Year : 2019 | Volume
: 18 | Issue : 5 | Page : 1--17
18 Anniversary Conference 20 Years Cyprus Society Of Nuclear Medicine (CYSNM20) Limassol Cyprus, 6th – 10th November 2019
|How to cite this article:|
. 18 Anniversary Conference 20 Years Cyprus Society Of Nuclear Medicine (CYSNM20) Limassol Cyprus, 6th – 10th November 2019.World J Nucl Med 2019;18:1-17
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. 18 Anniversary Conference 20 Years Cyprus Society Of Nuclear Medicine (CYSNM20) Limassol Cyprus, 6th – 10th November 2019. World J Nucl Med [serial online] 2019 [cited 2022 Jan 27 ];18:1-17
Available from: http://www.wjnm.org/text.asp?2019/18/5/1/269742
101: Patient-Specific Dosimetry of 177Lu-DOTATATE Peptide Receptor Radionuclide Therapy with High Activities
Beykan Seval1, Eberlein Uta1, A Werner Rudolf1, Lapa Constantin1, K Buck Andreas1, Kudlich Theodor2, Lassmann Michael1
Departments of1Nuclear Medicine and2Gastrology, University of Würzburg, Würzburg, Germany
Objectives: The aim of the study is to provide the first pre- and peri-dosimetry analyses of 177Lu-DOTATATE patients with neuroendocrine tumors receiving higher activities compared to the standard 177Lu-DOTATATE treatment and to compare the results of three different computer codes used for calculating the absorbed dose to the kidneys. In addition, the blood-based and image-based techniques were applied to estimate bone marrow absorbed doses were analyzed to find an optimal way to estimate bone marrow absorbed doses. Methods: Multiple blood samples (up to 96 h), 24 h SPECT/CT data and a series of WB planar images (up to 95 h) were acquired after an administered therapy activity of 14.4 - 19.3 GBq. The administered activities were chosen based on pre-dosimetry kidney absorbed dose coefficients obtained without kidney protection with the aim not to exceed a kidney absorbed dose of 23 Gy after a single administration of 177Lu-DOTATATE (170-237 MBq). Time-activity curves (TAC) and the corresponding time-integrated activity coefficients (TIACs) for kidneys, blood, whole-body and lumbar vertebrae 2-4 (representing bone marrow) were calculated. Based on these data, patient-specific kidney absorbed dose coefficients were obtained with NUKDOS, OLINDA1.1 and IDAC-Dose 2.1. Absorbed doses to the blood were calculated as described by Eberlein et al. Image-based and blood-based bone marrow absorbed doses were analyzed and compared. Results: In blood we observed lower than 8% of the injected activity 2 h after injection (assuming a blood volume of 5.3 liter). Compared to the standard therapy (7.4 GBq) the absorbed dose to the blood after 48 h is higher (mean: 186±54 mGy vs. 79±16 mGy (1)). Image-based (NUKDOS) and blood-based bone marrow absorbed doses ranged from 0.3-0.8 Gy (LV2-4-based) and 0.1-0.3 Gy (blood-based), respectively. After injection of 14.4 - 19.3 GBq 177Lu-DOTATATE, patient-specific kidney absorbed dose coefficients and doses were identical for NUKDOS, OLINDA 1.1 and IDAC-Dose 2.1 and well below 23 Gy (Pat 1: 0.7 Gy/GBq, 9.6 Gy; Pat 2: 0.3 Gy/GBq, 4.8 Gy; Pat 3: 0.4 Gy/GBq, 7.0 Gy). Conclusions: This study provides the first pre- and peri-therapeutic dosimetry data of 177Lu-DOTATATE patients receiving patient-specific higher activities compared to the standard 177Lu-DOTATATE treatment. The results of this study show that high 177Lu-DOTATATE activities can be administered safely based on pre-therapeutic kidney dosimetry. In addition, blood-based bone marrow absorbed doses are by a factor of three lower compared to image-based bone marrow absorbed doses advocating the use of image-based dosimetry. When patient-specific kidney masses are used, OLINDA 1.1 and IDAC-Dose 2.1 provide similar results with NUKDOS which uses patient-specific voxel-based S-values.
- Eberlein U, Nowak C, Bluemel C, Buck A, Werner R, Scherthan H, et al. DNA damage in blood lymphocytes in patients after 177Lu peptide receptor radionuclide therapy Eur J Nucl Med Mol Imaging 2015;42:1739–1749.
102: Establishing Positron Emission Tomography/CT and Cyclotron Unit in Skopje-(Our Experience)
Marina Zdraveska Kochovska1, Ana Ugrinska1, Maja Velichkovska1, Meri Angjeleska1
1PHI University institution of positron emission tomography in North Macedonia
Objectives: New institution, a Centre for Positron Emission Tomography (PET) and cyclotron unit has been established at the end of 2016 in Skopje. The aim of this presentation is to share two years of operational experience of PETtrace medical cyclotron and to extend working knowledge on the same. Methods: The basic equipment consists of a bunker shielded medical cyclotron PETtrace 860 manufactured by General Electric Medical Systems. It is an isochronous cyclotron that is able to accelerate negative hydrogen ions (H-) up to 16,5 MeV and negative ions of deuterium (D-) up to 8,4 MeV. The beam of accelerated particles can be directed on one of six output ports. In our case the cyclotron is equipped with four targets for the production of the main radionuclides of interest for PET (11C, 13N and two for targets for 18F). Chemical processing modules are part of the production unit and consist of: eight hot cells, four modules for synthesis of FDG, one for 11C, one for 68Ga and one for NH3. Two CLIO dispensers are available for the final product in multi vials and syringes. Two fully equipped QC laboratories for radiopharmaceuticals where it will be certified whether the specifications of the final pharmaceutical product meet the requirements of the European pharmacopoeia. Results: During period of two years about 430 runs have been performed on cyclotron. The operational parameters which influence the yield of 18F were observed during runs. The mean duration of bombardment in this number of production runs of the 18F target was (49±18) min. Mean value of produced activity delivered to hot cell is (2720,39±1035,29) mCi; min-322 mCi; max-4944 mCi. The effect of target rinsing is still under observation and not implemented. First measurements after target rinsing show residual activity about 6 GBq up to 10 GBq. The trend line and correlation between the duration of bombardment (min) and activity at the end of bombardment will be presented. Until now about 1860 patients have benefited from PET/CT diagnostic. The number of patients is increasing continuously, 362 patients were scanned in 2017, 1120 patients were scanned in 2018 and it is expected that until the end of this year about 2000 patients will be scanned for PET/CT imaging. Conclusions: The radiation monitoring of the cyclotron facility during the production runs in and out the cyclotron vault has shown that gamma and neutron levels are well within proposed limits. Continuous monitoring of parameters is very important to optimize the process of production of 18F to reduce the exposure to the staff and to ensure that radiation safety of operator's is adequately managed.
103: [99mTc]Demobesin Analogs with Different Length PEG Spacers: Effects on Biological Responses in Gastrin-Releasing Peptide Receptors-Positive Cells and Animal Models
Panagiotis Kanellopoulos1, Aikaterini Kaloudi1, Ioannis Giannoutsos1, Marion de Jong\2, Eric P Krenning3, Berthold A Nock1, Theodosia Maina1
1Molecular Radiopharmacy, INRASTES, NCSR “Demokritos,” Athens, Greece,2Department of Radiology and Nuclear Medicine, Erasmus MC,3Cyclotron Rotterdam BV, Erasmus MC, Rotterdam, The Netherlands
Objectives: The overexpression of gastrin-releasing peptide receptors (GRPRs) on the surface of prostate cancer cells provides the molecular basis for delivering diagnostic or therapeutic radionuclides to cancer sites via GRP-like peptide carriers. Radiolabeled GRPR-antagonists, despite their inability to internalize in GRPR-expressing cancer cells, have often shown higher localization in pathological lesions and faster background clearance than their agonist-based counterparts and are safer for injection in human. We herein present three different Demobesin (DB) analogs, whereby an acyclic tetraamine chelator is coupled to the potent GRPR-antagonist DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-NHEt via different length PEGx spacers (x= 2, DB7; x= 3, DB13; and x= 4, DB14) and compared their biological responses in GRPR-positive cells and animal models. Comparison of metabolic patterns in mice was carried out as well. Methods: Competition GRPR-binding assays were performed in human prostate cancer PC-3 cell membranes. Cell binding tests were conducted by 1 h incubation of 99mTc-DB7/13/14 in PC-3 cells at 37oC. In vivo radioligand stability was studied by HPLC analysis of blood samples collected 5 min after injection of the radioligands without or with coinjection of the neprilysin (NEP)-inhibitor phosphoramidon (PA) in mice. Biodistribution patterns at 4 h post-injection (pi) were compared in mice bearing PC-3 xenografts without or with PA-coinjection. Results: DB7/13/14 displayed single-digit nanomolar affinities for the human GRPR. The uptake in PC-3 cells was comparable and consistent with a radioantagonist profile showing a slight trend 99mTc-DB7>99mTc-DB13>99mTc-DB14. The radiotracers were found ≈70% intact in mouse blood with this percentage rising >94% after coinjection of PA. Their 4 h pi tumor uptake without or with PA-coinjection followed the trend: 99mTc-DB7, 4.5±1.2%ID/g to 6.1±1.1%ID/g > 99mTc-DB13, 4.1±0.8%ID/g to 5.8±1.2%ID/g > 99mTc-DB14, 3.7±1.0%ID/g to 4.0±0.3%ID/g. Conclusions: The present study has shown that the introduction of PEGx spacers in the 99mTc-DB motif allows for good in vivo stability, but cell-uptake turned out to be sub-optimal. By increasing the PEGx length from x= 2 to x= 4, a marginal decrease in cell uptake and tumor localization was observed. Treatment of mice with PA lead to in situ stabilization of the new radiotracers in mice circulation and enhancement of tumor uptake.
