|ABSTRACTS OF THE 14TH INTERNATIONAL CONFERENCE ON RADIOPHARMACEUTICAL THERAPY (ICRT 2019) & WORLD ASSOCIATION OF RADIOPHARMACEUTICAL AND MOLECULAR THERAPY (WARMTH), 22-25 AUGUST 2019, NANJING
|Year : 2019 | Volume
| Issue : 3 | Page : 317-323
|Date of Web Publication||9-Aug-2019|
|How to cite this article:|
. Oral Presentations. World J Nucl Med 2019;18:317-23
| Oral Presentations|| |
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First-in-Human Molecular Imaging Using Ga-68 Labeled Novel Somatostatin Receptor Antagonist NODAGA-LM3 in Paraganglioma Patients
Aviral Singh1, Jingjing Zhang1, Harshad R Kulkarni1, Christiane Schuchardt1, Dirk Mueller2, Helmut Maecke3, Richard P Baum1
1Theranostics Center for Molecular Radiotherapy and Precision Oncology, Zentralklinik Bad Berka, 2Department of Radiopharmacy, Zentralklinik Bad Berka, Bad Berka, 3Department of Nuclear Medicine, University Hospital Freiburg, Freiburg im Breisgau, Germany
Objectives: The aim of this study was to analyse the diagnostic utility and clinical safety of the somatostatin receptor (SSTR) antagonist Ga-68 NODAGA-LM3 (NODAGA = 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid, LM3 = [p-Cl-Phe-cyclo(D-Cys-Tyr-D-4-amino-Phe(carbamoyl)-Lys-Thr-Cys)D-Tyr-NH2]) for PET/CT imaging of paraganglioma patients, compared to the SSTR agonist Ga-68 DOTATOC. Methods: From March 2017 to June 2018, ten paraganglioma patients (7 males, 3 females; age 35 - 66 y, mean age 48.4 ± 11.0 y) underwent PET/CT based molecular imaging with Ga-68 NODAGA-LM3 following written informed consent. Whole-body PET/CT image acquisitions were performed at 45-55 min after intravenous injection of Ga-68 NODAGA-LM3 (mean activity = 285 MBq, radiochemical purity > 95%). The acquired PET/CT images were analyzed qualitatively (visual assessment) and semi-quantitatively (SUVmax and SUVmean) and compared with those of Ga-68 DOTATOC PET/CT, performed either before (n=6) or after (n=4) the Ga-68 NODAGA-LM3 studies. Regions of interest were drawn manually over target lesions (TL) as well as reference tissues (RT), namely, liver, kidney, spleen, and gluteus muscle. Tumor-to-background ratios (TBR) were calculated using a volume of interest (VOI) based SUVmax for TL and SUVmean for RT for the corresponding Ga-68 labeled NODAGA-LM3 and DOTATOC studies. To assess the clinical safety of Ga-68 NODAGA-LM3, patients were clinically observed for possible adverse reactions and laboratory analysis (complete blood counts, liver and renal function tests) was performed before the study and during the next scheduled follow-up. Results: Ga-68 NODAGA-LM3 PET/CT showed positive findings in all (10/10) patients with SUVmax ranging between 2.51-299.95 [mean ± SD, 53.78 ± 183.2]. The comparative physiological uptake of Ga-68 NODAGA-LM3 to Ga-68 DOTATOC (SUVmean [mean ± SD], Ga-68 NODAGA-LM3 : Ga-68 DOTATOC) in the liver, spleen, kidneys, bone marrow were 5.55 ± 1.57 vs. 9.73 ± 2.30 (P < 0.01), 20.47 ± 6.93 vs 31.14 ± 7.50, 12.88 ± 4.57 vs 10.28 ± 2.02, and 1.16 ± 0.36 vs 0.98 ± 0.49, respectively. Compared with Ga-68 DOTATOC PET/CT, Ga-68 NODAGA-LM3 PET/CT detected significantly more lesions (243:177) overall, including lymph nodes (27:18), liver (11:3) and bone metastases (190:143). With reference tissue as background, LM3 associated TBR were TL-liver 15.7, TL-kidney 6.8, TL-spleen 5.4, TL-gluteus 156.5. The mean value of all target lesions (AL) compared to RT were AL-liver 8.9, AL-kidney 3.8, AL-spleen 2.4, and AL-gluteus 57.5. No clinical or biochemical adverse events were reported in relation to the application of Ga-68 NODAGA-LM3. Conclusion: This first-in-human study demonstrates that PET/CT imaging with the SSTR-antagonist, Ga-68 NODAGA-LM3, is able to detect significantly more SSTR expressing lesions with a higher contrast compared to the SSTR agonist, Ga-68 DOTATOC. Due to the distinctively higher TBR, Ga-68 NODAGA-LM3 was particularly capable of detecting more liver and bone metastases. The biodistribution of the antagonist NODAGA-LM3 was similar to that of the agonist, DOTATOC, and its intravenous application was safe and well tolerated by all patients during and after PET/CT imaging. These results emphasize the immense potential of the SSTR antagonist Ga-68 NODAGA-LM3 for Theranostics (diagnostics and possible targeted SSTR-therapy) of patients with paraganglioma.
