uptake in tumor tissue of 4.05±0.64 %ID/g at
HTK03027, 68Ga-HTK03029 and 68Ga-HTK03041, respectively. At 4.5 h, and rapid clearance from other organs including kidney
3h p.i., uptake of 68Ga-HTK03041 in tumor further increased to (0.41±0.16 %ID/g at 4.5 h). On the other hand, 68Ga-labeled
28.2±9.2 %ID/g. SPECT imaging showed both 177Lu-PSMA-617 FC701, FC703, FC705 showed tumor uptake of 7.20±3.39,
and 177Lu-HTK03041 had good tumor uptake and high target- 10.48±1.05, and 14.2±0.0 %ID/g at 4.5 h, respectively. The result
to-background contrast, and were mainly excreted by the was consistent with the relative albumin-binding ability of each
kidneys. Biodistribution results showed the tumor uptake of compound. Although kidney retention seemed to gradually
177
Lu-PSMA-617 peaked at 1 h p.i. (15.1±5.6 %ID/g) and gradually increase as albumin-binding ability increase, it is probably due
reduced over time (7.9±2.8 %ID/g at 120h p.i.). Conversely, the to prolonged blood circulation. Conclusion: Carboxylic acid
tumor uptake of 177Lu-HTK03041 at 4h p.i. was 18.7±3.0 %ID/g was found to increase the binding affinity of our new ligands
and remained stable over time (22.3±6.9 %ID/g at 120h p.i.). to PSMA protein. It is probably due to the salt bridge interaction
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S440

with the arginine patch region. It also serves to reduce non- response in HER2-positive patients. References: None.
specific binding by maintaining the hydrophilicity of the
compounds. MicroPET studies of 68Ga-labeled PSMA ligands
have shown that FC701 is suitable for PET imaging and FC705 is EP-0125
promising for therapeutic radioligand. References: None. Structure-activity-relationship investigation of an
albumin-binding motif to improve tumor-to-kidney
therapeutic index of PSMA-targeting agents
EP-0124 H. Kuo1, Z. Zhang1, C. Uribe1, H. Merkens1, C. Zhang1, F. Bénard1,2, K.
Application of 99mTc-3PRGD2 imaging for early predicting Lin1,2;
pathological response to neoadjuvant chemotherapy in 1
Department of Molecular Oncology, BC Cancer, Vancouver,
breast tumors and axillary lymph nodes BC, CANADA, 2Department of Radiology, University
W. Miao, Z. Chen; of British Columbia, Vancouver, BC, CANADA.
The First Affiliated Hospital of Fujian Medical
University, Fuzhou, CHINA.
Aim/Introduction: Albumin-binder-conjugated prostate
specific membrane antigen (PSMA)-targeting radiopharma­
Aim/Introduction: The aim of this study was to investigate ceuticals have been reported to improve tumor uptake and
the value of 99mTc-3PRGD2 imaging for predicting pathological enhance treatment efficacy of prostate cancer. Recently we
response to neoadjuvant chemotherapy (NAC) in stage II- evaluated 177Lu-HTK01169[1], a 4-(p-iodophenyl)butanoyl]-
III breast cancer patients compared with 18F-FDG imaging. Glu-conjugated 177Lu-PSMA-617 derivative, which delivered
Materials and Methods: Forty-one patients were underwent 8.3-fold higher absorbed dose to LNCaP tumor xenografts than
both 99mTc-3PRGD2 imaging and 18F-FDG imaging before NAC 177
Lu-PSMA-617 and achieved single dose tumor eradication.
(baseline), after the first and fifth cycle of NAC. The tumor-to- However, 177Lu-HTK01169 also resulted in higher absorbed
background (T/B) ratios of 99mTc-3PRGD2 imaging, standardized dose to kidneys, leading to ~50% reduction in tumor-to-kidney
uptake values (SUVmax) of 18F-FDG imaging in breast tumors therapeutic index compared to 177Lu-PSMA-617. The aim of this
and metastatic axillary lymph nodes (ALNs), and the relative study was to optimize the design of albumin binder to improve
changes of T/B (ΔT/B) and SUVmax (ΔSUVmax) regarding to the tumor-to-kidney therapeutic index while maintaining high
baseline scans were calculated. A pCR (pathological complete absorbed dose delivered to tumors. Materials and Methods:
response) was defined as the absence of residual invasive tumor 4-(p-R-substituted-phenyl)butanoyl]-Gly-conjugated (R=I, Br, Cl,
cells in all breast and axillary node specimens. Statistical analysis F, CH3, OCH3, NO2, NH2, H) PSMA-617 derivatives were synthesized
was carried out by the univariate analyses, logistic regression, on solid phase. 68Ga labeling was performed in HEPES buffer (2 M,
receiver operating characteristic (ROC) analysis and Z test. pH 5.0). A biodistribution study was performed in LNCaP tumor-
Results: A pCR was achieved in 13 of 41 patients after NAC in bearing mice. The best candidate was selected, radiolabeled
the prospective study. Logistic regression analysis indicated with 177Lu, and a dosimetry study was conducted in LNCaP
that tumor size and HER2 status were significantly associated tumor-bearing mice. Radiation dosimetry was calculated using
with pCR (all P < 0.05). In ROC analysis for predicting pCR after the OLINDA v.1.2. Results: Blood retention (%ID/g at 1h and 3h
first and fifth cycle, the area under curve (AUC) of ΔT/B in both pi) of 68Ga-labeled albumin-binder-conjugated PSMA-targeting
tumors and ALN combined were 0.859 and 0.778, respectively agents followed the lipophilicity order of the substituents:
(all P < 0.01). For ΔSUVmax, the ROC-AUC were 0.918 and 0.909, I(27.0±5.63, 23.9±1.03)≈Br(26.7±3.02, 21.2±2.21)>Cl(22.1±2.04,
respectively (all P < 0.01). ROC-AUCs of ΔT/B in breast tumors 17.4±1.15)>CH3(16.8±2.14, 13.6±1.23)>OCH3(12.1±0.60,
for predicting the primary tumor pathological response were 6.60±0.84)>NO2(6.69±0.27, 2.52±0.69)≈F(5.73±0.93,
0.827 (P < 0.01) and 0.687 (P > 0.05), and 0.859 (P < 0.01) and 2.10±0.48)>H(4.68±1.09, 1.17±0.36)>NH2 (1.74±0.11, 0.52±0.08).
0.713 (P < 0.05) for ΔSUVmax. The ROC-AUCs for predicting the Conversely, the tumor uptake (%ID/g) at 1h pi was inversely
ALN pathological response were 0.859 (P < 0.01) and 0.778 (P correlated to the lipophilicity of the substituents: H(25.9±3.21
< 0.05) for ΔT/B, and 0.572 (P > 0.05) and 0.802 (P < 0.01) for )>NO2(21.7±2.48)≈NH2(20.7±3.79)>F(18.8±3.35)≈OCH3(17.8±2.
ΔSUVmax. AUCs between ΔT/B and ΔSUVmax after first cycle 89)≈Cl(17.2±1.67)>Br(11.2±3.33)>CH3(8.54±0.74)>I(7.34±0.10).
had no statistical difference for predicting breast tumors Tumor uptake was further increased from 1h to 3h pi for all
pathological response (Z = 0.33, P = 0.74). However, AUC of early compounds except the NH2-substituted derivative. The Cl-
ΔT/B was higher than ΔSUVmax in ALN (Z = 2.10, P = 0.035). In substituted derivative (HTK03055) which showed relatively
HER2-positive patients, the early ΔT/B in responder group was faster blood clearance, high tumor uptake (30.1±3.12 %ID/g at
higher than that of non-responder group. While early ΔSUVmax 3h pi) and lower kidney uptake (35.6±7.23 %ID/g at 3 h pi) was
in responder group showed higher than non-responder group evaluated further with its 177Lu derivative. Compared with 177Lu-
in ER-positive patients. Conclusion: 99mTc-3PRGD2 imaging and HTK01169, 177Lu-HTK03055 had similar blood retention and peak
18
F-FDG imaging showed a comparable prediction for pCR to tumor uptake (55.9±12.5 vs 53.4±1.53 %ID/g), but much lower
NAC. 99mTc-3PRGD2 imaging showed an earlier predictive value kidney uptake (%ID/g) (1h (51.1±4.07 vs 31.7±5.13), 4h (85.7±7.11
than 18F-FDG imaging in ALNs pathological response. 99mTc- vs 44.2±4.86), 24h (125±16.4 vs 26.2±4.69), 72h (37.8±18.7
3PRGD2 imaging may be earlier for predicting pathological vs 11.5±1.17), 120h (8.63±2.51 vs 2.86±1.08)). Dosimetry
S441 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

calculations showed that compared to 177Lu-PSMA-617, 177Lu- with US (1.36%± 0.16 %ID/cc). After 72h post-US, no significant
HTK03055 delivered 8.9-fold higher absorbed dose to LNCaP difference between the US and the control cohorts was observed.
tumor xenografts and an 1.85-fold improvement in tumor-to- Heterogeneity of the diffusion of 89Zr-Cetuximab within the
kidney therapeutic index. Conclusion: We conducted structure- brain was obvious and showed a maximum of accumulation
activity-relationship investigation on the 4-(p-R-substituted- under the area where US were applied. Conclusion: Here, PET
phenyl)butanoyl]-Gly pharmacophore to optimize the selection was successfully combined with therapeutic US to demonstrate
of albumin-binding motif. We demonstrated that it was possible the efficiency of this strategy for mAb delivery into brain which
to maximize tumor uptake while improving the therapeutic raises potential application for tumor treatment. References: 1)
ratio to normal organs with this strategy. This approach can Westphal, M., et al (2017), CNS Drugs; 31(9): 723-735. 2) Escoffre,
lead to the development of therapeutic radiopharmaceuticals J. M., et al. (2013), Mol Pharm 10(7): 2667-75.
that require lower activities of expensive radioisotopes with
potentially improved safety and efficacy profiles. References:
Kuo H-T, et al. Molecular Pharmaceutics 2018;15:5183-5191. EP-07
Oncology: PSMA Imaging and Therapy
EP-0126
Impact of global ultrasound-induced blood-brain barrier October 12 - 16, 2019 e-Poster Area
opening on the distribution of full monoclonal antibody
cetuximab
C. Truillet1, V. Tran1, A. Novell2, M. Gerstenmayer1, A. Bouleau1, H.
Nozach1, B. Kuhnast1, N. Tournier1, B. Larrat1; EP-0127
1
CEA, Orsay, FRANCE, 2CNRS, Orsay, FRANCE. Unexpected high incidence of positive 68Ga-PSMA-11
PET/CT performed during androgen deprivation therapy
in biochemical recurrent patients, showing low PSA values
Aim/Introduction: Epidermal growth factor receptor (EGFR) (<0,5 ng/mL)
involved in cell proliferation and migration, is overexpressed in L. Muraglia1,2, F. Mattana1,2, A. Farolfi1,2, F. Ceci3, P. Castellucci2,1, L.
50% of glioblastomas. This suggests a relevance for molecularly- Calderoni1, V. Cervati1, R. Mei1, S. Fanti1,2;
targeted therapy using anti-EGFR based strategies using 1
Università di Bologna, Bologna, ITALY, 2Metropolitan
monoclonal antibodies (mAb), such as cetuximab, for therapy. Nuclear Medicine, Policlinico Sant’Orsola-Malpighi, Bologna,
Clinical trials have shown the beneficial effects of cetuximab in ITALY, 3Università degli studi di Torino, Torino, ITALY.
various EGFR-expressing peripheral tumors, but failed in patients
with recurrent glioblastoma.(1) One of the main issues is the
poor penetration of mAb into the central nervous system (CNS) Aim/Introduction: Primary aim of this retrospective single-
due to the presence of the blood-brain barrier (BBB). Recently, centre analysis was to investigate the detection rate of 68Ga-
ultrasound (US) in combination with microbubbles has been PSMA-11 PET/CT in patients with prostate cancer (PCa) and PSA
used to transiently open the BBB and promote the delivery failure after radical prostatectomy (RP) and low but increasing
of therapeutic agent to CNS.(2) Non-invasive, dynamic and PSA values (<0.5 ng/ml) during androgen deprivation therapy
quantitative methods such as PET imaging using radiolabeled (ADT) at the time of PET/CT scan. Materials and Methods:
mAb may provide a translational imaging method to address 68Ga-PSMA-11 PET/CT is performed at our institution through
the efficacy of US for the delivery of mAb into brain. Materials a prospective, singlecenter, open label study (Eudract:
and Methods: Cetuximab was conjugated to DFO and labeled 201500458927 OsSC). We retrospectively analysed consecutive
with 89Zr at 0.5 MBq/µg. Affinity comparison between human PCa patients with biochemical recurrence whom referred
and murine EGFR with cetuximab has been done. In vivo PET to our institute for a PET/CT scan. Inclusion criteria were: PSA
imaging and biodistribution were conducted in healthy nude levels under 0.5 ng/ml at the time of the 68Ga-PSMA-11 PET/
male mice (no US vs US groups, n=8) in order to follow the CT investigation, ongoing therapy with ADT and no prior ADT
kinetics of the 89Zr-Cetuximab overtime. Brain uptake of 89Zr- (abiraterone/docetaxel/enzalutamide or similar). 68Ga-PSMA-11
Cetuximab was initially monitored by dynamic PET, followed by PET/CT performance was evaluated in terms of detection rate
static PET imaging at different time points post-injection. The on a per-patient and a per-region basis (local vs distant lesions).
time activity curves allowed the determination of the transfer Results: According with inclusion criteria, we enrolled 26 PCa
rate constants between the blood and the brain. Results: patients (mean age 70 yo, range 53-83) with mean PSA level
Cetuximab exhibits an approximate 10-fold greater affinity with at the time of PET/CT of 0,28 ng/ml (median 0,29 ng/ml, range
human EGFR compared to mouse counterpart. In control mice, 0,10-0,50 ng/ml). T staging was ≥ pT3a in 23/26 cases (88%), N
the brain distribution of 89Zr-Cetuximab was negligible (transfer staging was pN1 in 14/27 cases (54%), Gleason Score was ≥8 in
rate = 0 ± 0.006 min-1). The transfer rate increased up to 1.3 ± 17/26 cases (65%), mean time to relapse (TTR) was 17 months
0.23 min-1 when US were applied. The brain uptake without (range 1-70 months). PET/CT scan was positive in 17/26 patients
US remained constant at 0.7± 0.09 %ID/cc overtime whereas it (65%). PSMA pathologic uptake was observed only in the
reached 1.34± 0.15 %ID/cc at 1h and stay stable during 48 hours prostate bed or in pelvic nodes in 3/17 patients (18%), only in
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S442

extra-pelvic region in 12/17 patients (71%) and both in pelvic patients, 1 had non-visualisation of the SN on SPECT/CT, 1 also
nodes and extra pelvic region in 2/17 patients (11%). Among had distant metastases, and 3 had a recurrence on PSMA-PET/
positive patients, 15/17 (88%) were oligo-metastatic (≤ 3 CT at the exact same location as the SN on SPECT/CT during
lesions) and 2/17 (12%) multi-metastatic. PSMA positive findings primary treatment (SN not reached or excised). Conclusion:
were detected in the following subregions: 2 prostate bed, 4 In 80% of pN0 patients who developed a BCR and showed a
pelvic nodes, 6 extrapelvic nodes, 19 bone. Mean SUVmax value lymph node metastasis/recurrence on PSMA-PET/CT, this was
of the lesions detected in our PET/CT scans was 18,2 (range due to a technically unsuccessful procedure or non-excised
8-86). Conclusion: Our results showed that the detection rate SN. This supports the accuracy of the SN procedure for lymph
of 68Ga-PSMA-11 PET/CT, in a population with low/moderate node staging in PCa patients and the potential importance of
PSA values, is significantly higher than the one expected from removing SNs outside the ePLND area. References: 1.Grivas N,
literature in similar population showing low PSA values (< Wit EMK, Kuusk T, KleinJan GH, Donswijk ML, van Leeuwen FWB,
0.5ng ml). This could be related to the influence of ADT on et al. The Impact of Adding Sentinel Node Biopsy to Extended
PSMA expression expecially in patients showing increasing PSA Pelvic Lymph Node Dissection on Biochemical Recurrence in
levels during ADT. Such elevated detection rate could influence Prostate Cancer Patients Treated with Robot-Assisted Radical
greatly the therapeutic approach in such population allowing a Prostatectomy. J Nucl Med. 2018 Feb;59(2):204-9.
prompt instauration of a personalized therapy. Main limitations
of our study are the small number of patients enrolled and its
retrospective design. References: None. EP-0129
Prospective evaluation of 68Ga-PSMA-11 PET/CT sensitivity
in patients with early biochemical relapse
EP-0128 O. Alonso Nunez1,2, G. dos Santos1,2, M. Rodriguez Taroco1, E.
Location of biochemical recurrences after robot-assisted Silvera2;
radical prostatectomy with sentinel node biopsy and 1
Uruguayan Centre of Molecular Imaging (CUDIM),
lymph node dissection: analysis with PSMA-PET/CT and Montevideo, URUGUAY, 2Clinical Hospital, University
comparison with initial SPECT/CT of Uruguay, Montevideo, URUGUAY.
O. R. Brouwer1, E. Wit1, P. J. van Leeuwen1, F. W. B. van Leeuwen2, H.
G. van der Poel1;
1
The Netherlands Cancer Institute, Amsterdam, NETHERLANDS, Aim/Introduction: We present our preliminary results as part of
2
Leiden University Medical Center, Leiden, NETHERLANDS. a prospective multicentre study sponsored by the IAEA (E13046)
aiming to evaluate the diagnostic values of 68Ga-PSMA-11 PET/
CT in patients with prostate cancer and biochemical relapse
Aim/Introduction: Robot-assisted radical prostatectomy after initial treatment. Our objective was to assess the sensitivity
(RARP) with extended pelvic lymph node dissection (ePLND) is of this technique in patients with early biochemical relapse.
generally applied as treatment for patients with intermediate Materials and Methods: We enrolled 86 patients between
and high risk prostate cancer (PCa). Sentinel node (SN) biopsy October 2017 and March 2019 with confirmed prostate cancer
has the potential to increase the diagnostic accuracy of ePLND. and biochemical relapse. From this sample, we analized 59
Furthermore, it has been shown that incorporating SN biopsy in patients (median age: 66, range: 47-85 years) with PSA < 4.0 ng/
the procedure can lead to prolonged biochemical recurrence mL (median: 0.61, range: 0.2-3.6 ng/mL) and with a follow-up
(BCR) free survival [1]. This study aimed to analyse the frequency of at least 3 months after PET/CT scanning (median: 11, range:
and imaging results of patients with biochemical recurrence 3-16 months). Images were acquired using a 16 or 64-slice PET/
using PSMA-PET/CT. Materials and Methods: Follow-up data of CT scanner with TOF correction and a dose of 2.0 MBq/kg 68Ga-
patients who were included in a prospective randomized phase PSMA-11. Patients were initially treated with prostatectomy
II study aiming to investigate the influence of the location of SN- (n=50, 85%) or radiation therapy (n=9, 15%). PET results were
tracer injection was analysed. Ethical Committee approval was validated by 3 blinded readers on a per patient basis and using a
obtained. All patients underwent RARP with SN biopsy followed composite reference standard including histopathology (when
by ePLND. The patients with a biochemical recurrence at follow- available), conventional imaging or serum PSA behaviour after
up were identified and evaluated. Results: Between 2013- salvage therapy. The study was approved by our local review
2016, 113 patients were included. 37 patients had 1 or more board and written informed consent was obtained from all
tumorpositive lymph nodes at histopathology (33%). In 35 of patients. Results: 68Ga-PSMA-11 PET/CT identified abnormal
these patients, the SN was als tumorpositive (95%, false negative tracer foci in 30 patients (positivity rate: 51%) in the following
rate 5%). Mean follow-up after surgery was 29,3 months (median sites: prostate gland (n=13), lymph nodes (n=36), bone (n=15)
27,5). 29 patients developed BCR (26%). Additional imaging was and lung (n=1). Forty-two patients were identified with prostate
performed in 25/29 patients (86%, PSMA-PET n=20, choline-PET cancer relapse by means of the composite standard during
n=4, nano-MRI n=1). Imaging revealed lymph node metastasis follow up and PET correctly identified 28 patients (sensitivity
in 15/25 patients (60%). The recurrence was localised in a was 0.67; 95% CI: 0.50-0.80). Sensitivity significantly increased
regional pelvic lymph node in the majority of patients (87%). with PSA: 0.48 for PSA ≤ 0.61 ng/mL to 0.86 for PSA > 0.61 ng/
5/15 patients were stages pN0 at SN+ePLND (33%). Of these mL (P=0.020). Conclusion: Our single centre results suggest
S443 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

that 68Ga-PSMA-11 PET/CT has a clinically relevant sensitivity for PSA levels. References: None.
the detection of prostate cancer lesions in the early biochemical
recurrence setting with potential impact on prompt salvage
therapy planning. References: None. EP-0131
Potential of molecular imaging with 99mTc-EDDA/HYNIC-
iPSMA SPECT in brain tumors
EP-0130 P. Vallejo Armenta1, J. Soto Andonaegui1, K. Contreras Contreras1,
Retrospective Study Of Patterns Of Response To Androgen G. Ferro Flores2;
Deprivation Therapy On 68Ga-PSMA PET/CT In Prostatic 1
Instituto Mexicano del Seguro Social, CDMX, MEXICO, 2Instituto
Adenocarcinoma Patients Nacional De Investigaciones Nucleares, Estado De México, MEXICO.
N. S. Mhatre, V. Rangarajan, A. Agrawal, N. Purandare, S. Shah, A.
Puranik;
Tata Memorial Hospital, Mumbai, INDIA. Aim/Introduction: Brain tumors (BT) are highly treatment
resistant and their marked angiogenesis attracts interest as a
potential therapeutic target. Several researchers have proved
Aim/Introduction: With limited literature on the abilities of that PSMA is expressed in the tumor-associated neovasculature
68Ga PSMA PET/CT as a treatment response assessment tool in of glioblastoma (GBM) and brain metastases (BM). Molecular
patients with prostatic adenocarcinoma, we explore the patterns imaging PET/CT is not as widely available; thus, a SPECT tracer
of disease response on this modality with respect to biochemical is more cost-effective alternative.99mTc-EDDA/HYNIC-iPSMA
response based on S.PSA, after medical or surgical androgen radiopharmaceutical has been shown high radiopharmaceutical
deprivation therapy. This may lead to further understanding of stability, specific receptor binding, high tumor uptake that due
the in vivo effect on PSMA expression and disease volume, which to the longer half-life (6.06 h) and increased lipophilicity1,2. The
may enhance its value in routine clinical practice. Materials and aim of the study was to assess the feasibility of using SPECT
Methods: Whole Body PET/CT scans with 68Ga labelled PSMA- with 99mTc-EDDA/HYNIC-iPSMA for imaging BT. Materials and
11 ligand, of 60 high risk prostatic adenocarcinoma patients Methods: 21 patients with suspected BT underwent preoperative
who underwent a baseline scan for staging, followed by a follow brain SPECT scan 3 hours after intravenous injection of 750 MBq
up scan after androgen deprivation therapy (ADT) ,with mean 99mTc-EDDA/HYNIC-iPSMA: 13 with indeterminate brain tumor
interval of 5.7 months between 2 scans ,were included in this (IBT) and 8 with suspected glioma recurrence. Both visual and
retrospective study. Treatment response on PSMA PET/CT based semiquantitative analyses were performed. Maximum target-
on quantitative volumetric PET parameter PSMA-Tumor Volume to-background ratio(TBRmax) was calculated using contralateral
(PSMA-TV); in the lines of PERCIST criteria, was compared with tissue uptake as background. PSMA expression was assessed
biochemical response based on S.PSA levels ; by inter-rater by immunohistochemistry (IHC) using PSMA monoclonal
agreement evaluation using Cohen’s kappa coefficient. Lesion- antibody. TBRmax was correlated with IHC findings and WHO
wise response pattern was studied. Results: Overall PET based grade tumor: low-grade glioma (LGG), high-grade gliomas
response with PSMA-TV showed no significant agreement with (HGG). Results: 8 HGG (gliosarcoma, 2 anaplastic astrocytoma,
biochemical response measured with S.PSA (Cohen’s kappa 5 GBM); 2 LGG (oligodendroglioma, astrocytoma); 3 BM (breast
value (κ) being 0.07).Overall PET based response with PSMA- cancer, poorly differentiated carcinoma); 6 recurrent gliomas
TV showed partial response in 64.2% and stable disease in 16.6 and 2 reactive gliosis were found. Among the 13 cases with
% of the patients with a complete biochemical response. Only IBT, scan was positive in 8 patients with HGG (TBRmax 19±11.01)
14.2% of patients who had complete biochemical response and 3 patients with BM (TBRmax 24.8±11.17), whereas 2 patients
showed concordant results on PET/CT. 2 cases even showed with LGG were negative. TBRmax was significantly correlated
progressive disease with complete biochemical response. with glioma grading (Spearman r=0.92,p<0.001). Among the 8
Complete volumetric resolution of metastatic regional/distant cases with suspected recurrence, scan was positivein 6 patients
lymph nodes in 50 % and skeletal lesions in 66% of the patients with glioma recurrence (TBRmax7.1±3.78), whereas 2 patients
with the respective lesions. Primary site disease was the least with gliosis were negative. The optimal cut-off value of the
responsive with 84% cases showing persistent or progressive TBRmax for the detection of malignant brain tumor (HGG, BM
disease. Conclusion: Discordance between the volumetric or recurrent glioma) was determined. By using 3.4 as the value
response on PET/CT (using PSMA-TV) and biochemical response for the threshold, the sensitivity and specificity were 89.5% and
endorses a possibility of the true objective representation of the 100%, respectively. PSMA was highly expressed in the vascular
post therapy disease burden by 68Ga PSMA PET/CT. Response endothelium of HGGand BM, while its expression in LGG was
to ADT differs lesion wise with primary disease showing very low and completely absent in gliosis. Conclusion: 99mTc-
persistence or progression in a strong majority of patients, EDDA/HYNIC-iPSMA brain SPECT is a feasible and potentially
whereas metastatic nodal and bony lesions show complete useful imaging tool for assessing of glioma grading (negative
resolution in majority of the patients with the particular lesions scan in LGG), to detect tumor recurrence (negative scan in
respectively. Thus, post therapy PET/CT response may be used treatment-related changes), planning treatment and biopsy
as a guide to plan local therapy with curative intent, following guidance (the background uptake in normal brain parenchyma
ADT. It is particularly useful in cases with low pre-therapy serum is absent, thus enhancing tumor detection). The PSMA binding
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S444

agents might be promising diagnostic and therapeutic option. EP-0133


References: 1. DOI: 10.1016/j.nucmedbio.2017.01.0122. DOI: Clinical Utility of 18F-PSMA 1007 in Prostate Cancer
10.1016/j.nucmedbio.2017.05.005. M. Joseph1, K. Vasan2;
1
Jeeyo PET-CT and Nuclear Imaging Centre, Mumbai, INDIA,
2
Jeeyo PET CT and Nuclear Imaging Centre, Mumbai, INDIA.
EP-0132
68
Ga-PSMA uptake variability: A test-retest study
J. olde Heuvel1, L. J. de Wit - van der Veen1, M. L. Donswijk1, Aim/Introduction: 68Gallium (68Ga) labelled prostate-specific
C. H. Slump2, M. P. M. Stokkel1; 1Netherlands Cancer Institute membrane antigen (PSMA), a well-established tracer in the
Antoni van Leeuwenhoek, Amsterdam, NETHERLANDS, imaging of prostate cancer, has several shortcomings such as
2
Univ of Twente, Enschede, NETHERLANDS. non-ideal energies, limited availability of the 68Ga generator,
requirement of high investment into synthesis modules and
Aim/Introduction: 68Ga-PSMA-11 is an emerging imaging a high urinary excretion, which can obscure detection of the
agent with unprecedented accuracy in prostate cancer (PCa) primary or residual disease. We present the clinical utility of
staging, yet repeatebility of uptake over time is unknown. The 18
F-PSMA-1007 which has a longer half-life, high labeling yields,
aim of this study was to assess the variability of 68Ga-PSMA-11 outstanding tumor uptake and fast, non-urinary background
uptake in primary prostate cancer (PCa) patients in a four-week clearance. Materials and Methods: Total 68 patients were
interval. Materials and Methods: Inclusion criteria were age scanned with 18F-PSMA-1007. Group A consisted of 50 patients
>18 years, histologically confirmed PCa and one of the following that were suspected cases based on elevated PSA levels with
criteria to perform a 68Ga-PSMA PET/CT scan: ≥cT3, Gleason high clinical suspicion. Histopathology was available in 40
score ≥7 or PSA ≥20 ng/mL. The first scan was performed on patients, deemed as Group A1. Histopathology could not be
clinical indication, after which the second scan was scheduled traced of 10 patients, deemed as Group A2. Group B consisted
approximately 4 weeks later. Patients were excluded if no of 18 patients who had proven disease, having received
substantial PSMA expression was visible in the prostate on the treatment, referred for disease status evaluation. Results: The
first scan or when treatment was started in between scans. sensitivity of 18F-PSMA for detection of disease in group A1 was
Acquisitions were performed on a Vereos digital PET/CT system, found to be 89.74%, PPV = 97.22%, accuracy = 87.50% based
45 min after injection of 100 MBq 68Ga-PSMA-11, from base of on pathological diagnosis. The SUVmax, SUVlbm and tumor
skull to mid-thigh. Acquisition time was 3 min per bed position background ratios, were found to have a small to medium
for the pelvis and 2 min for the remainder of the scan range. correlation with pathological grade (r < 0.3) and cores involved
Image reconstruction was performed using 3i15ss and 3mm (0.3 < r < 0.5). In Group A2, sensitivity, specificity, PPV and NPV
Gaussian. Semi-quantitative measures (SUVmax, SUVmean) based on PSA levels were found to be 100% with an accuracy
were determined in Osirix MD viewer using volumes-of-interest of 100%. Loco-regionally advanced disease was found in 27 of
(>2cm diameter) in the prostate tumour, normal tissues, and both Group A1 and A2 (42% of 50) and metastases were found
blood pool. The difference between the scans was evaluated in 20 out of 50 (40%), resulting in upstaging in 94% of patients.
using Wilcoxon-signed-rank tests. Results: Until April 2019, In Group B patients, 15 out of 18 (83%) patients were found
12 patients were included in this ongoing study. The median to have metastatic disease. There was no correlation between
injected activity was not statistically different between the PSA values and the present or absence of a positive scan in this
scans (99.4 MBq at scan 1 and 103.3 MBq at scan 2; p=0.08), group (r < 0.1). 18F-PSMA detected local recurrence in 3 out 4
as well as the time between injection and scan (45 and 47.5 (75%) patients who had undergone prostatectomy. Based on
min respectively; p=0.42). The median absolute difference in ROC analyses an SUVmax cutoff of > 4.1 was calculated to have
the prostate tumour uptake between both scans was 0.98 the highest sensitivity, specificity (92.1%, 50% respectively) for
SUVmax (range 0.27-1.60) and 0.49 SUVmean (range 0.06- detection of the primary disease in the prostate and SUVmax
0.89). Median absolute differences in liver, parotid, and kidney cutoff of > 3.5 was calculated for detection of nodal, lung
uptake were 0.36, 1.23, 3.24 SUVmax, respectively and 0.35, 0.94, and bone metastases (93.3% sensitivity, 100.00% specificity).
1.95 SUVmean. Blood pool activity showed median absolute Conclusion: 18F-PSMA-1007 is a robust tracer, demonstrating
differences of 0.17 SUVmax and 0.11 SUVmean. Median variation good sensitivity for the detection of primary and metastatic
of all measurements was below 11% for both SUVmax (range disease, staging and re-staging in patients of prostate cancer. It
5-31% tumour, 0-21% normal) and SUVmean (range 3-39% overcomes practical limitations of 68Ga-labelled PSMA targeted
tumour and 0-46% normal) and none of the differences (tumour, tracers. References: None.
normal tissues and blood pool) were statically significant.
Conclusion: Preliminary results of test-retest 68Ga-PSMA-11
PET/CT scans in a four-week interval show that 68Ga-PSMA-11 EP-0134
uptake is comparable, with a clinical irrelevant variation in Interobserver and Intraobserver Agreement for the
tumor and physiological distribution. Based on the presented Proposed miTNM Classification for the Interpretation of
repeatable uptake, 68Ga-PSMA PET/CT scans could potentially 68
GaPSMA-I&T PET/CT Imaging
be used for surveillance and response monitoring. References: A. Gültekin, O. Yaylali, T. Şengöz, D. Yüksel, H. Şenol;
None. Pamukkale University Medical Faculty, Denizli, TURKEY.
S445 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

Aim/Introduction: Prostate cancer(PCa) is the second Aim/Introduction: In patients with biochemically recurrent
most common cancer in men. Prostate spesific membrane prostate cancer (PCa), highly sensitive localisation of recurrence
anjigen(PSMA) is the most favorable tumor specific biomolecule is crucial, so patients may undergo salvage treatment as early
found in molecular imaging studies. In recent years, 68Ga-PSMA as possible. 68Ga-PSMA-PET/CT has become a routinely used
PET/CT has been used in diagnosis of PCa. This method is technique in the evaluation of these patients. MRI is known to
rapidly spreading due to the important clinical benefits. Before be superior to CT in soft tissue contrast and offers additional
widespread clinical adoption of PSMA targeted PET imaging, its functional data through diffusion-weighted sequences, so
intraobserver and interobserver variability and agreement need the combination of PET with MRI might increase detection
to be established. There are very few studies on this subject. In of recurrent disease. The aim of this prospective study was to
this study, we aimed to determine the intra and inter observer investigate the incremental value of PET/MR versus PET/CT
agreement levels of 68Ga-PSMA I&T PET/CT according to miTNM using 68Ga-PSMA in patients with biochemically recurrent PCa.
classification. Materials and Methods: Between March and Materials and Methods: Patients were prospectively included
June 2018, a total of 80 patients with 68Ga-PSMA PET/CT with and underwent routine 68Ga-PSMA PET/CT (Siemens Biograph
histologically proven PCa were evaluated twice, blindly by four Truepoint 40; 69 min p.i., range 57-141min), followed by PET/
nuclear medicine specialists at 4 weeks intervals. 68Ga-PSMA MR (GE Signa 3T; 127 min p.i., range 80-167). All PET scans were
synthesized in our department for PET/CT imaging was injected evaluated by three nuclear medicine physicians for number
intravenously at a dose of 145-166mBq. After 60 minutes of of lesions, location and maximum and mean standardized
injection, whole body scan images were created with the PET/ uptake values (SUV). The CT and MR images were assessed by a
CT device. PET/CT evaluations were performed according to uroradiologist. The findings were then combined in consensus
miTNM classification over standard forms. We used Cohen’s to an overall PET/CT and PET/MR result. Results: A total of 34
Kappa and Fleiss’ Kappa analysis for to analyse agreement inter patients were included with a mean age of 68 (± 7) years, mean
and intra observers. Statistical analysis was performed using R PSA of 2.1 ng/mL and initial Gleason score between 6 and 9. 63
(version 3.4.3, Vienna, Austria) in RStudio (Version 1.1.463 - © lesions were detected by PETCT, 69 by PETMR, 31 by CT only and
2009-2018 RStudio, Inc.). Package that we used for the analysis 44 by MR only. All lesions detected by PETCT were also detected
were ”irr”. Results: When 68Ga-PSMA PET/CT findings are by PETMR, while 6 additional lesions were detected by PETMR
evaluated according to miTNM (tumor, lymph node, distant (69 vs 63, p = n.s.). No PETCT detected lesions were missed by
metastasis) classification, the obtained kappa values are as PETMR. There was no significant difference in detection of local
follows. Intraobserver Cohen’s kappa coefficient was found to recurrence, bone or soft tissue lesions. Additional lesions to the
be 0.754±0.202 (substantial agreement), 0.907±0.007 (almost PETMR findings on MRI where two bone lesions. One patient
perfect agreement), 0.935±0.047 (almost perfect agreement showed multiple PSMA negative liver lesions on the MRI. An
) for miT, miN, miM, respectively. In interobserver assessment, additional finding on CT was one PSMA negative lung lesion.
interobserver adaptation for miT was good, agreement for miN, Overall combined interpretation showed 72 lesions on PET/
and agreement for miM was almost perfect. In the interobserver MR, PET/CT showed 66 lesions, but this difference was not
evaluation between four observers, the kappa coefficient significant. SUVmean and SUVmax values were significantly higher
was 0.502±0.295 for miT(moderate agreement), 0.722 on PETMR than on PETCT in lymph nodes (all p < 0.01), which may
±0.149(substantial agreement) for miN, and 0.837± 0.062(almost be related to the scan order (PET/CT first) and spatial resolution/
perfect agreement) for miM. Conclusion: In the literature, there contrast differences (time of flight on the PET/MR). Conclusion:
is no research on the intraobserver agreement study of 68Ga- In this prospective study, 68Ga-PSMA PET/MR was able to detect
PSMA PET/CT. Our findings are the first results. The intraobserver localisation of biochemically recurrent PCa at least as accurate
agreement of PSMA PET/CT is almost perfect. PSMA PET/CT has as PET/CT. References: None.
moderate interobserver compliance in the evaluation of the
primary tumor, but it has excellent interobserver agreement
levels in local lymph node metastasis and distant metastasis EP-0136
evaluation. References: None. The Diagnostic Performance of18F-PSMA-1007 PET/CT In
Prostate Cancer Patients With SuspectedRecurrence After
Definitive Therapy
EP-0135 T. Lengana1, K. Kopka2, I. Lawal1, T. Boshomane1, K. Mokoala1, M.
Prospective comparison of hybrid 68Ga-PSMA PET/CT and Vorster1, F. Giesel3, M. Sathekge1;
PET/MR in patients with biochemically recurrent prostate 1
Department of Nuclear Medicine, Steve Biko Academic Hospital
cancer and University of Pretoria, Pretoria, SOUTH AFRICA, 2Division
S. Jentjens1, C. Mai1, L. De Coster2, N. Ahmadi Bidakhvidi1, N. of Radiopharmaceutical Chemistry, German Cancer Research
Mertens1, W. Everaerts1, S. Joniau1, R. Oyen1, K. Van Laere1, K. Center, Heidelberg, GERMANY, 3Department of Nuclear Medicine,
Goffin1; Heidelberg University Hospital, Heidelberg, GERMANY.
1
University Hospitals Leuven, Leuven, BELGIUM,
2
Europe Hospitals, Brussels, BELGIUM.
Aim/Introduction: The prostate bed is the commonest site
of early recurrence of prostate gland. The currently used PSMA
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S446

ligands (68Ga-PSMA and 99mTc-PSMA) undergo early urinary for qualitative (visual) assessment of suspicious nodes and
clearance resulting in interfering physiological activity within assessment of quantitative parameters of the primary tumour in
and surrounding the prostate. This can result in sites of cancer the prostate (SUVmax, total activity (PSMAtotal) and PSMA positive
recurrence being obscured.18F-PSMA-1007 has an advantage of volume (PSMAvol)). Sensitivity and specificity of quantitative
delayed urinary clearance thus the prostate region is reviewed PET parameters to predict nodal metastasis were assessed with
without any interfering physiological activity.The aim of this study receiver operating characteristics (ROC) analysis. A multivariable
was to determine the diagnostic performance of 18F-PSMA-1007 logistic regression model combining visual nodal status on PET
PET/CT in patients with biochemical recurrence after definitive and primary tumour PSMAtotal was built. Net benefit at each
therapy. Materials and Methods: Forty-six Prostate cancer risk threshold was compared with five nomograms: MSKCC
patients (mean age 66.6±7.66, range 48-87 years) presenting nomogram, Yale formula, Roach formula, Winter nomogram
with biochemical recurrence (mean PSA 2.37±2.81ng/ and Partin tables (2016). Results: Overall, pathology of ePLND
ml, range 0.05 - 9.97) underwent non-contrast-enhanced specimens revealed 31 pelvic metastatic lymph nodes in 12
18
F-PSMA-1007 PET/CT. Areas of abnormal tracer uptake above patients. 68Ga-PSMA-11 PET correctly detected suspicious nodes
background activity outside of organs with physiologic tracer in 7 of them, yielding a sensitivity of 58% and a specificity of
biodistribution were considered as suggestive of prostate 98%. The area under the ROC curve for SUVmax was 0.70, for
cancer recurrence. PET/CT findings were evaluated qualitatively PSMAtotal 0.76 and for PSMAvol 0.75. The optimal cut-off for nodal
and semiquantitatively (SUVmax) and compared to the results involvement was PSMAtotal > 49.1. The combination of a PSMAtotal
of histology, Gleason score, and conventional imaging. Results: > 49.1 and visual positive nodes yielded a sensitivity of 100%
Twenty-four of the 46 (52.17%) patients demonstrated a site of and a specificity of 69% in our cohort. Furthermore, the PET
recurrence on 18F-PSMA-1007 PET/CT. Oligometastatic disease model including those two PET parameters had a persistently
was detected in 20 (43.5%) of these patients. Of these 9 (37.5%) higher net benefit compared to all clinical prediction models.
demonstrated intra-prostatic recurrence, whilst lymph node Conclusion: Our model combining visual lymph node analysis
only disease was noted in 8 (33.3%) whilst a single patient on 68Ga-PSMA-11 PET with PSMAtotal of the primary tumor
demonstrated isolated skeletal recurrence. The detection rates performed better than currently used clinical prediction models
for PSA levels 0 - <0.5, 0.5-<1, 1-2, >2 were 31.3%, 25%, 55.6% and to predict lymph node metastasis. Although this result has to be
76.5% respectively. 7 (29,2%) of the positive patients had been validated, 68Ga-PSMA-11 PET showed the potential to improve
described as negative or equivocal on conventional imaging. patient selection for ePLND and reduce unnecessary surgical
Lowest detected PSA value was at 0.19ng/ml. Conclusion: procedures. References: None.
18
F-PSMA-1007 demonstrated good diagnostic performance
detecting sites of recurrence at PSA values as low as 0.19ng/ml.
Its superior ability to detect recurrence missed by conventional EP-0138
imaging will have a significant impact on patient management. Head To Head Comparison Of 18f-fch And 18f-psma-1007
References: None. Pet/ct In Biochemically Relapsed Prostate Cancer Patients -
Preliminary Results
E. Witkowska-Patena1,2, A. Giżewska1,2, M. Dziuk1,2, J. Miśko2, A.
EP-0137 Budzyńska1,2, A. Walęcka-Mazur3;
68
Ga-PSMA-11 PET surpasses clinical nomograms for 1
Military Institute of Medicine, Warsaw, POLAND,
prediction of lymph node metastasis in patients with 2
Affidea Mazovian PET/CT Medical Centre, Warsaw,
intermediate to high-risk prostate cancer POLAND, 3Synektik Pharma, Kielce, POLAND.
D. A. Ferraro, U. J. Muehlematter, H. I. Garcia Schüler, N. J. Rupp, T.
Hermanns, I. A. Burger;
University Hospital of Zurich, Zurich, SWITZERLAND. Aim/Introduction: The aim of the study was to prospectively
compare diagnostic performance of 18F-FCH and
18F-PSMA-1007 PET/CT in patients with biochemical relapse
Aim/Introduction: Radical prostatectomy with extended (BCR) of prostate cancer and low prostate-specific antigen (PSA)
pelvic lymph node dissection (ePLND) is a curative treatment levels. Materials and Methods: We prospectively enrolled 40
option for patients with clinically significant localized prostate BCR patients after radical treatment of prostate cancer and
cancer. The decision to perform an ePLND can be challenging PSA levels ≤2.0 ng/ml (median, 0.7 ng/ml, range, 0.01-2.00).
because the overall incidence of lymph node metastasis is 18F-FCH and 18F-PSMA-1007 PET/CT imaging was performed
relatively low and ePLND is not free of complications. Using within a mean interval of 54±21 days. Skull to mid-thigh scans
current prediction models to identify patients with nodal were done 87±10 min and 95±12 min after injecting 248±35
involvement, approximately 84-94% of ePLNDs performed are MBq and 295±14 MBq of 18F-FCH and 18F-PSMA-1007,
negative. The aim of this study was to compare the ability of respectively. Rate of negative, equivocal or highly suspicious of
68
Ga-PSMA-11 PET with established nomograms to predict malignancy scan results was compared in per-patient analysis.
lymph node metastasis in men with prostate cancer. Materials Per-lesion, identified lesions were grouped as equivocal or
and Methods: 68Ga-PSMA-11 PET scans of 60 patients highly suspicious for malignancy and then compared for their
undergoing radical prostatectomy with ePLND were reviewed number, localisation (local relapse, lymph nodes, bones) and
S447 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

SUVmax values. Results: 18F-FCH and 18F-PSMA-1007 PET/ SA.KuE and the fluoro-derivatives Ethylfluoride.SA.KuE and
CT scans were positive (showed any lesions) in 17 (42.5%) 4-Fluoroethoxybenzyl.SA.KuE were determined in a competitive
and 35 patients (87.5%), respectively. Out of positive scans, cell assay using PSMA-expressing LNCaP-cells. LNCaP cells were
12% of 18F-FCH and 69% of 18F-PSMA-1007 PET/CT scans incubated with 0.75 nM [68Ga]Ga-PSMA-10 in the presence of
were highly suspicious of malignancy. The remaining 88% different concentrations of the non-labeled PSMA-ligands. After
and 31%, respectively, were equivocal. Per-patient, 18F-FCH incubation at RT and removal of free radioactivity, cell-bound
and 18F-PSMA-1007 PET/CT scan results were alike in 25% activity was measured. PSMA-11 was used as reference. Data
of cases. In 70% of scans, 18F-PSMA-1007 PET/CT upgraded were analyzed in GraphPad Prism 5 using nonlinear regression.
18F-FCH PET/CT results. 18F-PSMA-1007 scans also showed Male Balb/c nu/nu mice were subcutaneously inoculated with
significantly more lesions (184 vs 63, p=0.0006). Local relapse, 5.106 LNCaP-cells. After i.v. administration of [68Ga]Ga.DATA.
lymph node and bone lesions accounted respectively for 9%, SA.KuE (~10 MBq/nmol), the mice were sacrificed 1 h p.i. and the
58% and 33% of 18F-PSMA-1007 and 5%, 89% and 6% 18F-FCH radioactivity of the organs was measured. % ID/g values were
of PET/CT findings. Highly suspicious lesions accounted for calculated. Results: Radiolabeling of AAZTA5.SA.KuE and DATA.
74% of 18F-PSMA-1007 and 11% of 18F-FCH PET/CT findings. SA.KuE showed radiochemical yields of >95 % in 5 minutes for
In 18F-PSMA-1007 PET/CT, highly suspicious lesions accounted 10 nmol at RT. The IC50 values of AAZTA5.SA.KuE and DATA.SA.KuE
for 75%, 70% and 80% of local relapses, lymph node and bone exhibit a nanomolar binding affinity (52.1 ± 4.0 nM and 51.1 ± 5.5
findings, respectively. In 18F-FCH PET/CT all local relapses (n=3) nM respectively). 4-Fluoroethoxybenzyl.SA.KuE shows a 7-fold
and bone lesions (n=4) as well as 88% of lymph node findings higher binding affinity than Ethylfluoride.SA.KuE (40.8 ± 4.9
were equivocal. SUVmax values of the assessed lesions are nM vs. 279.4 ± 3.7 nM). Tumor uptake of [68Ga]Ga.DATA.SA.KuE
now undergoing statistical analysis. Conclusion: In early BCR was high (4.65 ± 0.58 %ID/g) and resulted in a high tumor-to-
patients 18F-PSMA-1007 showed higher detection rate than blood ratio of 9.3. Kidney uptake was remarkably low 12.82 ±
18F-FCH PET/CT, especially of bone lesions. The former also 4.84 %ID/g. Conclusion: The results of the competitive binding
showed more lesions in total, more highly suspicious lesions assay on LNCaP cells showed a nanomolar binding affinity for
and less equivocal lesions. References: None. the chelator.SA.KuE derivatives and 4-Fluoroethoxybenzyl.
SA.KuE. Biodistribution data revealed the potential of SA in
reducing kidney uptake. References: None.
EP-0139
Novel squaric acid coupled KuE-based PSMA inhibitors:
Synthesis, radiolabeling with gallium68 and first in vitro EP-0140
and ex vivo evaluation Use of 68Ga-PSMA-11 PET/CT in the detection of prostate
H. Lahnif1, L. Greifenstein1, T. Grus1, R. Bergmann2, M. cancer recurrence of non metastatic castrate-resistant
Schreckenberger3, M. Miederer3, S. Pektor3, F. Roesch1; patients: posivity rate and impact on patient management
1
Johannes Gutenberg University Mainz, Mainz, GERMANY, M. Gauthé, A. Fourquet, C. Aveline, F. Montravers, J. Talbot;
2
Helmholtz-Zentrum Dresden-Rossendorf, Dresden, GERMANY, Hôpital Tenon, Paris, FRANCE.
3
University Medical Center Mainz, Mainz, GERMANY.

Aim/Introduction: We aimed to evaluate the detection rate


Aim/Introduction: Introduction: Prostate cancer (PC) is and the impact on therapeutic management of PET/CT using
one of the most common cancer types worldwide. Prostate- prostate-specific membrane antigen ligand labeled with
specific membrane antigen (PSMA) has been identified as an gallium-68 (PSMA-11) in non-metastatic prostate cancer (PCa)
ideal target in diagnostic and therapy of PC since it is 1000-fold patients developing castration-resistance. Materials and
overexpressed in PC-cells. As target vectors for PSMA, urea- Methods: Not metastatic PCa patients who were referred for
based-scaffolds have been established. KuE (L-lysine-urea- PSMA-11 PET/CT because of a rise of prostate-specific antigen
L-glutamate) moiety is the most used binding motif in PSMA (PSA) serum level despite castrate serum testosterone inferior
inhibitors. Aims: In preliminary studies, we have identified the to 50 ng/dl between April 2016 and April 2018 were included.
squaric acid (SA) as a promising linker moiety between the Abnormal foci detected on imaging were quoted in multiple
pharmacophore unit and radiolabeling unit. The application of anatomical areas (prostate/prostatic lodge, pelvic lymph nodes,
SA as a coupling agent allows an easy synthesis, e.g. avoiding paraaortic lymph nodes, supra-clavicular lymph nodes, bone
challenging protection group chemistry, and enables a fast and other locations) according to a 3-point scale (no suspicious
and selective coupling. In this study, we investigate the impact uptake, equivocal uptake and pathologic uptake). Patients
of SA on the binding affinity and the pharmacokinetics of the were categorized as metastatic if imaging detected at least a
potential PSMA ligands [68Ga]Ga.AAZTA5.SA.KuE, [68Ga]Ga.DATA. pathologic foci outside the prostate/prostatic lodge area, and
SA.KuE and 4-[18F]F Fluoroethoxybenzyl.SA.KuE. Materials oligometastatic if imaging detected at best 3 pathologic foci.
and Methods: AAZTA5.SA.KuE, DATA.SA.KuE, Ethylfluoride. The impact on therapeutic management was assessed by
SA.KuE and 4-Fluoroethoxybenzyl.SA.KuE were synthesized. comparing changes decided during multidisciplinary meeting
Binding affinities of chelator.SA.KuE derivatives [natGa] before and after PSMA-11 PET/CT. Results: Thirty-eight patients
Ga.AAZTA5.SA.KuE, AAZTA5.SA.KuE, [natGa]Ga.DATA.SA.KuE, DATA. in total were included, among whom 25 (66%) had history of
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S448

prostatectomy. The mean age was 72 years-old and the median 0.62) and fair agreement for visceral lesions (ƙ = 0.22). Region-
PSA serum level the day of the imaging was 3 ng/ml. The median based analysis according to the PIP-RADS classification showed
follow-up time after imaging was of 12 months. PSMA-11 PET/ fair to substantial agreement for all tumor sites, except for
CT was pathologic in 89%, equivocal in 3 % and negative in 8% visceral lesions (ƙ = 0.22). Conclusion: The structured PIP-RADS
of cases. At least one pathologic focus was found in 39% of cases classification provides substantial interobserver agreement in
in the prostate/prostatic lodge, 34% in pelvic lymph nodes, localizing PCa tumor sites on 68Ga-PSMA PET/CT and may be
32% in paraaortic lymph nodes, 8% in supra-clavicular lymph used to further optimize PET-interpretation in daily practice.
nodes, 26% in bone and 13% in other locations. Twenty-seven References: None.
(71%) patients were categorized as metastatic and 14 (37%)
as oligometastatic. PSMA-11 PET/CT results led to a change
in management in 77% of cases (evaluated on 26 patients), EP-0142
statistically superior in oligometastatic patients by guiding Can patient selection based on 68Ga-PSMA-11 PET improve
stereotactic radiation therapy of metastasis. Conclusion: PSMA- the outcome of radical prostatectomy in prostate cancer
11 PET/CT is useful in PCa patients developing a castration- patients?
resistance by identifying residual disease in 89% of cases. It also I. A. Burger, D. A. Ferraro, U. J. Muehlematter, H. I. Garcia Schüler, D.
induces a change in therapeutic management of 3 patients out Eberli, T. Hermanns;
of 4, especially in oligomestatic patients. References: None. University Hospital Zurich, Zurich, SWITZERLAND.

EP-0141 Aim/Introduction: Accurate patient selection for invasive


Interobserver agreement in 68Ga-PSMA PET/CT with therapy is of major importance for patients with new diagnosed
structured PIP-RADS classification prostate cancer. Recently, the use of the new PET tracer targeting
L. van Kalmthout1, P. Kaldeway2, A. Braat1, M. Lam1, H. van Melick2, the prostate specific membrane antigen (PSMA) for staging
J. Lavalaye2; was suggested for superior detection of metastatic disease.
1
Academic hospital, Utrecht, NETHERLANDS, 2St. However, it is still unclear whether this superior sensitivity
Antonius Ziekenhuis, Nieuwegein, NETHERLANDS. would translate into a significant impact on outcome. The aim
of this study was to assess the biochemical recurrence (BCR)
ratio in patients that underwent radical prostatectomy (RPE)
Aim/Introduction: Gallium-68 (68Ga)-PSMA PET/CT has after a 68Ga-PSMA-11 PET for staging and compare it to recently
evolved as standard imaging procedure for prostate cancer published data reporting a BCR rate of 32% within 12 months
(PCa) (re)staging due to its easy readability and presumed high after RPE1. Materials and Methods: In this retrospective
interobserver agreement. To further optimize interpretation analysis, approved by the local ethics committee, from 137
and subsequent clinical applicability of PSMA PET/CT, however, patients that underwent 68Ga-PSMA-11 PET scans for staging
structured reporting methods are required. This study aims to intermediate or high-risk prostate cancer between April 2016
determine interobserver agreement in PSMA PET/CT reporting, and May 2018, 116 patients gave written informed consent for
using the newly proposed PIP-RADS classification. Materials retrospective analysis of their data. In 96 patients local therapy
and Methods: From May 2015 up to June 2018, all consecutive was considered an appropriate option after the PET scan and
68
Ga-PSMA PET/CT scans for primary staging and restaging 58 of those patients underwent RPE with extended pelvic
of PCa were retrospectively included in two institutions and nodal dissection in our institution and were included in this
evaluated by two blinded experienced nuclear medicine analysis. PSA follow up was collected at 12 months after RPE,
physicians. The prostate region, regional and distant lymph as well as information about the need of additional salvage
node sites, bone lesions and visceral lesions were scored on radiotherapy due to PSA persistence or recurrence. A PSA level
the PIP-RADS 5-point scale, with 1 being benign and 5 being >0.2 ng/ml was considered BCR. Results: Twelve months after
highly suspicious of malignancy. Interobserver agreement was RPE additional salvage radiotherapy was necessary in 9 patients.
evaluated using Cohen’s kappa, both on TNM-basis (prostate 49 patients did not have any additional therapy after RPE. In
region (T-stage); regional lymph nodes (N-stage); distant 42 of them the PSA was undetectable after 12 months and 5
lymph nodes (M1a-stage); bone lesions (M1b-stage) and patients had a PSA below 0.2 ng/ml. Therefore, only 11 of 58
visceral lesions (M1c-stage) and, more specific, on region-basis (19%) of patients selected for RPE based 68Ga-PSMA-11 PET had
(including various anatomical lymph node sites). Results: A total biochemical recurrence after 12 months. Three patients with
number of 58 68Ga-PSMA PET/CT scans for primary staging and non-pathologically enlarged but 68Ga-PSMA-11 PET positive
60 for restaging of PCa were analyzed. Their clinical conclusions common iliac lymph nodes were selected for RPE, all had an early
yielded a wide variety of terms. TNM-based evaluation of all BCR. If these three patients would not have been considered
patients according to the PIP-RADS classification showed surgical candidates, only 8 of 55 (15%) would have had BCR
substantial interobserver agreement for the prostate region (ƙ after 12 months. Conclusion: With the current data we could
= 0.67); substantial agreement for regional lymph node sites (ƙ show that there is some first evidence, that 68Ga-PSMA-11 PET
= 0.62); moderate agreement for distant lymph node sites (ƙ = might reduce the rate of BCR in patients undergoing RPE from
0.43). substantial interobserver agreement for bone lesions (ƙ = up to 30% to 15% after 12 months, despite the bias of a higher
S449 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

risk patient population. References: Skove SL et al. Timing of PET/CT is a useful tool in primary staging of PCa with detection
Prostate-specific Antigen Nadir After Radical Prostatectomy and rates and PSMA expression of PCa lesions rising with GSC, PSA
Risk of Biochemical Recurrence. Urology. 2017 Oct;108:129-134. level and risk group of disease. References: None.

EP-0143 EP-0144
Advantages of 68Ga-PSMA I&T PET/CT in primary staging of 99m
Tc-PSMA-SPECT/CT in Patient With Prostate Cancer
prostate cancer I. Farkas, Z. Besenyi, A. Maráz, Z. Bajory, A. Palkó, G. Sipka, S. Urbán,
W. Cytawa1, T. Bandurski1, J. Tran-Gia2, A. Schirbel2, K. Fukushima2, L. Pávics;
H. Wester3, P. Lass1, B. Brockhuis1, W. Połom1, A. K. Buck2, C. Lapa2; University of Szeged, Szeged, HUNGARY.
1
Medical University of Gdansk, Gdansk, POLAND,
2
University Hospital Würzburg, Würzburg, GERMANY,
3
Technische Universität München, Munich, GERMANY. Aim/Introduction: Several PSMA-specific ligands -mostly PET
tracers - have been developed in the last few years. PSMA-
PET/CT have higher detection rate than conventional imaging
Aim/Introduction: Prostate cancer (PCa) is the second most modalities to detect primary prostate cancer, tumor recurrences
common malignancy in men worldwide. In spite of curatively and metastases as well. We examined the clinical application
intended treatment options in localized disease including of a 99mtechnetium-labeled PSMA-radiopharmaceutical as part
radical prostatectomy (RP) or external beam radiation therapy of the routine diagnostics of prostate cancer. Materials and
(EBRT), up to 30% of patients will experience tumor recurrence. Methods: We examined 61 male prostate adenocarcinoma
One of the key issues in clinical management of PCa patients (Gleason-score 8; 2-10), with suspicion of progression or
is the accurate preoperative staging of the disease, in which recurrence of the disease (serum PSA level 3,05; 0,08 - 93,31).
conventional imaging yields unsatisfactory results.The aim of the Whole-body PSMA-SPECT/CTs (Mediso AnyScan TRIO) and
study was to retrospectively assess the PSMA-avid distribution multiparametric MRIs (GE Healthcare Discovery MR750w 3.0
of PCa disease prior to planned definitive treatment in 68Ga- Tesla) of the prostate and the pelvic regions were performed
PSMA I&T PET/CT. Materials and Methods: Eighty two patients within three weeks. We used 690 ± 97 MBq of 99mTc-mas3-y-
with biopsy proven, treatment-naïve PCa were included in the nal-k(Sub-KuE) for the PSMA-SPECT scans. The images were
study. All patients underwent 68Ga-PSMA I&T PET/CT (PSMA I&T evaluated visually and semi-quantitatively. Results: In case of
SCINTOMICS GmbH, Fürstenfeldbruck, Germany) for primary 41 patients 77 PSMA-positive lesions were detected (10 primer
staging of the disease. Focal radiotracer accumulation within prostate cancer; 11 local recurrence; 25 lymph node-, 28 bone-
the prostate gland was considered as positive primary tumor and 3 visceral metastases). 28 of them were localized outside,
uptake, whereas focally increased uptake within the lymphatic 49 were within the MRI’s field of view. From these 49 lesions,
drainage areas was regarded as lymph node metastasis (LNMs). 25 matched with the SPECT/CT. In case of ten lesions MRI
Bone metastasis (BMs) or other distant metastasis were also raised suspicion of a metastasis but there was no associated
reported, according to PROMISE criteria. Results: Patients pathological tracer uptake on the SPECT san. Six months follow
main characteristics: mean age 66.7 ± 7.3 years (range 53-83), up showed 4 of these were false positive findings. In 20 patients
median Gleason score (GSC) 7 (range 6 - 10), median PSA level no PSMA abnormality was found. Despite the negative PSMA-
11.0 ng/ml (range 0.7-872.5). Low-risk disease was present in 11, SPECT/CT during the follow up period clinical data proved
intermediate-risk in 32, and high-risk in 39 patients (according the presence of local recurrence in 12 cases. Tumor-to-normal
to D’Amico classification). Sixty-six (80.5%) patients presented activity concentration ratios were 30,32 ± 36,32 (3,34-193,77).
with positive primary tumor uptake. PSMA positive LNs were The tracer uptake correlated with serum PSA level (Spearman’s
reported in 17 patients (20.7%). Distant metastases were found rank correlation; P < 0.05). No correlation was found between
in 12 (14.6%) patients, predominantly in bones. Presence of Gleason and tracer uptake. Conclusion: PSMA-SPECT/CT with
N+ disease correlated considerably with GSC and PSA values, 99mTc-mas3-y-nal-k(Sub-KuE) is a promising method in the
and hence with disease risk group: positive LNs were reported evaluation of prostate cancer patients. It is capable of visualizing
in 3/32 (9%) patients with intermediate-risk and 14/39 (36%) bone metastases, local recurrences and visceral metastases as
patients with high-risk disease. Similar to LNMs, incidence of well. Semiquantitative analysis revealed relationship between
distant lesions increased with disease risk group: 2/32 (6%) PSMA ligand uptake and disease activity. References: None.
patients with intermediate-risk and 12/39 (31%) individuals with
high-risk disease presented with retroperitoneal LNMs and/or
BMs. No metastases were present in patients with low-risk PCa.
We found a significant positive correlation (r=0.51, p<0.001)
between the SUVmax of primary tumor uptake and PSA level,
and between primary tumor SUVmax and GSC (r=0.38, p<0.001).
Primary tumor uptake was also significantly higher in patients
with LNMs (mean SUVmax 24.9±16.0) vs. patients without LNMs
(mean SUVmax 14.1±12.6, p=0.039). Conclusion: 68Ga-PSMA I&T
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S450

EP-0146 EP-08
Characterization And Targeting Of 177Lu-PSMA617 Induced Inflammation & Infection: Molecular imaging in
Prostate Cancer Cell Stress Response Signaling To Improve Infection and Inflammation
Therapeutic Efficacy
K. Lueckerath, A. D. Stuparu, S. Poddar, J. R. Capri, T. M. Le, K. October 12 - 16, 2019
e-Poster Area
Current, C. Cheng, C. G. Radu, J. Czernin; Univ. of California
Los Angeles, Los Angeles, CA, UNITED STATES OF AMERICA.

EP-0147
Aim/Introduction: Only ~50% of patients with PSMA+ Clinical usefulness of 18F-FDG PET/CT in patient with
tumors respond to PSMA directed radioligand therapy (RLT) cardiac implantable electronic device
and relapses occur uniformly in this group. We explored links C. Ferrari, A. Ungaro, A. R. Pisani, A. Gaudiano, V. Lavelli, C. Altini, A.
between RLT-induced signaling alterations and actionable G. Nappi, G. Rubini;
resistance mechanisms, and provide proof-of-principle for Nuclear Medicine Unit, Interdisciplinary Department of
new, rationally designed RLT-based combination therapies Medicine – University of Bari “Aldo Moro”, Bari, ITALY.
using clinical stage inhibitors. Materials and Methods: 177Lu-
PSMA617 RLT-induced (phospho)proteomic alterations in the
C4-2 PC mouse model were profiled using mass spectrometry. Aim/Introduction: The use of cardiovascular implantable
The relevance (i) of significantly altered pathways for mediating electronic device (CIED) has been increasing in the last decade.
resistance to RLT, and (ii) of pharmacological targeting these Long-term complications include device-related infections that
pathways in combination with RLT was validated across a panel may develop in the pocket, leads or cardiac valve. Currently, the
of PSMA+ PC cells (immunoblot, flow cytometry, tumor cell diagnosis of CIED makes use of positive bacteriological samples
growth inhibition), and in vivo using the C4-2 and 22Rv1 PC associated with transthoracic echocardiography (TTE) and
mouse models (treatment efficacy as determined by computer transoesophageal echocardiography (TEE) according to Duke’s
tomography). Results: Our (phospho)proteomic datasets Criteria. 18F-FDG PET/CT is also performed for inflammatory
revealed that activation of the DNA damage and replication processes in addition to oncologic purpose. The aim of this
stress response (DDR/RSR) and TP53-signaling can occur in study was to evaluate the role of 18F-FDG PET/CT in patient
response to RLT, and identified drugable key-effectors in these with suspected infection of CIED. Materials and Methods:
pathways such as ataxia telangiectasia and Rad3-related (ATR). Fifteen patients who performed a 18F-FDG PET/CT from 2013
In vitro, inhibition of ATR (ATRi) in combination with ionizing to 2019 for suspicion of CIED were retrospectively analyzed.
radiation (IR) sensitized PC cells to IR, by increasing DNA damage The same number of patients (n=15), with implanted CIED,
(pH2A.X) and cell death (Annexin V/PI), and impairing DNA that underwent to PET/CT imaging for oncological reasons,
damage signaling (pCHEK1/2) and colony forming capacity. which resulted negative and asymptomatic, was retrospectively
In mice with C4-2 tumors, combining 177Lu-PSMA617 RLT with evaluated as control group. Patients suspected of infection
ATRi resulted in synergistic tumor growth inhibition. However, were previously evaluated according to Duke’s criteria. 18F-FDG
tumors started to re-grow ~80 days post-RLT. Based on our PET/CT studies were firstly visually analyzed on the basis of
phosphoproteomic dataset we hypothesized that adding presence of hot spots around box or leads in the first group.
inhibitors of ataxia-telangiectasia mutated (ATM) or poly ADP Values of Sensitivity (Se) and Specificity (Sp) were estimated.
ribose polymerase (PARP) to the ATRi/RLT combination might A semiquantitative analysis was performed using the maximal
improve therapeutic efficacy. In vitro, both triple combination standard uptake value (SUVmax) inside a region of interest (ROI)
regimens resulted in significantly enhanced DNA damage, cell within the hotspots. Similar ROI were drowned in the control
death, and cell growth inhibition compared to ATRi/IR alone in group on the boxes. The final diagnosis was obtained from the
all cell models tested. We are currently testing in two different bacteriological data after device culture or during follow-up
PC mouse models (C4-2 [TP53wt/wt, BRCA2wt/wt], 22Rv1 [TP53mut/ according to Duke’s criteria, both considered as gold-standard.
wt
, BRCA2mut/mut] tumors) if concomitant administration of ATRi/ Concordance between gold-standard and 18F-FDG PET/CT was
ATMi and ATRi/PARPi, respectively, outperforms application of calculated with Fisher’s Test. Results: All devices were implanted
ATRi alone, and enhances the efficacy of RLT. Conclusion: Our since at least 6 months. Cardiac device was harvested in 12/15
study identified DDR/RSR signaling as liability of PC tumors that patients and confirmation of device culture was observed
can be exploited to sensitize genetically divers PC models to RLT. in 11/12 patients. The final diagnosis of the 3/15 patients left
We will expand our investigations to more stringent PC mouse was based on negative follow-up according to Duke’s Criteria.
models and analyses of biopsies from patients undergoing The agreement between 18F-FDG PET/CT and explantation or
RLT. Our analytical approach may provide the rationale for negative follow-up was statistically significant (p< 0.05). Se and
future clinical trials of new RLT-based combination therapies. Sp were respectively 91% and 75%. Semiquantitative analysis
References: None. had shown in the control group a mild diffuse uptake around
the box significantly higher than the opposite side: SUVmax:
1.97±0.5 vs 1.59±0.3; p< 0.05. Furthermore, patients with proven
infection had higher uptake compared to control group SUVmax:
S451 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

4.42±1.85 vs 1.5±0.34; p<0.01. A SUV value equal or > 2.47 EP-0149


discriminated all positive patients from controls. Conclusion: Role Of F-18 FDG PET-CT In The Evaluation Of Patients
In agreement with literature, this study underlines the clinical With Fever Of Unknown Origin
usefulness of 18F-FDG PET/CT in patients with CIED infection J. Mandarapu;
due to its higher sensibility, repeatability and non-invasiveness. Continental Hospitals Limited, Hyderabad, Telangana, INDIA.
References: None.

Aim/Introduction: Analysing whole body 18F-FDG PET-CT


EP-0148 in the evaluation of patients with FUO to Localise the source
99m
Tc-White Blood Cell Scintigraphy With SPECT/CT in the of FUO. Estimate the extent of involvement. Suggest the sites
Diagnosis of Vascular Graft Infection of biopsy, thereby usefulness in obtaining histopathological
M. de la Rubia Marcos, P. Garcia Alonso, C. Mena Melgar, B. diagnosis. Materials and Methods: Study area : Department of
Tagliatori Nogueira, A. Herrero Muñoz, C. Sandoval Moreno, C. Nuclear Medicine, Apollo Gleneagles PET/CT centre, Hyderabad.
Paniagua Correa, L. Castillejos Rodriguez, A. Ortega Valle, M. Balsa Study design : A prospective, observational study of 48 patients
Breton; for a period of 24 months.Study population : 48 patients were
Hospital Universitario de Getafe, Getafe, SPAIN. included in the study among which 22 were male and 26
female. Results: Of the 48 patients male to female ratio is 0.8:1.
PET-CT showed abnormalities (positive) in 36 patients and was
Aim/Introduction: Vascular graft infection is a rare complication normal (negative) in 12 patients. Among 36 PET-CT positive,
that occurs in 1 to 6% of all prosthetic vascular procedures, with 20(55.5%) patients were diagnosed as infective etiology.
a high morbidity and mortality. It is associated with mortality 15/20 (75%) were diagnosed as tuberculosis. Histopathology
rates of up to 75%, and 70% of peripheral prosthetic graft confirmed the diagnosis of tuberculosis in 7/15.In 8/15 patients
infection lead to limb amputation. Early diagnosis is essential to where histopathology showed non diagnostic/in conclusive
establish an adequate treatment. CT is generally considered the and in high clinical suspicious for tuberculosis, patient was
initial imaging modality of choice in these patients. However, started on ATT. In view of clinical response to ATT, the diagnosis
99m
Tc-HMPAO labeled white blood cell scintigraphy (99mTc- of tuberculosis was confirmed. Imaging (CT/USG) guided
WBC) with SPECT/CT is showing promising results in improving drainage of abscess and pus culture and sensitivity confirmed
imaging assessment of vascular graft infection. The aim of our the diagnosis of liver abscesses in 2/5(10%).PET/CT diagnosed
study was to assess the accuracy of 99mTc-WBC scintigraphy with as pneumonia in 1/5 patient (5%), cholecystitis in 1/5 patient
SPECT/CT in the diagnosis of vascular graft infection. Materials (5%), bilateral polycystic kidney disease in1/5 (5%) patient and
and Methods: We retrospectively analyzed thirty 99mTc-WBC the diagnosis was confirmed with clinical improvement of the
scintigraphies with SPECT/CT performed in our center in thirty patients with higher antibiotics in all 3 patients. Neoplastic
patients with suspicion of vascular prosthesis infection (3 etiology was found in 5/36 (13.8%) patients. Histopathology
women and 27 men, with an age range 33 - 87), between April confirmed the diagnosis of malignancy in all 5 patients.4/5 (80%)
2014 to November 2018. Planar images were performed at 30 patients were diagnosed as Non Hodgkin`s lymphoma (NHL)
minutes, followed by delayed planar and SPECT/CT images at 2 and 1/5(20%) as gastro intestinal stromal tumour (GIST). Non
hours. Studies were considered positive for graft infection if the infectious inflammatory diseases were found in 5/36 (13.8%)
intensity of activity involving the graft was the same as or greater patients. Non specific false positive FDG uptake in small sub
than the liver or bone marrow activity (spine and pelvis). Results: centimeter lymph nodes, spleen and bone marrow was seen in
Final diagnosis of infection was established in 10 patients, based 5/36 (13.8%). Among 12 patients with PET-CT negative, 2(16.6%)
on Fitzgerald criteria. Scintigraphy was positive in 11 patients, patients were diagnosed to have infective etiology 1(8.3%) of
with only one false positive result. No false negatives were the 12 patients had systemic lupus erythematous (SLE). In the
obtained. The values ​​of sensitivity and specificity were 100% rest 9/12 (75%) PET-CT negative patients, fever resolved and had
and 95% respectively, with a PPV of 91% and a NPV of 100%. uneventful course. Conclusion: Etiologies of FUO in the study
25 patients had a CT performed prior to scintigraphy, in 9 cases were infection (45.83%), malignancy (10.41%), non infectious
the result was positive and in the remaining 16 was negative. inflammatory diseases (12.50%), miscellaneous causes (2.08%)
CT sensitivity and specificity obtained in our study were 62.5% and undiagnosed fever (29.16%). Sensitivity, specificity, PPV
and 76% respectively, with a PPV of 55.6% and a NPV of 81.3%. and NPV of FDG PET/CT in FUO in the study were 91.1%, 64.2%,
Diagnosis of infection led to prosthesis exeresis in 8 cases (all 86.1% and 75% respectively. PET/CT significantly contributed to
of them had a positive microbiological study of the extracted the final definite diagnosis in 86.1% of the patients with FUO (P
material), while the remaining 2 patients were treated with value = <0.05). References: None.
antibiotic therapy alone due to high surgical risk. Conclusion:
Our results suggest a high accuracy for 99mTc-WBC scintigraphy
with SPECT/CT in the assessment of clinically suspected arterial EP-0150
graft infection, even more than CT. References: None. The role of “after washing imaging” in evaluation of tear
drainage system by dacryoscintigraphy
R. Sadeghi, T. Masoudi, H. Shayegani;
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S452

Nuclear Medicine Research Center, Mashhad University of made was based on a combination of microbiological, clinical
Medical Sciences, Mashhad, IRAN, ISLAMIC REPUBLIC OF. and imaging follow up. Accuracy of interpretation methods was
compared using pairwise comparisons of receiver operating
characteristic curves. Results: Twenty-three studies (n=23) of 24
Aim/Introduction: The aim of this study was to evaluate SVGIs were included (21 patients, 8 female, mean age 62.3 years).
the efficacy of “after washing” imaging in interpretation of Of all SVPGIs investigated, 18 were proven to be infected while
dacryoscintigraphy as a functional imaging technique used in in 6 infection was excluded. Visual interpretation of 3-hr images
evaluation of tearing problems. Materials and Methods: 300 alone classified 23 cases correctly and resulted in 1 false positive.
nasolacrimal systems were studied. 100 μCi of technetium-99m Visual interpretation of white cell accumulation over 24-hr
sodium pertechnetate as drops of activity (10 μL) were placed classified 18 cases correctly and resulted in 1 false positive and 5
into the inferior fornix of each eye. Dynamic images were false negatives. Finally, interpretation based on an accumulation
obtained for 15 minutes in the sitting position. “After washing” index alone correctly classified 12 cases but resulted in 3 false
phase was done by placing a drop (10 μL) of normal saline positives and 9 false negatives. Visual interpretation at 3-hr
in each eye and external ocular massage for an additional 10 was statistically more accurate than visual assessment for
minutes. The imaging patterns for each eye in the first dynamic accumulation over 24-hr (p = 0.0265). Conclusion: We found no
phase and after washing phase were recorded, separately. evidence to suggest that assessment of progressive white cell
Results: First dynamic phase demonstrated a sensitivity of accumulation improves diagnostic accuracy of WCS for SVPGI.
97.4% and specificity of 22.6%. After washing phase showed a To the contrary, early visual assessment at 3 hours appears to
sensitivity of 91.2% and specificity 75.5%. After washing test, the result in the highest accuracy in this context. References: None.
obstruction pattern changed to “patent nasolacrimal duct” or
“further progression” of the radiotracer to the nasolacrimal duct
in the 25.1% and 24.4% of the nasolacrimal systems, respectively. EP-0152
Conclusion: After washing imaging is a useful method in 18
F-FDG PET/CT Assessment of Sarcoidosis Extension and
dacryoscintigraphy which can improve the specificity of scan Activity - A Single Center Experience
for diagnosis of lacrimal duct obstruction. It can also improve M. Silvestre, T. C. Ferreira, I. P. Carvalho, M. R. Carvalho, D. Ferraz, D.
the localization of obstruction level in the lacrimal systems. Fraga, F. N. Brandão, P. Ratão, R. Sousa, L. Salgado;
References: None. Instituto Português de Oncologia de Lisboa, Lisbon, PORTUGAL.