104: Preclinical Comparison of 99mTc-DT1 and 99mTc-DT6: The Impact of Cell Internalization and In Vivo Stability on Radiotracer Uptake in Neurotensin Subtype 1-Positive WiDr Xenografts in Mice
Panagiotis Kanellopoulos1, Aikaterini Kaloudi1, Eric P Krenning2, Berthold A Nock1, Theodosia Maina1
1Molecular Radiopharmacy, INRASTES, NCSR “Demokritos,” Athens, Greece,2Cyclotron Rotterdam BV, Erasmus MC, Rotterdam, The Netherlands
Objectives: The neurotensin (NT) radiotracers 99mTc-DT1 ([99mTc-N4-Gly7]NT(7-13)) and 99mTc-DT6 ([99mTc-N4-βAla7,Dab8,Tle12]NT(7-13), Dab= diaminobutyric acid) were previously studied for potential use in the imaging of human tumors expressing the NT subtype 1 receptor (NTS1R), such as exocrine ductal pancreatic adenocarcinoma. Despite the higher stability of double-stabilized 99mTc-DT6 in vitro, the radiotracer failed to reliably visualize NTS1R-positive lesions in patients, presumably due to rapid in vivo degradation. Neutral endopeptidase (NEP) and angiotensin converting enzyme (ACE) have been implicated in the degradation of NT analogs. In the present study, we first compared the internalization of 99mTc-DT1 and 99mTc-DT6 in WiDr cells. Next, we studied the effects induced by coinjection of the NEP-inhibitor phosphoramidon (PA), or the ACE-inhibitor Lisinopril (Lis), or both (PA+Lis), on the in vivo profile of 99mTc-DT1 and 99mTc-DT6 in WiDr tumor-bearing mice. Methods: The internalization of 99mTc-DT1 and 99mTc-DT6 was compared in colorectal adenocarcinoma WiDr cells expressing the human NTS1R. The in vivo stability in mice was compared 5 min post-injection (pi) of radioligand alone (control), or with coinjection of PA, or Lis, or PA+Lis. Biodistribution of 99mTc-DT1 or 99mTc-DT6 was compared at 4 h pi in WiDr tumor-bearing mice, using the animal groups described above. SPECT/CT was performed in 99mTc-DT1 controls and PA+Lis groups without or with gelofusine coinjection at 4 h pi. Results: Non-modified 99mTc-DT1 internalized significantly higher in WiDr cells than 99mTc-DT6, revealing a negative effect of double Arg8/Dab8 and Leu12/Tle12 modifications. In contrast, stability in mice peripheral blood improved (>52% of 99mTc-DT6 was detected intact at 5 min pi vs. <2% of 99mTc-DT1). Interestingly, 99mTc-DT1 could profit most from the PA+Lis coinjection (56% intact). The tumor uptake of 99mTc-DT1 in controls (1.2±0.2%ID/g) reached the highest values of this study by the PA+Lis combination (7.7±1.2%ID/g vs. 3.5±0.3%ID/g of fully stabilized, but less internalizing 99mTc-DT6). These results were visualized by SPECT/CT. Conclusions: This study has shown that in situ NEP/ACE-inhibition represents a powerful tool to improve the bioavailability of NT(8-13)-based radiotracers without negatively affecting other important biological features, such as cell-uptake and internalization. As a result, tumor targeting and overall pharmacokinetics could be notably improved.
105: 89Zr-Radiolabelled Monoclonal Antibody Ramucirumab Bound to Vascular Endothelial Growth Factor Receptor 2 Positive Tumour Cell Lines Both In Vitro and In Vivo
Pavel Barta1, Jiri Janousek2, Zbynek Novy3, Milos Petrik3, Frantisek Trejtnar2
Departments of1Biophysics and Physical Chemistry and2Pharmacology and Toxicology, Faculty of Pharmacy in Hradec Kralove, Charles University, Hradec Kralove,3Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic
Objectives: The process of angiogenesis is important for the appropriate nutrition supply of proliferating tumour tissue. The key factors determining angiogenesis are vascular endothelial growth factor (VEGF) and its receptors (VEGFRs), particularly VEGFR2. The knowledge of the angiogenesis principle enabled the preparation of compounds aiming at the angiogenesis process suppression. These compounds include either VEGF blocking molecules like bevacizumab, or VEGFR activity supressing factors. The group of receptor-suppressing molecules consists of either tyrosine kinase inhibitors or VEGFR2 binding site blocking compound, the monoclonal antibody ramucirumab (RAM). The fully humanized IgG1 high affinity anti-VEGFR2 monoclonal antibody RAM targets the extracellular receptor binding site and thus prevents interactions with natural ligands from VEGF family. Besides therapeutic uses, the antibody might be potentially employed for radioimmunoimaging of the VEGFR2-positive tumours. The aim of the presented study was to prepare RAM with PET imaging agent zirconium 89 and characterize in vitro and in vivo its biological properties important for possible VEGFR2-positive cancer visualization. Methods: The monoclonal antibody was conjugated to p SCN Bn deferoxamine (DFO) at pH 9.0 and the ratio of conjugation was assessed with the use of Arsenaso III method. The purification to clear off free DFO molecules was followed by the radiolabelling reaction with zirconium-89 in the form of (89Zr)Zr oxalate at pH 5.5. The prepared radioimmunoconjugate was analysed on radiochemical purity by instant thin layer chromatography (iTLC). Firstly, the binding ability of prepared (89Zr)Zr DFO RAM to the target receptor was tested in vitro employing saturation method for dissociation rate constant (KD) assessment in the two human carcinoma cell lines, prostate adenocarcinoma (PC-3) and ovary adenocarcinoma (SKOV-3), with proven VEGFR2 expression. Secondly, PET/CT imaging and ex vivo biodistribution experiments were performed in SCID mice bearing PC-3 and SKOV-3 xenografts tumours respectively. The PET/CT scan in mice was repeatedly performed following intraorbital administration until the 6th day post injection. Results: The conjugation of monoclonal antibody with the chelating agent resulted in the number of 1.2 (± 0.7) DFO molecule per one molecule of RAM in average. Radiochemical purity of prepared (89Zr)Zr-DFO-RAM reached 94-95 %. In vitro experiments revealed a strong binding ability of (89Zr)Zr-DFO-RAM to VEGFR2 positive PC-3 and SKOV-3 cell lines with the KD values 65.8 (± 4.2) and 37.6 (± 7.3) nM, respectively. The obtained biodistribution data showed the uptake in PC-3 and SKOV-3 tumours about 8.7 (± 0.2) and 12.1 (± 1.6) %ID/g respectively, when the tumour/blood ratio for 1, 3 and 6-days p. i. was 0.4, 0.6 and 0.8 and 0.5, 1.0 and 1.3 for PC-3 and SKOV-3 tumours respectively. PET/CT images gained after (89Zr)Zr-DFO-RAM application in mice showed high activity accumulation in the tumour from the 1st day p. i. The best PET/CT images were obtained 6 days p. i. with low interfering signals coming from heart, spleen and liver. Conclusions: According to our findings, the preparation of (89Zr)Zr-DFO-RAM rendered a anti-VEGFR2 radiopharmaceutical with high binding to the target receptors both in vitro and in vivo. The purification following radiolabelling was needed to obtain the radiolabelled compound of the required quality (minimally 95 %). Although, the binding ability of radiolabelled RAM to VEGFR2 in vitro was lower than that of native RAM (KD ≈ 3 nM), it is still sufficient for the specific targeting. The results of in vivo experiments proved the potency of (89Zr)Zr DFO RAM to target and highlight VEGFR2-positive tumours. However, some other organs were characterized with the increased accumulation of radiopharmaceutical too. Based on the measured data, (89Zr)Zr DFO RAM appears to be a promising probe for in vivo non-invasive visualization of VEGFR2-positive tumour.
106: Quality and Safety Aspects of Nuclear Medicine Practice in Greece
Ioannis Iakovou1, Evanthia Giannoula1, Panagiotis Bamidis2, Nikolaos Karatzas1
1Department of Academic Nuclear Medicine, Aristotle University of Thessaloniki,2Lab of Medical Physics, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
Objectives: Nuclear medicine is a specialty characterized by the use of open sources of radioactivity for diagnosis and therapy. Hence, quality and safety assurance in such an environment should not be considered a luxury. Although, several reports have been issued, including guidelines on how qualitative and safe management of patients in nuclear medicine departments should be done, limited data are available worldwide in terms of the level of service provided and patients' perceptions regarding them. In this context the objective of the current study was not only the assessment of in-patient satisfaction level for medical, nursing, organization and hotel services in the Therapeutic Nuclear Medicine department of the Aristotle Univesity of Thessaloniki in General Hospital Papageorgiou but also the evaluation of their attitude to radioiodine therapy as well. Methods: The survey was contacted by using the CASC type questionnaire, which was completed by personal interviews at patients' exit from the hospital. 127 patients who received therapeutic doses of 131I enrolled in this study. Results: High level satisfaction was measured from the medical services (average of patient satisfaction 0.87) and the nursing facilities (0.86). Patient satisfaction was obviously lower in respect with organization (0.71) and hotel facilities (0.69). There were no statistically significant differences in patient satisfaction observed according to sex, age, health insurance except to their education level. Patients' attitude towards radiation treatment efficacy and safety matters was good enough leading the necessity for further informative campaign. Conclusions: The results of our study come into agreement with these of similar surveys conducted in Greece, which establish high levels of in-patient satisfaction for the care provided by physicians and nurses and less satisfaction regarding the organization and hotel services of hospitals.