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The Roles of Positron Emission Tomography/Computed Tomography in Predicting the Prognosis of Chimeric Antigen Receptor T Cell Therapy Treated Patients with Diffuse Large B Cell Lymphoma
Chong Yang Ding1, Yi Xin Zou1, Tian Nv Li1
1Department of Nuclear Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China
Chimeric antigen receptor T cell (CAR-T) therapy is an effective treatment for relapsed or refractory (r/r) diffuse large B cell lymphoma (DLBCL) patients. Positron emission tomography/computed tomography (PET-CT) played an important role in DLBCL in the era of immunochemotherapy, while its value in CAR-T therapy remained undetermined. In this study, we retrospectively explored the role of PET-CT in 13 r/r DLBCL patients who were receiving CAR-T therapy. Parameters reflecting tumor metabolic burden, such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG), were measured before and after CAR-T treatment. Patients with larger baseline MTV or longer sum of longest diameters had shorter overall survival (OS) than those with low tumor burden. Patients who achieved complete response (CR), partial response (PR) and minor response determined by response evaluation criteria in lymphoma (RECIL) at 12 weeks had superior progression-free survival and OS than those with no response. In addition, we found that 2 patients with residual masses classified as PR by contrast-enhanced CT had complete metabolic response by PET-CT imaging. In general, in r/r DLBCL patients, PET-CT at baseline and at 12 weeks after CAR-T therapy could predict the prognosis, while early PET-CT at 4 weeks failed to predict long-term outcomes. CR rate was higher when detected by PET-CT than contrast-enhanced CT. Therefore, PET-CT showed great value in prognosis assessment and response evaluation in CAR-T-treated r/r DLBCL patients.
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Peptide Receptor Radionuclide Therapy Using Somatostatin Receptor-Antagonists: Biodistribution and Dosimetry of Lu-177 DOTA-LM3 Compared to Lu-177 DOTATOC
Christiane Schuchardt1, Stefan Wiessalla1, Aviral Singh1, Jingjing Zhang1, Harshad R Kulkarni1, Dirk Müller1, Richard P Baum1
1Theranostics Center for Molecular Radiotherapy and Molecular Imaging (PET/CT), Bad Berka, Germany
Aim: Since over two decades somatostatin receptor (SSTR) agonists are being used for molecular imaging of SSTR-expressing tumors. Clinical studies with SSTR-antagonist based PET/CT have shown a higher tumor detection rate in SSTR-expressing tumors than PET/CT applying the SSTR-agonist. Aim of this study was to determine the kinetics and dosimetry in patients undergoing peptide receptor radionuclide therapy (PRRT) using Lu-177 labeled DOTA-LM3 in comparison to DOTATOC. Methods: We examined 328 patients with metastasized neuroendocrine tumors. 317 patients received 7+/-1 GBq Lu-177 DOTATOC (SSTR expression verified before by Ga-68 DOTATOC PET/CT) and 11 patients were treated with 5.9+/-1.2GBq Lu-177 DOTA-LM3 (SSTR expression verified before by Ga-68 NODAGA-LM3 PET/CT). The biodistribution was determined based on planar whole-body scans & SPECT/CT and dosimetric calculations were performed using OLINDA software (MIRD Scheme). To analyze the kinetics, we used the following parameters (median values): effective half-life (hours) and uptake (%IA, fraction of injected activity), which were calculated using the fit of the time-dependent activity curve to a mono- or bi-exponential function. Results: The median uptake 20h p.i. of Lu-177 DOTA-LM3 was noticeably higher: Whole body: TOC 19%, LM3 72%; Kidneys: TOC 1.7%, LM3 6%; Spleen: TOC 1%, LM3 4%; Tumor: TOC 0.05%/ml, LM3 0.12%/ml. DOTA-LM3 showed a longer whole-body effective half-life (76h) compared to DOTATOC (50h), the same was true for the kidneys (LM3 85h, TOC 62h), spleen (LM3 90h, TOC 73h) as well as metastases (LM3 107h, TOC 73h). Resulting from the longer effective half-lives and the higher uptakes, mean absorbed organ- and tumor doses were higher for DOTA-LM3: Whole body: TOC 0.03Gy/GBq, LM3 0.12Gy/GBq; Kidneys: TOC 0.6Gy/GBq, LM3 2.0Gy/GBq; Spleen: TOC 0.7Gy/GBq, LM3 3.3Gy/GBq; Tumor: TOC 6Gy/GBq, LM3 21Gy/GBq. Concerning malignant lesions we distinguished between liver and bone metastases. Liver lesions demonstrated the highest uptake and longest effective half-life for therapy using DOTA-LM3 (0.14%/ml and 110h). The highest tumor dose was therefore estimated for liver metastases in case of DOTA-LM3 (TOC 7Gy/GBq, LM3 26Gy/GBq). Conclusions: As already proven for PET/CT examinations, these first results show a higher accumulation of the antagonist DOTA-LM3 in tumor lesions. Despite the higher mean absorbed organ and tumor doses, PRRT using DOTA-LM3 seems to be promising because much higher tumor doses can be achieved. However, future studies, including a larger number of patients, must confirm these preliminary results.