EP-0151 Aim/Introduction: Sarcoidosis is a multisystemic disease of


Progressive Accumulation of Radiolabeled White Cells in unknown cause, with formation of noncaseating granulomas
Scans Performed for Suspected Vascular Prosthetic Graft during its course1. Our center is dedicated mainly to oncology,
Infections however 18F-FDG PET/CT scans (PET) were performed for
J. Jooma, A. G. G. Doruyter, J. M. Warwick; sarcoidosis evaluation during the past few years. The aim of
Stellenbosch University, Cape Town, SOUTH AFRICA. this study is to retrospectively review our results assessing
disease extension and activity using PET, in patients (pts) with
sarcoidosis. Materials and Methods: From january-2014 until
Aim/Introduction: Vascular prosthetic graft infection is a serious march-2019 we performed 64 PETs for sarcoidosis evaluation.
complication which can be diagnosed using radiolabeled We excluded re-evaluation scans or pts undergoing treatment
white cell scintigraphy (WCS). Interpretation criteria proposed (n=24) and pts with other possible diagnosis (n=1). Data from
by a recent multicenter study, to diagnose or exclude soft the remaining 39 PETs was collected regarding sites involved
tissue infection on WCS, have not been validated in suspected - intra-thoracic lymph nodes (LN), extra-thoracic LN, lungs,
vascular prosthetic graft infections (SVPGI). No research has to bone, muscle, spleen, skin, gastrointestinal tract, eyes, liver
date investigated whether assessment of progressive white and pituitary - and respective standardized uptake values
cell accumulation improves the accuracy of WCS performed (SUVs). For cardiac sarcoidosis evaluation, we excluded PETs
for SVPGI. Materials and Methods: A retrospective analysis with unsatisfactory preparation (n=13). The remaining studies
was performed of all WCS scans performed for SVPGI between (n=26) were evaluated. Results: Our population had a mean
January 2004 and June 2018. Studies were only included if both age of 56 years (range 28-83) and 1:2 male to female ratio.
3-hr and 24-hr imaging were available. Initial 3-hr images were Active disease was seen in 79% (n=31). From these, 55% had
first classified as positive or negative on the basis of presence multisystemic disease (n=17). Sites most commonly affected
or absence of white cell activity at the site of the vascular graft. were intra-thoracic LN (74%), extra-thoracic LN (42%) and lungs
Next, by comparing 24-hr and 3-hr images, studies were scored (39%). SUVs distribution for each site is on tables 1, 2, 3 and 4.
as either positive or negative based on the presence or absence Only 2 of the 26 pts had sarcoidotic cardiac disease, with SUVs
of progressive white cell accumulation: both visually, and by 4,5 and 5,1. Conclusion: It is known that sarcoidosis affects
calculating an accumulation index using suitable regions of primarily lungs and intra-thoracic LN2. However, our results
interest with count values corrected for decay. A composite show extensive involvement of extra-thoracic LN, being the
reference standard according to which the final diagnosis was second most affected site, with lungs on third place. Published
S453 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

literature makes reference to a considerable amount of extra- demonstrated no FDG uptake. Conclusion: 18F-FDG-PET/CT is
pulmonary disease3, although little is said regarding lymphatic a reliable imaging modality for the diagnosis, disease localization
system alone. The range of SUV values in sarcoidosis is not well and extent, follow up, treatment response evaluation and in
established. High SUVs can be observed3, and our results show decision making regarding treatment cessation. 18F-FDG-PET/
that a wide range of uptake can be seen in all the sites, especially CT should be considered as the imaging modality of choice in
in lymphatic system. References: 1. Hunninghake GW, Costabel the management of Malignant otitis externa. References: None.
U, Ando M, et al. ATS/ERS/WASOG statement on sarcoidosis.
American Thoracic Society/European Respiratory Society/
World Association of Sarcoidosis and other Granulomatous EP-0154
Disorders. Sarcoidosis Vasc Diffuse Lung Dis. 1999;16:149-173.2. Novel monitoring indices of osteomyelitis of the jaw using
Sobic-Saranovic D, Artiko V, Obradovic V. FDG PET Imaging in bone SPECT quantitative analysis: Preliminary study for
Sarcoidosis. Semin Nucl Med. 2013; 43:404-411.3. Soussan M, patients with ARONJ
Augier A, Brillet P, et al. Functional Imaging in Extrapulmonary H. Hata1, T. Kitao2, K. Imamachi1, J. Sato3, T. Asaka3, N. Ohga3, K.
Sarcoidosis. Clin Nucl Med. 2014; 39:e146-e159. Hirata4, T. Shiga5, Y. Kitagawa3;
1
Dentistry and oral surgery, Hokkaido Cancer Center, National
Hospital Organization, Sapporo, JAPAN, 2Radiology Department,
EP-0153 Hokkaido Cancer Center, National Hospital Organization,
Role of FDG PET/ CT in the Initial evaluation and Follow-up Sapporo, JAPAN, 3Oral diagnosis and medicine, Graduate
of Malignant Otitis externa school of dental medicine, Hokkaido University, Sapporo,
N. K. Seniaray, R. Verma, E. Belho, D. Malik, H. Mahajan; JAPAN, 4Nuclear medicine, Graduate school of medicine,
Mahajan Imaging Center, Sir Ganga Ram Hokkaido University, Sapporo, JAPAN, 5Hokkaido Cancer
Hospital, New Delhi, INDIA. Center, National Hospital Organization, Sapporo, JAPAN.

Aim/Introduction: Malignant otitis externa is an aggressive Aim/Introduction: The number of patients with antiresorptive
infective disease with significant morbidity and disease specific agent related osteonecrosis of the jaw (ARONJ) or osteomyelitis
mortality. The disease usually begins in the external ear and of the jaw (OMJ) is a growing social problem. However, the
spreads to the adjacent bones resulting in associated temporal role of diagnostic imaging in the evaluation of ARONJ has not
bone and skull base Osteomyelitis. Conventionally CT, MRI, been adequately established without good index to assess
gallium-67 and technetium-99m bone scan have been used for the antiphlogistic effect in osteomyelitis. Development of
the pre-treatment evaluation, however each modality has its quantitative analysis software has enabled several standardized
own limitations. 18F-FDG-PET/CT, which has been used primarily uptake values (SUV) for analysis in SPECT bone scintigraphy.
in oncology, is increasingly being used as a marker for localizing The present retrospective study was undertaken to evaluate
infective foci and can be used as an effective alternative to the usefulness of SUV evaluations in SPECT to establish the
technetium-99m and gallium-67 scans for diagnosis, assessment curative effect of OMJ by comparing the states before and
of response and follow-up in patients with Malignant otitis after the antiphlogistic therapy including hyperbolic oxygen
externa. Materials and Methods: : A retrospective analysis of therapy (HBO). Materials and Methods: Fifteen ARONJ
22 patients clinically diagnosed with Malignant otitis externa patients participated in the study. The patients underwent
was done. All the subjects underwent regional 18F-FDG-PET/CT SPECT prior to and after the pre-operative HBO. The baseline
scanning to evaluate the extent of involvement and localisation was assumed as that at the time of the SPECT imaging before
of infective foci. The disease was further evaluated based on the start of the preoperative HBO. We used the mean SUVmax
the standardised uptake value (SUV Max) of FDG and extent of of the bilateral cranial bones as the control [C] and attempted to
erosion and sclerosis within the involved skull bones on PET/CT. adjust the SUVmax of the lesion [L] as expressed in the following
4 patients underwent additional technetium-99m bone scan equation: adjusted SUVmax (aSUVmax) = [L] - [C]. The optimum
and the extent of skeletal lesions was compared with PET/CT. threshold to calculate the Metabolic bone volume (MBV) was
Follow up low dose regional 18F-FDG-PET/CT after antibiotic determined to be [C] + 3. Retrospectively, we calculated the
treatment was done in 6 patients. The data was analysed using SUVmax and MBV of the SPECT using quantitative analysis
appropriate statistical methods Results: FDG avid lesions software to evaluate the intensity and volume of inflammation
were located in the external ear canal (n=18) with associated in the OMJ. Results: The mean aSUVmax of all cases was
Osteomyelitis involving the petrous and mastoid temporal significantly reduced from 11.53 to 9.16 after HBO (p < .05).
bones (n=21), sphenoid bone (n=7), temporo-mandibular joint Similarly, the mean MBV of all cases was significantly reduced,
(n=5) and nasopharyngeal regions (n=4). 6 patients underwent from 17.90cm3 to 15.19cm3, after HBO (p < .05). We compared
a second low dose regional PET/CT scan after active otitis the clinical course with the change in aSUVmax and MBV before
resolved and after at least 6 weeks of antibiotic treatment. The and after the HBO for all patients. After the anti-inflammatory
scan demonstrated no or substantially reduced FDG uptake and treatment including HBO, there were sharp decreases in values
treatment was stopped. One patient had significant uptake, for 6 patients who had high aSUVmax (> 15) and/or had a large
and antibiotic treatment was continued until a third scan MBV (> 20cm3) at the baseline. These cases were also subject
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S454

to clinically severe infections at the baseline. Conclusion: This EP-0156


is a first study applying SPECT quantitative analysis software to Diagnostic Role Of Three-phase Bone Scintigraphy In
determine the curative effect of OMJ by comparing the states The Differentiated Choosing Of The Component Of
before and after antiphlogistic therapy including HBO. We Endoprosthesis In Patients With Septic And Aseptic
propose two equations for the adjusted SUVmax and threshold Osteoarthrosis Of The Hip Joint
SUV to enable data comparisons between cases. The overall P. Korol1, M. Tkachenko2;
aSUVmax and MBV were significantly reduced after HBO, and all 1
Clinical City Hospital #12, Kiev, UKRAINE, 2A.A. Bohomolets
of the SPECT quantification data reflected the specific clinical National Medical University, Kiev, UKRAINE.
findings. References: None.

Aim/Introduction: To determine the diagnostic value of


EP-0155 three-phase bone scintigraphy in the differentiated selection
Polymyalgia Rheumatica as Paraneoplastic syndrome of endoprosthesis components (“friction units”) in patients
on18F-fluorodeoxyglucose Positron Emission Tomography/ with septic and aseptic osteoarthrosis (OA) of the hip joints.
Computed Tomography Materials and Methods: 187 patients with septic and aseptic
G. Silov, S. Karacavus, H. Gencer; OA (109 women and 78 men) aged 34 to 75 years were
Health Sciences University, Kayseri City Hospital, imaged by bone scintigraphy: I stage - angiographic stage,
Department of Nuclear Medicine, Kayseri, TURKEY. II stage - early stage, 3 stage - delayed static phase. 3 hours
after the intravenous administration of 740 MBq 99mTc MDP.
Results: According to the results of microbiological analysis
Aim/Introduction: Polymyalgia rheumatica (PMR) is of diagnostic puncture of the hip joints, the patients were
characterized by inflammatory pain and stiffness of the shoulder divided into two cohorts. The first cohort included 104 patients
and pelvic girdles, with biochemical evidence of inflammation. with aseptic OA of the hip joint, the second - 85 patients with
Polymyalgia rheumatica (PMR) is one of the inflammatory septic OA (in 58 cases was detected S. aureus, in 27 cases -
rheumatic diseases that can potentially be detected by positron St. haemolyticus). A significant increase in arterial inflow (t =
emission tomography/CT. Several studies reported a PMR 2.48; p <0.05) and integral perfusion (t = 2.65; p <0.05) in the
syndrome as a presenting manifestation of various malignant angiographic phase of patients with septic OA was determined
diseases. However, PMR patients have an increased risk of due to intensification osteoblastic activity and angiogenesis,
malignancies. In this study, we aimed to reveal relationship PMR compared with patients with aseptic OA. In patients with septic
and malign diaseases. Materials and Methods: We investigated OA, there was a significant predominance of retention (t = 3.29;
52 patients with any cancer history underwent 18-FDG PET/ p <0.05) and specific accumulation of the radiopharmaceutical
CT. FDG uptake in large joints, bursas and vertebral spinous in the early (t = 2.23; p <0.05) and delayed static phase of three-
processes was evaluated by calculating maximum standardised phase bone scintigraphy ( t = 2.36; p <0.05) as compared with
uptake values. Results: In cancer patients (16 lymphoma, 9 indicators for aseptic OA. When endoprosthetics of patients with
lung non small cell cancer, 8 breast cancer, 8 gynecological aseptic OA using the component of endoprosthesis - «ceramics-
cancer, 7 GIS, 2 prostate adenocancer, 1 malignant melanoma, ceramics» in the postoperative period, no implant-associated
1 lower lip SCC) were detected increased F-18 FDG uptake in complications were detected. In patients with septic OA,
ischial tuberosities (SUV max: 3.23 ± 1.43), greater trochanters paraprosthetic complications were not recorded when using
(SUV max: 2.98 ± 0.73), and lumbar spinous processes (SUV max: the «metal-ceramic» component. Conclusion: The parameters
2.24 ± 1.04), shoulders (SUV max: 3.68 ± 1.62), sternoclavicular of the distribution kinetics of the radiopharmaceutical of three-
(SUV max: 2.14 ± 0.79). Positive results at two or more of these phase bone scintigraphy have diagnostic value in patients
sites showed high sensitivity (86.5%) and specificity (89.2%) with aseptic and septic OA of the hip joint when choosing
for the diagnosis of PMR. In this study remitting seronegative the components of the endoprosthesis, especially when it is
symmetrical synovitis with pitting edema (RS3PE) was seen in impossible to perform a diagnostic puncture of the hip joint.
five patients including malignant melanoma, lower lip SCC, References: None.
two non small cell lung cancer and prostat adenocancer.
Conclusion: 18F-Fluorodeoxyglucose-PET/CT may be useful for
the detection of unknown PMR lesions and RS3PE with cancer EP-0157
patients which are difficult to identify using other methods. FFDG PET/CT Identifies A Extra-Cardiac Target For Biopsy
Presence of RS3PE five cancer patients as a paraneoplastic In Patients With Suspected Cardiac Sarcoidosis
syndrome, and thereafter concurrent with clinical presentation D. Weinreb;
of PMR, suggests a common trigger factor for RS3PE from a 16 Birkdale Court, Slingerlands, NY, UNITED STATES OF AMERICA.
these cancer and PMR. References: None.

Aim/Introduction: The 2014 Heart Rhythm Society Guidelines


allow for a diagnosis of cardiac sarcoidosis to be established
in patients with a histologic diagnosis of systemic sarcoidosis
S455 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

and for whom FDG PET demonstrates patchy, non-segmental years) who underwent a whole body scan (WBS) in anterior
hypermetabolism. These guidelines obviate the need for and posterior projection after 3 hours of the i.v injection of 740
invasive endomyocardial biopsies. The objective of this study is MBq 99mTc-DPD. A thoracic SPECT was also performed. Visual
to determine whether FDG PET may identify a relatively non- analysis of the cardiac uptake and the global distribution of the
invasive target for biopsy to establish a histologic diagnosis of radiotracer following the Perugini scale were carried out by two
systemic sarcoidosis in patients presenting with non-ischemic nuclear medicine specialists. Visual scores 0-1 were considered
cardiomyopathies. Materials and Methods: Eight cases of negative for cardiac amyloidosis and scores 2-3 as positive. For
patients referred to FDG PET were retrospectively reviewed. semiquantitative analysis, ROI´s were drawn over the heart
None of these patients had an established histological or clinical on the anterior projection of WBS. Number of counts in the
diagnosis of systemic sarcoidosis. All presented with non- heart was divided by the number of counts in WBS imaging,
ischemic cardiomyopathies. FDG PET imaging was performed excluding the counts derived by bladder and kidneys, following
contemporaneously with stress-rest myocardial perfusion the next index: Heart ROIc / WBS ROIc - (Bladder ROIc + Kidneys
imaging. Results: In seven of the eight patients, the FDG PET ROIc). The visual and semi-quantitative analysis of the cardiac
study demonstrated both evidence of cardiac and extra-cardiac deposit and the radiotracer distribution in WBS was correlated
sarcoidosis. The classic pattern of patchy hypermetabolism in a with the echocardiographic data of LVEF and thickness of IVS.
non-segmental distribution was present in the cases. All seven Results: On visual analysis, 27 out of 60 patients (45%) had
cases also exhibited evidence for extra-cardiac sarcoidosis, negative bone scan. On the other side, 33 out of 60 patients
including hypermetabolic supraclavicular, mediastinal (55%) had positive bone scan .The semiquantitative analysis
and inguinal lymph nodes, as well as hepatic, splenic and was only available in 57 patients. In the 27 patients who had
intramuscular granulomas. One of the cases demonstrated negative bone scan the Heart/Whole body ratio (H/W) was
intense FDG avidity involving the suprahepatic IVC as well as the 1.6±0.3. In the 33 patients who had positive bone scan the H/W
femoral veins. Of note, the sites of supraclavicular and inguinal mean value was 7.7±0.5 (p<0.0001). The LVEF did not show
lymph nodes were not enlarged or intrinsically suspicious on CT statistically differences between positive and negative patients
and therefore would have not prospectively identified as targets (p=0.74). However statistically differences were observed
for a biopsy in the absence of FDG PET imaging. The eighth between the thickness of IVS for positive and negative patients
patient exhibited no evidence of either cardiac or systemic (19.17±2.94mm vs 14.85±5.01mm, p=0.005). Conclusion:
sarcoidosis. Conclusion: These observations suggests that FDG Patients with cardiac uptake of 99mTc-DPD and high suspicion
PET is a valuable tool in establishing the diagnosis of sarcoidosis of transthyretin amyloidosis showed significantly greater IVS
with cardiac involvement in a population of patients presenting hypertrophy than whom were considered negative for cardiac
with a non-ischemic cardiomyopathy. Specifically, FDG PET uptake of radiotracer. A direct relationship was found between
identifies sites amenable to relatively non-invasive biopsies the uptake pattern in bone scintigraphy and the presence of
to confirm the presence of non-caseating granulomas, while myocardiopathy. No relationship was observed between LVEF
simultaneously demonstrating the classic pattern indicative of and the cardiac uptake pattern on bone scan. References:
cardiac involvement. References: None. None.

EP-0158 EP-0159
Correlation between bone scan findings and 99m
-Technetium Diphosphonates in Transthyretin Cardiac
echocardiography parameters in patients with cardiac Amyloidosis. Extracardiac Uptake Evaluation in Our Centre
amyloidosis A. Andres Gracia1,2, D. Nogueira Souto1, L. Tardin Cardoso1, M.
N. A. Martinez Amador1, O. Cuenca Vera1, I. Martínez Rodriguez1, Delgado Castro1, P. Razola Alba1, C. Lahuerta Pueyo3,2, M. Aibar
M. De Arcocha Torres1, R. Quirce1, J. Jiménez Bonilla1, A. Sánchez Arregui4,2, E. Prats Rivera1, D. Abos Olivares1;
Salmon1, M. Zarauza Navarro2, G. Molina Mendoza1, I. Banzo1; 1
Unidad Clínica Multihospitalaria de Medicina Nuclear de
1
Department of Nuclear Medicine. Marqués de Valdecilla Aragon, Zaragoza, SPAIN, 2IIS ARAGON, Zaragoza, SPAIN,
University Hospital. Molecular Imaging Group (IDIVAL). 3
Servicio de Bioquímica Clínica. Hospital Universitario “Miguel
University of Cantabria, Santander, SPAIN, 2Department Servet”, Zaragoza, SPAIN, 4Servicio de Medicina Interna-Hospital
of Cardiology. Marqués de Valdecilla University Hospital. Clínico Universitario “Lozano Blesa”, Zaragoza, SPAIN.
University of Cantabria, Santander, SPAIN.

Aim/Introduction: To evaluate the extracardiac deposit of


Aim/Introduction: To evaluate the correlation of the 99m
Tc-labeled diphosphonates (DPD) in patients with suspected
cardiac uptake in bone scan using 99mTc-DPD with the thransthyretin cardiac amyloidosis hereditary or wild-type.
echocardiographic parameters of left ventricular ejection Materials and Methods: We performed 153 scans in 151
fraction (LVEF) and thickness of the interventricular septum (IVS) patients referred for clinical suspicion of cardiac amyloidosis
in patients with suspected cardiac amyloidosis. Materials and (heart failure with preserved LVEF or with minimal repercussion
Methods: This retrospective study included 60 patients with 148 scans) or for being asymptomatic carriers of the disease
suspected cardiac amyloidosis (48 men. mean age: 74.7±12.2 (3 patients / 5 scans). Average age 74’72 (23-93 years), 66’7%
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S456

men and 33’3% women, from 11/21/2013 to 4/16/2019. All of were included in this retrospective analysis. We calculated
them have been screened with 99mTc-DPD at 3 hours after its sensitivity (S), specificity (Sp) and positive and negative predictive
administration. For the evaluation of cardiac activity, Perugini’s values for the initial Duke classification, echocardiography, PET/
visual scale was used (0, 1, 2, 3), considering it positive in the CT and post-PET Duke classification. Post-PET Duke included
cases of grade 2 and 3 uptake. Likewise, the locations of 18
F-FDG uptake in leads, valves or endocardium as a major
extracardiac radiotracer uptake have been evaluated (soft tissue, criterion. The gold standard was either the culture of explanted
organs and osteoarticular) and a review of the clinical history material or the final decision of the endocarditis team revised
and biopsy and analytical data was performed to check whether after 1-year follow-up. Net Reclassification Improvement (NRI)
there was a histological evaluation of the affected organs. was used to assess the percentage of correct changes over the
Results: In 153 exams, 72.5% corresponded to scans with score initial Duke classification based on PET/CT results. Results: Forty-
0 (107) or 1 (4), while 27.5% corresponded to score 2 or 3 and five studies met inclusion criteria (mean age 66.9±13.9). The
therefore compatible with transtyrethin cardiac amyloidosis initial suspicion of CID-related infection was based on systemic
(aTTR) in the absence of free light chains. In 42 patients with (60%), local (35%) and mixed signs/symptom. Pacemaker was
positive scintigraphy, two patients had a positive genetic study the most frequent CID (22 patients) and most had 2 or more
(TTR gene (c.424G>A (p.Val122Ile) and c-220G>C(p.Glu74Gln)), leads. Prevalence of definite infective endocarditis (IE) was 56%.
in 18 patients the genetic study was negative (wild-type) and Infection limited to the pocket was established in 11% of patients
in 22 had not been determined. Most of the patients (82.3%) and CID-related infection was ruled out in 33%. For the diagnosis
presented no pathological uptake or degenerative osteoarticular of IE, post-PET Duke reached the highest S (0.92 (95%CI 0.82-
pathology. The remaining 27 patients (17.64%), 5 presented 1.0)) while PET/CT accounted for the highest Sp (0.94 (95%CI
relevant bone pathology exclusively (2 cases of Paget’s disease 0.84-1.0)). Echocardiography had the poorest S and Sp (0.42 and
and 3 cases, metastatic bone disease), in 14 patients in soft 0.67 respectively). S and Sp PET/CT for the detection of pocket
tissues (gluteal region, pelvis, mediastinum, abdomen, pectoral infection were 0.84 and 0.92. According to NRI PET/CT improved
muscles and left thigh), in 4 patients lung uptake, in 3 patients the initial Duke classification in 52% of the cases. Also, PET/CT
liver uptake and in 1 case thyroid uptake. In 22 patients with detected septic embolism in 31% of the cases, 3 unsuspected
non-bone extracardiac uptake, a biopsy was performed in 6 primary tumours and provided an alternative diagnosis in 4 out
patients. In the 3 cases in which the biopsy was performed on of 14 cases in which CID-related infection had been excluded.
the site indicated by the scintigraphy, the result of the biopsy Conclusion: PET/CT constitutes an accurate diagnostic tool in
was positive for amyloidosis: one in abdominal fat, another in suspicion of CID-related infections with good performance in
liver and another in mediastinal lymph nodes with a diagnosis the evaluation of IE as well as pocket infection. PET/CT results
of amyloid lymphadenopathy. As an interesting finding, all correctly re-classified more than a half of the initial diagnoses.
of the 4 patients with lung uptake had myocardial Perugini PET/CT enables the detection of septic embolism, unsuspected
score 3 uptake. Conclusion: Non-bone extracardiac uptake of primary tumour and alternative diagnosis References: None.
99m
Tc-DPD- can guide the biopsy if histologic confirmation of
amyloidosis is needed. References: None.
EP-0161
Contribution of 18F-FDG-PET/CT in Treatment Decision
EP-0160 Making in Patients with Suspected Cardiac Implantable
Contribution Of 18F-FDG-PET/CT In Patients With Device Infection
Suspected Cardiac Implantable Device Related Infection B. Rodriguez-Alfonso, M. Mitjavila-Casanovas, L. Canales-
B. Rodriguez-Alfonso, A. Ramos-Martinez, V. Castro Urda, M. Rodriguez, V. Castro Urda, M. Cobo-Marcos, A. Ramos-Martinez;
Cobo-Marcos, I. Sanchez-Romero, J. Toquero-Ramos, A. Restrepo- Hospital Universitario Puerta de Hierro, Majadahonda, SPAIN.
Cordoba, M. Mitjavila-Casanovas;
Hospital Universitario Puerta de Hierro, Majadahonda, SPAIN.
Aim/Introduction: Accurate diagnosis of the localization and
extension of cardiac implantable device (CID) related infections
Aim/Introduction: Cardiac implantable devices (CID)-related enables the correct treatment decision. Definite infective
infections are globally increasing. Echocardiography and endocarditis (IE) requires complete CID removal while in some
modified-Duke criteria are the cornerstone in suspicion of CID- cases of superficial infection or inflammation CID can be left
related infections, but their yield is suboptimal in this scenario, in place. Patients who are at high risk for CID explant may be
with a significant percentage of over or underdiagnoses. treated only antibiotics and, in these cases, it is also important
Because these processes constitute a life-threatening situation, to be aware of the infection severity to adjust duration. The aim
a more prompt and accurate diagnosis is mandatory. The aim of of this study was to analyze the impact of PET/CT results on
this study was to evaluate the usefulness of 18F-FDG-PET/CT in treatment choice and/or duration in patients with CID-related
suspected CID-related infections in the clinical setting, analysing infection. Materials and Methods: We retrospectively analyzed
its performance and its influence over the final diagnosis. the treatment choices in all the patients who underwent a
Materials and Methods: All 18F-FDG-PET/CT studies carried out PET/CT at our institution because of a suspected CID-related
at our institution because of a suspected CID-related infection infection. We compared the initial attempt to treat with the final
S457 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

treatment, after being aware of PET/CT results. Changes were the clinical monitoring of all patients either following the result
registered as major changes when inter-modality (from explant of the microbiological culture or after response to the medical
to left in place or vice versa) and minor changes when intra- and/or surgical treatment. Results: 36 negative results (36 TN
modality (adjustments in the duration of antibiotic therapy). and 0 FN) and 20 positive results (17 TP y 3 PF) were obtained.
Results: Forty-five patients met inclusion criteria. According According to these results, 100 % sensitivity, 92% specificity
to the initial suspicion, 15 patients were referred for superficial were obtained. A positive predictive value of 85 % and negative
infection/inflammation or infection limited to the pocket, 13 for predictive value of 100 %. Conclusion: - The semiquantitative
“possible EI-CID”, 9 for “definite EI-CID” and 8 because unspecific analysis of the studies with 99mTc-Besilesomab in the diagnosis
systemic sings or symptoms. The first attempt to treat was of infectons of the musculoskeletal system supports the
complete removal of CID ± antibiotic therapy in 17 patients diagnostic decision after visual assessment and it contributes to
and antibiotic therapy or watchful waiting in 19. In 9 patients, the final decision in those cases in which the visual assessment is
although the most indicated treatment was removal of CID, it uncertain or not conclusive.- It is a reproducible procedure, not
was not considered because of a high risk. After performing PET/ operator dependent which reduces intra-operator variability.
CT studies, treatment strategies changed in 30 patients (66.7%). References: None.
Inter-modality treatment changes happened in 11 patients, in
6 it changed from removal to antibiotic management and in
5 from antibiotic to removal. In 16 patients there were minor EP-0163
changes affecting the duration of antibiotics (it was shortened Odontogenic and non-odontogenic mandibular
in 6 and increased in 10). In 3 patients the treatment focused osteomyelitis: Differentiating findings on bone
on a different pathological entity not related to CID, which scintigraphy
were considered as major changes. Conclusion: PET/CT is a K. Kawaji, M. Jinguji, M. Nakajo, A. Tani, T. Yoshiura;
very useful tool for the assessment of CID-related infections. Department of Radiology, Kagoshima University Graduate
Results of this imaging modality can lead to major changes in School of Medical and Dental Sciences, Kagoshima, JAPAN.
the therapeutic management in approximately 30% of patients.
Minor changes occurred even more frequently, in approximately
35% of patients. References: None. Aim/Introduction: Bone scintigraphy is often used to evaluate
osteomyelitis of the mandible. The major causes of osteomyelitis
in the mandible include dental infection (odontogenic) and
EP-0162 adverse effects of external radiation therapy or bone resorption
Musculoskeletical infections: contribution to definitive inhibitors (non-odontogenic). The purpose of this study was to
diagnosis of the semiquantitative analysis with 99mTc- investigate whether the pattern and degree of uptake in bone
besilesomab scintigraphy differ for the causes of mandibular osteomyelitis.
P. Guardia Jimena, A. Castro López, M. Martínez del Valle Torres, Materials and Methods: This retrospective study included
R. Arenas Aguaza, M. Bermúdez Morales, E. Moratalla Aranda, R. 20 consecutive patients with osteomyelitis of the mandible
Nieto Serrano, D. Becerra García; who underwent bone scintigraphy prior to treatment in our
San Cecilio University Clinical Hospital, Granada, SPAIN. hospital from January 2013 to March 2019. Among these
cases, 12 patients (8 males and 4 females; mean 57.0±4.5;
range 41-73 years) were diagnosed as having odontogenic
Aim/Introduction: Evaluate musculoskeletal infections through and remaining patients (6 males and 2 females; mean
visual and semiquantitative analysis with 99mTc-Besilesomab. 70.1±11.4; range 63-78 years) were diagnosed as having non-
Materials and Methods: We included 56 patients with age odontogenic osteomyelitis. In all cases, bone scintigraphy was
ranges from 19 years to 84 years with suspicion of osteomyelitis performed with 99mTc-HMDP. Regarding abnormal uptake
due to the presence of articular prosthesis, osteosynthesis in the mandible, the distribution was visually classified into
material or contagion via hematogenous route. Three phase three patterns (single nodular uptake, single long uptake, and
bone scan (Tc-99m-oxidronate) was previously performed on all multifocal uptake), and the degree of uptake was grade into 3
patients with positive result in all cases.The infection study was levels (grade 1: uptake equal to or less than surrounding bone;
performed after injection of 555 MBq 99mTc-Besilesomab with grade 2: uptake between grade 1 and 3; grade 3: uptake equal
static imaging 4 and 24 hours post injection, once the absence to or higher than the bladder). Furthermore, the lesion-to-orbit
of human anti-murine antibodies (HAMA) was confirmed. uptake ratio was calculated from the maximum counts within
The evaluation of the study was made visually and after the region-of-interest. For the visual evaluation, the differences
semiquantitative analysis, making regions of interest (ROIs) on between odontogenic and non-odontogenic groups were
the suspicious areas of infection both in early and late images, evaluated using chi-square test. Lesion-to-orbit uptake ratio
with the same intensity scale in all images and considering the was compared between the two groups using Mann-Whitney
total counts of each ROI. The studies whose quantification was U test. Results: The visual uptake pattern was significantly
equal or superior in 24 hours images in comparison with 4 hours different between odontogenic (single-nodular: 66.7%, single-
images were considered as positive, considering the decay of the long: 33.3%, multifocal: 0%) and non-odontogenic (single-
radiopharmaceutical. The definitive diagnosis was made after nodular: 12.5%, single-long: 12.5%, multifocal: 75.0%) groups
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S458

(P=0.001). As for the degree of visual uptake, there was no in the diagnosis work-up. In 4 patients, the MRI was negative
significant difference between odontogenic (grade 1: 0%, grade for spondylodiscitis, but became positive in an early control.
2: 33.3%, grade 3: 66.7%) and non-odontogenic (grade 1: 0%, Conclusion: In patients with spondylodiscitis, 18FFDG-PET-CT
grade 2: 50.0%, grade 3: 50.0%) (P=0.648). However, the uptake can be more sensitive in detecting vertebral lesions and can
ratio in odontogenic group (8.21±2.93) was significantly higher show the origin and extension of the infection, even earlier than
than that in non-odontogenic group (5.34±1.81) (P=0.016). MRI. Our data suggest that antibiotic treatment may not affect
Conclusion: In bone scintigraphy of mandibular osteomyelitis, 18F
FDG-PET-CT positivity and that the earlier the 18FFDG-PET-CT is
odontogenic cases showed higher uptake ratio than non- done after the onset of symptoms, the higher the SUVmax value
odontogenic cases. In addition, non-odontogenic cases tended in the lesion is. There may be a relationship between values of
to present multifocal uptake pattern while odontogenic cases CPR and MV/TLG. We need more sample to confirm statistically
more often showed single uptake patterns. The pattern and the tendency of our data. References: None.
degree of uptake in bone scintigraphy may provide clues about
the causes of mandibular osteomyelitis. References: None.
EP-0165
Bone extension of histiocytosis: Assessment with bone
EP-0164 scan and FDG-PET/CT
18F
FDG-PET-CT in patients with spondylodiscitis: image, A. Palomar Muñoz1, M. Cortés-Romera1, A. Sabaté-Llobera1, L.
clinical and laboratory findings in 10 cases Rubio-Álvarez1, X. Solanich-Moreno2, J. A. Narváez-García3, J. J.
J. Bernal, M. Agudelo-Cifuentes, B. Martinez-Sanchis, A. Yepes- Robles-Barba1, J. Mestres-Martí1, A. Rodríguez-Gasén1, C. Gámez-
Agudelo, A. Utrera-Costero, J. Fragio, P. Sopena-Novales, P. Bello- Cenzano1;
Arques; 1
Unit PET/CT (IDI)- Department of Nuclear Medicine. Hospital
Hospital La Fe, Valencia, SPAIN. U. de Bellvitge-IDIBELL, L’hospitalet de Llobregat (Barcelona),
SPAIN, 2Department of Internal Medicine. Hospital U. de
Bellvitge-IDIBELL., L’hospitalet de Llobregat (Barcelona),
Aim/Introduction: Spondylodiscitis is the third cause of SPAIN, 3Department of Radiology. Hospital U. de Bellvitge-
osteomyelitis in elderly patients. Although MRI is the gold IDIBELL., L’hospitalet de Llobregat (Barcelona), SPAIN.
standard imaging method at the diagnosis, 18FFDG-PET-
CT can be helpful when MRI is not clear or impossible to
perform, providing unique metabolic parameters. Our aim is Aim/Introduction: To determine the differences in the
to describe 18FFDG-PET-CT metabolic parameters along with assessment of histiocytosis bone extension between bone
clinical and laboratory findings in 10 patients with confirmed scintigraphy (BS) and positron emission tomography/computed
spondylodiscitis. Materials and Methods: Retrospective and tomography with 18F-fluorodeoxyglucose (FDG-PET/CT).
descriptive study of patients with confirmed spondylodiscitis Materials and Methods: We retrospectively evaluated all the
that had an 18FFDG-PET-CT done in the work-up, between patients referred to our center with the diagnosis of histiocytosis,
2014 and 2019. We collected data from 18FFDG-PET-CT image in which BS and FDG-PET/CT were available. The extension of
(number, localization of lesions, SUVmax, metabolic volume the disease in skull, spine and limbs was assessed, as well as
(MV), total lesion glycolysis (TLG), extraosseous foci), laboratory the number of areas with tracer uptake in both techniques.
(CRP, pathogen), clinical history (duration of symptoms and Radiotracer uptake was classified into three types of patterns:
antibiotic treatment before 18FFDG-PET-CT, diabetes mellitus, A) concordant (same locations and uptake areas), B) partially
infection foci) and MRI. Results: We had 10 patients and 13 concordant (same locations but different uptake areas), and C)
lesions on 18FFDG-PET-CT. The two diabetic patients presented not concordant (different location). Results: Seven patients (2
with more than 1 lesion. Lesion localization was: 7 lumbar women) were included in the study. Three of them had Erdheim-
(54%), 4 thoracic (31%) and 2 cervical (15%), being L3-L4 Chester disease, 3 Langerhans cell histiocytosis and 1 mixed
space the most frequently affected (n=4). The main cause of histiocytosis. We observed 5 patterns A (71%), one B and one C.
spondylodiscitis was endocarditis (5 patients). The pathogen In the partially discordant pattern the FDG-PET/CT determined
was detected in 9 patients: bacteria in 8 (E.Faecalis was the a greater number of uptake areas in the limbs but without
most frequent: 3 cases) and C.Albicans in 1. All 18FFDG-PET-CT additional locations. In the discordant patient, the BS showed
were positive, although most patients had antibiotic treatment uptake in a pelvic lesion and in the proximal tibia, both without
(9/10). SUVmax and TLG were not lower in patients with long clear evidence of FDG uptake (attributable to the disease and to
antibiotic treatment (>15 days before PET-CT). Mean SUVmax post-surgical changes, respectively). In studies with concordant
was 7,1 (4,6-12,7), mean MV was 41,4cm3 (15,2-122cm3), mean patterns, FDG-PET/CT additionally allowed assessing the soft
TLG was 166,1 (55-415,7). All patients that had 18FFDG-PET-CT tissue component associated with bone lesions in one of the
done early after the onset of symptoms (<2 weeks) had lesions patients, in addition to the assessment of extraosseous locations
with a higher SUVmax (above mean value). Most of lesions with (4 patients, 57.1%). Conclusion: There were a 71% of concordant
high MV and TLG (above mean value) were found in patients cases between both techniques. BS is very sensitive for the
with high levels of CRP (>75 mg/L). In 5 patients the 18FFDG-PET- detection of bone disease in histiocytosis, but FDG-PET/CT was
CT found extraosseous infective foci. All patients had MRI done able to detect additionally soft tissue disease surrounding bone
S459 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

lesions and demonstrates extraosseous locations (up to 57% of EP-0167


cases). References: None. 18
F-FDGPET/CT with early and delayed imaging in infective
endocarditis andimplantable cardiac electronic device
infection
EP-0166 H. Navalon Martinez1,2, L. Vidal1,2, S. Rubí1,2, A. Morcuende1,2,
SPECT/CT imaging in dacryoscintigraphy for the A. Repetto1,2, N. Orta1,2, B. Luna1,2, M. Valiente1,2, C. Medina1,2, C.
anatomical localization of nasolacrimal duct obstruction Peña1,2;
C. C. M. Fernandez1, K. Bayardo1,2, E. Silvera1, S. Rodriguez1, A. 1
Hospital Universitario Son Esapases, Palma De
Masso1,2, R. Hitateguy2, J. Vilar1,2, R. Ferrando1,2; Mallorca, SPAIN, 2IdISBa, Palma de Mallorca, SPAIN.
1
Clinical Hospital, University of the Republic.,
Montevideo, URUGUAY, 2Ferrari Ferrando Páez Nuclear
Medicine Clinic, Montevideo, URUGUAY. Aim/Introduction: Our aim was to evaluate the diagnostic
accuracy of FDG-PET/CT in patients with suspected prosthetic
valve(PV) infectious endocarditis(IE) and implantable-cardiac-
Aim/Introduction: Nasolacrimal duct obstruction is more electronic-device(ICED) infection, in whom modified Duke
frequent in women over 40 years of age and may be due to criteria were inconclusive; also assessing the added value
infectious, inflammatory, congenital and/or traumatic causes. of performing a delayed image acquisition. Materials and
Dacryoscintigraphy is a dynamic method that allows non- Methods: A retrospective study of 53 consecutive patients
invasive evaluation of lacrimal kinetics, contributing to the (total pool of 24PVs and 36ICEDs) where an FDG-PET/CT for
diagnosis and therapeutic management of the obstruction. suspected IE and ICED infection was performed between Jun-
Sometimes it can be difficult to determine the site of obstruction 2015 and Jan-2019. Earlywhole-body (65min p.i.) and delayed
in planar images. The objective is to determine if SPECT/CT thoracic (180min p.i.) FDG-PET/CT were acquired in all patients,
imaging adds information to define the location of nasolacrimal following a myocardial uptake suppression with unfractionated
obstruction. Materials and Methods: Dacryoscintigraphy was heparin and diet. Considered positive if, at least, one of the
performed by instilling 99mTc-pertechneciate in the lower early or late images demonstrates: intense-focal or markedly-
fornix of both eyes, with dynamic images for 30 minutes, heterogeneous uptake around the valvular plane (or around
followed by a static image. SPECT/CT of the area of interest
​​ with the subcutaneous generator on ICEDs), and negative if no-
low-dose CT was performed only if some grade of obstruction uptake or mild-moderate diffuse homogeneous uptake. Any
was identified in planar images. Finally, 22 patients (15 women, focal or segmental uptake along the ICED wires was considered
mean age 64 years, range 34-82) with diagnosis of epiphora positive. The remaining was considered doubtful. Final IE or ICED
(11 unilateral and 11 bilateral) were included. The studies were infection diagnosis was established according to microbiologic
performed in two gamma cameras: Infinia Hawkeye 4 and analysis of explant samples when available, or clinical follow-
Mediso AnyScan 16. Results: The topographic diagnosis of up.Added value of delayed images was evaluated in terms of
the lacrimal obstruction by planar images was concordant to their capacity to change the final report of FDG-PET/CT, i.e. to
that obtained by SPECT/CT in 15/22 patients. Planar images provoke a switch from a negative or doubtful scan in the early
identified complete obstruction prior to the sac in 6 (5 right imaging into a conclusive delayed positive or negative scan.
eyes [RE], 2 left eyes [LE]), partial obstruction prior to the sac SUVmaxvalues when visually positive were also assessed. Results:
in 3 (1 RE, 2 RE), complete obstruction in the sac in 3 (3 RE, 2 From 60 studied devices, infection was confirmed in twenty-
LE), partial obstruction in the sac in 8 (1 RE, 3 LE) and complete seven. Overall, FDG-PET/CT was positive in 17/60 devices and
obstruction in the duct in 3 (1 RE, 3 LE). SPECT/CT detected doubtful in 7/60, and showed a sensitivity, specificity, positive
partial obstruction prior to the sac in 1 patient (both eyes) with predictive value and negative predictive value of 63%, 97%,
obstruction in the sac in the planar images, partial obstruction 94%, and 76%, respectively. In the ICED subgroup, FDG-PET/
in the sac in 1 patient that had been identified prior to the sac, CT showed 8 positive studies, (7 generators and 1 proximal
and passage to the nostril in 2 patients with partial obstruction wire) where S, E, PPV and NPV were 67%, 100%, 100%, and
in the sac and 3 cases with complete obstruction (1 prior to 75%, respectively. In the PV subgroup FDG-PET/CT showed 9
the sac, 1 in sac and 1 in duct) modifying the obstruction to positive studies, whit S, E, PPV and NPV were 60%, 95%, 100%
partial. Conclusion: SPECT/CT can define the localization of the and 77%, respectively. In 7 of 17 PET-positive studies (41%)
lacrimal obstruction more accurately than planar images. This there were morphological changes on late images, with 6 of 7
information can help in the therapeutic decision selecting a SUVmax augmentation. Overall, delayed images made possible a
non-invasive or surgical treatment depending on the site and diagnostic change from doubtful to positive in 4 scans (finally
magnitude of the obstruction. References: None. confirmed as true-positives) and from doubtful to negative in 1
scan (finally deemed as a false-negative). Conclusion: FDG-PET/
CT is a useful tool with a high specificity in the diagnosis of PV
and ICED infections in patients with inconclusive previous Duke
criteria,. The acquisition of a delayed image may improve the
diagnostic certainty of infection. References: None.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S460

EP-0168 EP-0169
The potential clinical role of18F-FDG PET-derived metabolic MRI-based validation of 99mTc-HDP SPECT/CT in
parameters in extrapulmonary tuberculosis among HIV- sacroiliitis - preliminary results
infected patients: An explorative prospective study Z. Besenyi1, A. Bakos1, G. Sipka1, I. Farkas1, S. Urbán1, R. Hemelein2,
G. Boshomane, I. O. Lawal, T. Lengana, P. Rheeder, K. M. G. L. Kovács2, L. Pávics1;
Mokoala, M. Vorster, M. M. Sathekge; 1
University of Szeged Department of Nuclear Medicine,
University of Pretoria, Pretoria, SOUTH AFRICA. Szeged, HUNGARY, 2University of Szeged Department
of Rheumatology, Szeged, HUNGARY.

Aim/Introduction: 18F-FDG PET/CT is a useful imaging


modality to quantify the extent of tuberculous in clinical practice. Aim/Introduction: Spondyloarthropathies (SpA) belong
The baseline disease extent has been shown to be prognostic to the group of inflammatory arthritis which comprises the
predicting response to standard regimen of anti-tuberculous ankylosing spondylitis, reactive arthritis, psoriatic arthritis/
treatment (ATT) as well as duration of treatment. HIV-infected spondylitis, and arthritis/spondylitis associated with
individuals are susceptible to reactivation of old tuberculosis inflammatory bowel diseases. Common finding between these
(TB) and the acquisition of new disease. We herein report our different form of axial SpA is sacroiliac joint inflammation.
preliminary results on an-going study evaluating the role of The gold standard in diagnosis of sacroiliitis is magnetic
18
F-FDG in quantifying disease extent among HIV-infected and resonance imaging (MRI). The aim of this study is to compare
HIV-uninfected patients with extra-pulmonary TB. Materials the efficacy of dual phase 99mTc-HDP-SPECT/CT and MR in
and Methods: Thirty-three patients with extrapulmonary diagnosis of sacroiliitis in axial- spondylarthritis (SpA) patients.
tuberculosis were prospectively recruited to undergo a 18F-FDG Materials and Methods: Nineteen patients (8 females, 11 males,
PET/CT scan prior to the initiation of ATT. 18F-FDG PET-derived mean age: 36 years) were involved into the study. The patients
metabolic parameters including SUVmax, SUVmean, MLV and were selected according to clinical features with inflammatory
TLG were computed for all tuberculous lesions in each patient. type low back pain raising the suspicion of axial SpA. All patients
We compared these clinical characteristics and PET-derived were therapeutic-naive for glucocorticosteroids, DMARDs or
metabolic parameters between HIV-positive and HIV-negative TNF-α inhibitors. First, sacroiliac MR examination was performed
patients. Results: The mean age was 38.1 years. Twenty patients in the following sequences: T2- weighted STIR for the bone
(60%) were female whilst thirteen (40%) were males. A total of marrow edema (BME) and T1-weighted sequence for the fat
63.6% of the patients were HIV-positive. The HIV-infected patients metaplasia (FM). Within one-week 99mTc-HDP-SPECT/CT
were older compared with the HIV-uninfected patients (37.0 vs. (Mediso, AnyScan Trio) were performed. SPECT/CT and MR
33.0). There was a preponderance of females among HIV-infected images were evaluated visually by two independent observers.
patients (66.7% of all HIV-infected patients) compared with HIV- For quantitative evaluation MR slices were registered to CT
uninfected patients (54.5% of all HIV-uninfected patients). Of the (SPECT/CT). According to different structural lesions based on
HIV-infected patients, only four patients were immunologically appropriate MR and CT slices VOI-s were determined manually.
controlled with a CD 4 count >200 cells/uL. The median CD 4 Bone marrow edema, which characteristic for active process, and
count for the HIV-infected patients was 132 cells/uL (range: 32 chronical changes: fat metaplasia and sclerosis were contoured.
- 1008). Subjects who were HIV-positive had a higher SUVmax As reference region an intact sacrum part was chosen. In each
(16.6 vs 9.8), SUVmean (4.4 vs 3.6), MLV (186.3 vs. 104.2) and defined VOI average tracer uptake were calculated. Results: Six
TLG (757.5 vs. 369.9) when compared to HIV-negative patients active sacroiliitis and 5 chronic sacroiliitis without active lesions
suggesting higher disease burden in HIV-infected patients. were diagnosed according to the MR results. On the other
Conclusion: Our preliminary data demonstrates the potential of 8 patients the sacroiliitis was excluded based on normal MR
18
F-FDG PET-derived metabolic parameter in the assessment of findings. By the 99mTc-HDP-SPECT/CT 6 active and 5 chronical
disease extent in patients with extra-pulmonary TB. HIV-positive sacroiliitis were found, in 8 patients there were no pathological
patients demonstrated higher disease burden compared with changes characteristic for sacroiliitis. Intermodality analysis
HIV-uninfected patients. This suggests that immunologically showed excellent agreement (Cohen-kappa, ƙ=0.84). In our
uncontrolled HIV-infected patients may respond less favourably patient group overall agreement was 89 %, in active sacroiliitis
to ATT and require longer treatment duration compared with 89 %. On the bone SPECT tracer uptake was the highest in bone
HIV-uninfected patients. References: None. marrow edema, in sclerotic lesions was moderate and lowest
in fat deposition. Conclusion: According to our initial results
comparing MR and 99mTc-HDP SPECT/CT imaging in diagnosis
of sacroiliitis we can state: 99mTc-HDP SPECT/CT is useful tool
to detect active sacroiliitis in SpA patients. Furthermore, HDP-
uptake can be helpful distinguish between early and chronic
stages of sacroiliitis. Possible advantages of HDP-SPECT/CT
compared to MR may include investigation of additional disease
manifestation/joint involvement. Clinical relevance of this fact is
under further study. References: None.
S461 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

EP-0170 EP-09
Diagnosis of infected hip and knee prostheses with Cardiovascular: Vascular Imaging
Tc-99m Sulesomab: the utility of delayed (20-24hours)
imaging October 12 - 16, 2019
e-Poster Area
O. Mbakaza, O. A. Ayeni, K. Purbhoo, M. D. T. W. Vangu;
University of the Witwatersrand, Johannesburg, SOUTH AFRICA.

EP-0171
Aim/Introduction: To evaluate the clinical utility of a delayed Medical mimics and incidental findings diagnosed on
(20-24hours) imaging in a dual-time acquisition with Tc- PET/CT for investigation of possible giant cell arteritis: a
99m Sulesomab (LeukoScan) scintigraphy in the diagnosis of pictorial review
infection in painful hip and knee prostheses. Materials and S. L. Ayesa, A. M. Sammel, R. Laurent, P. J. Roach, E. Hsiao, G. P.
Methods: Patients referred to the Nuclear Medicine Department Schembri;
of 2 tertiary hospitals affiliated with the University of the Royal North Shore Hospital, St Leonards, Sydney, AUSTRALIA.
Witwatersrand, Johannesburg, South Africa with suspicion of
infected hip and knee prostheses, who had dual-time acquisition
protocol (4 hour and delayed 20-24 hour imaging) between Aim/Introduction: Giant cell arteritis (GCA) has a wide range
January 2015 and November 2018 using Tc-99m Sulesomab of clinical manifestations including headache, scalp tenderness,
scintigraphy were retrospectively enrolled in this study. All jaw claudication, visual loss, aortic arch syndromes and stroke
patients had clinical and/or biochemical suspicion of infection. (1). With the increasing use of PET/CT for investigating GCA,
The scintigraphic data was assessed visually by three nuclear medical mimics are often identified on imaging.We reviewed
medicine physicians blinded to laboratory and radiographic alternative diagnoses and significant incidental findings found
results. The images were independently reported as: positive, on PET/CT during the prospective cross-sectional study of Giant
equivocal or negative for infection based on existing guidelines Cell Arteritis and PET Scan (GAPS) (2). Materials and Methods:
on data interpretation. The delayed images were compared The prospective GAPS study imaged 64 new patients with
to early images and visually graded as more intense, same suspected GCA with time-of-flight PET/CT from skull vertex to
intensity, less intense and no abnormal uptake. An increase in diaphragm, within 72 hours of commencing corticosteroids
uptake intensity was considered consistent with infection, same and prior to temporal artery biopsy. Images were read by PET
intensity was considered equivocal, and less intense pattern experienced nuclear medicine physicians blinded to clinical
was considered a negative result. In equivocal cases on delayed history, biopsy and serology results. Incidental findings and/
LeukoScan imaging, Tc-99m nanocolloid bone marrow scan or alternative diagnoses were recorded, considered clinically
was performed and the final result was determined thereafter. significant if they lead to eventual diagnosis or treatment.
Results: There were 39 females and 22 males; mean age was Results: GCA was the clinical diagnosis in 21/64 patients,
60.3 years. Sixty two percent (n=38) had hip prosthesis and 38 with biopsy proven GCA in 12/21. Incidental findings and/or
% (n=23) had knee prosthesis. Following visual analysis, early alternative diagnoses were identified in 30/64 studies, the finding
LeukoScan images were considered negative in 30% of studies. clinically significant in 13/30 patients. In 11/13, the alternative
On delayed images, about half of the studies were negative, diagnoses contributed to patient presentation. 5 patients were
15% positive, while a third were regarded as equivocal. There diagnosed with malignancy - 4 with lung cancer (2 metastatic),
was non-conformity in the interpretation of images on direct and 1 with thyroid cancer. Lung malignancy was the final
comparison of early vs delayed images in more than half of the diagnosis in 3 patients, with 2 true incidental cancers detected
patients (55%). The difference in this early vs late comparison (thyroid and lung). Typical polymyalgia rheumatica symptoms,
was significant (p<0.001). More than two thirds (69%) of the of likely paraneoplastic cause, were recorded in 1 patient with a
overall study had nanocolloid imaging as a final interpretative final diagnosis of lung cancer.7 diagnoses of infection included
study. Both early and delayed images had a significant difference pneumonia (3), maxillary sinusitis (3) and cervical osteomyelitis
when compared to the final conclusion after nanocolloid (1). 2/3 patients with sinusitis were clinically diagnosed with
imaging (p=0.03) and (p=0.002) respectively. Conclusion: biopsy negative GCA. 1 patient was diagnosed with clinically
Despite no concrete consensus on the use of delayed imaging significant thyroiditis. The most common presenting symptoms
with Tc-99m Sulesomab (LeukoScan) scintigraphy, our data in patients with a clinically significant alternative diagnosis
suggest that the utility may be in reducing the number of false was headache (12) and scalp tenderness (7). Jaw pain and
positive studies interpreted on early imaging. However, for cases scalp tenderness were present in all 3 patients with sinusitis.
considered positive on early images; delayed images may not Conclusion: GCA is associated with a range of non-specific
be necessary if colloid imaging is readily available to improve symptoms. The reporting physician should be alert to the
specificity. References: None. range of possible alternative diagnoses for GCA and incidental
findings, as many will be clinically relevant. References: 1.
Salvarani C, Cantini F, Hunder G. Polymyalgia rheumatic and
giant cell arteritis. Lancet. 2008;372:234-45.2. Sammel AM, Hsiao
E, Schembri G, Nguyen K, Brewer J, et al. Diagnostic Accuracy of
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S462

PET/CT Scan of the Head, Neck and Chest for Giant Cell Arteritis: characteristics of coronary atherosclerosis did not improve the
The Double-Blinded Giant Cell Arteritis and PET Scan (GAPS) prognostic model. Conclusion: Segment Stenosis Score, CT_SS
Study. Arthritis Rheumatol. 2019 [ePub ahead of print, published as well as noncalcified structure and circular geometry of the
online March 8 2010]. atherosclerotic plaques are the most significant independent
predictors of moderate and large stress perfusion defects.
These CT morphological characteristics could be used for risk
EP-0172 stratification in patients with intermediate pretest probability of
Relationships between the results of computed SCAD. References: None.
tomography coronary angiography and myocardial
perfusion abnormalities on SPECT
K. Zavadovskiy, A. Maltseva, K. Kopeva, A. Mochula, E. Grakova; EP-0173
Cardiology Research Institute, Tomsk National Usefulness of 18-Fluordesoxiglucose PET/CT semi-
Research Medical Centre, Russian Academy of quantification in the diagnosis of large vessel vasculitis: a
Sciences, Tomsk, RUSSIAN FEDERATION. retrospective study
D. Lisei Coscia, C. Vigil, O. Rodriguez, C. Salvat, A. Laverde, M.
Domínguez, B. Fernandez, N. Martín, F. Gonzalez García;
Aim/Introduction: Currently myocardial perfusion imaging Hospital Universitario Central de Asturias, Oviedo, SPAIN.
(MPI) is one of the most common methods to identify
myocardial ischemia. Coronary computed tomography coronary
angiography (CCTA) is well-established method of coronary Aim/Introduction: Large vessel vasculitis (LVV) is an arteries
atherosclerosis diagnosis, but it doesn’t allow to identify disease with two major variants, Takayasu arteritis and giant
myocardial ischemia. The purpose of this study was to assess cell arteritis. Many arteries can be affected, mostly thoracic
the relationships between morphological CT-characteristics of aorta and its main branches; with polymyalgia rheumatica
coronary atherosclerosis and myocardial perfusion downstream (PMR) also belonging to this disease spectrum. The use
in patients with intermediate pretest probability of stable of 18-Fluordesoxiglucose PET/CT (FDG-PET/CT) has been
coronary artery disease (SCAD). Materials and Methods: increasing in last years, although definitive diagnosis can be
Materials and Methods: The study group comprised 68 patients difficult due to the lack of accepted definitive criteria, which
(42 men, age 63 (56;68) years) who underwent coronary turns into a limitation of this technique. According to previous
computed tomography angiography (CCTA) as well as stress- evidence using aorta to liver ratios, we decided to evaluate
rest MPI (with CT attenuation correction) on the hybrid system the use of FDG-PET/CT semi-quantification parameters in our
GE Discovery NM/CT 570С equipped with with dedicated series. Materials and Methods: We performed a retrospective
cardiac Cadmium-Zinc-Telluride gamma camera. The following analysis in a series of 33 patients with FDG-PET/CT. 22 of them
CCTA features were assessed: Agatston calcium score, maximal have been previously diagnosed of LVV and 11 were considered
stenosis degree, positive remodeling index, total atherosclerotic as controls (most had symptoms of vasculitis or previous history
plaque length, the sum of stenoses, the presence of at least one of vasculitis/PMR, but without evidence of activity according
stenosis >50%, plaque structure and geometry. The Segment to clinical, radiological, o laboratory parameters at the time
Involvement Score, Segment Stenosis Score and CCTA based of FDG PET/CT acquisition). Thoracic/main aorta branches
Syntax Score (CT_SS) were calculated as measures of global SUVmax (SUVmax A) and right hepatic lobe SUVmax (SUVmax
atherosclerosis burden. The patients were divided into two L) were obtained, plus erythrocyte sedimentation rate (ESR) and
groups: 1) moderate and large stress perfusion defect extent C-reactive protein (CRP) of all patients. Continuous variables
(SSS≥9); 2. small perfusion defect extent (SSS<9). Results: The MPI were compared using T-Test, receiver operating characteristic
parameters Summed Stress Score (SSS) and Summed Difference (ROC) analysis was performed for SUVmax A absolute value and
Score (SDS) had moderate correlation with CT-characteristics also for SUVmax A/SUVmax L ratio (A/L ratio). Pearson correlation
of coronary atherosclerosis: SSS with Segment Stenosis Score was performed between CRP/ESR and SUVmax A. Results:
(ρ=0,25, p=0,0099), CT_SS (ρ=0,37, p=0,00003), the sum of No significant differences between case-control groups were
stenoses (ρ=0,27, p=0,0033) and maximum stenosis (ρ=0,41, found in demographic variables, ESR and CRP values. Aortic arch
p=0,0002); SDS with CT_SS (ρ=0,31, p=0,00002) and maximum was the most frequently involved region visible in FDG-PET/CT.
stenosis (ρ=0,34, p=0,0005). According to the univariate logistic Significant differences were found between SUVmax A in LVV
regression, maximum stenosis (OR 1,04; CI 1,02-1,06; p=0,0001), patients vs. controls: 3.86 (95%CI 4.12-3.59) vs. 3.12 (95%CI 3.47-
the sum of stenoses (OR 1,01; CI 1,00-1,01; p=0,02), Segment 2.77) (p<0.001) and between A/L ratio: 1.04 (95%CI 1.12-0.95) vs.
Stenosis Score (OR 1,14; CI 1,04-1,25; p=0,04) and CT_SS (OR 0.82 (95%CI 0.88-0.76) (p<0.001). In ROC analysis, the area under
1,32; CI 1,12-1,56; p=0,01), the presence of stenosis >50% (OR the curve (AUC) obtained for SUVmax A was 0.826 (p<0.003),
5,4; CI 1,69-17,16; p=0,004), noncalcified (OR 1,79; CI 1,11-2,87; enhaced when using A/L ratio: AUC= 0.872 (p<0.001). A mild
p=0,017) and circular features (OR 2,99; CI 1,48-6,04; p=0,002) of positive correlation was found between SUVmax A and ESR
the atherosclerotic plaques were the independent determinants r=0.538, p<0.01. Conclusion: The use of 18-Fluordesoxiglucose
of moderate and large perfusion defect. By the results to PET/CT allows an accurate diagnose in patients with suspected
multivariable logistic analysis the combination of several CT- LVV with inflammatory activity. Among all parameters, the
S463 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

semi-quantitative ratio using artery/liver uptake proved to be EP-0175


more precise than absolute SUVmax of the involved vessels. Molecular imaging of carotid artery atherosclerosis with
References: None. pet: a systematic review
R. Piri, O. Gerke, P. F. Høilund-Carlsen;
Department of Nuclear Medicine, Odense
EP-0174 University Hospital, Odense C, DENMARK.
Arterial inflammation detected with PET-TC 18F-FDG at
staging and end of treatment after ABVD for Hodgkin Aim/Introduction: Carotid artery atherosclerosis is the
lymphoma leading cause of cerebrovascular events. Therefore a decent
A. L. Gutiérrez Cardo1, B. Azzaoui Jiménez2, A. J. Mesas Ruiz3, M. opportunity is provided by investigating the carotid arteries
Lillo García4, M. A. Sánchez Chaparro2, P. Valdivielso Felices2; before any adverse outcome. We conducted a systematic review
1
Hospital Regional Universitario de Málaga. Servicio of articles on PET imaging of carotid artery atherosclerosis with
Andaluz de Salud, Málaga, SPAIN, 2Universidad de Málaga, emphasis on clinical usefulness. Materials and Methods:
Málaga, SPAIN, 3Hospital Universitario Virgen de la Victoria. Research articles in English reporting carotid artery PET
Servicio Andaluz de Salud, Málaga, SPAIN, 4Fundación imaging until November 2018 were systematically searched
General de la Universidad de Málaga, Málaga, SPAIN. for in Medline/PubMed, Scopus, Embase, Google Scholar, and
Cochrane Library. Duplicates, editorials, letters, case stories,
conference abstracts, and patients with end-stage disease
Aim/Introduction: Hodgkin lymphoma survivors are at or receiving immunosuppressive medication were excluded.
increased cardiovascular risk. Positron emission tomography All eligible articles were reviewed by one observer (RP) to
(PET) with 18F-FDG is a potential predictor of long-term provide a PRISMA diagram. Included articles were grouped
cardiovascular risk and at least two PET-CT scans are performed into the following categories: diagnostic performance, risk
at staging and end-of-treatment. The purposes were to study factors, laboratory findings, imaging modalities, or treatment,
the feasibility of performing vascular 18F-FDG uptake in both and the main information they provided was summarized.
scans and compare which study could show higher values: Results: Of 1718 primary hits, 57 studies were included. Being
staging-PET affected by disease-induced inflammatory state or applied in 49 and 5 studies for imaging inflammation and
end-of-treatment PET after chemotherapy-induced endothelial microcalcification, respectively, 18F-fluorodeoxyglucose (FDG)
damage. Materials and Methods: Scans from 23 patients with and sodium fluoride (NaF) (5/57) were the most frequently
classic Hodgkin lymphoma, and complete remission after the used tracers. In summary, it has been shown that Normal
last cycle of ABVD were included. Data recorded included sex, carotid arteries have the lowest FDG uptake. Further that
age, histological type, cardiovascular risk factors and time after patients with symptomatic atherosclerosis have higher uptake
last chemotherapy. Measurements of TBRmax and TBRmean than asymptomatic patients and that atherosclerotic carotid
were performed including thoracic aorta, common carotids and lesions ipsilateral to a cerebrovascular event had increased FDG
iliac arteries, SUV medium of VOIs traced in spleen and bone uptake compared to the contralateral carotid artery, but that
marrow (lumbar vertebrae) in initial and final PET. Data have this difference tends to decrease with time, apparently due to
been analysed with a Student’s t-test for paired simples, Wilcoxon reduced local inflammation in the ipsilateral carotid artery and
signed-rank test for non parametric data and Spearman’s rank increased inflammation in contralateral carotid artery. It was
for time after chemotherapy and vascular uptake correlation. found that FDG uptake is significantly associated with increased
Results: Of the 23 studies carried out, 15 were men and 8 age, male gender, body mass index (in healthy individuals), and
women, with an average age of 40 ± 18 years (14-82). Of these, 18 with arterial hypertension, hypercholesterolemia, and diabetes
(78%) had no spleen involvement and 19 (82%) had no marrow mellitus. Histological assessment indicated a strong correlation
involvement. In every patient vascular ROIs could be traced between microcalcification and NaF uptake in symptomatic
avoiding specific lymphomatous uptake. There was a significant patients, but a negative correlation with FDG uptake. FDG
increase in TBRmean in aorta and carotids in the second PET of uptake was associated with increased macrophage count and
0.83 and a significant decrease in metabolic activity in spleen CD68 count, both accounting for increased local inflammatory
and bone marrow of 0.44 and 0.35 respectively, both including response. FDG uptake was correlated with hypoechogenicity
or excluding those with initial infiltration (5/23 22% spleen; 4/23 and microembolic signals on ultrasonography. FDG uptake
18% bone marrow). A weak negative correlation was found was inversely correlated with CT-derived calcium score and
between time after chemotherapy acquisition and vascular directly with intima-media thickness on CT. In PET/MRI, FDG
uptake (-0,258 non significant). Conclusion: It is possible to uptake correlated positively with necrotic lipid-rich core volume
measure vascular uptake for cardiovascular risk evaluation in of plaques. Conclusion: While FDG-PET ‘visualizes’ the current
Hodgkin lymphoma even in staging-PET.The increase of arterial status of carotid atherosclerosis inflammation and its possible
inflammation after treatment, and the negative correlation clinical features enabling risk stratification of atherosclerotic
between it and the time elapsed between the last cycle of ABVD plaques, NaF-PET appears to indicate long-term consequences
and the PET performance could be due to the endothelial toxic of ongoing inflammation by ‘visualizing’ microcalcification
effect of chemotherapy. References: None. enabling detection of atherosclerosis even in apparently normal
carotid arteries. References: None.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S464

EP-0176 EP-0177
Short-term discontinuation of vagal nerve stimulation Utility Of PET-CT With 18F-FDG In The Study Of Large
alters 18F-FDG blood pool activity in humans Vasculitis
E. Boswijk1,2, R. Franssen1, G. H. E. J. Vijgen3, R. Wierts1, J. van der C. Mena Melgar, C. Paniagua Correa, M. de la Rubia Marcos, B.
Pol1, A. M. A. Mingels4, E. M. J. Cornips5, M. H. J. M. Majoie6,7,8, W. D. Tagliatori Nogueira, A. Herrero Muñoz, C. Sandoval Moreno, P.
van Marken Lichtenbelt9, F. M. Mottaghy1,10, J. E. Wildberger1,2, J. Garcia Alonso, L. Castillejos Rodriguez, A. Ortega Valle, M. Balsa
Bucerius1,2,10; Breton;
1
Department of Radiology and Nuclear Medicine, Maastricht Hospital Universitario de Getafe, Getafe, SPAIN.
University Medical Center (MUMC+), Maastricht, NETHERLANDS,
2
Cardiovascular Research Institute Maastricht (CARIM),
Maastricht University, Maastricht, NETHERLANDS, 3Department Aim/Introduction: To analyze the usefulness of PET-CT
of Surgery, Erasmus Medical Center, Rotterdam, NETHERLANDS, in the study of patients with suspicion or follow-up of the
4
Department of Clinical Chemistry, Maastricht University Medical inflammatory process of the vascular system, focused on
Center (MUMC+), Maastricht, NETHERLANDS, 5Department of the involvement of large vessels. Materials and Methods:
Neurosurgery, Maastricht University Medical Center (MUMC+), We retrospectively analyzed the PET-CT studies, performed
Maastricht, NETHERLANDS, 6Department of Neurology, Maastricht during the last three years in our center, to 28 patients with
University Medical Center (MUMC+), Maastricht, NETHERLANDS, suspicion or follow-up of vasculitis of large vessels (22 women
7
Epilepsy Center Kempenhaege, Heeze, NETHERLANDS, 8MHENS and 6 men).A large number of requests (23) were made in the
School of Mental Health & Neuroscience, Maastricht University, initial study of patients with suspected large vessel vasculitis,
Maastricht, NETHERLANDS, 9School of Nutrition and Translational especially in cases with an atypical presentation and / or to
Research in Metabolism (NUTRIM), Maastricht University, assess the extent; while the rest of the included studies (5) were
Maastricht, NETHERLANDS, 10Department of Nuclear Medicine, performed on patients with known pathology and suspected
University Hospital RWTH Aachen, Aachen, GERMANY. reactivation or response to treatment. All patients underwent
PET-CT after the administration of 18F-FDG, with tomographic
metabolic imaging at 45min post-injection and whole-body CT
Aim/Introduction: Vagus nerve activation has a direct impact for attenuation correction and anatomical localization. For the
on inflammation. Therefore, we investigated whether vagal analysis of the results, we compared the result of the PET-CT,
nerve stimulation (VNS) influences arterial wall inflammation using Meller’s visual scale (which compares tissue uptake with
as measured by 18F-FDG uptake. Materials and Methods: Ten respect to liver uptake, being an equal or superior uptake valid
patients with left-sided VNS for refractory epilepsy were studied to evaluate the degree of inflammation and the activity of it);
during stimulation (VNS-on) and in the hours after stimulation with the recognized gold-standard technique (arteriography
was switched off (VNS-off ). In nine patients, 18F-FDG uptake for Takayasu arteritis and temporal artery biopsy in the case of
was measured in the right carotid, aorta, bone marrow, spleen giant cell arteritis) and / or with the clinical diagnosis made by
and adipose tissue. Target-to-background ratios (TBRs) were the requesting physician. Results: Of the 28 patients, 18 had
calculated to normalize the respective standardized uptake a negative PET-CT study, with 18 of them TN. Only 4 of them
values (SUVs) for venous blood pool activity. Median values were considered as FN when the subsequent diagnosis was
are shown with their interquartile range and were compared established by the clinician. Note that 3 of these 4 patients were
using the Wilcoxon signed rank test. Results: Arterial SUVs were in active treatment with corticosteroids at the time of PET-CT,
higher during VNS-off than VNS-on [SUVmax all vessels 1.8 (1.5- which may be the cause of these FN.In the case of patients who
2.2) vs. 1.7 (1.2-2.0), p=0.051]. However, a larger difference was were considered healthy at the end of the study, we found that
found for venous blood pool, reaching statistical significance all of them had a negative PET-CT study, showing a specificity of
in the superior cava vein [meanSUVmean 1.3 (1.1-1.4) vs. 1.0 (0.8- 100%.In turn, we observed that in all 6 patients with positive PET-
1.1); p=0.011], resulting in non-significantly lower arterial TBRs CT study for vasculitis, all of them had this diagnosis confirmed
during VNS-off than VNS-on [TBRmax all vessels 1.5 (1.4-1.6) vs. by the gold-standard technique recognized, establishing a
1.7 (1.5-1.9), p=0.086]. Albeit in the same direction, differences 100% PPV + in our study. Conclusion: PET-CT is very useful
in the remaining tissues were not significant. Insulin levels were in the study of large vessel vasculitis, especially due to its
increased after VNS was switched off (55.0 pmol/l (45.9-96.8) high specificity and PPV +, identifying the patient with active
vs. 48.1 pmol/l (36.9-61.8); p=0.047]. However, the concurrent pathology with sufficient certainty. References: None.
increase in glucose levels did not reach statistical significance [4.8
mmol/l (4.7-5.3) vs. 4.6 mmol/l (4.5-5.2); p=0.053]. Conclusion:
Short-term discontinuation of VNS readily influenced arterial
18
F-FDG uptake. However, VNS significantly decreased the
venous blood pool activity, possibly due to a systemic effect on
glucose metabolism. The observed change in arterial 18F-FDG
uptake seems therefore less likely to be related to a direct effect
on arterial inflammation. References: None.
S465 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

EP-0178 EP-0179
18F-FDG PET/CT and CT angiography in the evaluation of Measurement of epicardial adipose tissue with FDG-PET/
immunosuppressive therapy in large vessel vasculitis CT in patients with type-2 diabetes mellitus
M. M. S. Moragas1, M. Andreu2, J. Martín1, A. Caresia1, M. D. Dezso1, K. Zámbó1, Z. Ritter1, Z. Bán1, Z. Szabó1, B. Bódis2, E.
Monteagudo3, C. Diaz1, A. Rodríguez1, Z. Bravo1, L. Bernà1; Várady3, S. Szukits3, A. Tóth3, O. Nemes2, K. Rucz2, S. Szujó2, E.
1
Servei Medicina Nuclear. Parc Taulí Hospital Universitari, Sabadell Mezősi2, L. Bajnok2, E. Schmidt1;
(Barcelona), SPAIN, 2Servei Radiologia. Parc Taulí Hospital 1
University of Pécs Department of Nuclear Medicine,
Universitari, Sabadell (Barcelona), SPAIN, 3Servei Medicina Interna. Pécs, HUNGARY, 2University of Pécs 1st Department
Parc Taulí Hospital Universitari, Sabadell (Barcelona), SPAIN. of Medicine, Pécs, HUNGARY, 3University of Pécs
Department of Radiology, Pécs, HUNGARY.

Aim/Introduction: 18F-FDG PET/CT (FDG-PET) and CT Aim/Introduction: Type 2 diabetes (T2DM) is a leading risk
angiography (CTA) are useful in diagnosis of large vessel factor of cardiovascular diseases. There is a strong correlation
vasculitis (LVV), but more limited data are available on their between coronary artery diseases and the volume of epicardial
contribution in treatment response assessment. The aim of the adipose tissue (EAT) deposits located between myocardium
study was to compare FDG-PET and CTA in the evaluation of and visceral pericardium. This metabolically active ectopic
immunosuppressive therapy in LVV. Materials and Methods: adipose tissue is in strong relationship with visceral adipose
12 patients diagnosed of LVV have been studied twice with tissue developmentally and correlates with its amount. EAT has
FDG-PET and CTA before (basal scan) and after treatment has been investigated intensively in the last few years, including
been started or finished (monitoring scan). Patients were studied its effect on cardiovascular risk. The aim of our work is to study
simultaneously in the same PET/TC device, with a mean follow the relationship between vascular calcification, subcutaneous
up of 18 months. CTA diagnostic LVV criteria were circumferential adipose tissue and EAT in the diabetic population studied
aortic wall thickening >2 mm and >1 mm in aortic branches, with FDG-PET/CT. Materials and Methods: Examinations
and/or wall enhancement (> 40 UH), and/or irregular thickening of 18 T2DM patients’ (8 men, 10 women, mean age 67±6.3)
extending to peri-vascular tissue, and/or structural vascular and 62 non-diabetic patients (35 men, 27 women, mean age
changes as complications. FDG-PET diagnostic LVV criteria 60±10.6) were investigated during our retrospective study. The
were diffuse FDG uptake in aorta wall and/or its main branches volume of EAT was determined in 16 patients with coronary
using Meller visual scoring index, that compares vessel and CT angiography (CTA) and FDG-PET/CT scans using Slicer
liver uptake. Positive scan: score>2 for thoracic aorta and ≥ 2 4.10.0 software (https://www.slicer.org, open source software
for other vascular regions. Changes in basal and monitoring package)[1]. In 64 cases only FDG-PET/CT data (Interview Fusion
scans results were compared, and correlated with laboratory software, Mediso) were applied. SUVmax (Standardized Uptake
acute phase reactants (AFR). Results: Basal scan: All patients Value), the volume of calcified arterial plaque (density above
had a positive FDG-PET, 10 a CTA positive scan and 9 an AFR 130 Hounsfield Units) and EAT were measured and the results
elevation. Monitoring scan: FDG-PET: 5 patients scan normalized were evaluated using SPSS software. Results: Early results of our
in all vascular segments (complete response CR), 5 patients ongoing research showed no significant difference between
had reduction in number and/or metabolic activity of vascular BMI-corrected EAT volume (p=0.465) measured on CTA and
segments (partial response PR), and 2 patients had increased FDG-PET/CT, however, the values ​​ were strongly correlated
in number and/or metabolic activity of vascular segments (r=0.949, p<0.001). Significant correlation was found between
(progression P). Of 5 patients with FDG-PET CR, 2 had CTA CR EAT volume and the calcification of the vascular system on the
(no inflammation nor structural changes), 1 had CTA PR (no whole examined population (r=0.266, p<0.05). The amount of
inflammation or no estructural changes), 1 had no changes on EAT (p<0.001), SUVmax (p<0.05) and the degree of vascular
CTA (no response NR) and 1 CTA was negative as basal scan. Of calcification (p<0.05) in patients with T2DM were significantly
5 patients with FDG-PET PR, 3 had a CTA PR, 1 NR, and 1 was higher than in the control group. EAT SUVmax ​​in both groups
negative as basal scan. Of 2 patients with FDG-PET R, CTA was were significantly higher (p<0.001) than subcutaneous adipose
also positive for R. There were not CTA CR with FDG-PET NR or tissue SUVmax, and the subcutaneous adipose tissue SUVmax
PR. AFR only normalized in 3/9 patients, 1 RC, 1 PR and 1 P in was significantly higher (p<0.05) in T2DM patients compared
FDG-PET. Conclusion: FDG-PET seems to be more sensitive to the control group. Conclusion: Based on our results, both
than CTA and AFR in detecting CR in LVV. Both FDG-PET and CTA and FDG-PET/CT tests are suitable to quantify EAT. Patients
CTA are sensitive in detecting progression. Value of FDG-PET with T2DM have significantly higher levels of EAT, higher FDG
PR has to be studied by following the patients, as it can be real uptake, and vascular calcification. According to our results, the
response vs no response. References: None. higher epicardial fat deposits may contribute to the higher
cardiovascular risk in T2DM patients. References: [1] Fedorov A.,
Beichel R., Kalpathy-Cramer J., Finet J., Fillion-Robin J-C., Pujol S.,
Bauer C., Jennings D., Fennessy F., Sonka M., Buatti J., Aylward S.R.,
Miller J.V., Pieper S., Kikinis R. 3D Slicer as an Image Computing
Platform for the Quantitative Imaging Network. Magnetic
Resonance Imaging.2012 Nov;30(9):1323-41.PMID:22770690.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S466

EP-10 exercise. After certain threshold those pathophysiological


Cardiovascular: Myocardical Perfusion Imaging processes result in chest pain in IPAH patients, and assessment
of those impairments as a pain substrate is useful with 99mTc-
October 12 - 16, 2019 MIBI SPECT. References: None.
e-Poster Area

EP-0181
EP-0180 Visual identification of coronary calcifications on
Myocardial ischemic patterns in patients with idiopathic diagnostic chest CT improves diagnostic accuracy of Tl-
pulmonary arterial hypertension 201 CZT SPECT myocardial perfusion imaging
A. A. Ansheles1, I. G. Guryanov2, T. V. Martynyuk1, V. B. Sergienko1; H. Chen, Y. Chang, Y. Huang;
1
National Medical Research Center of Cardiology, Department of Nuclear Medicine, Kaohsiung Chang
Moscow, RUSSIAN FEDERATION, 2National Economics Gung Memorial Hospital, Kaohsiung, TAIWAN.
Research Institute, Moscow, RUSSIAN FEDERATION.