107: Colaboration between Functional and Structural Imaging on Node Involving in Endometrial Cancer
Irena Cristina Grierosu1,2, Claudia Cirja1,3, Ana Maria Statescu1, Teodor Ionescu1, Cati Raluca Stolniceanu1, Cipriana Stefanescu1,2, Camelia Mihaela Tirnovanu2,4
1Nuclear Medicine Laboratory, Emergency Clinical County Hospital “St. Spiridon,”2Faculty of Medicine, University “Grigore T. Popa,”3Department of Radiology, Emergency Clinical County Hospital “St. Spiridon,”4Department of Obstetrics and Gynecology, Obstetrics and Gynecology Hospital “Cuza Voda,” Iasi, Romania
Objectives: Endometrial cancer seems to become the most common cancer of the female genital system in the last years, being favored by the increase in average life time, the incidence of obesity and the use of estrogen replacement therapy in menopausal women. The diagnosis of endometrial neoplasm is based on a complex algorithm including histopathological evaluation, structural and functional imaging technics. Our main objective is to stage more accurate the endometrial cancer in order to establish a personalized therapy for each case. Methods: In one year period of time 11 patients, aged between 49 years and 72 years, were diagnosed with endometrial cancer by endovaginal ultrasound method by means of IETA criteria (endometrial thickness and ultrasound appearance, presence of bright edge, regularity of the endometrial-myometrium junction, vascular parameters). Complementary, these patients were also investigated by pelvic MRI. The imaging of sentinel lymph node was performed 30 minutes and 90 minutes after intra-cervical injection of 99mTc-Nanocoll, using a Siemens DIACAM dual head gamma camera. The scintigraphics results were correlated with the tumor appearance described by IETA principles, with MRI's information and, finally, with the histophatological results of sentinel lymph node. Results: Endometrial cancer was confirmed in all cases after surgery (stage IA, IB and, only one case, stage II). Ultrasonography shows in one patient less than 50 % of myometrium invasion and low vascularization, and more than 50 % of myometrium invasion with increased vascularization for the others patients. From these last cases, only in one there was no correlation between functional and structural imaging: lymph nodes were suspects in MRI, but with no metastasis in sentinel lymph node after surgery. In total, for 10 patients the sentinel lymph nodes were free of metastasis, and in a single case the anatomy confirmed malignant infiltration. Conclusions: The first step in imaging the endometrial cancer is endovaginal ultrasonography, so IETA evaluation by tracking morphological and vascular parameters provides good predictability with regard to the malign or benign nature of the lesion with good correlation with scintigraphics findings in all our cases. Our results, which are part of a prospective study, certifies that sentinel lymph node with 99mTc-Nanocoll is very helpful to reduce morbidity and optimize lymph node evaluation in women with endometrial cancer.
108: Simulation of 68-Ga Radiopharmaceutical Binding Metastases in Tissue Phantoms for PET-CT
Kusins Toms1, Sembele Liga2, Kalnina Marika2, Rozensteins Harijs3,4, Saleniece Kristine3,5Shvirksts Karlis3,6, Kovaldins Ricards3,7, Mazkalnina Liva3,6, Kristiana Mace3, Kokorevs Pavels5, Grinbergs Andrejs3
1Clinical Department of Nuclear Medicine, Riga East University Hospital,2The Latvian Maritime Medical Centre,3Kodolmedicinas Klinika Ltd,4Institute of Biomedical Engineering and Nanomedicine, Riga Technical University,5Arbor Medical Corporation Ltd,6Faculty of Biology, University of Latvia,7Faculty of Chemistry, University of Latvia, Riga, Latvia
Objectives: The objective of this study is to evaluate refurbished PET/CT imaging capabilities using phantom created from soft and bone animal tissue with simulated metastases. Authors of the study aimed to determine if more than 10 years old, refurbished PET/CT scanner (PHILIPS Gemini 2005), designed for 18F examinations, can construct images suitable for clinical examination and pre-therapy dosimetry using tissue phantoms and with 68Ga simulated metastases. Methods: Synthesis of Ga68-PSMA-11 was done in NMC 50-68 Ga, TEMA Sinergie, Italy isolator under strict GMP conditions using a fully automated Scintomics GRP module. The activity of synthesized product was more than 500 MBq which was 89,9% of theoretically possible radiochemical yield. All the necessary quality control analyses were done according to GMP. The product was dispensed in 19 (0.5mL) (dimensions of sample Ø5×21mm) and 16 (2mL) (Ø7x23mm) Eppendorf type containers (point source) 200μL (7.44MBq) and 400μL (14.88MBq) of sample respectively. As an acceptable comparison for the human soft and solid tissue for phantom a carcass of a pig was chosen. The point sources were inserted into the soft tissue approximately 30 mm under the outer surface and in bone structures (minimum distance 2cm between containers) A dry cotton pieces were submerged into two of the radiopharmaceutical samples and inserted approximately 30mm under the surface of the outer liver layer to observe the radiopharmaceutical absorption within tissue. Carcass object with point sources inserted was examined twice with an hour interval by following settings. For CT: FOV 600mm; thickness 5mm; increment 5mm; 120kV, 60mAs/slice (low dose CT); resolution - standard; collimator 16x1.5; pitch 0.1813; rot. time 0.5sec; matrix 512. For PET: was fixed - Administered. Activity in MBq and Administration Time. Scanning FOV 576mm; emission frames 1min/per bed; reconstruction protocol: body-ctac-nac lorcin. After examinations containers containing radioactivity were removed, the phantom was transferred to SPECT device and containers each with 200μL 5MBq of 131-I were inserted in same locations and images were acquired. Results: As a result, Nuclear medicine physician confirmed that all inserted radioactive point sources were clearly visible and detectable, no artefacts or reconstruction errors occurred. Comparison between estimated volumes and distances of metastases from PET/CT and SPECT images reveals that SPECT-CT overestimates volume of the metastases, compared to PET/CT and actual volume of simulated metastases. Conclusions: This study as well as regular technical maintenance and performance testing approves that more than 10 years old PET/CT scanner can construct images suitable for examination. This type of PET/CT examination is also a great practice for radiographers and Nuclear medicine physicians. Results confirm, that in therapy planning and dose estimation, volumes estimated with PET/CT should be used. Tissue phantoms are used because of the availability, versatility and price in comparison with dedicated PET phantoms. Also tissue phantoms provide results, that are visually close to images from live patients.
This study was supported by the University of Latvia Foundation and the “MIKROTĪKLS” Ltd.a donation project “Development and introduction of innovative methods in clinical practice for the diagnosis and treatment of malignant tumors using molecularly targeted radionuclides produced in Latvia.”
109: Preclinical Investigation on the Effects of 68Ga-[Ga]-HA-DOTATATE on Breast Cancer Cell Lines In Vitro
Cakstina Inese1, Kusins Toms2, Mazkalnina Liva3, Rozensteins Harijs3, Kovaldins Ricards3,4, Rubena Elza5, Berzina Antra2, Saleniece Kristine3,6, Nitisa Dina1, Grinbergs Andrejs3
1Laboratory of Molecular Genetics, Institute of Oncology, Riga Stradins University,2Clinical Department of Nuclear Medicine, Riga East University Hospital,3Kodolmedicinas Klinika Ltd,4Institute of Chemical Physics, University of Latvia,5Institute of Microbiology and Biotechnology, University of Latvia,6Arbor Medical Corporation Ltd, Riga, Latvia
Objectives: Breast tumors are one of the leading cancer forms in women in the world. While there are several therapy possibilities for most forms of breast tumors, triple negative breast cancers lack effective treatments due to the absence of main cancer targets (e.g ER, PR, Her2). In addition to conventional cancer diagnostic approaches PET-CT with [18F]-FDG is becoming standard for cancer diagnostic and therapy control. Receptor specific radiopharmaceuticals (RFP) are being used for cancer diagnostics, such as 68Ga-[Ga]-HA-DOTATATE for neuroendocrine tumors (NET) with SSTR2 markers. In recent studies it has been discovered that HA-DOTATATE is also binding with non-NET cancer cells, which leads to objective of this study, to test possibility of using 68Ga-[Ga]-HA-DOTATATE for breast cancer diagnosis. Methods: Three breast cancer cell lines (MCF-7, MDA-MB-231, SkBr3) and one human dermal fibroblast cell line (HDFa) were seeded onto suspension 6-well plates in serum free media (DMEM-F12/p/s) and cultured for 24 h prior the addition of 68Ga-[Ga]-HA-DOTATATE. Partial hypoxia was achieved keeping the plates wrapped in parafilm for 4 h prior the addition of the 68Ga-[Ga]-HA-DOTATATE. The synthesis of 68Ga-[Ga]-HA-DOTATATE was achieved in hot-cell using Scintomics GmBH automatic synthesis module and ABX disposable materials and reagent kit. Fully automatic synthesis of 68Ga was obtained from 68Ge/68Ga generator (iThemba) in form of 68GaCl3. For labelling with 68Ga, a 20 μg/80 μl HA-DOTA-TATE was used. Final product was diluted in PBS. For Quality control synthesized 68Ga-[Ga]-HA-DOTATATE was tested according to European Pharmacopeia. Tests such as HPLC, TLC, gamma spectrometry, pH, HEPES and endotoxin check were carried out. To observe binding or internalization 68Ga-[Ga]-HA-DOTATATE was added to cell cultures according to cell count and incubated for 40 minutes (+37 °C, 5% CO2). After incubation cells were transferred to 15ml tube and washed with 2mL PBS 3 times and centrifuged (4 min 300G) after each wash. After last centrifugation samples were resuspended in 1ml PBS and measured in BSI gamma spectrometer. Results: Binding of 68Ga-[Ga]-HA-DOTATATE was detected in three breast cancer cell lines in three separate experiments. Some binding was observed in HDFa that was used as a control. This observation is not in line with previous documented experiments with fetal dermal fibroblast cell line (Hs68). Overall the binding of 68Ga-[Ga]-HA-DOTATATE in breast cancer cells was higher than in dermal fibroblasts. Highest binding was observed in SkBr3 and MDA-MB-231 cell lines. Binding of 68Ga-[Ga]-HA-DOTATATE in cells kept in partial hypoxia overall showed lower levels than cells in normoxia. Cells treated with 10 μM sulforaphane, exhibited differences in morphology but not in binding levels. In further experiments a detailed cell counting is mandatory for more accurate evaluation of results. Conclusions: The preliminary data show the binding of 68Ga-[Ga]-HA-DOTATATE in breast cancer cell lines and in adult dermal fibroblasts, which might widen the use of RFP in diagnostics. It might provide evidence of possible false positive results when used in diagnostic of prostate cancers and NET. The further investigation on the effects of hypoxia and addition of sulforaphane are necessary.