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18FAlF-PSMA-11 as a Novel Tracer for Theragnostic and Initial Staging of High Risk Prostate Cancer Patients
Gerardo dos Santos1, Monica Rodriguez Taroco1, Enzo Silvera2, Laura Vera3, Juan Hermida2, Eugenia De Marco2, Sergio Rodriguez2, Omar Alonso1
1CUDIM, 2Centro de Medicina Nuclear, Hospital de Clinicas, Montevideo Uruguay, 3National Institute of Oncology (INCA), Montevideo, Uruguay
177Lu-PSMA-617 is increasingly becoming a valuable therapeutic option in patients with castration-resistant metastatic prostate cancer, while [18F] AIF-PSMA-11 (a novel tracer produced in our Centre) could replace 68Ga-PSMA-11 for PET/CT imaging prior to therapy. The aim of this study was to compare the biodistribution of 18F-AlF-PSMA-11 and 177Lu-PSMA-617 before first cycle of therapy in patients with metastatic castration resistant prostate cancer. Besides, we compared the diagnostic performance of 18F-AlF-PSMA-11 and 68Ga-PSMA-11 for the detection of metastasis in patients with high-risk prostate cancer at initial staging. Four patients underwent 18F-AlF-PSMA-11 PET/CT 60 minutes after radiopharmaceutical injection (4.0 MBq/kg). After two weeks they received 6.0 GBq of 177Lu-PSMA-617. Post-therapy SPECT/CT images were performed after 48 hours. Additionally, 59 patients (mean age: 64 years; range: 51-78 years) with high-risk biopsy proven prostate cancer prior therapy (Gleason ≥ 7; mean PSA: 27.95 ng/mL, range: 1.7-137.0 ng/mL) underwent routine 18F-AlF-PSMA-11 and 68Ga-PSMA-11 PET/CT scanning within a time window of 1-2 weeks. Histopathology, correlative imaging and/or clinical follow-up were considered as reference standard. Biodistribution and visual quality was very similar for 18F-AlF-PSMA-11 and 177Lu-PSMA-617. Moreover, 22/59 patients (37.29%) had evidence of metastatic disease by at least one PET tracer. We calculated a sensitivity and specificity of 0.69 (95% CI: 0.48-0.85); 0.77 (95% CI: 0.57-0.91) and 0.96 (95% CI: 0.84-0.99); 0.96 (95% CI: 0.83-0.99) for 68Ga-PSMA-11 and 18F-AlF-PSMA-11, respectively. 18F-AlF-PSMA-11 PET/CT is a potential imaging technique for the evaluation of metastasis of prostate cancer patients at initial staging. 18F-AlF-PSMA-11 and 177Lu-PSMA-617 seem to be a potential theragnostic tandem.