Aim/Introduction: Single photon emission tomography


Aim/Introduction: According to Russian registry, 42% of (SPECT) myocardial perfusion imaging (MPI) can provide
idiopathic pulmonary arterial hypertension (IPAH) patients valuable diagnostic and prognostic information in patients with
manifest with chest pain. The aim of current research was to known or suspected coronary artery disease (CAD). Recently,
assess myocardial perfusion in IPAH patients with 99mTc-MIBI the development of cadmium-zinc-telluride(CZT) SPECT MPI
SPECT, to justify LV/RV ischemia patterns as probable cardialgias provided satisfactory sensitivity but suboptimal specificity for
substrate in this group. Materials and Methods: 74 patients with detecting CAD. Coronary artery calcification(CAC) is a useful
confirmed IPAH (70 women), mean age 38,2±9,4, formed group CAD indicator when assessed by dedicated calcium scoring CT
I (with cardialgia, n=36) and group II (without chest symptoms, scan. Simultaneous CAC scoring with CZT SPECT MPI offered
n=38), all underwent myocardial perfusion CT-corrected 99mTc- incremental diagnostic and prognostic information over CZT
MIBI SPECT at rest and after treadmill cardiopulmonary exercise SPECT alone using Tc-99m sestamibi. The aim of this study is
test. LV perfusion abnormalities were evaluated using standard to assess diagnostic implications of CAC incorporated with
SSS/SDS parameters, RV was assessed visually, IVS/LW and RV/ Thallium (Tl)-201 CZT SPECT MPI. Materials and Methods:
LV uptake ratios were calculated, in comparison with Holter We retrospectively analyzed patients who underwent invasive
and six-minute walking test (6MWT) results. Results: Group coronary angiography (ICA) within 6 months of SPECT MPI.
I demonstrated worse 6MWT results (439±107 vs 489±99m, Patients who received diagnostic chest CT within 6 months
p=0.04), higher rate of ischemic signs at Holter (22,2% vs 2,6%, prior to ICA were included (N=126). The MPI and CT images
p=0.03), shorter exercise duration (4,9±2,1 vs 5,9±2,4 min, were interpreted by experienced nuclear medicine physicians
p=0.06). Typical myocardial perfusion SPECT results, that did not and radiologists without knowledge of clinical history. For
differ in both groups, included visible, severely dilated RV (mean assessing the location and severity of perfusion defects, 17
EDV=103±51 ml) with low EF (22±6%), diffusely inhomogeneous segmentation scores and a 5-point scale were used. The global
MIBI uptake. RV accumulation level was comparable to LV lateral summed stress score (SSS) was calculated by adding all scores
wall (LW) (RV/LV ratio=0.60±0.09), that indicates RV hypertrophy. in 17 segments on stress images. MPI results were considered
SSS/SDS values were somewhat higher in group I (8 [6-10] vs abnormal when SSS ≥4 . Identification of any calcified region
6 [5-7], p=0.09, 3 [2-4] vs 2 [1-4], p=0.14, respectively). Stable (HU >130) within coronary artery territories on non-contrasted
perfusion defects were located in IVS in all cases, mean IVS/LW CT scan was defined as CAC positive. A coronary stenosis ≥50%
was lower in group I (0.56 ± 0.06 vs 0.60±0.07, p=0.01). Stable on ICA was considered obstructive CAD. Results: The specificity
defects spread at stress images in 67% of patients in group I and of MPI plus CAC were higher than in MPI alone (86% vs 71%; p=
in 32% of patients in group II. Moreover, 5 patients from group 0.004). The sensitivity showed no significant difference between
I (14%) demonstrated stress-induced apical and/or anteroseptal MPI plus CAC and MPI alone (75% vs 78%; p= 0.5). PPV of MPI
perfusion defects, that were suspicious for IHD, followed by plus CAC is 86% but only 76% in MPI alone (p<0.001). NPV
coronary angiography, that showed intact coronary arteries showed no significant difference (75% vs 73%; p = 1.0). Both
in all cases. Conclusion: Myocardial perfusion impairments in SSS and CAC were independent factors predicting obstructive
IPAH include increased and inhomogeneous MIBI accumulation CAD. Conclusion: CAC provides additional diagnostic values by
in dilated RV, impaired IVS perfusion presumably due to its improving the specificity of Tl-201 CZT SPECT MPI. References:
compression by dilated RV, and perfusion defects spreading 1. Gimelli A, Liga R, Duce V, Kusch A, Clemente A, Marzullo
on stress images, in some cases involving not only IVS, but also P. Accuracy of myocardial perfusion imaging in detecting
adjacent LV segments. Those ischemic patterns are not due to multivessel coronary artery disease: A cardiac CZT study. J
direct damage of epicardial arteries, but due to combination Nucl Cardiol. 2017;24:687-695.2. Patchett ND, Pawar S, Miller EJ.
of perfusion/demand disbalance in hypertrophied RV and Visual identification of coronary calcifications on attenuation
microcirculatory impairments in compressed IVS, that get worse correction CT improves diagnostic accuracy of SPECT/CT
with myocardial pressure overload increase during physical myocardial perfusion imaging. J Nucl Cardiol. 2017;24:711-
S467 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

720.3. Mouden M, Ottervanger JP, Timmer JR, et al. The influence stenosis may be responsible for acute coronary syndromes.
of coronary calcium score on the interpretation of myocardial The aim of the study was to evaluate myocardial perfusion
perfusion imaging. J Nucl Cardiol. 2014;21:368-374. scintigraphy with cardiac dedicated CZT (cadmium-zinc-
telluride) gamma camera in patients with intermediately
stenosed LAD and estimated FFR. Materials and Methods:
EP-0182 Twenty two patients (median age of 69 years) with intermediate
Effect of Brown Adipose Tissue Activation on Myocardial (40-70%) stenosis in LAD on coronary angiography and normal
[18F]FDG Uptake left ventricular ejection fraction had estimated FFR under central
S. Alenezi1, S. Dannoon1, N. Alnafisi1, S. Asa’ad2, M. Osman3, A. vein adenosine infusion at 140µg/kg/min. Myocardial perfusion
Elgazzar1; imaging (MPI) with cardiac dedicated CZT gamma camera was
1
Kuwait University, Kuwait, KUWAIT, 2Jaber Al-Ahmad Center for performed no later than 2 months post coronary angiography.
Nuclear Medicine and Molecular Imaging, Kuwait, KUWAIT, 3St. Exercise treadmill stress test was performed in 15 out of 22
Louis University, St. Louis, MO, UNITED STATES OF AMERICA. patients, the remaining 7 patients had pharmacological stress
test with regadenoson injection. The rest MPI was performed
when stress supine/prone images were classified as abnormal.
Aim/Introduction: The aim of this study is to investigate the The perfusion images were obtained approximately one hour
relationship between brown adipose fat (BAT) activation and post injection of 99mTc-sestamibi with activity of 296-592 MBq
myocardial [18F]FDG uptake in terms of intensity and patterns. and were evaluated by two experienced nuclear medicine
Materials and Methods: The patients were divided into two physicians. Results: In most of the stenosed LAD (16/22) FFR
groups; BAT and control group. The BAT group consists of 34 values were at or above 0.8 (normal). In remaining 6 patients
cases that showed BAT uptake. The control group, with no FFR values ranged between 0.74 and 0.79 (range of 0.75-0.79
BAT uptake, included 68 patients that were matched for BMI, is considered as grey zone). MPI did not reveal significant
gender and season. The scans were retrospectively reviewed perfusion abnormalities in the vast majority of patients (20/22).
by two nuclear medicine physicians who visually evaluated Only in two patients reversible perfusion abnormalities involved
the intensity of myocardial [18F]FDG uptake. The myocardial more than 10% of left ventricular myocardium (both had
[18F]FDG uptake was visually classified into three patterns; pharmacological stress test). In these two patients FFR values
diffuse, heterogeneous and focal. The regions of activated BAT were at 0.75 and 0.8. One patient had subsequent percutaneous
distribution were noted. Results: The mean myocardial [18F] coronary intervention (PCI) with stent implementation into LAD
FDG uptake was 2.50 ± 0.75 for the BAT group and 2.13 ± 0.88 stenosis and had no acute coronary syndrome or further PCI in
for the control group with a statistically significant difference course of 2-year follow-up observation. The second patient was
(P = 0.031). The myocardial [18F]FDG uptake pattern was similar excluded from further observation due to the lack of contact.
in the BAT and control groups with the diffuse pattern being Conclusion: The study showed good correlation between FFR
the most common followed by the heterogeneous and less and MPI results in the patients with intermediately stenosed
commonly focal. In the BAT group, the anatomical distribution LAD. Further studies with greater number of patients are
of BAT was mainly in supraclavicular, paravertebral and axillary necessary for appropriate statistical analysis to obtain reliable
and to a lesser extent in cervical regions. Conclusion: BAT group outcomes. References: None.
had significantly higher intensity of [18F]FDG myocardial uptake
compared to control group. Presence of activated BAT did not
affect the pattern of myocardial uptake. Knowledge of these EP-0184
findings may help in understanding the variability of myocardial Evaluation of myocardial perfusion in patients with
[18F]FDG uptake and consequently in avoiding misinterpretation asymptomatic Beta-thalassemia major using myocardial
of cardiac findings in PET/CT studies. References: None. perfusion SPECT and its possible association with severity
of hematopoiesis
M. Assadi, P. Rahimizadeh, A. Omrani, E. Jafari;
EP-0183 Bushehr University of Medical Sciences (BUMS),
The evaluation of myocardial perfusion with CZT gamma Bushehr, IRAN, ISLAMIC REPUBLIC OF.
camera in patients with intermediately stenosed left
anterior descending coronary artery and estimated
fractional flow reserve Aim/Introduction: Beta-thalassemia, a kind of hereditary blood
S. Piszczek, K. Tkaczewski, A. Mazurek, S. Osiecki, M. Dziuk; disorders, is a chronic hemolytic anemia caused by impaired
Military Institute of Medicine, Warsaw, POLAND. synthesis of the beta chain of hemoglobin. For survival, regular
blood transfusion and chelation treatment are so important in
these patients but these transfusions lead to siderosis in the
Aim/Introduction: Fractional flow reserve (FFR) has become myocardium which is the main cause morbidity and mortality
routinely performed in intermediate stenosis of coronary in TM patients. Since heart failure can be detected with cardiac
arteries to assess the hemodynamic significance. Left anterior gated SPECT and also it can be used for evaluation of extent
descending artery (LAD) is one of the 3 main coronaries, LAD and intense of hematopoiesis in bone, we decided to evaluate
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S468

cardiac dysfunction in TM patients with 99mTC-MIBI cardiac has been found in 4 patients (1 normal, 1 ischemia, 1 DCM,
gated SPECT and hematopoiesis with whole body MIBI scan and 1 MI) with MPS and 5 patients with Echo (superior to 88 in
and compare cardiac gated SPECT with echocardiography and women and 111 in men). The patient with discordance between
blood tests. Materials and Methods: Patients with TM who Echo and MPS had a concentric hypertrophy (normal MPS).
were referred for blood transfusion and checkup periodically, Conclusion: LVMI calculated by MPS correlated significantly
were included in this cross-sectional study. A questionnaire with Echo, but with smaller values. Similar results has been
containing demographic data was provided from patients. then, found in previous studies (2,3). This had not a significant impact
myocardial perfusion scan, echocardiography and blood tests in our group on the detection of increased LVMI. References: 1.
including LDL, HDL, Chol, Tg, ALT, AST, Hb, ferritin were performed Prognostic Significance of Increased Left Ventricular Mass Index
for each patient. Results: 24 patients included 14 men (58.3%) to Mortality and Sudden Death in Patients with Stable Coronary
and 10 women (41.7%) aged from 15-36 years and average Heart Disease (From the Heart & Soul Study) Mintu P. Turakhia,
of 24.3±6.5 years old were enrolled in this study. Myocardial MD.2. Left ventricular mass index measured by quantitative
perfusion scan (MPS) was normal in all patients. Mean of EF gated myocardial SPECT with 99mTc-tetrofosmin: a comparison
measured for patients was 58.88±13.45. Whole body MIBI was with echocardiography. Kaoru MARUYAM.3. Left ventricular
obtained mild for 19 patients (79.2%) and severe for 5 patients mass measured by myocardial perfusion gated SPECT. Relation
(20.8%). There was no significant relationship between scan to three-dimensional echocardiography. Akinboboye O.
EF with whole body mibi (p=0.825) and echocardiography EF
(p=0.657). The results showed a significant relationship between
the level of Hb with amount of blood transfusion (p=0.023) and EP-0186
the level of ferritin with amount of blood transfusion (p=0.002). Lower Event Rate In Obese Patients With Transient
Conclusion: Myocardial perfusion imaging was within normal Ischemic Dilatation Oof LV Cavity on Gmpi: Is Obesity
limits in all asymptomatic patients but diastolic dysfunction was Friend or Foe
present in all cases. References: None. N. Fatima1, M. u. Zaman1, A. Zaman2, U. Zaman2, S. Zaman3;
1
Department of Radiology, Aga Khan University Hospital
(AKUH), Karachi, PAKISTAN, 2Civil Hospital, Karachi,
EP-0185 PAKISTAN, 3Dow Medical College, Dow University of
Left ventricular mass index measured by myocardial Health Sciences (DUHS), Karachi, PAKISTAN.
perfusion scan: Correlation with echocardiography
M. Abdi1, Q. Naili1, D. Djermane2, M. Habbache1, B. Said1;
1
Centre d’Imagerie Scintigraphique, Blida, ALGERIA, Aim/Introduction: Background: Obesity is considered as a
2
CHU Mustapha Bacha, Algiers, ALGERIA. major modifiable risk factor for coronary artery disease (CAD).
But once CAD has been established, the correlation of obesity
with all-cause mortality, cardiovascular mortality, infarction, and
Aim/Introduction: Left ventricular mass index (LVMI) has a revascularization is unclear. Transient ischemic dilatation (TID) of
prognostic value of mortality and sudden death in patients left ventricular cavity (LV) in GMPI is a known predictor of severe
with stable coronary heart disease, even when left ventricular CAD and worse prognosis. In this study we evaluated the impact
ejection fraction (LVEF) is normal (1). The aim of this work is to of obesity (BMI ≥30) for fatal and non-fatal myocardial infarction
evaluate the correlation between LVMI value calculated with (FMI and NFMI respectively) in patients with TID. Materials
a myocardial perfusion scan (MPS), and 2D echocardiography and Methods: Material and Methods: This is a continuation of
(Echo). Materials and Methods: Randomly selected, 50 patients a previously published study which revealed TID as a reliable
that were oriented to our department for MPS, from July 2018 predictor of multivessel CAD and NFMIs than FMIs. Patients with
to January 2019, had an M-mode Echo the same week. There TID on GMPIs performed during 2008-2012 were categorized on
was 26 men and 24 women, with mean age of 63.96 ± 11.05 the basis of BMI <30 (non-obese) and ≥ 30 (obese) and were
(±SD). MPS protocol was a stress-rest or stress only Sestamibi followed till December 2017. During follow-up period data was
Gated SPECT. 32 patients had a normal scan, 8 myocardial collected about NFMIs, revascularization (PCI and CABG) and
infarction (MI), 5 ischemia, and 5 dilated cardiomyopathy (DCM). FMIs. Patients with significant change in BMI during follow up
Left ventricular mass (LVM) was evaluated automatically, throw (from non-obese to obese and vice versa) were excluded from
Corridor 4DM, on MPS. LVM was calculated in Echo according the cohort. Results: Results: During study period (2008-2017)
to Devereux’s method, by an experienced cardiologist. Second 386 patients were found to have TID but 69 patients lost to
lecture was done for all patients. LVMI was calculated by dividing follow-up. 36 patients who had significant change in BMI during
LVM on body surface area, and expressed with g/m2. Results: study period were excluded. 281 patients constituted study
Mean value of LVMI calculated by MPS was lower than Echo cohort and 230 had BMI <30 (Non-obese; Mean BMI: 24.274
(71.1 ± 15.94 and 78.88 ± 16.97, respectively). Same observation ± 2.982) while 51 had BMI ≥30 (Obese; Mean BMI: 37.433 ±
has been found on a previous study (2). MPS LVMI was plotted 4.202). Mean age and male domination was not significant in
against Echo. Significant correlated has been found (y = 0.645x two groups. Incidence of hypertension and dyslipidemia was
+ 20.15, r = 0.68, p<00001). Correlation coefficient in our study significant higher in obese group. No significant difference was
was similar to an other study with 3D Echo (3). Increased LVMI found for diabetes, family history and smoking in two groups.
S469 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

GMPI was positive for perfusion abnormalities in 94% and 92% Interpretation of coronary collateral by myocardial
without significantly different fixed to reversible defect ratio perfusion gated spect
between non-obese and obese groups. But obese group had S. Ozdemir1, A. Barutcu2, Y. Z. Tan1, E. Aksit2, A. Duygu2, F. K. Ozturk1;
higher mean left ventricular ejection fraction than non-obese 1
Onsekiz Mart Universty Faculty of Medicine Department of
group (%LVEF: 52 vs. 45%; significant p value). During follow- Nuclear Medicine, Canakkale, TURKEY, 2Onsekiz Mart University
up period, NFMIs and FMIs were higher in non-obese with Faculty of Medicine Department of Cardiology, Canakkale, TURKEY.
significant p-value for NFMIs only. Conclusion: Conclusion:
Obesity (BMI ≥30) in patients with TID on GMPI is associated
with lower FMI and NFMIs. Our findings will contribute to body Aim/Introduction: Coronary collateral circulation(CCC) is a
of data favoring obesity paradox and reverse epidemiology natural anostomosis in response to ischemia caused by severe
in patients with CAD. In view of growing controversies about or total occlusion in coronary circulation. Well developed
impact of obesity upon outcomes in patients with CAD, larger coronary collaterals are thought to reduce the severity of
prospective trials are warranted. References: None. ischemia and infarct. Myocardial perfusion scintigraphy(MPS)
is an accurate technique for the simultaneous evaluation of
left ventricular wall perfusion, motion and thickening. For this
EP-0187 reason the aim of this study was to retrospectively evaluate
Prognostic Value of Stress Gated MPI SPECT and Coronary the effect of collaterals on myocardial perfusion, wall motion
Artery Calcium Score in Patients with Diabetes Mellitus and thickening. Materials and Methods: Study patiens were
M. Havel1, M. Kaminek1,2, P. Koranda1, L. Quinn1, I. Metelkova1, M. retrospectively selected among patiens who underwent
Budikova1, L. Henzlova1, V. Kincl2; myocarial perfusion gated SPECT imaging and coronary
1
Department of Nuclear Medicine, Faculty of Medicine angiography within 3 months, between 2015-2018. Only the
and Dentistry, Palacky University Olomouc and patiens witj stenosis ≥80% in at least one of the major coronary
University Hospital Olomouc, Olomouc, CZECH arteries were included in this study. In total 96, patiens ( 69 men
REPUBLIC, 2International Clinical Research Center, Center and 27 women, with a mean age of 63.12 ± 10.77 years) were
of Molecular Imaging, Brno, CZECH REPUBLIC. included in the study. The patients were divided into two groups
in accordance with coronary angiography results: Group1: who
had not-well-developed collateral arteries (Rentrop grade 0-1)
Aim/Introduction: Patients with diabetes mellitus (DM) are in (n = 58). Group2: who had well-developed collateral arteries
an increased risk of cardiovascular disease and cardiac death. (Rentrop grade 2-3) (n = 38). Results: There were no statistically
Assessment of prognosis in such subjects could be essential significant difference in summed stress score(p=0,531), summed
for adequate therapy to minimise eventual unfavourable difference score (p=0,634), wall motion score(p=0,957) and wall
outcome. The aim of this study was to assess impact of thickening score (p=0,717) parameters between the patients
Myocardial perfusion imaging (MPI) SPECT and its combination with and without CCC groups. Conclusion: Our study showed
with coronary artery calcium score (CACS) for such purposes. that CCC with different Rentrop grades, as shown by CAG, had
Materials and Methods: We analysed retrospectively results no significant correlation with myocardial perfusion defined by
of stress gated MPI SPECT and CACS evaluation in 334 patients MPS. References: None.
with DM (average age 65 ± 10 years, 211 males). Adverse cardiac
events as cardiac death, myocardial infarction (MI) or necessity
of revascularization were recorded in this population and EP-0189
prognostic value of examination were statistically evaluated. Interreader Reproducibility Between A Conventional
Results: We recorded 77 CE during the median follow-up period And A CZT/SPECT Camera In The Myocardial Perfusion
of 17 months. CE were more often in patients with detected Scintigraphy (MPS): A Multicentric Study
ischemia on gated SPECT MPI (75.3% vs. 15.2%, P < 0.0001), the N. Mansour1, E. Reyes2, G. Angelidis3, P. Georgoulias 3, C.
CACS was significantly higher in such patient, too (median 225 Anagnostopoulos 4, P. Bravo5, I. Bruno6, A. Guarneri 6, A.
vs. 977, P<0.0001). One-year CE rate was 42.2% for patients with Flotats 7, F. Fuentes-Ocampo7, R. Di Dato8, F. Keng9, L. Kessler10,
ischemia vs. 3.3% without ischemia detected, 24.7% for patients M. Papathanasiou 11, R. Sciagrà 8, P. Soman 12, S. Nekolla1, C.
with CACS >1000 vs 6.0% for CACS ≤ 1000. One-year CE rate in Rischpler10;
patients with negative MPI SPECT and CACS >1000 was 7.9% 1
Nuklearmedizinische Klinik des Klinikums rechts der Isar,
vs. 1.9% in those with CACS ≤1000. Conclusion: Gated MPI Munich, GERMANY, 2Royal Brompton Hospital, London,
SPECT and CACS are both non-invasive methods suitable for UNITED KINGDOM, 3Nuclear Medicine Department, University
CE predictions in population of patients with DM. What is more of Thessaly, Larissa, GREECE, 4BRFAA - Biomedical Research
important, in patients with negative gated MPI SPECT, CACS Foundation Academy Of Athens, Athens, GREECE, 5University
score helped additionally to identify subjects with unfavourable of Pennsylvania, Philadelphia, PA, UNITED STATES OF AMERICA,
outcome. References: None. 6
Fondazione Policlinico Universitario - IRCSS- “A. Gemelli”, Rome,
ITALY, 7Hospital de la Santa Creu i Sant Pau, Barcelona, SPAIN,
8
Nuclear Medicine Unit, Department of Experimental and Clinical
EP-0188 Biomedical Sciences ‘‘Mario Serio’’, Florence, ITALY, 9National
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S470

Heart Centre, Singapore, SINGAPORE, 10University Hospital Essen, EP-0190


Department of Nuclear Medicine, Essen, GERMANY, 11Department IInvestigation of clinical factors affecting the myocardial
of Cardiology, West German Heart and Vascular Center, blood flow and flow reserve using Tl dynamic SPECT with
University Hospital, Essen, GERMANY, 12University of Pittsburgh a CZT gamma-camerain limited patients with normal
Medical Center, Pittsburgh, PA, UNITED STATES OF AMERICA. summed stress score
S. Shiraishi, F. Sakamoto, N. Tsuda, K. Ogasawara, M. Nakagawa, Y.
Yamashita, S. Tomiguchi;
Aim/Introduction: CZT camera systems are currently growing Kumamoto University, Kumamoto-city, JAPAN.
in popularity as a non-invasive cardiac imaging tool. They
were reported to have higher sensitivity, neverthelessthere
is still insufficient data to compare this technology with Aim/Introduction: Relative myocardial perfusion imaging can
conventional SPECT cameras, especially in terms of interreader- underestimate or misdiagnose “balanced” ischemia in patients
and intrapatient- reproducibility. Materials and Methods: with significant coronary artery disease (CAD) or microcirculatory
83 patients with an indication for MPS, each of whom were disorders due to other clinical risk factors. Recently, some studies
examined using a CZT camera (D-SPECT, Spectrum Dynamics) have demonstrated improved diagnostic accuracy for detecting
as well as a conventional SPECT camera (Siemens E.CAM or CAD by using absolute quantification of the myocardial blood
Symbia T, Siemens Medical Solutions) were included in this flow (MBF) or the myocardial perfusion reserve (MPR). In this
study. The patients were recruited in the period between study, we evaluated clinical factors affecting myocardial blood
March and September 2013 during the clinical routine in the flow and flow reserve in specifically limited to patients with
University Hospital Klinikum rechts der Isar in Munich. For 10 normal myocardial perfusion SPECT (summed stress score<3).
patients, results of a cardiac catheterization were also available. Materials and Methods: We selected 125 consecutive
Anonymous standard stress/rest reports including static images patients that underwent coronary angiography (CAG) and both
and images of the short and horizontal/vertical long axes and adenosine stress and rest with 201Tl dynamic SPECT to calculate
polar maps were then distributed to 15 international readers MBF using a CZT semiconductor gamma-camera. The MPR in the
varying in expertise: (Group A), Five readers with experience in entire left ventricular myocardium was calculated by dividing
both D-SPECT and conventional SPECT; (Group B), five readers stress-MBF by rest-MBF from the dynamic SPECT. We analyzed
with extensive experience in conventional SPECT ; and (Group the correlation between various clinical risk factors including
C), five readers without extensive interpretation experience of the number of CAD and quantitative values (rest-/stress- MBF
MPS. The reports were then evaluated with respect to image and MPR). Results: In the multivariate regression analysis, the
quality, artefacts, diagnosis and diagnostic certainty. The readers rest-MBF values showed statistically significant correlation with
had no access to patient’s clinical data. Results: Both group A male gender (r=-0.341, p=0.01), estimated glomerular filtration
(ps<0.05) and group C (ps<0.05) reported the CZT systems to rate (eGFR) (r=-0.268, p=0.001), and left ventricular ejection
deliver a significantly better image quality than conventional fraction (LVEF) (r=0.290, p=0.019), the stress-MBF values with
SPECT. Consistent with these observations, conventional-SPECT HDL-cholesterol (r=0.326, p=0.001), LVEF (r=0.290, p=0.003),
images showed more attenuation artifacts (ps<0.05). In Group A, age (r=-0.191, p=0.002), male gender (r=-0.285, p=0.011), and
the images from 33/83 patients were non-evaluable due to poor the number of CAD (r=-0.279, p=0.034), and the MPR correlated
image quality. In contrast to CZT-SPECT with only 7/83 patient with the number of CAD (r=-0.543, p=0.001), eGFR (r=0.279,
images were non-evaluable (ps<0.05). Notably, no significant p=0.002), and age (r=-0.347, p=0.004), respectively. Conclusion:
differences were evident between CZT-SPECT and conventional- This study suggests that microcirculatory disorders due to age,
SPECT in the remaining artefacts: signal-to-noise-ratio, liver- and gender, HDL-CHO, GFR in addition to CAD are also important
bowel-activity, and low myocardial counts. As to the interreader factors that affect the myocardial blood flow and flow reserve.
variability, the diagnosis results of groups A and B (readers References: None.
with experience) differed significantly from that of group C
(inexperienced) (ps<0.05).However, the diagnosis results within
the expert groups showed no significant differences between EP-0191
CZT-SPECT and conventional-SPECT. Conclusion: Collectively, SPECT-CT 16 Slices Myocardial Perfusion Imaging vs
this study demonstrates that CZT camera systems show higher Prone Acquisition In Minimizing Artifactual Defects
image quality with evidently less attenuation artifacts. The Interpretation
assessment and detection of ischemia and/or scar within the E. Papadaki, N. Kapsoritakis, O. Bourogianni, M. Stathaki, A.
groups were not affected by the imaging systemruling out, thus, Tsaroucha, M. Alefantinou, S. Koukouraki;
the necessity of a special training for the evaluation of images Heraklion University Hospital, Iraklion - Crete, GREECE.
when introducing a CZT camera. References: None.

Aim/Introduction: Myocardial perfusion imaging (MPI) for


coronary artery disease assessment often has false positive
results due to attenuation correction mainly in the inferior and
anterior myocardial wall. The aim of the study is to evaluate
S471 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

myocardial perfusion attenuation defects using SPECT/CT >85% Results: Overall, the TST was positive on 38patients and
16 slices vs prone SPECT imaging for excluding false positive negative on 14 (sensitivity= 73%). According to the PTP, the
results in order to use it as a gate keeper for patients (pts) results were:Group PTP 15-65% :Over 14patients, 9 were positive
who will benefit from coronary angiography. Materials and TSTand 5 negative (Sensitivity =64% )Over the 5 negative TST,
Methods: From 12/2018-3/2019, 188 pts underwent a treadmill 4had single vessel disease involvement on CA, and 2 have a
99mTc-tetrofosmin MPI. 84/188 pts (group A) were subjected to large reversible ischemia ≥ than 5 segments on MPS in LAD
scintigrams using a low-dose SPECT-CT γ-camera and 104 pts territory.Group PTP 66-85% : Among 28 patients , 21 were
(group B) underwent SPECT in supine and prone position in positive TST and 7negative (75% of sensitivity)On the negative
order to clarify the inferior/anterior wall perfusion defects. The TST group , all patients have multi-vessel involving (≥2 ) on CA
choice of each modality was random. The final diagnosis was and 2 have a large reversible ischemia (7/17 segments) on MPS
based on coronary angiography. Results: Group A: In 68/84 pts in LAD territory.PTP >85% :Of the 10patients, 8 were positive TST
(80.95%) SPECT/ CT managed to correct the perfusion defect and 2 négative TST (Sensitivity 80%)Among the patients with
qualitatively and quantitatively with an increase in Summed negative TST, all have ≥4 segments reversible ischemia on MPS
Stress Score (SSS:10-32). There was no need for an additional and multi-vessels disease (≥2 ) involving in CA Conclusion: The
rest MPI study. 16/84 pts (19.04%) underwent a rest SPECT-CT. overall sensitivity of the TST in patients with confirmed SCAD
4/16 had an unknown infarction of the inferior wall, 6/16 had is 71% (67% in the literature (ACC/AHA Guidelines 2002)). This
ischemia of the inferior wall and 6/16 showed attenuation and sensitivity increases with the initial clinical risk of coronary
scar. Group B: In 77/104 pts (73.1%) prone SPECT MPI managed artery disease, it is therefore higher in case of high risk, or high
to correct the perfusion defect (increase SSS 8-25). 27/104 pts intermediate. Some of the patients with negative TST , have
(26.9%), underwent rest MPI study. 5/27 pts had an unknown a large extent of ischemia, with sometimes, a multi-vessel
infarction of the inferior wall, 8/27 pts had ischemia of the inferior involving, especially in patients classified at high clinical risk of
wall and 7/27 pts showed attenuation and scar. In the remaining coronary disease. Therefore, a negative TST in high-risk patients
7/27 pts prone interpretation was abnormal in spite of normal does not rule out sometimes extensive or multi-vessel coronary
coronary angiography. Conclusion: The addition of SPECT/CT disease References: None.
to stress MPI decreases false positive rates. Moreover it has a key
benefit in reducing the number of rest studies and minimizing
radiation exposure, investigation time, costs and unnecessary EP-0193
referrals to coronary angiograms. References: None. Could end-diastolic images in myocardial perfusion
imaging performed on CZT camera determinate
significant changes in ischemia assessment in Patients
EP-0192 with diastolic dysfunction compared to Patients with
Sensitivity of the treadmill stress test according to the normal diastolic function?
risk stratification by clinical evaluation of the stable M. Bonacina1, D. Albano1, M. Bertoli1, F. Dondi1, R. Durmo1, A.
corany artery disease, confirmed whether by myocardial Mazzoletti1, E. Cerudelli1, P. Bellini1, M. Gazzilli1, F. Bertagna2, R.
perfusion scan and coronary angiography Giubbini2;
M. Habbeche1, Q. Naili1, M. Abdi1, B. Said1, D. Djermane2; 1
ASST Spedali Civili, Brescia, ITALY, 2Università
1
Centre d’imagerie scintigraphique, Blida, ALGERIA, 2Service degli Studi di Brescia, Brescia, ITALY.
de cardiologie CHU Mustapha Bacha, Alger, ALGERIA.

Aim/Introduction: to evaluate in myocardial perfusion imaging


Aim/Introduction: The treadmill stress test (TST) is know as (MPI) performed on a CZT camera if end-diastolic images can
one of the first line diagnostic test to detect the stable coronary determinate significant changes in ischemia assessment in
artery disease (SCAD), due to its simplicity and lower cost.The Patients with diastolic dysfunction compared to Patients with
aim of this study is to evaluate the sensitivity of this test related normal diastolic function. Materials and Methods: from
to the risk stratification by clinical evaluation of the SCAD, October 2018 to March 2019 we included 34 patients without a
confirmed whether by myocardial perfusion scan (MPS) and previous diagnosis of CAD and without left bundle branch block,
coronary angiography (CA). Materials and Methods: From pacemaker or atrial fibrillation. Diastolic function was defined
2016 to 2018, 52 patients (41males and 11femele, sex ratio using echocardiogram as reference. Seventeen Patients (12 M,
3,7) has been enrolled for this study.The inclusion criteria were: 5 F, mean age 68,5) had diastolic dysfunction (Group 1) and 17
Only the TST performed according the Bruce protocol has been (8 M, 7 F, mean age 75) had normal diastolic function. All images
validated . All the patients have a reversible ischemia more were acquired on a CZT camera, elaborated for both Groups
than 10% (2segments) detected on MPS. All the patients have with end-diastolic (Method 1) and routinely all-phases software
a positive coronary angiography (stenosis ≥to 50% ) performed (Method 2), and evaluated by 2 blind expert readers, who had
less than 1month. Are excluded from the study patients with to rate images with an ischemia scoring system (0 no ischemia,
dilated cardiomyopathy. The patients were classified regarding 1 mild, 2 moderate, 3 severe). For each reader, we registered if
the risk stratification by clinical evaluation (2013 ESC guidelines) ischemia scoring increased, reduced or unchanged in both
on 3 groups :Pre test probablily (PTP) 16-65% , 66-85%, and Groups with Method 1 compared to Method 2. A Yates test was
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S472

performed to compare the proportions of scoring changes in relatively limited diagnostic power, especially in rule-out the
both Groups for both readers. Results: for reader 1 in Group 1, functional CAD. The corresponding PTP values for PET were ≥
Method 1 increased ischemia score in 52,94% (9/17 Patients), 51% (44-58) and ≤ 42% (32-54), respectively. Conclusion: CZT-
was concordant in 29,41% (5/17 Patients) and reduced the SPECT demonstrated a similar sensitivity as PET but significantly
ischemia in 17,65% (3/17); while in Group 2, Method 1 increased higher sensitivity than A-SPECT in predicting FFR determined
ischemia score in 41,18% (7/17 Patients), was irrelevant in significant CAD; all CZT-SPECT, PET and A-SPECT had similar
47,06% (8/17 Patients) and reduced ischemia in 11,76% (2/17). specificities on per-vessel analysis. Besides, they have different
For reader 2 in Group 1, Method 1 increased ischemia score in optimal performance ranges for ruling out and in functionally
47,06% (8/17 Patients), was stable in 29,41% (5/17 Patients) and significant CAD. References: None.
reduced ischemia in 23,53% (4/17); while in Group 2, Method
1 increased ischemia in 35,29% (6/17 Patients), was stable in
52,94% (9/17 Patients) and reduced ischemia in 11,76% (2/17). EP-0195
For both reader there was a significantly higher rate of ischemia Clinical impact of the use of ultralight exercise with
score increasing in Group 1 compared to Group 2 with Method adenosine stress myocardial perfusion imaging
1 (p 0,002 for reader 1 and p<0,001 for reader 2 respectively); E. Tateishi, K. Kiso, Y. Kawahara, S. Higuchi, T. Nishii, Y. Ota, A. Kono,
there was no significant difference between the two readers T. Fukuda;
scoring variation with Method 1 compared to Method 2 both National Cerebral and Cardiovasclar Center, Suita, Osaka, JAPAN.
in Group 1 (p 0,33) and in Group 2 (p 0,44). Conclusion: end-
diastolic images caused major changes in ischemia assessment
in myocardial perfusion imaging on CZT camera in Patients with Aim/Introduction: Adenosine is commonly used in
diastolic dysfunction, further studies are needed to validate the pharmacological stress myocardial perfusion SPECT imaging
clinical impact of these results. References: None. (MPI); on the other hand, the side effects of adenosine occur
with a high frequency. Recently, the combination of low-level
exercise during adenosine infusion has been increasingly
EP-0194 performed for the reduction of the adenosine-related side
Comparison of CZT-SPECT with A-SPECT and PETfor effects. However, the utility of very easy exercise with almost no
DiagnosingHemodynamically SignificantCoronaryArtery intensity; ultralight exercise (UL-Ex), during adenosine infusion
Disease: A Bivariate Meta-analysis has not been well studied. We investigated the clinical impact
N. Dai, J. Ge; of two types of UL-Ex in combination with adenosine stress
Zhongshan Hospital of Fudan University, Shanghai, CHINA. MPI by evaluating the incidence of the side effects. Materials
and Methods: Seven hundred and twenty-seven patients
(68.7% male, mean age 76.3±9.0, range 27-96 years) underwent
Aim/Introduction: This meta-analysis determined the adenosine stress MPI with UL-Ex. Either supine leg ergometer
diagnostic utility of single-photon emission computed with zero intensity (SE group, n=667) or handgrip exercise
tomography (SPECT) using cadmium-zinc-telluride (CZT) with 0.7kg strength (HG group, n=60) was performed during
cameras (CZT-SPECT), positron emission tomography (PET) adenosine infusion. Adenosine was given as a continuous
and conventional SPECT with Anger cameras (A-SPECT) versus infusion of 120 micrograms/kg/min for 6 minutes. One hundred
FFR as a reference standard for detection of hemodynamically sixty patients undergoing adenosine stress MPI without any
significant coronary artery disease (CAD) Materials and exercise were evaluated as controls. Results: Of the 727
Methods: PubMed and EMBASE were searched for clinical patients who underwent adenosine stress testing with UL-Ex,
studies comparing CZT-SPECT or A-SPECT or PET and FFR. 415 patients experienced the side effects of adenosine (57.1%),
Bayesian random effects analysis was used to compute pooled which was significantly lower than the incidence of the side
sensitivity, specificity, positive and negative likelihood ratios effects in the control group (81.3%). The majority of the side
(LRs), and the summary receiver-operating characteristic curve effects were minor, such as chest discomfort (41.4%), flushing
of the index tests. The pre-test probability (PTP) ranges for each (30.9%), and headache (13.4%). Intermittent atrioventricular
technique to rule-in or rule-out significant CAD were determined block was observed in 9 cases. The variability of systolic blood
according to LRs. Results: On vessel-based analysis, CZT-SPECT pressure was significantly smaller in patients with UL-Ex than in
had a similar sensitivity as PET (0.76 vs. 0.79, P=0.61) but higher controls (-3.6±1.6 mmHg vs. -9.8±1.9 mmHg, p=0.014). No major
sensitivity than A-SPECT (0.76 vs. 0.59, P=0.02); all CZT-SPECT, side effects occurred requiring the interruption of adenosine
PET and A-SPECT demonstrated similar specificities (0.87 vs. 0.86 infusion in either the SE or HG group. Comparing the SE and HG
vs. 0.87, P>0.05), CZT-SPECT and PET showed trend of higher groups, there was no significant difference in the incidence of
area under SROC (AUROC) than A-SPECT (0.86 and 0.89 vs. 0.83, the side effects (57.6% vs. 51.7%, p=ns). Conclusion: Regardless
P>0.05), but none of these achieved statistical significance. of the type of exercise, the use of UL-Ex during adenosine stress
A-SPECT can rule-in and rule-out functionally significant CAD testing is beneficial for the reduction of the adenosine-related
only when PTP is≥56% (48-63) and ≤ 27% (22-33), respectively. side effects including drops in blood pressure. As a result, the
CZT-SPECT is able to rule-in functional CAD at a PTP ≥ 50% (40- addition of UL-Ex during pharmacological stress enables it
60) and rule-out at a PTP ≤ 39% (32-44), indicating A-SPECT had to be performed more safely in patients with hypotension or
S473 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

cerebrovascular diseases. Moreover, handgrip exercise is easy, Aim/Introduction: Myocardial perfusion SPECT-CT plays
and anyone can perform it in any position. It may be possible to a crucial role in the diagnosis of coronary artery disease,
apply UL-Ex in vasodilator stress myocardial perfusion imaging providing a noninvasive tool to monitor ischemia and infarction.
with not only SPECT but also other modalities. References: The findings can have a profound impact on diagnosis and
None. management in these patients. However, incidental noncardiac
findings on low dose CT can also affect management. The
intent of this study was to illustrate several subtle noncardiac
EP-0196 abnormalities within nuclear cardiac imaging that can have
Does prone myocardial perfusion imaging improve an impact on patient management and follow-up. Materials
inferior and anterior perfusion defects? and Methods: In this retrospective monocentric study,
Z. AL Bimani1,2, K. Whinfield1, R. Klein1, W. Zeng1; from December 2017 to April 2019, 200 patients referred for
1
University of Ottawa, Ottawa, ON, CANADA, 2Oman Medical myocardial perfusion were reviewed. Results: Our analysis
Speciality Board (OMSB), Muscat, Sultanate of Oman, OMAN. focused on 200 patients referred for myocardial perfusion. The
overall prevalence of incidental extracardiac abnormalities was
47% (94 patients). Two patients (1%) have been identified with
Aim/Introduction: Myocardial perfusion Imaging (MPI) malignant lesions that have been taken care, one patient with
traditionally images patients in supine position. The aim of this lung cancer and one patient with breast cancer. For 20 patients
study was to assess the extent of perfusion defects improved (10%), extracardiac abnormalities explained the symptoms that
by prone imaging and identify the subgroup of patients who motivated the realization of the myocardial TEMP. The most
might benefit the most from having prone images. Materials common abnormalities were micronodules and pulmonary
and Methods: Rest and stress supine and stress prone from nodules (70% of patients) who were most often classified as
639 consecutive patients (age: 64.7±11.1, F:M=269:370) with indeterminate and required follow-up, followed by hiatal hernia
suspected or known CAD were reviewed. Summed stress score (20% of patients), thyroid nodules tracer avid (8% of patients),
(SSS) of the supine and prone and rest (SRS) of the inferior wall renal cycts (4% of patients), breast lesion (1% of patients),
(3/17 segments) and the anterior wall (3/17 segments) was calcified axillary nodules (1% of patients), adrenal lesions (1%
obtained on 4DM SPECT (INVIA, Ann Harbor, MI). The difference of patients), and liver lesions (1% of patients). Conclusion: The
in SSS between the supine and prone images (DSSS) was lack of interpretation of extracardiac structures, on the scanner
evaluated for correlation with sex and BMI using Student’s t test performed for the attenuation correction, could cause delays
and Pearson’s coefficient. Results: The mean summed score of diagnosis and management of malignant lesions. On the other
the inferior wall was 1.72 ± 2.21, 1.64 ± 2.20 and 0.60 ± 1.59 for hand, numerous abnormalities detected, which finally are
rest, stress supine and stress prone, respectively. The mean DSSS benign, lead to the realization of additional investigations with
was 1.04 ± 1.67 (p<0.001), with a statistical difference between dosimetric consequences and significant economic outcomes.
male and female (1.23 ± 1.76 vs. 0.78 ± 1.49, p= 0.001). There were References: None.
similar findings in the infero-lateral wall. The mean summed
score of the anterior wall was 0.50 ± 1.33, 0.42 ± 1.24 and 0.30 EP-11
± 1.09 for rest, stress supine and stress prone, respectively.
The mean DSSS was 0.12 ± 0.86, with no statistical difference
Dosimetry: Dosimetry
between sexes ( p= 0.61). Of the 639 patients, 29 (5%) had larger,
317 had equal (50%), and 293 (45%) had smaller stress scores in October 12 - 16, 2019 e-Poster Area
the inferior wall on prone compared to supine. The median BMI
was 27.1. The mean DSSS in the inferior wall was similar between
BMI≥27.1 (0.94 ± 1.66) and BMI<27.1 (1.12 ± 1.65) with no
statistical significance (p=0.18). There was negligible correlation EP-0198
between DSSS and BMI ( r=-0.01, p=0.015). Conclusion: The Fast heterogeneous convolution algorithm used in
addition of prone acquisition improves soft tissue attenuation absorbed dose calculation for beta emitters
artifact in the inferior wall region, as demonstrated by decreased A. Vergara Gil1, E. Mora Ramirez1,2, J. Pouget3, P. Kotzki3,4, L.
perfusion defect score, in both male and female patients, but Santoro4, E. Deshayes4,3, M. Bardies1;
not in the anterior wall. BMI and sex do not predict changes in 1
CRCT, UMR 1037, INSERM, Université Toulouse III, Paul
inferior wall defect scores by prone imaging. References: None. Sabatier, Toulouse, FRANCE, 2Universidad de Costa Rica,
Escuela de Fisica, CICANUM, San Jose, COSTA RICA, 3Institut
de Recherche en Cancérologie de Montpellier, Montpellier,
EP-0197 FRANCE, 4Département de Médecine Nucléaire, Institut
Incidental Findings on Myocardial Perfusion SPECT/CT Régional du Cancer de Montpellier, Montpellier, FRANCE.
Images
I. El Bez, R. Tulbah, I. Munir, F. Alghamlas, M. Alharbi;
KFMC, nuclear medicine department, Riyadh, SAUDI ARABIA. Aim/Introduction: Absorbed dose calculations algorithms
may be designed depending on the relationship between
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S474

activity spatial sampling and radiation range. The aim of this (5), unifocal (18) and multifocal autonomy (15). The image matrix
work is to propose a fast-heterogeneous convolution algorithm and size of the scans were normalized and standardized. The
(FHCA) and compare dosimetric results with local energy intensity distribution of the tracers was calculated parametrically
deposition (LE), homogeneous convolution (FFT) and Monte and displayed as 3D images. The processed scans were pairwise
Carlo (GATE) modelling, i.e. the 3 most frequently proposed compared visually and computerized. Results: Pretherapeutic
approaches in a context of clinical dosimetry, for a medium Tc-99m versus iodine-131 intratherapeutic scan: Visually, in two
range beta emitter such as 177Lu. Materials and Methods: cases (4.2%) a comparable intensity distribution was shown,
FHCA consists in a matrix convolution using an homogeneous in 46 cases (95.8%) the intensity distribution was different. The
absorbed dose kernel (HDK). The HDK was calculated using computer analysis showed in 11 cases (22.9%) an equal intensity
the dose point kernel approach1 with GATE, up to 2cm from distribution, in 37 cases (77.1%), the intensity distribution was
central voxel and activating the ion source implementation. divergent. Pretherapeutic iodine-131 (radioiodine test scan)
This produced a 9x9x9 kernel matrix, small enough to be used versus iodine-131 intratherapeutic scan: In seven cases (14.6%)
in matrix convolution. While performing the first convolution, a similar intensity distribution was visually evident; in 41 cases
another kernel was considered to determine the influence of (85.4%) the intensity distribution was unequal. The calculation
patient density (from the CT image) in the source-target path. showed in 34 cases (70.8%) a consistent intensity distribution,
The influence of the media for the HDK was removed by density in 14 cases (29.2%), the intensity distribution was different.
multiplication. Absorbed dose rate results were compared in a Conclusion: The developed software allows an easy and reliable
context of clinical dosimetry of Lutathera2 for the four mentioned qualitative and quantitative comparison of the different scans.
algorithms, by considering only electronic emissions3. Results: As it was to be expected our results reveal a good visual and
For liver, spleen and L/R kidneys, relative differences to Gate in especially a better computational comparability of the two I-131
absorbed dose rate results varied from -6.6 to 3.1% for LE, -1.1 scans in comparison to the pretherapeutic Tc-99m scan and
to 9.1% for FFT and -1.4 to 4.5% for FHCA, among all organs, I-131 scan performed intratherapeutically. Tc-99m scintigraphy
for all time points. Calculation time for all time points were provides a helpful guide to assess the function of the thyroid in
negligible for LE and FFT, lower than 10 minutes for FHCA but order to make the preliminary diagnosis. We recommend the
required more than 6 hours for Gate (on the same computer). additional pretherapeutic I-131 scintigraphy in clinical routine
Conclusion: Preliminary results in terms of accuracy vs. speed that provides valuable additional information to verify and
are encouraging. Further validation in more heterogeneous adjust the diagnosis by using the new program, and thus to
media (lungs, bones) is ongoing. References: 1Franquiz et al. optimize the determination of the individual therapeutic dose
Med Phys 30, 1030 2003; 2Mora-Ramirez et al. Eur J Nucl Med leading to a better outcome of the treatments of the patients.
Mol Imaging 45(Suppl 1), S180 (2018); 3Eckerman and Endo. References: None.
Radionuclide Data and Decay Schemes, SNM 2008.

EP-0200
EP-0199 Estimation Of The Absorbed Dose In Patients Treated With
Analysis of nuclide distributions of pre-therapeutic thyroid Ra223
scintigraphies with I-131 and Tc-99m in comparison to M. Alonso Rodriguez, C. Andrés Rodríguez, J. Gómez Hidalgo, C.
intra-therapeutic I-131 scintigraphies in the context of Gamazo Laherrán, B. Pérez López, V. De la Llana Granja, M. A. Ruíz
radioiodine therapy in benign thyroid dysfunctions by Gómez, M. Agulla Otero, P. J. Turbay Eljach, N. Álvarez Mena, R.
means of parametric evaluation and 3D imaging Torres Cabrera, R. Ruano Pérez;
U. Lützen, S. Meyenburg, Y. Zhao, M. Marx, M. Jüptner, M. Zuhayra; Hospital Clínico Universitario de Valladolid, Valladolid, SPAIN.
UKSH, Kiel, GERMANY.

Aim/Introduction: Preliminary experience acquired in


Aim/Introduction: Prior to each radioiodine therapy (RIT), a estimating the absorbed dose in metastatic bone lesions of
thyroid scintigraphy with Tc-99m pertechnetate (Tc-99m) is made prostate cancer patients treated with Ra223 (Xofigo) in our
for the diagnosis of benign thyroid dysfunction. The radioiodine center is shown. Materials and Methods: We studied a total
study with iodine-131 serves for the individual determination of of 50 lesions of 15 patients treated with Ra223 (Xofigo, Bayer
the therapy activity. As is known, the two radiopharmaceuticals Pharmaceuticals Inc., Germany). The usual treatment procedure
differ in their pharmacokinetics and dynamics. The aim of is 6 intravenous administrations (with a separation between
this work was to compare the differences in the intensity them of at least four weeks) of Ra223 for 55KBq/kg. In average,
distribution of the tracers visually and by a new computer-aided the activity injected was 4.0MBq. The images are acquired
quantification of the pre- and intratherapeutic scintigraphies with an SPECT-CT system Siemens Symbia T2, which has been
by means of a subtraction analysis and a 3D representation. previously characterized in all its physical parameters. Prior to the
Materials and Methods: Pre- and intratherapeutic first Ra223 administration, a bone scintigraphy and a SPECT-CT
scintigraphies were performed with Tc-99m and iodine-131 in with Tc99m are adquired for the morphological characterization
48 patients (age: 42-94 years, median age: 74 years, 36 women (size, density and depth) of the lesions. 48 and 168 hours after
and 12 men) suffering from Graves’ disease (10), disseminated Ra223 administration, 20 minutes planar adquisitions are
S475 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

taken (acquisition window of 82 keV ± 20%, Medium energy is required. Program input data are the volumes of the healthy
collimator). Through image analysis software, each lesion is liver and the tumor and also the 99mTc MAA SPECT dicom file. All
localized in Ra223 images using the bone scintigraphy as a this information is processed and the obtained uptake threshold
reference and the activity of Ra223 is quantified in each lesion. values are showed in order to make a visual validation of them
Subsequently, the absorbed dose and the effective half-life of in the SPECT-CT images if desired. Voxel size is also showed as
the isotope are estimated following the MIRD methodology. additional information. The final output of the software is the
Considering that a relative biological effectiveness (RBE) of 5 for tumor to normal tissue ratio. All the process can be delivered
alpha particles, the RBE-weighted absorbed dose (DRBE) is also in a few seconds in a standard PC. Results: This tool allows a
calculated. Results: The RBE-weighted absorbed dose in each very reproducible estimation of tumor to normal tissue ratio
lesion per Ra223 injection was, on average, 9.45±2.50 Gy, finding and therefore of tumor and liver absorbed doses. Calculations
a big difference between lesions with a very low uptake (DRBE are automatic and the only possible user dependence is derived
below 1.25 Gy per injection) and other with a high absorbed from differences in previous volume measurements. For a safe
dose (up to 27.5 Gy per injection). The resulting average DRBE use of the software, the threshold based segmentation validity
for the complete treatment was 56.7±15.0 Gy for each lesion. is needed. This assumption may not be true in cases where
The half-life of the radionuclide in the lesion was 6.2±0.8 days. SPECT is not an exact surrogate of the spheres distribution:
Due to the low activity injected, the number of Ra223 accounts widely spread metastases, presence of high necrosis areas or
detected in the lesion was sometimes below limit of detection extrahepatic activity shunts. Conclusion: Simple and intuitive
with respect to the background, which made it difficult to software is presented for the implementation of the Partition
accurately characterize the absorbed dose. On the other Method in hepatic radioembolization therapy. Standard
hand, intestinal uptake present in the 48h image can make it calculation tools like this should help to reduce the derived from
impossible to estimate the effective half-life in certain lesions. the user or institution dependence. References: None.
Conclusion: The procedure and preliminary results obtained in
our center in the dosimetry of metastatic lesions treated with
Ra223 are presented. The values obtained are similar to other EP-0202
preliminary studies about of dosimetry in this kind of treatments. Different settings for the calculation of absorbed doses in
References: None. therapy with radioactive somatostatin analogues
E. Grassi1, E. Page2,3, D. Finocchiaro1,4, A. Versari1, A. Filice1, L.
Braglia1, M. Iori1, J. Tipping2, F. Fioroni1;
EP-0201 1
AUSL - IRCCS di Reggio Emilia, Reggio Emilia, ITALY,
Partition method-based treatment planning in 2
The Christie NHS Foundation, Manchester, UNITED
radioembolization with microspheres: software for tumor KINGDOM, 3University of Manchester, Manchester, UNITED
to normal tissue ratio calculation KINGDOM, 4Università di Bologna, Bologna, ITALY.
F. Mañeru, D. Martínez, A. Fernández, L. Bragado, F. Caudepón, R.
Estrada, N. Fuentemilla, M. Ribelles;
Complejo Hospitalario de Navarra, Pamplona, SPAIN. Aim/Introduction: the work was focussed on the comparison
between the absorbed dose results obtained using different
combinations of anthropomorphic phantoms ( ORNL-type
Aim/Introduction: The Partition Method is a widely used option phantoms based on the Oak Ridge models, or NURBS-type
for dose estimations in liver radioembolization treatments with phantoms based on the masses defined by ICRP89) and
microspheres and its key parameter is the tumor to normal radionuclide decay dataset to produce the dose factors (legacy
tissue uptake ratio (TN). The correct use of this method requires data versus decay series). These combinations are the same
an accurate identification of the interface between health implemented in commercial software, such as OLINDA/EXM
and tumor regions. This process has a high dependence on 2.0 and DOSEFX. Materials and Methods: a real dataset of 39
the chosen criteria to do so and even the user. The presented patients enrolled in a clinical trial for therapy with radioactive
software offers a reproducible way to delimiting both regions somatostatin analogues (labelled with 90Y and 177Lu) was
and their uptake ratio. Materials and Methods: Tumor to considered. The absorbed dose calculation (for 90Y and 177Lu)
normal tissue ratio is estimated from pre-treatment 99mTc was performed using the combinations: A) Legacy data and
macroaggregated albumin SPECT study (99mTc MAA SPECT). One ICRP89 phantoms; B) Legacy data and ORNL phantoms; C)
of the bases of the partition method is that high, intermediate Decay series and ICRP 89. Input data for every combination
and low uptake regions match tumor, normal liver and non- were the same numbers of disintegrations for the time-activity-
irradiated areas respectively. From previously estimated liver curves of liver, kidneys and spleen. The dataset was personalised
and tumor volumes, the software obtains the thresholds count for the real patient data (gender, weight of body and organs
values corresponding to their boundaries. Then, total counts in at risk) in all combinations for a more realistic approach. The
each region are integrated and TN is derived as the quotient statistical analysis was performed using R 3.3.3, studying also
between uptake by volume in both regions. For all this process, the Lin’s agreement correlation coefficient for the comparisons:
software has been developed with Python code. The software B versus A and C versus A for 90Y and 177Lu and for each organ.
is presented as an executable file and no previous installation Confidence intervals (CI) were calculated considering a 0.95
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S476

confidence level. Results: Considering the Lin’s coefficients for chain was summed up after applying weighting factors in the
the various pairs of data, the concordance of the paired data is two possible pathways of the 225Ac decay, 2 % for 209Tl and
very high, also in relation to the respective CI, showing very similar 98 % for 213Po. Results: 64Cu-DOTA-rituximab self irradiation
results coming from different settings chosen for calculations. in live, kidney, and tumor were 2.12E-02, 6.77E-02, and 3.28E-
The coefficients lie in the range: for liver 0.82-0.99; for kidneys 01 mGy-g/MBq-hr, respectively. 225Ac-DOTA-rituximab self
0.97-0.99; 0.94-0.97. In all cases the values are included in the CI. irradiation in live, kidney, and tumor were 5.01E+00, 1.65E+01,
Conclusion: the high agreement of the results obtained with and 2.75E+01 mGy-g/MBq-hr, respectively. The 64Cu-DOTA-
different patterns of radionuclide decay data and phantoms rituximab absorbed dose in liver, kidney, and tumor were
show that the calculation of absorbed dose for the analysed 2.08E-02, 3.45E-02, and 1.05E-01 mGy-g/MBq, respectively. The
organs (liver, spleen and kidneys) and for the two considered 225
Ac-DOTA-rituximab absorbed dose in liver, kidney, and tumor
isotopes produce concordant values. References: [1] Josefsson were 2.08E-02, 3.45E-02, and 1.05E-01 mGy-g/MBq, respectively.
A, Hobbs RF et al: Comparative Dosimetry for 68Ga-DOTATATE: Comparison of the tumor absorbed dose of 225Ac labeled DOTA-
Impact of Using Updated ICRP Phantoms, S Values, and Tissue- rituximab has 58.7 fold change to 64Cu-DOTA-rituximab tumor
Weighting Factors; J Nucl Med 2018; 59:1281-1288 ; [2] - Cristy absorbed dose. Conclusion: In this study, evaluates the image-
M, Eckerman KF. Specific Absorbed Fractions of Energy at based 64Cu and 225Ac DOTA-rituximab internal dosimetry using
Various Ages from Internal Photon Sources. III. Five-Year-Old. Oak self- and cross-irradiation of Monte Carlo simulation. This result
Ridge, TN: Oak Ridge National Laboratory; 1987:1-42. ORNL/TM- of study applies to the monitor the NHL patient treatment
8381/V3; [3] - Stabin M, Siegel JA RADAR Dose Estimate Report: as well as their targeted alpha therapy using 225Ac-DOTA-
A Compendium of Radiopharmaceutical Dose Estimates Based rituximab. References: 1. Plosker, Greg L., and David P. Figgitt.
on OLINDA/EXM Version 2.0 J Nucl Med 2018; 59:154-160. “Rituximab.” Drugs 63.8 (2003): 803-843.2. Forrer, Flavio, et al.
“Radioimmunotherapy with 177Lu-DOTA-rituximab: final results
of a phase I/II Study in 31 patients with relapsing follicular,
EP-0203 mantle cell, and other indolent B-cell lymphomas.” Journal of
64
Cu/225Ac-DOTA-rituximab internal dosimetry in mice Nuclear Medicine 54.7 (2013): 1045-1052.
using image-based Monte Carlo simulation
S. Woo1,2, W. Kim1, C. Lee2, I. Lim2, K. Song3, S. Lim2;
1
Division of applied RI, Korea Institute of Radiological and EP-0204
Medical Sciences, Seoul, KOREA, REPUBLIC OF, 2Department Accuracy of personalized kidney dosimetry in 177Lu-DOTA-
of Nuclear Medicine, Korea Institute of Radiological TATE based on a simplified single-time-acquisition with
and Medical Sciences, Seoul, KOREA, REPUBLIC OF, segmentation-free small-volume method
3
Department of Urology, Korea Institute of Radiological X. Hou1, W. Zhao2, J. Beauregard3,4, A. Celler1;
and Medical Sciences, Seoul, KOREA, REPUBLIC OF. 1
Radiology Department, University of British Columbia, Vancouver,
BC, CANADA, 2Department of Physics and Astronomy, University
of British Columbia, Vancouver, BC, CANADA, 3Department of
Aim/Introduction: Rituximab is used for non-Hodgkin’s Medical Imaging and Oncology Division of Research Center,
lymphoma, chronic lymphocytic leukemia and other CHU de Québec – Université Laval, Quebec, QC, CANADA,
autoimmune disease types of cancer. 64Cu labeled DOTA- 4
Department of Radiology and Nuclear Medicine and Cancer
rituximab agent can be acquired PET image for non-Hodgkin’s Research Center, Université Laval, Quebec, QC, CANADA.
lymphoma (NHL) patients to monitor lymphoma therapy.
The aim of this study was the evaluation of 64Cu and 225Ac
labeled DOTA-rituximab internal dosimetry using Monte Carlo Aim/Introduction: Peptide receptor radionuclide therapy
simulation. Materials and Methods: 64Cu-DOTA-rituximab (PRRT) with 177Lu- radiolabeled-DOTA-TATE is an effective
was administered intravenously (263 ± 32.0 μCi) in a mouse treatment option for inoperable neuroendocrine tumours
xenograft model (n=3). Small animal PET imaging was acquired (NETs). To ensure patient safety and improve treatment efficacy, a
on a dedicated small animal PET/CT system (InveonTM, Siemens personalized kidney dosimetry has been suggested as a routine
Preclinical Solution, Knoxville, TN). PET data were acquired a procedure in PRRT clinical studies. Dosimetry, however, requires
3-time points after the 64Cu-DOTA-rituximab administration complicated and time-consuming procedures, including
(2, 24, 48 hours). 64Cu-DOTA-rituximab residence times were multiple scans and challenging organ/tissue segmentations.
calculated via time-activity curves of the defined region of Our study aims to propose a practical, yet accurate, dosimetry
interest (ROI). Image-based internal dosimetry was calculated method to simplify segmentation procedures and minimize
by residence time and Monte Carlo based S-value. S-value number of scans. Materials and Methods: Twenty-nine NETs
was calculated by Geant 4 Monte Carlo simulations. S-value patient data with forty-three 177Lu-DOTA-TATE therapy cycles
was calculated self irradiation as well as cross irradiation with were analyzed. Three SPECT/CT scans, acquired at about 4h(D0),
liver, kidney and tumor region. 225Ac-DOTA-rituximab internal 23h(D1) and 70h(D3) after injection, were performed to measure
dosimetry was calculated by 64Cu-DOTA-rituximab residence the radiotracer biokinetics in kidneys. Segmentation-free small-
time and 225Ac S-value which was include all decay chain (221Fr, volume (SV) kidney dosimetry was estimated based on our in-
217
At, 213Bi, 213Po, 209Tl, and 209Pb). The absorbed dose in all decay house-developed automatic, observer-independent method
S477 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

for SV localization. The accuracy of SV doses, based on different contributions. A total of 3.2x108 decays were sampled to achieve
location selections, was evaluated by comparing them with a statistical uncertainty of less than 5% in all voxels considered.
those from whole-kidney (WK) segmentation. Meanwhile, to In addition, the impact of decay position within the source voxel
simplify SPECT acquisition schedules, for each dataset, both WK on VSVs was investigated by sampling the source uniformly
and SV doses, based on a single-time-point (STP) method using within the source voxel. Results: All VSVs agreed well with
a mono-exponential curve with the population mean effective values published in the literature for the same voxel resolution.
half-life and normalized to kidney activities at D0 or D1 or D3 The percent differences between the source VSVs calculated in
points, were calculated. The accuracy of WK+STP and SV+STP this work and those used in the NukDose software(1) were 2.8%,
methods was evaluated by comparing the WK dosimetry with 3 6.1% and 7.4% for 131I, 177Lu, and 90Y, respectively. Assuming 212Pb
time point acquisitions (WK+3TP). Results: The kidney effective is in secular equilibrium with its daughter products, the VSVs for
half-lives obtained from SV+3TP agreed to within 10% with the source voxel of 212Pb was two orders of magnitude higher
those obtained from the WK+3TP. The ratios of SV doses to WK than the other isotopes. The maximum percent differences
doses were equal to 1.8±0.2. Comparing different methods of between VSVs determined from sampling the source at the
SV location selections, independently selecting SV in images center of the source voxel versus uniformly within it was
from each of the three acquisitions has been proved to be the 52%, 54%, and 5.2% for 131I, 177Lu, and 90Y, respectively. These
most accurate approach. For STP dosimetry, the errors of both discrepancies are dependent on the voxel resolution and the
WK and SV doses, normalized to the D3 scan, remained below endpoint energies of the beta-particle emitted during decay.
10% relative to those estimated using 3 time points. While, STP Conclusion: The tool presented in this work can generate VSVs
doses, normalized to D0 and D1 scans could be > 40%. The linear for any radionuclide, at any voxel resolution, and using sampling
correlation coefficient between SV+STP dose (normalized to distribution within the source voxel. The ultimate goal of this
D3) and WK+3TP dose was about 0.9 (p<0.001). Conclusion: An work is to make VSVs more readily available to the scientific
automatic observer-independent SV location selecting method community for clinical use. References: (1) Kletting P et al. Z
was developed and its good accuracy has been demonstrated Med Phys. 2015 Sep;25(3):264-74.
by comparing it with the WK dosimetry. For STP dosimetry,
mono-exponential curve, with the population-based mean
effective half-life, normalized to the late data points (48-72h EP-0206
for kidneys) produced <10% errors. The clear linear relationship PRRT: standardized activity and dose quantification for
between SV+STP dose and WK+FT dose demonstrated its dosimetry of NETs patients treated with 177Lu
potential for use in clinical studies. References: None. S. Di Biaso1, E. Tonini2, G. Di Domenico1, A. Turra2, L. Uccelli3,
A. Barboni2, D. Farina3, L. Lodi3, E. Zappaterra3, S. Zaccaria3, S.
Romani3, E. Govoni3, S. Bertelli3, D. Bortolotti3, A. Massimi3, M.
EP-0205 Bartolomei3;
A Geant4-based Voxel S-value Generator For 1
Department of Physics and Earth Sciences, University of
Radiopharmaceutical Therapy Ferrara, Ferrara, ITALY, 2Medical Physics Unit, Sant’Anna
B. Bednarz; University Hospital, Ferrara, ITALY, 3Nuclear Medicine
University of Wisconsin, Madison, WI, UNITED STATES OF AMERICA. Unit, Sant’Anna University Hospital, Ferrara, ITALY.

Aim/Introduction: Radiopharmaceutical therapy is Aim/Introduction: The Council Directive 2013/59/EURATOM


experiencing tremendous growth due to the incorporation fixes the necessity for a personalized dosimetry for patients
of novel radiopharmaceuticals into the armamentarium of treated with radionuclides. In order to fulfil the directive, an
oncologists. Accompanying this growth is a renewed interest absolute quantification of the absorbed activity in organs of
in performing voxel-level dosimetry calculations in patients to interests and in lesions becomes necessary: a correct activity
help guide clinical decision making and optimize therapeutic estimation is, in fact, the base for a correct dose evaluation.
efficacy. While voxel S-values (VSVs) provide an efficient way Therefore, initially, counts need to be corrected for scatter,
of performing voxel-level dosimetry, the availability of VSVs in attenuation and CDR (Collimator to Detector Response); then,
the literature is sparse and limited to only a few isotopes. The the Calibration Factor (CF) has to be evaluated for 177Lu. Recovery
purpose of this work was to develop a generalizable, multi- Coefficients (RCs) need to be computed to correct for partial
radionuclide VSV generator for clinical use. Materials and volume effect (PVE). Finally, the absorbed dose estimation
Methods: All S-values (Gy/MBq-s) were calculated using the through MIRD scheme has been evaluated. The aim of this study
Monte Carlo code Geant4.9.6. Radioactive decay was simulated was to provide a complete and accurate procedure for absorbed
by evoking the G4RadioactiveDecay class which models the dose estimation for the NETs patients treated in Sant’Anna
decay of more than 2000 radioactive nuclei using the ENSDF University Hospital in Ferrara, enrolled under the FENET-2016
database. Point-isotropic sources were defined at the center of protocol (EudraCT:2016-005129-35). Materials and Methods:
a water phantom with a voxel size of 0.5 mm x 0.5 mm x 0.5 mm. Attenuation, scatter and CDR was corrected by Symbia NET
Four different isotopes were considered 131I, 177Lu, 90Y, and the Workflow (Siemens’ software to reconstruct and analyse SPECT/
decay chain of 212Pb. The VsVs included both electron and photon CT projection images). Moreover, CF computation can be done
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S478

using a uniform Jaszczak phantom. Then, RC evaluation study head Siemens SYMBIA T-2 gamma camera, crystal thickness of
has been performed with a Nema image quality PET phantom 9.5 mm and LEHR collimators. SPECT is acquired with 32 frames,
with both hot spheres and filled pockets, in order to study 30 s/frame, 128×128 matrix and 4.8 mm voxel. CT parameters
volumes of clinical interest up to 1000 ml. In the last part of the are: 110 kVp, 63 mAs, 75 rpm. Reconstruction is done with
work, the complete evaluation of the absorbed dose in kidneys Siemens Flash3D™, 8 iterations 4 subsets, CDR compensation,
and lesions has been computed, through the use of OLINDA CT-derived Attenuation Correction and energy window-based
2.0 software. Results: The Calibration Factor for our SPECT/CT is Scatter Correction. Analysis of images were performed using
equal to 17.2±0.8 cps/MBq. Moreover, a complete curve RCs vs IMAGEJ and Simplicity® Results: The best recovery coefficient
Volume (ml) for Lutetium, with volumes up to 1000 ml, has been for A, V and c are obtained with thresholds of 100%, 26% and
evaluated; its fit has been used to correct PVE for all volumes 50%, respectively. We obtain reconstructions of high precision
of clinical interest. The absorbed dose and its uncertainty have with total counts better than 90%. The distribution of activity
been evaluated for kidneys and lesions. Conclusion: Nowadays, at the voxel level is estimated well with the corresponding
a correct dose evaluation is important in order to quantitatively accounts with a 50% threshold. The percentage of true treated
study the efficiency of the PRRT therapy on patient with NETs. liver volume is estimated well with the voxels contained in the
Moreover, the precise knowledge of the absorbed dose and its threshold image of 26%. Conclusion: The physical phantom
uncertainty can help in making a decision over a possible re- developed can provide a good approach for the SPECT
treatment, verified that the total absorbed dose does not exceed quantification to TheraSpheres™ Y90 dosimetry. References:
critical values reported in literature. In this work, a reproducible None.
and accurate procedure for a complete dose evaluation has
been presented, in order to achieve the most personalized
possible image-based dosimetry, given the boundaries of the EP-0209
MIRD scheme. References: None. Torch: A Treatment Planning System for Personalized
Radiopharmaceutical Therapy
J. Grudzinski, K. Sorensen, M. Gracz, B. Bednarz, P. Wickre;
EP-0207 Voximetry, Middleton, WI, UNITED STATES OF AMERICA.
Thresholds in SPECT image for quantification in the
planning of TheraSpheres™ Y90 treatments
M. Barquero Sanz, C. Andres, M. Martin Veganzones, R. Ruano, J. Aim/Introduction: Through many years of experience with
Velasco, C. Gamazo, A. Sainz, J. Gomez; external beam radiotherapy (XRT), it is well-known that patient-
SACYL, Valladolid, SPAIN. specific absorbed dose is an excellent predictor of treatment
efficacy and toxicity. A similar approach of determining
patient-specific absorbed doses to achieve clinical objective s
Aim/Introduction: In individualized dosimetry for SIRT with for each patient can be used in radiopharmaceutical therapy
TheraSpheres™Y90 for hepatic tumor/MTX metastases it is (RPT). We have developed a proprietary treatment planning
necessary to determine the activity to be perfused A (GBq), system, called Torch, for RPT that includes adaptation of
the perfused and tumor volume V and the distribution of single-photon emission computed tomography (SPECT) or
activity in each voxel within the tumor c. Planning consists in positron emission tomography (PET) imaging to interface
an arteriography study to determine the vascular pathway to with computer hardware and specialty software algorithms.
access the tumor followed by the perfusion of 5-8 mCi 99mTc- Materials and Methods: There are three main modules
MAA through this pathway to acquire an SPECT-CT study. The included in Torch: Torch-PK, Torch-MC, and Torch-Bio. Torch-PK
quantification of these SPECT images allows to determine uses nuclear medicine imaging data to model pharmacokinetic
regional or voxel-level activities to evaluate the absorbed (PK) behavior of the radiopharmaceutical as a function of time
doses in the later therapeutic perfusion of the 90Y u-spheres to generate time activity curves (TACs) for each voxel within
by the same vascular pathway. The optimal threshold that regions of interest (ROI). TAC’s are then analytically integrated
gives the best estimate of V is not necessarily the same as to determine the number of disintegrations that occur within
the threshold that gives the best estimate of A nor the best each voxel. This data is then imported into Torch-MC where
estimation of c. Then 3 thresholds are needed to estimate Monte Carlo radiation transport is performed to estimate the
the corresponding recovery coefficients RC. As the volumes three-dimensional dose distribution in the patient. A simpler
treated with TheraSpheres™Y90 (200-800 ml) are greater than dose calculation method was also developed which uses dose-
those simulated with recent physical phantoms (0.5-200 ml), kernels (called Torch Lite). Torch-Bio uses the dose distribution
in this work we build a new phantom designed specifically for generated from Torch-MC or Torch Lite to estimate biologically-
the correct determination of these thresholds. Materials and equivalent dose metrics that are often used to characterize RPT.
Methods: The phantom consists of 12 identical bottles of 30-40 Torch will leverage the enormous computing power of graphics
ml each one united to simulate a heterogeneous tumor of ~450 processing units (GPUs) to perform patient-specific dose
ml and filled with an aqueous solution of 99MTc. The assembly calculations accurately and quickly for busy, resource-limited
is introduced into the IEC-Standard 61675-1 phantom filled with nuclear medicine and radiation oncology departments. Results:
non-radioactive water. SPECT/CT image is acquired with a dual- Torch-PK automatically fits the best PK model to each ROI. Torch
S479 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

Lite computes voxel-based dosimetry in a matter of seconds by tissue. The software includes separate transfer of progenies
performing GPU-convolution of the cumulative activity map with and creates a unique biokinetic model based on the biokinetic
MC generated dose-kernels e.g. 177Lu, 131I, 90Y, 67Cu, etc. Torch-MC parent data. Including the biokinetics of the progenies will often
performs MC radiation transport in a matter of minutes for beta, lead to a dose reduction as retention in the urine are included.
alpha, and Auger-electron emitting radionuclides. Dosimetry References: Taprogge J, et al. Compartmental model for
results are displayed as either cumulative or differential dose 223Ra-Dichloride in Patients with metastatic bone disease from
volume histograms. Voxel-based BED can also be exported to castration-resistant prostate cancer.
be combined with XRT dosimetry. Torch is radionuclide agnostic
where dosimetry can be calculated for any radiopharmaceutical
regardless of isotope, enabling greater flexibility/adaptability EP-0211
among treatment protocols. Conclusion: Torch will enable Development and Verification of a Software Tool to
more precise and accurate treatment planning where optimal Calculate Absorbed Doses at the Voxel Level in Molecular
assessments can be completed in minutes, as opposed to tens Radiotherapy Treatments
of hours by leveraging the enormous computing power of GPUs T. Monserrat, M. Peinado, N. Montenegro, D. Álvarez, J. Herrero, D.
coupled with MC simulation. For patients and clinicians, Torch Bruzos;
enables a promise of personalized medicine yet to be realized in Hospital Universitario Central de Asturias, Oviedo, SPAIN.
the field of nuclear medicine. References: None.

Aim/Introduction: The treatment planning systems for


EP-0210 molecular radiotherapy are a fundamental tool for the physicist
Idac-alpha - An Alpha Dosimetry Program For Healthy responsible for dosimetry and they are in growing demand,
Tissue especially after the publication of the 2013/59/EURATOM
M. Andersson; Directive. However, they require an economic investment and
Medical Radiation Physics, Malmö, SWEDEN. some of them are limited to a single radioisotope. Our objective
was to develop a program to calculate doses at the voxel level
directly on the clinical images of individual patients in molecular
Aim/Introduction: The aim of this project is to develop radiotherapy treatments with Lu-177, Y-90 and I-131. Materials
dosimetry for eight alpha emitting radiotherapeutics (Ac-225, and Methods: Software was developed in Python 2.7. It allows
At-211, Bi-212, Bi-213, Pb-212, Ra-223, Tb-149 and Th-227), the user to load images from a hybrid SPECT/CT system, delineate
including their progenies. Currently, it is usually assumed that the VOI (volumes of interest) and calculate the absorbed dose to
the progenies decay in the same location as the parent nuclide. each of them, following the MIRD methodology. As input data,
without further biokinetic transport. IDAC-Alpha is both a the user must manually enter the isotope used (Lu-177, Y-90 or
biokinetic and dosimetric software, which includes separate I-131), the calibration factor (MBq/count/s) and the residence
biokinetic transport models for all progenies. For progenies time of each VOI. The partial volume effect correction factors
generated in the kidneys the software will include the retention can be incorporated in the quantification of activity in small
from kidneys to the urinary content. Materials and Methods: VOI. The program loads the S-voxel factors corresponding to the
IDAC-Alpha was applied on a compartmental model for Ra-223 voxel size of the SPECT images and the selected radioisotope.
dichloride in mCRPC patients (Taprogge J, et 2017). The software These S-voxel factors are taken from the database published
performs the absorbed dose calculations in two steps. First, a in 2012 by Lanconelli et al. As a result, the program generates
unique biokinetic model is created based on the input data a dosimetric report with the average doses absorbed to all of
of the biokinetic model of the parent. Secondly, the software the VOI and their corresponding dose-volume histograms. In
modifies the data to create a full biokinetic model covering all order to test the accuracy of the calculated doses, different VOI
decays which can therefore be solved numerically. Each nuclide were delineated on 12 phantom and 12 clinical images of Lu-
and decay are tracked for each organ and absorbed doses are 177 with different activity concentrations. The dose calculated
calculated. To keep the computational time below 1 second for by the program was compared with the theoretical dose that
both the dosimetric and biokinetic calculations the radionuclides would be received in each zone assuming self-absortion of
are tracked for 1 year in the body, which is long enough to ensure the mean beta emission. Results: The doses estimated by the
that no significant activity is left in the body. Absorbed doses program are in good agreement with the theoretical ones,
are calculated for the Ra-233 model for the mCRPC patients in being on average (2.63 ± 0.69) % higher than those predicted
two ways. A) all progenies decay at the same site as the Ra-233 by the theory. This overestimation is attributed to the fact that
and B) the progenies have separate biokinetic models. Results: the theoretical doses have been calculated by making the
The biggest differences in absorbed dose will be in the bone assumption of beta emission only, while the program takes into
surface, the red marrow and the kidneys. This is due to the fact account the whole spectrum of the isotope. Conclusion: The
that the Ra-223 progenies have a lower bone uptake than their program presented calculates absorbed doses at the voxel level
parent radionuclide. Conclusion: IDAC-Alpha is a biokinetic, for different isotopes from SPECT / CT images of the patient,
user friendly software with a graphical interface, developed to which allows us to perform individualized dosimetries and thus
perform more realistic alpha dosimetry calculations for healthy optimize treatments. References: None.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S480

EP-0212 Aim/Introduction: Yttrium-90 (Y-90) microsphere treatment


Iodine Internal Dosimetry using Anthropomorphic is an internal radiation treatment in which hepatic tumors are
Voxelized Phantom in GATE selectively targeted via arterial route owing to unique circulation
N. G. Cavedini, C. M. Dartora, A. M. Marques da Silva; pattern of the liver. One major questionable aspect of this
PUCRS, Porto Alegre, BRAZIL. treatment is the heterogeneity of intra-tumoral microcirculation
and its effect on theraphy response as well as the amount of
Aim/Introduction: To investigate absorbed dose in organs at activity to provide maximum tumor dose along with minimum
risk in iodine therapy using voxelized phantom. Materials and background dose. This study aims to give a vision to uncover
Methods: GSF Golem voxelized phantom (male, 38 years, 121 these issues with use of a novel patient-based dosimetric
structures) was used in GATE Monte Carlo simulation application. approach. Materials and Methods: A total of 90 treatments
β particles (89.3%, with 606 keV) and gamma photons (82.2% with which were performed with Y-90 glass microspheres in the
364 keV) from 131I decay were simulated separated, to verify the same university hospital between the years 2012 and 2018
contribution of each one in absorbed dose at risk organs. Thyroid were re-planned retrospectively based on a novel personalised,
gland was filled with homogeneous 0.1 MBq of 131I. Risk organs patient-based dosimetric approach. During planning, a software
studied were: thyroid gland (d=1.04 g/cm3), esophagus (d=1.05 that provides a voxel-based dosimetric approach through
g/cm3), trachea (d=1.03 g/cm3 ), spinal cord (d=1.03 g/cm3) and anatomical and functional sequence images of the patient
cervical vertebrae (d=1.92 g/cm3). Results: Thyroid absorbed was used. The retrospective dosimetric re-planning for each
dose per injected activity were 2.65 and 1.85 mGy/MBq for β- patient gave an evaluation in terms of targeted effective tumor
and gamma, respectively. This corresponds to a contribution dose and critical organ doses. The relation between Y-90 glass
of 58.91% of β- particle energy. Results for esophagus were microsphere activities and perfused tissue volume, perfused
2.62.10-3 and 3.00.10-1 mGy/MBq for β- and gamma, respectively. tumor volume and absorbed doses was investigated. The
Trachea absorbed doses were 3,02.10-3 for β- and 2,50.10-1 mGy/ planning steps of the software used in this study were reviewed
MBq for gamma. For spinal cord, the results showed absorbed in terms of parameters that would affect the dosimetric results,
doses of 1.16.10-3 mGy/MBq, for β-, and 2.14.10-1 mGy/MBq for and a standard was specified for these parameters followed
gamma emissions. Results for cervical vertebrae were 1.96.10-2 by comparison with those that were calculated pre-therapy
and 1.50 mGy/MBq for β- and gamma, respectively. For adjacent with semi-dosimetric approach. Results: Novel patient-based
organs of thyroid, contribution was mostly by gamma emission, retrospective plannings showed that the amount of Y-90 glass
representing 99.14%, 98.80%, 99.46%, 98.71% for esophagus, microsphere activity, which were used under current conditions
trachea, spinal cord and cervical vertebrae, respectively. and calculated taking a reference of absorbing a dose of 120 Gy
Results are compared to Shahbazi-Gahrouei and Ayat (2015), of the lobar volume alone, were lower than the pre-calculated
with thermoluminescent dosimeters (TLD) in phantom neck activity for 14 /90 (~%16) therapies and higher for 76 /90
above thyroid region and MCNP Monte Carlo simulation with (~%84) therapies when considering the critical organ tolerance
mathematical phantom. Gamma absorbed dose measured doses. Conclusion: This study showed that the patient-based
with TLD (8.53.10-1 mGy/MBq) in Shahbazi-Gahrouei and Ayat dosimetric approach, taking into account the anatomic variation
(2015) was 54% lower than that found in this work (1.85 mGy/ of the relevant patient, different tumor size and its localization,
MBq). MCNP simulation of thyroid absorbed dose (11.5 mGy/ is of vital importance with respect to provide maximum tumor
MBq) was 61% higher than than our work (4.50 mGy/MBq). The dose along with minimum background dose in accordance
differences are due to the characteristics between mathematical with the logic of internal radiation treatment. The findings of
and GSF voxelized phantom. Conclusion: Absorbed doses this preliminary study will be expected to give rise to proceed
for thyroid gland, esophagus, trachea, spinal cord and cervical with clinical studies in order to optimize treatment efficency.
vertebrae were simulated with GATE Monte Carlo simulation. References: None.
Thyroid gland gamma dose was comparable with previously
published data, showing the appropriateness of GATE MC as
an adequate tool for dose calculations, mainly with realistic EP-0214
voxelized phantoms. We did not find until now other papers Simple Bremsstrahlung SPECT Method for Whole-
showing the contribution of gamma and β-particle in iodine Liver Dosimetry in Treatments with 90Y-Microspheres -
therapy at risk organs. References: Shahbazi-Gahrouei D, Ayat Comparison with 90Y PET
S. Determination of Organ Doses in Radioiodine Therapy using K. Knesaurek, S. Heiba, R. Pyzik, S. D. Pasik, L. Kostakoglu;
Monte Carlo Simulation. World J Nucl Med. 2015;14(1):16. Ichan School of Medicine at Mount Sinai, New
York, NY, UNITED STATES OF AMERICA.