This study was supported by the University of Latvia Foundation and the “MIKROTĪKLS” Ltd. donation project 2201.
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- Kalnina Z, Shvirksts K, Rubena E, Grube M, Kusins T, Kovoaldins R, et al. In Vitro Model System for Biological Quality Control and Functional Research of Radiopharmaceuticals used for Targeted Radionuclide Therapy. Eur J Nucl Med Mol Imaging 2019;46 (Suppl 1): S682.
110: Simple Solution for Single Final Vial Filling of Radiopharmaceuticals in One Hot Cell Isolator at Small-Scale Radiopharmacy Laboratories under Aseptic Conditions
Harijs Rozensteins1,2, Toms Kusins3, Ingars Reinholds4, Rita Berzina5, Remo Merijs Meri5, Janis Zicans5, Liva Mazkalnina1, Karlis Shvirksts1, Gunta Kizane6, Andrejs Grinbergs1
1Kodolmedicinas Klinika Ltd,2Institute of Biomedical Engineering and Nanomedicine, Riga Technical University,3Clinical Department of Nuclear Medicine, Riga East University Hospital,4Institute of Food Safety, Animal Health and Environment “BIOR”,5Institute of Polymer Materials, Faculty of Materials Science and Applied Chemistry, Riga Technical University,6Institute of Chemical Physics, University of Latvia, Riga, Latvia
Objectives: The manufacturing processes of radiopharmaceuticals (RP) are subjected to high safety requirements for the control of microbial contamination and radiation safety of personnel [Elsinga P et al., Eur J Nucl Med Mol Imaging, 2010, 37:1049-1062; Alerts J et al., J Labelled Comp Radiopharm 2014, 57:615-620]. Synthesis of Ga-68 and other radionuclide-containing pharmaceuticals include several stages, namely, obtainment of radionuclides, transfer to hot cell isolators for the synthesis followed by the final product filling and dispensing. According to good manufacturing practice (EudraLex (2009), Vol. 4, Annex 1), synthesis can be done in class B or class C environment and vial dispensing in class A environment. Commonly to other small-scale laboratories, we are using single isolator (NMC 50 68Ga, TEMA Sinergie, Italy) for synthesis of RP and single final vial filling. This fact causes an issue to fulfill safety demands determined by the national drug agency, therefore, we have come up with a simple solution that involves use of multi-layer plastic bag sealing system. Methods: The system includes a three-layer microbial contamination protection (outer layer - the transporting layer, mid and inner layer that contain a before prepared evacuated vial with an air filter filled with N2). The mid and inner layers are sterilized by 50kGy gamma irradiation (Cobalt-60) with the vial inside. Afterwards the two layers are put into outer layer and the space between outer and mid layer is decontaminated using hydrogen peroxide dry mist. The production of sealing bag system is performed based on ethylene–octene copolymer (EOC) with 1-octene comonomer content 38 wt%. A hydraulic laboratory press LP-S-50/S.ASTM (Labtech Engineering Co. Ltd., Thailand) was used to obtain rectangular films (180 mm × 120 mm × 0.7 mm). Results: The developed sealing materials have several benefits compared to commercial plastic bags made of polyethylene (PE). The regularly branched structure and super elastic behavior of EOC ensures its reverse deformations, thus enabling safety demands in mid and inner layers after piercing by needle through the layers into the vial. Our previous studies have shown that low density PE may form a micro-gel even at doses of 50 kGy that may affect change of mechanical properties, including reversible deformation due to the formation of cross-links [Pizele D. et al. (2008), Mech Comp Mater, 44:191-196]. That study has also shown that pristine EOC do not form micro-gel fraction and the structure has minor change after irradiation up to the doses typical for sterilization. Conclusions: The developed simple method allows sustaining of both microbial and radiation safety demands during the manufacture of RP with reduced costs for small-scale laboratory practices enabling the class A environment for final filling of Ga-68 RP. This is only one of wide range of possible applications for this technology.
This study was supported by the University of Latvia Foundation and the “MIKROTĪKLS” Ltd. donation project “Development and introduction of innovative methods in clinical practice for the diagnosis and treatment of malignant tumors using molecularly targeted radionuclides produced in Latvia.”
111: Tips and Tricks for Full Filling GMP Requirements for Small-Scale Radiopharmacy Laboratory
Harijs Rozensteins1,2, Toms Kusins3, Karlis Shvirksts1, Ricards Kovaldins1,4, Gunta Kizane4, Andrejs Grinbergs1
1Kodolmedicinas Klinika Ltd,2Institute of Biomedical Engineering and Nanomedicine, Riga Technical University,3Clinical Department of Nuclear Medicine, Riga East University Hospital,4Institute of Chemical Physics, University of Latvia, Riga, Latvia
Objectives: The general GMP regulations, which have been developed for large-scale and centralized manufacturing, are not easily applicable for small-scale manufacturing, inevitably there is a need to find ways how to adopt to these requirements by coming up with safe and costless innovative solutions [Elsinga P et al. EJNMMI 2010; 37: 1049–1062; Aerts J et al. European perspective. J Labelled Comp Radiopharm 2014; 57: 615–620]. In our case there is only one hot cell isolator, which is used for both synthesis and dispensing. Therefore, we have come up with few simple “do it yourself” technical solutions, which are in the agreement with GMP requirements (EudraLex (2009), Vol. 4, Annex 1) of microbial safety without installing new hardware at the same time decreasing costs. Methods: We are using a Nocospray 2 (Oxypharm Ltd., France) hydrogen peroxide dry mist (HPDM, which consists of dry mist disinfection based on hydrogen peroxide and silver molecules in order to eliminate living bacterial microorganisms and spores). Using biological indicators (Geobacillus stearothermophilus) we have proven that commonly used 12% (w/v) hydrogen peroxide is not effective enough and concentrated peroxide solution (36% w/v) is needed. Adding to this modification we also use a special dry mist outlet for easier decontamination. Results: First application is the cascade system that provides protection of microbial contamination level mitigation (6-log) during the transporting of materials and substances, used for synthesis, from not classified rooms to class A hot cell isolator. Cascade is based on three level HPDM decontamination. First the inner layer containing all the materials and substances and a special stand for effective hydrogen peroxide decontamination. Second the mid layer containing nothing and third the outer layer also containing nothing. All of the layers are decontaminated using HPDM. The procedure of transporting is done as follows. In the material air lock from not classified room to class D cleanroom the outer layer is opened. In the material air lock from class D and class C cleanroom the mid layer is left. In the class C cleanroom the inner layer is opened and all the materials and substances are transferred to the class A cleanroom through the class B grade isolator passing drawer, previously also sterilized using autonomous UV lamp.There are many types of isolators available in the market. At our laboratory we have NMC 50 68Ga, TEMA Sinergie (Italy) without automatic VHP decontamination installed which is necessary for achieving A grade environment, considering that hydrogen peroxide is the only substance able to achieve sporicidal decontamination. Therefore, we have come up with a simple solution based simple inflatable one-way boat valve, that is attached to gloves, which are used for preparing the synthesis or carrying out dispensing. Glove was tested with the water leakage test. HPDM is blown through the valve with a Nocospray 2 device with special modification described before in the text. Conclusions: These tips and tricks have reduced the costs in our small laboratory for hundreds of thousands at the same time allowing to sustain safety at GMP requirement level.