EP-0213
A Novel Patient-Based Dosimetric Approach for Y-90 Aim/Introduction: Bremsstrahlung SPECT/CT (bSPECT/CT) is
Microsphere Treatment the most common method for post-therapy imaging in liver
F. Çakir1, M. F. Bozkurt2, A. K. Özden2; cancer treatment with 90Y microspheres. However, quantitative
1
Hacettepe University, Ankara, TURKEY, 2Hacettepe bSPECT is very difficult due to scatter, septal penetration, the
University Faculty of Medicine, Ankara, TURKEY. continuous nature of the bremsstrahlung energy spectrum,
S481 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

and inefficient bremsstrahlung production. One way to address differences in absorbed dose values for 90Y-PET and 90Y-BRS-
these limitations is to use Monte Carlo (MC)-based bSPECT SPECT in comparison to a simplified Technetium-99m-MAA-
reconstruction (ref. 1), which is not always practical. Here, we are SPECT based 3D dosimetry for institutions without access to
proposing a simple approach for estimation of mean absorbed- 90
Y-PET Imaging. Materials and Methods: Seven patients
dose to the liver using bSPECT/CT in patients undergoing (in total ten therapy cycles) suffering from unresectable
treatment with 90Y microspheres. Materials and Methods: : hepatocellular carcinoma (HCC) received a 99mTc-MAA-SPECT/
In our previous study comparing 90Y dosimetry obtained using CT before 90Y-SIRT and accordingly post-therapeutic 90Y-BRS-
bSPECT/CT vs PET/CT, we found that there was a large difference SPECT/CT and 90Y-PET/CT. The therapy volume was segmented
between the mean doses to the liver. However, there was a high from low resolution 90Y-BRS-SPECT and the 99mTc-MAA-SPECT
linear correlation between the doses, presenting an opportunity was scaled with the 90Y therapy activity within this volume.
for quantitative assessment using bSPECT/CT 90Y imaging, This scaled 99mTc-MAA-SPECT based activity image as well as
provided appropriate scaling and image enhancement. After the 90Y-BRS-SPECT and 90Y-PET activity images were convolved
treatment with 90Y microspheres, 40 patients were immediately with a pre-simulated 90Y dose kernel for soft tissue to obtain 3D
imaged on a dual-head Infinia SPECT/CT gamma camera and dose images. To compare tumor doses a spherical VOI (d=2cm)
on a mCT PET/CT system . Local deposition method with known was drawn and placed in the tumor. Healthy liver doses were
activity of 90Y was used for dosimetry calculations utilizing MIM calculated for all patients showing activity uptake in healthy liver
6.8 software. Images from 25 of the patients, randomly selected, by averaging the doses of three spherical VOIs (d=2cm), which
were used to calculate the correlation of mean liver doses were placed in healthy liver tissue. Results: The mean tumor
obtained from bSPECT/CT vs. PET/CT. For the remaining 15 doses for all patients were found to be 133 (±34) Gy/GBq for the
patients, the calculated correlation was used to estimate doses scaled 99mTc-MAA-SPECT dosimetric approach, 84 (±12) Gy/GBq
obtained from bSPECT/CT, which were then compared to the for 90Y-BRS-SPECT and 176 (±18) Gy/GBq for 90Y-PET, respectively.
doses obtained from PET/CT, considered the gold standard for The deviation of tumor doses in comparison to 90Y-PET were
quantitative analysis. Results: From the 25 selected patients, 20% for scaled 99mTc-MAA-SPECT and 50% for 90Y-BRS-SPECT.
the calculated linear correlation between bSPECT/CT and The mean healthy liver doses for all patients were found to
PET/CT 90Y doses was high ( r^2 =0.99), with a slope of 2.97 be 19 (±8) Gy/GBq for the scaled 99mTc-MAA-SPECT dosimetric
and an intercept of -3.43. This linear fit was used to calculate approach, 22 (±3) Gy/GBq for 90Y-BRS-SPECT and 42 (±9) Gy/
the bSPECT/CT doses for the remaining 15 patients. For these GBq for 90Y-PET,respectively. The scaled 99mTc-MAA-SPECT values
patients, the mean whole-liver dose obtained from bSPECT/ deviated 49% from 90Y-PET while the 90Y-BRS-SPECT based
CT fitted data vs that obtained from PET/CT were 47.3 Gy and deviated 39%. Conclusion: With our study on seven HCC SIRT
48.3 Gy, respectively. The average relative difference was 3.4 % patients (10 therapy cycles), we observed a significant tumor
(range -12.8 % to 13.0 %). Conclusion: Although quantitative dose underestimation for 90Y-BRS-SPECT based 3D dosimetry.
bremsstrahlung imaging is difficult, as mentioned above, it Dosimetry based on a scaled 99mTc-MAA-SPECT showed
is possible to calculate adequate estimates of whole-liver comparable tumor dose values within the given standard
dosimetry from bSPECT/CT 90Y imaging that is calibrated using deviation. The deviation of scaled 99mTc-MAA-SPECT compared
its correlation with post-therapy PET/CT 90Y images. References: to 90Y-PET tumor doses was overall smaller than those of 90Y-BRS-
Gustafsson J, Knešaurek K. Monte Carlo-Based Bremsstrahlung SPECT based tumor doses. However, for healthy liver doses the
SPECT Reconstruction for Whole-Liver Dosimetry in Treatments scaled 99mTc-MAA-SPECT approach showed a larger deviation
with 90Y-Microspheres - Comparison with 90Y PET. EJNMMI 44, than the 90Y-BRS-SPECT based values. We therefore conclude,
supp 2, S397, 2017. that post-therapeutic 3D dosimetry based on scaled 99mTc-MAA-
SPECT is feasible for tumor doses, while its application to healthy
liver doses is limited. References: None.
EP-0215
Image-based 3D Dosimetry Techniques For Yttrium-90
SIRT Of HCC: Quantitative Comparison Of Tumor And EP-0216
Healthy Liver Absorbed Doses The joint use of MAA SPECT/CT and CBCT enables better
J. Brosch, A. Gosewisch, H. von Zimmermann, L. Kaiser, P. dosimetry planning for SIRT procedures
Bartenstein, H. Ilhan, A. Todica, G. Böning; M. Rodríguez-Fraile, M. Morales, A. Ezponda, M. Calvo, F. Grisanti,
Department of Nuclear Medicine, University P. Berián, L. Sancho, A. Erhard, V. Morán, M. Iñarrairaegui, B. Sangro,
Hospital, LMU Munich, Munich, GERMANY. J. Bilbao;
Clínica Universidad de Navarra, Pamplona, SPAIN.

Aim/Introduction: Most of the dosimetric approaches for


Yttrium-90-SIRT rely on 1D averaged tumor and healthy liver Aim/Introduction: To determine if MAA SPECT/TC and CBCT
tissue doses, while 3D image-based dosimetry for treatment allow better dosimetry planning by means of a better definition
verification would be preferred. Depending on the institute, of the target volume and the activity to be administered in each
either 90Y-bremsstrahlung-(BRS)-SPECT or 90Y-PET is used for injection. Materials and Methods: 24 consecutive patients
post-therapeutic imaging. Aim of this study was to investigate treated with SIRT using 90Y resin microspheres from 11/2018
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S482

to 03/2019 (20 hepatocellular carcinoma, 3 cholangiocarcinoma Based on our clinical experience, we present the feasibility of
and 1 neuroendocrine tumor), were prospectively studied. a routine 3D-dosimetric planning for the management of SIRT
Target volumes were obtained during SIRT planning from patients. Materials and Methods: We have implemented a
contrast-enhanced CT (CECT) in 23 patients, 99m-TC MAA patient-specific dosimetry named yPOD (yttrium Personalized
SPECT/CT (MAA) in 24 and from cone-beam CT (CBCT) in 15, Optimized Dosimetry) for each patient in SIRT procedure. Our
and were compared to the final target volume (FTV) obtained yPOD approach is a personalized voxel-based dosimetry using
from 90Y-microspheres PET/CT (90YPET/CT) in all patients. commercialized 3D dosimetry software. We defined a specific
For MAA and 90YPET/CT, target volumes were drawn using a volume nomenclature to take into account all interest organs
VOI with isocontour (Syngo.via, Siemens). CBCT was also used for the 3D dosimetry: Tumor(s) (T), Total Liver (TL), Lungs (L),
to define the percentage of tumor volume perfused by each Perfused Volume (PV=threshold segmentation set at 5% of the
branch/artery. To assess agreement between studies, the Lin maximum count value), Healthy Perfused Liver (HPL=PV-T), Non-
concordance coefficient correlation (CCC) was used and to Perfused Liver (NPL=TL-PV). All these volumes are delineated on
define which study predicts better FTV, the determination the pre-therapeutic 99mTc-macroaggregated-albumin SPECT/
coefficient (R2) from the regression model. Results: In 75% of CT. The dose calculation is realized from voxel S-values dose
patients, SIRT was performed through segmental or tumor kernel convolution algorithm. The density correction is applied
feeding arteries. Only in 4 patients (16%), MAA and SIRT even if hepatic heterogeneity has a low effect on the dose
administrations differed due to patient motion during SIRT (1), calculation. The mean absorbed dose is computed for each
vasospasm (1) or minimal deliberate changes (2). Mean (SD) segmented volume and specific dosimetric criteria are further
target volumes in ml were 749 (577) for CECT, 828 (521) for MAA, defined for the healthy perfused liver (HPL) and the tumor: the
806 (701) for CBCT and 1011 (562) for 90YPET/CT. Isocontour HPL volume to receive a dose of 70 Gy and the dose received
mode was 3% (range=1-9%) for MAA (67% patients) and 90YPET/ by 95% of the tumor volume. The yPOD and the prescription
CT (71%). In 25% of patients, CBCT defined percentage of tumor of the administered activity to the patient are systematically
volume perfused by each artery (when >1 feeding artery) validated by a medical-technical team composed of radiologist,
and consequently the percentage of activity to administer by nuclear medicine physician, radiopharmacist and medical
each. The concordance with 90YPET/CT FTV was moderate for physicist. Results: 15 patients have already benefited of an
CBCT (CCC=0.6; IC=0.6-0.9) and substantial for CECT (CCC=0.7; yPOD. Consequently, each of these patients has undergone a
IC=0.46-0.84). MAA reached maximal concordance (CCC =0.81; personalized and optimized SIRT by dosimetry-guided. The
IC=0.64-0.91), being better when the 4 patients with changes processing time for our 3D dosimetry method is on order of
in the administrations were excluded (CCC =0.85; (IC=0.68-0.93) 1 hour including 15 minutes to prepare the dosimetric study,
Interestingly, MAA showed almost a perfect concordance with 40 minutes to delineate volumes and 5 minutes to obtain the
CECT in lobar or total administrations (CCC Lin=0.96; IC=0.8- dose-volume histogram. Conclusion: In the SIRT procedure,
0.99), in which anatomical volumes are accurately defined with treatment planning based on 3D dosimetry in clinical routine is
CECT. The three studies predicted linearly the FTV with a weak R2 a reality, but it requires a significant resource, including a specific
for CBCT (R2=0.5, p<0.05), moderate for CECT (R2=0.65, p<0.01) treatment planning system, a clinical dosimetry procedure and
and strong for MAA (R2=0.8, p<0.01). Conclusion: MAA SPECT/ a dedicated time to medical-technical staff. References: [1]
CT predicts 90YPET/CT FTV better than CBCT or even than the Stokke et al. “Dosimetry-based treatment planning for molecular
conventional method (CECT). CBCT allows defining the activity radiotherapy: a summary of the 2017 report from the Internal
to be administered through each artery. Therefore, the joint use Dosimetry task force” EJNMMI Physics 2017.
of both techniques enables better dosimetry planning for SIRT
procedures. References: None.
EP-0218
Normal organs and tumor absorbed doses of 188Re-human
EP-0217 serum albumin microsphere in GP7TB hepatoma model
The 3D dosimetry-based treatment planning in clinical L. Chen, W. Lee, C. Ho, Y. Chang, C. Chang;
routine for SIRT: reality or illusion ? Institute of Nuclear Energy Research, Taoyuan City, TAIWAN.
J. Badel1, S. Parisse-Dimartino1, F. Khayi1, A. Martin1, J. Labour1,2, D.
Sarrut1,2, D. Kryza1, C. Mastier1, T. Mognetti1;
1
Centre Leon-Berard, Lyon, FRANCE, 2CREATIS, Lyon, FRANCE. Aim/Introduction: The aim of this study was to investigate
the dosimetry of 188Re-human serum albumin microsphere
(188Re-HSAM) in GP7TB hepatoma model via intraarterial (i.a.)
Aim/Introduction: The 3D dosimetry-based treatment planning administration. Materials and Methods: Male F344 rats were
in SIRT aims to optimize the tumor control by administering intrahepatic inoculation with GP7TB 1 mm3 cubes. At 26 days
the highest possible activity in target volume while limiting after tumor inoculation, dosimetry data was collected after
complications irradiation to organs at risk. However, its clinical injection of 188Re-HSAM. Pharmacokinetic data of 188Re-HSAM
implementation is often perceived as complex and leads to were obtained for estimation of absorbed doses in tumor and
its abandonment in favor of simplified dosimetric methods, normal organs. Radiation dose estimates for normal tissues and
so less optimized such as the BSA method for example [1]. tumor were calculated using the OLINDA/EXM program with
S483 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

ICRP 30 GI Model and Voiding Bladder Model. Results: Based inter-variability. Additionally, the accuracy and reproducibility of
on excretion studies, urinary excretion was assumed to be the activity calibration factors determined for each technique
27% and intestinal excretion was assumed to be 16%. Higher were evaluated. Results: For GC, the uncertainties due to device
absorbed doses in normal organs were observed in the liver performance are mostly below 5% when using an appropriate
(2.2 mSv/MBq), lower large intestine (1.8 mSv/MBq), upper large measurement protocol. For SPECT, errors due to partial recovery
intestine (1.2 mSv/MBq) and kidneys (0.67 mSv/MBq). The red of activity account for an underestimation of at least 20% of the
marrow absorbed dose was estimated to be 0.016 mSv/MBq. kidney activity. Also the ROI size has a large impact on SPECT
The effective dose was 0.36 mSv/MBq. The tumor radiation image quantification. SPECT measurements resulted in lower
absorbed dose for the i.a. administration of 188Re-HSAM was also variability between time-specific kidney activities of different
calculated in this study. Tumor-absorbed doses for 188Re-HSAM mice than GC, and resulted also in a lower variability in the
were 4.3 mGy/MBq at 1 g tumor sphere. The T-NT ratio was 1.9 estimated residence time (±10%, vs ±25% for GC). SPECT was
in liver. Conclusion: The tumor-absorbed dose demonstrated also less prone to large (>15%) errors in the determination of
obvious tumor localization and concentration of HSAM the activity calibration factor. When using an appropriate SPECT
therapeutics loaded with 188Re. Therefore, i.a. administration ROI size, kidney activities from SPECT and GC agreed mostly
of 188Re-HSAM could provide a benefit and it is a promising within 20%. Conclusion: Micro-SPECT allows reproducible and
strategy for delivery of 188Re-HSAM in oncology applications. reasonably accurate quantification of 131I in murine kidneys. This
References: None. opens the possibility to perform longitudinal biodistribution
studies and kidney dosimetry for the same animals used for
long-term toxicity studies. References: None.
EP-0219
Quantification of 131I activity in mouse kidneys using
micro-SPECT and ex vivo gamma counting: experimental EP-0220
evaluation of uncertainties Comparison of 6 MeV electrons scattering at the edges of
C. Saldarriaga Vargas1,2, L. Struelens1, M. D’Huyvetter2, J. L. Eersels2, metal and 3D-printed plastic collimators
V. Caveliers2, P. Covens2; S. Stuchebrov1, I. Miloichikova1,2, Y. Cherepennikov1, A. Krasnykh1,
1
Belgian Nuclear Research Centre (SCK-CEN), Mol, B. Gavrikov3;
BELGIUM, 2Vrije Universiteit Brussel, Jette, BELGIUM. 1
Tomsk polytechnic university, Tomsk, RUSSIAN
FEDERATION, 2Cancer research institute of Tomsk national
research medical center of the Russian academy of
Aim/Introduction: As opposed to conventional ex vivo gamma sciences, radiotherapy department, Tomsk, RUSSIAN
counting (GC) of dissected tissues, micro-SPECT offers the FEDERATION, 3Moscow city oncology hospital №62, 1st
possibility to perform in vivo longitudinal studies on the same Radiological department, Istra, RUSSIAN FEDERATION.
animal. In order to derive the pharmacokinetic parameters
necessary for tissue dosimetry and the evaluation of the dose
dependence of biological response, micro-SPECT must be Aim/Introduction: Electron external beam radiation therapy is
quantitative and allow an accurate and reproducible assessment a highly effective tool in cancer treatment. Currently, individual
of the radiopharmaceutical activity in the relevant tissue. metallic collimators manufactured by cutting or melting are
This study aims to evaluate the accuracy and reproducibility used to form complex electron fields. The authors propose
associated with the mouse pharmacokinetic assessment of an alternative approach to forming a transverse profile of the
131
I-labeled single-domain antibody fragments (sdAb) using clinical electron beam fields by samples made of plastics using
micro-SPECT, against GC ex vivo biodistribution studies. The additive technologies. Plastic collimators are thicker than
focus is on the kidneys, where uptake of the 131I-labeled sdAb metal ones, so it is necessary to consider the effect of the edge
is significant. Materials and Methods: Biodistribution studies scattering on the dose distribution. The purpose of this study
were done on healthy C57BL/6 mice. The pharmacokinetic is to compare the scattering effects for a 6 MeV electron beam
profile of 131I-labeled sdAbs in the kidneys was determined at the edges of metal and plastic collimators. Materials and
from tissue activity measurements at different time points Methods: We experimentally obtain the dose field profiles
post injection, both with micro-SPECT and GC. SPECT/CT for an ONCOR Impression Plus medical linear accelerator (the
acquisitions were performed with a VECTor micro-SPECT/PET/ electron energy is 6 MeV) using GafChromic EBT3 dosimetry
CT (MILabs). Following the last SPECT acquisition, the activity films. The metal collimator is melted in a special CIVCO furnace
of dissected tissues was assessed in a gamma counter (Cobra- using an A-158 alloy consisting of bismuth (50%), lead (26.7%),
II, Canberra-Packard). Several sources of uncertainties were tin (13.3%), and cadmium (10%), while the HIPS-plastic one is
evaluated experimentally for each technique. For SPECT: system manufactured by rapid prototyping using Up!Plus2 printer. The
performance in terms of activity recovery coefficients (phantom thickness equals 15 mm for the metal sample and 40 mm for
study) and measurement reproducibility, mouse inter-variability, the plastic one. In the experiment, flat edged metal and plastic
and size of the image quantification ROI. For GC: device samples are placed in the path of the electron beam to block a
performance in terms of measurement reproducibility, cross-talk, part of the particle flux. A dosimetry film is placed at a 100 cm
sample volume effects and response linearity; as well as mouse distance from the source. One part of the beam falls on the film
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S484

without an absorber, and the other part is completely absorbed activity per unit mass for the first administration was about
in the material under study. This allows us to explore the blurred 380 MBq/kg (ranging from 155 MBq/kg to 617 MBq/kg). Even
boundaries of these two areas for metal and plastic samples. if the injected activity per body mass for repeated treatments
Results: In accordance with the common approach, the beam were roughly in the same order of magnitude, a high variability
penumbra (the distance between 80% and 20% isodoses) serves in tumor absorbed doses, ranging from 13 to 464 Gy (median:
as a parameter to determine the electron boundary scattering. 255 Gy) was observed and the mean effective half-time was
The penumbra of the beam formed by a plastic sample is on estimated as 39h in a range of 19h - 79h. Dosimetric data related
average 0.8 mm larger than that of the metal-formed one. The to tumor absorbed doses were converted into BED values
maximum difference does not exceed 1.0 mm. It is shown resulting in a mean value of 644 Gy. Conclusion: A personalized
that the dose gradient does not differ for the region between approach, combining patient-specific dosimetry, biological
5% and 100% isodose. Conclusion: The comparison of the effects examination and clinical outcome, enables the delivery
electron beam scattering at the edges of the metal and plastic of as high as possible activities that can be tolerated by patients.
collimators shows the applicability of plastic for the collimation For neuroblastoma treatments, WB and red-marrow absorbed
of 6 MeV electron beams. The greater thickness of the plastic doses could be individually prescribed, nevertheless, tumor
collimator has a negligible effect on the dose distribution. This absorbed dose values show high variability mostly depending
work is supported by the Russian Science Foundation, project on different 131I-MIBG uptakes and effective half-life in tumor
No. 18-79-10052. References: None. lesions making difficult the outcome prediction. References:
None.

EP-0221
Tumor Dosimetry And Radiobiological Study For High- EP-12
Activity 131I-mIBG Therapy In The Management Of
Refractory/Relapsed Neuroblastoma
Clinical -> Diagnostic study -> Adult study
C. Polito1, B. Cassano1, E. Genovese1, M. Longo2, S. Donatiello1, T.
-> Non-oncology study -> Endocrinology ->
Insero1, S. Valeri1, M. F. Villani1, A. Castellano1, M. C. Garganese1, V.
Endocrinology, benign
Cannatà1;
1
IRCCS Bambino Gesù Children’s Hospital, Rome, ITALY, October 12 - 16, 2019 e-Poster Area
2
Arcispedale Sant’Anna Hospital, Ferrara, ITALY.

EP-0222
Aim/Introduction: Neuroblastoma is the most common SPECT/CT with 99mTc-MIBI in Diagnosing Primary
paediatric neuroendocrine solid tumor. The tandem high Hyperparathyroidism
activity therapy based on two administrations of 131I-meta- P. O. Rumyantsev1,2, K. Slaschuck1, M. Degtyarev1, S. Serzhenko1, A.
iodobenzylguanidine (131I-mIBG) is a modality of treatment Trukhin1, Y. Sirota1, P. Nikiforovich1, M. Sheremeta1, O. Baranova1;
now largely employed for patients having a wide range of 1
Endocrinology Research Center, Moscow, RUSSIAN FEDERATION,
tumor burdens and disease sites. The purpose of this study is 2
Endocrinology Research Centre, Moscow, RUSSIAN FEDERATION.
to report dosimetric data on tumor absorbed doses in patients
affected by neuroblastoma and to investigate on the biological
effects associated to 131I-MIBG tandem therapy thorough Aim/Introduction: Accurate anatomic localization of
biologically effective dose (BED) evaluation. Materials and independent hyperfunctioning parathyroid glands allows
Methods: This study included 28 131I-MIBG administrations performing radical surgery. SPECT/CTwith 99mTc-sestamibi
given to 14 enrolled patients (with age varying from 4 to 20 (99mTc-MIBI) provides three-dimensional visualization of any
years) treated for relapsed/refractory high risk neuroblastoma. hyperfunctioning gland(s) localized in the neck or mediastinum.
All patients were treated twice (the mean interval between both In addition to surgical anatomy, the method allows evaluating
administrations ranged from 15 to 21 days). The whole-body the metabolic activity of hyperfunctioning parathyroid glands.
(WB) absorbed dose resulting from the first administration was Materials and Methods: Assessment of SPECT/CT diagnostic
used to determine the activity to inject during the second one in value in HTP visualization and improvement of management
order to reach a total WB absorbed dose of 4 Gy. Absorbed dose algorithms in patients with HTP. Results: Prospective study
to tumors having detectable 131I-MIBG uptake and measurable included 110 patients aged 21 - 80 years (mean age 57.1±2.7).
masses (evaluated through CT and MRI images) were calculated Female to male ratio was 10:1. The follow-up period ranged
by conjugate-view planar imaging. In order to investigate the from 3 to 24 months, the mean being 6 months. In all cases of
biological effects induced by high-activity 131I-MIBG therapies biochemically confirmed HTP, the average preoperative levels
and to acquire suitable information for patient tailored were: Ca total - 2.85±0.05mmol/l; Ca ionized - 1.4±0.03mmol/l,
therapy, a BED analysis was performed. The α/β radiobiological PTH=196±52pg/ml; 25OH-VitD=23.3±4.7ng/ml. Scintigraphy
parameter value considered in this study was 13.08 Gy as found was performed with SPECT/CT (GE model 670 NM/CT).
in literature for neuroblastoma, a kind of tumor having high Ultrasonography (US) was done with Voluson E8 (GE) by means
cellular radiosensitivity. Results: The median value of injected of 10MHz linear probe. Conclusion: The exact localization
S485 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

of hyperfunctioning parathyroid gland was identified in 102 11 vs. analog: 8; p>0.05). Parathyroidectomy was performed in
(92.7%) out of 110 patients by means of SPECT/CT combined all patients, demonstrating solitary OPa in 82% of the patients.
with neck US. All 102 patients had surgery, with the diagnosis In the 3 patients with digital PET+ and analog PET-, all lesions
being confirmed by histological examination: 90 adenomas were <10 mm. Moreover, in the patients with OPa confirmed
(88%), four of which were multiple tumors from 2 to 4 by pathology the elevated baseline preoperative parathyroid
parathyroid glands. 6 (6%) patients had hyperplasia; 4 (4%) hormone plasma levels decreased 10 minutes after the
patients had parathyroid carcinoma; 2 (2%) patients had atypical parathyroidectomy (16.6 pmol/L ± 11.4 pmol/L vs. 2.8 pmol/L
adenomas. HPT coexisted with papillary thyroid cancer, mostly ± 3.3 pmol/L). Improved imagen quality in the digital over
microcarcinomas, in 6 patients. Ca and PTH levels normalized the analog PET/CT was observed in 82% of the patients. The
in all 102 (100%) operated patients; the other 8 patients are still percentage of interrater concordance of detectability of OPa
under observation. The accuracy of neck US, planar SPECT and between both systems was 98%, with a high measure agreement
SPECT/CT methods in HPT visualization was 83.6%, 90.9, and between the observers (κ=0.9; p <0.0001). Conclusion: Digital
97.3%, respectively. Specificity of all methods was similar - 80%, PET/CT offers improved detectability and image quality in the
while sensitivity was 84%, 92%, and 99%, correspondingly. PPV assessment of occult parathyroid adenoma in patients with
was comparable (97.7%, 97.9%, and 98%). However, NPV was primary hyperparathyroidism. References: None.
33.3%, 50%, and 88.9%, respectively. References: The study
demonstrates that SPECT/CT is the most accurate method
(97.3%) when combined with neck US. Modern intraoperative EP-0224
navigation techniques (gamma-probe and ICG-fluorescence) An evaluation of a new TripleSPECT+ protocol for
help to provide precise surgical removal of hyperfunctioning localisation of surgically proven parathyroid lesions, with
parathyroid gland(s). Further accumulation of clinical data and assessment of both conventional and surface rendered
their advanced analysis are underway. image review
H. Ilyas1, H. Ahmad1, S. Hafeez2, J. Fowler1;
1
Guy’s and St.Thomas’ NHS Foundation Trust, London, UNITED
EP-0223 KINGDOM, 2Darent Valley Hospital, Dartford, UNITED KINGDOM.
Digital PET/CT with 18F-Fluorocholine improves the
detection of Occult Parathyroid Adenoma
D. A. Lopez Mora1, M. Sizova1, A. Flotats1, V. Camacho1, A. Aim/Introduction: To assess effectiveness of a TripleSPECT+
Fernandez1, F. Fuentes-Ocampo1, J. Duch1, A. Domenech1, J. Perez2, protocol in correctly localising parathyroid lesions compared
A. Moral2, M. Estorch1, I. Carrio1; to the original Planar+ protocol. Materials and Methods:
1
Nuclear Medicine Department. Hospital de la Santa Creu i Sant Retrospective study with analysis of parathyroid scintigraphic
Pau, Autonomous University of Barcelona, Barcelona, SPAIN, scans in sequential patients with surgically proven parathyroid
2
Department of Surgery. Hospital de la Santa Creu i Sant Pau, lesions. 30 patients scanned performed before and 30 after the
Autonomous University of Barcelona, Barcelona, SPAIN. introduction of the new TripleSPECT+ protocol were evaluated.
The original Planar+ protocol: 400MBq intravenous 99mTc-MIBI
with early and late planar images reviewed by the reporting
Aim/Introduction: To compare the detectability of occult physician who could request additional studies: SPECT, SPECT/
parathyroid adenomas (OPa) and image quality between CT and/or 80MBq pertechnetate thyroid planar scan. The
digital and analog 18F-Fluorocholine PET/CT in patients new TripleSPECT+ protocol: 40 MBq pertechnetate thyroid
with primary hyperparathyroidism (PHPT). Materials and SPECT study followed immediately with early MIBI SPECT after
Methods: Eleven patients (8 females; 63 ± 16 years) with PHPT 900MBq 99m Tc-MIBI injection, with delayed MIBI SPECT-CT at
(mean ± SD: parathyroid hormone 16.6pmol/L ± 11.4pmol/L; 2 hours. TripleSPECT+ datasets could be viewed conventionally
calcium 2.8pmol/L ± 0.1pmol/L) and negative (n=9) or and also be used for advanced post processing including
inconclusive (n=2) 99mTc-MIBI scintigraphy and SPECT/CT surface rendering according to the reporter’s preference.
were prospectively included from April to September 2018. Histopathology results were obtained from electronic patient
All patients, who accepted to be scanned by the two systems, records. Location of parathyroid lesions was compared with the
consecutively underwent a single day, dual imaging protocol scan report and the percentage of localised lesions in terms of
(digital and analog PET/CT) after the intravenous injection of right, left or ectopic was quantified as a percentage. For patients
18F-Fluorocholine. Three nuclear medicine physicians evaluated who were scanned according to the TripleSPECT+ protocol a
the lesion detectability identifying foci of radiotracer uptake comparison was made between those who had conventional
suspected of OPa. Image quality was assessed using a 4-point image review and those which had also been surface rendered.
scale (-1, poor; 0, fair; 1, good; 2, excellent). Differences were Results: 30 patients were scanned using the Planar+ scan, with
considered significant for a p value <0.05. Results: In 8 out of 11 53% of lesions being correctly localised (60% adenomas, 40%
patients, both systems detected OPa (PET+). The digital system hyperplasia). 30 patients were scanned using the TripleSPECT+
was positive in 3 patients (27%) in whom the analog system scan, with 80% of lesions correctly localised (60% adenomas,
did not detect OPa (PET-). There was no significant difference in 40% hyperplasia). Both protocols correctly localised adenomas
the total number of OPa detected by the two systems (digital: in 78% of cases, however when conventional image review
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S486

was performed of TripleSPECT+ studies only 55 % of adenomas target-to-background -ratios of the 130 mg adenoma for the
were correctly localised which increased to 100% when surface traditional and the CZT camera were 5.0 and 5.6, respectively.
rendered were also considered.The correct side localisation The edge artefact was faintly visible in both datasets with more
of hyperplastic glands showed wide disparity between the emphasized appearance in the CZT dataset. Conclusion: The
protocols: 17% Planar+ compared to 83 % TripleSPECT+. Surface new digital CZT gamma camera appears to improve the target-
rendering did not show any advantage with both groups to-background -ratio of the adenoma compared to a traditional
showing 83% positivity Conclusion: From this small pilot study, gamma camera. However, this improvement did not have
the new TripleSPECT+ protocol improved correct localisation any clear effect on the visual appearance of these two targets
of parathyroid lesions when compared to the Planar+ protocol representing small adenomas. Further studies are needed to find
from 53% to 80%. Inclusion of surface rendering resulted in out if careful optimization of CZT camera acquisition parameters
further improvement in adenoma localisation with 100% correct would further emphasize this difference and improve the visual
localisation. We recommend a TripleSPECT+ protocol, with appearance of an adenoma. References: None.
surface rendering being performed in cases where conventional
review is unproductive. References: None.
EP-0226
Self-comparison of 18F-FDG PET/MRI and 18F-FDG PET/CT in
EP-0225 the Detection of Functional Pituitary Microadenoma with
Does the digital CZT detector improve the results of Inconclusive MRI Findings
99m
Tc-sestamibi/123I subtraction SPECT/CT in parathyroid H. Sui, H. Wang, J. Zang, L. Lu, B. Hou, Q. Liu, Z. Zhu;
scintigraphy? Peking Union Medical College (PUMC) Hospital, Beijing, CHINA.
V. Tunninen1, M. Seppänen2, T. Noponen3,4;
1
Department of Clinical Physiology and Nuclear Medicine,
Satakunta Central Hospital, Pori, FINLAND, 2Department of Aim/Introduction: To compare 18F-fluorodeoxyglucose
Clinical Physiology and Nuclear Medicine and PET centre, (18F-FDG) positron emission tomography (PET)/magnetic
Turku University Hospital, Turku, FINLAND, 3Department of resonance imaging (MRI) and 18F-FDG PET/computed
Clinical Physiology and Nuclear Medicine, Turku University tomography (CT) in terms of image quality and lesion detection
Hospital, Turku, FINLAND, 4Department of Medical in patients with hormone-producing pituitary microadenoma.
Physics, Turku University Hospital, Turku, FINLAND. Materials and Methods: Twenty-nine patients with elevated
pituitary hormone levels but inconclusive or negative MRI
findings were recruited in this study. All patients underwent
Aim/Introduction: The major challenge in dual-isotope both brain PET/CT and PET/MRI scans after intravenous injection
parathyroid SPECT/CT with 123I and 99mTc-sestamibi is the close of 18F-FDG (5.55 MBq/Kg body weight). Then, twenty-six patients
proximity of photon energies of these isotopes combined accepted transsphenoidal adenomectomy within 2 weeks
with the limited energy resolution of a traditional gamma and pituitary microadenomas were confirmed in eighteen
camera. The aim of this preliminary phantom study was to patients by surgical and pathologic findings, including 5 with
evaluate whether the new digital CZT SPECT/CT camera with primary pituitary microadenoma and 13 with recurrent pituitary
better energy resolution improves the outcome of 123I/99mTc microadenoma. Eight of the 26 patients were lack of confirmed
-sestamibi subtraction SPECT/CT in parathyroid scintigraphy pathologic findings in pituitary microadenoma. The remain
when compared to a traditional gamma camera. Materials and three patients did not undergo surgeries. We detected the
Methods: For the purpose of this study, an antropomorphic lesion by visual analysis and the maximum standardized uptake
phantom mimicking a parathyroid patient with two small value (SUVmax) was measured. Results: For all these 18 patients
adenomas (equivalent to 250mg and 130 mg adenomas in pathologically diagnosed with pituitary microadenoma, PET/
patient) was set up. The phantom was acquired using standard MRI provided definitive diagnosis in 18/18 (100.0%) patients,
clinical protocols with Discovery NM/CT 670 CZT camera (GE while PET/CT showed obvious lesions in 16/18 (88.9%) patients.
Healthcare, Tirat Hacarmel, Israel) and with Symbia T6 SPECT/ The two patients with negative PET/CT findings were both
CT camera (Siemens Healthineers, Erlangen, Germany).Two recurrent. The SUVmax of 18F-FDG PET/MRI was significantly
subtraction SPECT/CT datasets were generated as in clinical correlated with that of PET/CT (P=0.000,r=0.893). The difference
practice (Hermes Medical Solutions, Stockholm, Sweden) of SUVmax between the PET/MRI and PET/CT images was of no
and will be referred as traditional dataset and CZT dataset. significance (5.4 ± 3.6 vs 4.6 ± 2.3, P=0.073). In comparison with
Subtraction images were evaluated visually on the basis of PET/CT, PET/MRI performed superiorly in the image quality, and
adenoma appearance. For quantitative analysis, target-to- it showed more precise extent of tumor and provided greater
background -ratios were calculated for both adenomas with detail in the evaluation of pituitary tumor. Conclusion: The use
phantom background area as a background. The general of PET/MRI is clinically feasible in pituitary microadenoma. Our
appearance of subtraction artefacts was also evaluated. Results: study proved that compared with 18F-FDG PET/CT, 18F-FDG
Both adenomas were clearly visible in both datasets. The PET/MRI displayed more accurate tumour location of functional
target-to-background -ratios of the 250 mg adenoma for the pituitary microadenoma undetectable or inconclusive using
analog and the CZT camera were 8.0 and 11.0, respectively. The contrast-enhanced MRI alone. References: None.
S487 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

EP-0227 Aim/Introduction: i)To evaluate the power of 18F-FCH PET/


Preoperative accuracy in parathyroid adenoma MR in primary hyperparathyroidism ii)to compare with 18F-FCH
localisation with contrast enhanced SPECT/CT PET/CT results, iii)to compare PET/MR and MR only results.
P. Sandqvist1, I. Nilsson1, P. Grybäck1, A. Sanchez-Crespo1, A. Materials and Methods: Primary hyperparathyroidism patients
Sundin2; with unlocalised disease who underwent 18F-FCH PET/MR
1
Karolinska University Hospital, Stockholm, SWEDEN, were involved. Exclusion criteria were i)secondary or tertiary
2
Uppsala University Hospital, Uppsala, SWEDEN. hyperparathyroidism ii)existence of chronic renal disease iii)
evidence of any other malignancy including thyroid and
parathyroid carcinoma. All PET/MR images were reevaluated
Aim/Introduction: Primary hyperparathyroidism is a common by a nuclear medicine physician and all MR studies by a
endocrine disease, mainly affecting elderly patients. The only radiologist blinded to the PET data. Compatibility of the results
known curative therapeutic approach is surgery. A good of PET/MR and MR studies and comparative results of PET/
preoperative localisation is an important prerequisite for MR and PET/CT in patients who also underwent PET/CT were
minimally invasive surgery. This in turn may decrease the risk investigated. Results: 34 patients (12M, 23F, mean age:49.5 ±
for postoperative complications and need of inpatient care. 13.5 min:18 max:70) were enrolled. In 17/34 patients (50%) who
The performance of multiphase contrast enhanced 99mTc- had a negative 18F-FCH PET/CT study, PET/MR was performed.
Sestamibi SPECT/CT for preoperative localisation of parathyroid In 26/34 patients (76%), 18F-FCH PET/MR was reported as
adenoma remains to be determined. In this prospective study positive. In 18/26 patients (69%), confirmation was done
we aim to compare non-enhanced SPECT/CT with multiphase histopathologically and in 2/26 patients (7%) by PTH washout.
contrast enhanced SPECT/CT. Materials and Methods: 192 6/26 patients (23%) were accepted as clinically true positive
patients were eligible between May 2015 to May 2017. The but surgery could not be performed and medical therapy
patients underwent a one-stop shop preoperative examination was started. In 8/26 (30%) patients who had a negative PET/
with multiphase (native, arterial and venous phase) contrast MR were clinically accepted as true negatives and taken under
enhanced 99mTc-Sestamibi SPECT/CT. The non-enhanced follow up. Explorative surgery was performed to none of them.
SPECT/CT image set was firstly reviewed, and findings recorded. In 23/34 patients (68%), 18F-FCH PET/MR and MR alone were
Thereafter the same procedure was made using the complete concordant (K=0,31 p<0.05). In 11/34 patients (32%), 18F-FCH
examination image set. A clinical report was written as guidance PET/MR and MR alone were discordant. In 7/11 discordant
for the surgeon. Surgical report, histopathological analysis of patients, MR findings were false positive, as confirmed by
the surgical specimen and postoperative biochemical follow histology in 4/7 and clinically in 3/7 of them. In 4/11 patients, MR
up, were used to confirm the initial parathyroid adenoma was false negative as the lesion which could not be specified as
localisation. The likelihood for correct localisation was then a parathyroid pathology with MR alone was 18F-FCH avid and
investigated with regards to adenoma weight. Results: 149 surgical resection showed a parathyroid adenoma.Sensitivity,
patients with histopathological confirmation of at least one specificity, PPV, NPV and accuracy for MR alone evaluation and
parathyroid adenoma and biochemical follow-up indicating PET/MR were found as 80%, 50%, 70%, 64%,68% and 100%, 100%,
cure, were finally included in the study. The median adenoma 100%,100%,100% respectively. 17/34 patients underwent PET/
weight was 330 mg. The overall sensitivity and specificity for MR following a negative PET/CT study. In 12/17 patients PET/MR
non-enhanced SPECT/CT were 81% and 96% respectively and was found positive. Confirmation was made by histopathology
for multiphase contrast enhanced SPECT/CT the corresponding in 7/12, washout in 2/12 and clinically in 3/12 patients. In 5/12
results were 90% (p=0.003) and 98% (p=0.077). The gain in patients, PET/MR was also negative. Conclusion: 18F-FCH PET/
likelihood for correct detection using contrast enhancement MR has an excellent performance for preoperative localisation
compared to non-contrast enhanced SPECT/CT heavily of parathyroid adenomas and PET data has an important
increases with decreasing adenoma weight. Approximately additive value over MR only imaging. 18F-FCH PET/MR may also
above 500 mg, there is no differences in probability for correct considered as an effective tool in patients whom 18F-FCH PET/
adenoma localisation between non-enhanced and contrast CT failed References: None.
enhanced SPECT/CT. Conclusion: Multiphase iodine contrast
enhanced SPECT/CT outperforms non-enhanced SPECT/CT
for preoperative localisation of small parathyroid adenomas. EP-0229
References: None. Assessment of Intrahepatic Transplantation of Islet of
Langerhans Grafts using Dynamic [68Ga]Ga-NODAGA-
exendin-4 PET Imaging
EP-0228 T. Jansen1, M. Buitinga1,2, M. Boss1, E. de Koning3, M. Engelse3, M.
Detectability Of 18F-Choline PET/MR In Primary Nijhoff3, O. Korsgren4, O. Eriksson4, M. Brom1, M. Gotthardt1;
Hyperparathyroidism With Negative Neck Ultrasound And 1
Radboud university medical center, Nijmegen, NETHERLANDS,
Tc-99m MIBI Scintigraphy 2
KU Leuven, Leuven, BELGIUM, 3Leiden University Medical Center,
M. Araz, D. Nak, C. Soydal, E. Peker, I. Erden, S. Gullu, N. O. Kucuk; Leiden, NETHERLANDS, 4Uppsala University, Uppsala, SWEDEN.
Ankara University, Ankara, TURKEY.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S488

Aim/Introduction: Patients with complicated type 1 diabetes bilateral PA as well as adrenocortical function by conventional
(T1D) and unstable glycemic control can receive islet grafts CT imaging for therapeutic management. Chemokine receptor
via intrahepatic transplantation as treatment. This procedure type4 expression elevated in aldosterone-producing tissue.
results in an improved glycemic control and quality of life. Graft We aimed to evaluate the diagnostic performance of 68Ga-
function will however deteriorate over time due to various pentixafor PET/CT targeting CXCR4 in PA patients. Materials
factors. A tool to assess transplantation success and monitor islet and Methods: We prospectively recruited twenty-five PA
survival and functionality would be of great clinical value. We patients (10 males and 15 females, 46±10 years old) in our study.
applied dynamic PET imaging with the beta cell-specific tracer All patients initially underwent adrenal regional 68Ga-Pentixafor
68
Ga-labeled exendin-4 to study the presence of transplanted imaging prior to surgery (n=24) or adrenal venous sampling
islets in T1D patients. Materials and Methods: Dynamic PET (AVS), (n=3) with follow-up time of 2-5 months. The SUVmax of
scans (60 min) were acquired after intravenous injection of lesions, lesion to liver ratio (LLR), and lesion to a contralateral ratio
[68Ga]Ga-NODAGA-exendin-4 of 5 T1D patients who previously (LCR) were calculated and correlated with pathological and AVS
underwent intrahepatic islet transplantation (Tx-group: 2 men, results as wells as patients prognosis. Operating characteristic
3 women). Graft function in these patients was biochemically (ROC) analysis was performed to determine the threshold of
proven prior to imaging with a mixed-meal tolerance test SUVmax to differentiate aldosterone-producing adenomas (APA)
(MMTT). In addition, 3 control patients that awaited islet from Non-APA. Results: Based on the visualization, 20(80%)
transplantation were imaged (2 men, 1 woman). Thresholding patients were observed increased 68Ga-Pentixafor focal uptakes.
was applied to identify areas with high hepatic tracer uptake. All patients were cured of hypertension post adrenalectomy of
Kinetic modeling was then used to measure the accumulation hot 68Ga-Pentixafor lesions. 5(20%) patients present negative
of the exendin-based tracer in these areas by determining metabolic nodules, unilateral adrenal lesions were showed on
the distribution volume. Islet function was expressed as the CT in 4 patients and 1 were bilateral. 3 (75%) patients’ symptoms
area under the curve of the measured c-peptide in the MMTT. didn’t improved after surgery guided by CT. The analysis of
Islet function was compared to the PET signal obtained from these scans revealed an overall sensitivity of 95.2%, specificity
the analysis of the dynamic PET data. Results: The average of 100%, positive (100%) and negative predictive value (80%) for
transplanted islet equivalents (IEQ: measure for islet volume) in PA patients respectively. A total of 32 adrenal lesions in twenty-
the Tx-group was 9.6*105±3.5*105. The control and Tx-group did five patients were analyzed. The mean SUVmax =18.0±9.0 of APA
not differ in age (58.7±5.5 vs. 54±9.5 years, p=0.57), BMI (24.5±4.5 was significantly elevated than unilateral or bilateral adrenal
vs. 21.8±1.4 kg/m2, p=0.57) and HbA1c (62.3±6.1 vs. 45.4±12.8 hyperplasia (3.3±1.1),(P<0.0001) and adrenal incidentaloma
mmol/mol, p=0.14). Transplanted patients had a significantly (4.4±1.1), (P=0.003). To differentiate APA from Non-APA, the
higher c-peptide production during the MMTT (22.6 vs. 151.8 threshold level of LLR ≥1.72 was associated with sensitivity
nmol.min/L, p<0.05). The distribution volume of the PET tracer (100%) and specificity (100%) and optimal cut-off of LCR ≥1.93
obtained through kinetic modeling was significantly higher in was associated with sensitivity (92.3%) and specificity (100%).
the Tx-group (0.53±0.02 vs. 0.77±0.06, p=0.036), indicating an Conclusion: 68Ga-pentixafor PET/CT might be non-invasive
increased retention of the tracer in the liver i.e. the presence of approach to detect PA lesions, as well as could distinguish
intrahepatic islets. There was no significant correlation found APA from Non-APA lesions, which representing a prognostic
in the Tx-group between Vt and IEQ, neither between Vt and classification of PA patients. References: None.
c-peptide production. Conclusion: The data of this explorative
study indicate that dynamic PET imaging using 68Ga-labeled
exendin-4 is a highly promising tool to assess intrahepatic EP-0231
transplantation of pancreatic islet grafts in T1D patients. This Assisted visual reading using semi-quantitative analysis
technique could offer the opportunity to further optimize islet of pheochromocytoma and paraganglioma (PPGL) with
transplantation protocols to improve islet survival. References: 18F-FDOPA PET/CT
None. F. L. Grisanti, M. I. Morales-Lozano, J. J. Rosales, E. Hernández-
Acero, J. F. Bastidas, C. Perdomo, J. C. Galofré, C. Salvat, J. Arbizu;
Clinica Universidad de Navarra, Pamplona, SPAIN.
EP-0230
Imaging of chemokine receptor type4 expression in
primary aldosteronism using 68Ga-pentixafor PET / CT Aim/Introduction: We aimed to define semi-quantitative
J. Ding1, L. Huo1, Y. Luo1, F. Li1, H. Xing1, A. Tong1, J. Wen1, Y. Zhang1, parameters that could help visual reading of 18F-FDOPA PET/
X. Li2, M. Hacker2; CT in the evaluation of patients with clinical, biochemical
1
Peking Union Medical College Hospital, Beijing, CHINA, and/or conventional imaging characteristics suggestive of
2
Vienna General Hospital, Vienna, AUSTRIA. pheochromocytoma or paraganglioma (PPGL). Materials
and Methods: Sixty patients (77% females, median age: 50
years [IQR 36.5-61]) with suspected PPGL and referred for
Aim/Introduction: Primary aldosteronism (PA) is the common a 18F-FDOPA PET/CT between 2011 and march 2019 were
surgically curable complication of hypertension which is retrospectively evaluated. PET scans were analysed visually
challenging to accurately differentiate unilateral PA from and semi-quantitatively by obtaining different parameters:
S489 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

Tumor SUVmax, Tumor SUVmax/SUVmean liver (TLR), and standardized thick slice containing the retrobulbar space. The
Asymmetry Index (SUVmax pathologic adrenal gland/normal clinicians mainly used this method for differentiating active
adrenal gland; AIndex). K-sample equality-of-medians test was from non-active ophtalmopathy, with 10x10-6 ID/mL as
performed to compare semi-quantitative values between PPGL threshold. We investigated the potential of quantitative SPECT/
and normal adrenal glands. Receiver operating characteristic CT by more available software and more reproducible VOI
curves were determined and areas under the curve were positioning to simplify the method. Materials and Methods:
compared for different cutoffs of each parameter. The presence SPECT projection images of twenty-six retrobulbar regions of
of a genetic predisposition was identified. Definitive diagnosis 13 patients with suspected active GO were acquired 20 min
of paragangliomas and pheochromocytomas was achieved after administering 400 MBq [Tc-99m]DTPA (128 projections x
based upon biopsy or clinical follow-up. Results: Twenty- 30 sec, 128x128 matrix with ... mm pixel size); followed by a CT
one out of 60 patients had a definitive diagnosis of PPGL (16 (120 kV, 40 mAs, 1.5 pitch, 90/min rotation with abdomen filter).
pathologically, and 5 through clinical follow-up): 26 lesions OSEM iterative reconstruction included CT-based attenuation
were paragangliomas and 9 lesions were pheochromocytomas. correction, Monte Carlo-based scatter correction, and resolution
All of the PPGL identified pathologically were positive on recovery. We drew three sets of VOIs, utilizing both SPECT and CT
18F-FDOPA PET/CT scan by visual analysis (sensitivity=100%), information. Method A: 2 cm diameter sphere to the retrobulbar
and the specificity was 87,2% due to 6 false positives (n=1: area showing the highest uptake; method B: a cone covering
adrenal hyperplasia, n=5 had subsequently normal biochemical the whole retrobulbar territory; and Method C: an 1 mL standard
tests). Median Tumor SUVmax and TLR for paragangliomas sphere to the highest activity in the retrobulbar area. The uptake
were 10.15 [IQR:6.09-17.3] and 5.81 [IQR 2.78 -8.93] respectively; was expressed as (a) activity concentration, (b) total VOI activity,
whereas for pheochromocytomas they were 10.35 [IQR:8.63- or (c) maximal concentration; each normalized to the injected
19.4] and 5.64 [IQR: 4.85-9.89] respectively. These values were dose. The same parameters were tested when normalized to
significantly higher than in normal adrenal glands (median body weight as well. For each quantitative measure Pearson’s r,
SUVmax=1.79;[IQR 1.53-2.01]; median TLR=1,14; [IQR 0.96-1.33]; and Kendall’s tau-b correlation coefficients were calculated with
p<0.01). The median AIndex was significantly was higher in the former method as reference. Results: Total and maximal VOI
pheochromocytomas (2.61; [IQR 2.27-4.05]) than in normal uptake values as well as measures corrected for body weight
adrenal glands (1.07 [IQR 1.02-1.14]; p<0.01). An AIndex > 1.57 had showed weaker correlation with the reference method than
the highest diagnostic performance for pheochromocytomas mean activity concentrations. We obtained better correlation
(sensitivity, specificity and AUC=100%). For paragangliomas, with the larger sphere (2 cm vs. 1.2 cm diameter), and even
TLR > 1.6 had a sensitivity of 100% and a specificity of 94.9% slightly better with the conical VOI. Conclusion: We found that
(AUC=0.99), while Tumor SUVmax > 2.94 had a sensitivity of defining the retrobulbar area is much easier when utilizing the
96.2% and a specificity of 94.9% (AUC=98%). Fourteen patients CT image as well. For the sake of simplicity and reproducibility,
had positive genetic testing (67%): eleven patients (78%) had we select the sphere with 2 cm diameter as the VOI of choice,
SDHD, two patients (14%) had NF-1, and one patient (7%) had since drawing the conical region is more subjective. As the
RET mutation. Conclusion: Semi-quantitative analysis assists present analysis aimed at the best correlation with the reference
the visual reading of 18F-FDOPA PET/CT by increasing the method that did not take body size into account, we plan to
diagnostic accuracy in the evaluation of PPGL. In spite of the consider activity concentration normalized to body weight
limited sample size, the AIndex is a promising parameter for the as well during the forthcoming clinical evaluation based on a
evaluation of adrenal glands in pheochromocytomas, and TLR larger patient group. References: None.
for paragangliomas. References: None.

EP-0233
EP-0232 Parathyroid Imaging With 18F-fluorocholine PET/
Quantitative retrobulbar SPECT/CT measurement in CT As A First Line Imaging Modality In Primary
Graves’ ophtalmopathy Hyperparathyroidism, A Retrospective Cohort Study
S. K. Barna1, I. Garai1, L. Galuska2, E. Nagy V.3, J. Varga2; W. Broos, M. Wondergem, R. J. J. Knol, F. M. van der Zant;
1
Scanomed Ltd, Debrecen, HUNGARY, 2Division of Nuclear Northwest Clinics, Alkmaar, NETHERLANDS.
Medicine and Translational Imaging, Department of Medical
Imaging, Faculty of Medicine, University of Debrecen, Debrecen,
HUNGARY, 3Division of Endocrinology, Department of Medicine, Aim/Introduction: 18F-fluorocholine (FCH) PET/CT is a
Faculty of Medicine, University of Debrecen, Debrecen, HUNGARY. promising technique for visualizing hyperfunctioning
parathyroid tissue in hyperparathyroidism. It is still under debate
whether to use this technique as a first line imaging modality, or
Aim/Introduction: Graves’ ophtalmopathy (GO) in to use it when conventional techniques such as 99mTc-sestamibi
immunologically active or incative state requires different scintigraphy or ultrasonography are inconclusive. This study
treatments. We have examined more than 1000 patients’ evaluates FCH PET/CT as a first line modality. Materials and
retrobulbar uptake with [Tc-99m]DTPA in the last 15 years, Methods: Patients with primary hyperparathyroidism, referred
evaluated by a custom software using manual ROIs on a between June 2015 and December 2018 for FCH PET/CT as
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S490

first line imaging method, were included in this study. Baseline between 2.5 x 5.5 mm and 7 x 11 mm. SUV max uptake values
characteristics, clinical data, scan results and type of treatment ranged from 3.4 to 12.9 with a mean of 6.7 and a median of 5.5.
were recorded. The detection rate was calculated on a per In our cohort, we detected at least one lesion in 7/7 patients
patient-based and a per lesion-based analysis. The reference (sensitivity of 100%). Pathology analysis confirmed the diagnosis
standard comprised histopathological results, intraoperative for the 4 patients who underwent surgery. Conclusion:
response to parathyroidectomy and clinical follow-up. Results: As already shown, 18F-Choline PET/CT allows to detect
Two hundred and seventy-two patients were included, of which hyperactivity of parathyroid glands before surgery. In the last 5
139 patients underwent parathyroidectomy, 47 were treated years, published studies generally described lesions above 5mm
with calcimimetics and 86 patients received further follow-up with scan duration between 2 to 10 min/bed position and dose
without active treatment. For the surgical treatment group (77% between 1.5 to 3.5 MBq/kg. In our preliminary study, PET/CT was
women and 23% men, mean age 60 years, range 29-81), the rapid and efficient, allowed to detect parathyroid adenomas
detection rate was calculated. A single adenoma was detected of less than 3 mm with a dose of 1.5 MBq/kg and 1 min/bed
in 127 scans, double adenoma in three scans, and in one scan position acquisitions. In addition, PET/CT was more sensitive
three hyperfunctioning glands were detected. In eight scans, no than ultrasound imaging modality. References: [1] Degenhardt
lesions were visualized. A total of 154 parathyroid glands were C, Rodrigues P, Trindade A, et al. Performance evaluation of a
surgically removed. Calculated patient-based detection rate was prototype positron emission tomography scanner using digital
95% and lesion-based detection rate was 90%. Conclusion: This photon counters (DPC). IEEE Nucl Sci Symp Med Imaging Conf
retrospective cohort study shows high detection rates of FCH Rec. 2012:2820-2824.
PET/CT in primary hyperparathyroidism, which is in accordance
to literature. Use of FCH PET/CT as a first line imaging modality
in preoperative planning of parathyroid surgery seems an EP-0235
appropriate choice. References: None. Association Between 18F-FDG PET/CT Findings and Bone
Mineral Densitometry Results
A. Hassanzadeh-Rad, H. Amini, M. Eftekhari, B. Fallahi, A. Fard-
EP-0234 Esfahani, A. Emami-Ardekani, D. Beiki;
18
F-Choline digital PET/CT Imaging for parathyroid Research Center for Nuclear Medicine, Shariati Hospital, Tehran
adenoma detectability University of Medical Sciences, Tehran, IRAN, ISLAMIC REPUBLIC OF.
C. Provost, R. Brahmi, C. Leite Nascimento, S. Hescot, L. Champion;
Institut Curie, Saint Cloud, FRANCE.
Aim/Introduction: Osteoporosis is a major risk factor for
skeletal fractures. Patients with malignancies are at risk for
Aim/Introduction: Primary hyperparathyroidism is a common trabecular bone loss leading to osteopenia or osteoporosis.
endocrine disorder and about 85% is caused by a solitary Hence, prompt diagnosis of osteopenia or osteoporosis has
adenoma of the parathyroid glands. In the 90s, PET modality was significant value to avoid fractures. Decreased bone marrow
introduced to increase diagnostic performance for localization of metabolism may be observed in subjects with decreased Bone
parathyroid adenoma. Several PET tracers have been evaluated Mineral Density (BMD), possibly in response to adipose tissue
and one of them, choline-based PET tracer, a precursor for deposition in the bone marrow. We aim to correlate 18F-FDG
the biosynthesis of phospholipids, appears to be promising. PET/CT findings with bone mineral densitometry results in order
In clinical practice, 18F-choline PET/CT has acquired general to suggest Dual-Energy X-ray Absorptiometry (DEXA) for some
acceptance to localize parathyroid adenoma but it remains patients. Materials and Methods: After excluding patients with
unclear whether it could replace conventional scintigraphy with major confounding variables, 105 patients referred for 18F-FDG
99mTc-sestamibi SPECT/CT. In our preliminary study, 18F-Choline PET/CT were included. Prior to FDG PET/CT study, bone mineral
is more efficient than conventional scintigraphy in parathyroid densitometry was performed by DEXA. Semi-quantitative and
adenoma diagnostic, confirmed by pathology results. Moreover, quantitative analyses were done on both DEXA and FDG PET/
digital PET/CT, equipped by new type of scintillation detector CT results. BMD, T-score, Z-score , Standardized Uptake values
and digital photon counters increased the lesion detectability (SUVmax and SUVmean) and Hounsfield Units (HUmax and
[1]. Materials and Methods: 7 patients, with a mean age of HUmean) were calculated for all three Regions Of Interest (ROIs)
73 years old [51-85], underwent 18F-Choline PET/CT because (trabecular bones of lumbar vertebrae and bilateral femoral
of inconclusive diagnostic of suspicious parathyroid adenoma necks). To find out correlation between these findings, statistical
after normal 99mTc-sestamibi scintigraphy. For 5 patients, neck analysis was performed using SPSS version 22 (SPSS Inc, Chicago,
ultrasound was performed: 3 normal and 2 suspicious. PET IL). Results: Mean SUVmax,SUVmean,HUmax and HUmean were
images were performed in Vereos digital PET/CT (Philips) with greatest in patients with normal BMD, followed by osteopenic
2.5 MBq/kg of 18F-Choline. Acquisition was centered on the and osteoporotic patients in all three ROIs ( P-values < 0.0001)
cervicothoracic region (1 min/bed position), 20 minutes after with significant positive Pearson’s correlation between SUVs and
tracer injection. Curative surgery was performed for 4 patients T-scores. Using Receiver Operating Characteristic (ROC) curve
with pathology results, and planned for 3 patients. Results: PET/ analysis, trabecular lumbar vertebrae SUVmax could distinguish
CT revealed 8 lesions in all 7 patients. Detected size lesions were group of patients with diminished BMD from normal group with
S491 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

L1-L4 SUVmax cut-off value=2.78 (sensitivity=78 %, specificity= corrections. Results were scored positive, inconclusive or
72 %, P-value < 0.0001). Considering left femoral neck negative after double blind reading and were compared to the
SUVmax=1.59, ROC curve analysis was also able to distinguish surgical and pathological findings and the biochemical follow-
two groups with normal and abnormal BMDs ( sensitivity=80 %, up. Results: PTA could be clearly detected in 25 patients (68%)
specificity=82 %, P-value < 0.0001). More or less similar results and all the location predicted by our hybrid PET/CT imaging
were obtained with HUs and SUVs of all other corresponding matched surgical findings as well as follow-up. PET was rated
ROIs. Conclusion: Findings of this study strongly suggest as negative in 9 cases and 3 patients were rated as inconclusive
meaningful positive correlations between metabolic activities or showed discordances between the two experienced readers.
of trabecular bones in lumbar vertebrae and bilateral femoral Only one of these negative patients was referred to neck
necks and BMDs of these regions. By applying SUVmax cut-off dissection at the time of writing. Histological sections revealed
values obtained in this study for all three corresponding ROIs, lymph nodes in the retro-thyroid space, but no PTA. Late PET-
18
F-FDG PET/CT may be used as a screening tool and in addition imaging showed better diagnostic performance in detecting
to main findings regarding metabolic activities of tumoral PTA (sensitivity, specificity, PPV and NPV were respectively 0.77,
lesions, those patients with corresponding SUVmax below the 1.00, 1.00 and 0.33 for early imaging and 0.88, 1.00, 1.00 and 0.50
cut-off values calculated in this study can be referred for DEXA, for late imaging). No statistically significant difference was found
leading to prompt diagnosis of trabecular bone loss and may between both readers. Conclusion: Our preliminary results
avoid osteoporotic fractures with earlier treatment. References: demonstrate the high accuracy of F18-fluorocholine PET/CT to
None. detect PTA in PHPT-patients with negative or inconclusive neck
ultrasonography and sestamibi imaging. It may replace first line
conventional imaging techniques in preoperative planning of
EP-0236 parathyroid surgery. Larger, prospective studies are needed to
Establishing F18- fluorocholine PET as a Second Line confirm these findings. References: None.
Imaging Technique in the Localization of Parathyroid
Adenomas before Surgery in Patients with Primary
Hyperparathyroidism and Negative or Inconclusive Neck EP-0237
Ultrasonography and Sestamibi Imaging Parathyroid imaging by 18F-Fluorocholine PET/MR in
S. Röck1, C. Barkhausen2, P. T. Meyer1, C. Goetz1; patients with hyperparathyroidism
1
Department of Nuclear Medicine, Medical Center of the University B. Emsen1, S. Mule1, E. Evangelista1, R. Braham2, L. Baranes1, J.
of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Chalaye1, L. Lerman1, M. Abulizi1, C. Dubouchet1, O. De Barry1, E.
GERMANY, 2EURO-PET GmbH, Medical Center of the University Calvo-Bota1, S. Sahbai1, J. Israel1, A. Luciani1, E. Itti1;
of Freiburg, University of Freiburg, Freiburg, GERMANY. 1
SyMPTOm PET/MRI platform, Henri Mondor Hospital,
Créteil, FRANCE, 2Department of Endocrinology,
Henri Mondor Hospital, Créteil, FRANCE.
Aim/Introduction: Localization of pathologic parathyroid
glands in patients bearing primary hyperparathyroidism (PHPT)
is recommended before carrying out targeted minimal invasive Aim/Introduction: We sought to evaluate the diagnostic
surgery in single parathyroid lesion thus potentially reducing the performance of 18F-Fluorocholine (FCH) PET/MR imaging to
durations of surgery and the rate of complications. Preoperative identify parathyroid glands in patients with hyperparathyroidism
localization may also prevent failures of surgical treatment (PHPT). Materials and Methods: 13 patients with PHPT were
related to multiglandular disease or ectopic parathyroid retrospectively included. PET/MR images were acquired on a
glands. Our aim was to investigate the accuracy of a choline- Biograph mMR scanner (Siemens, Erlangen, Germany), 10 min
based tracer in localizing parathyroid adenoma (PTA) in case of after injection of 4.5 MBq/kg FCH, and consisted of 2 emission
negative or inconclusive ultrasound and scintigraphic results. steps over the neck and chest for 15 min; simultaneously,
Materials and Methods: A total of 37 patients (mean age 64 MR imaging included T1 and T2 (STIR) weighted sequences,
+/- 13 years, 70% female) biochemical diagnosed with PHPT and diffusion weighted sequences, and post-gadolinium T1 (VIBE)
referred in our institution to localize PTA were retrospectively enhancement. Results were interpreted blindly by a radiologist
pooled. All included patients underwent neck ultrasonography and a nuclear medicine physician. Some patients already had
and Tc99m-MIBI imaging prior to PET. Both methods failed a dual-isotope 123I/99mTc-sestaMIBI parathyroid scintigraphy
to detect a PTA and an additional F18-fluorocholine PET with (n = 8) or/and neck ultrasonography (US) (n = 13). In some
subsequent low-dose CT was performed before allowing a instances, FCH PET/MR was performed after inconclusive or
focused surgical approach. Mean Parathyroid hormone level discrepant results between these two modalities. Results:
were 134 pg/ml and Calcium 2.68 mmol/l. Early (15 minutes Average [extremes] patient age, calcium level and parathyroid
p.i.) and late (60 minutes p.i.) PET-images of the neck and hormone (PTH) level were 71 years [58-91], 2.82 mmol/L [2.53-
upper mediastinum were acquired after injection of 165 +/- 26 3.45] and 118.89 ng/L [34-277], respectively. A positive PET (i.e.
MBq F18-fluorocholine (Vereos Digital PET/CT, Philips Medical identification of abnormal FCH uptake) was found in 9 patients
Systems B.V., Eindhoven, The Netherlands) and iteratively (69%), with an average SUVmax of 4.5 [2.6-9.1]. Only 4 patients
reconstructed using PSF-modeling, scatter and attenuation underwent a parathyroidectomy, confirming the results of
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S492

PET. Higher parathyroid uptake was observed compared to slices reconstructed from SPECT data and its results were visually
physiological thyroid uptake (SUVmax = 2.96 [2.0-4.1], P = 0.01). compared with the results of routine interactive subtraction
Among the 9 positive PET, only 4 were positives on MR after procedure. Results: In 15 patients, there was an agreement
blinded interpretation, but second unblinded interpretation between visual assessment of PCA and standard difference
(in view of the PET results) allowed the radiologist to identify images. Seven clearly positive findings were easily recognized
the remaining 5 parathyroid glands. No case of positive MR but with PCA, too. In 8 equivocal findings (low uptake, small lesions,
negative PET was observed. No case of ectopic mediastinal tissue overlaps, residual misregistration artefacts) PCA did not
focus of uptake was observed. In only one patient, we founded help to resolve the problem producing equivocal results either.
2 foci of abnormal uptake. PET was positive in 37.5% of patients Visual assessment of interactively subtracted images seemed
with a negative sestaMIBI scintigraphy and in 66.7% of patients to be somewhat less sensitive to misregistration while PCA was
with negative US. Among the 3 patients with both negative much faster without any user interaction. Conclusion: In a pilot
sestaMIBI and US, PET was positive in 2 cases. A trend for higher study, diagnostic information obtained from PCA was equivalent
PTH level was observed with positive PET (P = 0.05), whereas to that obtained by interactive subtraction procedure. Good
no significant difference was observed between calcium level performance of both methods requires perfect registration
and PET results (P = 0.40). No correlation was found between of input images. Image features extracted automatically by
calcium or PTH levels and intensity of parathyroid uptake PCA are potentially useful in machine learning. Performance
identified on PET. Intensity of physiological thyroid uptake did of machine learning procedures in double-tracer parathyroid
not depend on the delay between injection and beginning of scintigraphy will depend on their ability to differentiate residual
PET acquisition (P = 0.68). Conclusion: FCH PET/MR appears to misregistration artefacts from pathological uptake of the tracer
be a suitable imaging tool for the evaluation of PHPT, particularly in one of the two images. References: None.
in patients with a negative dual-isotope 123I/99mTc-sestaMIBI
scan. References: None.
EP-0239
Molecular Imaging to the surgeons rescue: 68Gallium-
EP-0238 DOTA-exendin-4 PET/CT in pre operative localisation of
Unsupervised Image Subtraction in Parathyroid Insulinomas
Scintigraphy as a Prerequisite for Machine Learning P. U N, D. B Sen, D. Thakral;
I. Marikova1,2, J. Trnka1,2, D. Chroustova1,2, D. Zogala1,2, M. Samal1,2; Fortis memorial research institute, Gurgaon, INDIA.
1
Charles University, 1st Faculty of Medicine, Prague, CZECH
REPUBLIC, 2General University Hospital, Prague, CZECH REPUBLIC.
Aim/Introduction: Insulinoma is an islet-cell adenoma that
secretes insulin. It is usually localized to the pancreas and is often
Aim/Introduction: Despite progress in imaging techniques the most common cause of endogenous hyperinsulinemic
and image processing, detection of parathyroid adenomas hypoglycaemia in non-diabetic adult patients. Surgical excision
remains challenging. Therefore the examination is an obvious with a curative intent is the standard modality of treatment,
candidate for testing the machine learning approach using and it requires precise localization of tumor tissue. 68Gallium-
k-means clustering and classification methods. A prerequisite DOTA-exendin-4 PET/CT scan is a clinically reasonable and
for machine learning is to select the features with good sensitive scan for the identification of insulinoma. The aim of
predictive power. The aim of our study was to test principal this retrospective study was to determine the overall accuracy
component analysis (PCA) of double-tracer parathyroid of 68Gallium-DOTA-exendin-4 PET/CT scan in the detection
scintigraphy for automatic subtraction of 99mTc-pertechnetate of insulinoma. Materials and Methods: Eight patients with
from 99mTc-MIBI images. Our hypothesis was that PCA will fasting hyperinsulemic hypoglycaemia with neuroglycopenic
emphasize differences between the two images regardless of symptoms were enrolled in this study. Whole body PET/CT
their different scaling. Materials and Methods: In a pilot study, scan was performed on a Philips time of flight PET/CT scanner,
we have examined data of sequential double-tracer parathyroid 60 minutes after injection of 68Gallium-DOTA-exendin-4. The
SPECT in 15 consecutive patients selected from a database. imaging findings were compared to the histopathological
Before principal component analysis, the data were registered diagnosis in six out of eight patients and to subsequent follow
in 3D using in-house written software. Principal component up in the remaining two patients who did not undergo surgery.
analysis was performed in Matlab (www.mathworks.com). With Results: The sensitivity and specificity of 68Gallium-DOTA-
the two input images (99mTc-MIBI and 99mTc-pertechnetate), Exendin-4 PET/CT scan in insulinoma detection was found to
PCA results in two principal components (PC). In fact, it rotates be 75% and 100% respectively. Overall accuracy was 87.5%.
original image coordinates (the axes of the graph with pixel Conclusion: 68Gallium-DOTA-Exendin-4 PET/CT scan is highly
values of the two images plotted against each other) in such a sensitive for identification and exact localization of insulinoma
way that the first PC approximates the average image and the which can guide better surgical exploration. However
second PC the differences between the two original images. randomised controlled trials are needed to assess the accuracy
An advantage of PCA is that ‘subtraction’ does not need user of 68Gallium-DOTA-Exendin PET/CT scan in localization of
interaction. PCA was applied to transversal, frontal and sagittal insulinoma. References: None.
S493 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

EP-0240 Choline PET/CT in parathyroid imaging: a systematic review.


Optimizing 18F-Fluorocholine PET/CT procedures in Broos WAM1, van der Zant FM, Knol RJJ, Wondergem M.
parathyroid imaging: a proposal
I. Bossert1, M. Hodolic2,3, S. Chytiris4, D. D’Ambrosio5, A. Marchetto1,
C. Vellani1, L. Croce4, B. Rivolta6, L. Chiovato4, G. Trifirò1; EP-13
1
Nuclear Medicine Unit, Istituti Clinici Scientifici Maugeri Spa SB
IRCCS, Pavia, ITALY, 2Nuclear Medicine Research Department, Iason,
Clinical -> Diagnostic study -> Adult study
Graz, AUSTRIA, 3Nuclear Medicine Department, Faculty of Medicine
-> Non-oncology study -> Endocrinology ->
and Dentistry, Palacký University, Olomouc, CZECH REPUBLIC,
Thyroid, benign
4
Unit of Internal Medicine and Endocrinology, Istituti Clinici
Scientifici Maugeri Spa SB IRCCS, Pavia, ITALY, 5Medical Physics October 12 - 16, 2019 e-Poster Area
Unit, Istituti Clinici Scientifici Maugeri Spa SB IRCCS, Pavia, ITALY,
6
Endocrinology Unit, Istituto Clinico Città di Pavia, Pavia, ITALY.
EP-0241
Patients with Hashimoto Nodular Goiter: Relation to
Aim/Introduction: Identification of pathological parathyroid Differentiated Thyroid Carcinoma and Outcome
glands in primary hyperparathyroidism, traditionally based on J. Mihailovic, J. Roganovic, V. Cimbaljevic, D. Stojanovic;
neck ultrasound (US) and/or 99mTc-SestaMIBI (MIBI) scintigraphy, Institute of Oncology, Sremska Kamenica, SERBIA.
is often challenging. PET/CT with 18F-Fluorocholine (FCH) can
improve detection of pathologic parathyroid glands, thanks to
its better spatial resolution and lesion-to-noise ratio with respect Aim/Introduction: To analyze patients with Hashimoto
compared to MIBI scan. Currently, Authors apply different nodular goiters, the relation between autoimmune disease and
protocols, with variations in administered activity, scanning time differentiated thyroid carcinoma (DTC) and outcome of DTC.
and bed time duration. The aim of our study was to propose a Materials and Methods: This retrospective study included
protocol for the FCH-PET/CT imaging which can optimize every 4447 patients with thyroid nodules who were treated in a
variable preserving the good quality of the exam. Materials single institution between 2007 and 2018. Out of 4447 patients
and Methods: We reviewed the literature of the past 4 years who underwent surgery, 700 were histologically confirmed as
about FCH PET/CT in parathyroid imaging. On the basis of differentiated thyroid carcinoma (DTC), while 158/700 (22.6%)
these results and of our PET/CT scanner (DIscovery 690 VCT, DTC patients had Hashimoto thyroiditis. Median patients’ follow-
GE Healthcare) we decided to inject less than 2,5 MBq/kg of up was 51.5 months (range, 2-134 months). A multivariate
FCH, perform a dual-time point PET/CT acquisition at 15 and 60 logistic regression analysis was used to analyze the Hashimoto
minutes after the injection with a duration of 3 minutes per bed thyroiditis as a predictive factor for thyroid malignancy. Results:
(neck and upper mediastinum), and to skip dynamic acquisition. Among 700 DTC patients, 158 (22.6%) patients had autoimmune
To test our method we plan to enroll 50 patients with primary disease [140 (88.6%) females and 18 (11.4%) males; <45 years=
o tertiary hyperparathyroidism and negative or inconclusive 33 (20.9%), ≥45 years=125 (79.1%) patients; mean age 57.8
conventional sestaMIBI scan. PET results will be confirmed with years, (range, 22-88 years). All DTC patients underwent total
cito-hystological examination whenever possible. Results: We thyroidectomy. Radioiodine therapy was applied in 45/158
noticed a high eterogenity about injected activity, timing and (28.5%) patients, once or in several course if needed, according
protocol acquisition in literature. Until now, we prospectively to the Tumor Board decision. Cumulative activity of I-131 ranged
enrolled 16 patients. We administered a median activity of FCH between 3.7-22.2GBq. The significant independent predictors
of 2,3 MBq/kg (range 2,1-2,46), for a median amount of activity of thyroid malignancy are: gender (p<0.001), age ≤45 years
of 173,6 MBq per patient (range 112,9-246,7). FCH-PET/CT was (p<0,001), and Hashimoto thyroiditis (p= 0.035). At the last follow
positive in 15 out of 16 patients. One patient had bilateral up, all patients were alive. Complete remission was achieved
lesions (patient undergoing dialysis) and 1 patient had a focal in 111 (70.3%) patients, partial remission in 5 (3.2%) patients,
FCH uptake in the supero-anterior mediastinum. So far only two stable disease in 3 (1.9%) patients, and proggressive disease
patients had a cito-hystological confirmation of FCH PET result. in 39 (24.6%) patients. There were no disease-related deaths.
Conclusion: Although we have a small number of patients, Conclusion: Gender, age and Hashimoto thyroiditis are strong
our method showed a good sensitivity allowing a reduction in independent predictors for thyroid malignancy in patients
patient’s dose and exposure, bed time duration and avoiding with thyroid nodules. Adequate diagnostics is necessary in
dynamic acquisition, resulting in an easier patient’s management. patients with thyroid nodules, in particular in males, elderly and
References: - J Endocrinol Invest. 2019 Apr;42(4):419-426. doi: Hashimoto thyroiditis. If treated properly, DTC patients related
10.1007/s40618-018-0931-z. Epub 2018 Aug 9.PETC/CT with to Hashimoto nodular goiter have good prognosis, survival and
18F-Choline localizes hyperfunctioning parathyroid adenomas outcome. References: 1. Jonklaas J, Sarlis NJ, Litofsky D, et al.
equally well in normocalcemic hyperparathyroidism as in overt Outcomes of patients with differentiated thyroid carcinoma
hyperparathyroidism.Bossert I, Chytiris S, Hodolic M, Croce L, following initial therapy. Thyroid 2006;16:1229-1242. 2. Haugen
Mansi L, Chiovato L, Mariani G, Trifirò G. - Nucl Med Commun. BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, et al.
2019 Feb;40(2):96-105. doi: 10.1097/MNM.0000000000000952. 2015 American Thyroid Association Management Guidelines
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S494

for Adult Patients with Thyroid Nodules and Differentiated clinical hypothyroidism and hyperthyroidism compared to
Thyroid Cancer. The American Thyroid Association Guidelines control postpartum women. Conclusion: Significantly higher
Task Force on Thyroid Nodules and Differentiated Thyroid percentage of T regs in normal pregnancy indicates that these
Cancer. Thyroid 2016;26:1-133. 3. Sawka AM, Brierley JD, Tsang cells have a central role in regulating immune responses
RW, Thabane L, Rotstein L, Gafni A, Straus S, Goldstein DP. An during pregnancy. Furthermore, our results suggest that T regs
updated systematic review and commentary examining the might be the key players in inducing the immune tolerance
effectiveness of radioactive iodine remnant ablation in well- mechanisms in pregnant and postpartum women with AITD.
differentiated thyroid cancer. Endocrinol Metab Clin North Am References: None.
2008;37:457-480.

EP-0243
EP-0242 Diagnostic Algorithm for Assessment of Papillary Thyroid
The Role Of Regulatory T Cells In Pregnant And Carcinoma in Presence of Hashimoto Thyroiditis
Postpartum Women With Autoimmune Thyroid Disease V. Sukhov1, K. Zaplatnikov2;
T. Bogovic Crncic1, S. Grbac Ivankovic1, N. Girotto1, I. Mrakovcic 1
NRCEM, St.Petersburg, RUSSIAN FEDERATION, 2MAZ
Sutic2; Nuclear Medicine Clinic, Nürnberg, GERMANY.
1
Dept. of nuclear medicine, Clinical Hospital Centre,
Rijeka; University of Rijeka, School of Medicine, Rijeka,
CROATIA, 2Dept. of physiology and immunology, University Aim/Introduction: Papillary thyroid carcinoma (PTC) is not
of Rijeka, School of Medicine, Rijeka, CROATIA. infrequently diagnosed yet not very aggressive form of thyroid
cancers, especially in iodine-deficient areas. Hashimoto
thyroiditis (HT) is a frequent autoimmune thyroid disease,
Aim/Introduction: Regulatory T cells (T regs) are a subtype known to be the most common cause of hypothyroidism in
of the adoptive immune cells that have unique immune nonendemic goiter areas. Coexistence of these two diseases
modulating capabilities and play a central role in regulation of is possible but not often; although such cases are especially
autoimmunity. These cells actively control, induce or suppress difficult for diagnostics in presence of so-called ,,gray zones“:
the function of other immune cells. The aim of our study was to many hypoechogenic pseudonodules in HT, and poorly-
investigate the changes of T regs in pregnant and postpartum differentiated PTC can show concurrent cancer types with foci
women with autoimmune thyroid disease (AITD) and to compare of high grade changes (necrosis, focal loss of papillary-type
the results to normal pregnancy and postpartum. Materials nuclei, and foci with overall aberrant morphology). The fine
and Methods: The study included 185 pregnant women with needle aspiration is not possible for all patients, so we tried to
no prior history of thyroid disease; 111 women in 1. half of establish algorithm for differential diagnosis. Materials and
pregnancy (6-20 weeks), 74 in 2. half of pregnancy (21-36 weeks) Methods: Patients with PTC/HT(+) (Gr.A, n=27) and PTC/HT(-
and 77 women in postpartum period (3 weeks-9 months after ) (Gr.B, n=32) were prospectively studied. We analysed age,
delivery). Peripheral blood and sera obtained from women were sex, location, clinical data, tumor dimensions, angioinvasion,
screened for thyrotropin, free thyroxine, free triiodothyronine capsular infiltration, multifocality and lymphnode metastases,
values, titres of thyroid peroxidase and thyroglobulin therapy history by means of consequentially performed clinical
autoantibodies as well as thyrotropin receptor stimulating examination, thyroid hormone (fT4, fT3, TSH) and anti-TPO/
antibodies. According to laboratory findings women were anti-Tg antibodies levels assessment, thyroid sonography with
divided into 9 groups: normal pregnancy, normal postpartum Doppler DS, 99mTc-scitigraphy, MIBI-scitigraphy and FNAC. Every
women, euthyroid pregnant and postpartum women with case of PTC was confirmed by patho-histological examination.
AITD, pregnant women with autoimmune subclinical/clinical Results: Statistically significant (P=0.001) difference in tumour
hypothyroidism and subclinical/clinical hyperthyroidism size was found in two Groups: the average diameter was found
in pregnancy and postpartum and nonpregnant controls. to be 1.721+/-0.5812 and 1.145+/-0.871 cm in Gr.A and in Gr.B,
Peripheral blood mononuclear cells were separated from blood respectively. Capsular infiltration was present only in Gr.A in 3
samples by gradient centrifugation. Simultaneous staining of cases. The angioinvasion was found in 8 cases of Gr.A and 1 cases
surface antigens on lymphocyte subpopulations was performed in Gr.B (P=0.310). Multifocality was found in 19 patients in Gr.A
and analysed on fluorescence-activated cell sorter (FACS): and in 2 in Gr.B (P=0.0009). There were no statistical differences
CD4+CD25+FoxP3. Results: The percentage of T reg cells was in sex (P=0.423) and age (P=0.330). All pts in Gr.A expressed
significantly higher in normal pregnancy and in euthyroid high levels of thyroid Abs. 51.5% Abs+ pts with US suspicious
pregnant women with AITD compared to nonpregnant women. multifocal non-uniform thyroid goiter revealed scintigraphic
Furthermore, the percentage of T regs was significantly higher cold lesion, in Gr.B 60% nodes were undetectable in scans.
in 1. and 2. half of pregnancy in women with autoimmune Informativity of 33% of Gr.A pts MIBI-scans was low for focal
subclinical/clinical hypothyroidism and hyperthyroidism uptake by reason of high background in thyroid tissue and all
compared to normal pregnancy. The percentage of T regs was pts of Gr.B had distinctive foci with retention at delayed images.
also significantly higher in euthyroid postpartum women with More than 50% of Gr.A pts had nodules with histologicaly proven
AITD and in postpartum women with autoimmune subclinical/ features of poorly-differentiated (solid variant) PTC. Conclusion:
S495 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

We justified necessity of screening for PTC in population with EP-0245


concomitant HT, as potentially predisposable for malignization Тhe Role of Pertechnetate Thyroid Scintigraphy in the
and assuming them to have more aggressive tumors. Combined Initial Workup of a Thyroid Diseases
data of clinical and laboratory examination, US with Doppler, T. Andjelkovic, F. Velickovic, M. Rajic, M. Stevic, M. Vlajkovic;
99mTc- and MIBI-thyroid scans, US guided FNAC (in some cases) Center of Nuclear Medicine, Clinical center Nis, Nis, SERBIA.
will guarantee a precise diagnosis. References: None.

Aim/Introduction: With the emergence of new echosography


EP-0244 techniques accompanied by a thin needle biopsy, Tc-99m-
The Incidence of Thyroid Nodules Incresases with Age in perthnetate scintigraphy of the thyroid gland has lost its
Women of Reproductive Age diagnostic primacy even though it is still almost routinely
K. Zaletel1, E. Pirnat1, T. Ušaj2, K. Tuta2, K. Bajuk Studen1, N. indicated in patients with thyroid gland diseases.The aim of
Bedernjak Bajuk1, M. Jesenko1, N. Ostaševski Fernandez1, S. this paper was to analyze the diagnostic contribution of the
Gaberšček3; findings obtained by the Tc-99m-perthnetate scan in patients
1
Department of Nuclear Medicine, University Medical Centre who are referred to thyroid gland scintigraphy during the
Ljubljana, Ljubljana, SLOVENIA, 2Faculty of Medicine, University initial workup. Materials and Methods: We retrospectively
of Ljubljana, Ljubljana, SLOVENIA, 3Department of Nuclear analyzed the findings of 350 subjects, 296 women and 54 men
Medicine, University Medical Centre Ljubljana; Faculty of aged 56.4 ± 13.4 years in whom scintigraphy with Tc-99m-
Medicine, University of Ljubljana, Ljubljana, SLOVENIA. perthnetate was indicated for the first time due to suspected
thyroid gland disease. Ultrasound examination of the thyroid
gland was performed in all subjects, as well as some of the
Aim/Introduction: By ultrasound examination, thyroid nodules following laboratory analyses: thyrotrophic hormone, free
are found in 19 to 65% of unselected individuals. In the older age thyroxin, thyroid-peroxidase and thyroglobulin antibody,
groups, the incidence of thyroid nodules increases with age. In thyroglobulin, calcitonin. Results: Multinodular goiter was
the younger age groups as well as in pregnant women, data on the most commonly obtained scintigraphy finding on Tc-
the incidence of thyroid nodules is scarce. The aim of our study 99m-pertechnetate scan, as it was diagnosed in 164 patients
was to establish the incidence of thyroid nodules in pregnant (46.9%), in 103 of whom the findings had additional diagnostic
and non-pregnant women of reproductive age. Materials significance. In all 17 examinees (4.9%) with autonomous
and Methods: In this prospective clinical study we included thyroid nodules findings and 26 (7.4%) with diffuse toxic goiter,
142 pregnant and 306 non-pregnant female volunteers of the scintigraphic finding were useful for deciding on the
reproductive age. Women with the known thyroid disease were further treatment either by radioiodine therapy or by surgery.
not included in the study. In every volunteer, thyroid ultrasound Solitary cold nodules were detected in 87 subjects (24.9%), in
was performed using a 7.5-MHz linear transducer. The number 82 of whom scintigraphic findings had additional diagnostic
of volunteers with thyroid nodules was detected. Results: significance for the evaluation of the nature of the nodules. Five
Pregnant women were significantly older than non-pregnant subjects were diagnosed with smaller, insignificant nodules. An
women (32.9±5.1 and 29.8±7.1 years, respectively, p<0.001). “empty” scintigram was detected in 10 subjects (2.9%) and all
Thyroid nodules were detected significantly more frequently scintigraphy was of great significance for the confirmation of
in pregnant than in non-pregnant women (21.2% and 12.7%, either subacute or amiodarone caused thyroiditis. Microscopic
respectively, p=0.032). Furthermore, in the larger group of nodular goiter was detected in 46 subjects (13.1%) and the
non-pregnant women of reproductive age, the frequency of scan results showed additional diagnostic significance only in
thyroid nodules significantly increased with age (p<0.001). In 18 patients. In the total of 256 subjects (73.1%) with thyroid
the age group up to 24 years, thyroid nodules were detected in gland diseases the Tc-99m-pertechnetate scan had additional
4.1% of women, in the age group 25-30 years, thyroid nodules diagnostic significance in the initial workup. Conclusion:
were detected in 7.2%, in the age group 31-35 years, thyroid The results of this study have shown that the scintigraphy Tc-
nodules were detected in 12.7%, and in the age group above 99m-pertechnetate scintigraphy continues to be significant
35 years, thyroid nodules were detected in 31.2% of women. in the initial diagnostics of thyroid gland diseases. This simple
Conclusion: Our results show that the incidence of thyroid procedure provides valuable information for reaching the final
nodules in women of reproductive age significantly increases diagnosis as well as making the decision concerning additional
with age. With the increasing age of pregnant women, beside testing or thyroid gland diseases treatment. References: None.
Hashimoto’s thyroiditis also thyroid nodules may represent a
challenge in the screening strategy. References: None.
EP-0246
Ectopic Thyroid Glands - Presentation of Six Cases with
Diagnostic and Therapeutic Approach
T. Jukic1,2, I. Mihaljević3, I. Blažeković4, M. Ivkić5, M. Franceschi1,2;
1
University Department of Oncology and Nuclear Medicine,
Sestre Milosrdnice University Hospital Centre, University of
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S496

Zagreb, School of Medicine, Zagreb, CROATIA, 2Faculty of EP-0247


Medicine Osijek, Josip Juraj Strossmayer University of Osijek, Scintigraphic findings in a patient with hyalinizing
Osijek, CROATIA, 3Clinical Institute of Nuclear Medicine and trabecular tumour of the thyroid
Radiation Protection, University Hospital Osijek , Faculty of J. Baumgarten, C. Happel, K. Jung, D. Gröner, A. Sabet, F. Grünwald;
Medicine Osijek, Josip Juraj Strossmayer University of Osijek, University Hospital Frankfurt, Frankfurt, GERMANY.
Osijek, CROATIA, 4University Department of Oncology and
Nuclear Medicine, Sestre Milosrdnice University Hospital Centre,
Zagreb, CROATIA, 5Unimedic Centre, Zagreb, CROATIA. Aim/Introduction: Hyalinizing trabecular tumors (HTT) of the
thyroid are relatively rare and mainly benign neoplasms.The lack
of defined scintigraphic characteristics as well as the considerable
Aim/Introduction: Ectopic thyroid gland is a rare entity. It resemblance to malignant entities in both ultrasound and
may be located anywhere from the base of the tongue to the cytological examination necessitates histopathological
mediastinum. Other locations are rare. Six patients (pts) with assessment. In this report we present scintigraphic findings
ectopic thyroid glands are presented: four with lingual and in a patient with HTT. Materials and Methods: A 25-year-old
two with submandibular ectopic thyroid tissue. Materials female patient was referred with a recently diagnosed nodule
and Methods: Median pts age at the time of presentation of in the right thyroid and pressure sensation. Ultrasound showed
lingual thyroid was 24 (15 - 36) years, while ectopic thyroid marked hypo-echogenicity, a regular margin demonstrating
tissue in right submandibular region was recorded in 49-year taller than wide shape with no microcalcifications (ATA 4) and
old male and 57-year old female patient. Diagnostic approach considerable growth from 0.6 ml to 4.9 ml. 99mTcO4- scintigraphy
included serum thyroid hormones and thyrotropin (TSH), showed an increased uptake in the right lobe and a total uptake
thyroid scintigraphy with 99m-TcO4- or I-131 SPECT/CT, neck of 0.63 %. The TSH-level of 1.31 mU/l under goiter preventive
ultrasound (US), magnetic resonance imaging (MRI), fine needle medication with levothyroxine 75 µg/d and iodine 200 µg/d
aspiration biopsy (FNAB) and endoscopy. Results: Patients was not indicative of thyroid autonomy. 99mTc-MIBI scintigraphy
with lingual thyroid presented with swelling at the base of the demonstrated a markedly increased intra-nodular uptake after
tongue and dysphagia while pts with submandibular thyroid 10 min and a persisting retention after 60 min. Fine needle
tissue presented with swelling in submandibular region. All pts aspiration biopsy (FNAB) showed an oxyphilic transformation
with lingual thyroid and a male patient with submandibular of a follicular neoplasm. Results: Given the presence of the
thyroid had subclinical hypothyroidism at the time of diagnosis cervical symptoms and for definite exclusion of malignancy,
and L-thyroxine (L-T4) was introduced. A 25-year old female hemi-thyroidectomy was performed. Histopathological workup
patient with large lingual thyroid and dysphagia was treated revealed a partly follicular, partly solid trabecular tumour with
with laser surgery. A 28-year old female patient with lingual and a prominent hyalinization. Immune histochemistry with Ki67
pre-hyoid thyroid tissue and no symptoms is under follow up on and TTF-1 positivity confirmed a HTT. Conclusion: This is the
L-T4 therapy during the last 5 years. Two male pts with lingual first description of scintigraphic features of a HTT. The presented
thyroid aged 15 and 36 years and dysphagia were referred case underlines the significance of 99mTcO4- scintigraphy for the
to surgery. A 49-year old male patient with ectopic thyroid diagnostic workup of thyroid nodules, especially in patients
tissue in right submandibular region had previous diagnosis of with inconclusive FNAB. References: None.
congenital hypothyroidism. However, he stopped L-T4 before
presentation. Ectopic thyroid was surgically removed and
pathohistology revealed normal thyroid tissue. A 77-year old EP-0248
euthyroid female patient with ectopic thyroid tissue in right Assessment of Somatostatin Receptor Expression in
submandibular region has normally located right thyroid lobe Thyroid Associated Orbitopathy with 68Ga-DOTANOC PET/
while left lobe was surgically removed due to nodular goiter. CT
Ectopic submandibular thyroid tissue was diagnosed 20 years N. Damle, M. Angamuthu, S. Arora, K. Lata, K. Shankar, R. Meel, S.
ago and followed-up with US without progression in size. Sharma, N. Tandon, C. Bal, M. Tripathi;
Thyroid scintigraphy with SPECT/CT diagnosed ectopic thyroid All India Institute of Medical Sciences, New Delhi, INDIA.
tissue in all pts. FNAB was performed in submandibular and
pre-hyoid ectopic thyroid tissue locations. MRI was performed
to reveal anatomic relations with other structures. Patients Aim/Introduction: Somatostatin receptor expression is seen
were followed-up with US and TSH. Conclusion: Subclinical on lymphocytes and lymphocytic infiltration is known to play
hypothyroidism was common finding in pts with ectopic a role in Thyroid Associated Orbitopathy. To assess somatostatin
thyroid gland. Surgery is the preferred treatment of choice in receptor (SSTR) expression in thyroid associated orbitopathy
pts with symptoms. However, pts without symptoms and signs using 68Ga-DOTANOC PET/CT and correlate with clinical activity
of malignancy can be followed-up on L-T4 therapy. Ectopic score. Materials and Methods: In this ethically approved
thyroid tissue was diagnosed in adult age in almost all patients. prospective study, 8 patients underwent a Ga-68 DOTANOC
References: None. PET/CT 45 minutes after intravenous administration of 3 mCi
(111MBq) of tracer. Scans were obtained on a 64 slice PET/CT
scanner with acquisition from vertex to manubrium. All patients
S497 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

were also assessed for clinical activity score (CAS) The images is widely accepted modality providing both anatomical and
were visually interpreted using the following criteria- • Thickening functional information, and has been used in many nuclear
and radiotracer uptake in extraocular muscles (EOM) • Retro- medicine fields. Here, we would like to share some cases where
orbital fat stranding and radiotracer uptake • Enlargement and we made accurate diagnosis by application of regional SPECT-
radiotracer uptake in the lacrimal gland To quantify the uptake, CT on hepatobiliary scintigraphy. Materials and Methods: All
a ratio of EOM/Fat/Lacrimal gland to pituitary and thyroid patients underwent 99mTc-mebrofenin (185 MBq) hepatobiliary
uptake was derived Results: The study group comprised of 4 scintigraphy and successive regional SPECT/CT. The SPECT
male and 4 female patients. The median age was 35 years (16-65 images before and after fatty meal administration over the
years). Four patients had clinical activity score <4 and four had liver area were acquired for 1 min followed by low-dose spiral
a clinical activity score ≥4. All the patients who had CAS more CT images. Results: SPECT/CT increased the reliability in the
than 4 showed one or more extraocular muscle thickening, diagnosis of typical acute cholecystitis and chronic cholecystitis.
lacrimal gland enlargement with increased DOTANOC uptake Moreover, SPECT/CT lead to more specific diagnoses from
and increased uptake ratios. Inspite of retroorbital fat stranding indeterminate or equivocal findings of planar hepatobiliary
noted in all four patients, no significant DOTANOC uptake was scintigraphy. It was possible to make the differential diagnosis
seen. In patients with CAS less than four, no similar findings for non-visualization of GB on hepatobiliary scintigraphy as
were noted except for one patient who had subtle extraocular follows: acute cholecystitis with cystic duct stone, GB collapse
muscle thickening, lacrimal gland enlargement, retroorbital fat due to chronic cholecystitis, GB filling due to prolonged NPO
stranding with no significant tracer uptake. Spearman correlation state, and secondary edematous GB wall thickening from liver
coefficient between CAS and SSTR expression was found to cirrhosis. It was also useful to detect chronic cholecystitis at
be 0.775, consistent with good correlation. Conclusion: SSTR distal part of bicameral GB, which was not possibly interpret
expression, as assessed by 68Ga-DOTANOC PET/CT in Thyroid on planar hepatobiliary scintigraphy. It was also helpful to
Associated Orbitopathy has significant positive correlation with detect and localize biliary leakage in postoperative patients.
clinical activity score. It can therefore be used for the assessment Conclusion: As illustrated here, the application of SPECT-CT on
of disease activity as well as response to treatment in an hepatobiliary scintigraphy could improve diagnostic accuracy in
objective manner. This may also help in screening patients with the evaluation of various GB disorders by exact localization of GB
steroid resistant ophthalmopathy who are likely to benefit from and by specifying the scintigraphy findings, which might also
long acting octreotide as a therapeutic option. References: 1. affect treatment and management of the patients. References:
Krassas GE. Octreoscan in Thyroid-Associated Ophthalmopathy. None.
Thyroid. 2002 Mar;12(3):229-31. 2. Atkinson H, England JA,
Rafferty A, Jesudason V, Bedford K, Karsai L, et al. Somatostatin
receptor expression in thyroid disease. International Journal of EP-0250
Experimental Pathology. 2013 Jun;94(3):226-9. Dynamic liver scintigraphy - quantitative tool in chronic
liver disease?
D. Jocius1, D. Vajauskas2, A. E. Tamosiunas1;
EP-14 1
Vilnius University Hospital Santaros Klinikos, Vilnius, LITHUANIA,
2
Lithuanian University of Health Sciences, Kaunas, LITHUANIA.
Clinical -> Diagnostic study -> Adult study ->
Non-oncology study -> Other clinical studies ->
Gastroenterology, benign Aim/Introduction: Chronic liver disease is multi-causal liver
injury affecting significant amount of people in the world.
October 12 - 16, 2019 e-Poster Area Fibrosis (and cirrhosis) is a common pathway despite multiple
different etiologic factors such as viral hepatitis B and C infection
or chronic alcohol consumption. The diagnosis of chronic liver
disease is made by laboratory tests, medical imaging and
EP-0249 liver biopsy in selected cases. Transient elastography is the
Improving Diagnostic Accuracy by Application of SPECT/ most widely used technique, with nowadays implemented
CT on Hepatobiliary Scintigraphy: Pictorial Essay new 2D shear-wave elastography and magnetic resonance
J. Kim1, K. Yoo1, S. Baek2, S. Lee1, Y. Choi1; elastography. Dynamic liver scintigraphy with 99mTc-
1
Hanyang University Medical Center, Seoul, KOREA, REPUBLIC OF, mebrofenin (iminodiacetic acid derivate) has well established
2
Kangdong Sacred Heart Hospital, Seoul, KOREA, REPUBLIC OF. indications in liver imaging including functional assessment
before liver surgery or acute cholecystitis and biliary atresia,
but systemic use of 99mTc-mebrofenin in chronic liver
Aim/Introduction: Hepatobiliary scintigraphy has been used imaging has never been used. The aim of this prospective
to evaluate various GB disorder. However, sometimes it is study is to investigate the value of dynamic liver scintigraphy
difficult to diagnose by itself or leads to discordant result with with 99mTc-mebrofenin in primary diagnosis of chronic liver
the clinical findings. Recently, hybrid single photon emission disease and to compare it with both 2D-SWE and histologic
computed tomography/computed tomography (SPECT/CT) examination of liver biopsy specimen. Materials and Methods:
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S498

We prospectively enrolled patients with primary diagnosis Imaging was performed in a supine position using a gamma
of chronic liver disease (viral hepatitis B and C ) who were camera equipped with a high-resolution low energy collimator
hospitalised for liver biopsy and who confirmed their agreement 4 hours after radiotracer administration. Scintigraphic imaging
by signing informed consent. Liver dynamic scintigraphy was showed presence of tracer into the right hemithorax, confirming
performed after injection of 99mTc-mebrofenin with planar pleural peritoneal communication on the right side.Patient
static scintigraphy at 30 minutes. Several parameters including underwent surgical correction of the leakage. Conclusion:
time to peak (TTP), time to half peak (1/2 TTP) and remaining Peritoneal scintigraphy is a simple, safe and effective method
liver uptake after 30 minutes were calculated. In addition liver for the identification of dialysate leakage in patients with CAPD.
2D shear wave elastography measuring liver stiffness (in kPa) References: None.
was performed to make head to head comparison between
two imaging modalities. Live biopsy was performed shortly
after both imaging tests. Results: Since now 32 patients with EP-0252
both HCV and HBV chronic infections were enrolled. In our SPECT/CT - solving the dilemma of hepatic hemangioma
preliminary results we found positive correlation between both N. Manevska, S. Stojanoski, T. Makazlieva, N. Bozinovska, D.
scintigraphic parameters (TTP, remaining liver uptake at 30 Miladinova;
min.) and 2D shear wave elastography. Also we found positive Medical Faculty, Skopje, NORTH MACEDONIA.
correlation between scintigraphic parameters and histological
examination results. Conclusion: Recent quantitative radiologic
methods (ultrasound and MR elastography) have little value Aim/Introduction: Hemangiomas, or hemangioma-like
evaluating liver parenchyma function. On the other hand liver appearing lesions, are frequently detected in liver often as an
scintigraphy with 99mTc-mebrofenin may show normally incidental finding on computed tomography (CT) scans. Once
functioning liver cells trough receptor mediated uptake detected, they can be a clinical dilemma as they need to be
mechanism thus enabling to evaluate remaining liver function characterized. Materials and Methods: We retrospectively
in chronic liver parenchymal disease. References: 1 Burden analyzed 108 patients, 62 females, (57.4%) and 45 males (41.67%),
of liver disease in Europe: Epidemiology and analysis of risk with mean age 50.05±11.92 years, sent to our Department for
factors to identify prevention policies. Journal of Hepatology. SPECT/CT of the liver to conclude or exclude the presence of
2
SNM Practice Guideline for Hepatobiliary Scintigraphy 4.0* J. hepatic hemangioma. Either ultrasound (US) or CT diagnostic
Nucl. Med. Technol. scan, or both, were previously performed. SPECT/CT of the
liver was performed with in vivo method, two hours after
intravenously (i.v) administration of 550MBq 99mTcO4 labelled
EP-0251 erythrocytes. Results: US was performed in 88 patients (81.48%),
Diagnosis of pleuroperitoneal communication as a while CT in 74 patients (68.52%). Mostly the hemangiomas were
complication of continuous ambulatory peritoneal dialysis localized in the right lobe. More than half of the patients (n=66,
by peritoneal scintigraphy - a case report 61.11%) had one lesion only, while two or more lesions were
A. N. B. Marques, F. Abreu, C. Gaspar, S. Pintão; seen on ultrasound or CT in (n=36, 33.33%). US demonstrated
Hospital de Santa Cruz - Centro Hospital de hyperechoic lesion, in some cases mixed echogenicity was seen,
Lisboa Ocidental, Carnaxide, PORTUGAL. while CT scans described mostly hypodense liver lesions. The
size of the lesion varied from to 6-140 mm (46.04 ± 27.1); 13
hemangiomas were giant. SPECT/CT confirmed hemangioma
Aim/Introduction: Continuous Ambulatory Peritoneal Dialysis in 11 patients negative on US, and 4 patients negative on CT.
(CAPD) is an effective renal function replacement technique In 40 patients hybrid imaging excluded the benign lesion of
that can be complicated by the formation of hydrothorax, a hemangioma. Most of the patients had benign diagnosis, while
potential life threatening complication.The main mechanisms of 12 had malignant diagnosis in whom in (n=7, 58.33%) metastasis
hydrothorax formation include mainly a primary diaphragmatic was excluded and SPECT/CT detected hemangioma. Positive
defect and anomalous lymphatic drainage motivated by correlation between US and SPECT/CT, as well as between CT
increased intra-abdominal pressure.Peritoneal scintigraphy with and SPECT/CT was detected in 43 patients (n=43, 39.81%) in
technetium-99m macroaggregated human albumin (99mTc- both groups. CT together with US, had the highest sensitivity,
MAA) helps to establish the diagnosis by evaluating possible accuracy and negative predictive value compared to SPECT/CT
dialysate leakage. Materials and Methods: Description of as refference, while CT alone and US alone had lower (94.4%,
clinical case. Results: A 61-year old female patient undergoing 72.6%, 71.2% vs, 91.5%, 68%, 66.7% vs, 79.6%, 64,4% and 54.2%,
CAPD treatment for three months, presented with dyspnea respectively). Conclusion: The hybrid imaging of SPECT/CT is a
and right pleuritic chest pain accompanied by incomplete simple, efficient and useful method for detecting and localizing
drainage of peritoneal dialysate, with a consequent increase in lesion of radioactivity concentration and solve the dilemma
abdominal volume.Chest x-ray showed right pleural effusion. of differential diagnosis of hepatic hemangioma. References:
Peritoneal scintigraphy was performed. A dose of 185 MBq (5 None.
mCi) of 99mTc-MAA was injected into a dialysate bag and instilled
into the peritoneal cavity via the indwelling Tenckhoff catheter.
S499 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

EP-0253 Fatima Hospital, Daegu, KOREA, REPUBLIC OF,


1

Gastrointestinal transit scintigraphy in patients with Raphael Hospital, Daegu, KOREA, REPUBLIC OF.
2

chronic constipation; an uncommon test. constipation; an


uncommon test
M. Moreno-Caballero, J. Infante-de la Torre, A. Martínez-Esteve, J. Aim/Introduction: Hepatobiliary scintigraphy (HBS) with 99mTc-
Rayo-Madrid, P. Jiménez-Granero, A. Cobo-Rodríguez, J. Serrano- hepatoiminodiacetic acid (HIDA) has been a useful diagnostic
Vicente; imaging study for biliary pain and suspicious gallbladder
Hospital Universitario de Badajoz, Badajoz, SPAIN. (GB) abnormalities. Using cholecystokinin or a fatty meal,
gallbladder ejection fraction (GBEF) can be easily calculated
to assess GB contractility quantitatively. GBEF is commonly
Aim/Introduction: Chronic constipation is a common used as a biological parameter for selection of patients to
pathology in children and adults. It is a serious condition that undergo a cholecystectomy. So far, there are limited data about
compromises quality of life, social functioning, and requires clinical impact of GBEF on patient management and follow-
investigation including blood test, colonoscopy, radio-opaque up. This study was to determine the usefulness of GBEF in the
marker study, and/or scintigraphy. The aim of this paper was to management of biliary pain or GB abnormalities. Materials
evaluate the usefulness of gastrointestinal transit scintigraphy and Methods: Among 225 patients who underwent HBS from
in patients with chronic constipation. Materials and Methods: January to June in 2016, 160 patients who had fatty meal HBS
We evaluated 12 patients, 10 children (mean age 9, range 6-15) with GBEF calculation were enrolled. Subjects ingested 2 raw
and 2 adults (49 and 58 year old), sent to our department with eggs (10 g fat) all at once. GBEF was calculated at 60 minutes
a diagnosis of chronic constipation refractory to treatment. after fatty meal intake. GBEF of ≥33% was used as the normal
All of them were subjected to clinical exam, biochemical cutoff value according to previous reports. Patients had
determination, radiological imaging study and rectal biopsy. cholecystectomy or were treated medically. Patients were
Clinical evolution time with constipation was at least 2 years. We divided into groups on the basis of GBEF and management:
performed a complete study protocol, including liquid gastric EFN-TXC group with normal GBEF and cholecystectomy, EFN-TXM
emptying scintigraphy and small and colonic transit times, group with normal GBEF and medical treatment, EFL- TXC group
following international guideline. Medications that affected with low GBEF and cholecystectomy, and EFL- TXM group with
gastrointestinal transit were withheld before and during the low GBEF and medical treatment. The follow-up period ranged
entire test. After oral administration of 37 MBq of 111In-DTPA in 2-48 months. Blood samples were taken to analyze an association
water accompanying with unlabeled standard solid meal, serial with GBEF and biochemical parameters. Results: Average GBEF
abdominal planar images were obtained for as long as 72 hours was 67.20±31.04%. There was no significant difference in GBEF
using a dual-head γ-camera. Regions of interest were defined in between men and women. In TXC group, the histopathologic
stomach, terminal ileum and in 6 regions of the large intestine findings were not significantly different between EFN and
together with determination of colon geometric center. EFL groups. In TXM group, there was no significant difference
Results: 11 patients showed altered scintigraphy study with in the follow-up of symptoms between EFN and EFL groups.
a pattern of functional rectosigmoid obstruction in 5 of them, However, serum total bilirubin, alanine aminotransferase (ALT),
generalized slow colon transit pattern in 4, colonic inertia in 1 aspartate aminotransferase (AST), gamma-glutamyltransferase
and slow gastric empty and slow small-bowel transit in 1. Normal (γ-GTP) levels were significantly higher in EFL group (p=0.0066,
radiological explorations were seen in 9 subjects. Radioisotopic p=0.0039, p=0.0240, p=0.0303, respectively). Also, there was a
study changed diagnosis in 8 patients and in other 3 patients negative correlation between serum total bilirubin, ALT, AST
contribute to clarify it, since discordance between normal levels and GBEF (Pearson r=-0.1949, p=0.0135, Pearson r=-
radiological tests and/or abnormal rectal biopsy. One of the 0.2013, p=0.0107, Pearson r=-0.1948, p=0.0136, respectively).
patients showed concordance between each imaging modality. Conclusion: The histopathologic findings of gallbladder and the
The results of the test changed the therapeutic management symptoms after medical treatment were not different between
in 8 cases. Conclusion: Gastrointestinal transit scintigraphy patients with normal GBEF and low GBEF. GBEF levels were
provided physiological, and useful information in the study higher in patients with elevated liver enzymes or total bilirubin
of chronic constipation, been a reproducible and accurate level. Also, there was a negative correlation between serum
method. This uncommon test determined both global and total bilirubin, ALT, AST levels and GBEF. Therefore, GBEF should
regional gastrointestinal transit time. The scintigraphy patterns be interpreted cautiously with hepatobiliary scan findings and
are easily recognizable, can be evaluated quantitatively and other clinical features. References: None.
help to determine appropriate therapeutic strategy in patients
with constipation. References: None.

EP-0255
EP-0254 Utility of Bile Acid Malabsorption Test 75SeHCAT in the
Clinical Utility Of Gallbladder Ejection Fraction: Is It Evaluation o Functional Chronic Diarrhea
Reliable By Itself? V. Godigna Guilloteau, M. Marín Ferrer, E. Martínez Albero, A.
J. Seo1, J. Oh2, H. Kim1, J. Park1; Galiana Morón, D. Vega Pérez, A. Gardellini Guevara, S. Ruiz Solis, P.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S500

Pilkington W, J. Esténoz Alfaro; Aim/Introduction: Salivary gland SPECT/CT (SG-SPECT/CT)


Hospital universitario 12 de Octubre, Madrid, SPAIN. is a promising nuclear medicine tool for functional evaluation
of salvary glands. Quantitative approach for the SG-SPECT/
CT would generate useful parameter of %injected dose (%ID).
Aim/Introduction: To determine the impact of bile acid But manual drawing of individual salivary glands may elicit a
malabsorption test in the evaluation of funtional chronic diarrhea. problem of reproducibility because the glands are not well
Materials and Methods: We retrospectively analyzed data of contrasted in SG-SPECT/CT without iodine-contrast. Here, we
39 patients (p) with funtional chronic diarrhea (26 women and investigated the reproducibility of manual segmentation of
13 men, average age 49.12 years (range 17-84 y) from January salivary glands on the SG-SPECT/CT. In addition, we explored
2017 to April 2019, referred to the Nuclear Medicine department whether the early CT could be used for late SPECT %ID after
to rule out bile acid malabsorption (BAM). Past medical history: mis-coregistration correction. Materials and Methods: Thirty
3p atrophic gastritis, 2p Rheumatoid arthritis, 1p Lupus, 1p patients (male:female=9:21, age=52.27±18.40y [mean±SD])
Myasthenia gravis, 1p Crohn’s disease (CrD), 1p Multiple Sclerosis, who underwent the SG-SPECT/CT (NMCT670, GE) from Aug
1p Ulcerative Colitis and 3p Hashimoto’s disease. Past surgical 2017 to Sep 2018 were retrospectively enrolled. The SG-SPECT/
history: 10 cholecystectomy, 3 ileal resection (1 CrD) and 2 right CT protocol was Tc-99m pertechnetate (15mCi) injection, early
hemicolectomy with resection of ileum (<5cm). The following SPECT/CT at 20min, sialogogue stimulation, and then late SPECT
tests were performed: 39p colonoscopy, 33p lactose intolerance at 40min either with (n=19) or without CT (n=11). Quantitative
(LI) test, 19p bacterial overgrowth (BO) test, 32p celiac disease SPECT approach was employed for the measurement of
(CD) screening. Oral administration of 0.01mCi of 75-Selenium- %ID using quantitative software (Q.Metrix, GE), which also
homocholic acid taurine (75SeHCAT) was performed in all of provided the salivary volume data from corresponding CT. The
them. We measured the abdominal retention of radiolabelled reproducibilities of manual segmentation were assessed by
taurine-conjugated bile acid analogue after seven days (AR7). intraclass correlation coefficient (ICC). Inter-operator and intra-
AR7 of <15% was considered positive for BAM: mild 10-15%, operator ICCs were calculated using 30 patients (60 parotid
moderate <10-5% and severe <5%. Furthermore, BAM can and 56 submandibular glands) data of early SPECT/CT for %ID
be classified according to its etiology: ileal dysfunction (type by SPECT and volume by CT. Additionally, in 19 patients with
I), idiopathic (type II) or associated with other gastrointestinal 38 parotid and 34 submandibular glands who had 40min CT
entities (type III). According to the final diagnosis, cholestyramine available as a reference, 40min %IDs were calculated using
was administrated, analyzing its efficacy. The follow-up period 20min CT before and after correction for mis-coregistration, and
ranged from 2 months to 2 years (average 8.2 months). Results: the possibility for use of 20min CT for 40min %ID was examined.
Positive BO test in 10/19p. Positive LI test in 11/33p. CDscreening Results: Manual segmentation required multiple sessions of
positive in 1/32p. Colonoscopy: 11/39p with nonspecific region-of-interest (ROI) drawings for parotid (~30 ROIs) and
changes, 8/39p diverticula-polyps and 1/39p collagenous submandibular (~20 ROIs) glands on trans-axial CT images.
colitis. 75SeHCAT results were: Normal (16/39p): 5p LI (13.8%), The ICCs for intra- and inter-operator reproducibilities for %ID
4p BO (11,3%), 1p collagenous colitis (2,7%), 3p Irritable Bowel and volume were excellent. The ICCs for %IDs were greater
Syndrome (8,4%) and 3p pending results. Positive (23/39p): than those for CT-derived volume, and the intra-operator ICCs
4p with mild AR7, 8p with moderate and 11p with severe. 17p were higher than inter-operator ICCs. The 40min SPECT %IDs
(47,2%) with only BAM, 6p (16,6%) with BAM associated with derived from 40min CT as a reference were 0.087±0.041% for
another pathology (4 LI, 1 autoimmune enteropathy and 1 parotid and 0.071±0.038% for submandibular glands, while
multifactorial cause). These were classified as: Type: I (4p), II (10p) those from 20min CT before correction were 0.068±0.033%
and III (9p). Twenty-two of 23p with positive 75SeHCAT received and 0.052±0.035%, and after correction 0.090±0.038%
cholestyramine, 16p improved symptoms, 1p with worse clinical and 0.072±0.036%, for parotid and submandibular glands,
symptoms and 5p pending clinical follow-up. Conclusion: respectively. Thus, bias±repeatability coefficients for %IDs
SeHCAT is a usefull imaging test for the diagnosis of BAM and before correction significantly improved after the correction.
should be considered in all patients with functional chronic Conclusion: The reproducibility of salivary gland segmentation
diarrea, specially when other tests are negative of inconclusive. from manual drawing during the salivary gland SPECT/CT
References: None. was excellent. Single CT scan may be sufficient enough to be
applied to both pre- and post-stimulatory SPECTs, which may
reduce radiation exposure to the patients. References: None.
EP-0256
The Reliability of Manual Drawing for Salivary Gland
Segmentation of Quantitative Tc-99m pertechnetate EP-0257
Salivary Gland SPECT/CT Added value of SPECT/CT in localizing the correct site of
W. Lee1, D. Oh2, J. Kim2, J. Han2, J. Park3, J. Lee3; gastrointestinal bleeding
1
Seoul National University College of Medicine, Seong-Nam, F. Di Gregorio, M. Rensi, D. Capobianco, M. Povolato, G. Ferretti, F.
KOREA, REPUBLIC OF, 2Seoul National University College of Giacomuzzi;
Medicine, Seong-Nam, KOREA, REPUBLIC OF, 3Seoul National Nuclear Medicine Unit - University-Hospital, Udine, ITALY.
University College of Medicine, Seoul, KOREA, REPUBLIC OF.
S501 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

Aim/Introduction: Blood loss from the gastrointestinal levels of this protein in addition to other tests may indicate a risk
tract can be an acute and life-threatening event. In particular of progression to smoldering myeloma, myeloma, lymphoma,
gastrointestinal bleeding can be occult with only positive fecal light-chain amyloidosis or Waldenstrom macroglobulinemia.
occult blood. For the treatment of gastrointestinal bleeding, it is The objective of this study is to evaluate the possible role of
important to accurately detect gastrointestinal bleeding and to 18
F-FDG PET/CT in the correct classification and monitoring of
localize the sites of bleeding. Bleeding scintigraphy is a useful these patients Materials and Methods: Retrospective analysis
imaging technique to detect gastrointestinal bleeding but planar of patients who underwent 18F-FDG PET/CT, after diagnosis
imaging has a low accuracy in localizing the bleeding site. The of monoclonal gammopathy (2012/2016) classified in three
aim of this study was to retrospectively assess the added value subgroups according to the risk of progression to myeloma
of SPECT/CT in the localize the correct site of gastrointestinal (low, intermediate, high). A positive PET/CT study for myeloma
bleeding. Materials and Methods: A retrospective analysis in is considered if it presents areas of focal hypermetabolism
the past 5 years of 75 patients (44 males and 31 females; age outside of physiological distribution areas or diffuse increase
range 48-90 years) with anemia and positive fecal occult blood in bone marrow of activity, superior to the background seen in
was conducted. No evidence of gastrointestinal bleeding was patients without infiltration of the marrow. We have performed
identified by endoscopy during the clinical course. All patients a statistical analysis describing the numerical variables as mean
underwent gastrointestinal bleeding scintigraphy with 99mTc- and standard deviation and the qualitative ones as frequencies.
labelled red blood cells. Planar images of abdomen and pelvis To compare the variables between the different groups, a
were acquired initially with a blood perfusion phase dynamic bivariate analysis (Student’s T-test and chi-square test) was
imaging and after 60, 120, 240 and 360 minutes with static performed, considering a p value <0,05 as significant. Analysis
planar imaging. Abdominal SPECT/CT was performed after has been performed using the ROC curve in case of significance.
24 hours or when an abnormal tracer uptake was evident at SPSS 24. Results: A total of 156 patients with MGUS (81 men, 75
planar images. Results: Dynamic imaging was not able to women) were included, mean age 68,8 years old. PET/CT was
identify bleeding site. Planar scintigraphy was positive in 64 positive in 18, 9 in diagnosis and 9 in follow-up (average time
patients and negative in 11 patients. In planar static imaging to progression: 28 months). Significant differences were found,
we found bleeding site on early images (< 120 minutes) in 16 when comparing the groups with a positive and negative
out of 64 positive patients. SPECT/CT imaging was positive in 69 results in PET/TC, in the age (p=0,022) and the monoclonal
patients and negative in 6 patients. The source of bleeding was component (0,015). There are no significant differences in sex,
accurately diagnosed in 29 patients by the planar imaging and type of immunoglobulin, light chain ratio or risk classification.
in 69 patients by the planar + SPECT/CT imaging.The diagnostic No relations were observed between the time to progression
ability of planar and SPECT/CT imaging in detecting the site of to myeloma and the qualitative variables. Using ROC analysis,
bleeding was respectively 29% and 100%. Conclusion: Our data the relation between the monoclonal component rate and
show that gastrointestinal bleeding scintigraphy in combination the PET/CT result, with and area under the curve of 0,744, was
with SPECT/CT is a noninvasive and useful tool for the correct studied. For cut-off point of 0,9 g/dL, figures of sensitivity of
localization of gastrointestinal bleeding site. References: None. 77,8% and specificity of 59,2% were obtained. Additionally 22
incidentalomas were diagnosed, 7 of them confirmed by other
diagnostic tests. Conclusion: The PET/CT study allows the
EP-15 correct classification of patients with MGUS. The age and the
monoclonal component rate seem to be the variables most
Clinical -> Diagnostic study -> Adult study -> related to the probability of presenting a positive PET/CT for
Non-oncology study -> Other clinical studies -> myeloma References: None.
Hematology, benign

October 12 - 16, 2019 e-Poster Area EP-0259


Splenic volume assessment by heat denaturated red blood
cells SPECT : validation against unenhanced low-dose
EP-0258 SPECT/CT CT volumetry by OsiriX MD
18
FDG PET/CT in evaluation of patients with monoclonal G. Arsos1, A. Siozopoylos2, L. Kirkineska1, S. Georga1, A.
gammopathy of undetermined significance (MGUS) Kalaitzogloy1, K. Michailos1, D. Katsampoukas1, E. Moralidis1, V.
T. Rudolphi-Solero, R. Sánchez Sánchez, A. González Jiménez, M. Perifanis3, T. Vasiliadis1;
Rashki, E. Triviño-Ibáñez, J. Llamas Elvira; 1
3rd Dept. of Nuclear Medicine, Aristotle University of
SAS, Granada, SPAIN. Thessaloniki School of Medicine, Thessaloniki, GREECE,
2
Dept. of Anatomy, Democritus University of Thrace School
of Medicine, Alexandroypolis, GREECE, 31st Propedeutic
Aim/Introduction: Monoclonal gammopathy of undetermined Dept. of Internal Medicine, Aristotle University of
significance (MGUS) is an asymptomatic condition in which Thessaloniki School of Medicine, Thessaloniki, GREECE.
there is a presence of an abnormal M protein in the blood. It is
important that these conditions be monitored, since increasing
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S502

Aim/Introduction: Splenic volume (SV) is superior compared isotopic dilution technique with red blood cells (RBC) labeled
to the linear dimensions as a splenic size index. 99mTc-heat with Cr-51, considered gold standard, to Tc-99m technique.
denaturated red blood cells (99mTc-hdRBC) is the ideal We assess its accuracy. Materials and Methods: Two blood
radiotracer for functional spleen imaging and Functional Splenic samples (10ml) were obtained from healthy volunteer and were
Volume (FSV) termed as the percentage of the injected activity respectively labeled with 5,4MBq of 99mTcO4Na and 2,2MBq of
of 99mTc-hdRBC per SV unit has been proposed for splenic 51CrO4Na. Both samples were centrifuged at 700g and washed
function quantification. Thus, for FSV calculation, SV assessment with 40ml of physiological salt solution. A 1ml aliquot of each
is required. We aimed to compare a simple gamma-camera standard was taken and diluted in a 250ml flask, being the
Nuclear Medicine segmentation tool applied on SPECT only rest of the blood reinjected. 5ml of blood was extracted from
data, against a validated, FDA approved, DICOM viewer software the contralateral arm after 60 minutes. In order to obtain the
applied on CT data of 99mTc-hdRBC SPECT/CT scans, in SV final averaged values, activity (cpm) of 1ml of blood samples,
assessment. Materials and Methods: Forty-two adult patients 1ml of the diluted standard samples and background were
were enrolled, 37 with cirrhosis (Child-Pugh score 5-12, class measured in quadruplicate for each isotope the day of the test
A-C) for detection of functional hyposplenisn, 4 with normal and two days later (Cr-51). Correct energy peak and window
liver function for definitive spleniculi characterization and 1 with must be selected for both isotopes in the well counter for this
ITP recurrence after splenectomy. All patients had 99mTc-hdRBC, purpose. The need to apply the Tc-99m decay correction during
low-dose, unenhanced SPECT/CT scans (64x64 matrix size, 60 the counting was checked. The expression to obtain the total
steps, 15 sec/step, 120 kV, 30 mA) 2-3 hours post injection, with injected radioactivity (A) was: A=SRVs • S(cpm/ml): Radioactive
a dual-head GE NM/CT Optima 640 gamma-camera. SV were concentration of diluted standard. • R: Weight(g) of labeled red
first assessed by applying the easy to use NM segmentation cell suspension injected/Weight of labeled red cell suspension
tool of the XELERIS (GE) work station to the SPECT data sets with added to flask. • Vs: Dilution volume of standard. The expression
a threshold value of 0.46 (SV-NM). Then, the DICOM CT data for red cell volume (RCV) calculation was: RCV=AHv/B • Hv:
sets were transferred to a Mackintosh unit for segmentation Venous haematocrit. • B(cpm/ml): Radioactive concentration
and volumetric measurements using the OsiriX MD (v. 9.0) of blood sample. The expression PV=BV-RCV was applied for
software. Due to low contrast between spleen and adjacent calculation of plasma volume (PV), where BV is blood volume
structures, manual segmentation was undertaken by tracing a calculated with BV=RCV/(f Hv). An average value of f=0,91 was
ROI at the periphery of the spleen in every single slice in which considered. Results of RCV, PV and BV for each radioisotope
it was visible and SV (SV-CT) was calculated by multiplying the were compared with predictions of normal blood volumes
sum of the areas outlined by slice thickness according to the based on body surface area with formulas recommended by
Chavalieri’s principle. Difference between SV-CT and SV-NM was the Expert Panel on Radionuclides of the ICSH. Results: More
assessed by Wilcoxon test, their relationship by linear regression than 10K counts were measured during the 5 minutes counting
analysis and their agreement by Bland-Altman analysis. Results: of the Tc-99m samples, being enough to get good statistical
SV-CT ranged from 7 to 2.000 ml. SV-CT and SV-NM did not values. Conclusion: Measurement of the Tc-99m RCV after
significantly differ (637±424 vs 634±418 ml, p=0.750) and decay correction guarantees comparable results to the Cr-51
closely correlated (SV-CT (ml) = 14,1 + 0.974 SV-NM, R=0.988, RCV. According to our results, the 1 minute counting would
p<0.0001) and agreed each other (bias -3 ml, 95% CI -129 - 123 be enough being negligible the decay correction. References:
ml). Conclusion: Splenic volume assessment using SPECT data 1. Gómez Perales JL. Blood volume analysis by radioisotopic
and inherent gamma-camera software only is as accurate and dilution techniques: state of the art. Appl Radiat Isot. 2015; 96:71-
more convenient compared to a more sophisticated, validated 82. 2. Perales JL. Mendoza AG. Development of a comprehensive
CT volumetry software. Apart from spleen, the volume of other software application for calculations in nuclear medicine and
sharply delineated organs like the kidneys in 99mTc-DMSA radiopharmacy. J Nucl Med Technol. 2010;38(3):153-62.
scans could be potentially measured accurately with this simple
method. References: None.
EP-0261
Comparison of two calculation methods for isotopic
EP-0260 measurement of plasma volume
Comparison of blood volume calculation by radioisotopic P. Orhon, M. Tempier, F. Cachin, S. Levesque;
dilution techniques with red lood cells abelled with Cr-51 Centre Jean Perrin, Clermont-Ferrand, FRANCE.
and and Tc-99m administered simultaneously
A. Agudo Martinez, I. León-Asuero-Moreno, G. Sabatel-Hernández,
M. Maniega-Pérez, P. de la Riva-Pérez, F. García-Gómez, I. Marín- Aim/Introduction: Isotopic measurement of total blood
Melero, C. Calvo-Morón; volume is commonly used for diagnosis of polycythemia. In our
Virgen Macarena University Hospital, Seville, SPAIN. clinical practice, red blood cell volume and plasma volume are
determinate separately by isotope dilution methods to provide
two independent measurements. Radioactive iodinated Serum
Aim/Introduction: The progressive extinction of the Cr- Albumin is used for the Plasmatic Volume (PV) determination.
51makes imperative to adapt the blood volume calculation by 99m
Technetium-labelled red blood cells used to determine the
S503 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

globular volume also allows, associated to the hematocrit, an Aim/Introduction: The mucous plug syndrome refers to an
indirect calculation of the PV. The present study was conducted acute bronchial obstruction by mucous plugs. It could be
to determine if these two methods for PV determination, on a manifested clinically by dyspnea, hypoxemia, and respiratory
statistically representative sample, provided similar results or alkalosis mimicking pulmonary embolism. Materials and
not. Materials and Methods: From March 2017 to March 2019, Methods: A 69 years old female patient was hospitalized for
data from 194 patients were retrospectively collected. For all of traumatic fall at home, she was diagnosed an amyotrophic
them, two independent isotopic measurements for red blood lateral sclerosis one year before. Three days after hospitalization,
cell volume and PV were performed. For each patient, an Excel she presented dyspnea, low oxygen saturation, tachycardia,
file was designed with the values of PV determined directly hypoxemia, hypocapnia, and increased D-Dimer. In order to
after injection of 125I-serum albumin and those deduced by diagnose a pulmonary embolism, a single photon emission
indirect calculation from the globular volume labelled with computed tomography ventilation/perfusion (SPECT/CT V/Q)
technetium-99m. These values were reported in a table for was performed. It wasn’t in favour of pulmonary embolism
statistical Wilcoxon comparison test. Results: We collected but showed a total abolished ventilation of the right lung. A
194 PV measurements using both 125I-serum albumin and the bronchoscopy was performed and found a mucous plug (Fig
indirect calculation method. The population studied consists 1) which was completely occluding the right main bronchus.
of 163 men and 31 women with an average Body Mass Index The plug was removed by aspiration with Acetylcysteine.
(BMI) of 27.1 kg/m². An overall comparison of the PV values from The symptoms disappeared and a control SPECT/CT V/Q was
these two measurements was performed with the Wilcoxon performed 2 days later, and showed a normalized ventilation and
test (matched samples). The result of this statistical test reveals perfusion, in both lungs. Results: SPECT/CT perfusion (99m Tc-
a significant difference between these two measurements (p < MAA) and ventilation (Technegas) images were acquired with a
0.001). As overweight and obesity can lead to changes in PV, we CZT dual head gamma camera (NM/CT 670 CZT, GE). A software
classify these patients into two sub-populations according to of 3D lobar quantification (Q.Lung, GE) is used for calculating
their BMI: 68 normo-weighted patients (BMI [18.5-24.9] kg/m²) the distribution. The first SPECT/CT V/Q (Fig 2: upper line)
and 126 overweighted/obese (BMI >25 kg/m²). This comparison shows a total abolished ventilation with relative conservation
with the sub classification depending on BMI highlights none of perfusion of the right lung and without parenchymatous
statistical difference between PV measurements for the normo- abnormality on the low-dose CT. The quantification (Fig 3)
weighted population whereas a statistical difference (p < 0.001) shows, for left vs right lung, a ventilation of 100% vs 0% and a
is observed in the overweighted/obese group. Conclusion: perfusion of 74% vs 26%. This result highlights a total obstruction
The independent measurement of PV by injection of 125I-serum of the right bronchus, and a beginning decrease of the right
albumin could be considered as the reference method because lung perfusion. Two days after removing the mucous plug,
it excludes the error on venous hematocrit. In clinical practice, the second SPECT/CT V/Q of control (Fig 2: lower line) shows a
this method may present inconvenience for the patient reestablished ventilation for the right lung, as the quantification
(repeated samplings of blood, radiation exposition and long illustrates (Fig 3): for left vs right lung, a ventilation of 46% vs
liver period of iodine 125). Therefore, our results suggest that the 54% and a perfusion of 50% vs 50%. Conclusion: In patient with
indirect method may be sufficient for normo-weighted patients neuromuscular disease such as amyotrophic lateral sclerosis,
contrary to overweighted/obese patients. References: None. bronchial mucous plugging is more common and represents
the main precipitating factor of acute respiratory failure. As a
differential diagnosis of pulmonary embolism, it is important to
EP-16 recognise it for not delaying its management. The lung SPECT/
CT is a valuable tool in this situation, because the early accurate
Clinical -> Diagnostic study -> Adult study ->
diagnosis prevents the complication such as lung collapse
Non-oncology study -> Other clinical studies ->
(1). References: 1. Nair, Pearson. Images in clinical medicine.
Pulmonology, benign
Mucous plug in the bronchus causing lung collapse. NEJM 2002.

October 12 - 16, 2019 e-Poster Area


EP-0263
FDG PET/CT Findings in Cavitary Form of IgG4-Related
EP-0262 Lung Disease
The Mucous Plug Syndrome Mimicking A Unilateral S. Kesim, T. Öneş, S. Özgüven, K. Öksüzoğlu, S. İnanır, H. T. Turoğlu,
Pulmonary Embolism Revealed By Lung SPECT CT: A Case T. Y. Erdil;
Report Marmara University Istanbul Pendik Education
J. T. Zhang-Yin1,2, B. Durand2, H. Lemasle2, R. Ahond-Vionnet2; And Research Hospital, Istanbul, TURKEY.
1
Service de Médecine Nucléaire, Hôpital Tenon,
Paris, FRANCE, 2Service de Médecine Nucléaire,
Hôpital Pierre Beregovoy, Nevers, FRANCE. Aim/Introduction: Immunoglobulin G4 related disease
(IgG4-RD) is a rare progressive fibroinflammatory disorder that
recently defined in literature in which IgG4-positive plasma cells
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S504

and lymphocytes infiltrate single or multiple organs. Although positive, 75.9% were negative and 3.4% were undetermined.
various radiological findings of lung involvement has been Patients with high D-dimer (more than 500 ng / mL) were
reported in many IgG4-RD studies, the literature information positive in 22.4% cases, 75.3% were negative and 2,3% were
is very limited for the type of cavitary form. Herein, we discuss undetermined. Patients with low D-dimer (less than 500 ng /
FDG PET/CT findings of a case with cavitary form IgG4-related mL) or without determination of D-dimer were positive in 18.7%
lung disease. Materials and Methods: A 50-year-old male cases , 76.6% were negative and 4.7% were undetermined. Out
patient was enrolled with cough, sputum and hemoptysis who of 148 patients with DVT, 28.4% were positive, 69.6% were
did not response to the treatment of pneumonia. Biopsy was negative and 2% were undetermined. Out of 58 patients with
performed and the histopathological findings was consisted PHT, 5.2% were positive, 91.4% were negative and 3.4% were
with IgG4-related lung disease. With this pathological diagnosis, undetermined. Out of 29 patients with chronic PE, 20.7% were
the patient was referred to our department and FDG PET/CT positive and 79.3% were negative, without undetermined cases.
was performed. Results: FDG PET/CT showed heterogeneous Conclusion: with the experience in our center we can conclude
and intense FDG uptake (SUVmax = 8.2) in the areas of that ventilation/perfusion SPECT obtains a percentage of
parenchymal consolidation and peribronchial ground glass positive studies comparable to the traditional planar study, while
opacities with occasional cavitary formation in the posterobasal allowing a significant decrease in the number of undetermined
segment of the left lower lobe. In addition, mild FDG uptake results. References: None.
(SUVmax = 2.7) was observed in mediastinal lymph nodes of
level 4L, 5 and 7 and the left hilar / peribronchial nodes, one
inch in diameter. No other evidence of malignancy was noted EP-0265
elsewhere in the whole body images. With the pathology Evaluation of bronchopleural fistula with Technegas
report, the findings were evaluated in favor of benign FDG ventilation scintigraphy
uptake with chronic inflammatory response associated with Z. AL Bimani1,2, S. Samaan1, W. Zeng1;
IgG4. There was no evidence of systemic involvement in the 1
University of Ottawa, Ottawa, ON, CANADA, 2Oman
rest of the body. Conclusion: IgG4-RD can mimic malignancy. Medical Speciality Board (OMSB), Muscat, OMAN.
In these cases, diagnosis is made by clinical evaluation, specific
serum markers and finally histopathological validation. The gold
standart treatment is steroids and immunosuppressive drugs. In Aim/Introduction: To Present a case of bronchopleural fistula
the literature, it has been reported that FDG PET/CT is a useful diagnosed by the ventilation scan.To Review the presentation
diagnostic tool in the evaluation of the spread of the disease, in of bronchopleural fistula and associated radiological and
the detection of the lesion site for biopsy and in the follow-up nuclear medicine image findings. Materials and Methods:
of the treatment response. There are a few metabolic imaging A bronchopleural fistula (BPF) is a direct connection between
studies evaluating lung findings for this disease. Our case was the bronchial tree and the pleural space, usually divided
the first that discuss FDG PET/CT findings in cavitary form of as central (involves the trachea or a lobar bronchus) and
IgG4 related lung disease. References: None. peripheral (involves a distal airway). The incidence of BPF ranges
from 0.5% to 3.0% after lobectomy and from 2% to 20% after
pneumonectomy. Although rare, a BPF is one of the most
EP-0264 serious life-threatening complications of pulmonary resection.
Decrease in number of undetermined studies with Therefore, prompt diagnosis and treatment are crucial. Nuclear
ventilation/perfusion SPECT medicine ventilation scan can accurately diagnose BPF by
J. Deportos, V. Vallejos, S. Lafuente, M. Solà, M. Salcedo, J. Riba, G. visualizing radiotracer at the pleural space, as described in the
Moragas; abstract. Results: A 72-year-old male presented with shallow
Hospital Universitari Germans Trias i Pujol, Badalona, SPAIN. breathing during sleep two weeks post right pneumonectomy
for recurrent solitary fibrous tumor of the right pleura. His CXR
showed increased lucency of the right hemithorax and CT chest
Aim/Introduction: to assess the number of undetermined showed large right pneumothorax associated with pleural
studies with ventilation / perfusion SPECT in the suspicion effusion. Chest tube was inserted subsequently. The patient
of pulmonary thromboembolism. Materials and was suspected of having a BPF and a diagnostic ventilation scan
Methods: between March 9th and December 31st 2018 was requested. The ventilation scan was performed following
we retrospectively reviewed 559 patients (270 men, 289 inhalation of approximately 37 MBq of Tc-99m Technegas. Both
women, 22 - 99 years) who underwent ventilation / perfusion planar images and SPECT/CT of the chest were acquired. On
SPECT to rule out pulmonary thromboembolism (PE). the planar images, there was accumulation of Technegas at the
Results: 324 out of 559 patients were referred to rule out acute right central airways with gradually increased uptake in the right
PE, 148 patients had a diagnosis of deep vein thrombosis (DVT), plural space over time, confirmed by SPECT/CT, and indicative
58 patients had a diagnosis of pulmonary hypertension (PHT) of a central BPF. The diagnosis of the BPF was subsequently
and 29 of chronic PE. 21.1% out of 559 patients were positive for confirmed by flexible bronchoscopy, which showed breakdown
PE, 76% were negative and only 2.9% were undetermined. Out of the bronchial staple line in the lateral third of the right main
of 324 patients cited to rule out acute PE , 20.7% of them were bronchial stump at the site of the fistula. The patient was
S505 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

managed by antibiotics and multiple exploratory thoracotomies determined based on the correlation of lung ventilation scans,
for debridement, packing and Claggett window. The follow-up clinical history, and findings from additional imaging modalities,
bronchoscopy demonstrated the healing of the right main particularly contrast-enhanced CT. References: None.
bronchial stump. Conclusion: In this poster, the pathology and
aetiology of the BPF will be discussed. The image findings from
plain radiograph, CT and nuclear medicine ventilation scan will EP-0267
be discussed. References: None. Analyzing the influence of bronchodilators in 99mTc-MAA
imaging
V. Mendi Barcina, S. Rizkallal Monzon, B. Martinez De Miguel, E.
EP-0266 Orihuela Pantoja, E. Dobra, H. Garcia Ruiz, E. Martinez Montalban;
Spectrum of unilateral hypoperfusion or absent perfusion Hospital Universitario La Paz, Madrid, SPAIN.
on pulmonary scintigraphy
N. Uyama1, H. Otsuka2, Y. Otomi1, M. Harada1;
1
Department of Radiology, Tokushima University Hospital, Aim/Introduction: Evaluate the clinical relevance of
Tokushima, JAPAN, 2Department of Medical Imaging/ pharmacological interactions between different bronchodilators
Nuclear Medicine, Institute of Biomedical Sciences, Tokushima (glucocorticoids, anticholinergics, beta-2 adrenergic agonists)
University Graduate School, Tokushima, JAPAN. in pulmonary perfusion images with 99mTc-MAA. According to
the specifications of the summary of product characteristics,
bronchodilators can modify the biological distribution of
Aim/Introduction: A finding of a globally diminished 99m
Tc-MAA and thus alter the quality of the image and the
pulmonary artery blood flow to unilateral lung with or without diagnosis. Given the numerous patients with this treatment,
an associated ventilatory abnormality is uncommon on lung we decided to assess the importance of this interaction and
perfusion scintigraphy (LPS). In the clinical setting, when these the possible modification of the treatment. Materials and
abnormalities are encountered, pulmonary embolism (PE) should Methods: Retrospective study of 50 patients underwent a
be considered. However, PE is an infrequent cause, and any of a pulmonary perfusion test with 185 MBq of 99mTc-MAA, between
wide variety of diseases is the more likely culprit. In this exhibit, September 2018 and February 2019. The mean number
we consider the spectrum of unilateral lung hypoperfusion or of particles administered was 264.240,978 (±43.792,902).
the absence of perfusion altogether on LPS with combinations Bronchodilators were divided in 3 groups: 1=glucocorticoids,
of additional imaging modalities, particularly contrast-enhanced administered to 34% of patients (beclomethasone, fluticasone,
computed tomography (CT). Materials and Methods: Between budesonide), 2=anticholinergics to 36% (tiotropium,
April 2010 and April 2019, we reviewed the scintigraphic and CT umeclidinium, ipratropium, glycopyrronium, aclidinium) and
findings in the database and medical records of our institutes. 3=Beta-2 adrenergic agonists to 42% (albuterol, terbutaline,
A total of 634 lung scans were reviewed, and we identified 46 salmeterol, formoterol, olodaterol, indacaterol, vilanterol). We
scans from 37 patients (men, 23; age, 42.2±31.3 years) with evaluated the labeling activity with 99mTcO4- of the different kits
unilateral lung hypoperfusion or absent perfusion on LPS who and the percentage of radiochemical purity (%RQP) by thin
had a clinical definitive diagnosis. Results: Of the 37 patients, 18 layer radiochromatography. % RQP must be ≥95%. Images
(men, 8; age, 13.1±16.6 years) were associated with congenital acquisition was done with SPECT-CT (INFINIA HAWKEYE 4) and
anomalies, such as a postoperative state of tetralogy of Fallot planar images using gammacamera (PHILPS BRIGTVIEW). The
(TOF) or transposition of great arteries (TGA) or hypoplasia of the evaluation of the images quality was done by two independent
pulmonary artery or vein. Eleven patients (men, 10; age, 69.5±5.7 nuclear physicians, classifying them in 3 groups: A=Good,
years) were associated with mediastinal and hilar masses, B=Poor, C=Average. Statistical analisys was performed with SPSS
such as primary bronchogenic carcinoma, and metastatic program, using test of Chi-square with the exact test of Fisher.
tumors. Six patients (men, 5; age, 67.8±7.5 years) are associated Results: The 3 groups of drugs present significant statistically
with parenchymal lung disease, such as chronic obstructive association with the image quality: - (Group=0) Patients without
pulmonary disease (COPD), idiopathic and secondary interstitial bronchodilator treatment: 100% present group image (A). -
pneumonia, atelectasis from pleural effusion. Only 2 patients (Group=1) Glucocorticoid vs. Image: p=0.047 64.7% presents
(both women; 74 and 81 years of age) with PE showed unilateral group image (A) and 35.3% group image (C). - (Group=2)
hypoperfusion or no perfusion, accounting for approximately anticholinergics vs. Image: p=0.00 50% presents group image
5% in our series. Large central emboli were able to be excluded, (A) and 50% group image (C). - (Group=3) beta-2 Agonists
with alternative causes detected by contrast-enhanced CT. vs. Image: p=0.02 61.9% presents group image (A) and 38.1%
Unilateral lung hypoperfusion or absent perfusion is a more group image (C).We didn’t detect any differences between
common finding in cyanotic congenital heart disease and drugs in the same pharmacological group (i.e: albuterol vs.
mediastinal and hilar masses than in PE. Conclusion: A variety salmeterol). Labeling activity interval was 3.515-3.959 MBq,
of diseases may present with unilateral lung hypoperfusion or mean: 3.704,107 MBq. % RQP mean was 99.975% (±0.175). There
absent perfusion on LPS; such findings are uncommon in cases was no statistical difference between the images obtained in
of PE, and alternative causes should be considered in order to each gammacameras (p>0.05). Conclusion: In the light of the
avoid a false-positive diagnosis. The correct diagnosis may be evaluated cases, concomitant treatment of bronchodilator
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S506

drugs may interfere with the images quality obtained with 99mTc- EP-0269
MAA, so we should consider treatment suppression. It would Comparison of Relative Renal Function with 99mTc-DMSA
be necessary to study how long we should suspend treatment SPECT assessed by a CZT 360° VERITON and Anger
before the study with 99mTc-MAA. On the other hand we didn’t cameras
obtein any poor quality images(B). References: None. C. Nganoa1, A. Bouthiba1,2, N. Roth3, N. Aide1,4, B. Enilorac1, C.
Lasnon4, D. Agostini1,2;
1
Nuclear Medicine Department, University Hospital, Caen,
EP-17 FRANCE, 2Normandy University, EA 4650, Caen, FRANCE,
3
Spectrum Dynamics Medical Ltd, Caesarea, ISRAEL, 4INSERM
Clinical -> Diagnostic study -> Adult study -> 1199 ANTICIPE, Normandy University, Caen, FRANCE.
Non-oncology study -> Other clinical studies ->
Uro-nephrology, benign
Aim/Introduction: 99mTc-Dimercaptosuccinic acid (DMSA)
October 12 - 16, 2019 e-Poster Area renal imaging is a useful and reliable mean for renal parenchyma
analysis (urinary tract infection, unilateral or bilateral renal
disease) and assessment of relative renal function. The aim of this
EP-0268 study was to compare Relative Renal Function (RRF) with 99mTc
PSMA PET imaging allows accurate determination of split DMSA SPECT between a conventional dual head ANGER camera
renal function as compared with MAG-3 scintigraphy (ECAM®, Siemens) and a CZT 360° VERITON camera. Materials
M. Ries, P. Pauly, F. Rosar, F. Khreish, A. Schäfer, S. Ezziddin; and Methods: With the Ethical committee agreement, we
Universitätsklinikum des Saarlandes, Homburg, GERMANY. evaluated patients who underwent routine static DMSA scan
on a conventional dual head ANGER camera and agreed to
perform 2 additional SPECT scans (Anger and CZT) the same
Aim/Introduction: Split-renal function (SRF) determination, day without CT or additional radiopharmaceutical injection.
i.e. quantification of side-specific relative contribution of Anger and CZT SPECT data were respectively acquired for
renal function, is valuable in various clinical settings including 10.7min and 11.73 ± 2.16min. Both studies were reconstructed
management of prostate cancer patients. Well-established using OSEM iterative algorithm (4iterations, 8subsets). Images
methods are comprised of renal scintigraphy using 99mTc labelled were quantified automatically or semi-automatically using
MAG-3 and DMSA with dynamic and static imaging, respectively. MIM software Renal SPECT workflow defining renal and
Our aim was to evaluate the feasibility of SRF estimation by cortical regions of interest for the left and right kidneys.
PSMA-PET/CT, as renal tubular PSMA expression seems to be an A normal RRF is stated to be 45-55% for each kidney. We
indicator of functioning parenchyma. Materials and Methods: compared RRF values with Anger vs CZT using a semi-automatic
PSMA-PET derived and MAG-3 scintigraphy based SRF were and automatic workflow. RRF from planar clinical routine were
compared in n=98 patients with advanced prostate cancer who compared to CZT SPECT Results: To date, DMSA renal SPECT
had PET/CT and renal scintigraphy in close temporal relationship imaging have been acquired in 7patients (age: 55±20 years,
(< 1 week apart). The PSMA PET derived split renal function 5 females) injected with 108.5±8.0 MBq of 99mTc-DMSA. Mean
(SRFPSMA) was obtained from 68Ga-PSMA11 images acquired 60 RRF for left kidney on VERITON were 56.78%±25.48 for semi-
min post-injection. The product of SUVmean and volume in a VOI automatic (observer1), 56.75%±25.12 for semi-automatic
with semi-automatical definition of 30% of SUVmax isocontour (observer2) and 57.96%± 24.74 for automatic. Friedman’s test
was calculated in both kidneys, resulting in relative proportions showed no significant difference between groups (p=0.867).
of each side. SRFMAG-3 was calculated with standard algorithms Mean RRF for left kidney on ANGER were 57.13%±23.66 for
employing manual planar ROI selection and calculation of side- semi-automatic (observer1), 57.08%±24.28 for semi-automatic
specific represention of the secretion phase of renogram. The (observer2), 58.26%± 24.50 for automatic and 59.61%±24.74
values for the right kidney resulting from SRFPSMA and SRFMAG-3 for planar images. On pairwise comparisons using Hollander
were compared and correlated. Results: Mean SRF of the & Wolfe’s procedure, no significant difference was found.
right side was 50.5% (range: 11 - 96%) and 50.7% (range: 1.2 - A statistical analysis combining both semi-automatic and
99.7%) using MAG-3 and PSMA PET, respectively. The correlation automatic quantifications showed good correlation between
between both methods of SRF was good (r=0,89, p<0,001) VERITON SPECT and ANGER SPECT (R2=0.9992). Conclusion:
and comparable to the correspondence of MAG-3 and DMSA RRF assessed by CZT SPECT and ANGER SPECT show good
scintigraphy. The correlation was good in both reduced as well correlation and Inter-user reproducibility. References: None.
as normal overall renal function. Conclusion: Renal tubular
PSMA expression seems to be intra-individually proportional to
renal function allowing to accurately assess split renal function EP-0270
by 68Ga PSMA PET/CT imaging. Function loss of one kidney can DMSA scintigraphy in orthotopic kidneys: Do we really
be reliably indicated by PSMA PET and will be confirmed by need to perform geometric mean assessment?
functional renal imaging. References: None. I. El Bez, R. Tulbah, I. Munir, F. Alghamlas, M. Alharbi;
KFMC, nuclear medicine department, Riyadh, SAUDI ARABIA.
S507 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

Aim/Introduction: For assessment of split renal function overweight and obesity groups according to the BMI range
of static renal scintigraphy with Tc-99m-dimercaptosuccinic were compared. Intra class correlation coefficient (ICC) was
acid (DMSA) the calculation of the geometric mean of counts employed to evaluate the relationship among kidney depths
from the anterior and posterior view is recommended. Aim of from standard, Itoh and CT correction. Results: The total GFR
this retrospective study was to find out, if the anterior view is (mL/min) from standard (GFRstd), Itoh (GFRItoh) and CT (GFRCT)
necessary to receive an accurate relative renal function (RRF) correction were 75.53 ± 21.49, (89.38 ± 25.16 and 91.13 ±
by calculating the geometric mean compared to calculating 27.32, respectively. Significant differences were found between
the split renal function using the counts of the posterior view GFRstd and GFRItoh, GFRstd and GFRCT (all p<0.001). There was no
only. Furthermore, we evaluated to what extent the patient’s significant difference between GFRItoh and GFRCT (p>0.05). The
age influenced these differences. Materials and Methods: A same statistical results were found in the comparison of split
total of 300 renal scintigraphies with 99mTc-DMSA performed GFR analyses. Comparison of GFRs, different kidney depths in
at our Department in the last two years were studied. Only hydronephrosis kidneys and non-hydronephrosis kidneys also
patients with orthotopic kidneys were included. The mean and showed no differences between Itoh and CT correction. The Scr
standard deviation of the differences as well as the correlation level was not corelated with GFRs in hydronephrosis kidneys
coefficient between both methods were calculated. The scans (all p>0.05). However, the correlation efficiency of Scr level
were performed using a dual head gamma camera, low energy and GFRstd, GFRItoh and GFRCT in non-hydronephrosis kidneys
ultra high resolution collimator, matrix 256 x 256, 300 kcts/view. was 0.45, 0.45 and 0.49, respectively (all p<0.05). There were
Background corrected values from both kidneys anterior and no differences in kidney depths among different BMI groups
posterior were obtained. The difference between the right renal (all p>0.05). ICC analysis showed correlation between GFRstd
function in posterior view and the right renal function obtained and GFRCT, GFRItoh and GFRCT (r=0.91, r=0.91, p<0.05) in non-
using the geometric mean was calculated for all the patients. hydronephrosis kidneys. Conclusion: GFR and kidney depth
The Student’s T test was applied to determine whether the using Tonnesen formula were underestimated. Itoh formula
differences between both methods were statistically different had the similar estimation of kidney depth and GFR with CT
from zero. Results: The differential function of the right and correction, and could be used in hydronephrosis patients
the left kidney was no significantly changed when compared instead of CT correction. In hydronephrosis patients, Scr did not
to the calculation of the geometric mean (p<0.1), for all age. well corelate with GFR. No differences of kidney depth and GFR
Conclusion: The calculation of the RRF from the posterior was found in hydronephrosis patients with or without normal
view only was not statically different when compared to the BMI. References: None.
calculation of the geometric mean in orthotopic kidneys, so that
in these cases the anterior view is not necessary. References:
None. EP-0272
Is geometric mean calculation of renal split function
applicable to patients with impaired renal function?
EP-0271 O. K. I. Kotbi1,2, A. Albatly1,3, B. Ziebarth1, E. Leung1, A. Rezk1, R.
Effect of kidney depth correction in GFR measured by Klein1, R. Klein1, W. Zeng1;
renal dynamic SPECT in patients with hydronephrosis 1
The Ottawa hospital, Ottawa, ON, CANADA, 2King Abdullah
Q. Zhao, J. Cao, J. Tian, J. Luo; medical city in holy capital, Meccah, SAUDI ARABIA, 3Prince
General Hospital of Ningxia Medical University, Yinchuan, CHINA. Sultan Millitary Medical City, Riyadh, SAUDI ARABIA.