112: Transthyretin Cardiac Amyloidosis: A Personalized Approach for a More Accurate Detection
Teodor Ionescu1, Cati Stolniceanu1,2, Ruxandra Ţibu1, Livia Costan1, Ana-Maria Stătescu1, Irena Grierosu1,2, Mihai Guţu1,2, Adrian Gavrilescu3, Antoniu Petriş2,3, Radu Sascău4, Cipriana Ştefănescu1,2
1Nuclear Medicine Laboratory, Emergency County Hospital “Sf. Spiridon,”2University of Medicine and Pharmacy “Grigore T. Popa,”3Department of Cardiology, Emergency County Hospital “Sf. Spiridon,”4Institute of Cardiovascular Disease, Clinical Hospital “Dr. C. I. Parhon,” Iasi, Romania
Objectives: Amyloidosis is a multi-etiological protein deposit disease, which is determined by more than 30 proteins. Cardiac amyloidosis seems to be caused by 5 of these proteins. Transthyretin cardiac amyloidosis (ATTR) is a localized infiltration of the myocardium and coronary arteries, accompanied by clinical manifestations. It is often difficult to diagnose in clinical practice. Endomyocardial biopsy is the gold standard technique for detecting this pathology. But this procedure has its limitations as it cannot differentiate the subtype of ATTR involved. Genetical testing can detect the subtype involved but it is an expensive procedure and not always available. The objective of this paper is to present a personalized diagnosis technique using visual scoring and a modified semiquantitative method in order to obtain a clearer, more precise detection and diagnostic for a better evaluation of the infiltration of the myocardium. Methods: Nineteen patients diagnosed clinically and through echocardiography with cardiac amyloidosis were sent for bone scintigraphy examination. The patients underwent a whole body early and late bone scan (low energy high resolution parallel collimator; matrix = 256x1024; zoom = 1) followed by static image centered on the thorax (low energy high resolution parallel collimator; matrix = 256x256; zoom = 1) and SPECT centered on the thorax (low energy high resolution parallel collimator; matrix = 128x128; rotation at 180 degrees; zoom = 1; 64 views – 15 seconds per view). The images were acquired using a dual head Siemens-Diacam gamma camera, at 10 minutes and 2 and a half hours after the i.v. administration of 99mTc-HDP. Each image was interpreted by two nuclear medicine physicians and the visual score was calculated (scores 0 – absent cardiac uptake and normal bone uptake; 1 – mild cardiac uptake, inferior to bone uptake; 2 – moderate cardiac uptake accompanied by attenuated bone uptake; 3 – higher cardiac uptake or equal to the intensity at the bone level). The protocol that we used is a modified version of the one presented to us by Glaudemans et al. We applied visual scoring and a modified semiquantitative method realized on the SPECT and/or static images (ratio using regions of interest on the myocardium and on the controlateral side). Results: After the positive bone scan result, three patients got the diagnosis confirmed by other investigations (genetical testing, IRM), and the fourth was an incidental diagnostic of ATTR. For them, we obtained a visual score of three for two patients, two for one patient and one for one patient. Conclusions: This personalized approach is an easy and accurate method for detecting the presence of ATTR amyloidosis with the help of bone scan. Bone scan should be included in the diagnostic algorithm of cardiac amyloidosis. The approximated ratio obtained helped us classify the uptake using the scale from the visual score. This is an easy and accurate method for detecting ATTR, endomyocardical biopsy being the gold standard, which is an invasive technique.
113: A Visual Functional Grading Scale for Somatostatin Receptor Scintigraphy Images
Cati Raluca Stolniceanu1,2, Teodor Marian Ionescu2, Irena Cristina Grierosu1,2, Mihai Gutu1,2, Ana Maria Statescu2, Milovan Matovic3,4, Christina Ungureanu5, Cristina Preda5, Cipriana Stefanescu1,2
1Department of Biophysics and Medical Physics, “Grigore T. Popa” University of Medicine and Pharmacy,2Nuclear Medicine Laboratory, “St. Spiridon” Emergency County Hospital, 5Endocrinology Clinic, “St. Spiridon” Emergency County Hospital, Iasi, Romania,3Center for Nuclear Medicine, Clinical Center Kragujevac,4Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia
Objectives: Somatostatin receptor scintigraphy (SRS) has proven valuable for neuroendocrine tumors (NETs) diagnosis. The purpose of our study was to develop a visual functional grading scale (VFGS) for assessing SRS images: whole body scan (WBS), SPECT and spot scintigraphy for patients with primary and metastatic NETs. Methods: Our prospective study during 12 months included SRS images of 44 patients, with a female/male ratio of 0.45:1, mean (±standard deviation (SD)) age 51.3-year-old (±9.3),with primary and metastatic NETs, from two centers: Clinical Center Kragujevac, Serbia and Department of Nuclear Medicine, “Sf. Spiridon” Emergency County Hospital Iasi, Romania. We used 99mTc-Tektrotyd and gamma camera Siemens e cam Dual Head, equipped with LEAP collimators and appropriate software for acquisition and processing. Study design: early dynamic scintigraphy (60 images, 1 image/second, 128x128 matrix), spot scintigraphy (10 minutes/image, 256x256 matrix), WBS (matrix 256x1024, 6cm/min bed movement) and SPECT (128x128 matrix, 132 images). Images were acquired at 10 minutes, 2-4 and 24 hours after i.v. administration of 10.57 MBq/kg bw 99mTc-Tektrotyd. We defined and used a VFGS, (3 grades, based on the uptake intensity) to assess quantitatively SRS images for the pathological uptakes Also, in order to quantify the pathological uptakes, we defined a target standard right thigh background region, using a ROI of 240 pixels, with a maximum of 25 counts. Results: We quantified a total of 88 pathological radiopharmaceutical uptakes (PRU), variable grades from G1-3. More than half (57%) (n=50) were G3, mostly of them 65,7% (n=28) liver metastases. 26 PRU (30%) were G2 and 12 (11 %) G1. G3 abdominal uptake was found in 17 patients, G1-2 in 7. In eight cases was observed G2-3 cervicothoracic uptakes and G1 in another three. In whole group of 88 PRU, only six G1 lung uptakes was seen. Conclusions: Our dependable VFGS, based on the PRU features, is allowing an enough detailed analysis for further statistically evaluations and can be used for research purposes.
114: Importance of PET/CT in the Detection of a Second Septic Focus in a Patient with Sepsis: Case Report
M Agolti1, L Solari1
1Nuclear Medicine Center in Clinica Modelo, Parana, Entre Ríos, Argentine
Objectives: The location of a septic focus is very important in septic patients, particularly when they have multiple external central venous access which can cause other septics focus. Methods: Female patient 77 years old, in dialysis for chronic renal failure who underwent a surgery for a new arterio-venous access in right superior member which was malfunctioning , with a new right dialysis jugular catheter placed recently, 2 days ago. The woman is hospitalized in Intensive Care unit for the acute respiratory failure with bilateral pneumonia, a new central venous access was placed in left jugular vein. Haemoculture were positive for staphylococcus aureus meticiline sensitive, the patient improve fever and respiratory insufficiency but after two days she started with more fever and bad evolution. She was sent to nuclear medicine department for evaluation with FDG PET CT, looking for new septical focus. Results: In PET CT we found increased focal uptake (SUV max 3,7) in jugular dialysis access catheter. And air space consolidation is seen in both-pulmonary inferior lobes with very little FDG increased uptake, (SUVmax 0,5), which is reported as Neumonía in improvement. Catheter is removed and it had positive culture for SA with more than 15 UFC, after the catheter removal, and under the same antibiotics treatment the patient improved general state and is home discharged. Conclusions: Common complications of central venous access are thrombosis and infections, in this case it is crucial to remove the septic device to get patient improvement. Another etiology for new fever in a treated patient could be the presence of a distance septic focus. This case emphasizes the potential utility of FDG PET/CT scanning as a diagnostic tool in establishing the presence and extent of both the Central venous catheter infection and remote metastatic infectious focus. Should be indicated in septic patients with bad evolution.
115: Association of Radioactive Iodine Treatment with the Onset of Second Primary Malignancies: Myth or Reality?