Aim/Introduction: Kidney depth is one of the most important Aim/Introduction: The split renal function is routinely assessed
factors for the calculation of glomerular filtration rate (GFR) with by renal scan based on the posterior images. It is believed that
99m
Tc-DTPA dynamic SPECT imaging using Gates method, which geometric mean (GM) calculation could partially correct for
defaults the Tonnesen formula to estimate the depth of the soft tissue attenuation artifact due to the difference in kidney
kidney. We compared the effect of kidney depth in GFR measured positioning. Dual-headed cameras have become routine
by renal dynamic SPECT imaging hydronephrosis patients . equipment and enable GM calculation. In this study we
Materials and Methods: 64 patients (32 males, 32 females) with assessed the split function by GM calculation in patients with
hydronephrosis who underwent renal dynamic SPECT imaging normal and abnormal renal function, and compared the results
from January to December 2018 in General Hospital of Ningxia from routine (posterior only) image measurements. Materials
Medical University were retrospectively enrolled. The body mass and Methods: We reviewed consecutive renal scans with 99mTc-
index (BMI) and serum creatinine (Scr) level were recorded. The MAG or 99mTc-DTPA from 103 patients who had both anterior
depth of kidney was calculated by Tonnesen formula (standard), and posterior images. For GM calculation, region of interest of
Itoh formula (Itoh) and CT correction (CT) separately. Total each kidney and the background was drawn by 2 experienced
and split renal GFRs were measured by renal dynamic SPECT operators blinded to clinical data on Hermes HybridViewer V2.6,
imaging using Gates method using different kidney depths. The in a similar manner as clinical routine. Serum creatinine closest
GFRs were compared and the correlations between GFRs and to the renal scan date was obtained. 3 patients were excluded
Scr level were analyzed. Kidney depth of underweight, normal, due to poor image quality and 12 cases with renal masses were
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S508

analyzed separately. Additional 10 patients were excluded (MR positive/DMSA negative in 18 patients, and DMSA positive/
due to the lack of recent creatinine (most with normal remote MR negative in 8 patients). Conclusion: MR imaging is more
creatinine). The split function of the right kidney calculated sensitive than DMSA scan in detecting renal parenchymal
from the posterior and GM were compared with student t-test. abnormalities in acute pyelonephritis. In chronic pyelonephritis,
Continuous variables were presented as mean ± standard- MR imaging and DMSA scan has equal sensitivity in detecting
deviation. Results: Of 78 patients with renal scans (age: 54.9 ± scars. However, studies in larger number of patients with more
14.8, F:M=39:39), 44 had normal creatinine (69.3±15.5, group 1) established MR protocols can provide more accurate results
and 34 had abnormal creatinine (138.9±79.0, group 2), with the on sensitivity of MR imaging and DMSA scan in detecting
interval of 27.9±23.5 days. The mean split function of the right parenchymal abnormalities in pyelonephritis. References:
kidney was 51.6±12.1% from GM, compared to 51.0±12.5% from None.
posterior for group 1, and 49.9±13.7% from GM, compared to
47.7±14.5% from posterior for group 2. The difference in right
kidney split function between GM and posterior view was EP-0274
2.26±1.77% for group 1 and 3.59±2.14% for group 2 (t-test, A comparison of the renographic results from living and
p=0.004). There was a moderate to strong correlation between cadaver donors in kidney transplantation
kidney split produced by both operators (Pearson’s correlation A. N. B. Marques, F. Abreu, C. Gaspar, S. Pintão;
coefficient: 0.67). Of the 12 patients with renal masses, the Hospital de Santa Cruz - Centro Hospitalar
difference between the GM and posterior view split function Lisboa Ocidental, Carnaxide, PORTUGAL.
was 6.2±4.9%. Conclusion: The GM method is applicable to
patients to patients with normal and abnormal renal function.
The study demonstrated that GM calculation may be more Aim/Introduction: The renographic evaluation of the renal
clinically significant in patients with impaired than normal renal graft in the immediate post-transplant period is a valuable
function (2.3% vs. 3.6% difference). Considering no additional method to provide graft information, such as the kidney
radiation exposure or additional imaging time for the geometric transplant blood flow, function and possible complications,
method, it should be used in the routine assessment of renal and can also be used as a baseline study for future comparative
split function. References: None. evaluations.We analyzed our hospital’s renal transplant
population and compared renographic evaluation results
with donor status (living vs cadaver donor). Materials and
EP-0273 Methods: We retrospectively analysed epidemiological data
DMSA scan versus MR imaging in pyelonephritis: A Meta- and up to 5 day post-transplant renal scan findings of all the
analysis patients submitted to renal transplantation since 2010 until
I. Sarikaya1, A. Sarikaya2, A. Albatineh1; now.Renographic images were acquired with 99mTc-MAG3,
1
Kuwait University Faculty of Medicine, Kuwait, KUWAIT, according to the department protocol and a normal scan was
2
Trakya University Faculty of Medicine, Edirne, TURKEY. considered one to be with preserved perfusion and time-
activity curve. Epidemiological data were gathered from patient
files.Statistical analyses were made using PAWS-23®. Results:
Aim/Introduction: The aim of this study was to compare the 421 renal transplant recipients were studied, being 63.2% male,
reported results of 99mTc-dimercaptosuccinic acid (DMSA) scan with a median age of 52 years old (16-68). The donors were 54%
and magnetic resonance (MR) imaging in detecting renal female, with a median age of 55 (4-77) and 79.1% of the renal
parenchymal abnormalities in patients with pyelonephritis. grafts came from a cadaver donor.In renographic studies, 32.8
Materials and Methods: Systematic searches of PUBMED % of the transplant recipients had decreased perfusion and
and EMBASE databases were performed to extract studies 59.7% showed signs of Acute Tubular Necrosis (ATN). Median
performing both DMSA scan and MR imaging in patients Effective renal plasma flow (ERPF) was 177 (10-528). Median
with pyelonephritis. We used a search algorithm based on a ERPF changed according to donor status [204 (living donor)
combination of terms. Relevance of articles was assessed by vs 174 (cadaver donor), p=0.008]. The likelihood of having a
two authors according to predefined in- and exclusion criteria. normal renal scan did not changed according to donor status.
English-language publications were selected. Review articles, Conclusion: The study concluded that the overall renal scan
abstracts, case reports, editorials and studies in other diseases results of kidney transplants did not changed according to
were excluded. Meta-analysis was performed in per-patient donor status. However, the graft function was better in the living
and per-kidney basis. Results: Seven (7) studies (164 patients) donors than in the cadaver donors group. References: None.
were analyzed. MR imaging was positive in 107 patients (65.2%)
and DMSA scan was positive in 96 patients (58.5%). In acute
pyelonephritis (95 patients), MR imaging was positive in 75 EP-0275
patients (78.9%) and DMSA scan was positive in 63 patients Validation of the Glomerular Filtration Rate determination
(66.3%). When assessing for scar (69 patients), MR imaging was using Technetium-99m Diethylenetriaminepentaacetic
positive in 32 patients (46.4%) and DMSA scan was positive in acid instead of Chromium-51 Ethylenediaminetetraacetic
33 patients (47.8). There were discordant results in 26 patients acid
S509 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

I. Romero, I. Gil-Viciano, L. Fernandez-Romero, P. Notta, L. (type 2) whole curve measurement error; and (type 3) individual
Rubio-Alvárez, M. Ysamat-Marfà, C. Munuera-Sañudo, E. Pineda- point measurement error [2]. Volume of distribution (vdist) has
Fernández, M. Bueno-Raspall, C. Gámez-Cenzano; traditionally been included as a quality control (QC) check for
Nuclear Medicine-PET Unit, Hospital Universitari de slope-intercept GFR (SI-GFR) measurements. However recent
Bellvitge, L’Hospitalet de Llobregat, SPAIN. work has found vdist to be both non-specific and insensitive
for the detection of type 1 errors [1]. Type 2 and 3 errors are
probably uncommon in research environments, but may be
Aim/Introduction: In our department over 150 Glomerular more frequent in clinical environments where GFR studies are
Filtration Rate (GFR) determinations are performed yearly. The performed by generically functioning technologists and/or
radiopharmaceutical that we used was chromium-51 ethylene trainees under supervision. The aim of this study was to evaluate
diamine tetra-acetic acid (51Cr-EDTA) is no longer available. vdist for the detection of type 2 and type 3 errors. Materials and
There is a well-established alternative, the complex technetium- Methods: Using a dataset of 786 3-sample GFR measurements
99m diethylene triamine penta-acetic acid (99mTc-DTPA). The aim performed in patients with cancer, chronic kidney disease, and
of this study was to validate our procedure to determine GFR potential kidney donors, we introduced errors of varying size to
with 99mTc-DTPA by comparing the results obtained with both (i) the standard counts (type 2) or (ii) one of the sample counts
radiopharmaceuticals. Materials and Methods: Simultaneous (type 3). Only “plausible” studies (GFR between 0 and 160 ml/
measurements of the clearance rate of 3 MBq of 51Cr-EDTA and min/1.73m2 and progressively decreasing sample counts) were
37 MBq of 99mTc-DTPA were performed in 27 patients. After the included. GFR errors > 20% were considered significant. Cases
intravenous bolus administration of 51Cr-EDTA followed by 99mTc- in which vdist in litres was beyond 8.19 times body surface area
DTPA, blood samples were withdrawn from the contralateral arm ±43% (2.5 SD) were considered to have failed QC [2]. Results:
at 2, 3 and 4 hours. After centrifuging, 1 ml of plasma samples in Despite using a donor-derived reference range for vdist [2], it
duplicate and standards in triplicate were counted in a gamma- remained applicable in this pathologically mixed sample with
counter Wizard 2 Perkin Elmer model, for each energy windows 1.9% of unaltered studies being “falsely” positive. GFR changed
99m
Tc and 51Cr. For the 99mTc-DTPA, the dose measurements significantly for type 2 errors >20%. For gross errors in the
at dose calibrator and at well gamma-counter were decay standard (< -50% or > 120%) vdist had a sensitivity of > 80%. For
corrected to time of administration.The GFR calculation was the significant type 3 errors, the correlation coefficient (r<0.985) was
slope-intercept method characterizing the late exponential and an excellent QC check, far more sensitive than vdist. However
applying the Bröchner-Mortensen’s correction for the missing for a 2-sample SI-GFR (where a correlation coefficient is
fast exponential. The GFR was normalized to body surface unavailable), vdist had a sensitivity of > 80% for large errors of the
area calculated by Dubois and Dubois formula. The calculated 2- or 3-hour samples (< -50% or > 40%). Conclusion: For SI-GFR
GFR (BSA corrected), using 99mTc-DTPA and 51Cr-EDTA, was measurements based on only 2 samples, or performed without
compared and the mean percentage of differences obtained. injection site imaging, vdist enables the detection of large type
It was evaluated the correlation between the percentage of 2 and type 3 errors that may be otherwise undetectable.
differences and the absolute value of GFR (BSA corrected). References: 1. McMeekin H, Wickham F, Barnfield M, Burniston
Results: The mean values of GFR were 84.9 (SD=19.7) ml/ M. Effectiveness of quality control methods for glomerular
min/1.73m2 for 51Cr-EDTA and 87.6 (SD=21.1) ml/min/1.73m2 filtration rate calculation. Nucl Med Commun 2016; 37:756-766.
for 99mTc-DTPA respectively. The linear regression showed a 2. Holness JL, Fleming JS, Malaroda AL, Warwick JM. 99mTc-DTPA
highly correlation (r=0,960) between the GFR values obtained volume of distribution, half-life and glomerular filtration rate in
with both radiopharmaceuticals. The mean percentage of normal adults. Nucl Med Commun 2013; 34:1005-1014.
paired differences was 3.2 % (SD= 5.9), systematically higher for
99m
Tc-DTPA. This result is consistent with published studies. No
correlation was found between the percentage of difference and EP-0277
the GFR value. (r=0.023). Conclusion: The 99mTc-DTPA clearance SPECT/CT for detection of dialysate leakage in patients
is a validated alternative to the 51Cr-EDTA in the assessment of on continuous ambulatory peritoneal dialysis - a
GFR. The differences between the two radiopharmaceuticals are retrospective study
small enough to be clinical significance. References: None. D. Chroustova1, J. Trnka1, M. Havrda2;
1
General University Hospital and 1st Faculty of Medicine, Charles
University, Prague, CZECH REPUBLIC, 21st Department of Internal
EP-0276 Medicine, Faculty Hospital Kralovske Vinohrady and Third Faculty
Does volume of distribution make a contribution to QC of of Medicine, Charles University, Prague, CZECH REPUBLIC.
GFR measurement?
J. M. Warwick, J. L. Holness;
Stellenbosch University, Cape Town, SOUTH AFRICA. Aim/Introduction: Continuous ambulatory peritoneal dialysis
(CAPD) offers several advantages over hemodialysis, but some
complications including dialysate leakage may occur. In this
Aim/Introduction: Errors during GFR measurement fall into 3 retrospective study we investigated the value of peritoneal
categories: (type 1) failure of the single-compartment model; scintigraphy using 99mTc-MAA SPECT/CT in evaluation of
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S510

dialysate leakage and its localization in patients undergoing interest (ROIs) using the clinical renogram processing software
CAPD. Materials and Methods: 23 patients (13 males 9 females, (Hermes) both on posterior images (PI) and geometric-mean
aged between 31 and 78 years with an average age of 54,7 years) of anterior-posterior projections (GM). In addition, both PI and
underwent CAPD between 2010 to 2018, and those suspected GM values were corrected for 140 keV photon attenuation
to have dialysate leakage or dialysate retention in peritoneal using anterior and posterior soft-tissue depths of each kidney
cavity were enrolled into study. Peritoneal scintigraphy was as measured on CT and assuming uniform linear attenuation
performed after administration of 100 MBq 99mTc-MAA in dialysis of water (0.154 cm-1) (ACPI and ACGM respectively). Balanced
solution into peritoneal cavity. Initial dynamic imaging and kidney function was assumed for 45%≤RFK≤55%. Results:
subsequent ANT/POST WB imaging and SPECT/ (low dose) Of the 80 patients included, 18 (23%) had abnormal kidney
CT examination using INFINIA Hawkeye gamma camera were locations. GM estimated higher average RKF than PI (p=0.01)
performed. Results: Dialysate leakage was demonstrated by for both normal and abnormal groups (by 1.0% and 4.1%
peritoneal scintigraphy in 10 patients. The pleuroperitoneal respectively). Similarly, ACPI had higher values by 0.9% and 4.5%
communication was detected in one woman, periumbilical leaks (p<0.05 for both). GM and ACGM did not significantly differ
were found in three women, scrotal leakages in three men (one (p>0.2) in either group, nor with ACGM and ACPI, indicating that
case on the right side and two cases on the left side), inguinal GM sufficiently corrected for photon attenuation. Furthermore,
leaks in three men (two cases on right side and one case on the smallest variability (standard-deviation) was achieved in GM-
left side), vaginal leak was found in one woman. In five cases, a ACGM differences (2.2% and 3.7% for normal and abnormal
combination of abdominal wall defect with another leak type groups) which used identical ROIs and AC influence was
was found with advantage of hybrid CT image. The dialysate negligible. In comparison, variabilities of PI-GM were 2.8% and
volume adjustment was performed in 12 non-leakage patients 5.8% and were even greater for ACPI-ACGM (3.9% and 8.6%) due
who had symptoms of the dialysate retention. They were to ROI variability and introduction of additional noise on depth
investigated and followed for further mechanical complications: measurements. Prevalence of balanced function increased from
catheter obstruction or dislocation, or solution leakage around 57% with PI to 65% with GM in normal and from 33% to 50%
the catheter. Conclusion: Peritoneal scintigraphy is simple and in abnormal anatomies (p<0.01). Conclusion: Geometric-mean
effective method for detecting structural abnormalities and of anterior-posterior renal scintigraphy for split renal function
localizing the origin of leakage. According to our experience, measurements are more accurate than posterior imaging, and
SPECT/CT is very helpful for detection and more accurate precision may be degraded by attenuation correction using
localization of dialysate leakage, especially in cases of the CT-based depth measurements. Considering no additional
leakage defects via abdominal wall, which are not always clearly radiation exposure or imaging time, geometric-mean should be
visible on ANT/POST projections. References: None. used in routine assessment of split renal function. References:
None.
EP-0278
Practical attenuation correction in renal scintigraphy for
precise split renal function measurements EP-0279
R. Klein1,2, A. Rezk3, O. Kotbi2, A. Abdulrahman2, E. Leung2, B. Replacing 51Cr-EDTA with 99mTc-DTPA in GFR
Ziebarth1, Z. Wanzhen2; measurement : a prospective comparative study
1
The Ottawa Hospital, Ottawa, ON, CANADA, G. Arsos1, E. Moralidis1, A. Kalaitzogloy1, D. Katsampoukas1, C.
2
University of Ottawa, Ottawa, ON, CANADA, Sachpekidis2;
3
Department of Physics, Ottawa, ON, CANADA. 1
3rd Dept. of Nuclear Medicine, Aristotle University of Thessaloniki
School of Medicine, Papageorgiou Gen Hospital, Thessaloniki,
GREECE, 2Dept. Of Nuclear Medicine, Inselspital, Bern University
Aim/Introduction: Split renal function measurements using Hospital, University Of Bern, Bern, SWITZERLAND.
planar scintigraphy in living kidney donors and patients with
suspected renal obstruction are vital metrics. They are typically
performed using posterior imaging (PI) which assumes similar Aim/Introduction: 51Cr-EDTA is traditionally the main
kidney tissue depths and hence similar photon attenuation. radiotracer for GFR measurement usually by the single
Attenuation corrections (AC), which may be especially important injection-multiple sampling technique in Europe, while 99mTc-
in abnormal kidney anatomies, have been previously proposed DTPA, alternatively proposed by the current guidelines, is less
but their optimal clinical use is not conclusive. Materials and commonly used. Although similar, 99mTc-DTPA and 51Cr-EDTA
Methods: This retrospective study included patients which may give significantly different GFR values, depending on DTPA
had undergone 99mTc-MAG3 or 99mTc-DTPA renal imaging on exact formulation. Due to recent 51Cr-EDTA (GE) withdrawal,
a dual-head gamma camera and had an abdominal region centers based upon this radiotracer and now shifted towards
CT within 1 year. An experienced nuclear medicine physician 99mTc-DTPA use, may experience problems of consistency in
classified each patient into normal or abnormal kidney anatomy patients follow-up, GFR adjusted chemotherapy dosing and
groups by visual assessment. Right kidney differential function kidney transplant donation GFR cut-off values. The aim of
(RFK) was obtained from the area under the activity curve from our prospective study was to explore equivalence between
1-3 minutes post-injection using manually drawn regions-of- one commercially available, widely used DTPA preparation
S511 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

and 51Cr-EDTA (GE) in GFR measurement. Materials and EDTA were simultaneously injected. Standard doses of each
Methods: Between 5/12/2018 and 22/2/2019, 42 consecutive radiotracer with half-dose were diluted in 1000ml of water.
patients aged 18-86 years, 15 F, referred for radionuclide GFR Patient and standard doses were measured by weighing of the
measurement had simultaneous GFR measurement with both syringes and the correction for residual dose by subtraction
99mTcO4- labelled TechneScan DTPA (Mallinckrodt) and ready of empty from full syringe weights was done. Blood samples
to use 51Cr-EDTA (GE) preparations. After simultaneous bolus of 10ml were obtained from the contralateral arm at 120, 180
i.v, administration of both radiotracers, 10 blood samples were and 240min postinjection. Plasma samples were centrifuged
obtained between 5 min to 4 hours post-injection and plasma at 1500g for 5min to isolate the plasma. Samples of 1ml of
99mTc and 51Cr activities measured on the same and two days plasma, standard and water (background) activity (cpm),
later respectively. For both radiotracers, GFR was calculated by were counted per duplicated, in ɣ-counter the same day of
: a) two-compartment bi-exponential kinetic analysis using 10 study (Tc-99m-standard-samples) and two days later (Cr-51-
samples (GFR10, ml/min), allowing also for extracellular fluid standard-samples). Same set of plasma and background were
volume (ECFV, l) assessment and b) by “slope-intercept”, one- used during the counting , after selection of correct energy
compartment mono-exponential analysis with 2 samples at peak. Decay correction was applied relative to time between
2 and και 4 hours post-injection and Brochner-Mortensen counting of patient samples and standard samples. All samples
correction (GFR2, ml/min), according to British guidelines. were background-corrected. Plasma activity (Pt) disappearance
GFR10, GFR2 and ECFV were scaled for body surface area (BSA) reflects GFR and this one-compartimental model follows a
calculated according to Haycock formula (SGF10, SGFR2 both in single exponential: Pt=P0 exp(-Kt); P(t)=plasma concentration
ml/min/1.73 m2 and SECFV in l/1.73 m2 respectively). Results: (cpm/ml) at t-time P0=plasma concentration (cpm/ml) at
99mTc-DTPA and 51Cr-EDTA, values of GFR2 GFR10, ESV, SGFR2, injection-time K:constant of exponential clearance GFR=VdxK.
SGFR10 and SESV were : 65.3±34.3 vs 64.6±34.0, p=0.047; Vd=volume of distribution.Slope-Intercetp Method by back
58.1±29.4 vs 57.5±29.2, ns; 72.6±35.9 vs 72.7±36.2, ns; 64.7±30.5 extrapolation to zero-time was used to give the estimated
vs 64.6±30.5, ns; 14.9±3,2 vs 16.1±3.3, p less than 0.0001; 13.4±2.6 activity per unit volume (Po) in the volume of distribution,
vs 14.4±2,7, p less than 0.0001, respectively. The corresponding and Vd=A/P0 where A=injected activity.To calculate A, the
99mTc-DTPA-51Cr-EDTA correlations were strong with R2 greater measurement of standard activity (cpm/mlstandard) and relation
than 0.99 and p less than 0.0001 in all cases. 99mTc-DTPA GFR of patient (Wpatient) and standard (Wstandard) dose weights are
and ECFV values within the corresponding 51Cr-EDTA values used: A=cpm/mlstandardxVstandardx(Wpatien/Wstandard) The GFR was
±10%, exceeded 95 and 83% respectively. Conclusion: GFR normalized by correction to surface area (BSA) of 1.73m2 and
measurement with ΤechneScan DTPA (Mallinckrodt) shows then the correction of Brochner-Mortensen (GFRcorr) was applied
values almost identical to those by 51Cr-EDTA (GE) in a wide to allow the one-pool assumption. We also calculated half
range of renal function by both the “slope-intercept” technique clearance as quality assurance check (T1/2(min)=Ln2/K(min-1)).
and the 10 sample kinetic analysis. As expected by the slightly Results: Expected Vd in adult is 8 times the BSA (2-SD variation
higher molecular weight of 99mTc-DTPA compared to 51Cr- of +/-25%) and T1/2 is between 100-120min. GFR measurement
EDTA, ECVF is slightly underestimated by appox. 1 l. References: by both radiotracers were comparable. Vd and T1/2 values would
None. improve by using Tc-99m according to expected if the first point
was not taken into account. Conclusion: GFR measurement by
Tc-99m-DTPA clearance is an accurate and feasible test using
EP-0280 three-point monoexponential plasma method but we suggest
Simultaneous measurement of Glomerular starting plasma extraction after 120 minutes. References: None.
Filtration Rate (GFR) with Tc-99m-labelled
diaethylenetriaminepentaacetic acid (Tc-99m-DTPA) and
Cr-51-labelled ethylenediaminetetraacetic acid (Cr-51- EP-0281
EDTA) Renal Clearance Function Index - Preliminary Assessment
A. Agudo Martinez, A. Moreno-Ballesteros, F. García-Gómez, T. of Clinical Usefulness of a New Dynamic Renal
Cambil-Molina, R. Fernández-Sanz, C. Calvo-Morón; Scintigraphy Parameter
Virgen Macarena Hospital, Seville, SPAIN. P. Cichocki1, K. Filipczak2, M. Surma1, A. Płachcińska2, J. Kuśmierek1;
1
Department of Nuclear Medicine, Medical University of Łódź,
Łódź, POLAND, 2Department of Quality Control and Radiological
Aim/Introduction: GFR can be measured through radionuclide- Protection, Medical University of Łódź, Łódź, POLAND.
based techniques, being Cr-51-EDTA the gold-standard. The
production of Cr-51 is decreasing, making imperative to adapt
the Tc-99m technique. We compare GFR assessment through Aim/Introduction: Split function of both kidneys (SF), one of the
plasma clearance of Tc-99m-DTPA and Cr-51-EDTA following basic quantitative dynamic renal scintigraphy (DRS) parameters,
the same simple-injection technique, to assess its accuracy. has significant limitations. Its relative nature makes it unreliable
Materials and Methods: Two healthy volunteers and one for example in case of lack or a trace function of the other
patient participated in this pilot study. Following hydration kidney, or bilateral renal disorders. This study aims to determine
with 300ml water, 10MBq of Tc-99m-DTPA and 3MBq of Cr-51- normative values of the original parameter reflecting renal
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S512

clearance in the absolute values - renal clearance function index Renal Disease (MDRD), Chronic Kidney Disease Epidemiology
(CFi), and preliminarily assesses its usefulness in selected clinical Collaboration (CKD-EPI) and Janowitz-Williams (JW) equations.
situations. Materials and Methods: Study included 2 groups: The population was then randomly and equally divided into
[1] - control - 20 healthy volunteers (40 kidneys); [2] - 41 patients development and validation sets. A Microsoft Excel add-
with a single functioning kidney (with lack or trace function in (Solver) was used to optimise the equations’ parameters
of the other kidney - SF <10%), and 15 patients (30 kidneys) using the development set data. The bias, precision, accuracy
with bilateral obstructive uro-/nephropathy - cumulative and agreement of all original and adapted equations was
renographic curves with no or poor response to diuretic test, determined using the validation set data. The impact that use
in total 56 patients (71 kidneys). DRS was performed according of eGFR would have had on management decisions was also
to a standard protocol - after intravenous administration of assessed. Results: Data of 435 patients were included. Of the
111MBq 99mTc-EC, 120 sequential images were acquired (10s original equations, the Janowitz-Williams was least biased and
each). If necessary, study was extended by a diuretic test (“F+20” most precise. The original equations all overestimated GFR by
protocol). CFi was calculated for all kidneys using an in-house 7.9 to 16.0 ml/min/1.73m2. Bias of the adapted equations was
developed software. Its normative values were determined significantly lower (-2.2 to 3.4 ml/min/1.73m2, p<0.0001). The
based on the control group (40 kidneys). In standard DRS original equations had interquartile ranges (IQRs) of 21.8-30.4
evaluation, kidneys of patients from group 2 were classified ml/min/1.73m2. Adapting the equations reduced the IQRs to
as nephropathic if they met 2 out of 3 criteria: SF <45%, TMAX 21.2-24.0 ml/min/1.73m2. The accuracy, measured as P30 values,
>7min and/or peripheral cortical lesions in visual assessment. improved significantly from 57.1%-73.7% to 78.3%-82.9%
This routine diagnosis was compared with CFi results. Results: after adapting the equations (p≤0.0001). The 95% confidence
Mean CFi values in control group were 23,6 ± 4,4. CFi ≥15 (mean intervals (CI) were ± 42.3, 34.4, 32.9 and 33.3 ml/min/1.73m2 for
- 2SD) was determined as a normative limit. In group 2, 24/71 the adapted CG, MDRD, CKD-EPI and JW equations respectively.
kidneys were classified as nephropathic according to classic Using eGFR with a CI allows for reliable exclusion of patients with
criteria. Application of CFi changed the classification in 14/71 impaired renal function, however eGFR remains equivocal in a
kidneys (20%) and affected 13 out of 56 patients (23%). This significant proportion of patients. Conclusion: The JW equation
parameter was within normal range in 4/24 kidneys classified in provides the most accurate unadapted estimate. Adapting the
conventional DRS as nephropathic and was below normal limit in equations for a population of mixed ancestry improved their
10/47 kidneys without features of nephropathy in conventional performance. While reliable to exclude low GFR when eGFR is
DRS. Conclusion: CFi, which reflects the clearance function of normal to high, in the GFR range where most critical clinical
each kidney in absolute values, extends diagnostic capabilities decisions are made, the uncertainty of GFR estimates is large.
of DRS. This parameter is particularly useful in situations when In these cases there is no alternative to GFR measurement.
assessment of SF is unreliable. It was demonstrated that such References: 1. Janowitz T, Williams EH, Marshall A, et al. New
situations may occur, among others, in patients with a single model for estimating glomerular filtration rate in patients with
functioning kidney - to assess its actual performance, or with cancer. J Clin Oncol. 2017;35(24):2798.
bilateral urinary tract obstruction - to differentiate between
obstructive uropathy and nephropathy. References: None.
EP-0284
Is there a role for renal perfusion on the evaluation of
EP-0283 urinary tract obstruction?
Can Glomerular Filtration Rate Estimation be Adapted for M. Monteiro1, R. Silva1,2, T. Saraiva1, G. Costa1,2, J. Pedroso de
Local Oncology Patients? Lima1,2,3;
J. L. Holness, H. M. Simonds, P. Barnardt, J. M. Warwick; 1
Centro Hospitalar e Universitário de Coimbra, Coimbra,
Stellenbosch University, Cape Town, SOUTH AFRICA. PORTUGAL, 2Faculdade de Medicina da Universidade
de Coimbra, Coimbra, PORTUGAL, 3Instituto de Ciências
Nucleares Aplicadas à Saúde (ICNAS), Coimbra, PORTUGAL.
Aim/Introduction: Creatinine-based glomerular filtration rate
(GFR) estimating equations tend to perform poorly in cancer
patients. The Janowitz-Williams model is a new equation Aim/Introduction: Urinary tract obstruction (UTO) is a common
developed from a large Caucasian cancer population1. clinical problem and a frequent cause of renal impairment. It is
Our study evaluates the performance of this equation and defined as a physical blockage to urine flow, which may result
three commonly used CKD equations in a genetically and in hydronephrosis and ultimately renal parenchymal damage.
socioeconomically diverse cancer population. It also evaluates Renal scintigraphy provides important functional data to assist in
the utility of a simple tool to improve GFR estimation by the diagnosis and management of patients with UTO, however
adapting the equations’ parameters to better fit the data. renal perfusion has not been demonstrated to contribute to
Materials and Methods: GFR was measured from the plasma interpretation. With this retrospective work, we aim to assess
clearance of 99mTc-DTPA using the slope-intercept method. GFR the value of perfusion on diuretic renal scintigraphy in adults
was estimated (eGFR) from standardized serum creatinine levels with suspected upper UTO (UUTO). Materials and Methods:
using the original Cockcroft-Gault (CG), Modification of Diet in One hundred and fifty diuretic renal scintigraphies with [99mTc]
S513 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

Tc-MAG3, performed in adults between January and December 1 minute) was assessed. Data were processed using STATA.
2018, were retrospectively reviewed. Patients with previous The two groups were compared using a Wilcoxon rank-sum
urologic surgeries or double J stent and with suspected lower (Mann-Whitney) test. Results: The mean GFR after donation
UTO were excluded. Also, some scans were excluded due to was lower averaging 52±8.6ml/min/1.73m2 in the >60y group
technical errors (inconsistent time zero, patient motion and vs. 69±9.6ml/min/1.73m2 in the <60y group (p=0.01). The AI
non-bolus injection). Drainage status, renal perfusion and of the remnant kidney after kidney donation was 10.4±1.7% in
function, both in absolute and differential terms, and all other the > 60y group vs. 12.5±0.8% in the <60y group (p=0.03). The
relevant data, including demographic variables were recorded. A increase of AI of the remaining kidney was lower in the >60y
parenchyma to perfusion count ratio, corrected for background group (20±26% vs. 49±28% in the <60y group; p=0.04). The
and time, was calculated. A ratio between parenchymal phase GFR decreased by 30±14% after donation in the >60y donors
and vascular phase counts, adjusted for time and background, vs. 27±23% in the <60y (p=0.54). None of the patients in both
was calculated (F/P). Statistical analysis was performed using groups had a GFR of less than 30ml/min/1.73m2 after >6months
SPSS version 25.0. Results: 57 patients were selected (28 women, after kidney donation. Conclusion: In our study, donors over 60y
29 men; age: 56.21±18.98, 19-95 years), with 114 kidneys, which had a GFR decrease following kidney donation comparable to
were categorized as: group one - no suspected UUTO (31 right younger donors less than 60y. Thus, living kidney donation from
kidneys [RK], 26 left kidneys [LK]); group two - suspected UUTO older patients appears to be safe based on the pre-donation
without obstructive pattern (20 RK; 17 LK) and group three GFR and separate kidney function assessed by renography.
- suspected UUTO with obstructive pattern (6 RK; 14 LK). The The significance of the lower increase of AI of the remaining
median F/P was 3.63 (interquartile amplitude=1.65;1.14-10.84) kidney in the >60y group remains to be further investigated.
for group one, 3.81 (interquartile amplitude=1.58;2.19-9.56) for References: None.
group two and 2.23 (interquartile amplitude=1.72;0.95-5.77)
for group three. Statistically significant differences for F/P were
found between group three and the other two (Krustal-Wallis EP-0286
with Bonferroni correction, p<0.001 for both groups 3-1 and Gravity-dependent Diuretic-renography: A Rational
3-2). No statistically significant difference was found between Approach For Functional Evaluation Of Urinary Diversion
group one and two. Conclusion: Despite further larger and G. Tartaglione1, N. Foschi2, S. M. Recupero2, M. Racioppi2,3, R.
prospective studies are warranted, in our series, the F/P ratio Bientinesi2, G. Palermo2, M. Ragonese2, L. Di Gianfrancesco2, E.
seems to be statistically different between obstructed and non- Sacco2, F. P. Ieria1, F. Pinto2, P. F. Bassi2,3;
obstructed kidneys. References: None. 1
Nuclear Medicine, Cristo Re Hospital, Rome, ITALY,
2
Department of Urology, Fondazione Policlinico
Universitario “A. Gemelli” IRCCS, Rome, ITALY, 3Urology,
EP-0285 Università Cattolica del Sacro Cuore, Rome, ITALY.
Outcome of Kidney Function after Kidney Donation in
Donors over 60 Years Old
M. A. E. Nicod Lalonde, J. Venetz, C. Geldhof, G. Allenbach, N. Aim/Introduction: Urinary diversion is anyone of several
Schaefer, J. O. Prior, A. Boubaker; surgical procedures that divert the flow of urine to a
University Hospital of Lausanne, Lausanne, SWITZERLAND. replacement bladder (neobladder) or through an opening in
the abdominal wall (stoma), connecting ureters with a tract of
bowel. A stricture of the uretero-ileal anastomosis might appear
Aim/Introduction: The aim of this study was to evaluate the in 1:5 of patients. The right identification of patients who would
outcome of kidney function following live kidney donation in benefit from surgical treatment is a significant clinical challenge.
donors aged over 60 years (>60y) compared to live donors under We proposed Gravity-Dependent Diuretic-Renography (GDDR)
60 years (<60y). Materials and Methods: We prospectively with method F+10(sp) (Seated Position), in patients with urinary
enrolled 27 living donors in the >60y group (15F/12M) with diversion and a suspected stenosis of the urinary tract. Materials
a mean age at kidney donation of 65±5y [range 60-78y] and and Methods: 39 patients with CT or ultrasound evidence of
4 donors in the <60y group (4F) with a mean age of 44±5y hydronephrosis in 44 Renal Units (RUs), and/or impairment
[37-48y]. The enrollment of the <60y group was terminated of renal function parameters were enrolled. All subjects
early because of unavailability of Cr-51-EDTA. All but two underwent GDDR with method F+10(sp) whereby the patient
donors had an estimation of renal function by I-123 hippuran received IV a dose of MAG3-99mTc (150 Mbq, 0,3 mL) at time 0,
renal scintigraphy (RS) prior to kidney donation. All but four drank 400 to 500 mL of water at the 5 minute, and received an
donors had an estimation of glomerular filtration rate (GFR) IV injection of 20 mg of Furosemide as a bolus at the 10 minute
by measuring plasma clearance of Cr-51-EDTA prior to kidney after tracer injection [F+10 (sp)] during dynamic acquisition in
donation. A second assessment was made for all donors >6 seated position. Post-voiding static images at 20’ and 60’ were
months after kidney donation (mean 3.0±1.7y [0.6-5.7y] in the acquired. Test evaluation was based on Semi-quantitative
>60y group and mean 4.0±2.2y [2.4-7.2y] in the <60y group). parameters: Tmax (nv <7 min), Diuretic T1/2 (nv <8 min), Ratio
The accumulation index (AI) acquired during RS (defined as the 20min/peak (nv <0.25). The results were classified as: Dilation
percentage of injected activity extracted by the kidney during (Tmax >7 min, Ratio 20min/peak <0,25), Obstruction (Tmax >7
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S514

min, Ratio 20min/peak >0.25), or Equivocal. Results: F+10(sp) of 3 (31.89%). Of the 39 patients without biopsy, the renogram
test showed: Dilation in 7/44 RUs (15.6%); Obstruction in 36/44 was normal in 14 patients (36%), 12 had discrete acute tubular
RUs (81.8%); Equivocal results in 1/44 RUs (2,3%). No side effects necrosis (ATN) (30.77%), 11 moderate ATN (28.2%) and only 1
were reported. In 10 patients anastomosis stenosis caused RUs showed poor vascularization but it was secondary to intra-
impairment and a nephroureterectomy was performed. In 7 out surgical hemorrhage. The only case with a SCORE 0 showed
of 10 patients RUs failure occurred < 6 months after surgery. a normal renogram. Of the 12 patients with SCORE 1, 3 cases
In selected patients, diagnostic work-up involved a retrograde were normal (25%), 5 had discrete ATN (41.66%), 3 moderate
cystography or a loop-graphy to confirm ileal-ureteral reflux. ATN (25%) and 1 showed vascular thrombosis (8.33%). Of the 27
The equivocal result was related to an ileal-ureteral reflux. patients with SCORE 2, 5 cases were normal (18.5%), 12 discrete
Conclusion: In urinary diversion the urine drainage is clearly ATN (44.4%), 2 moderate ATN (7.4%), 7 severe ATN (26%) and 1
dependent by patient position. The GDDR with method F+10sp vascular thrombosis (3.7%). And of the 37 cases with SCORE 3, 9
exploiting gravity, better evaluates the gravity-dependent patients presented a normal renogram (24.3%), 11 discrete ATN
urine drainage, discriminating obstruction from simple urinary (29.72%), 9 moderate ATN (24.32%), 6 severe ATN (16.21%), 1
dilation. Thanks to a reduced dose of Furosemide (20 mg) and urine leak (2.7%) and 1 vascular thrombosis (2.7%). Conclusion:
a better timing, the test avoids the side effects typical of other the renogram shows a good correlation with the SCORE
methods (bladder filling, disruption because voiding, and obtained in the histopathology of the kidney graft biopsy.
diuretic-related-hypotension) increasing accuracy. Considering Higher SCOREs show more pathological scintigraphic findings
the high rate of early stenosis (<6 months) of the uretero-ileal (moderate-severe ATN and surgical complications): no biopsy
anastomosis, this diagnostic approach might be suggested (28.2%), SCORE 1 (33.3%), SCORE 2 (37.1%), SCORE 3 (45.93%).
during first months after surgery. References: 1) Taylor AT, et al References: None.
Semin Nucl Med. 2018 Jul;48(4):377-3902.

EP-0288
EP-0287 Importance of 99mTc-DTPA renal scintigraphy in
Viability Of The Transplanted Renal Graft. Correlation evaluating renal function in the pre-operative and post-
Between Renal Biopsy And Isotopic Renogram 24h Post- operative elective F/BEVAR phases TAAAs
Transplant V. Frantellizzi1, L. Cosma1, M. Ricci1, M. Orrico2, N. Mangialardi2, M.
J. Gómez Hidalgo1, M. Ruiz Gómez1, N. Álvarez Mena1, P. Liberatore1;
Turbay Eljach1, B. Pérez López1, C. Gamazo Laherrán1, M. Alonso 1
Sapienza University of Rome, Rome, ITALY, 2San
Rodríguez1, A. Sainz Esteban1, M. Méndez Pascual2, S. De Pablo Camillo Forlanini Hospital, Rome, ITALY.
Leonardo2, M. González Soto1, R. Ruano Pérez1;
1
Hospital Clínico Universitario de Valladolid. Medicina
Nuclear, Valladolid, SPAIN, 2Hospital Clínico Universitario de Aim/Introduction: The objective of this study is to evaluate any
Valladolid. Unidad de trasplante renal, Valladolid, SPAIN. variation of renal function detected by dynamic renal scintigraphy
with 99mTc-DTPA after elective fenestrated or branched
endovascular aneurysm repair ( F/BEVAR) for thoracoabdominal
Aim/Introduction: to relate the histopathological assessment aortic aneurysms (TAAAs) and to assess whether branches and
(SCORE) of the renal graft in patients transplanted with the fenestrations have different early-term effects on renal function.
isotopic renogram performed at 24 post-transplant. Materials Materials and Methods: Between January 2018 and March
and Methods: we studied 116 patients with cadaver kidney 2019, 26 patients (13 males, 13 females) underwent elective F/
transplantation. The protocol of the histopathological BEVAR for TAAAs. To assess renal function 99mTc-DTPA perfusion
assessment in the kidney transplant is by wedge biopsy; the scintigraphy was performed two weeks pre-operatively and
processing of it is by freezing and is performed in those donors at 3 and 6 months post-operatively. Overall, 51 kidneys were
> 60 years old or between 40-60 years with hypertension and/ analyzed: 19 in patients treated with branches and 32 with
or diabetes. The SCORE of the renal biopsy is obtained from fenestrations. Primary end points were peri-procedural technical
the sum of 4 sections: percentages of glomerular sclerosis (0- success, 30-days Medication administration errors (MAEs) and
3), intimal fibrous arterial hyperplasia (0-3), tubular atrophy (0- Glomerular Filtration Rate (GFR) variations between the pre-
3) and interstitial fibrosis (0-3). Renal grafts with a total SCORE operative and the post-operative dynamic renal scintigraphy.
> 3 or one of the 4 sections with a score ≥ 2 are rejected. Secondary end points were significant alterations of other
Twenty-four hours after transplantation we performed a 30 parameters at the 99mTc-DTPA renal scintigraphy (time to
minutes renogram study focusing on the abdomen in anterior peak, percentage of kidneys’ perfusion and radioisotope uptake
projection after the administration of 370 MBq of 99mTc-DTPA percentage). Results: The mean pre-operative global GFR was
followed by planar images at 30 and 180 minutes. Results: we 53.2 ml/min (SD 20.2 range 18.02 - 95.5 ml/min). In 11 patients
studied 116 patients (age: 61+/-12). In 39 transplanted grafts (4 treated with renal branches, 7 with renal fenestrations) the
(33.62%) no biopsy was performed (not necessary). Of the rest renal function was normal (pre-operative GFR > 60 ml/min); 11
of cases, only 1 presented a SCORE of 0 in the biopsy, 12 showed patients (5 treated with branches, 6 with fenestrations) had mild
a SCORE of 1 (10.34%), 27 SCORE of 2 (23.27%) and 37 SCORE to moderate chronic kidney disease (CKD) (pre-operative GFR
S515 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

between 60 and 30 ml/min) and 4 patients (1 treated with renal calculated by full characterisation of the plasma clearance
branches, 3 treated with fenestrations) had severe CKD (pre- curve with 9-samples from 5 minutes to 8 hours post injection.
operative GFR < 30 ml/min). The GFR of the kidneys in which For both cohorts, applying the formula derived by Brochner-
the renal arteries were managed by a side branch decreased Mortensen and Rodbro1 to model inulin clearance to the 51Cr
significantly after 3 months (Z -2.03; p = 0.05) while no EDTA measurements removed the difference with 99mTc DTPA.
significant GFR’s variations were noted after the treatment with Conclusion: There is a small systematic difference between
fenestrations (Z -0.7; NS). The time to peak was also significantly normalised GFR measured with 51Cr EDTA and 99mTc DTPA, which
reduced after the treatment with branches (Z -1.8; p = 0.05) but is removed when GFR is calculated by full characterisation of the
showed no significant modifications with fenestrations’ (Z -1.5 plasma clearance curve. However, this is not clinically significant
;NS). There were no further alterations regarding the remaining in the context of intra-patient variability of GFR measurement,
scintigraphic parameters. Conclusion: The use of branches for especially when GFR is measured without exercise restriction.
renal arteries is associated with a significant decrease of the GFR 99m
Tc DTPA is more closely matched with inulin than 51Cr EDTA.
compared to the use of fenestrations and the alterations are References: 1. Brochner-Mortensen, J. and P. Rodbro, Selection
evident at early stage. Longer follow-up on a larger population of routine method for determination of glomerular filtration rate
submitted to 99mTc-DTPA renal scintigraphy will be useful in in adult patients. Scandinavian Journal of Clinical & Laboratory
evaluate separately renal function, clarifying the natural history Investigation., 1976. 36(1): p. 35-43.
of these alterations and their clinical implications. References:
None.
EP-0290
Comparison Of Simultaneous Plasma Clearance Of 99mTc-
EP-0289 DTPA And 51Cr-EDTA - Can One Tracer Replace The Other?
51
Cr EDTA vs 99mTc DTPA vs inulin for GFR measurement: is L. Petersen, T. Andersen, L. Jødal, N. Nielsen;
there a systematic difference? Department of Nuclear Medicine, Aalborg, DENMARK.
H. McMeekin1, F. Wickham2, M. Barnfield3, M. Burniston1;
1
Barts Health NHS Trust, London, UNITED KINGDOM, 2Royal
Free London NHS FT, London, UNITED KINGDOM, 3Leeds Aim/Introduction: Aim: Both 99mTc-DTPA and 51Cr-EDTA are
Teaching Hospitals NHS Trust, London, UNITED KINGDOM. widely used for determination of glomerular filtration rate
(GFR), but direct comparative studies are few in numbers.
Shortage of 51Cr-EDTA makes a direct comparison highly
Aim/Introduction: The study aimed to investigate whether relevant. The aim of the study was to investigate if there is any
a systematic difference exists between 51Cr EDTA and 99mTc clinical relevant difference between plasma clearance of 99mTc-
DTPA for measurement of glomerular filtration rate (GFR), DTPA and 51Cr-EDTA. Materials and Methods: Materials and
and to see how each tracer compares with modelled inulin Methods: Patients ≥ 18 years of age referred for routine GFR
clearance using the formula of Brochner-Mortensen and measurement by 51Cr-EDTA were prospectively enrolled. The
Rodbro.1 Materials and Methods: GFR results from candidates two tracers (10 MBq 99mTc-DTPA and 2.5 MBq 51Cr-EDTA, both
attending the Royal Free Hospital nuclear medicine department 0.5 mL) were intravenously injected at time zero. A standard
for assessment of suitability for kidney donation during the 4-sample technique was applied with samples collected at 180,
period October 2008 to May 2015 were reviewed. The clinical 200, 220, and 240 minutes if estimated GFR (eGFR) was ≥ 30
protocol for GFR measurement had changed from using 51Cr mL/min. Plasma clearance were calculated according to a one-
EDTA to 99mTc DTPA in October 2012, allowing the comparison pool model. Results: Results: Fifty-six patients (69% men) were
of measured GFR distribution in the normal population before enrolled into the study. All patients had an estimated GFR > 30
and after the change of radiopharmaceutical. A second cohort mL/min/ 1.73 m2. No patients suffered from ascites or significant
of oncology patients attending Leeds Teaching Hospitals oedema. The mean 51Cr-EDTA plasma clearance was 82 mL/
NHS Trust underwent simultaneous GFR measurement with min (range 16-226). Plasma clearances determined by the two
both tracers. Results: From the first cohort, 184 GFR studies methods were highly correlated (r=0.993). Plasma clearance of
performed with 51Cr EDTA and 154 performed with 99mTc 51
Cr-EDTA was statistically lower when measured by 51Cr-EDTA
DTPA were included in the analysis. A systematic difference than 99mTc-DTPA (P=0.01), but the numerical difference was
of 5.8% (95% confidence interval: 1.5% - 10.1%) was found minimal (mean difference -1.4 mL/min; 95% limits of agreement
in the normalised GFR, with 99mTc DTPA giving the higher (LOA) -6.6 to 9.4). The difference between the two methods
result. This difference was found to be statistically significant, was independent of the level of renal function. Conclusion:
with a p-value of 0.008. From the second cohort, 50 patients Conclusions: No clinically relevant difference was found
underwent simultaneous GFR measurement with both tracers. between 99mTc-DTPA and 51Cr-EDTA one-pool plasma clearance.
A systematic difference of 2.9% (95% confidence interval: 1.8% Therefore, 99mTc-DTPA can replace 51Cr-EDTA and vice versa
-3.9%) was found in the normalised GFR, with 99mTc DTPA giving when needed. References: None.
the higher result. This difference was found to be statistically
significant, with a p-value of 0.00001. There was no statistically
significant difference between the tracers when the GFR was
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S516

EP-0291 more difficult in many countries, and another method using a


Accuracy of 24h Single Sample Measurement for Low GFR 24-hour urine collection is sometimes inaccurate depending
and Comparison with Same Day Slope-Intercept GFR on the patient’s cooperation. In this study, we showed the
N. Sizer1, H. McMeekin1, F. Wickham2, B. Fongenie2, M. Burniston1; correlation between the GFR measured using 51Cr-EDTA and
1
Barts Health NHS Trust, London, UNITED KINGDOM, 2Royal Free the total bladder activity measured by quantitative 99mTc-DTPA
London NHS Foundation Trust, London, UNITED KINGDOM. SPECT-CT, and derived a formula estimating GFR. Materials and
Methods: Among the patients who visited Korea University
Ansan Hospital from November 2016 to April 2017 with
Aim/Introduction: The accuracy of a single sample GFR (SS- decreased renal function, those who agreed were prospectively
GFR) technique with a sample taken at 24 hours (24h) post- enrolled. There was no specific patient preparation except 500
injection for patients with GFR lower than 30 ml/min/1.73m2 ml of water was provided for good hydration. Quantitative SPECT
was investigated. A comparison with the results from same day images were acquired with Siemens Symbia Intevo SPECT-CT at
slope-intercept GFR (SI-GFR) was also performed. Materials 40 minutes after the intravenous administration of 99mTc-DTPA
and Methods: Data from patients referred for GFR assessment (290~444 MBq). The SPECT acquisition protocol was as follows:
to inform the management of chronic kidney disease at the 30 views per each detector, 10 seconds per view, using a low-
Royal Free Hospital were reviewed. 4-sample SI-GFR calculation energy high resolution collimator in step-and-shoot mode over
with samples at 2h, 4h, 6h, and 24h post-injection was taken 360 degrees with circular orbit, and a 256*256 matrix. SPECT
as the reference measurement to which the Gref and Karp SS- images were reconstructed using the xSPECT Quant method
GFR (24h sample) [1] and same day SI-GFR (2h, 4h samples) with 24 iterations, 2 subsets, and 10 mm Gaussian filter. Using
were compared. In addition, 4-sample SI-GFR calculations with MIM Maestro, the volume of interest (VOI) of bladder was drawn
samples at 2h, 3h, 4h and 24h post-injection from patients with based on CT image, and a sphere with a diameter of 3 cm drawn
measured low eGFR at Barts Health NHS Trust will be reviewed in abdominal cavity was used to correct background activity.
for comparison with the Gref and Karp SS-GFR and same day SI- Mean percent of the injected dose per unit volume (%ID/ml)
GFR. Results: 47 GFR examinations with reference GFR less than and the volume of each VOI were used for calculation. All the
30 ml/min/1.73m2 were included in the analysis from the Royal statistics were performed using GraphPad Prism, and Pearson
Free Hospital. Bland-Altman analysis gave mean differences of correlation coefficients were obtained because all data sets were
0.5 (95% confidence interval: -0.2 - 1.3) ml/min/1.73m2 for SS-GFR satisfactory with normality tests. Results: Among 22 enrolled
(24h) and 2.4 (95% confidence interval: 1.3 - 3.6) ml/min/1.73m2 patients, 2 patients had polycystic kidneys and 11 patients had
for same day SI-GFR. 95% limits of agreement were -4.3 - 5.4 previous kidney transplantation. The correlation coefficients
ml/min/1.73m2 for SS-GFR (24h) and -8.1-12.9 ml/min/1.73m2 for the groups of patients with transplanted kidney, without
for same day SI-GFR. Results from the Barts Health NHS Trust transplanted kidney, and all patients were 0.858, 0.892 and
patient cohort will be presented at the conference. Conclusion: 0.877 respectively, showing good correlation and no significant
SS-GFR with a 24h sample is more accurate than same day SI- difference between the groups. The following formula to
GFR in patients with GFR less than 30 ml/min/1.73m2. Using estimate GFR from %ID of 99mTc-DTPA collected in bladder was
SS-GFR with a 24h sample in routine clinical practice will result obtained: GFR [ml/min] = 2.35* total bladder activity [%ID] +5.75.
in clinically insignificant differences in GFR result compared The Pearson correlation coefficient between the estimated GFR
with the reference technique, whereas a same day SI-GFR from this formula and the measured GFR using 51Cr-EDTA was
measurement could cause large inaccuracies. References: 0.877 (0.723~0.948; 95% C.I.). Conclusion: The total bladder
[1] Gref MC, Karp KH. Single-sample 99mTc-diethylenetriamine activity measured by quantitative 99mTc-DTPA SPECT-CT shows
penta-acetate plasma clearance in advanced renal failure by the good correlation with GFR measured using 51Cr-EDTA, and can
mean sojourn time approach. Nucl Med Commun 2009, 30:202- be a possible method to estimate GFR. References: None.
205.

EP-18
EP-0292 Clinical -> Diagnostic study -> Adult study
Glomerular filtration rate can be estimated from the total
bladder activity measured by quantitative 99mTc-DTPA
-> Oncology study -> General oncology ->
SPECT-CT
Radioguided surgery
C. Kim1, J. Cha1, Y. Kang1, D. Cha1, K. Kang2;
1
Korea University Ansan Hospital, Ansan, KOREA, October 12 - 16, 2019 e-Poster Area
REPUBLIC OF, 2Seoul National University College
of Medicine, Seoul, KOREA, REPUBLIC OF.
EP-0293
Sentinel lymph node biopsy in prostate cancer: a modified
Aim/Introduction: A method using 51Cr-EDTA is considered as injection technique targeting the tumor index lesion
a gold standard for measuring glomerular filtration rate (GFR). A. Mestre Fusco1, L. Fumadó2, J. Abascal2, L. Reixach3, M. Suárez-
However, the availability of 51Cr-EDTA is becoming more and Piñera1, N. Juanpere4, S. Vidal-Sicart1,5, L. Cecchini2;
S517 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

1
Nuclear Medicine, Hospital del Mar - Parc de Salut Mar, Barcelona, Aim/Introduction: Secondary lymphedemas usually occur
SPAIN, 2Urology, Hospital del Mar - Parc de Salut Mar, Barcelona, after lymphadenectomies and there is an increasing surgical
SPAIN, 3Universitat Autònoma de Barcelona, Barcelona, SPAIN, possibilities in their treatment beyond microsurgery,as lymph
4
Pathology, Hospital del Mar - Parc de Salut Mar, Barcelona, node transfer,when conventional measures are inefficient.
SPAIN, 5Nuclear Medicine, Hospital Clínic, Barcelona, SPAIN. Our aim is to study the utility of lymphoscintigraphy in this
context,evaluate patterns of lymphedema improvement
after lymph node transfer and establish an intra-surgical role
Aim/Introduction: The concept of sentinel lymph node biopsy for lymphoscintigraphy. Materials and Methods: Reviewed
(SLNB) in Prostate Cancer (PCa) was introduced in order to avoid 15p,14p lymphedema upper limb and 1p lower limb(grade
the invasiveness of extended pelvic lymphadenectomy (ePLND). II-III).Pilot protocol:lymphoscintigraphy pre-surgery,after
SLNB in PCa is still nowadays considered experimental. Our aim interdigital injection of 4 mCi 99mTc-Nanocol in both extremities,
is to study a modified injection of 99m-Tc to the Index Lesion followed by planar images after 15-30 min and 2 h(+SPECT-
(IL) to perform sentinel node dissection in PCa. Materials and CT), and measurements(cms) of both limbs.Surgery day:
Methods: A prospective study performed between June 2016 2mCi of 99mTc-Nanocol injected into donor lower limb(“revers
and October 2018. The study involved a cohort of 41 patients mapping”).All donor areas were from inguinal lymph nodes.
diagnosed as intermediate to high-risk PCa. MRI was performed, Intraoperative images of inguinal region are obtained by
with an IL and confirmed pathology. All patients underwent portable gamma camera(Sentinella) to mark the physiological
laparoscopic radical prostectomy (LP) with sentinel lymph node drainage of the lower limb to design the flap,also confirmed
study (SLN) and ePLND. A preoperative lymphoscintigraphy with gamma probe. After cleaning fibrosis of the axillar
with radiotracer 99mTc-colloid was performed (day before receptor area, lymph node transfer was done.At 1-2y follow-
surgery, 240-300 MBq in 0.6 cc volume). Dose was injected to up, measurements of upper limbs and lymphoscintigraphy
the IL and its peripheral area through cognitive fusion technique underwent again.Pre and post-surgery drainage patterns are
guided by transrectal ultrasound (TRUS). A lymphoscintigraphy correlated with clinical and limb measurements. Results:
was subsequently performed with planar images taken at 8/15p had presurgical lymphoscintigraphy:lymphatic
30 minutes and 3-4 hours post-injection. Radioactivity of SLN drainage(4p), dermal backflow(6p), functioning lymph node
was intraoperatively measured by a gamma probe. Analysis levels II-III(3p) and supraclavicular activity(1p).5/8p underwent
included size and localization of the tumor, SLN drainage surgery,4 with revers mapping protocol.In 1p, an intra-surgical
and histopathology findings. The outcome determined were lymphoscintigraphy of the receptor axilla was also evaluated
sensitivity, specificity and PPV. Results: Lymphoscintigraphy to safeguard funtioning lymph nodes.Counting radiation
demonstrated no uptake drainage in 2 patients. Sentinel nodes of the lymph node flap showed<10% of total activity of
were positive in 10 patients (30.3%). No cases of negative physiological lymph node drainage to be preserved.Postsurgical
sentinel nodes resulted in any pN1, this is a NPV of 100%. lymphoscintigraphy:drainage improvement in 2/5p(less dermal
Sensibility, specificity and PPV were also 100%. A total of 524 backflow, uptake in axillary lymph nodes level III not related to
lymph nodes were harvested, 108 (20.6%) sentinel nodes. In flap tissue), and correlating with clinical improvement in 3/5p, as
total, 24 were positive, 14 within the sentinel area. Mean surgical well as reduction >1 cm in measurements on affected extremity.
time for LP + SLNB + ePLND was 208 minutes (IQR 180-240). There is no case of iatrogenic lymphedema of the lower limb
Although 13 patients suffered any type of intra or postoperative donor.7/15p had just postsurgical lymphoscintigraphies (2y
complication, only 2 cases are directly associates with SLNB follow-up):drainage improvement in all cases(uptake related
procedure: first one a symptomatic UTI related to TRUS tracer to lymph node transfer tissue/surgical clips or in some dense
injection and a second one, an ureteral injury that required tissue corresponding to lymphatics close to the flap or practical
surgical repair during the SLNB when a paraaortic SLN was absence of dermal backflow).Clinical improvement was only
being excised. Conclusion: Selective injection of radiotracer of seen in 5p but changes on measurements were not significant.
99mTc-nanocolloid to the prostate index lesion is a feasible and Conclusion: Lymph node transfer procedure is useful in clinical
safe technique in prostate cancer, with excellent results in terms improvement of chronic lymphedema.Lymphoscintigraphy
of patient staging. Negative SLNB is a predictor of negative seems to play a role in evaluating the viability of the lymph node
ePLND. References: None. flap based on changes in the lymphatic drainage, reduction of
the dermal backflow or flap tissue uptake, and that correlates
with clinical and morphological changes.Revers mapping
EP-0294 protocol of the donor limb is essential to avoid iatrogenic.Also
Role Of Lymphoscintigraphy In The Assessment Of intraoperative lymphoscintigraphy of upper limb receptor
Lymphedema Of Extremities In Microsurgery Of Lymph axilla could be useful to preserve functional lymph nodes.
Node Transfer References: None.
C. Sampol1,2, O. Roca1,3, J. Estrada1,3, N. Orta1,2, A. Repetto1, M.
Villar1, H. Navalon1, C. Peña1,2;
1
Hospital Universitari Son Espases, Palma De Mallorca,
SPAIN, 2IdISBa, Palma de Mallorca, SPAIN, 3Reconstructive
And Plastic Surgery, Palma de Mallorca, SPAIN.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S518

EP-0295 EP-0296
Feasibility Of The Radioguided Surgery During Concordance Between Intracervical and Fundal Injections
Transaxillary Endoscopic Parathyroidectomy for Sentinel Node Mapping in Patients With Endometrial
C. Sampol1,2, S. Pascual3, J. Julian3, J. Cifuentes3, A. Repetto1, N. Cancer?: A Study Using Intracervical Radiotracer and
Orta1,2, B. Luna1, M. Villar1, C. Peña1,2; Fundal Blue Dye Injections
1
Hospital Universitari Son Espases, Palma De Mallorca, R. Sadeghi1, M. Hassanzadeh Mofrad2, M. Farazestanian2, Z.
SPAIN, 2IdISBa, Palma de Mallorca, SPAIN, 3Hospital Yousefi2, S. Kadkhodayan2, L. Zarifmahmoudi1;
Son Llatzer, Palma De Mallorca, SPAIN. 1
Nuclear Medicine Research Center, Mashhad University of
Medical Sciences, Mashhad, IRAN, ISLAMIC REPUBLIC OF,
2
Women’s Health Research Center, Mashhad University of
Aim/Introduction: Radioguided surgery of the parathyroid Medical Sciences, Mashhad, IRAN, ISLAMIC REPUBLIC OF.
glands using unilateral cervical exploration is widely
established, replacing the bilateral cervical exploration. The
technical improvement of gamma probes and the application Aim/Introduction: Major controversy in sentinel node (SN)
of the sentinel node biopsy in laparoscopy would allow us to biopsy of endometrial cancer is the injection site of mapping
extrapolate that to endoscopic surgery of any pathology where material. We compared lymphatic drainage pathways of the
a radioguided surgery has its application.The objective of our uterine cervix and uterine body in the same patients by head-
study is to assess the feasibility of parathyroid radioguided to-head comparison of intracervical radiotracer and fundal
surgery using a minimally invasive surgical approach of the blue dye injections. Materials and Methods: All patients with
neck, which is the transaxillary endoscopic parathyroidectomy. pathologically proven endometrial cancer were included. Each
Materials and Methods: Included 7p, 3M/5W, mean age patient received 2 intracervical injections of Tc-phytate. At the
61yo,with a suspected diagnosis of primary hyperparathyroidism time of laparotomy, the uterus was exposed, and each patient
after an increase of PTHtest. All underwent cervical ultrasound/ was injected with 2 aliquots of patent blue V (2 mL each) in the
scintigraphy 10min and 2h after injection of 20mCi 99mTc-MIBI, subserosal fundal midline locations. The anatomical locations of
and early SPECT-CT. The surgery day we re-injected 10mCi of all hot, blue, or hot/blue SNs were recorded. Results: Overall,
99m
Tc-MIBI, and after transaxillary endoscopic approach of the 45 patients entered the study. At least 1 SN could be identified
neck, radioguided surgery of the adenoma was carried out using in 75 of 90 hemipelves (83.3% overall detection rate, 82.2% for
an endoscopic gamma probe. In 2 cases we used intravenous radiotracer [intracervical] alone, and 81.1% for blue dye [fundal]
indocyanine green(ICG). Intraoperatively,at 5 and 10 min after alone). In 71 hemipelves, SNs were identified with both blue
removing the suspected gland,blood samples of PTHhormone dye (fundal) and radiotracer (intracervical) injections. In 69 of
level were obtained and finally the specimen was sent for these 71 hemipelves, at least 1 blue/hot SN could be identified
anatomopathological confirmation. Results: All 7p had positive (97.18% concordance rate). In 10 patients, para-aortic SNs were
MIBI, predominantly left and inferior location. The ultrasound identified. All of these nodes were identified by fundal blue dye
was clearly coincident in 2p, uncertain in 3p and negative in injection, and only 2 were hot. Conclusion: Our study shows
2p. All adenomas in SPECT-CT were normotopic and directly that lymphatic drainage to the pelvic area from the uterine
related to the thyroid gland, excepting 1p which had an ectopic corpus matches the lymphatic pathways from the cervix, and
gland located in the thyro-thymic ligament. The mean basal both intracervical and fundal injections of SN mapping materials
PTH was 273.74pg/ml dropping to 25.4 pg/ml after removing go to the same pelvic SNs References: None.
the suspicious gland. Mean counts radiation of invivo adenoma
(gammaprobe) were 1116.66cps and 446.66cps exvivo.
Anatomopathological examination confirmed parathyroid tissue EP-0297
in all cases, with average weight of 0.71g(0.3-1.2) and average Findings in sentinel lymph node biopsy in 19 patients with
size 1.3cms. No remarkable complications during or immediately ovarian cancer
after surgery, including a patient with a pacemaker ipsilateral to A. Utrera, M. Agudelo-Cifuentes, J. Bernal, P. Bello-Arques, L.
the axillary approach. There were technical difficulties removing Matute, V. Lago, A. Yepes-Agudelo, G. Figueroa, V. Vera;
the ectopic gland due to the premediastinal location and the Hospital La Fe, Valencia, SPAIN.
millimeter size, finally proceeding to unilateral anterior neck
exploration. Both cases of using combination of radioactivity
and ICG, the fluorescence clearly helped in the delimitation Aim/Introduction: Our aim is to describe our experience
and removing adenomas. Conclusion: Transaxillary endoscopic with sentinel lymph node biopsy (SLNB) in ovarian cancer,
radioguided surgery of parathyroid adenomas is feasible and between 2017 and 2019. Materials and Methods: We have
safe method, similar to minimally invasive anterior cervical neck carried out a study with 19 patients whose ages range from 26
exploration, although it requires training, especially in ectopic to 74 years old (which average is 50 years old). The technique
location. The combined use of intravenous ICG helps and speeds we used consisted in one injection of 1mCi of 99mTc-albumin
up the process of identification and resection of the adenoma. nanocolloid in the ovarian ligaments or in the stump, during the
The radioguided protocol for surgical intervention is the same, surgery, followed by acquisition of static image with portable
eliminating cervical scar. References: None. gamma camera to assess migration and further localization
S519 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

of the sentinel nodes with gamma probe. In 53%, the surgical by standard lymphodissection. Between 04.2015 and 12.2018,
approach was laparoscopic. In all cases systematic aortic and 37 patients were enrolled in the study Results: Sentinel lymph
pelvic lymphadenectomy (SAPL) was performed. Results: In 2 nodes were visualized in all but one patient. Bilateral lymph flow
out of 19 patients, technical failures occurred regarding to the from the tongue cancer was detected in 17 (47%), monolateral
administration of radionucleid (extravasation and incomplete - in another 19 (53%) patients. Among evaluated 36 patients,
injection). The application of the tracer was performed in 63% metastases in SLN were detected in 6 cases. Additional non-
of the cases in the stump and 37% were injected in the ovarian sentinel lymph nodes were involved in 5 of these 6 patients,
ligaments. We detected sentinel nodes in 88% of the patients, in 4 cases metastases were detected distally from the level of
57 % in abdominal lymphatic area and 43% in pelvic area. We involved SLN. In 4 patients with non involved SLN examination
removed a mean of 3 nodes (1-7). We classified the SLNB as: of LN removed by standard lymphatic dissection identified LN
abdominal lymph nodes (paraortic, paracaval, interaortocaval) metastases. In all 4 cases these nodes were localized on the next
and pelvic lymph nodes (common iliac, external iliac, interiliac level distally from the SLN basin. According to presented data
and obturator) In the anatomopathological study of the lesions, sensitivity of SLN biopsy was 60%, false negative rate - 40%. If
it could be verified that the majority of the tumour pieces biopsy of SLN would be supported by dissection of SLN basins
corresponded to endometrial subtype with a frecuency of 35%, and one level distally than sensitivity of the procedure would
followed by 24% of clear cells, 18% serous, 6% mucinous, 12% reach 100% with false negative rate - 0%. Conclusion: In our
borderline and others 6%. We had only one case of bilateral patients with the oral tongue cancer (cT1-2N0M0) biopsy of SLN
ovarian cancer; it was an atypical borderline tumor. From the charachterised by low sensitivity (60%) and high false negative
sample studied, without taking into account two technical rate (40%) that can be explained by skip metastases one level
failures, the following results could be observed: In one case we distally. Combination of SLN biopsy with SLN basin dissection
didn’t find any sentinel lymph node and the lymphadenectomy and dissection of LN one level distally can be promising tool
was negative for metastatic spread. One patient was positive for for safety and not-traumatic treatment of these patients.
metastatic infiltration at lymphadenectomy despite negative References: None.
sentinel node. Other case presented with a positive sentinel
node, without invasion of the other nodes at lymphadenectomy,
it was a borderline bilateral cancer Conclusion: In our EP-0299
experience the SLNB in ovarian cancer has shown promising Sentinel node biopsy in breast ductal carcinoma in situ:
results, with a high detection rate and specificity. It could lead to our experience
a future limitation of systematic lymphadenectomies in patients P. Fernández-Rodriguez, Á. De Bonilla Damiá, R. Álvarez Pérez, R.
with ovarian cancer, avoiding its side effects. More sample Fernández López, D. Tamayo Carabaño, J. Jiménez-Hoyuela García;
and prospective studies are needed to collect stronger data. Department of Nuclear Medicine. Universitary
References: None. Hospital Virgen del Rocío, Sevilla, SPAIN.