Evanthia Giannoula1,2, Emmanouil Panagiotidis2, Anna Paschali2, Nikitas Papadopoulos2, Paraskevi Exadaktylou1,2, Stylianos Mandanas3, Pashalia Iliadou3, Kalliopi Pazaitou Panagiotou3, Vasiliki Chatzipavlidou2
1Academic Nuclear Medicine Department of Aristotle University of Thessaloniki,2Nuclear Medicine Department of Theagenio Cancer Hospital,3Department of Endocrinology, Theageneio Cancer Center, Thessaloniki, Greece
Objectives: The administration of therapeutic doses of 131I has been implicated with the onset of second primary malignancies (SPMs). The aims of the current study are: a) to estimate the incidence of second primary malignancy in patients with thyroid cancer b) the timing of occurrence in relation to thyroid cancer c) to analyze demographic, clinical characteristics and confounders of patients who were diagnosed with SPM after RAI and d) to investigate whether there is a causal association between radioiodine and the onset of second primary malignancies. Methods: All the records of patients with thyroid cancer attended in our hospital from a period of 25 years were retrospectively analyzed. Patients' inclusion criterion was the presence of two (or more if existed) primary malignancies in the same patient, one of which was thyroid carcinoma. Patients were categorized into 3 groups: group A included patients with thyroid cancer as the first diagnosis, group B those who were initially diagnosed with primary malignancy other than TC and group C included patients diagnosed and treated simultaneously both for thyroid cancer and other primary malignant tumors. Data analysis was performed with the SPSS statistical package (version 20.0, SPSSInc., Chicago, IL). Results: 165 patients [40 male (24.2%) and 125 female (75.8%)] met the eligibility criterion and were included in the current study. The whole population mean age (±SD) at diagnosis of the first diagnosed cancer (thyroid or any other cancer) was 51.6 ± 12.5 years and for the second primary, the mean age was 58.4 ± 11.8 years. 11.5% of the total population developed more than two cancers. Differentiated thyroid carcinoma (DTC) accounted for 90.3%. Myeloid, low differentiated, mixed cancers and anaplastictype contributed with 4.2%, 1.2%, 3% and 0.6% respectively for the malignant tumors of the thyroid gland. The other primary tumor was detected mainly in the breast (41.2%), skin (8.5%), larynx/vocal cord (6.1%) and large intestine (5.5%). The primary tumor site differed between two sexes; larynx/vocal cord, prostate and lung cancer were the most common types in males. Group A included 61 patients (37%), group B 75 (45.5%) and group C 29 patients (17.6%). Radioiodine therapy was administrated to 96 patients (62.3%): 38 from group A, 42 (56%) from B and 16 (55.2%) from group C (p=0.422). The mean age of thyroid cancer varied (group A: 49.3 ± 12.4, group B: 60.5 ± 10.7, group C: 55.2 ± 13.5 years, p <0.001). The second primary tumor appeared 9.6 ± 7.1 years after thyroid cancer onset (group A). Thyroid cancer occurred 8.4 ± 7.3 years after the second primary tumor (group B). 18,5% patients were diagnosed with a second primary malignancy in less than 2 years after RAI (29.4% breast Ca, 11,8% lung Ca) Patients from group A with a diagnosis of an SPM more than 2 years after RAI, developed breast Ca (40%), Colon Ca (7,7%), lung Ca (4,6%). Conclusions: The discovery of multiple malignancies in patients with TC is not uncommon, and has been associated with the administration of therapeutic doses of 131I. Co-occurrence ratio of thyroid cancer and SPM was relatively high, occurred in all organ systems, varying between two sexes. However, there was no statistically significant risk for SPM after radioactive iodine treatment in patients with DTC. Patients who initially developed thyroid cancer were younger. Thyroid cancer more often is preceded by other malignancies or occurs simultaneously rather than appears as the first malignant neoplasm. The appearance of a second primary tumor appears to be independent of complementary treatment with radioactive iodine. Genetic abnormalities are probably responsible for the appearance of a second primary tumor.
116: 18F-FDG PET/CT Imaging in Bone and Soft-Tissue Pediatric Sarcomas: Experience from the Children's Hospital of Greece
Stayros Kallivokas1, Ioannis Kandarakis1, Eleutherios Labdas1, Panagiotis Liaparinos1, Maria Gavra1, Maria Chasiotou1, Dimitrios Verganelakis1, Vasilios Papadakis1, Haroula Tsipou1, Natalia Tourkantoni1, Euthymia Rigatou1, Dimitrios Demenagas1, Vassiliki Lyra1
1Aghia Sofia' Children's Hospital of Greece - Elpida Oncology Unit, Athens, Greece
Objectives: Our study aim to assess the role of 18F-FDG PET/CT imaging in initial staging, restaging and/or recurrence detection in pediatric sarcoma and its correlation with conventional imaging modalities (CIMs). Although 18F-FDG PET/CT scan is still not mandatory, its use, in the current international protocols for the management of pediatric sarcoma, is recommended. Methods: We retrospectively evaluated all sarcoma patients from the start of operations of the new PET/CT department of the Children's Oncology Hospital of Greece. During a time period of 3.2 years (May 2016 – July 2019), 76 18F-FDG PET/CT whole-body scans were performed at 45 children and adolescents (mean age of 11.9 ± 4.8 years), 42 of them with a diagnosis of bone or soft-tissue sarcoma and 3 of them with a diagnosis of neurofibromatosis type 1 (NF-1). Bone sarcomas (26/45, 57.7%) included 15 Ewing sarcomas (ES) and 11 osteosarcomas (OS) of the pelvis and extremities. Soft-tissue sarcomas (18/45, 40.0%) included 2 extraskeletal ES, 11 rabdomyosarcomas (RMS), 2 angiosarcomas, 1 carcinosarcoma and 2 malignant peripheral nerve sheath tumors (malignant PNSTs). Almost half of the children (21/45, 46.6%) had 18F-FDG PET/CT scan during initial staging and slightly more than half (24/45, 53.3%) during restaging. All these children had contemporary CIMs (computed tomography, magnetic resonance, bone scan).Results: 18F-FDG PET/CT whole-body scans revealed more bone/bone marrow metastases compared to bone scan in 11 multiple bone metastatic sarcomas (8 bone sarcomas, 1 RMS, both extraskeletal ES) with a sensitivity of 100% (11/11) and a specificity of 97.0% (33/34), on a patient-based analysis. Bone scan was negative in two children with bone/bone marrow metastases (sensitivity of 81.8%, 9/11). However, in one of the two children with extraskeletal ES, two small focal bone metastases of the skull dome were revealed only by bone scan and not by 18F-FDG PET/CT scan. 18F-FDG PET/CT scan revealed lymphnode metastases, confirmed by biopsy, in 6 metastatic sarcomas (5 RMS, 1 OS), with a sensitivity of 85.7% (6/7) and a specificity of 100% (39/39). More false negative and false positive results were found by CIMs, with a combined sensitivity of 71.4% (5/7) and a specificity of 92.1% (35/38). Moreover, 18F-FDG PET/CT scan accurately revealed aggressive transformation of PNSTs in children with NF-1 and local recurrent disease in all except two cases, demonstrating a slightly higher accuracy (91.6%, 22/24) compared to CIMs (87.5%, 21/24). Although CIMs accurately revealed local recurrent disease in one of the children missed by 18F-FDG PET scan, they were inconclusive in three cases. Conclusions: Despite the small sample size of our study population, 18F-FDG PET/CT scan was the most powerful imaging tool in the detection of metastatic disease in pediatric sarcoma patients and highly accurate in the detection of local recurrent disease. In case of availability, 18F-FDG PET/CT scan should be performed due to its significant impact in modifying staging and consequently, treatment approach. Bone scan and even bone marrow biopsy could be safety omitted in some cases.
117: Stability and Efficacy of a Therapeutic Dose of Lu-Dotatate Prepared at a Remote Centralized Radiopharmacy: The Initial Clinical Results (Work in Progress)
Masha Maharaj, Siphiwe Gambushe, Nisaar Ahmed Korowlay, Otto Knoesen
1Department of Nuclear Medicine, Umhlanga Molecular Imaging and Therapy Centre, Netcare Umhlanga Hospital, Umhlanga, South Africa
Objectives: To assess the stability in using Lu Dotatate prepared from a centralized radiopharmacy then transported to a remote Therapy centre. This may create therapy opportunities for many remote centres in different countries with no direct access to onsite production. Methods: The current radiopharmacy, NTP Radioisotopes, is situated in Pelindaba, 634.5 km (approximately 394 miles) from the Therapy Centre (Umhlanga, Kwa-Zulu Natal). Pelindaba receives the Lu-177 on a Wednesday morning (from ITG in Germany), labels it with Dotatate using protocols obtained from two sources in Germany. The protocols are adapted to suit our conditions and the product is then suitably stabilised. This process is usually completed by 09h00. Standard doses of 7400 MBq are prepared. The doses are then taken by NTP Logistics to the airport (OR Tambo International airport) for clearance for the scheduled flight (duration of flight one hour). In Durban (King Shaka International airport), NTP logistics wait on site for the labelled product to be cleared and it is taken directly to the practice for administration. We analysed 19 therapies to determine the stability of the product from preparation to injection. The following were used for analysis: biodistribution of post therapy imaging vs diagnostic scan lesion uptake, and clinical therapeutic response. Injection, therapy and imaging protocols were standardized. Results: The mean time from production to injection was 4.93 hours (+/- 1.07 SD). The mode was 4.5 hours. The longest time between preparation and injection was 7.33 hours. The interim clinical evaluation of 6 patients who received Lu Dotatate therapy: 16% complete response (CR), 33% partial response (PR), 50% stable disease (SD). Conclusions: Our Centre experience with Lu Dotatate received from a central radiopharmacy suggests that the labelled compound remains stable both invivo and invitro with good target delivery and effective clinical outcomes.