EP-0298 Aim/Introduction: Ductal carcinoma in situ (DCIS) of the breast


Sentinel lymph node biopsy in patients with oral tongue is a preinvasive neoplasm without periductal stromal invasion
cancer: prospective single center study that represents about 20-25% of all breast malignancies. The
P. Krzhivitckii1, S. Novikov1, S. Kanaev1, Z. Radgabova1, M. Kotov1, incidence has experienced an important increase with the
O. Ponomareva1, A. Artemyeva1, M. Girshovitch1, Y. Melnik1, M. introduction of mammography screening. DCIS is a subtype
Bisyarin2; of breast cancer theoretically unable to metastasize; therefore,
1
N.N. Petrov National Medical Research Center of Oncology, sentinel lymph node biopsy (SLNB) procedure for DCIS is
St Petersburg, RUSSIAN FEDERATION, 2N.N. Petrov Research controversial and is not standard of care. However, nodal
Institute Oncology, St Petersburg, RUSSIAN FEDERATION. involvement for DCIS patients is reported. Aim of our study
was to identify preoperative features predictive of nodal
involvement in DCIS patients. Materials and Methods: We
Aim/Introduction: The purpose of the study was to evaluate have retrospectively reviewed 78 patients with a median age
sensitivity and false negative rate of sentinel lymph node (SLN) of 55 years old [35-86] from January 2016 to December 2017
biopsy compared to with the standard lymph nodes (LN) with a preoperative diagnosis of DCIS following a vacuum-
dissection in detecting metastatic disease. In addition, we tried assisted breast biopsy (VABB), and undergoing surgery with
determine optimal amount of LN sampling. Materials and sentinel node biopsy. Only patients with a preoperative
Methods: All patients with T1-2N0 clinical stage of oral tongue histopathology of pure DCIS without microinvasive disease and
cancer were eligible for inclusion in this prospective single without ultrasound or MRI evidence of lymphadenopathy (pTis
center study. Lymph node mapping was obtained by injection cN0) were included in the analysis. Variables distribution was
of 99mTc-nannocolloids (100-150MBq in 0.3-0.4ml) in 4 points compared between patients upstaged to invasive cancer at final
around the primary lesion. SPECT-CT visualization of sentinel pathology and patients with a confirmed DCIS, and between
lymph nodes started 60-120 min after injection. SLN biopsy positive vs negative sentinel node patients. Results: Lymph
started 8-12 hours after mapping and in all cases was followed node biopsy was positive in 15 (19.2%) patients, with 8 (53.3%)
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S520

macrometastases and 7 (46.6%) micrometastases. These patients Lymphatic outflow in urachal cancer can be bilateral or unilateral.
presented several factors were predictive of nodal involvent Preoperative scintigraphic assessment of lymphatic drainage
like nuclear grade 2-3 (86,6%), Breast Imaging Reporting and with hand held gamma probe verification of SLNs in urachal
Data System (BI-RADS) index >4 (93,3 %), lesion extension >20 cancer allows minimally invasive, targeted lymphadenectomy.
mm (66.6%), cribiform and solid type (73,3%), and upstaging No recommendations about extension of lymphadenectomy
disease (66.6%), although upstaging could not be predicted were proposed. References: None.
preoperatively. Therefore, these factors should be considered
for axillary evaluation. Axillary dissection was performed in
46,6% of these patients. Conclusion: The role of SLNB in DCIS EP-0301
patients is controversial, but routine abstention may increase Sentinel Lymph Node Detection in Patients with
the risk of understaging and subsequent undertreatment of Melanoma on the Shoulder and Upper Trunk - a Guidance
some patients. The presence of macrometastatic axillary nodes for Surgical Planning
in DCIS would change the subsequent adjuvant treatment, M. Punda, I. Milas, J. Staničić, Z. Puljiz, M. Bosak-Butković, M. Šitum,
and even micrometastases could be suitable in order to plan M. Franceschi, T. Jukic;
a appropiate follow-up. A particular subgroup of DCIS with UHC Sestre Milosrdnice, Zagreb, CROATIA.
higher risk for positive SLNB could be identified, in which axillary
evaluation would be required to define the most appropriate
clinical management. References: None. Aim/Introduction: Cutaneous melanoma of the trunk shows
potential to drain to multiple and uncommon lymphatic basins.
The aim of the study was to determine the location of common
EP-0300 and uncommon sentinel lymph nodes (SLNs) in patients
Radionuclide-guided sentinel lymph node mapping in with melanoma on the shoulder and upper trunk related to
urachal cancer anatomic subareas of primary melanoma and its impact on
W. Cytawa, W. Połom, B. Brockhuis, P. Lass, M. Matuszewski; surgical planning. Materials and Methods: The study included
Medical University of Gdansk, Gdansk, POLAND. 172 patients (61.6% men, mean Breslow thickness 2.941±2.82
mm) who underwent SLN biopsy from January 2015 to January
2019. For the analysis, we defined six anterior and nine posterior
Aim/Introduction: Urachal cancer is a rare non-urothelial anatomic sub-areas of the upper trunk and two of the shoulders.
carcinoma with the incidence rate of 0.35 to 0.7 % of all bladder We considered all other locations outside of axilla as uncommon.
cancers and 22 to 35 % of adenocarcinomas of the bladder. It After peritumoral injection of 99mTc-nanocolloid, dynamic and
forms from the malignant transformation of enteric epithelium static planar imaging was performed. SPECT/CT was performed
in the urachus (or its remnants) located between dome of in 9.3% of patients. Results: Melanoma distribution was mainly
the bladder and the umbilicus. The purpose of this study was in the upper sub-areas of the upper trunk: in 22/26 patients with
to perform the radionuclide-guided mapping of lymphatic anterior and among 104/121 patients with posterior location.
drainage with the use of preoperative lymphoscintigraphy Anterior melanomas showed axillary drainage in 24 (92.3%)
and intraoperative gamma probe detection in patients with of patients; 95.8% unilateral. Uncommon SLNs were detected
urachal cancer, and try to propose the lymphadenectomy in 5/26 patients: 3 supraclavicular, 1 infraclavicular and 1
template. Materials and Methods: A prospective study was subcutaneous SLN near the scar. Among patients with posterior
conducted on 5 patients with urachal cancer. In each patient melanoma, 93.4% had axillary drainage. Out of them, 43.4% had
the region around the primary tumor was injected with 99mTc- bilateral axillary drainage; 28.1% from medial trunk sub-areas. In
nanocolloid during cystoscopy the day before surgery. SPECT/ 37/121 posterior melanomas we detected 47 uncommon SLNs:
CT lymphoscintigraphy was performed using dual-head gamma 22 supraclavicular, 12 inside the triangular intermuscular space,
camera short before surgery. The sites of focal tracer uptake were 8 nuchals and 5 in other locations. Melanoma on the shoulders
reported and verified intraoperatively using hand held gamma (14 right, 11 left) in all but one patient drained to ipsilateral
probe. All radioactive lymph nodes were considered sentinel axilla, 4/25 patients had ipsilateral supraclavicular SLNs. In total,
lymph nodes (SLNs) and surgically removed during sentinel we identified 57 uncommon SLNs in 47 (27.3%) of patients,
lymph node biopsy (SLNB) procedure. Lymphadenectomy of drained mostly (81% of SLNs) from the posterior upper trunk.
the remaining lymph nodes within a given lymphatic basin Eleven (23.4%) of patients showed single uncommon SLNs,
was additionally performed. Results: In all patients lymphatic without axillary involvement. The neck region was a drainage
outflow from the urachal tumor to the lymph nodes was present. basin for 42 uncommon SLNs among 31 patients. Out of 43
Preoperative SPECT/CT revealed focal activity of radiotracer in excised uncommon SLNs in 34 patients, 5 were tumor-positive.
the common iliac regions in all 5 patients, in 3 cases bilaterally, in Fourteen uncommon SLNs in 13 patients were not removed
the remaining 2 cases unilaterally. All preoperatively visualized by the surgeon as not identified; 4 patients out of them had
lymph nodes were found with the use of gamma probe and tumor-positive axillary SLNs. Conclusion: Uncommon SLNs
excised during lymphadenectomy. None of the resected SLNs were detected in more than a quarter of our patients, mostly
contained metastases. Conclusion: Radionuclide-guided drained from the posterior upper trunk. The neck region was a
mapping of the lymphatic drainage in urachal cancer is possible. drainage basin among two thirds of patients with uncommon
S521 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

SLNs. We suggest that current multimodal approach in radio- have appeared such as Radioiodine Seed Localization (RSL),
guided surgery planning should be refined in order to achieve which uses 125-I titanium coated seeds introduced in
effective surgical treatment. References: None. pathological lymph nodes (clip-marked prior to NST) to help
diminish false negative results compared with SNLB alone.
These techniques are paving the way to the possible reduction
EP-0302 of the number of axillary lymph node clearances (ALNC)
The comparative study of the validation for Tc-99m Tin- needed. The aim of this study is to describe the first results
colloid and Tc-99m Phytate in sentinel node detection in obtained in our center using radioiodine seeds alone or in
breast cancer patients combination with SLNB to adequately perform the axillary
J. Seok; staging in breast cancer patients after receiving NST. Materials
Chung-Ang University, Colleage of Medicine, and Methods: Eight breast cancer patients aged between
Seoul, KOREA, REPUBLIC OF. 43 and 75 have been studied. Proven tumour positive axillary
lymph nodes were localized using ultrasound and subsequently
clip-marked. After the completition of NST and 24 hours before
Aim/Introduction: Lymphoscintigraphy and sentinel node the surgery, a 125-I seed, was inserted using ultrasound in the
biopsy has become a standard method for detection of axillary clip-marked node. SNLB was performed using methylene blue,
lymph node metastasis in breast cancer patients, but the standard and 99m-Tc nanocolloids. In the operating room all the lymph
radiopharmaceutical was not prepared. About detection of nodes of interest were detected using a surgical gammaprobe
axillary lymph node metastasis by lymphoscintigraphy and and visual inspection for methylene blue colored nodes, and
sentinel node biopsy in breast cancer patient, we compared the then examined by experienced pathologists. All patients
results of Tc-99m Tin-colloid and Tc-99m Phytate by subareolar had an ALNC. Results: 7 patients out of 8, had a radioiodine
injection. Materials and Methods: This study included 1,152 seed correctly placed in lymph nodes (2 patients had nodal
breast cancer patients who were performed operation during conglomerates marked with one seed, 1 patient had 2 seeds
2001-2019. Four hundred twelve patients were injected 0.8 placed). The remaining patient had an incorrectly inserted seed.
ml of Tc-99m Tin-colloid (37-185 MBq) by subareolar injection. Out of 7 patients with radiodine seeds adequately placed, only
Seven hundred forty patients were injected 0.8 ml of Tc-99m one patient had a false negative result in RSL localized node
Phytate (37-185 MBq). Lymphoscintigraphy was performed in with one metastasis node found in its ALNC sample. The same
supine position and sentinel node localization was performed patient was the only case of no migration with nanocolloids. No
by hand-held gamma probe in operation. Results: Among 412 false negative case was found with SNLB techniques. Detection
patients by Tc-99m Tin-colloid, 374 cases (90.8%) were localized rate of axillary metastasis was 75% using RSL and 100% for
the sentinel node by lymphoscintigraphy and 367 cases (89.1%) SNLB, either alone or combined with RSL. Migration rate for
were localized by gamma probe. Among 740 patients by Tc-99m nanocolloids was 87,5%. Coincidence rate of patients with
Phytate, 723 cases (97.7%) were localized by lymphoscintigraphy nanocolloid positive nodes and radioiodine seeds was 71,43%
and 725 cases (98.0%) were localized by gamma probe. The (5/7). Conclusion: Preliminary results are promising, and show
detection rate by lymphoscintigraphy and gamma probe was an adequate staging of axillary nodes, using both techniques.
superior for Tc-99m Phytate compared to that for Tc-99m Tin- Further studies are being carried to establish more consistent
colloid, with a statistically significant difference. (p<0.05, p<0.05) conclusions. References: None.
Conclusion: Tc-99m Phytate is a better choice for localization of
sentinel node than Tc-99m Tin-colloid in breast cancer patients.
References: None. EP-0304
Comparison of 1 day protocol and 2 day protocol of
lymphoscintigraphy by subareolar injection in the
EP-0303 detection of sentinel lymph nodes in breast cancer
Axillary Node Staging After Neoadjuvant Systemic patients
Therapy Using Sentinel Node Biopsy and Radioiodine J. Seok;
Seed Localization in Breast Cancer Patients. First Chung-Ang University, Colleage of Medicine,
Experiences in our Center Seoul, KOREA, REPUBLIC OF.
Á. Galiana, M. Tabuenca, M. Marín, S. Aragón, E. Ciruelos, J. Torrens,
S. Ruiz, E. Martínez, V. Godigna, D. Vega, J. Estenoz;
Hospital Universitario 12 de Octubre, Madrid, SPAIN. Aim/Introduction: Lymphoscintigraphy and sentinel node
biopsy were used for the detection of axillary lymph node
metastasis in breast cancer patients. We compared the results of
Aim/Introduction: Sentinel lymph node biopsy (SNLB) is a subareolar injections on the day of surgery (1 day protocol) with
proven technique used for the axillary staging of breast cancer. injections the day before surgery (2 day protocol). Materials
With the surge of Neodajuvant Systemic Therapy (NST) axillary and Methods: This study included 1,152 breast cancer patients
staging of these patients using only SNLB has demonstrated who underwent surgery between 2001 and 2019. For the 1 day
relatively high false negative results. Therefore other techniques protocol 0.8 ml of Tc-99m Tin-Colloid (37MBq) was injected in
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S522

789 patients in the subareolar region on the morning of the (80,6%), the breast specimen had clear and large margins.
surgery. For the 2 day protocol 0.8 ml of Tc-99m Tin-Colloid Despite intraoperative examination of the specimen, a total
(185MBq) was injected in 363 patients on the afternoon before of 19, 4% (6 out of 25) patients required a second re-excision
surgery. Lymphoscintigraphy was performed in the supine procedure for involved margin and in the all cases had finally
position and sentinel node identification was performed by clear margins. Lymphocistingraphy showed axillary drainage
hand-held gamma probe during surgery. Results: Among in every patients and 38 SLN samples (1,23 SLN/patient) were
789 patients with the 1 day protocol, 757 cases (95.9%) were analyzed. Axillary lymph nodes were histologically negative in
identified by sentinel node lymphoscintigraphy, and 762 25 patientes (80,6%) and positive in 6 patients (17,4%). Follow-
cases (96.6%) were identified by gamma probe. Among the up 10 years. Complete referal: 29 patients. Metastatic recurrence:
363 patients, in the 2 day protocol, 340 cases (93.7%) had the 2 patients (one axillary recurrence, 31 month , treated with
sentinel node identified by lymphoscintigraphy, and 330 cases lymphadenectomy and other one pulmonary relapse, 24
(90.9%) had the sentinel node identified by the gamma probe. month, treated with chemotherapy), both free of disease at
There was no significant difference in the identification rate of the current time. Conclusion: Sentinel node and occult lesion
the sentinel node between the 1 day and 2 day protocol by localisation as a therapeutic option in breast cancer patients
lymphoscintigraphy and the gamma probe. Conclusion: The after neoadjuvant chemotherapy. References: None.
results of the identification of the sentinel node according to
1 day or 2 day protocols showed no significant differences.
Because the 2 day protocol allows for an adequate amount EP-0306
of time to perform the lymphoscintigraphy, it is a more useful Study of Recurrence in Cervical Cancer after Selective
protocol for the identification of sentinel nodes in patients with Lymph Node Biopsy
breast cancer. References: None. M. Calderón Calvente, L. Nieto Morcillo, G. Guzmán Prudencio,
M. Falgás Lacueva, P. Navarro Beltrán, L. De la Cueva Barrao, M.
Sangrós Sahún, S. Álvarez Ruiz, D. Abós Olivares;
EP-0305 Hospital Universitario Miguel Servet, Zaragoza, SPAIN.
Radioguided Occult Lesion Localization Plus Sentinel
Node Biopsy After Neoadyuvant Chemotherapy In Breast
Cancer Aim/Introduction: In view of the recent evidence regarding
I. Cepedello Boiso, C. Ramirez Tortosa, J. Jimenez Anula, J. Ramirez survival and recurrence of patients treated with cervical cancer
Ferrol; treated with a laparoscopic approach, our aim is to assess the
Complejo Hospitalario De Jaen, Jaén, SPAIN. effectiveness, relapse, and disease free survival (DFS) of patients
who underwent laparoscopic surgery of cervical cancer with
sentinel lymph node biopsy (SLNB). Materials and Methods:
Aim/Introduction: The feasibility, accuracy and clinical We retrospectively studied 25 consecutive patients, who had
significance of sentinel node and occult lesion localization SLNB performed as part of the surgical treatment of cervical
(SNOLL) for patients with breast cancer after neoadyuvant cancer from November 2013 to November 2018. The patients’
chemotherapy has not yet determinate. The aim of this study relapse was studied until April 2019, with follow-up period
was to investigate these questions. Materials and Methods: ranging from 64 to 4 months. Results: 23 patients were
This is a prospective study performed from January 2009 to May included in our study. One patient underwent laparotomy and
2019. Radioguided occult lesion localization plus sentinel node was therefore excluded. 24 of the 25 patients underwent a
biopsy was performed after neoadyuvant chemotherapy in laparoscopic procedure, of those another patient was excluded
patients with breast cancer ( tumor size > 3 cm or tumor size < 3 from the study because he did not meet the ESMO guidelines
cm not suitable for breast-conserving surgery and axilary node recommendations for the performance of SLNB. We detected
negative). Axillary status was established by physical examination, recurrence of the disease in 1/23 patients (8.3%). This patient
ultrasound-guided core needle biopsy of any suspicious lymph had a negative result in SLNB and locally relapsed 22 months
node. SNOLL were carried out using standar 99mTc sulfur colloid after surgery without signs of nodal invasion, showing no sign
(activity of 3 mCi and 0,2-0,5 ml volumen) injected directly into of disease at the time of revision. 2/23 (8.69%) of patients had a
the lesion (guided by ultrasound or computer tomography) positive result in SLNB, and neither have shown signs of nodal or
and in the cases of no lymphatic migration, realised subdermal local disease in the follow up. Average DFS for patients treated
injection. An intraoperative macroscopic examination of the with laparoscopy and SLNB was 60’76 months (IC95%:54.68-
specimen with margins evaluation was always performed. The 66.85). Conclusion: SLNB in the course of laparoscopic
Sentinel Lymp Node (SLN) were analysed by One-Step Nucleic treatment of cervical cancer has proved to be a safe technique
Acid Amplification (OSNA). SLN was considered to be positive in our experience for nodal staging and a useful tool to make
if macrometastases or micrometastases were found, and in therapeutic decisions. References: None.
such cases axillary dissection was consequently implemented.
Results: A total number of 31 patients was recorded (all woman,
37-66 years old, mean age 49,32 years). SNOLL located all the
occult breast lesions successfully. In 25 out of the 31 patients
S523 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

EP-0307 Aim/Introduction: SLNB is an important prognostic tool for


Tc-99m Phytate Lymphoscintigraphy In Breast Cancer: nodal staging in patients with early breast cancer, although,
Comparison Of Different Injection Technique in patients with LABC diagnosis treated with neoadjuvant
B. Hung, P. Lee, Y. Huang; chemotherapy, the technique continues in validation process
Department of nuclear medicine, Koo Foundation because of the high false negative rates and the low detection
Sun Yat-Sen Cancer Center, Taipei, TAIWAN. rates.We evaluate in our center the successfully detection rate
and the false negative rate(FNR) of SLNB performed after NAC
in order to validate this valuable technique. Materials and
Aim/Introduction: Breast cancer surgery has evolved towards Methods: Retrospective study (January/2012-April/2019).
minimizing morbidity and maximizing cure rates and sentinel Inclusion criteria: consecutive patients, diagnosed with
lymph node (SLN) biopsy is becoming standard practice in LABC (TNM-AJCC-7&8th-Edition); scheduled for neoadjuvant
most centers. However, there are still controversies about chemotherapy; with evaluation of the radiological response
several aspects of lymphatic mapping for breast cancer, following RECIST 1.1 criteria; who underwent to mastectomy/
including injection site of radioisotope and the best agent to lumpectomy, SLNB and axillary lymphadenectomy(LDN); with
be used in this procedure. We aim to evaluate the efficacy of evaluation of the pathological response Miller&Payne criteria
Tc-99m phytate lymphoscintigraphy in identifying SLN with and Residual Cancer Burden calculation(RCB) and with a follow-
subdermal and intradermal injection technique. Materials and up at least 6 months after chemotherapy. Results: 65 patients
Methods: A total of 1187 women with biopsy-proved breast met the inclusion criteria, (average age: 50,3 years), 2 with
cancer underwent Tc-99m phytate lymphoscintigraphy. The bilateral involvement, in total 67 breasts. The initial T staging
radioisotope (37-96 MBq in a volume of 0.2mL) was administered was: cT1: 11(16%); cT2: 37(55%); cT3: 14(21%); cT4: 6(9%); The
by subdermal injection over peri-tumoral and peri-areolar sites initial N staging was: cN0: 26(39%) and cN(+): 41(61%). The cN(+)
in 587 patients (group A) and intradermal injection over peri- patients underwent to fine-needle aspiration biopsy(FNAB)
tumoral and peri-areolar sites in 633 patients (group B). Five- and 35(85%) were FNAB(+) and 6(15%) FNAB(-). Histological
minute static anterior-oblique images were obtained 0.5 to subtypes included: infiltrating ductal carcinoma(IDC): 57(85%),
6.5 hours after injection. Images were read independently and infiltrating lobular carcinoma(ILC): 5(7%), IDC+Ductal Carcinoma
the SLN location was marked on the skin. A surgical handheld in-situ(DCIS): 1(1,5%), HG-DCIS: 2(3%) and Medular Carcinoma:
gamma probe was used to explore the SLNs in all patients. 1(1,5%). The prognostic biomarkers status were: Luminal A:
Surgical specimens were evaluated histopathologically. The SLN 8(12%), luminal B: 16(24%), triple negative: 15(22%) and Her2:
identification rate and comparison of groups were evaluated 28(42%). After chemotherapy the radiological responses
by chi-square test. A p-value of less than 0.05 was considered by MRI were: 16(24%) complete responses(CR); 44(66%)
significant. Results: Among the 1187 patients (mean age 54.1 partial responses(PR); 5(7%) stable diseases(SD); and 2(3%)
± 10.6 years), ipsilateral axilla was the most common site of progressions(PG). The pathological responses to NAC were:
SLNs. Non-axillary drainage was uncommon and found only in 20(30%) complete responses(G5-RCB-0) 4(6%); minimal residual
7(1%) patients in group A and 12(2%) patients in group B. The disease(G2-RCB-I); 17(25%); moderate residual disease(G3,G4-
SLN identification rate by lymphoscintigraphy alone in group A RCB-II) and 25(37%) extensive residual disease(G1-RCB-III).
and B were 72% and 93%, respectively. The SLN identification 1 patient was non-valorable tumoral response for technical
rate by lymphoscintigraphy combined with surgical gamma problems processing the T staging. 14(34%) de 41 cN+ presented
probe in group A and B were 94% and 99%, respectively. The nodal response to pN(0). The SLNB after chemotherapy results
SLN identification rate was superior with intradermal injection were: 26(39%) SLNB(+): 9 G3,G4-RCB-II and 17 G1-RCB-III.
compared with subdermal injection to visualize the axillary 34(51%) SLNB(-): 18 G5-RCB-0; 4 G2-RCB-I; 7 G3,G4-RCB-II and 4
SLNs (p < 0.05). The highest identification rate (99%) for the G1-RCB-III. 7(10%) patients didn´t present tracer migration (NM):
axillary drainage was obtained with combination of intradermal 2 G5-RCB-0; 1 G3,G4-RCB-II and 4 G1-RCB-III. The LDN results
injection and surgical gamma probe. Conclusion: On the basis were: 20(31%) LDN(+): 12 SNLB(+); 4 SLNB(-) and 4 NM. 47(69%)
of this study, we conclude that intradermal injection of Tc-99m LDN (-): 14 SLNB(+); 30 SLNB(-) and 3 NM. 1 SLNB(-) presented
phytate combined with surgical gamma probe is an appropriate progression with bone and ovary metastasis. The 2 patients
and useful method of identifying SLNs with very high successful with radiological progression of the disease after chemotherapy
rate. References: None. were SLNB(+) and remain stable. Conclusion: In our center
the SLNB detection rate was 89,5%. The FNR was 10%(7/67)
according with previous studies. One of the SLNB (-) presented
EP-0308 progression. References: None.
Sentinel lymph node biopsy (SLNB) after neoadjuvant
chemotherapy (A-NAC) in patients with locally advanced
breast cancer (LABC). Preliminary results before validation
of the technique
J. Espejo Niño, M. Nevares Herrero, R. Valverde Jorge, P. Cobos
Baena, L. Andrés Álvarez, E. Rodeño Ortíz de Zarate;
Hospital Universitario Cruces, Barakaldo, SPAIN.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S524

EP-19 biological markers of DLBCL, can be used as benchmark to


stratify patients for novel or risk-adapted therapies. References:
Clinical -> Diagnostic study -> Adult study ->
None.
Oncology study -> General oncology -> Therapy
response assessment
EP-0310
October 12 - 16, 2019 e-Poster Area Role Of Pet-ct In The Evaluation Of The Effect Of
Stereotactic Body Radiotherapy (sbrt) In Patients With
Lung Metastases
EP-0309 I. Kostadinova1, G. Mateva1, N. Nedev2, M. Garcheva1, A. Demirev1;
Metabolic parameters at baseline 18-F-FDG PET/CT and 1
Clinic of nuclear medicine, Acibadem City Hospital-
MYC expression for the assessment of clinical outcome Oncology, Sofia, BULGARIA, 2Clinic of Radiotherapy,
and treatment response in diffuse large B-cell lymphoma Acibadem City Hospital-Oncology, Sofia, BULGARIA.
M. Cuzzocrea1, M. Spallino1, E. De Ponti2, I. Casaroli3, S. Bolis3, C.
Landoni1, L. Guerra1;
1
Nuclear Medicine Department, University Milan- Bicocca, Aim/Introduction: The purpose of this retrospective study is to
Monza, ITALY, 2Medical Physics Department, San Gerardo assess the effect of SBRT in patients with oligometastatic disease
Hospital ASST Monza, Monza, ITALY, 3Hematology Department, of the lung, using PET -CT and CT and to compare the obtained
San Gerardo Hospital ASST Monza, Monza, ITALY. information from the PET- and the CT part of the study. Materials
and Methods: We retrospectively reviewed 20 patients with
less than 3 lung metastases from different tumours treated
Aim/Introduction: The metabolic parameters assessed at with SBRT. The patient group included 7 patients with breast
baseline PET are promising prognostic tools in diffuse large carcinoma, 6 with colorectal cancer, 4 with lung carcinoma,
B-cell lymphoma (DLBCL), as reported by recent papers. A 2 with renal and 1 with gastric cancer. Prior to and after the
growing interest is emerging about the biological characteristics radiotherapy (3-6 months after completion of treatment) the
of DLBCL, that are predictive biomarkers. We evaluate the disease was evaluated with PET-CT. We have used PERCIST
prognostic value of metabolic parameters at baseline PET, also and RECIST criteria for evaluation of the results. The patients
combining immunophenotypic evaluation of MYC, in DLBCL were treated on Varian TrueBeam STx™ linear accelerator, the
patients. Materials and Methods: We retrospectively evaluated respiratory motion was assessed with 4D-CT, The average BED​
80 patients (48 men; mean age: 61 years, range 22-86) with newly 10​(biologically effective dose 10Gy) was 80.95Gy (range 59.5 -
diagnosed DLBCL, disease stage I-IV (8 stage I, 13 stage II, 19 198.72), delivered in 1 to 5 fractions. The effect of the treatment
stage III, 40 stage IV) referred to our Hospital between april 2011 was evaluated with the change of SUVmax and the sizes of the
and october 2017. The SUV derived parameters at baseline PET lesions and the results were compared. Results: A local control,
were calculated using a fixed threshold of 41% of the SUVmax. defined as lesions with complete response, partial response and
In a subgroup of 51 patients, we also evaluated phenotypic stable disease, was achieved in 86%. The average SUVmax was
expression of MYC (14 pos, 37 neg) with immunohistochemistry. 6.70 before treatment and dropped to 2.97 after the treatment.
Sum rank test and receiver operating characteristics (ROC) curves The decrease was statistically significant (p=0.03 ) with a strong
were performed for statistical analysis. Results: The median correlation between the values prior to and after the SBRT
of follow up was 25.5 months. In our series of 80 patients, 18 (r=0.76). Using CT and RECIST criteria, there was the same
died and 19 relapsed. Among the semi-quantitative parameters, ultimate therapeutic control - 86%, with a change of the average
only tMTV was statistically significant. The mean ± SD, median, size of lesions - from 15.6 mm to 12.1mm, but the difference was
and range of tMTV in non relapsed vs relapsed patients were not statistically significant comparing the pretreatment and post
314 ml ± 470, 107 ml (2-2067) vs 438 ± 435, 398 ml (22-1506) treatment sizes (p=0.39) with an average correlation (r=0.60).
respectively (p value = 0.076). The mean ± SD, median and Therefore the changes in the PET part of the study, with SUVmax
range of tMTV in alive vs dead patients were 335 ml ± 487, 115 appear earlier and are more pronounced than morphological
ml (2-2067) vs 716 ± 1368, 203 ml (22-5501) respectively (p value ones from CT-part. We did not find any correlation between
= 0.065). A tMTV cut-off value of 400 ml showed a PPV and NPV the delivered dose (BED​10​) and the change in SUVmax and
of 33% and 88% for DFS and 30% and 84% for OS respectively. between the BED​10​and the size of the lesions after the SBRT.
DFS was significantly different in patients with low vs high Conclusion: SBRT is an effective treatment for patients with
tMTV (p = 0.05). In the immunophenotypic sub-analysis, MYC oligometastatic lung disease. PET is the more sensitive part of
negative patients with poor prognosis were associated to high the hybrid study than CT for evaluation of treatment response.
tMTV both for DFS (p = 0.0019) and OS (p = 0.02). Conclusion: There is no correlation between the change of SUVmax and size
An optimal tMTV cut-off of 400 ml at baseline PET seems to be of the lesion with the delivered dose. References: None.
able to exclude disease recurrence or exitus with a good NPV
(84% for OS and 88% for DFS) in DLBCL patients. High tMTV in
MYC negative patients is associated with a worse prognosis. If
these results will be validated in a larger population, tMTV and
S525 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

EP-0311 EP-0312
Emphasizing role of post treatment surveillance PETCT The role of 18F-FDG-PET/CT in the response evaluation of
scan for radically treated non metastatic squamous cell primary systemic therapy in breast cancer
carcinoma of head and neck (SCHNC): Single Institution J. Torok1, S. Czibor1, T. Tőkés2, T. Gyorke1;
preliminary outcome. 1
Semmelweis University, Nuclear Medicine Center,
S. Gawde, A. Kasat, T. Basu, S. Parekh, A. Singhal; Budapest, HUNGARY, 2Semmelweis University,
HCG Cancer Centre, Mumbai, INDIA. Oncology Center, Budapest, HUNGARY.

Aim/Introduction: SCHNC is most common malignancy Aim/Introduction: 18F-FDG-PET/CT have a crucial role in
worldwide. For treatment response, accurate assessment is determining response to primary systemic therapy (PST) in
important since residual disease after radical chemoradiation breast cancer patients. The goal of our research is to compare
(CRT) is present in 30±60% patients. Physical examination the correlation between the visual and semiquantitative
and conventional imaging alone is not sufficient. Aim is to PET/CT response evaluation and the pathological remission
evaluate diagnostic performance of PET/CT for detecting detected after the PST. Materials and Methods: We performed
residual disease after radical CRT in patients with SCHNC. 18F-FDG-PET/CT scans in 28 patients before and after PST,
Materials and Methods: Single institutional retrospective examining an overall number of 29 lesions (one patient had
analysis of predominantly locally advanced SCHNC treated bilateral breast cancer). Core-biopsy was performed prior to
with radical chemoradiation from October 2017 to December treatment in every case, while PST was followed by surgery
2018 were evaluated, excluding metastatic and post operative and histological examination to assess the response to therapy.
cases at baseline. Patients had baseline radiological, physical, We formed pathologic complete (pCR) and partial regression
fiberoptic examinations and post-radical CRT PETCT imaging (pPR) subgroups based on the results of the latter. On PET/CT
at 10-22 weeks of treatment completion. Two blinded nuclear scans, FDG avidity of the primary tumor was evaluated using
medicine physician reviewed PETCT. Failures were categorized both visual assessment according to the Deauville-scale (DS)
into local, nodal failure and distant metastases. PET scan results and semiquantatively (rPET, qPET, ΔSUVmax, ΔSUVpeak) based
were compared with clinical, fiberoptic exams, EUA and pre- on standardized uptake values (SUV). These results were then
treatment PETCT scan. Results: 50 patients with median follow- compared to the postoperative histological findings. We
up time of 7 months (range: 3-15 months) were analysed. Most calculated the areas under the receiver operating characteristic
were males (80.6%) with locally advanced (90.3%), Stage IVA-B (ROC) curves (AUC) of the visual and semiquantitative methods
80.6%. HPV P16 available in 11 cases (only 4 HPV P16 +). T2, thereafter determined optimal cut-off values. Specificity,
T3 and N2c (38.7%) were predominant T and N stage. 77.4% sensitivity, positive (PPV) and negative predictive values (NPV) of
received concurrent chemotherapy and 22.6% had NACT. each method were evaluated based on PET-response categories
Majority (93.5%) received SIB-IMRT technique to dose of 66- defined by these cut-offs. Results: The results of the ROC
70Gy. Baseline PETCT was available in 41.9% with SUV max analysis were: AUC(DS)=0.76; AUC(rPET)=0.76; AUC(qPET)=0.78;
ranging from 7.2 - 23.3. Post surveillance second PETCT was AUC(ΔSUVmax)=0.85 and AUC(ΔSUVpeak)=0.85. The optimal
available only in 12.9%. At first follow up, complete response cut-off values were 0.849 and 0.953 for rPET and qPET, and
(CR) at primary site was seen in 77.4% on both fiberoptic -82.7% and -80.7% for ΔSUVmax and ΔSUVpeak, respectively.
laryngoscope (FOL) and PETCT. Residual local disease was seen Using chi2 test, those patients who were deemed PET-positive
in 22.6% on FOL and 38.7% (combined primary and nodal) on or PET-negative using DS1-2 or any of the semiquantitative
PETCT and distant metastasis was seen in 3 patients. There was methods had a pCR or pPR result that significantly correlated
significant concordance in assessing primary disease response with their PET-based category. Both ΔSUVmax and ΔSUVpeak
between PET and FOL (88%), among that 71% cases showed methods had an 82.7% diagnostic accuracy, surpassing DS1-
CR on both PET and FOL. As per last follow up, 61.3% were 2(65%), rPET (65.5%) and qPET (68.9%) results. ΔSUVmax had the
locoregionally controlled and 38.7% had combined local and highest sensitivity (82.3%) and NPV (76.9%), while DS1-2, rPET
nodal residual disease on PET, out of which residual disease was and qPET had the highest specificity (100%) and PPV results
biopsy proven in 32.3%. Conclusion: Surveillance PETCT shows (100%). DS1-2, rPET and qPET measurements had relatively high
high concordance with FOL for assessing primary disease and false negative results with an NPV below 60%. McNemar’s test
high sensitivity for detecting nodal disease. PETCT has potential demonstrated that ΔSUVmax had significantly higher diagnostic
to detect residual disease after radical CRT, with optimal time accuracy than DS1-2, rPET and qPET. Conclusion: Response to
for scanning between 12-16 weeks after therapy followed by re- therapy following PST can be evaluated with good accuracy by
evaluation around 10±12 months later to detect late recurrences. ΔSUV measurements between PET/CT examinations performed
Additionally, PETCT can guide decisions about neck dissection before and after PST. The evaluation of the post-PST PET/CTs in
and identify patients with poor prognosis. References: None. itself is less suitable to assess complete regression. References:
None.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S526

EP-0313 Sigrisi, M. Fanelli, G. Rubini;


18F-FDG PET/CT Is Useful In The Evaluation Of Treatment Nuclear Medicine Unit, Interdisciplinary Department of
Response With Tocilizumab In Patients With Large Vessel Medicine – University of Bari “Aldo Moro”, Bari, ITALY.
Vasculitis
E. Cerudelli1, G. Bosio2, D. Albano2, M. Gazzilli1, M. Bonacina1,
R. Durmo1, F. Dondi1, A. Mazzoletti1, P. Bellini1, F. Bertagna1,2, R. Aim/Introduction: The endpoint of our study was to validate a
Giubbini1,2; reliable but simple method to evaluate 223Ra-dichloride (223Ra)
1
Università degli studi di Brescia, Brescia, ITALY, 2Azienda Socio therapy response in metastatic castration-resistant prostate
Sanitaria Territoriale degli Spedali Civili di Brescia, Brescia, ITALY. cancer (mCRPC) patients with symptomatic bone metastases.
We used 18F-Fluorocholine (18F-FCH) PET/CT semiquantitative
analysis and compared PET parameters to bone scan (BS),
Aim/Introduction: 18F-fluorodeoxyglucose positron emission conventionally considered as gold standard for 223Ra-therapy
tomography (FDG-PET/CT) is useful in the detection of the efficacy evaluation. Materials and Methods: 30 patients (mean
arterial wall inflammation in patients affected by large-vessel age 75 years, range 57-89) with mCRPC underwent 223Ra-
vasculitis (LVV) as giant cell arteritis (GCA), Takayasu arteritis therapy at our Department, from February 2016 to September
(TA) and aortitis. The aim of this study was to investigate the 2018. A retrospective analysis was performed, selecting 12/30
usefulness of FDG-PET/CT in the evaluation of therapy response patients who completed the whole treatment (6 administrations,
with tocilizumab (TCZ), a humanized anti-interleukin-6 receptor 55 kBq/kg each one) and performed both BS and 18F-FCH-PET/
antibody, in patients affected by LVV. Materials and Methods: CT at baseline and 2 months after therapy. We selected the
We retrospectively evaluated 11 patients (7 female, 4 male; 3 most metabolically active skeletal lesions (a total of 36) at
56±19 years) with LVV treated with TCZ. FDG-PET/CT were baseline PET/CT and we monitored their post-treatment PET/CT
performed at baseline and with an interval of 3-26 months changes, calculating 5 semiquantitative parameters (SUVmax,
(13,18±7,69) after the initiation of TCZ therapy. PET images were SUVmin, SUVav, MATV, TLA) and pre-/post-treatment Δvalue
analysed visually and semi-quantitatively by measuring the (ΔSUVmax, ΔSUVmin, ΔSUVav, ΔMATV, ΔTLA). We defined an
maximum standardized uptake value (SUVmax) of the vascular Overall PET Response (OPR) for each of the 5 semiquantitative
wall of bilateral subclavian and common carotid arteries, parameters, considering the trend of the 3 lesions Δvalues. Based
ascending thoracic aorta, abdominal aorta and bilateral iliac on this index, we classified patients as PET responders (OPR-R)
arteries. Moreover, for each patient we selected the vessel and PET non-responders (OPR-NR). Patients were considered
with most increased uptake and we calculated the vessel-to- responder for a specific parameter (OPR-RΔSUVmax, OPR-RΔSUVmin,
liver SUVmax ratio pre- and post-treatment. The ΔSUV ratio OPR-RΔSUVav, OPR-RΔMATV, OPR-RΔTLA) if at least 2 of the 3 lesions
(pre-post treatment) was compared to changes of Erythrocyte showed reduction or stability. The BS response to therapy was
Sedimentation Rate (ESR) and changes in glucocorticoid (GC) based on the difference between lesions’ number in pre- and
therapy, both considered as indices of disease activity. Results: post-treatment examinations, dividing patients in BS responders
Nine patients had a complete disease remission after TCZ, in (BS-R) and non-responders (BS-NR). The concordance between
two there was a reduction of vessels uptake. SUVmax ratio pre- OPR and BS results was calculated by Cohen’s K. P<0.05 was
treatment showed a strong correlation with blood levels of ESR considered statistically significant. Results: According to BS,
(ρ 0,713; p 0,04). Vessel-to-liver SUVmax ratio was significantly 4/12 patients were BS-R (33%) and 8/12 patients BS-NR (67%).
decreased in post-treatment PET/CT (1,73±0,82 vs. 0,82±0,18; Referring to OPR analysis, 7/12 patients (58%) were OPR-RΔSUVmax,
p=0,002). We observed a complete normalization of ESR in OPR-RΔSUVmin, OPR-RΔSUVav and OPR-RΔMATV; 8/12 patients (67%)
all cases after TCZ therapy. Mean GC dose was tapered from were OPR-RΔTLA. A statistically significant agreement between
28,86±15,06 mg/day to 7,09±4,66 mg/day (p<0,001). The ΔSUV the two techniques was found for ΔSUVmax, ΔSUVmin and
ratio was significantly associated with reduction of GC therapy ΔSUVav (k=0.526; p=0.038). Conclusion: Our preliminary
(p<0,001) and of ESR (p=0,007). Conclusion: Vessels FDG uptake results suggest that 18F-FCH-PET/CT evaluation by “Overall PET
decreased significantly after the initiation of TCZ therapy in LVV Response” index could be a summary but very useful method
patients showing a good metabolic response. The reduction of for 223Ra-therapy response assessment, with a special reference
FDG uptake is related to decrease of blood levels of ESR and of to ΔSUV parameters, which could represent a guide for a steady
steroid therapy, confirming a reduction of disease activity. FDG- patient monitoring. References: None.
PET/CT could be used to evaluate treatment response in TCZ-
treated patients. References: None.
EP-0315
Intra Patient Sul Repeatability Of Background On 18F-FDG
EP-0314 PET/CT
“Overall PET Response” index based on 18F-FCH PET/CT R. Wang1, M. Su1, J. H. Miller2;
semiquantitative parameters: a useful method to evaluate 1
West China hospital, Chengdu, CHINA, 2Loma Linda University,
223Ra-dichloride therapy efficacy in mCRPC patients with School of Medicine, CA, CA, UNITED STATES OF AMERICA.
bone metastases
C. Ferrari, A. Niccoli Asabella, V. Lavelli, A. G. Nappi, S. Sisto, G.
S527 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

Aim/Introduction: The background activity of normal soft total, 112 skeletal lesions were identified.For mediastinal and
tissues is often used as reference to assess tumor treatment liver measurements, in all three groups (baseline, response
response on 18F-FDG PET/CT. Our objective was to find the evaluation, suspected relapse), the SUVmax values are higher
preferred background through assessing the repeatability on OSEM TOF reconstruction - being 8.5%, 2.3% & 1.2% higher
of different background activity, which was expressed by respectively in the mediastinum, and 10.2%, 7.5% & 8.9% higher
standardized uptake value normalized to lean body mass (SUL). respectively in the liver. For focal FDG avid skeletal lesions,
Materials and Methods: Patients who have had two scans average lesional SUVmax values are 1.9 ± 2.5, 2.1 ± 3.5, 2.0 ± 3.4
within several days were selected. Background SULs from aortic higher on the BPL reconstructions (24%, 12.8%, 27%, for baseline,
blood pool (ABP-SUL), liver (L-SUL) and muscle (M-SUL) were response evaluation and suspected relapse groups respectively)
recorded. Intra-class correlation coefficients (ICCs) and Bland- (p<0.001 for all three groups). Additional focal avid skeletal sites
Altman plots were used to evaluate the degree of repeatability are seen in 1 of the response evaluation and 5 of the suspected
between two scans. Then the intra-patient variation in SULs relapse cases on BPL reconstruction, not perceptible on routine
and factors which included blood glucose level (BGL), tracer TOF reconstructions. Adopting Deauville score as per IMPeTUs
uptake period and dose were calculated as relative changes criteria1, proposed for categorising treatment response, in
between two scans. Finally, a linear regression model was used the relevant group in our cohort would mean 8/27 (29.6%) of
for analyzing all relative changes to identify which factor had patients would be ‘up-graded’ if BPL reconstruction images
correlation with SULs variability. Results: Seventeen patients were used for clinical assessment instead of routine OSEM TOF.
were included. The SUL ICCs for ABP, liver and muscle were 0.66, Conclusion: A shift in PET reconstruction algorithm used in the
0.48 and 0.77 respectively. Similar results were obtained from FDG PETCT assessment of multiple myeloma patients would
Bland-Altman plots. According to liner regression analysis, there have a potentially significant impact in the clinical interpretation
were positive correlations between variations of L-SUL and of the study findings. References: Nanni C, Zamagni E, Versari A,
M-SUL and that of BGL (b=0.570and 0.492 respectively, p&lt0.05 Chauvie S, Bianchi A, Rensi M, et al. Image interpretation criteria
altogether), and between variation of M-SUL and that of tracer for FDG PET/CT in multiple myeloma: a new proposal from an
uptake period (b=0.591, p=0.006). Conclusion: The SUL of liver Italian expert panel. IMPeTUs (Italian Myeloma criteria for PET
is more sensitive to blood glucose level, therefore may not be USe). Eur J Nucl Med Mol Imaging. 2016 Mar;43(3):414-21.
suitable for the referential background. Activities within aortic
blood pool and muscle are stable, and should be the preferred
background for sequential patient evaluation. References: EP-0317
None. Prognostic role of basal bone scintigraphy and
18
F-Fluorocholine PET/CT in patients with prostate cancer
treated with 223Ra
EP-0316 E. Casillas Sagrado1, A. M. García Vicente1, N. Martínez Asensio2,
Impact of PET Reconstruction Algorithms on Assessment M. Amo-Salas2, M. J. Tello Galán1, I. García Carbonero3, J. Cassinello
and Quantification of FDG-PETCT Findings in Patients with Espinosa4, R. Gómez Díaz1, Á. M. Soriano Castrejón1;
Multiple Myeloma 1
Hospital General Universitario de Ciudad Real, Ciudad
S. Riaz, S. Arulogun, A. L. Smith, N. Rabin, S. Wan, J. Bomanji; Real, SPAIN, 2Castilla-La Mancha University, Ciudad Real,
NHS, London, UNITED KINGDOM. SPAIN, 3Hospital Virgen de la Salud, Toledo, SPAIN, 4Hospital
Universitario de Guadalajara, Guadalajara, SPAIN.

Aim/Introduction: The purpose of this study is to assess how


different PET image reconstructions may influence the clinical Aim/Introduction: To establish the prognostic value of bone
interpretation of FDG-PETCT studies, in patients with multiple scintigraphy (BS) and 18F-Fluorocholine PET/CT (FCH-PET/CT)
myeloma. Materials and Methods: Standard of care FDG- previous to 223Ra (basal) and compare it to clinical variables,
PETCT scans performed for assessment in multiple myeloma in patients with castration-resistant prostate cancer and bone
patients were retrospectively reviewed. Scans were grouped metastases (CRPC-BM). Materials and Methods: Prospective
under three broad indications: baseline assessment, response and multicentre study started in 2015 (ChoPET-Rad). 63 patients
evaluation & suspected relapse. In each case, OSEM TOF with CRPC-BM were consecutively included. Clinical variables as
and Bayesian penalized likelihood reconstruction algorithm Gleason score, basal PSA, LDH and AP, previous treatments and
(BPL) were available. A qualified nuclear medicine physician treatment failure were collected. Bone metastases characteristics
evaluated the following parameters on both sets of PET images: as location (axial vs. axial plus extra-axial), number, blastic or not
mediastinal and liver SUVmax, number of focal FDG avid on CT, bone marrow involvement (super-scan pattern), tumor
lesions (skeletal and extramedullary) & SUVmax of up to 3 focal burden, FCH uptake above the hepatic pool, among others,
skeletal lesions per patient. SUVmax values were compared were assessed. Patients underwent standardized follow-up and
using paired t-tests. Results: In the period evaluated, 71 PET- overall survival (OS) was obtained. The relation between imaging
CT scans were identified in 68 patients (average age: 64.3±10.3). variables and OS was analyzed by Kaplan-Meier and Long Rank
Indications were: baseline assessment (n=17), treatment (Mantel-Cox) tests. Multivariate analysis was performed by Cox
response evaluation (n= 27) and suspected relapse (n=27). In regression. Results: Median OS was 15 months. 39/63 patients
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S528

died during the follow-up.Treatment failure was observed in patients categorized as progression in final BS had a death risk 5.2
55.6%. BS and FCH-PET/CT demonstrated axial plus extra-axial times higher than the rest (p=0.004). Conclusion: Both interim
involvement in 61.9% and 56%, respectively. Polimetastatic and final 18F-fluorocholine PET/CT were good predictors of the
disease was more prevalent in BS with respect to FCH-PET/CT biochemical progression in patients treated with 223Ra. Neither
(74.6 vs 64%, respectively). 34% of lesions had a non-blastic interim nor end-of-treatment bone scintigraphy were useful to
dominance on CT. Super-scan pattern was observed in 28% predict biochemical response; nevertheless, progression in final
of BS and 24% of FCH-PET/CT. Multiple FCH-PET/CT variables bone scintigraphy was an adverse prognostic factor in terms of
were related to OS: axial plus extra-axial presence of metastases overall survival. References: None.
(HR=2.71;p=0.036), high tumor burden (HR=2.95;p=0.032),
non-blastic dominance on CT (HR=3.26;p=0.030), super-scan
pattern (HR=4.36;p=0.001), metastases with FCH uptake higher EP-0319
than liver (HR=3.90;p=0.004). In BS, only extent of disease A Prospective Study In 613 Patients Seeking For Predictive
and bone marrow involvement were associated to OS. On a Factors Of Physiological FDG Anal Uptake To Improve Post
multivariate analysis, only treatment failure (HR=6.06;p=0.003) Chemo-radiotherapy PET Scans Interpretation In Anal
and super-scan pattern on FCH-PET/CT (HR=4.57;p=0.004) Cancer
were simultaneously predictors of OS. Conclusion: Basal C. Lasnon1,2, N. Aide3,2,4, C. Nganoa3, B. Houdu3, J. Kammerer1,4, M.
18
F-fluorocholine PET/CT offered additional information in the Galais1, R. Ciapuccinni1, L. Tainturier1,4;
prediction of OS in patients with CRPC-BM treated with 223Ra, 1
Centre François Baclesse, Caen, FRANCE, 2ANTICIPE,
being superior to BS and clinical variables. References: None. INSERM U1086, Caen, FRANCE, 3Caen University Hospital,
Caen, FRANCE, 4Caen University, Caen, FRANCE.

EP-0318
Interim and end-of-treatment bone scintigraphy and Aim/Introduction: Anal cancer is a relatively rare tumor
18
F-Flourocholine PET/CT in the prediction of response in whose incidence increases in developed countries. 18F-FDG PET
patients with prostate cancer treated with 223Ra has been increasingly used for its post radio-chemotherapy
E. Casillas Sagrado1, A. M. García Vicente1, N. Martínez Asensio2, evaluation. However, several authors reported the risk of local
M. Amo-Salas2, M. J. Tello Galán1, I. García Carbonero3, J. Cassinello false-positive findings leading to low specificity and positive
Espinosa4, R. Gómez Díaz1, Á. M. Soriano Castrejón1; predictive values. These false positive results could result from
1
Hospital General Universitario de Ciudad Real, Ciudad post-radiotherapy inflammation or infection but certainly also
Real, SPAIN, 2Castilla-La Mancha University, Ciudad Real, from physiological anal canal uptake that is observed in a regular
SPAIN, 3Hospital Virgen de la Salud, Toledo, SPAIN, 4Hospital basis in clinical practice. The purpose of this prospective study
Universitario de Guadalajara, Guadalajara, SPAIN. (NCT03506529; HYPHYCA) was therefore to seek for predictive
factors of physiological anal canal hypermetabolism in order
to improve the specificity of post radio-chemotherapy PET
Aim/Introduction: To determine the aim of interim and evaluation. Materials and Methods: Over a two-month period,
end-of-treatment 99mTc-HDP bone scintigraphy (BS) and patients aged of 18 yo and more, referred for 18F-FDG PET-CT at
18
F-Fluorocholine PET/CT (FCH-PET/CT) in the response two EARL-accredited PET centres were included, after obtaining
evaluation of patients with castration-resistant prostate cancer their informed and written consent. They were asked to fill in
and bone metastases (CRPC-BM) treated with 223Ra. Materials a questionnaire including seven closed questions about usual
and Methods: Prospective and multicentre ChoPET-Rad study. intestinal transit, ongoing medications relative to intestinal
63 patients with CRPC-BM were consecutively included. Basal, transit, history of digestive, anal and/or pelvic diseases. Age,
after 3 (interim) and 6 doses (final) BS and FCH-PET/CT were gender, body mass index (BMI) were recorded.A single nuclear
performed.Clinical variables [Gleason score, basal PSA, PA and medicine physician visually and quantitatively analyzed anal
LDH, previous treatments, treatment failure], and degree of canal uptake (SUVmax_EARL) and assessed visual rectal content (air,
response (progression or not) of bone metastases in both imaging feces or both) and the largest rectal diameter (mm). Results: Six
techniques were assessed and their association with progression hundred and thirteen patients were included (sex ratio F/M= 0.99)
free survival (PFS), attending biochemical parameters, using and 545 (89%) questionnaires were entirely fulfilled. Significantly
Kaplan-Meier and Long Rank (Mantel-Cox) tests. Results: Of the more males presented with anal canal hypermetabolism (sex
patients included, 45% of them had Gleason score &#8805; 8, ratio (M/F) = 1.18 versus 0.85, p = 0.048). Moreover, patients with
73% were in their third or consecutive line. Median of PFS was anal canal hypermetabolism had higher BMI (27.6 (5.7) kg/m²
3 months. 39/63 patients died during the follow-up.Neither versus 23.9 (4.5) kg/m², p< 0.0001), higher rate of hemorrhoid
clinical variables nor degree of response on BS were significant history (43% versus 27%, p=0.016) and higher rate of rectum
predictors of PFS. Interim and final degree of response assessed filled with only feces (21% versus 12%, p = 0.019) as compared
with FCH-PET/CT were related to PFS (&#935;2=6.01; p=0.014 to patients with no anal canal uptake. On logistic regression,
and &#935;2=9.49; p=0.002, respectively).The patients identified all these variables were found to be independent predictors of
as progression in final PET presented a risk of biochemical the occurrence of an anal canal hypermetabolism. Odds ratio
progression 4 times higher than the rest (p=0.012). Likewise, the were 1.16 (1.12-1.20) per unit of BMI (kg/m²) (p<0.0001), 1.48
S529 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

(1.04-2.11) for males (p=0.029), 1.64 (1.10-2.45) for hemorrhoids EP-0321


history (p=0.015) and 1.94 (1.147-3.22) for the rectal filled with One versus five lesions for response assessment by
only feces (p=0.010). Conclusion: According to our study, the PERCIST in patients with lung cancer
predictive factors of physiological anal canal hypermetabolism S. Kwon, J. O, I. Yoo, S. Kim;
are high BMI, male gender, history of hemorrhoid and rectum Seoul Saint Mary’s Hospital, Seoul, KOREA, REPUBLIC OF.
filled with only feces. This paves the way to a more specific
interpretation of post radio-chemotherapy PET evaluations of
anal canal cancer and to the optimization of protocols by used Aim/Introduction: The number of lesions to evaluate when
of rectal enema. References: None. assessing treatment response is not validated for lung cancer.
We compared one and five lesion measurements for response
assessment by Positron Emission Tomography Response Criteria
EP-0320 in Solid Tumors (PERCIST). Materials and Methods: Patients
18F-FDG-PET early response assessment of PD1- with lung cancer who had pre- and post-treatment FDG PET/
Immunotherapy in melanoma patients CT from 2016 to 2017 were included and the standard uptake
D. Papamichail1, R. Hog1, C. Sachpekidis1, J. Hassel2, A. value corrected for lean body mass (SULpeak) of up to 5 hottest
Dimitrakopoulou-Strauss1; target lesions were measured. The percent change in the
1
Clinical Cooperation Unit Nuclear Medicine, German single hottest lesion (1-lesion-analysis), and percent change
Cancer Research Center, Heidelberg, GERMANY, in the sum of up to 5 hottest lesions (5-lesion-analysis) were
2
Universitätshautklinik, Heidelberg, GERMANY. computed. Response category was designated: complete
metabolic response (CMR) when no lesion with perceptible
FDG uptake remained; partial metabolic response (PMR), stable
Aim/Introduction: The aim of this ongoing study is to evaluate if metabolic disease (SMD), or progressive metabolic disease
18F-FDG-PET has the potential to predict the response of patients (PMD) determined using the PERCIST threshold of 30% and 0.8
with melanoma to PD1-therapy after two circles of therapy. unit change in SULpeak; unequivocal new lesion meant PMD.
Materials and Methods: From January 2015 to January Regression analysis was used to investigate linearity between
2019, 21 patients (13 females; average 56 y) with unresectable 1-lesion-analysis and 5-lesion-analysis, and the concordance
metastasized melanoma had a whole-body 18F-FDG-PET/ for response categorization was assessed by kappa statistics.
CT examination at three time points: Before therapy start Results: Total 26 patients (13 non-small cell; 13 small cell) were
(t1, base-line), after two circles of therapy (t2, interim) and included and all had FDG-avid lung cancer. The median interval
after completion of therapy (t3, reference standard). Therapy between pre- and post-treatment PET/CT was 18.5 weeks (7.7
response was assessed with European Organisation for -37.4 weeks). Average of 3.4 target lesions were measured for
Research and Treatment of Cancer (EORTC) criteria for PET/ 5-lesion-analysis at pre-treatment, and 3.6 at post-treatment.
CT and PET Response Evaluation Criteria for Immunotherapy R2 value was 0.48 (p<0.001) for all 26 patients, but increased to
(PERCIMT) [1]. Results: According to EORTC criteria, of the 0.92 (p<0.001) when one outlier categorized as PMD regardless
21 patients included in the study, 12 had disease progression of percent change due to new lesions was excluded. Response
(PMD) in PET at t3. Ten of these patients (83.3%) had shown PMD categorization with 1-lesion-analysis and 5-lesion-analysis was
in t2, one patient had shown stable metabolic disease (SMD) discordant in 1 patient (weighted kappa=0.94), who showed
and another patient partial metabolic response (PMR). Two 30.4% decrease by 1-lesion-analysis and 28.6% decrease by
patients who had complete metabolic response (CMR) in PET 5-lesion-analysis. In 3 patients, the response was PMD despite
at t3 had shown a complete response also at t2. According to less than 30% increase in SULpeak due to new lesions. Patients
PERCIMT, 8 patients had PMD in PET at t3. 5 of these patients with CMR demonstrated SULpeak changes in range of -76.7%
(62,5%) had shown PMD in t2, two patients had shown SMD to -79.5% by 1-lesion-analysis and -74.3% to -80.8% for 5-lesion-
and one patient had shown PMR. Again, two patients who had analysis. Conclusion: Measuring single and up to five hottest
CMR in PET at t3 had shown CMR also at t2. Two-years follow-up lesions from FDG PET/CT for response assessment by PERCIST
of all patients remains for further evaluation. Conclusion: The yielded high concordance rate in patients with lung cancer.
preliminary results of our study indicate that 18F-FDG-PET after References: None.
two circles of PD1-therapy can serve as a surrogate measure of
therapeutic efficacy in stage IV melanoma patients. This might
help to shorten therapy regimes or to consider earlier a different
treatment strategy. The results will be validated based on long-
term follow-up data. References: [1] Dimitrakopoulou-Strauss
A. Monitoring of patients with metastatic melanoma treated
with immune checkpoint inhibitors using PET-CT. Cancer
Immunol Immunother. 2019 May;68(5):813-822.
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S530

EP-20 seen in this subgroup. Osteoarthritic changes were commonly


seen in super-obese patients mainly involving facet joints
Clinical -> Diagnostic study -> Adult study -> (76.5%), knees (74.5%), small joints of feet (47.1%), and ankle
Oncology study -> Organ-based oncology (21.6%). Conclusion: 18F-NaF PET/CT retains its high diagnostic
-> Bone and soft tissues cancer primary and accuracy in super-obese patients (BMI >50Kg/m²) resulting in
metastatic cancers a low number of equivocal findings and therefore offers high
diagnostic confidence. It is less susceptible to artifacts induced
October 12 - 16, 2019 e-Poster Area by body habitus and may be the preferred functional imaging
modality for this patient group. References: 1. Clin Nucl Med.
2017;42:829-836. 2. Eur J Nucl Med Mol Imaging. 2015;42:1767-
1777.
EP-0322
The Role Of 18F-sodium Fluoride (Naf) PET/CT In The
Evaluation Of Metastatic Bone Disease In Extremely Obese EP-0323
(super Obese) Patients Test-retest Reliability Of Quantitative Bone SPECT/CT
M. Usmani1, F. al Kandari1, F. Marafi2, G. Gnanasegaran3, T. Van den Performed On Different Days
Wyngaert4; T. Yamane1, S. Shirotake2, T. Okabe2, K. Nishimoto2, G. Kaneko2, M.
1
Kuwait Cancer Control Center, Kuwait, KUWAIT, 2Jaber Oyama2, A. Seto1, K. Fukushima1, I. Kuji1;
Al-Ahmad Molecular Imaging Center, Kuwait, KUWAIT, 1
Department of Nuclear Medicine, Saitama Medical
3
Royal Free Hospital NHS Trust, London, UNITED KINGDOM, University International Medical Center, Hidaka, JAPAN,
4
Antwerp University Hospital Belgium, Antwerp, BELGIUM. 2
Department of Uro-Oncology, Saitama Medical University
International Medical Center, Hidaka, JAPAN.

Aim/Introduction: Obesity is an emerging public health crisis


all around the world and presents with unique challenges for Aim/Introduction: While the advancement of SPECT/CT
diagnostic imaging procedures, including the skeletal staging in technology improved quantitative evaluation of the uptake,
cancer. The quality of conventional bone scintigraphy is generally the reproducibility of the quantitative value has not yet been
poor in the obese patients. We have previously demonstrated clarified. The aim of this study is to confirm the test-retest
that 18F-NaF PET/CT has high diagnostic accuracy in morbidly reliability of quantitative value calculated by a novel SPECT/
obese patients (body mass index [BMI] >40kg/m²) with cancer CT of bone scans. Materials and Methods: This prospective
[1]. In the present work, we investigate whether these superior study included eleven male patients with prostate cancer who
imaging characteristics are preserved in super-obese patients performed SPECT/CT for the evaluation of bone metastasis.
(BMI >50kg/m2). Materials and Methods: Fifty-one extremely Written informed consents were acquired before enrollment
obese patients with BMI >50Kg/m2 (mean weight 126.2±14.5 in the study. Patients received a second bone scan (retest-scan)
kg; BMI 54.57±4.8 kg/m2; mean age 59.9 years [range 36 - 76]) after 4-10 days of a first bone scan (test-scan). For the bone scans,
and referred for 18F-NaF PET/CT for the osseous staging of a images were acquired by a novel quantitative SPECT/CT scanner
newly diagnosed malignancy or suspected/proven recurrence (Symbia Intevo, Siemens) after administration of [Tc-99m]
were retrospectively analyzed. All patients underwent 18F-NaF methylene diphosphonate. SPECT/CT images from shoulder
PET/CT scan after injection of 0.06 mCi/kg of 18F-NaF according to pelvis were reconstructed by Ordered Subset Conjugate-
to EANM guidelines [2]. Images were interpreted using a 5-point Gradient Minimizer. We set regions of interests (ROIs) at visually
scoring system as published previously [1]. Equivocal scores increased uptake areas on metastasis and degeneration, as
were classified as benign for the final analysis. The reference well as fundamental 12 normal areas. Uptakes of the ROIs were
standard was based on the combination of confirmation evaluated by standardized uptake value (SUV), and maximum
of metastatic status by other imaging modalities or clinical SUV (SUVmax) and peak SUV (SUVpeak) were used. Intra-class
follow-up. Diagnostic test characteristics were calculated correlation coefficient (ICC) was used to evaluate the difference
using traditional methods. Means with standard deviations of the 2 scans, and ICC of 0.8 or more was considered as almost
and proportions with 95% confidence intervals are reported. perfect correlation. Results: We analyzed 212 ROIs including
Results: The median duration of follow-up after imaging was 163 normal, 25 degenerative, and 24 metastatic lesions. Percent
13 months (range 06-18). 18F-NaF PET/CT was definitely benign differences (average ± standard deviation) for SUVmax were
in 25, possibly benign in 2, equivocal in 2, possibly malignant in 11.7 ± 9.1% for normal, 18.0 ± 14.4% for degenerative, 10.4 ±
7 and definitely malignant in 15 patients. The overall prevalence 8.1% for metastatic, and 12.3 ± 9.9% for all lesions, respectively.
of bone metastases according to the reference standard was Percent differences for SUVpeak were 11.0 ± 7.7% for normal,
41.2% (95% CI 27.6-55.8%). The sensitivity, specificity, PPV, NPV 16.0 ± 11.2% for degenerative, and 9.5 ± 8.0% for metastasis,
and accuracy of 18F-NaF PET-CT were 90.5% (95% CI 69.6-98.8%), and 11.4 ± 8.4% for all lesions, respectively. ICCs (and the 95%
90% (95% CI 73.5-97.9%), 86.4% (95% CI 65.1-97.1%), 93.1% (95% confidence interval in the parenthesis) of SUVmax were 0.91
CI 77.2-99.1%), and 90.2% (95% CI 78.6 - 96.7%), respectively. (0.88—0.93) for normal, 0.92 (0.83—0.96) for degenerative, 0.80
While few patients had BMI >60Kg/m² (n=6), similar results were (0.60—0.90) for metastatic, and 0.97 (0.96—0.98) for all lesions.
S531 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

ICCs of SUVpeak were 0.94 (0.96—0.98) for normal, 0.94 (0.86— PSMA-PET/CT) and Technetium-99m diphosphonate bone
0.97) for degenerative, 0.86 (0.70—0.94) for metastatic, and scintigraphy (BS) performance for bone metastases detection in
0.97 (0.96—0.98) for normal lesions, respectively. Conclusion: prostate cancer patients. Materials and Methods: Retrospective
The novel quantitative SPECT/CT provides almost perfect test- study of 73 patients that underwent 68Ga-PSMA-PET/CT and
retest reliability of SUVs among 2 bone SPECT/CT performed on BS between 01.01.2015 and 01.03.2019, with a maximum of 90
different days. References: None. days between them and without any therapeutic change in that
time period. The studies were classified as present, absent or
suspected metastases. Global and per anatomic region analyses
EP-0324 were performed. Cases suspicious of metastasis were redefined
Clinical Utility of hybrid versus planar images on bone as positive and negative to allow for a scenario analysis. The
scintigraphy for oncologic patients best valuable comparator was defined based on follow up data,
I. El Bez, R. Tulbah, I. Munir, F. Alghamlas, M. Alharbi; namely subsequent BS, 68Ga-PSMA-PET/CT, computerized
King fahd medical city, nuclear medicine tomography, magnetic resonance imaging, and histology
department, Riaydh, SAUDI ARABIA. when available. Specificity, sensitivity, positive predictive value,
negative predictive value and accuracy were calculated using
MedCalc software. Fisher test was used to assess the association
Aim/Introduction: To evaluate retrospectively the additional between the accuracy of each exam and prostate specific
diagnostic value of hybrid fused single photon emission antigen (PSA), alkaline phosphatase levels and clinical indication
computed tomographic with (SPECT-CT) images in assessing for performing the study (staging, biochemical recurrence and
possible bone metastases. Materials and Methods: We metastatic castration-resistant prostate cancer). Results: 68Ga-
identified 100 oncologic patients (75 female and 25 males). PSMA-PET/CT and BS were congruent in 58 (79.4%) patients,
Bone scintigraphy including planar and SPECT-CT imaging were (40 negatives, 17 positives and 1 suspicious for metastasis) and
performed for all patients. First, we analyzed the planar images, differed in 15 (20.6%) patients. 68Ga-PSMA-PET/CT identified
then the fused images and focused on the additional value correctly seven (9.6%) patients with metastasis (BS negative)
of fused images. Diagnostic confidence for each lesion was and BS identified correctly two (2.7%) patients with metastasis
scored. On the planar images we classified as confident (malign, (68Ga-PSMA-PET/CT negative). Considering both scenarios,
benign) or indeterminate Results: 100 oncological patients global specificity, sensitivity, positive predictive value, negative
were included (75 women, 25 man; mean age, 52.4 years ± 10.7. predictive value and accuracy varied between 97.7-100.0%, 89.5-
The planar images demonstrate 245 foci: 211 were confidents 93.1%, 96.4-100.0%, 93.6-95.6%, 96.0-96.0% for 68Ga-PSMA-PET/
(115 metastatic bone foci and 130 benign foci) and 34 were CT and 93.9-100.0%, 62.1-75.9%, 88.0-100.0%, 80.0-85.4%, 84.9-
indeterminate. After review of fused images: for the confidents 86.3% for BS, respectively. Comparing to BS, specificity, sensitivity,
lesions: there were two benign lesions which became suspicious positive predictive value, negative predictive value and accuracy
based on low dose CT. Almost all indeterminate became more were higher in 68Ga-PSMA-PET/CT also per anatomic region
confident in diagnosis with 25 benign lesions and 15 metastases. analyzes. There was no correlation between diagnostic accuracy
In addition, fused images demonstrated also 12 lesions non and clinical indication for performing the studies, PSA and
visualized on planar images. Conclusion: Results demonstrate alkaline phosphatase levels in both studies. Conclusion: In this
the increased diagnostic confidence obtained with fused review 68Ga-PSMA-PET/CT diagnostic performance for bone
SPECT/CT images compared to planar images in differentiating metastasis detection in prostate cancer was superior to BS. A
malignant from benign bone lesions. References: None. larger sample and prospective randomized trials are needed
in order to prove 68Ga-PSMA-PET/CT applicability in routine
prostate cancer bone metastasis imaging. References: None.
EP-0325
68Ga-PSMA-PET/CT vs Bone Scintigraphy in prostatic
cancer; are we postponing the future? EP-0326
S. Castro1, G. Ferreira1, L. Violante1, L. Fonseca2, I. Sampaio1, C. Whole-body SPECT/CT: Could Replace Bone Scintigraphy
Castro1, H. Duarte1; in Cancer Patients?
1
Instituto Português de Oncologia, Porto, PORTUGAL, 2Centro F. Manchon Adsuar, R. Diaz Expósito, V. López Prior;
Hospitalar Universitário do Porto, Porto, PORTUGAL. Fundación Instituto Valenciano de Oncologia, Valencia, SPAIN.

Aim/Introduction: Prostate cancer is the second most common Aim/Introduction: SPECT-CT is commoly used after equivocal
cancer in men and skeletal system is the most common site findings in the whole-body bone scan in the staging workup for
for distant metastasis. Therefore, it is very important in clinical cancer patients. Our objective was to investigate if whole-body
practice to have sensitive imagiological methods that allow SPECT-CT (3 FOV, field of view) could be applied and replace the
early detection of bone metastasis. The purpose of this study planar bone scan in cancer patients, mostly prostate and breast
was to compare Gallium-68 prostate specific membrane antigen cancer. Furthermore, our aim was to compare the sensitivity
positron emission tomography/computed tomography (68Ga- and specificity of both tests. Materials and Methods: In 29
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S532

patients (18 breast cancer, 10 prostate cancer, 1 rectum cancer), PET/CT is a useful tool in the staging of patients with STS.
whole-body scan SPECT-CT and bone scan were prospectively References: Németh Z, Boér K, Borbély K. Advantages of (18)
performed for staging and re-staging. All data were acquired F FDG-PET/CT over Conventional Staging for Sarcoma Patients.
with 3 FOV SPECT-CT, Discovery NM/CT870 General Electric Pathol Oncol Res. 2019 Jan;25(1):131-136. doi:10.1007/s12253-
gamma camera. Subsequently, the follow-up was clinical and/or 017-0325-0.
with other imaging modalities. Results: Based on planar image,
6 patients (20.69%) were positive for bone metastasis, and 23 (
79.31%) were negative. The sensitivity and specificity was higher EP-0328
with whole-body SPECT-CT than with planar images to detect Role Of 18F-FDG PET/CT In Management Of Malignant
bone metastases (87.5% and 95.5% vs 77.7% and 95%). Whole- Peripheral Nerve Sheath Tumors (MPNST)
body SPECT-CT reclassified 3 negative bone scan patients D. Yadav, S. A. Shamim, S. Rastogi, C. Bal;
into positives. The follow-up confirmed two of these patients. All India Institute of Medical Sciences, New Delhi, INDIA.
One positive patient by whole-body scan was downstaged by
whole-body SPECT-CT to nonmetastatic disease. In all cases,
whole-body SPECT-CT provided a better characterization Aim/Introduction: MPNST are malignant tumors arising from a
of both benign and malignant lesions. Conclusion: Adding peripheral nerve or in extraneural soft tissue and showing nerve
whole-body SPECT-CT images can result in a better patient sheath differentiation. They are rare and comprises about 5% of all
management and a more precise identification of bone soft tissue sarcomas. They are aggressive tumor associated with
metastases. This technique could replace whole-body scan in poor prognosis. 18FDG PET/CT has been used to differentiate
the near future in selected cases. References: None. between benign and malignant lesion in Neurofibromatosis (NF-
1). The purpose of our study is to evaluate further role of 18FDG
PET/CT in management of MPNST. Materials and Methods: We
EP-0327 have performed a retrospective analysis to include 12 patients
Utility of SUVmax, SUVmean AND SUVpeak values measured on of MPNST who has undergone FDG PET/CT imaging for staging
baseline 18F-FDG PET/CT to discriminate the high-grade and restaging. Mean and maximum standardised uptake values
from the low-grade soft tissue sarcomas (SUVmean, SUVmax) were measured for each primary/recurrent
R. H. Reyes Marlés, T. Moreno Monsalve, T. Rodríguez Locarno, and metastatic lesion. For measuring the SUVmean of reference
J. Navarro Fernàndez, J. Puertas García-Sandoval, F. Santonja, L. tissues, 1-cm diameter ROIs were placed on right liver lobe,
Mohamed Salem, L. Frutos Esteban, J. Contreras Gutiérrez, G. Ruiz aorta and left gluteal muscle, respectively. The SUVmax of PNSTs
Merino, M. Claver Valderas; was normalised to mean liver uptake, yielding a (T/L) tumor-to-
University Hospital Virgen de la Arrixaca, El Palmar, SPAIN. liver ratio (SUVmax Tumor/SUVmean liver). Univariate analysis
was performed using the SPSS software package (version 23.0;
IBM). Results: Twelve patients (9 males, 3 females) were enrolled
Aim/Introduction: To analyze the utility of the SUV (SUVmax, in the study, out of which 3 patients (25%) of NF-1 underwent
SUVmean and SUVpeak) values ​​measured on a baseline 18F-FDG FDG PET/CT to differentiate between benign and malignant
PET/CT to discriminate between histological high-grade and lesions. FDG PET/CT was done for staging in 5 patients, and it
low-grade soft tissue sarcomas (STS), according to the French identified metastasis in 2 patients at baseline. Seven patients
Federation of Cancer Centers (Fédération Nationale des Centres had recurrence post-surgical excision which was identified by
de Lutte Contre Le Cancer, FNCLCC). Materials and Methods: FDG PET/CT imaging. In follow-up imaging done in 3 patients
A retrospective study was conducted in 83 patients with STS for response assessment, they had progressive disease which
diagnosed between 2011-2018, having a baseline 18F-FDG prompted treatment intensification. SUVmax of primary lesion
PET/CT, that employed the histological grade according to the showed correlation with histopathological grade (r=0.612,
French Federation of Cancer Centers (Fédération Nationale des p=0.034). Metabolic Tumor Volume(MTV), Total lesion glycolysis
Centres de Lutte Contre Le Cancer, FNCLCC). They were sorted (TLG) and SUVmax showed correlation with event free survival.
out into two groups, high grade (grades 2 and 3) and low grade Conclusion: In MPNST, FDG PET/CT can be used for staging,
(grade 1). ROC curves were employed to evaluate the capacity​​ prognostication, restaging for recurrence and therapy response
of the baseline 18F-FDG PET/CT SUV values to differentiate the assessment, other than its already proven role in differentiating
high-grade from the low-grade lesions. Results: Statistical benign and malignant lesions in NF-1, predicting transformation
analysis using ROC curves found the following values ​​as optimal of plexiform neurofibroma into MPNST in NF-1. References: 1.
cut-off points to discriminate high-grade from low-grade STS: David Tovmassian, Muzib Abdul Razak, and Kevin London. The
-SUVmax 3.9 (AUC= 0.824; 95% CI = 0.717 - 0.931, sensitivity: 84%, Role of [18F]FDG-PET/CT in Predicting Malignant Transformation
specificity: 30%). -SUVmean 2.5 (AUC= 0.798; 95% CI = 0.682 - 0.914, of Plexiform Neurofibromas in Neurofibromatosis-1. Int J
sensitivity: 81%, specificity: 30%). -SUVpeak 3.7 (AUC = 0.817; 95% Surg Oncol. 2016; 2016: 6162182. 2. Salamon J1, Veldhoen S,
CI = 0.708 - 0.926, sensitivity 81%, specificity: 30%). Conclusion: Apostolova I, et al. 18F-FDG PET/CT for detection of malignant
- The SUVmax, SUVmean, and SUVpeak values ​​measured on a baseline peripheral nerve sheath tumours in neurofibromatosis type 1:
18
F-FDG PET/CT allowed to differentiation between high-grade tumour-to-liver ratio is superior to an SUVmax cut-off. Eur Radiol.
lesions from low-grade lesions in patients with STS. - 18F-FDG 2014 Feb;24(2):405-12.
S533 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

EP-21 ductal carcinoma (IDC) of the breast with coexisting ductal


carcinoma in situ (DCIS) (IDC-DCIS) show lower metastatic
Clinical -> Diagnostic study -> Adult study -> potential and recurrence and better overall survival than the
Oncology study -> Organ-based oncology -> patients with pure IDC. In this study we further assessed F-18
Breast, malignant fluorodeoxyglucose (FDG) positron emission tomography/
computed tomography (PET/CT) images of patients with newly
October 12 - 16, 2019 e-Poster Area diagnosed IDC to determine if PET findings can predict the
presence of DCIS and if there is any difference in PET findings
in coexisting DCIS-positive and negative cases. Materials and
Methods: FDG PET/CT images of patients with newly diagnosed
EP-0329 IDC of the breast who subsequently underwent breast surgery
Prognostic Value Of F-18 FDG PET/CT In Invasive Ductal and had histopathology result in our records were further
Carcinoma evaluated. Tumor grade, pathological staging, presence of DCIS
S. Kang; and its features were noted from the histopathology results.
Catholic University of Daegu School of Maximum standardized uptake values (SUVmax) of the primary
Medicine, Daegu, KOREA, REPUBLIC OF. tumor, other hypermetabolic foci in the breast (multifocal
uptake), and ipsilateral and contralateral normal appearing
breast tissues were measured. Presence of axillary and distant
Aim/Introduction: To determine the prognostic implications metastases were noted. Results: Fifty seven (57) patients with
of pretreatment F-18 FDG PET/CT (PET/CT) in patients with IDC met the inclusion criteria. Histopathology showed the
invasive ductal carcinoma (IDC), we evaluated the relationship presence of coexisting DCIS in 44 patients (77.2 %). Coexisting
between FDG uptake of the primary mass (pSUVmax) and DCIS was not present in 13 patients. Per histopathology, the
known prognostic parameters of breast cancer. Prognostic primary tumor was unifocal in 33 DCIS-positive (75 %) and 12
significance of pSUVmax for the prediction of progression- DCIS-negative (92.3%) cases, and multifocal in 11 DCIS-positive
free survival (PFS) was also assessed. Materials and Methods: cases (25 %), and 1 DCIS-negative case (7.7%). PET showed
Three-hundred eighty five female patients with IDC who multifocal breast uptake in 20 of DCIS-positive cases (45.5 %)
underwent pretreatment PET/CT were enrolled from 2005 to and 1 of DCIS-negative case (7.7%), and unifocal breast uptake
2016 year. The visual interpretation and pSUVmax of PET/CT was (only in primary tumor) in 24 of DCIS-positive (55.5 %), and 12
compared with clinicopathological parameters including ER, of DCIS-negative (92.3%) cases. Axillary lymph node metastases
PR, HER2, axillary lymph node metastasis (LNM) and stage. The were seen in all 13 DCIS-negative (100%), and 26 DCIS-positive
prognostic value of pSUVmax, for PFS was assessed using the (59%) cases. There was no significant difference in mean age,
Kaplan-Meier method. Results: Positive on tumor and axillary mean size of the tumor, mean SUVmax of the primary tumor,
lymph node by visual interpretation of PET/CT can predict and mean SUVmax of normal breast in DCIS-positive and
recurrence (P=0.0052, P<0.0001). pSUVmax was significantly negative cases (p>0.05). Conclusion: Multifocal breast FDG
higher in ERnegative tumors (P<0.0001), PR-negative tumors uptake and multifocal tumor were more common in patients
(P=0.0006), and positive LN metastasis (P=0.0001), but not with IDC-DCIS than pure IDC. This preliminary finding may raise
different according to HER2 status. pSUVmax was significantly the question if there could be radiologically/pathologically
higher in patients with progression compared to patients who undetected multifocal tumor in IDC-DCIS cases with unifocal
were disease-free (7.1±5.3 vs. 3.8±3.3, P<0.0001). A receiver- tumor. References: None.
operating characteristic curve demonstrated a pSUVmax of 4.0
to be the optimal cutoff for predicting PFS (sensitivity; 69.4%,
specificity; 66.8%). The patients with a high pSUVmax (more EP-0331
than 4.0) had significantly shorter PFS compared to patients Impact of Patient Involvement on a Clinical Study:
with a low pSUVmax (P<0.0001). Conclusion: PET/ CT before Experiences from a Study Analyzing FDG-PET/CT in
treatment can be useful marker for the prediction of progression Women with Advanced Breast Cancer
in patients with IDC. References: None. M. G. Hildebrandt1,2, M. Vogsen1,2, S. Geneser1, M. Rasmussen1, M.
Hoerder3, PREMIO - Centre for Personalized Response Monitoring in
Oncology;
EP-0330 1
Odense University Hospital, Odense C, DENMARK,
FDG PET Findings In Invasive Ductal Carcinoma Of The 2
University of Southern Denmark, Odense, DENMARK,
Breast With And Without Coexisting DCIS 3
University of Southern Denmark, Odense C, DENMARK.
I. Sarikaya1, A. Sarikaya2, A. Albatineh1, E. Tastekin2, Y. A. Sezer2;
1
Kuwait University Faculty of Medicine, Kuwait, KUWAIT,
2
Trakya University Faculty of Medicine, Edirne, TURKEY. Aim/Introduction: Patient involvement in health care research
has become of increasing interest in recent years. Researchers,
however, may be uncertain about the gain of involving patients
Aim/Introduction: Studies have reported that patients invasive in clinical studies. We aimed to evaluate the impact of patient
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S534

involvement on a clinical study of FDG-PET/CT in women with Aim/Introduction: The aim was to compare the prone versus
advanced breast cancer with regard to patient recruitment standard supine PET/CT acquisition for lymph node (LN) staging
and change of attitude within our research team. Materials in patients with newly diagnosed breast cancer. Materials and
and Methods: Two patient representatives from the Danish Methods: This retrospective cohort study evaluated women
Breast Cancer Organization were invited as partners of the with a recent diagnosis of breast cancer referred to our service
research team. The patient partners were asked to contribute for staging. All patients underwent dual time-point scans. The
in particular to participator information as well as to evaluate first acquisition was a supine whole-body scan from the head
ethical aspects in the study. The impact of patient involvement to the thighs performed 1 h after administration FDG (standard).
on patient recruitment was evaluated by comparing expected The prone scan was perfomed with a mean delay of 25 minutes
versus actual number of patients recruited, and by relating it using the same breast MRI coil. The SUVmax, SUVmean, SUVmax
to the patient recruitment from a previous study performed ratio (SUVmax LN/SUVmax liver), SUVmean ratio (SUVmeanLN/
without patient involvement in a comparable patient SUVmean liver) at both time points in the lymph node and
population at the same institution from 2011-2014 (1). The the retention index (prone SUVmax - standard SUVmax/
expected patient recruitment in the current study has been standard SUVmax X100) were calculated. The final diagnosis
registered at ClinicalTrials.gov (2). Results: The expected was confirmed by pathology. Results: Seventy seven patients
number of patients recruited was 135 patients per year (2). This were finally included. The prevalence of confirmed lymph
number was based on patient recruitment in a previous study node involvement was 71,43%. Standard PET/CT SUVmax had
in which 33 patients were enrolled per year, only (1). Compared excellent discriminatory power for lymph node metastasis
to this, 199 patients have been enrolled during the first year in (Sensitivity: 87,27% , Specificity: 95.45%, PPV: 98.00% NPV:
the current study - i.e. 147 % of the expected number. Having 75,00%; correctly classified: 89,61% at 1,46, AUC ROC: 0,93) and
patients as partners in the research team led to a major revision also for prone PET/CT SUVmax (Sensitivity: 89,09% , Specificity:
of the participator information material and the way ethical 86.36%, PPV: 94.22% NPV: 76,00%; Correctly classified: 88,31%
issues were addressed. An initial resistance within the research at 1,32, AUC ROC: 0,92). Although prone PET/CT had a better
team was observed against inviting patients as partners of the sensitivity and higer SUVmax values than standard, there were
team. The resistance resolved gradually during the process, not statistically significant differences in the predictive power of
and hence the most reluctant researchers from the beginning both standard and prone PET/CT (p=0,43). The criterion validity
applauded the collaboration and the ideas generated by analysis of SUVmax ratio, SUVmean and SUVmean ratio values
patient representatives in a later phase. Conclusion: Involving showed similar results and excellent discriminatory power
patients as partners in the research team resulted in major for both standard and prone acquisitions. The absolute and
changes of the patient participator information material and percentage difference between prone and standard SUVmax,
had a significant, positive impact on patient recruitment for the the SUVmean ratio values and the retention index showed
study. Furthermore an improvement of ethical issues relevant statistically significant less discriminatory power than the
for the patients was observed. Inviting and involving patients as standard PET/CT measurements. Conclusion: Although the
partners of our research team changed the researchers’ attitudes prone PET/CT had a better sensitivity, both standard and prone
towards patient involvement in research in a positive direction. PET/CT showed similar discriminatory power and criterion
References: 1. Hildebrandt MG et al. [18F]Fluorodeoxyglucose validity values for lymph node staging. The best diagnostic test
(FDG)-Positron Emission Tomography (PET)/Computed for predicting lymph node involvement was the standard PET/
Tomography (CT) in Suspected Recurrent Breast Cancer: A CT SUVmax value, followed by prone PET/CT SUVmax value.
Prospective Comparative Study of Dual-Time-Point FDG-PET/ References: None.
CT, Contrast-Enhanced CT, and Bone Scintigraphy. Journal of
clinical oncology. 2016;34(16):1889-97. 2. https://clinicaltrials.
gov/ct2/show/NCT03358589?term=mestar&rank=1 EP-0333
Should we insist on 18F-fluoride PET/CT for breast cancer
patients? Review of experience and incidental findings
EP-0332 E. Mehdi1, F. Novruzov1, J. Aliyev2, L. Mehmetbeyli1, S. Vatankha3;
Should prone 18FDG- PET/CT be used to improve lymph 1
Department of Nuclear Medicine, National Centre of Oncology,
node staging in breast cancer? Baki, AZERBAIJAN, 2Department of General Surgery, National
L. Sánchez Orduz1, M. Morales-Lozano2, B. Aradas-Cabado3, J. Centre of Oncology, Baki, AZERBAIJAN, 3Department of diagnostic
Rosales2, J. Bastidas2, F. Grisanti2, M. Ochoa4, M. Ribelles2, M. Garcia- radiology, National Centre of Oncology, Baki, AZERBAIJAN.
Velloso2, M. Rodríguez-Fraile2;
1
SPECT medicina nuclear S.A.S, UNAB, Bucaramanga, COLOMBIA,
2
Department of Nuclear Medicine, Clínica Universidad de Navarra, Aim/Introduction: 18F sodium fluoride 18F-NaF PET/CT scan
Pamplona, SPAIN, 3Department of Nuclear Medicine, Hospital in patients with breast cancer is important in influencing clinical
Clínico Universitario de Santiago de Compostela, Santiago de interpretation. Despite the numerous benefits of 18-F NaF PET/
Compostela, SPAIN, 4Department of public health, Universidad CT, it’s being highly sensitive rather than specific and often
Autónoma de Bucaramanga, Bucaramanga, COLOMBIA. cause challenges in clinical interpretation. Knowing the average
uptake values for normal bone and frequency of benign skeletal
S535 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

processes with influencing risk factors is important in diminishing mixed, papillary, mucinous, metaplastic, tubulary and anaplastic
the range of diagnostic false-positives. We provide valuable data types or according to estrogen receptor (ER) or progesteron
of benign findings with 18F NaF PET/CT standardized uptake receptor (PR) positivity. Also the SUVs in a group of patients with
values (SUVs) seen in breast cancer patients. Materials and lymph node metastasis (LNm) were investigated separately.
Methods: A retrospective analysis of 139 patient reports with The study patients divided into two groups according to Ki67
the diagnosis of breast cancer who underwent 18F-NAF PET/ index by a subjective cutoff value of lower than 20 and equal
CT at our EARL accredited institution between January 2019 or higher than 20 as well as according to the cerbB2 expression
and April 2019. All PET/CT scans were reviewed in consensus were also examined in terms of SUVs. Statistical analysis were
by two blinded nuclear medicine physicians. The findings made using ANOVA and students’ t test by Microsoft SPSS v20.0
were interpreted as benign if increased uptake correlated as appropriate. Results: 1. The maximum, mean and peak SUVs
to endplates, within osteophytes and around the joints or were found significantly different in MS (p=0.001). 2. There
radiological benign lesions seen on the morphologically were no significant difference between MS in terms of MTV.
oriented low dose CT images or follow-up magnetic resonance (p=0.303) 3. SUVs were not found statistically significant fort he
imaging. The maximum standardized uptake value (SUVmax) HG. 4. SUVs and MTV was not different in terms of ER or PR. 5.
of region of interest and mean standardized uptake value Maximum and peak SUVs were significantly different (p=0.004
(SUVmean) of bone marrows (sternum, lumbar vertebra and and p=0.001 resp.), but not mean SUV (p=0.061) in patients with
femur neck) were calculated per respective region. Statistical LNm. 6. Only maximum SUV was slightly different according to
data analysis was made using SPSS Statistics and Modeler cerbB2 scores (p=0.034). 7. All SUVs were found significantly
software. Results: The most common finding was osteophyte different in groups with Ki67 values lower or higher than 20,
uptake seen in 47 patients (34%) with mean SUVmax=19.7 but not MTV. Conclusion: This extended analysis in a small
(SD=8.6). Facet joint uptake was in 34 patients (24%) with number of patients with BC showed that SUVs are significantly
mean SUVmax=21.1 (SD=7.7). Endplate uptake was seen in 18 different among MS but not in HG of BC. Additionally, there are
(13%) with mean SUVmax 19.2 (SD 5.5). The lowest coefficient differences of SUvs when other relevant clinical parameters of
of variation for bone marrow SUVmean was seen in lumbar BC were individually considered. References: None.
vertebrae. There was negative correlation between SUVmean
values of sternum and age. (r=-0.28, p=0.001). The weight was
correlated significantly only with SUVmax values of knee joint EP-0335
uptake (r=-0.50, p=0.002) and presence of osteophyte uptake Comparison of prone and supine 18F FDGPET parameters
(p<0.05). Conclusion: Awareness of common benign findings of locally advanced breast cancer
knowledge in 18F-NAF PET/CT application is invaluable for E. Arslan, T. Aksoy, T. F. Cermik;
correct diagnosis and achieves faster study interpretation time. University Of Health And Science Istanbul Research and Training
References: None. Hospital Clinic Of Nuclear Medicine, Istanbul, TURKEY.