118: Correlation of Reduced Metabolic Activity of Waldeyer's Tonsillar Ring and Thoracic Aortic Wall Inflammation in Smoking Status
E Panagiotidis1, N Papadopoulos1, A Pasxali1, P Mitsakis1, E Giannoula1, T Kalathas1, A Pipintakou1, V Chatzipavlidou1
1Department of Nuclear Medicine, Theageneio Cancer Center, Thessaloniki, Greece
Objectives: Waldeyer's tonsillar ring contributes significantly to the immune system acting as the first line of defence. Smoking affects immune system lessening its response, while it has been considered as an important factor for atheroma generation in aortic wall and therefore vessel inflammation. Aim of our study is to investigate the correlation of Waldeyer's tonsillar ring and aortic activity in regards to smoking. Methods: Two hundrend twenty two adult patients (222 pts) (138 men, median age 65 years; age range 26-87 years) were identified having undergone clinical 18F-FDG PET/CT examinations at our centre, with no history of head and neck carcinoma or lymphoma, neck lymph nodes or disease, tonsillectomy, recent upper respiratory tract infection, liver metastases, recent antibiotic medication intake and previous radiotherapy in the head and neck area. Metabolic activity (SUVmax) was measured in the thoracic aortic wall at the level of the aortic arch, liver parenchyma and Waldayer's ring (a. Right palatine tonsil, b. Left palatine tonsil, c. Lingular tonsil, d. Nasopharyngeal tonsil). Pts have been categorized based on their smoking status as non-smokers (group 1), smokers (group 2), ex-smokers (group 3). Results: Sixty (27%, 36 men) out of 222 pts were no smokers, 59 pts (26.6%, 37 men) were smokers and 103 pts (46.4%, 65 men) were exsmokers. Using ANOVA there was a significant statistical difference of the mean average SUVmax among the three groups in the Waldeyer's tonsillar ring with the lowest for the group 2, followed by group 3: a. Right palatine tonsil (Group 1: 4.62, Group 2: 3.82, Group 3: 4.1, p<.006) b. Left palatine tonsil (Group 1: 4.65, Group 2: 3.86, Group 3: 4.11, p<.007) c. Lingular tonsil (Group 1: 4.62, Group 2: 3.82, Group 3: 4.1, p<.017) d. Nasopharyngeal tonsil (Group 1: 4.61, Group 2: 3.81, Group 3: 4.1, p<.037). Multivariate analysis of the other demographic variables confirmed that smoking acts as an independent factor predicting lower SUVmax for Waldeyer's tonsillar ring. The mean average metabolic activity of thoracic aortic walls at the level of aortic arch for the smoking group was higher (SUVmax: 2.9) compared to the non-smoking group (SUVmax: 2.57) (p=.001). The latter interestingly was similar with the ex-smoking group (SUVmax: 2.55). Conclusions: Smokers have lower levels of 18F-FDG activity in Waldeyer's ring compared to non-smokers probably reflecting the suppressive effect of smoking on tonsillar immunity. We also found highermetabolic activity of thoracic aortic walls in smokers compared to non-smokers.
119: Dr Saul Hertz and The Discovery of The Medical Uses of Radioiodine (RAI)
1Dr. Saul Hertz Archives
Objectives:1. Understand the discover of the initial uses of radioiodine (RAI) 2. Understand the origins and methodology of dosimetry-based radioiodine therapy of thyroid cancer 3. Analyze the legacy of the medical uses of RAI. Methods: A poster capturing the history of Dr. Saul Hertz, as the originator of the medical uses of radioiodine (RAI). The poster features key correspondence, newspaper articles, journal entries, vivid photos and the Data Charts of the first series of patients diagnosed and treated with RAI. The primary evidence- based documentation verifies Dr. Hertz's conception of the use of RAI to treat hyperthyroidism and thyroid cancer. Dr Hertz and his MIT collaborator were the first and foremost to develop the experimental data and apply RAI in the clinical setting. They made use of dosimetry that is the foundation of today's precision oncology. Results: Documentation of Saul Hertz, who conceived and brought from bench to bedside the medical uses of radioiodine( RAI). Dr Hertz overcame many challenges to bring his paradigm changing work to fruition. The poster serves as informational and provides inspiration for today's practitioners and researchers. Conclusions: Dr Saul Hertz's discovery of the medical uses of radioiodine is a seminal medical discovery of the 20th century. Radioiodine is the first and Gold Standard of targeted therapy as well as the first theranostics to diagnose and treat cancer.
120: Ongoing Risk Stratification for Differentiated Thyroid Cancer: Is Stimulated Serum Thyroglobulin before Radioiodine Ablation, the Most Potent Risk Factor?
Paraskevi Exadaktylou1,2, Nikitas Papadopoulos2, Evanthia Giannoula1,2, Athanasios Siolos3, Anna Paschali2, Emmanouil Panagiotidis2,Theodoros Kalathas2, Georgia Koutsouki1, Kalliopi Pazaitou-Panayiotou3, Ioannis Iakovou1, Vasiliki Chatzipavlidou2
13rd Academic Nuclear Medicine Department of Aristotle University of Thessaloniki, Papageorgiou Hospital,2Nuclear Medicine department of “Theagenio” Cancer Hospital of Thessaloniki,3Department of Endocrinology, Theageneio Cancer Center, Thessaloniki, Greece
Objectives: The discussion about which prognostic factors are the most reliable to adequately assess the risk of relapse in differentiated thyroid cancers (DTC) is still ongoing. Evidence supports the prognostic value of preablative stimulated thyroglobulin (Tg) for recurrent and persistent disease. The correlation of Tg with therapeutic response however has not been extensively studied. The objective of this study is to investigate the correlation of Tg and the trend of serial preablative thyroglobulin measurements (DTg) with the response to treatment restaging system proposed in 2015 American Thyroid Association guidelines. Methods: We conducted a retrospective study on patients with DTC who underwent total thyroidectomy and radioactive iodine (RAI) ablation in a tertiary referral hospital. Patients with missing data or positive anti-Tg Abs were excluded from the study and the rest were divided in three groups in terms of ps-Tg levels: group 1, ps-Tg<1 ng/ml (n=48), group 2, 1≥ps-Tg≤10 ng/ml (n=48), group 3, ps-Tg >10 ng/ml (n=19). Responses to therapy were divided in excellent (ER), biochemical incomplete (BIR), indeterminate (IR) and structural incomplete response (SIR) according to the new response to treatment system. Results: 115 patients were followed for a median of 60 months. SIR was detected in 3.4% in group 1, 8% in group 2, 20% in group 3. However, results were not statistically significant in the studied series (χ2=3.435, P=0.179). Conclusions: Preablative thyroglobulin may be correlated to therapeutic response.
121: Clinical Experience with Radium-223 in the Treatment of Patients with Advanced Castrate-Resistant Prostate Cancer and Bone Metastases
Exadaktylou Paraskevi1, Papadopoulos Nikitas1, Paschali Anna1, Panagiotidis Emmanouil1, Evanthia Giannoula1,Theodoros Kalathas1, Vasiliki Chatzipavlidou1
1Department of Nuclear Medicine, Theageneio Cancer Center, Thessaloniki, Greece
Objectives: To present our clinical experience and to identify baseline features that may predict outcome in 223-Radium therapy (223Ra). Methods: We retrospectively reviewed 30 patients with metastatic castration-resistant prostate cancer with >2 bone metastases and no visceral metastases who were administered in total 112 cycles of 223Ra in our department. The following parameters were evaluated prior, during and after 223Ra treatment: blood values, prostate-specific antigen (PSA), alkaline phosphatase (ALP), Eastern Cooperative Oncology Group (ECOG) performance status and pain score (WHO criteria). Skeletal burden on bone scan and use of prior therapies were also evaluated. Patients were followed up for median 6 months (1-13 months range). Results: The planned course of six cycles was completed in eleven patients (37 %), was interrupted in thirteen patients (43%), while six patients (20%) were still undergoing 223Ra treatment at the time of analysis. In the group that completed six cycles of 223Ra therapy, PSA and ALP values increased in nine pts (81%) (mean PSAdt=2.6mo, mean ALP increase=47%), did not demonstrate significant alteration in one patient and decreased in one patient with concomitant reduction in pain score. Patients tolerated well 223Ra therapy with mild adverse events. Four patients continued with other therapies after completion of 6 cycles 223Ra due to clear disease progression. Another patient died 3 months after completion of 223Ra treatment due to disease progression and concomitant bone marrow failure.In thirteen patients 223Ra treatment discontinued after median=2 cycles (range=1-4) due to disease progression and one or more of the following: hematologic toxicity (n=8, grade 2 anemia, grade 3 thrombocytopenia), declining ECOG status by two points (n=6) and severe side effects (n=2, nausea, anorexia, fatigue). Four patients were switched to another therapy and five out of thirteen patients died at a mean time of 8 months after cessation of 223Ra treatment due to disease progression. None of the patients presented acute skeletal events. Patients with borderline hematologic values, significant skeletal disease burden (>50foci), short PSAdt during initial evaluation and those who had received external beam radiation therapy, were more susceptible in hematologic toxicity /other adverse events and completed lesser cycles of 223Ra. Conclusions: Our initial experience on the use of 223Ra treatment denotes that patients with less aggressive and lower burden of disease having sufficient marrow reserves are more likely to complete 223Ra therapy and achieve better therapeutic outcomes.
122: Risk and Progression Factors for Differentiated Thyroid Cancer: A Retrospective Cohort Study in Low Risk Patients
Evanthia Giannoula1,2, Nikitas Papadopoulos2, Paraskevi Exadaktylou1,2, Gerakina Giannoula3, Vasiliki Chatzipavlidou2, Argyrios Doumas1, Ioannis Iakovou1
1Academic Nuclear Medicine Department of Aristotle University of Thessaloniki,2Nuclear Medicine Department of Theagenio Cancer Center of Thessaloniki, Greece,3Faculty of Medicine Comenius University, Bratislava, Slovakia
Objectives: Differentiated thyroid carcinomas (DTC), account for almost 90% of all thyroid carcinomas. The prognosis of DTC is generally good, depending on the biologic behavior of the tumor and on the appropriate initial treatment. However, a considerable number of patients, approximately have persistent or recurrent disease. The aim of this study is to investigate the factors (demographic, clinical, pathologic, treatment administrated characteristics) influencing treatment response or recurrence on pT1-2, Nx, M0 DTC patients, to determine the imaging modalities used to investigate treatment response and to suggest a prognostic model to a greater understanding of tumor behavior and clinical outcomes for DTC. Methods: Our cohort comprised all 420 patients with classical or follicular variants of papillary DTC or with follicular DTC, and with pT1–2, Nx, M0 status pre-ablation, who underwent a first radioiodine ablation procedure at our institutions. TSH levels were assessed for all patients at ablation time after stimulation (52,4% rhTSH) and were determined to be over 30 mIU/L for the whole cohort, thyroglobulin (Tg), anti-thyroglobulin autoantibodies (TgAb) and anti-thyroperoxidase autoantibodies (Anti-TPO), were measured as well. Thyroid remnant in post therapy WBS was retrospectively given classification scores based on visual assessment of the number of foci of thyroid bed uptake and their overall intensity on post-ablation WBS. Response to therapy was assessed with the following diagnostic methods: 131I SPECT/CT, US, 18F FDG PET/CT, MRI. Results: The mean age of our cohort patients was 47.36 years old. Cohort patients overwhelmingly comprised patients with papillary type including both classical and follicular variants while only 2.4% had follicular thyroid cancer. Despite favorable histotypes and primary tumor classifications, a large proportion of patients had characteristics suggested higher risk or uncertainty regarding risk, or both. Over one-fourth of the cohort had T2 disease (26.2%). Multifocality was detected in 33.4% patients. Invasiveness of the primary tumor was documented for 9.5% of the patients. Although 42.9% of the patients had Tg concentration <1 μg/L, in 14.3% of them Tg levels exceeded 10 μg/L. In addition, the majority of our cohort (69%) were TgAb-positive, with a mean TgAb concentration of 84.89 IU/mL. Virtually all patients had evidence of postsurgical thyroid remnant (thyroid bed uptake was absent in only 4.8 % of patients). Over half of the patients showed evidence of recurrent disease, during follow up which was significantly correlated with preablation Tg and antiTg levels (p=0.014 and 0.023 respectively), invasiveness, multifcocality and remnant scoring (p=0.024, 0.013 and 0.022 respectively). Finally a significant relation was found between recurrence and diagnostic method (p=0.001). Conclusions: A number of factors with potential prognostic implications for DTC have emerged and should be addressed. However, their role and possible inclusion in new staging systems has yet to be determined not only for achieving an adequate therapeutic approach, but also for avoiding overtreatment of low-risk patients.
123: Yttrium-90 Radiation Synovectomy in Knee-Activated Osteoarthritis and Rheumatoid Arthritis: A Prospective Evaluation at 6 and 18 Months
Ioannis Iakovou1, Dimitrios Jimmy Kotrotsios1, Evanthia Giannoula1, Christos Sachpekidis1, Konstantinos Badiavas1, Dimitrios Potoupnis1
1Academic Nuclear Medicine Department of Aristotle University of Thessaloniki, Greece
Objectives: Not only to assess, but also to compare the outcome of yttrium-90 radiation synovectomy (RSO) in patients with knee activated osteoarthritis (aOA) and rheumatoid arthritis (RA) in a 18 months follow-up period. Methods: We prospectively evaluated for a 18 months period 104 patients, 52 with osteoarthritic knee pain resistant to conventional therapy and 52 with rheumatoid knee arthritis referred for intraarticular yttrium-90 treatment, due to synovial inflammation, as demonstrated by early-phase bone scintigraphy. The outcome of treatment was evaluated by a questionnaire, reporting the relief of limiting the daily activities knee pain, as a percentage of the pretherapeutic joint discomfort, using a Visual Analogue Scale (VAS). Results: The overall response rate for all treated joints was 65% at 6 months and 60% at 18 months (P = ns). The mean improvement rate for the treated joints in RA was higher than aOA in total, with better results achieved in the cases of radiological minimal changes, but the mean VAS improvement for the 11 patients with early stage aOA (earlyOA) was comparable to RA at any time of evaluation, as shown in the following table. Conclusions: Yttrium-90 radiation synovectomy exerts a beneficial therapeutic effect in patients suffering of knee synovial inflammation, providing better results in rheumatoid arthritis than in osteoarthritis. Interestingly, the performance of synovectomy in patients with radiographicalyearly-stage activated osteoarthritis tends to be almost similar to rheumatoid arthritis.
124: Radiosynoviorthesis after Surgery in the Treatment of Patients with Ankle Pigmented Villonodular Synovitis
Ioannis Iakovou1, Panagiotis Symeonidis1, Dimitrios Jimmys Kotrotsios1, Evanthia Giannoula1, Christos Sachpekidis1
1Academic Nuclear Medicine Department of Aristotle University of Thessaloniki, Greece
Objectives: Pigmented villonodular synovitis (PVNS) of the ankle is a very rare, locally aggressive, proliferative disorder. Although surgical excision represents the standard curative treatment, PVNS relapse rate is high. We present our experience of five patients suffering from PVNS of the ankle, who were treated by arthroscopic debridement and adjuvant radiosynoviorthesis (RSO). Methods: Five young athletes (range 20-36 years) with histopathological diagnosis of PNVS of the ankle joint underwent arthroscopic synovectomy (4 arthroscopic, 1 open) followed by intraarticular RSO with the radiopharmaceutical erbium-169 (169Er). Patients were evaluated with the Foot Function Index (FFI) and a visual analog scale (VAS) for pain. Median follow up period was 37 months (range 26 – 44 months). Results: All five patients reported pain relief with improvement of their daily activities. In particular, the median FFI decreased from 77% (range 71.0 - 84.5%) pre-RSO, to 0.5% (range 0 – 6%) after RSO. Respectively, the median VAS score decreased from 4 (range 3-7) to 0 (range 0-1). Throughout the follow-up period there were no major complications regarding either therapeutic intervention (arthroscopic debridement, RSO). Conclusions: Adjuvant RSO with 169Er following surgical excision is effective and safe in the treatment of PVNS of the ankle. Level of Evidence: Level IV, therapeutic case series.
125: Predictive Factors of Failure in Radioiodine Therapy of Graves' Disease
Evanthia Giannoula1, Dimitrios Jimmys Kotrotsios1, Christos Sachpekidis1, Argirios Doumas1, Nikitas Papadopoulos1, Paraskevi Exadaktylou1, Konstantinos Badiavas1, Emmanouil Papathanasiou1, Ioannis Iakovou1
1Academic Nuclear Medicine Department of Aristotle University of Thessaloniki, Greece
Objectives: To retrospectively evaluate any factors that may limit the success rate of radioiodine therapy (RIT) in Graves' disease patients. Methods: Nighty six Graves' disease patients submitted for RIT in ourdepartments in a two years' period (2017-2018) enrolled in the study. A fixed dose of 12mCi (444MBq) of 131I was administered to all patients after antithyroid drug administration, in order to achievenormal FT3 serum values. Thyroid function outcome were assessed 10-12 months after RIT. Patient's sex, age, evidence of ophthalmopathy, ultrasound measurement of the thyroid volume and 99mTc thyroid uptake % prior to RIT were considered as potential interference factors for success. Multiplelogistic regression analysis was performed. Results: After RIT, 11 patients (11%) became euthyroid, 61 patients (63%) became hypothyroid and 24 (25%) remained hyperthyroid. No statistically significant association between treatment outcome and sex (p = 0.56), age (p=0.61) and ophthalmopathy (p =0.72) was found. On the contrary, 99mTc thyroid uptake % and thyroid volume were associated with success rate (thyroid uptake<13,4%, p< 0.001, odds ratio 3.9 and thyroid volume <61 ml, p < 0.001, odds ratio 7.6). Conclusions: A radioiodine fixed dose of 12 mCi (444MBq) for treatment of Graves' disease seems to be a practical and effective approach. However, this administration is not recommended for patients with large goiters and a high pre-RIT thyroid uptake, due to high failure rates observed in patients with thyroid volume more than 61ml and thyroid uptake higher than 13,4%.
126: 18F-FDG PET-CT in the Management of Patients with Metastatic Cancer with Unknown Origin
Raluca Mititelu1, Catalin Mazilu1, Dragos Cuzino1, Magdalena Iriciuc1, Carmen Tipar1, Mirela Tudoran1, Teodora Mititelu1
1Central University Emergency Military Hospital, Bucharest, Romania
Objectives: The aim of this paper was to reveal the importance of 18F-FDG PET-CT in the evaluation of patients with documented metastasis but with non- detectable primary tumor. Methods: We performed a retrospective analyse and we reviewed the cases of patients referred to our PET-CT department with documented metastasis but with non- detectable primary tumor after complete and extensive evaluation. We performed 18F-FDG-PET-CT in 36 patients referred to our department for metastatic disease with different localization, with no primary tumor previously detected. Each case was reviewed and patients with incomplete evaluation were excluded from the analyse. Results: Epidemiologic data were reviewed for all patients. We have divided patients in two groups: group 1 with 18F-FDG uptake at the site of documented metastasis (72% of included patients) and group 2 in which no focal uptake was identified. In group 2, there were 5 patients in which there was a unique metastatic lesion which was surgically removed prior to examination, for histologic evaluation. In group 1 there were 12 patients (57%) in which PET-CT was positive at different sites and those sites were consider for further investigations including biopsy. Conclusions: FDG-PET-CT is an important tool for cancer evaluation. Despite low specificity of glucose uptake, FDG-PET-CT can change management in an important proportion of patients with unidentified primary cancer site either with indicating the origin of primary tumor or providing promising sites for biopsy.