EP-0334 Aim/Introduction: Prone position 18F fluorodeoxyglucose


Comprehensive Analysis of Clinical Parameters used in positron emission tomography/computed tomography (FDG-
Breast Cancer with F-18 FDG PET/CT Standardized Uptake PET/CT) may improve the localization of the tumor, delineate
Values the exact distance from areola which is utmost important for
E. Akgun, O. O. Balkanay, H. B. Sayman; the surgical planning and separation of deep anatomic parts
IUC Cerrahpasa Medical Faculty, Istanbul, TURKEY. especially axillary lymph nodes. The aim of this study was to
compare the PET CT metabolic and anatomic parameters by
prone versus supine 18 FDG-PET in newly diagnosed breast
Aim/Introduction: Breast cancer (BC) is the first most common cancer. Materials and Methods: Locally Institutional Review
cancer in women after the skin cancer. The differentiation of Board approved this prospective ongoing study. Total of 58
molecular subtypes (MS) as well as histologic types of BC is breast cancer patients whom newly diagnosed underwent
important since they have different prognosis and response to both prone and supine FDG-PET/CT at the same scanning
therapy differently. In this study, we aimed to find out if there day. Two readers performed an independent review of all
is a relationship between SUVs and moleculer subtypes of BC. scans. Differences between the observers were resolved at a
Materials and Methods: In this retrospective study, we tried consensus reading session. Primary tumor SUVmax, SUV peak,
to find if SUVs obtained from 50 BC patients with different SUVmean40%, MTV40%, TLG40, Thresh40, SUVmean70%,
subgroups of molecular subtypes (Luminal A; Luminal B, HER2(-); MTV70%, TLG70, and Thresh 70 values were calculated for
Luminal B HER2(+); Triple negative/basal like) are with statistically both supine and prone positions. Also, differences between
significant difference or not. Moreover, we investigated the distance of primary tumor from the areola and pectoral muscle
metabolic tumor volume (MTV) from the same PET data if it involvements and axillary lymph node status were evaluated by
was also significantly different in between same groups. We two interpreters. Results: Prone position mean primary tumor
also searched weather the maximum, mean or peak SUV differs SUVmax was 11,34±6,79, supine position mean primary tumor
between the histologic groups (HG) of BC such as ductal, lobular, SUVmax was 11,57±7,26. There was no significant difference
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S536

between prone to supine position primary tumor SUVmax patients being staged for known malignancy, and the word
(p: 0,549). Categorization of anatomic disease distribution has “breast” was used in the search, which may have caused selection
concordant between prone and supine scanning in 54 patients. bias. Data from four studies (1-4) were eligible for meta-analysis;
Prone position; mean 40% MTV±STD:17,26±43,98 and mean one of them was performed in a large screening population
70%MTV±STD:2,04±2,83. Supine position mean40% MTV was from Japan including 62,054 asymptomatic women. A high
16,86±37,6 and mean70%MTV was 2,53±3,47. By far away degree of heterogeneity was observed for prevalence data(I2 of
prone position gives better anatomical location, exact distance 97.5%), while moderate heterogeneity was observed for data on
from the areola and gives better visual assessment ability of malignancy risk assessment(I2 of 62.8%). The pooled prevalence
pectoral muscle; as expected. In the 49 patients with breast and of FIBU in women was 0.61%(Range:0.56-0.66%), and the pooled
axillary disease, equal numbers of metastatic lymph nodes were prevalence of malignancy of FIBUs was 38.7%(range:34.4-43.0%).
identified on prone and supine scanning in 37 patients, whereas The most commonly detected malignancy was invasive ductal
in the remaining 12 patients, prone scanning diagnosed in carcinoma. Conclusion: FIBU occurs rarely on FDG-PET/
a higher number of visualized lymph nodes. Conclusion: CT although these results are dominated by a large study
Both prone and supine position FDG-PET/CT scanning gives performed in a screening population. FIBU on FDG-PET/
identical information on locoregional disease distribution in CT yields high risk of malignancy according to the results of
Locally Advanced Breast Cancer. But prone position scanning published papers. Therefore, it should be considered relevant
may perform better than supine for assessing the number to further elucidate patients with incidentally detected FDG-
of metastatic lymph nodes, distance from the areola and uptake in breast in clinical practice. References: 1.Dunne,RM.,
delineation of pectoral muscle involvement. Prone position et al., The role of the breast radiologist in evaluation of
FDG-PET/CT may be useful for surgical planning in future clinical breast incidentalomas detected on 18-fludeoxyglucose
and research studies, including PET and magnetic resonance positron emission tomography/CT.British Journal of
imaging (MRI) fusion applications. References: None. Radiology.86(1026):20130034. 2.Lim,S., et al., Role of combined
BI-RADS assessment using mammography and sonography for
evaluation of incidental hypermetabolic lesions in the breast on
EP-0336 18F-FDG PET-CT.Acta Radiologica.54(10):1117-24. 3.Shin,KM., et
Prevalence of focal incidental breast uptake on FDG-PET/ al., Incidental breast lesions identified by 18F-FDG PET/CT: which
CT and risk of malignancy: A Systematic Review and Meta- clinical variables differentiate between benign and malignant
analysis breast lesions?Journal of breast cancer,2015.18(1):73-9.
M. Naghavi-Behzad1,2, E. Aarstad1, P. Nordhaug1, L. Brønsro 4.Minamimoto,R., et al., Detection of breast cancer in an FDG-
Larsen3, M. Vogsen1,2,4, O. Gerke2, M. Grubbe Hildebrandt1,2; PET cancer screening program:results of a nationwide Japanese
1
Department of Clinical Research, University of Southern survey.Clinical breast cancer,2015.15(2):139-46.
Denmark (SDU), Odense, DENMARK, 2Department of
Nuclear Medicine, Odense University Hospital, Odense,
DENMARK, 3Department of Radiology, Odense University EP-0337
Hospital, Odense, DENMARK, 4Department of Oncology, Value Of Hybrid F-18 FDG PET/MRI In BIRADS 4 And 5
Odense University Hospital, Odense, DENMARK. Breast Lesions: Preliminary Results Of An On-Going Study
L. L. Uslu1, R. Yılmaz2, M. Velidedeoglu3, O. E. Sahin1, E. Akgün1, S.
Sager1, H. B. Sayman1, K. Sonmezoglu1;
Aim/Introduction: FDG-PET/CT is increasingly used for 1
Istanbul University-Cerrahpasa, Cerrahpasa Medical Faculty,
oncologic and inflammatory diseases. Focal incidental FDG- Department of Nuclear Medicine, Istanbul, TURKEY, 2Istanbul
uptake occurs rarely in breast tissue but has often significant University, Istanbul Medical Faculty, Department of Radiology,
consequences. This study aimed to systematically review Istanbul, TURKEY, 3Istanbul University-Cerrahpasa, Cerrahpasa
literature regarding focal incidental breast uptake (FIBU) on Medical Faculty, Department of General Surgery, Istanbul, TURKEY.
FDG-PET/CT in order to yield an update on prevalence and risk
of malignancy for FIBU. Materials and Methods: A systematic
search for relevant articles published between 2012-2018 Aim/Introduction: MRI is an efficient imaging modality for
was performed through Medline, Embase, and Cochrane detection and characterization of primary breast lesions.
databases. Studies addressing detection of FIBU in patients Although it has high sensitivity in detection of malignant breast
without previous history of breast malignancy were included. lesions it has limited specificity. Hybrid PET/MRI systems have
The QUADAS-2 was used for quality assessment, and eligible the potential to further increase the diagnostic accuracy of MRI
data were pooled using a fixed-effects model. I2 was calculated in primary breast lesions. The aim of our study is to compare the
for the heterogeneity between studies. Results: Eight studies diagnostic value of hybrid FDG PET/MRI and MRI in patients with
containing 180,002 scans were included in the systematic BIRADS 4 or 5 primary breast lesions. Materials and Methods:
review. The median prevalence of FIBU for both genders Twenty female patients with total 26 breast lesions, which were
was 0.52%(Range:0.18%-22.5%). Prevalence for women was scored as BIRADS 4 or 5 using breast USG and mammography
mentioned separately in five studies and varied from 0.51%- were prospectively enrolled in the study. All patients had
23.5%. One study reporting a high prevalence was based on whole-body hybrid TOF F-18 FDG PET/MRI in supine position
S537 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

and additional breast PET/MRI using dedicated MRI sequences metastases. Only one of those patients shows distant bone
and DCE-MRI in prone position using a breast MRI-coil. Gold- metastases. The mean SUVmax value and size for evaluated
standard was histopathology obtained after either tru-cut internal mammary lymph nodes was 5.2 ± 2.27 and 1.3±0.17
biopsy or breast surgery. Qualitative and quantitative analysis of cm (range,1-1.6 cm), respectively. The mean SUVmax of the
PET data including SUVmax, SUVmean levels and BIRADS scores associated primary breast tumor was 9.70 (SD, 4.4;range, 4.4-
were recorded. Different cut-off levels for MRI were selected 14.8). A total of 13 FDG avid internal mammary lymph nodes
to calculate sensitivity and specificity of MRI: BIRADS-5 only, were detected. FDG PET CT had higher sensitivity, PPV and
&#8805; BIRADS-4C and &#8805; BIRADS-4B. Combined PET/ accuracy of 100%, 92.3%, and 38.5% versus 83.3% & 46.1%; for
MRI data was evaluated according to the following criteria: All diagnostic CT; respectively. Conclusion: In an incidence of 9%,
BIRADS-5 lesions and BIRADS-4 lesions with FDG uptake were internal mammary lymph node metastasis in initial breast cancer
scored as malignant. Results: Total 19 lesions were malignant staging is believed to be related to IDC pathology, presence of
and 7 lesions were benign. Mean SUVmax (8.36 versus 2.39) and malignant axillary lymph nodes and high SUVmax of primary
SUVmean (5.12 versus 1.49) levels were significantly higher in breast lesion. FDG PET CT seems to be superior to diagnostic
malignant lesions compared to benign lesions (p=0.007 and CT in initial IM nodal detection with its subsequent alteration
p=0.008 respectively). Area under curve (AUC) for BIRADS-5, of therapy decisions and prognosis. Key words: FDG PET/CT,
&#8805; BIRADS-4C, &#8805; BIRADS-4B, qualitative PET, breast cancer, internal mammary, metastases. References:
SUVmax and SUVmean were 0.763, 0.876, 0.857, 0.759, 0.853 None.
and 0.846 respectively. AUC for combined PET/MRI data was
0.759. Sensitivity and specificity of MRI BIRADS-5 only, &#8805;
BIRADS-4C and &#8805; BIRADS-4B were 52.6%, 100%, 89.5%, EP-0339
85.7%, 100% and 71.4%, respectively. Sensitivity and specificity Correlation Between Primary Breast Tumor Size And
of qualitative PET data and combined PET/MRI were 94.7%, Prevalence Of Nodal And Distant Metastasis On FDG PET/
57.1%, 94.7% and 57.1%, respectively. SUVmax cut-off 2.62 has CT at Initial Staging
sensitivity and specificity of 84.2% and 85.7%, respectively for N. Fatima1, M. u. Zaman1, U. Zaman2, A. Zaman2, R. Tahseen3, S.
detection of malignant lesions. Conclusion: MRI is a sensitive Zaman4;
and specific imaging modality for detection of malignant breast 1
Department of Radiology, Aga Khan University Hospital
lesions with the highest AUC in our cohort. Combined PET/MRI (AKUH), Karachi, PAKISTAN, 2Department of Medicine,
for breast imaging may further increase the sensitivity of breast Dr Ruth Hospital,, Karachi, PAKISTAN, 3Department of
imaging. References: 1. Botsikas D et al. Eur Radiol. 2016;26:2297- Radiation Oncology, Aga Khan University Hospital (AKUH),
307. 2. Jena A et al. Am J Roentgenol. 2017;209:662-70. 3. Pinker Karachi, PAKISTAN, 4Dow Medical College, Dow University
K et al. Clin Cancer Res. 2014;20:3540-9. of Health Sciences (DUHS), Karachi, PAKISTAN.

EP-0338 Aim/Introduction: patients with breast cancer, it is thought


Added diagnostic value of FDG PET/CT in assessment that the risk of developing metastases increases monotonically
of internal mammary nodal metastasis in breast cancer with tumor size, because the larger the cancer at diagnosis, the
patients more cells are available to metastasize with increase disease
E. El-kholy1, L. Khaled2; specific mortality. Purpose of this study was to evaluate this
1
Nuclear medicine unit, National cancer Institute linear relation between primary tumor size and metastases
(NCI) Cairo University, Egypt, Cairo, EGYPT, 2Radiology (nodal and non-nodal) using FDG PET/CT. Materials and
department, Al-Azhar University, Egypt, Cairo, EGYPT. Methods: We recruited 214 consecutive breast cancer patients
who were referred for FDG PET/CT imaging for initial staging.
Patients were categorized in to four groups based on primary
Aim/Introduction: to evaluate the role of FDG PET CT in tumor size (T1: ≤ 2 cm; T2: >2 cm and ≤ 5 cm; T3: > 5 cm; T4: any
detection of internal mammary nodal metastases in breast size involving chest wall or skin). For each group we determined
cancer patients and their prognostic value. Materials and ipsilateral axillary nodal, extra-axillary (including contralateral
Methods: Consecutive 110 female patients, mean age: 54.1±13 axillary) nodal, visceral and skeletal metastases seen on FDG
with pathologically proven breast cancer in whom initial (pre- PET/CT imaging. Results: 47/214 patients had T1 tumor and
operative) FDG PET/CT scan were retrospectively assessed. found to have 15% axillary, 47% extra-axillary, 68% visceral and
Internal mammary nodal lesions analysis were conducted 38% skeletal metastases. 104/214 patients had T2 tumor and
in comparison to diagnostic CT. Pathological and clinical/ found to have 21% axillary, 45% extra-axillary, 61% visceral and
radiological follow-up for 3-15 months duration served as 37% skeletal metastases. 34/214 patients had T3 tumor and
standards of reference. Results: Internal mammary lymph node found to have 26% axillary, 47% extra-axillary, 76% visceral and
(LN) metastasis is reported in 10 patients (9%), their mean age 35% skeletal metastases. 29/214 patients had T4 tumor and
was 53.6±13.8. Invasive duct carcinoma was the pathology in 9 found to have 45% axillary, 69% extra-axillary, 79% visceral and
among 10 patients. All 10 patients have epsilateral axillary nodal 41% skeletal metastases. On regression analysis, highest positive
deposits, and 2 out of 10 have associated mediastinal nodal linear correlation was found for ipsilateral nodal metastasis (r =
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S538

0.945; significant p-value) followed by extra-axillary nodal (r = EP-22


0.772), visceral (r = 0.763) metastases. No significant correlation Clinical -> Diagnostic study -> Adult study ->
was found between primary tumor size and skeletal metastasis Oncology study -> Organ-based oncology ->
(r= 0.362). Conclusion: We found a linear correlation between Colorectal, malignant
primary tumor size and prevalence of metastases to nodes
(highest for ipsilateral nodes) and viscera and favoring the October 12 - 16, 2019
e-Poster Area
conventional linear model. However, no linear correlation was
found between prevalence of skeletal metastases and primary
breast tumor size. References: None. EP-0341
Value of 18F-FDG PET/CT metabolic parameters in patients
with locally advanced rectal cancer
EP-0340 L. García Zoghby, M. Coronado Poggio, A. Obesso de Diego,
Dedicated breast PET and prone FDG PET-CT to A. Guzmán Cruz, D. Monachello Araujo, D. Travaglio Morales,
characterise indeterminate breast lesions on MRI in S. Rizkallal Monzón, J. Cordero García, S. Rodado Marina, C.
patients with breast cancer Lancha Hernández, C. Escabias del Pozo, C. Huerga Cabrerizo, L.
T. L. J. Wagner, C. Papagiorcopulo, D. Ghosh, C. Constantinou, C. Domínguez Gadea;
Wickham, P. Tan, A. Malhotra; Hospital Universitario La Paz, Madrid, SPAIN.
Royal Free London NHS Trust, London, UNITED KINGDOM.

Aim/Introduction: The aim of this study was to assess the


Aim/Introduction: Breast MRI in patients with breast cancer to value of metabolic PET/CT parameters for predicting pathologic
assess extent of disease or multifocal disease can demonstrate response in patients with locally advanced rectal cancer (LARC),
indeterminate lesions requiring second-look ultrasound and undergoing neoadjuvant therapy. Materials and Methods: We
ultrasound or MRI-guided biopsies. PET-Mammi is a hanging retrospectively analyzed 29 patients (20 female, 9 male; mean
dedicated breast PET. Prone PET-CT is a dedicated acquisition age 67.6) with LARC, without metastatic disease. All patients
performed with a breast-supporting device on a standard PET- were treated with neoadjuvant chemoradiotherapy followed
CT scanner. We investigated if PET-Mammi and prone PET-CT by surgery, and were evaluated by 18F-FDG PET/CT before
were able to characterise these lesions further. Materials and neoadjuvant therapy, according to the standard protocol.
Methods: Eleven patients with breast cancer and indeterminate Metabolic parameters such as metabolic tumor volume
lesions on breast MRI were included. Patients underwent prone (MTV), total lesion glycolysis (TLG) and maximum standardized
PET-CT and PET-Mammi after injection of FDG subsequently on uptake value (SUVmax) were studied. Pathologic response
the same day. Patients then had second-look US, US- or MRI- to neoadjuvant therapy was assessed after surgery by tumor
guided biopsies and surgery. Imaging results were compared regression grade (TRG) classification by Dworak: 4 (no tumor
with biopsy and surgical pathology results. Results: PET- cells), 3 (very few tumor cells), 2 (dominant fibrotic changes with
Mammi and prone PET-CT respectively identified 7/8 and 6/8 few tumor cells), 1 (dominant tumor mass), 0 (no regression). We
malignant index lesions that were present on MRI. Out of the considered two different groups of patients depending on the
11 indeterminate lesions on breast MRI, 8 were malignant (3 x pathologic response: “complete pathologic response” (TRG = 4)
ductal carcinoma in situ, 2 x invasive ductal carcinoma (IDC), and “incomplete pathologic response” (TRG = 3 - 0). Correlation
3 x invasive lobular carcinoma (ILC) ) and 3 were benign (3 between basal PET/CT metabolic parameters and TRG was made
fibroadenomas). PET-Mammi and prone PET-CT respectively using non-parametric tests (Kruskal-Wallis and Chi-squared test).
identified 1/8 and 0/8 of the malignant lesions that were Cut-off values of metabolic parameters were determined by
indeterminate on breast MRI. PET-Mammi and prone PET-CT receiver operating characteristic (ROC) curve analysis. Statistical
identified 1/3 fibroadenomas that were indeterminate lesions significance was defined as P < 0.05. Results: We found
on breast MRI. SUVmax was significantly inferior on prone PET- “complete pathologic response” in 4 patients and “incomplete
CT than on PET-Mammi, with a range of 20-58% of PET-Mammi pathologic response” in 25 patients (TRG 3: 10 patients; TRG 2:
SUVmax. One lesion that was close to the chest wall was 7 patients, TRG 1: 7 patients; TRG 0: 1 patient). Mean MTV was
identified on prone PET-CT but not on PET-Mammi. PET-Mammi 12.19 cm3 (range, 3.83-26.13 cm3), mean TLG was 101 g/ml*cm3
identified two foci of malignancy that were not detected on (range, 40.54-249.96 g/ml*cm3) and mean SUVmax was 15.46 g/
prone PET-CT (18 mm IDC and 12 mm IDC). Conclusion: PET- ml (range, 4.94-25.26 g/ml). Patients with “complete pathologic
Mammi and prone PET-CT were not able to characterise further response” showed significantly lower MTV values than patients
indeterminate lesions on breast MRI. Most malignant lesions with “incomplete pathologic response” (P = 0.023). MTV cutoff
that presented as indeterminate lesions on breast MRI were not value was 12.2 cm3 (AUC 86%). Patients with MTV < 12.2 cm3
FDG-avid on PET-Mammi and PET-CT. 1/3 fibroadenoma that showed better pathologic response to neoadjuvant therapy
presented as indeterminate lesion on breast MRI was FDG-avid. than patients with MTV > 12.2 cm3 (P = 0.037). We did not found
References: None. significant correlation between TLG and SUVmax with TRG (P >
0.05). Conclusion: In patients with LARC, MTV in basal 18F-FDG
PET/CT is useful to predict pathologic response to neoadjuvant
S539 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

therapy. References: Kim SJ, Chang S. Clin Nucl Med 2015; 40: shown to be negative independent prognostic factors in these
930-5. patients. References: None.

EP-0342 EP-0343
Prognostic role of metabolic 18F-FDG PET/CT parameters 18
F-FDG PET/CT And Tumor Markers In Reccurent
and hematological prognostic indicators in patients with Colorectal Cancer: Is There A Correlation?
colorectal cancer F. Dondi1, D. Albano2, D. Rexhep2, M. Bonacina2, A. Mazzoletti1, E.
A. Cengiz1, Ö. Yersal2, I. Kurt Ömürlü3, Y. Yürekli1; Cerudelli2, M. Gazzilli2, P. Bellini1, F. Bertagna1, R. Giubbini1;
1
Adnan Menderes University, Faculty of Medicine, Department 1
Università degli Studi di Brescia, Brescia, ITALY,
of Nuclear Medicine, Aydin, TURKEY, 2Adnan Menderes 2
Spedali Civili di Brescia, Brescia, ITALY.
University, Faculty of Medicine, Department of Medical
Oncology, Aydin, TURKEY, 3Adnan Menderes University, Faculty
of Medicine, Department of Biostatistics, Aydin, TURKEY. Aim/Introduction: Serum tumor markers (TM) are a widely
accepted tool to monitor patients with previous diagnosis of
colorectal cancer (CRC). 18F-FDG PET/CT is increasing its utility
Aim/Introduction: Inflammatory markers such as neutrophil in the evalutation of reccurent CRC. The aim of this study is
to lymphocyte ratio (NLR) and platelet to lymphocyte ratio to determine a possible correlation between tumor markers
(PLR) may be prognostic biomarkers in solid tumors. Some and semiquantitative PET/CT parameters in patients with
tumor markers such as carcinoembryonic antigen (CEA), cancer CRC. Materials and Methods: We retrospectively included
antigen 19-9 (CA19-9), cancer antigen 125 (CA125) have also 72 patients (43 M, 29 F; mean age 65) who performed a total
been used as the indicators for post-operative surveillance. of 81 18F-FDG PET/CT scans in our department to evaluate
The aim of this study is to evaluate the role of preoperative possible reccurence of CRC after primary treatment. CEA and
18F-FDG PET/CT parameters including maximum standardized Ca 19.9 were collected within 3 months before or after PET/
uptake value (SUVmax), metabolic tumor volume (MTV) and CT. PET images were evaluated visually and semiquantitatively
total lesion glycolysis (TLG) and hematologic prognostic collecting SUVmax, SUVmean, SUVbsa, SUL, MTV and TLG
indicators in patients with colorectal cancer (CRC) in terms of of the hypermetabolic lesions if present. A combination of
predicting prognosis. Materials and Methods: One hundred clinical/imaging follow-up and/or histopathology was taken
and one patients (35 F, 66 M) with newly diagnosed CRC and into account as reference standard. Chi-square test was used
who had undergone 18F-FDG PET/CT for initial staging were to correlate PET results and TM positivity or negativity. Kruskal-
evaluated retrospectively. SUVmax, SUVmean, MTV and TLG Wallis test was used to correlate PET results with TM values and
values were calculated for primary tumor. Patient data including TM positivity or negativity with semiquantitave PET parameters.
pathologic stage at presentation, histology, tumor location ROC curve was applied to identify the best TM cutoff to
(right/left colon), overall survival (OS) were analyzed. Complete determine recurrence of disease. Rank correlation was used to
hemogram analysis and serum CEA (ng/mL), CA-125 (U/mL) and correlate semiquantitative PET parameters with quantitative TM
CA19-9 (U/mL) levels obtained within two weeks of the PET/CT values. Results: Among all PET/CT scans, 58 were positive (mean
examination were used for hematological data. NLR and PLR values: SUVmax 10,16, SUVmean 5,67, SUVbsa 2,57, SUL 7,50,
were calculated in all patients. Results: 40 out of 101 patients MTV 32,4, TLG 312,93) and 29 were negative; after comparison
died during the follow-up period. TNM stage, PET/CT parameters with reference standard, 51 PET/TC were true positive, 20 true
including SUVmax, MTV and TLG were found to be correlated negative, 8 false positive and 2 false negative. Sensitivity was
with survival rate in univariate analysis (p<0.05). Although 96,23% (IC 87.02% to 99.54%), specificity 71,43% (51.33% to
distant metastases were related with survival, LN metastases 86.78%). PPV 86,44% (77.98% to 91.99%), NPV 90,91% (71.57%
were not significantly correlated with survival time. Additionally, to 97.54%) and accuracy 87,65% (78.47% to 93.92%). CEA values
lesion location, histological type were not related with good were available for 74 exams (mean values 20,84): in 52 patients
prognosis. All hematological markers excluding PLR were also were higher than normal cutoff and in 22 lower. CA19,9 values
significantly associated with survival time. ROC analysis revealed were available for 47 exams (mean values 455,9): in 21 was higher
that optimal SUVmax cutoff value for predicting survival time than normal cutoff while in 26 it was lower. We didn’t found any
in patients with CRC was >17.9 (AUC=0.625; p=0.032). The correlation between all PET/CT parameters and tumor markers
calculated sensitivity and specificity values for this cutoff were values or TM positivity/negativity. Applying the ROC curves
60% and 65.7%, respectively. To predict the survival time in these analysis, we found a cutoff of 6,99 ng/mL for CEA (area under the
patients optimal MTV cutoff value was >34.29 (AUC=0.775; curve 0,559) and a cutoff of 8 U/mL for Ca 19,9 (area under the
p<0.001), (sensitivity=85%, specificity=62.3%). The cutoff value curve 0,510). Conclusion: We demonstrated that 18F-FDG PET/
for predicting survival time, optimal TLG value was >270.4 CT is a useful tool in the evaluation of recurrent CRC. We did not
(AUC=0.790; p<0.001), (sensitivity=77.5%, specificity=68.9%). found any correlation between PET/CT parameters and tumor
Conclusion: Preoperative 18F-FDG PET/CT metabolical markers (CEA and CA19,9). References: None
parameters are useful to predict prognosis in patients with
CRC. High preoperative NLR and high tumor markers were also
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S540

EP-0344 Clinical -> Diagnostic study -> Adult study ->


Lesion size-SUVmax relationships in local recurrence and Oncology study -> Organ-based oncology ->
distant metastases of colorectal cancer Endocrine, malignant
G. Arsos1, M. Lelegianni2, E. Timotheadoy3, E. Moralidis1, V.
Mpalaris1, D. Katsampoukas1, C. Papastergiou2; October 12 - 16, 2019 e-Poster Area
1
3rd Dept. of Nuclear Medicine, Aristotle University of
Thessaloniki School of Medicine, Papageorgiou Gen Hospital,
Thessaloniki, GREECE, 2Dept. of Radiology, Papageorgiou Gen
Hospital, Thessaloniki, GREECE, 3Dept. of Medical Oncology, EP-0345
Aristotle University of Thessaloniki School of Medicine, Diagnostic Accuracy Of Somatostatin Receptor
Papageorgiou Gen Hospital, Thessaloniki, GREECE. Scintigraphy In Patients With Suspected Tumor Recurrence
By Increase In Chromogranin A
N. Alvarez Mena, B. Pérez López, J. Gómez Hidalgo, P. J. Turbay
Aim/Introduction: 18F-FDG standardised uptake value (SUV) Eljach, C. Gamazo Laherrán, M. Alonso Rodríguez, M. A. Ruíz
of the neoplastic lesions is the widely accepted measure of their Gómez, M. J. González Soto, A. Sainz Esteban, R. Ruano Pérez;
glycolytic rate related (usually as SUVmax) to the malignant Hospital Clínico Universitario de Valladolid, Valladolid, SPAIN.
potential and aggressiveness of the neoplasms and its change
may quantify early response to treatment. Apart from tumor
type, histology and grade, known SUVmax determinants are Aim/Introduction: To asses the diagnostic yield of Somatostatin
body weight and composition and glucose blood levels, Receptor Scintigraphy (SRS) to evaluate the possibility of
currently incorporated in modified SUV forms. Interestingly, recurrence of the primary neuroendocrine tumor after surgery
lesion size seems to correlate with SUVmax value as has already and its relationship with levels of chromogranin A (CgA).
been reported for non small cell lung cancer (NSCLC). This Materials and Methods: Retrospective series of 51 monitored
effect could potentially affect both malignancy SUVmax cut-off patients after neuroendocrine tumor surgery, from January
values as well as the accuracy of SUVmax changes for response 2017 to March 2019. They were classified into two groups:
to treatment assessment purposes. As evidence on this group A with suspicion of tumor recurrence due to increase in
correlation in regard to local recurrence and distant metastases chromogranin A levels (36 patients) and group B with suspicion
of colorectal cancer (CRC) is currently missing, the aim of the of relapse or for postoperative restaging without chromogranin
present study is to explore the relationship between 18F-FDG A levels increased (15 patients). Variables such as age, gender,
SUVmax and the size of local recurrence and distant secondary type of neuroendocrine tumor, levels of chromogranin A (CgA),
lesions in CRC patients. Materials and Methods: 18F-FDG-PET/ scintigraphic result (SRS+/SRS-) and its concordance with CT
CT scans of 138 adult patients with histologically proven CRC and/or histology (H) were analyzed. Results: Average age 60
and evidence of hypermetabolic local recurrence and/or distant years (range 16-81 years); 57% women, 43% men. The primary
metastases were retrospectively analysed. Patients had been tumors were 43 typical carcinoids, 7 atypical carcinoids, and 1
referred for 18F-FDG-PET/CT scan because of conventional gastrinoma. Group A with suspicion of recurrence (CgA >100ng/
imaging or biochemical suspicion of disease recurrence during ml): it was observed that in 16/36 patients (44.4%), the SRS was
the years 2016-2017. For each patient, local recurrence mass positive with histological confirmation (only 4 had CT before the
and/or the more hyperbolic (in case of multiplicity) pulmonary SRS). In 19/36 patients (52.8%) the SRS was negative, of which 2
and/or liver lesion were analysed. For each examined lesion the had a CT+ (small bowel carcinoid) or H+ (pulmonary carcinoid).
SUVmax was calculated and its maximum diameter (Dmax) was Group B with suspicion of relapse or for postoperative restaging
measured on transverse CT slices. Correlation between Dmax (CgA<100ng/ml): in 3/15 patients (20%) the SRS was positive (1
and SUVmax was assessed by linear regression analysis. Results: true positive concordant with CT+; 1 true positive not concordant
Statistically significant positive linear correlation between Dmax with CT- but H+; and 1 false positive with CT- and H-). In 12/15
and SUVmax was found in local recurrence mass (R2=0.730, p patients (80%) the SRS was negative. Only 1 of the 12 patients
less than 0.001), lung lesions (R2=0.500, p less than 0.001).and with SRS-, with inconclusive prior CT, had a non-concordant test
liver lesions (R2=0.283, p less than 0.001) Conclusion: Similarly with H+ (false negative). Comparing group A (CgA>100ng/ml)
to NSCLC, the size of the local recurrence mass and of the with group B (CgA <100ng/ml) the percentage of positivity of
particular secondary CRC lesions, positively correlates to their the SRS was 44.4% vs 20% (X2, p <0.05). However, no differences
SUVmax. Τhis finding questions the accuracy of metabolic were found in detection in patients with CgA> 500ng/ml vs CgA
characterization of small lesions with low SUVmax in CRC and between 100-500ng/ml (38% vs 46%, p> 0.05). Conclusion: The
warrants further investigation. References: None. SRS in patients with suspected tumor recurrence has a higher
diagnostic yield with higher level of serum chromogranin A. In
patients with CgA levels <100 ng/ml, a SRS should be avoided
unless there is a morphological study that could increase the
possibility of detecting the recurrence. References: None.
S541 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

EP-0346 and unknown distant metastases. Despite CT is vastly available


Comparison of 68Ga DOTATOC PET/CT with morphological and MRI is preferred in case of liver metastases, 68Ga DOTATOC
imaging in staging of neuroendocrine tumors PET should be always considered in NET patients staging.
M. Finessi1, E. Pilati1, R. Passera1, V. Liberini1, C. De Angelis2, E. References: None.
Arvat3, N. Birocco4, M. Brizzi5, D. Campra6, G. Giraudo6, M. Bellò1, G.
Bisi1, D. Deandreis1;
1
Nuclear Medicine Unit, Department of Medical Sciences, EP-0347
University of Turin, AOU Città della Salute e della Scienza di Torino, Impact of Dual FDG and Ga68 DOTANOC PETCT on
Turin, ITALY, 2Gastroenterology Unit, Department of General outcomes in patients with WHO Grade 2 GEP-NETs:
and Specialist Medicine, AOU Città della Salute e della Scienza Experience from Tertiary Care Cancer Center in India
di Torino, Turin, ITALY, 3Endocrine Oncology Unit, Department A. Puranik, V. Rangarajan, A. Agrawal, S. Shrikhande, V. Chaudhari,
of Medical Sciences, University of Turin, AOU Città della Salute M. Bhandare, M. Bal, A. Ramaswamy, S. Shah, N. Purandare;
e della Scienza di Torino, Turin, ITALY, 4Medical Oncology, Tata Memorial Centre, Mumbai, INDIA.
Department of Medical Oncology, University of Turin, AOU
Città della Salute e della Scienza di Torino, Turin, ITALY, 5Medical
Oncology, Department of Oncology, University of Turin, AOU Aim/Introduction: WHO Grade 1 Gastro-enter-pancreatic
San Luigi Gonzaga, Orbassano, Turin, ITALY, 6Surgery Division, Neuroendocrine Tumors (GEP-NETs) show high grade SSTR
AOU Città della Salute e della Scienza di Torino, Turin, ITALY. expression. FDG uptake is indicator of poor prognosis in
tumors with Ki-67 greater than 20%. However, there is variable
receptor expression seen in Grade 2 tumors which can impact
Aim/Introduction: The aim of this study was to compare the management and outcome. We aimed at assessing outcome in
performance of 68Ga DOTATOC PET/CT in neuroendocrine patients with Grade 2 GEP-NETs who underwent dual imaging
tumor staging comparing to conventional imaging (CT or with FDG PET and Ga-68-DOTANOC PET/CT (DOTA PET/CT)
MRI). Materials and Methods: We retrospectively evaluated Materials and Methods: Retrospective analysis of 170 patients
35 consecutive patients that performed 68Ga DOTATOC PET/ (113 males, 57 females, age range - 47-74 years) with WHO
CT scan from February 2017 to January 2019 for occult primary Grade 2 (2010) GEP-NET who underwent whole body (base-
tumor detection of metastatic NET (28.6%, n=10) or for primary skull to mid-thigh) FDG and DOTA PET/CT, between December
known tumor staging (71.4%, n=25); patient underwent 2014 and April 2016 was done. All 170 patients had Kennings
CT (82.9%; n=29) and/or abdominal MRI (28.6%; n= 10). score - 3/4 and were then referred for FDG PET. Scan positivity
Concordance between 68Ga DOTATOC PET/CT and conventional was based on visual score (uptake more than liver was positive
imaging (CI) was assessed and patients were divided in 3 groups scan). Patients received treatment according to decision of NET
both for CT and MRI: concordant PET+/CI+, discordant PET+/ Joint-clinic as per established guidelines, and were followed
CI- and discordant PET-/CI+. Results: Among 35 patients, 40.0% up until death or till last out-patient visit upto August 2018.
presented with GEP-NET, 5.7% with lung, 28.6% with unknown Results: Analysis was based on FDG uptake irrespective of Ki-
site and 5.7% with other site (20.0% missing data); 40.0% had 67 values. 72/170 patients showed FDG positive scan while the
G1, 25.7% G2, and 5.7% G3 NET respectively. Of these patients rest showed negative study. Patients with FDG positive study
28.6% (n=10) presented with locally advanced, 31.4% (n=11) showed poor outcome in the form of short overall survival (OS)
with metastatic disease (28.6% liver, 2.9% bone and 5.7% brain) of 8.6 months, whereas FDG negative cohort showed better
at morphological imaging before PET evaluation. 68Ga DOTATOC outcomes, with OS not reached till the date of assessment.
PET/CT scan was positive in 85.7% of cases (n=30/35), allowing Other factors like age, size of primary, liver involvement were
the identification of primary lesion (T) in 71.4% of cases (n=25) not considered. Conclusion: FDG PET should be performed in
including 7/10 cases of unknown primary site, lymph-nodal all Grade 2 GEP-NETs irrespective of Ki-67 values. FDG uptake,
involvement (N) in 40.0% (n=14) and metastatic lesions (M) in as described in the study becomes a significant determinant of
37.1% (n=13). A total of 29/35 patients underwent CT scan that prognosis and outcome in patients with somatostatin receptor-
was positive in 89.7% of cases allowing the identification of T expressing WHO grade 2 GEP NET. References: Bucau M,
in 72.4% of cases (n=21), N in 37.9% of patients (n=11) and M Laurent-Bellue A, et al. Neuroendocrinology. 2018;106(3):274-
in 31% (n=9). MRI was positive in 10/10 patients, allowing the 282 18F-FDG Uptake in Well-Differentiated Neuroendocrine
identification of primary lesion in 80.0% of cases (n=8), lymph- Tumors Correlates with Both Ki-67 and VHL Pathway Inactivation.
nodal and metastatic involvement in 70% of cases (n=7). Sampathirao N, Basu S. J Nucl Med Technol. 2017 Mar;45(1):34-
Concordant findings PET+/CT+ were found in 17 patients (17 T, 41. MIB-1 Index-Stratified Assessment of Dual-Tracer PET/CT
5 N, 3 M); discordance PET+/CT- were found in 10 patients (4T, with 68Ga-DOTATATE and 18F-FDG and Multimodality Anatomic
2N, 5M); discordant findings PET-/CT+ were found in 4 patients Imaging in Metastatic Neuroendocrine Tumors of Unknown
(2T, 2N, 2M). Concordant findings PET+/MRI+ were found in 6 Primary in a PRRT Workup Setting.
patients (6 T, 2 N, 2 M); discordant PET+/RM- in 3 patients (1T, 2N,
1M) and discordant PET-/RM+ in 2 patients (2M). Conclusion:
Our data confirm the pivotal role of 68Ga DOTATOC PET/CT in
staging NETs, allowing the identification of occult primary site
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S542

EP-0348 EP-0349
Pitfall upon 99mTc-EDDA/HYNIC-TOC interpretation: uterine Relevance of different patterns of thyroid uptake
leiomyomas of 18F-fluorocholine in patients who undergo
P. Valsamaki, G. Ntali, S. Michopoulos, V. Papantoniou; 18
F-fluorocholine PET/CT for detection of parathyroid
University General Hospital “Alexandra”, Athens, GREECE. disease
E. Skorjanec Armic, S. Rep, J. Jamsek, K. Zaletel, L. Lezaic;
Department of Nuclear Medicine, University Medical
Aim/Introduction: Somatostatin receptor (sstr) scintigraphy Centre Ljubljana, Ljubljana, SLOVENIA.
constitutes a sine qua non step with proven high sensitivity and
specificity in the diagnostic armamentarium of neuroendocrine
tumours (NET). The modality also indicates the option of targeted Aim/Introduction: Patients who undergo PET/CT with
therapeutic “cold” or “hot” (radiolabelled) somatostatin analogue 18
F-fluorocholine (FCH) for detection of parathyroid disease
intervention. We herewith report cases of uterine leiomyoma(s) demonstrate different patterns of thyroid uptake. The aim of
as a new pitfall upon sstr imaging interpretation. Materials the study was to determine the relevance of imaging findings
and Methods: We present six cases of uterine leiomyomas and association with specific thyroid disease. Materials and
incidentally discovered by 99mTc-EDDA/HYNIC-TOC (Tektrotyd) Methods: We retrospectively analysed scans of 50 patients who
in women of different ages, referred due to suspected or biopsy- underwent a dual-phase (5 min, 60 min p.i.) FCH PET/CT for
proven NET. Whole-body, static and tomographic imaging was detection of parathyroid disease and had a known or suspected
conducted 75min up to 24h after injection of 740 MBq of the thyroid disease (based on clinical examination, laboratory
radiotracer. Sstr images with normal pelvic tracer distribution in workup, ultrasound, pertechentate scintigraphy and fine needle
women of corresponding age are presented as controls. Results: aspiration cytology - FNAC). Patients were grouped according to
Regions of abnormally increased uptake in the pelvis were thyroid pathology. The PET/CT images from the early scan were
optically revealed by scintiscans with 99mTc-EDDA/HYNIC-TOC evaluated visually as well as semi-quantitatively (SUVmax) and
and semiquantitatively analyzed by using corresponding regions then compared with thyroid findings. Results with p < 0.05 were
of interest (ROI) to estimate lesion-to-background (L/Bg) count considered statistically significant. Results: Euthyroid goiter:
ratio. Range of L/Bg was 1.5-2.5. Our results were co-evaluated 14/28 patients had visible changes on PET (size > 2 × FWHM)
with clinical, laboratory and other imaging findings, such as US, with SUVmax 6.3 ± 1.8. Nine of these patients demonstrated focal
CT and/or MRI. Somatostatin receptors may be expressed in the uptake, while 5 had heterogeneous or homogenous uptake.
uterus and in leiomyomas, irrespective of age. Conclusion: Our Hashimoto thyroiditis: 11/13 patients showed homogenous
data underline the significance of this pitfall in the differential uptake (SUVmax 7.7 ± 2.1). Graves’ disease: one patient showed
diagnosis of corresponding positive sstr scintigraphy and are homogenous uptake (SUVmax 3.9). Intrinsic thyroid autonomy:
compatible with limited existing literature reports. Moreover, out of 8 patients (2 with toxic multinodular goiter, 6 with single
the non-invasive identification of uterine leiomyoma(s) by sstr hyperfunctioning adenoma) 3 had diffuse and 5 had focal
scintigaphy and the indicated threshold values, propounds the (2 increased and 3 decreased) patterns of uptake. Healthy
targeted application of somatostatin analogues in the non- euthyroid patients: 4 demonstrated homogenous uptake
invasive treatment algorithm of these benign, yet potentially (average SUVmax 3.75) and 2 focal uptake (average SUVmax 6.1).
irritating, disease entities. Further broader studies, both Out of 14 patients with focal uptake 2 had toxic adenoma, 10 had
screening and follow-up, are warranted to define sstr scan visible nodules on imaging and 2 were healthy. Nine patients
sensitivity and specificity, as well as treatment effectiveness, with focal uptake underwent FNAC: results showed benign
ultimately avoiding surgical intervention. References: 1. Mena lesions in 7 patients (SUVmax 4,9 - 7,3) and thyroid carcinoma
LM, Martin F, Jime’nez I, Ramos A. In-111 pentetreotide uptake in 2 patients (SUVmax 7,6 and 4,5). Specific thyroid pathologies
in a uterine myoma. Clin Nucl Med. 2010;35:524-525.2. Zandieh had statistically significantly different patterns of FCH uptake
S, Schu¨tz M, Bernt R, Zwerina J, Haller J. An incidentally found (focal vs diffuse) on FCH PET/CT (chi-square p = 0,000795).
inflamed uterine myoma causing low abdominal pain, using Tc- Higher SUVs (One-Way ANOVA: p = 0.006130) were seen in
99m-tektrotyd single photon emission computed tomography- patients with Hashimoto thyroiditis (homogeneous uptake)
CT hybrid imaging. Korean J Radiol. 2013;14:841-844. 3. De Leo V, and visible nodules (focal uptake) compared to euthyroid
La Marca A, Vegni V, Raggi CC, Maggi M, Petraglia F. Quantitative patients. Conclusion: Our findings suggest that specific thyroid
determination of sst2 and sst5 gene expression in uterine pathologies exhibit different patterns and intensities of FCH
leiomyomata and the effect of treatment with somatostatin uptake, allowing for some inference on underlying etiology.
analogue. Fertil Steril. 2003;80:1058-1059. 4. Pirayesh E, Amoui Any focal changes or homogenous increase in uptake of FCH in
M, Assadi M. 99mTc-Octreotide Uptake in the Uterus and a the thyroid require referral to a thyroid specialist for clarification.
Subserosal Myoma Mimicking Tumoral Masses. J Nucl Med References: None.
Technol 2014; 42: 77-78.
S543 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

EP-0350 primary staging, in a private clinic in the Federal Capital of Brazil,


Spindle Cell Variant of Medullary Thyroid Cancer in during a period of 4 years. Materials and Methods: Descriptive
Hashimoto’s Thyroiditis observational study of 499 PET/CT scans with 68Ga-DOTATOC
D. Šnajder1, V. Blažičević2; for the evaluation of NET were performed between 2015 and
1
Clinical Institute of Nuclear Medicine and Radiation 2019. The exams were divided in 4 objectives: diagnosis, primary
Protection, Osijek, CROATIA, 2Clinical Institute of staging, follow-up and evaluation of therapeutic response. The
Pathology and Forensic Medicine, Osijek, CROATIA. focus of this study concerns in the evaluation of the exams
requested for primary staging. Results: From the 499 scans, 132
(26,4%) were performed for primary staging of the disease after
Aim/Introduction: Hashimoto’s thyroiditis is a common its histopathological diagnosis, via biopsy or surgical resection
autoimmune thyroid disease and often coexists with of the primary site (51%). The mean age of the patients was 54
differentiated thyroid carcinomas, but the link between years old (varying from 16 to 87 years) and 51% were female.
medullary thyroid carcinoma and Hashimoto’s thyroiditis The most common primary site was the rectum (26%), followed
is not established, so the cases of these diseases occurring by small intestine and stomach (23% and 14%, respectively).
simultaneously are rare in the literature. Here we report a case From these patients, 25% already had findings suggestive of
of spindle cell variant of the medullary thyroid carcinoma in secondary involvement - locoregional or distant - with lymph
underlying Hashimoto’s thyroiditis. Materials and Methods: A node metastasis the most common site (present in 61% of the
65-year old female was followed up in our centre because of metastatic cases). Conclusion: In the early 2000s, the incidence
hypothyroidism due to thyroid autoimmune disease. On neck of NET was estimated to be around 0,5% from all of the
ultrasound after 18 years from initial diagnosis, an 11x7x9 mm malignancies, however, nowadays, it is reported to correspond
hypoechoic nodule in the left thyroid lobe was found, and to about 2%. This rise is probably due to increase in knowledge
cytology was suggestive for spindle cell variant of medullary about NETs and consequently to an earlier diagnosis. Our
thyroid carcinoma. Calcitonin serum level was measured, and experience throughout these 4 years revealed metastatic
found elevated. Results: After total thyroidectomy, pathology involvement in 25% of the cases requested for primary staging.
was compatible with 10 mm spindle cell medullary thyroid We can conclude the importance of early PET/CT scan with 68Ga-
carcinoma and Hashimoto’s thyroiditis. Cancer cell were spindle- DOTATOC to minimize the diagnosis in advanced stages of the
like formed with round to oval small nuclei with coarsely clumped disease. References: Oronsky B, PC Ma, Morgensztern D, Carter
chromatin. The pathological diagnosis of Hashimoto’s thyroiditis CA. Nothing But NET: A Review of Neuroendocrine Tumors and
was made based on islets of epithelial eosinophilic cells and Carcinomas. Neoplasia. 2017;19(12):991-1002.
extensive lymphocytic infilitrate with germinal centre formation
around the tumour. Conclusion: Medullary thyroid carcinoma
in Hashimoto’s thyroiditis is rare, but must not be taken out of EP-0352
consideration when thinking about routine ultrasound check- Do 68Ga-DOTANOC PET/CT Have Incremental Value Over
ups in patients with non-nodular autoimmune thyroid disorder. 131
I-mIBG Scintigrapy in the Management of Patients with
References: None. Neuroendocrine Tumor?
J. Shukla, D. Singh, R. Walia, R. Vatsa, A. Chhabra, R. Kumar, B. R.
Mittal;
EP-0351 Post Graduate Institute of Medical Education
Secondary neoplastic involvement analysis in staging & Research, Chandigarh, INDIA.
Neuroendocrine Tumors with PET/CT with68Ga-DOTATOC:
Experience of 4 years
F. D. Kurkowski, L. M. P. Júnior, A. B. Sobrinho, R. R. Barra, G. A. Aim/Introduction: The primary aim of study was to compare
Beckmann, M. M. Silva, A. S. F. Alves, A. M. Reis, B. C. Neves; diagnostic role of 131I-MIBG and 68Ga-DOTANOC PET/CT in
Imagens Médicas de Brasília, Brasília, BRAZIL. NET patients. The secondary aims were to see the impact in
management of patients, and association of gene mutation.
Materials and Methods: 68Ga-DOTANOC PET/CT and 131I-MIBG
Aim/Introduction: Neuroendocrine tumors (NET) are whole body scans was performed in 106 patients (61 male, 45
neoplasms considered rare and difficult of diagnose, which female; mean age of 38.5 ± 16.2 years) of known or suspected
can produce symptoms that confuses with other diseases, are NET. Following scans, 16 patients who were found positive for
usually small (less than 1 centimeter) and don’t have a defined NET by histopathological examination were further evaluated
risk group. They can present several organs as primary site, for germline mutations. Results: 131I-MIBG scans detected 41
being the most common the gastrointestinal tract and lungs. lesions in 34 out of 106 patients with primary lesions in 29,
The average time for the diagnosis is estimated between 5 to regional lymph nodes in 2 and distant metastasis in 3 patients.
7 years, which frequently results in the detection of associated However, 68Ga-DOTANOC PET/CT scans detected 95 lesions in 55
metastasis, distant or locoregional. The purpose of this study patients and showed somatostatin receptor expressing lesions
consists in evaluating the secondary neoplastic involvement in 49 patients with mean SUVmax of 17.6 ± 26.5. It detected
detected by the PET/CT with 68Ga-DOTATOC, realized for primary disease in 46, primary with regional lymph nodes in 1,
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S544

primary with distant metastasis in 3, regional lymph nodes in 1 grade I and 26 were grade 2 with Mib ≤5%. Median age was
and distant metastasis in 4 patients. The mean duration of follow 52 years. All these were GEP NET cases. DOTANOC was positive
up was 20.6 ± 16.5 months. Management following scans were: in all patients. FDG was positive in 23 patients (41%). In rest of
surgery in 35 patients, showed positive histopathology in 34 the 33 patients (59%) FDG was negative or weakly positive. FDG
patients (131I-MIBG positive in 24/34, 68Ga-DOTANOC PET positive positivity changed management in only 6 patients (10.7%).
in 32/34, 68Ga-DOTANOC PET/CT positive in all 34 patients) and In these patients, additional Capcetabine-Temozolamide
negative histopathology in 1 patient; 177Lu-DOTATATE therapy chemotherapy was added. In only 10 patients (18%), there was
in 2 patients and chemotherapy in 1 patient who showed a clear reason for doing dual scan. In 6 to decide on the need
metastatic disease; conservative therapy in 34 patients, no for additional chemotherapy along with PRRT and in 4 due to
further therapy in 17 patients, 2 patients died following scans histological discrepancy in pathology report. In rest of the 46
and 3 were lost to follow-up. Among 12 previously operated patients (82%) there was no indication to do FDG PET/CT scan.
patients, 2 showed metastatic disease and 1 patient showed Conclusion: Even though FDG positivity was seen in 41% of the
residual disease. 68Ga-DOTANOC PET/CT demonstrated highest cases, FDG directed management change was seen in relatively
sensitivity and accuracy (Table) . The 15/16 patients underwent small number of patients. Moreover, there was no strong
genotypic analysis underwent surgery; 8 patients were positive indication for doing dual scan in most cases. So, we recommend
for germline mutations. Two gene mutations were detected in against routine FDG PET/CT for WD-NET with Ki67 ≤5%, and to
two patients. All these patients showed SSTR expressing lesions. reserve it for select few cases. References: None.
Mutations in SDHB and MDH2 genes were most prevalent,
followed by VHL, RET and SDHA. Deletion was observed in 1
patient in SDHB and substitution in all other mutations. Four EP-0354
novel mutations were observed in MDH2 (c.1005G>C, c.916G>A, Three Cases Of Somatostatin Receptors Scintigraphy With
c.580G>A) and SDHB (c.378_380delAAT). Conclusion: 68Ga- 99mTc-Edda-Hynic-Toc Showing Exquisite Accuracy
DOTANOC PET/CT is better than 131I-MIBG due to lower D. De Palma, S. Casagrande, C. Gobbo, I. Schiorlin, S. Scotti;
radiation exposure, decreased cost, better patient comfort, Ospedale di Circolo, Varese, ITALY.
improved image quality, better diagnostic accuracy and therapy
planning.68Ga-DOTANOC PET/CT needs be considered as first
line investigation for NET patients along with screening of Aim/Introduction: Somatostatin receptor radiopharmaceuticals
germline mutations. References: None. (SSR-RP) represent a well-established cornerstone of
diagnostic evaluation of Neuroendocrine Tumors (NET). After
about 30 years of 111-In labeled analogues monopoly, the
EP-0353 radiopharmaceutical (RP) panel was enriched first with 68-Ga
Impact of FDG PET/CT in directing management of well labeled PET RP (that need an “in house” production) and then
differentiated neuroendocrine tumours with Ki67 <5% with 99mTc- EDDA-Hynic-TOC (EHT). 68-Ga peptides availability
A. Agrawal, S. Choudhary, A. Puranik, V. Rangarajan, S. Shrikhande, improved with the registration of either generators and “cold”
M. Bal, V. Choudhary, M. Bhandare, A. Ramaswamy, N. Purandare, lyophilized kit, but the overall cost remains high for low-patients
S. Shah; throughput departments. EHT is a definite step forward against
Tata Memorial Hospital, Mumbai, INDIA. Indium-labeled RP, offering better quality images with a 2/3rd
lower radiation burden. Scanning 2 patients with a single kit
reduces the cost, too. Its sensitivity is reported around 80-90%.
Aim/Introduction: FDG PET/CT is traditionally used for staging Here we report 3 cases in which, in our opinion, EHT performed
poorly differentiated WHO grade III NET or to complement beyond expectations. Materials and Methods: We perform
somatostatin receptor PET/CT in well differentiated NET with wholebody-addressed SPECT/CT of three patients with clinically
Ki67 ≥5%. Based on FDG positivity octreotide therapy or suspect or histologically proven NET, using a Dual Head SPECT/
peptide receptor radionuclide therapy is complemented with CT equipped with a 2-slice CT (Symbia T2, Siemens), 4 hours
chemotherapy in metastatic WD-NET. This study was undertaken after administration of 600 MBq of EHT. Results: The first was
to see the proportion of FDG PET/CT positivity in WD-NET with a 72-yo male with a MEN-1 syndrome, with a newly diagnosed
Ki67 ≤5% and whether it results in FDG directed management malignant mass of the pancreatic tail and disease spread to
change. Materials and Methods: NET cases discussed in abdominal lymphnodes and right adrenal. EHT scan showed
hospital multidisciplinary clinic from January 2018 to March an additional <10 mm liver lesion undetected by CT. The
2019 were screened for this retrospective observational study. second was a 57-yo male with a recent removal of a malignant
After going through the electronic medical records (EMR) of 207 melanoma of the right arm and finding of two hepatic lesion
patients, 56 patients were found to have Mib index of ≤5% and and a mesenterial mass. FDG PET/CT showed uptake into liver
were included in the study. All these patients had dual imaging nodules only. EHT was taken up by mesenterial and liver lesions
with 68Ga DOTANOC and FDG PET/CT at a fixed time point. and into an additional 11 mm-peritoneal node, not reported by
Findings of each scan, reason for doing dual scan and whether CT. The third was a 66-yo male in which a NET focus was found
there was a change in the management due to FDG PET/CT after marsupialization of a liver cyst. The EHT scan correctly
were noted from the EMR. Results: Out of 56 patients; 30 were identified the primary neoplasm in the wall of the second portion
S545 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

of the duodenum, together with a satellite lymphoadenopaty nodes, in 2/16 hepatic lesions, in 4/16 pancreatic lesions, in 2/16
and a 9 mm lesion into the 6th liver segment. Conclusion: There ileal lesions and in 3/16 jejunum suspected lesions (however
are very few data in literature comparing accuracy of SPECT/ no histological confirmation was available for the latter three
CT and PET/CT SSR-RP scans against a true gold standard, and cases). Conclusion: Although recommended by current
using both modalities at their best. In our cases EHT was able guidelines, 68Ga-DOTA PET/CT is not often performed for GEP-
to pick up infracentimetric lesions also in anatomical positions NEN staging. PET/CT and CI were discordant in approximately
in which movement artifacts or 2-slice CT reconstruction easily 40% of cases: PET/CT detected additional lesions mostly at bone
hampers visual analysis . EHT represents then a good option for level or outside CI field of view. Therefore, PET may provide
overcoming a limited availability of 68-Ga labeled peptides. Its useful information especially in pts with suspected widespread
performance, more, is expected to improve with technologic disease at first diagnosis. References: None.
refinement of SPECT/CT systems. References: None.

EP-0356
EP-0355 18F-FDG and 68Ga-DOTANOC PET/CT imaging of lung NEN
GEP neuroendocrine tumour staging: 68Ga-DOTANOC S. Telo1,2, D. Calabrò1,2, N. Daddi3, M. Lugaresi3, N. Bonazzi2, G.
PET/CT versus conventional imaging Argalia1,2, E. Tabacchi1, L. Zanoni1, D. Campana3, S. Fanti1,2, V.
D. Calabro’1,2, S. Telo1,2, M. Guido2, G. Argalia1,2, E. Tabacchi1, L. Ambrosini1,2;
Zanoni1, C. Mosconi3, R. Casadei4, C. Ricci4, D. Campana4, S. Fanti1,2, 1
Nuclear Medicine, S.Orsola Malpighi Hospital, Bologna,
V. Ambrosini1,2; ITALY, 2DIMES University of Bologna, Bologna, ITALY,
1
Nuclear Medicine, S. Orsola-Malpighi Hospital, Bologna, 3
DIMEC University of Bologna, Bologna, ITALY.
ITALY, 2DIMES University of Bologna, Bologna, ITALY,
3
Radiology, S. Orsola-Malpighi Hospital, Bologna, ITALY,
4
DIMEC University of Bologna, Bologna, ITALY. Aim/Introduction: To evaluate double tracer PET/CT imaging
(18F-FDG and 68Ga-DOTANOC) in pulmonary NEN patients
(pts). Materials and Methods: Pts with confirmed pulmonary
Aim/Introduction: to assess conventional imaging (CI) NEN who underwent 18F-FDG and 68Ga-DOTANOC PET/
and 68Ga-DOTANOC PET/CT concordance in the staging CT within 6 months and with clinical/imaging follow-up data
of gastroenteropancreatic (GEP) neuroendocrine neoplasm were included in the study. Pts who underwent surgical or
(NEN) patients(pts). Materials and Methods: Inclusion criteria radio-chemo therapy with radical intent between the two
were: i) pts’ included in a CE-approved electronic archive; ii) examinations were excluded. Metabolic tumour volume (MTV)
either pathological confirmation or suspicion (on the basis of and receptor tumour volume (RTV) were evaluated with VCAR
equivocal CI) of GEP-NEN; iii) CI (CT, MRI, CEUS) performed within software (42% SUVmax threshold with manual adjustment
three months of the PET/CT scan. PET/CT and CI concordance when necessary) and the RTV/MTV ratio was calculated and
was evaluated for lesions sites and number. Results: Among correlated with pathology. Results: 26 pts were included: 16
784 pts studied between September 2017 and March 2019, typical carcinoids (TC), 8 atypical carcinoids (AC) and 2 large
104 performed 68Ga-DOTANOC PET/CT. Among 50 pts with cells neuroendocrine carcinomas (LCNEC). Ki67% ranges were
confirmed GEP-NEN, in 32/50 (27 pancreas, 3 jejunum, 1 ileum, [1-3] for TC, [6-21] for AC and [30-60] for LCNEC. Most pts
1 stomach) CI data were available. Concordance was observed presented with local disease (18/26 pts with a single pulmonary
in 22/32 pts (69%): PET was positive in all but one pt (false lesion), 8/26 pts with metastatic disease (pulmonary, nodes,
negative for a millimetric pancreatic lesion). In the remaining bone or liver). 68Ga-DOTANOC resulted true positive in 14/16
10/32 pts, PET/CT and CI were discordant. In 3/10 pts, PET/CT TC (SUVmax range: 2-80): 10/14 were also 18F-FDG positive
showed more lesions: multiple bone lesions in two pts, nodal (SUVmax range: 2,6-27,8). 18F-FDG and 68Ga-DOTANOC were
metastasis in one pt (out of the EUS field of view). In 6/10 pts, CI concordant in 7/10 pts (lesions’ number and site) while in 3/10
showed more lesions (2/6 lymph-nodes, 2/6 pancreatic lesions 18F-FDG was falsely positive (inflammatory findings in 2 and
(G2 and G3), 2/6 millimetric pancreatic lesions). In 1/10, PET/ non-NEN tumour in 1). 68Ga-DOTANOC was negative in 2/16
CT showed only one abdominal adenopathy, not reported in TC while 18F-FDG was faintly positive (uptake lower than the
the CT which, on the contrary, showed multiple PET-negative liver). In 5/8 AC 68Ga-DOTANOC was faintly positive: 18F-FDG
splenic lesions. Of the 54 pts with suspected GEP-NEN, in 41/54 showed more disease sites in 2 and the same lesions as 68Ga-
(10 ileum, 27 pancreas, 4 jejunum) CI data was available. In 23/41 DOTANOC in the remaining 3 (18F-FDG SUVmax range: 5,7-
pts (56%) PET/CT and CI were concordant: PET was positive in all 12,5). In 2/8 AC 68Ga-DOTANOC resulted positive (SUVmax: 6
cases and negative in one MRI-equivocal pt (pancreatic lesion, and 18,3) and 18F-FDG negative. In 1/8 AC both tracers resulted
reported however more likely to be benign). In 18/41 pts (44%), positive for the same NEN lesions. Both radiopharmaceuticals
PET/CT and CI were discordant. In two pts, PET/CT showed more were concordant and positive in the 2 LCNEC cases, although
lesions: bone lesions in one case and identified the ileal primary 18F-FDG uptake was higher. The RTV/MTV ratio was significantly
lesion in the other. In 16 pts, CI showed more lesions: two GIST different in TC and AC (p=0.004). The RTV/MTV ratio was>1 in
and one pancreatic adenocarcinoma (3/16 truly negative PET/ 14/16 (87,5%) TC. The RTV/MTV ratio was <1 in 2/16 TC, in 8/8
CT after histological confirmation), in 2/16 abdominal lymph- AC and in 2/2 LCNECs. Conclusion: Despite all the limitations
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S546

of a small population, most pts presented uptake of both EP-0358


radiopharmaceuticals (although to a variable extent) and the The Use [18F]-DOPA-PET/CT in the Detection of
RTV/MTV ratio significantly correlated with lung NEN pathology. Recurrence Localization in Patients with Biochemical
References: None. Relapse of Medullary Thyroid Carcinoma
D. Ryzhkova;
National Almazov Medical Research Centre,
EP-0357 St.Petersburg, RUSSIAN FEDERATION.
Added Value of 99mTc-Octreotide Scintigraphy and 18F-FDG-
PET/CT in Clinical Prognosis of Neuroendocrine Tumors
(NET) Aim/Introduction: The investigation of [18F]-DOPA-PET/
A. Cánoves-Llombart, I. Casáns-Tormo, H. Rodríguez-Parra, J. CT diagnostic efficiency in the detection of localization of
Sabater-Sancho, A. Amr-Rey, V. Carrero-Vásquez, M. Redal-Peña; medullary thyroid carcinoma (MTC) recurrence in the patients
Nuclear Medicine, University Clinic Hospital, Valencia, SPAIN. with biochemical relapse. Materials and Methods: 19 patients
(M:F 7:12; 43.5 years, range 30 - 71 years,) with increasing
calcitonin level after total thyreoidectomy were included in the
Aim/Introduction: In patients with NET we compare the study. The median of calcitonin 2182.5 pmol/l (range: 191-18690
detection of lesions with somatostatin receptors by 99mTc- pmol/l) and the median of cancer embryonal antigen (CEA) 27
octreotide planar and SPECT (with SPECT/CT fusion when ng/ml (range: 5.8-164 ng/ml). All the patients underwent whole
possible), and metabolic activity by 18F-FDG-PET/CT, and body PET/CT twice: 30 min and 60 min after administration of
evaluate their relation with Ki-67 proliferation index, tumor 300-350 MBq [18F]-DOPA. Additionally 5 patients with negative
differentiation, concordance and usefulness to assess disease results of [18F]-DOPA PET/CT were referred to whole body [18F]-
progression. Materials and Methods: We retrospectively FDG PET/CT. Results: PET/CT with [18F]-DOPA was positive in
reviewed 25 patients with NET initial diagnosis, with both 14 of the 19 patients. None had local recurrences of MTC. Neck
explorations in 75% of patients≤3months). They were excluded and mediastinal lymph nodal involvement was observed in 9
10 patients by: chemotherapy between the two studies(2), patients. We found metastases in lung (2 patients), in liver (6
no NET definitive diagnosis(3) and Ki-67 data not available(5). patients), and in bone (2 patients). We found the correlation
Finally, we analyzed 15 patients (42-75 y/o, 7 women), 10 lung between number of lesions and calcitonin (R Spearman = 0.65;
NET and 5 gastroenteropancreatic. We consider well/poorly p= 0.014) and CEA level (R Spearman = 0.79; p= 0.018). Moreover,
differentiated NET (based on NCCN 2017) and three groups we observed the relationship between SUV max and calcitonin
according to Ki-67(<3%, 3-20%, >20%). Clinical follow-up after level (R Spearman = 0.8; p= 0.005). Five patients with negative
the last test: 9-35 months in 13/15 patients and <3 months in results of PET/CT with [18F]-DOPA and increasing calcitonin
2 patients (classified as non-evaluable (NE)). Non-progressive level [18F]-FDG PET/CT revealed metastases in lymph nodes
disease (NPD) if absence of new lesions by CT/MRI after 9 (2 patient) and in liver (2 patient). PET/CT with [18F]-DOPA and
months. Results: 10/15 patients (66.6%) were positive with 99mTc- [18F]-FDG both was negative in one patient. Conclusion: The
octreotide positive and 7/15 (46.6%) with 18F-FDG, with general results are demonstrated the usefulness of PET/CT with [18F]-
agreement between both tests in 12/15 patients (80%). Positive DOPA in the detection of MTC recurrence in the patients with
concordance (PC) in 7/15 (46.6 %), negative concordance (NC) in biochemical relapse. [18F]-FDG PET/CT provides with additional
5/15 (33.3%) and discordance(D) in 3/15, all of them with positive data in when tumor lost differentiation. References: None.
99m
Tc-octreotide and negative 18F-FDG. There were 5 patients
with Ki-67<3%, 7 with 3-20% and 3 with >20%. In the group
with Ki67<3%, 3 patients had NC (2NPD and 1NE), 1 PC(death by EP-0359
progression) and 1D with NPD. In the group with Ki-67 between Value Of 99mTc-EDDA/HYNIC-TOC SPECT-CT Over Planar
3-20%, 2NC with NPD, 3PC (3 progression-1 death) and 2D with Scintigraphy In Gastroenteropancreatic Neuroendocrine
NPD. Finally, in group with Ki-67>20%, 3PC: 1 progressed, 1 initial Tumors
NPD but then deceased and 1 NE. Well differentiated NET(11)- B. Luna1, F. Cepa1, C. Sampol1,2, N. Orta1,2, A. Repetto1, M. Valiente1,
poorly(4). Of the 11 well differentiated, 5NC(4 NPD and 1NE), S. Rubí1, J. Muncunill1,2, C. Peña1,2;
3PC (3 progression-2 death) and 3D(3 NPD). Of the 4 poorly 1
Hospital Universitario Son Espases, Palma,
differentiated, all of them where PC (2 progressed, 1 initial NPD, SPAIN, 2IdISBa, Palma, SPAIN.
then deceased, and 1 NE). Conclusion: The general agreement
between 99mTc-octreotide and 18F-FDG was good. There were
more NC in patients with lower Ki-67 proliferation index and Aim/Introduction: To analyze the value of SPECT-CT with
with well tumoral differentiation, and more PC in patients with 99m
Tc-EDDA/HYNIC-TOC vs planar scintigraphy in the initial
higher Ki-67 and poorly differentiation. However, combined staging and in the restaging by progression/recurrence of
assessment of both tests, especially in intermediate Ki-67 index, gastroenteropancreatic neuroendocrine tumors (GEP-NETs).
allows to improve the prognostic evaluation and individualizes Materials and Methods: A retrospective study of 26 patients
the therapeutical decision making, although a larger number of (11women/15men; median age: 63.5 years) referred for 99mTc-
patients must be evaluated. References: None. EDDA/HYNIC-TOC scintigraphic evaluation in the initial staging,
S547 Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952

and in the restaging by progression/recurrence, of GEP-NET images, histological findings, Ki-67 proliferation marker
from May 2015 to February 2019, was performed. Whole and serum chromogranin values) were compared with the
body planar scans (WBS) were acquired at 2 and 4 hours after Tektrotyd-SPECT/CT (Mediso AnyScan Trio) results. The average
intravenous administration of 666-740 MBq 99mTc-EDDA/HYNIC- follow-up time was one and a half year (0,5-2,5 years) Results:
TOC in all patients; a SPECT-CT of the abdominal region was The Tektrotyd-SPECT/CT was positive in 36/51 patients from a
completed after the planar study at 2 hours postinjection. The total of 257 identified tumour suspicious lesions. On the SPECT/
images were obtained using a double-head camera (NM/CT CT 220 showed increased somatostatin receptor density. Only
D670, GE). The total number of tracer deposits in the WBS and 197 pathological abnormalities were identified by the previous
SPECT-CT was assessed. Any lesion with an uptake higher than imaging studies. During the follow-up, we have seen a close
hepatic activity was considered positive by visual analysis. The correlation between the results of somatostatin receptor
findings were correlated with the clinical, anatomopathological scintigraphy and the summarized results of subsequent studies
and/or radiological follow-up (mean: 13,38 months). Results: used in the verification process (Chi-squared test, p <0.0001).
Primary NETs localization was pancreatic(13), gastric(7) and Most of the SSTR-positive lesions were found in the lymph nodes
intestinal(6), 3 at small intestine and 3 at large intestine. All NETs (70/220) and bones (76/220). The majority of SSTR-negative
had histological grade 1 (15) or 2 (11). Of the total number of lesions were in the liver (19) and lung (14), while the majority
patients, 11 were referred for initial staging and 15 patients for of false positive cases were in the pancreas and small intestine.
re-staging by progression/recurrence. Patient-based analysis The Tektrotyd-SPECT/CT sensitivity was 88%, specificity was
showed: scintigraphy (S=69%, E=85%, PPV=82%, NPV=73% and 78% and its accuracy was 84%. Based on the somatostatin
accuracy=77%) and SPECT-CT (S=85%, E=100%, PPV=100%, receptor SPECT/CT the clinical treatment in 33 (65%) patients
NPV=87% and accuracy=92%). Lesion-based analysis showed had changed, PRRT or other therapeutic interventions and drug
that more lesions were detected with SPECT-CT (53) than with modifications had been required. Conclusion: The Tektrotyd-
WBS (34). The statistical analysis showed: scintigraphy (S=92%, SPECT/CT has high sensitivity and it makes it a suitable, easily
E=71%, PPV =82%, NPV =83% and accuracy=82%) and SPECT-CT accessible nuclear imaging method to detect neuroendocrine
(S=94%, E=100%, PPV =100%, NPV =91% and accuracy=96%). tumors. The treatment plan has modified in two thirds of the
The group of patients referred for initial staging obtained: patients, which demonstrates the usefulness of this imaging
scintigraphy (S=67%, E=80 and accuracy =73%) and SPECT-CT modailty in patient care. However the relatively high number of
(S=83%, E=100% and accuracy =91%). The group of patients false positive and negative lesions draw attention to the critical
referred for re-staging by progression/recurrence obtained: evaluation of Tektrotyd-SPECT/CT. References: None.
scintigraphy (S=71%, E=87% and accuracy =80%) and SPECT-
CT (S=86%, E=100% and accuracy =93%). Conclusion: 99mTc-
EDDA/HYNIC-TOC SPECT-CT is a reliable imaging method in EP-0361
the management of this type of tumors, with higher diagnostic Impact of 68Ga DOTATOC PET/CT in the Therapeutic
accuracy and a higher lesion detection rate than planar imaging. Management of Neuroendocrine Tumors
In addition, it provides a better characterization and anatomical E. Pilati1, M. Finessi1, R. Passera1, V. Liberini1, C. G. De Angelis2, E.
localization of lesions. References: None. Arvat3, A. Piovesan3, M. Gallo3, L. Ciuffreda4, N. Birocco4, M. P. Brizzi5,
D. Campra6, G. Giraudo7, M. Bellò1, G. Bisi1, D. Deandreis1;
1
Nuclear Medicine Unit, Department of Medical Sciences,
EP-0360 University of Turin, AOU Citta’ della Salute e della Scienza di Torino,
The impact of 99mTc-EDDA/HYNIC-TOC (Tektrotyd) SPECT/ Turin, ITALY, 2Gastroenterology Unit, Department of General and
CT upon the clinical management of neuroendocrine Specialist Medicine, University of Turin, AOU Città della Salute
tumors e della Scienza di Torino, Turin, ITALY, 3Endocrine Oncology
G. Sipka, Z. Besenyi, I. Farkas, A. Bakos, A. K. Augusztin, L. Pavics; Unit, Department of Medical Sciences, University of Turin, AOU
University of Szeged, Department of Nuclear Città della Salute e della Scienza di Torino, Turin, ITALY, 4Medical
Medicine, Szeged, HUNGARY. Oncology, Department of Medical Oncology, University of Turin,
AOU Città della Salute e della Scienza di Torino, Turin, ITALY,
5
Medical Oncology, Department of Oncology, University of Turin,
Aim/Introduction: The somatostatin receptor (SSTR) AOU San Luigi Gonzaga, Orbassano (Turin), ITALY, 64th General
scintigraphy is a valuable tool for neurendocrine cancers in Surgery, Department of Surgical Sciences, University of Turin,
staging and restaging. New therapeutic options become AOU Città della Salute e della Scienza di Torino, Turin, ITALY, 71st
available after receptor positivity, which can serve as a curative General Surgery, Department of Surgical Sciences, University of
solution. The purpose of our study was to compare the results Turin, AOU Città della Salute e della Scienza di Torino, Turin, ITALY.
of previous imaging studies with the Tektrotyd-SPECT/CT
and establish how the obtained information influences the
further treatment of patients. Materials and Methods: In Aim/Introduction: The aim of this study was to assess the
our retrospective analysis, 51 histologically confirmed, various impact of 68Ga DOTATOC PET/CT on therapeutic decision in
neuroendocrine cancer patients’ (25 women, 26 male, mean patients with NETs in our multidisciplinary team. Materials
age: 59 years) clinical data (CT, MRI, ultrasound, endoscopic and Methods: We retrospectively evaluated 160 consecutive
Eur J Nucl Med Mol Imaging (2019) 46 (Suppl 1): S1–S952 S548

patients (91 men, 69 women) with NETs referred to our is not recommended for baseline evaluation or post therapy
department from February 2017 to January 2019 to perform response assessment. Our objective was to evaluate the
68
Ga DOTATOC PET/CT scan for primary staging (n=57; 57.6%), prospect of 18F-FDG PET/CT in baseline staging and detection
including 10 patients for occult primary tumor evaluation, of residual and recurrent disease in ACC. Materials and
restaging (n=88; 55.0%) and follow up (n=15; 9.4%). 43/160 Methods: Retrospective evaluation was done of consecutive
patients (26.9%) underwent also 18F-FDG PET/CT to assess ACC patients referred for FDG PET between Feb 2017 and April
FDG avidity for high-grade NETs. The impact on therapeutic 2019. Patients were referred to our department for baseline
management was evaluated on the basis of multidisciplinary evaluation, response to therapy or recurrent disease. Details
group PET guided decision: eligibility to locoregional therapies, from conventional imaging done were collected along with the
indication for systemic therapies, Peptide receptor radionuclide reports of histopathology of biopsy or surgery specimens. PET/
therapy (PRRT) or association of locoregional plus systemic CT scans were visually assessed by two independent nuclear
treatment. Median follow up after 68Ga DOTATOC PET/CT was physicians. Ability of FDG-PET to detect primary, metastatic
12 months (range 1-23 months). Results: 53.8% of patients lesions and recurrence/residual disease was assessed. Results:
presented with GEP-NET, 13.1% with lung, 20.0% with other or In this study, data of 25 patients were analysed (8 females and 14
unknown site respectively (13.1% missing data). 33.8% had G1, males) with median age of 39 years (range-2-57). All the patients
34.4% G2 and 3.1% G3 NET respectively (28.8% missing data, were histopathologically proven cases of ACC and showed FDG
including patients with suspected NET). 35.0% (n=56) presented positive lesions on PET-CT. Out of 25 patient, 12 patients were
with locally advanced NET and 21.9% (n=35) with metastatic referred for staging and 13 for post therapy response assessment
disease; 55% of patients were treated with somatostatin and restaging. Common sites of distant metastasis were lung,
analouges only and 16.3% received previously therapies such us liver, abdominal wall and lymph nodes. PET/CT led to upstaging
chemotherapy, PRRT or interventional locoregional treatment. over conventional imaging in six patients, with detection of
68
Ga DOTATOC PET/CT was positive in 112/16

You might also like