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Preliminary Clinical Experience with Three Novel Peptide Based Radiotracers: 68Ga-NeoBOMB1, 68Ga-NODAGA-RGD and 111In-CP04
Gianpaolo Di Santo1, Hanna Svirydenka1, Roland Haubner1, Clemens Decristoforo1, Bernhard Nilica1, Christian Uprimny1, Elisabeth von Guggenberg1, Irene Virgolini1
1Department of Nuclear Medicine, Medical University Innsbruck, Tyrol, Austria
In prospective phase I/II clinical studies the safety and tolerability of different peptide-based radiotracers was evaluated. NeoBOMB1, a peptide antagonist targeting-gastrin-releasing peptide receptors (GRPR), has high potential for diagnosis and therapy of different tumour entities. NODAGA-RGD targeting integrin αvβ3 has potential indication in the planning and controlling anti-angiogenic tumour therapies. CP04, a minigastrin analogue targeting cholecystokinin-2 receptors, is promising for diagnosis and therapy of medullary thyroid cancer. For the preliminary evaluation of the radiotracers selected patient groups were enrolled in the studies. PET/CT with 68Ga-labelled NeoBOMB1 was performed in patients with advanced TKI-treated gastrointestinal stromal tumours at an injected dose of 150 MBq. Images were acquired 1 and 2 h p.i. PET/CT imaging with 150-185 MBq 68Ga-NODAGA-RGD was performed in patients with hepatocellular carcinoma at 10 min, 30 min and 75 min p.i. SPECT/CT imaging with 111In-CP04 was carried out in patients with advanced MTC up to 24 h p.i. The intravenous injection of all three radiotracers was well tolerated with no side effects. For 68Ga-NeoBOMB1 physiological uptake was revealed in pancreas, liver and kidney. 68Ga-NODAGA-RGD showed highest physiological uptake in kidney and spleen. 111In-CP04 showed physiological uptake in stomach, kidneys and intestine. In general a low background activity was found and first insights ware gained into the biodistribution profile and tumour targeting properties. The prospective phase I studies with the radiotracers have been successfully finalised. Due to the low background activity and limited uptake in critical organs the peptides show high potential for oncological application in diagnosis or therapy.
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Noninvasive Imaging of Programmed Death Ligand 1 Expression in Tumors with Positron Emission Tomography Using a Highly Specific Nanobody-based Radiotracer
Jianguo Lin1, Gaochao Lv1, Ling Qiu1, Qingzhu Liu1
1Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, China
Background: Although immunotherapy through programmed death 1 / programmed death ligand 1 (PD-1/PD-L1) checkpoint blockade has shown impressive clinical outcomes, not all patients respond to it. Recent studies have demonstrated that the expression level of PD-L1 in tumors is one of the factors that correlate with the PD-1/PD-L1 checkpoint blockade therapy. Thus, it is essential to analyze the PD-L1 expression in patients prior to treatment, which may avoid the ineffective cure and improve the success rate of immunotherapy. Herein, a novel 68Ga-labeled nanobody tracer, 68Ga-NOTA-Nb109, was designed and developed for specific and noninvasive imaging of PD-L1 expression in the melanoma-bearing mice model. Methods: The nanobody Nb109 was labeled with the radionuclide 68Ga through a NOTA chelator. In vitro binding assay was performed to assess the affinity and binding epitope of Nb109 to PD-L1. The clinical application value of 68Ga-NOTA-Nb109 was evaluated by the stability assay, biodistribution and pharmacokinetics studies as well as positron emission tomography (PET) imaging, autoradiography and immunohistochemical staining studies on the tumor-bearing models with different PD-L1 expression. Results: The tracer was obtained with >95% radiochemical yield and >98% radiochemical purity in 10 min, which showed a specific high affinity to PD-L1 with a KD value 2.9 × 10-9 M. In vitro binding assay demonstrated that Nb109 bind different epitopes with PD-1, in other words, Nb109 was a non-blocking nanobody toward PD-L1. All the biodistribution, PET imaging, autoradiography and immunohistochemical staining studies revealed that the tracer 68Ga-NOTA-Nb109 specifically accumulated in PD-L1 positive tumor (A375-hPD-L1) over PD-L1 negative tumor (A375, MCF-7) with a maximum uptake of 5.0 ± 0.35 %ID/g at 1 h. The radioactivity could be fast washout from the muscle and blood and stable in tumor, resulting in an excellent tumor-to-back ground contrast at all-time point over 10 min to 2 h. Conclusions: This radiotracer has great potential to evaluate the PD-L1 status of tumors by PET imaging studies and may ultimately benefit to predict therapeutic effect targeting immune checkpoints.
This work was financially supported by Natural Science Foundation of Jiangsu Province (BK20181128), the 333 Project of Jiangsu Province (BRA2016518, LGY2018086), the Key Youth Medical Talent Project of Jiangsu Province (QNRC2016626 and QNRC2016629).
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Prognostic Value of 18F-FDG Positron Emission Tomography/Computed Tomography in a Large Cohort of 495 Patients with Advanced Neuroendocrine Neoplasms Treated with Peptide Receptor Radionuclide Therapy
Jingjing Zhang1, Harshad R Kulkarni1, Aviral Singh1, Christiane Schuchardt1, Richard P Baum1
1THERANOSTICS Center for Molecular Radiotherapy and Precision Oncology, ENETS Center of Excellence, Zentralklinik Bad Berka, Bad Berka, Germany
Background: The aim of this study was to evaluate the role of 18F-FDG PET/CT in a large cohort of patients with advanced metastatic neuroendocrine neoplasms (NENs) who were treated with peptide receptor radionuclide therapy (PRRT) in a long-term follow-up beyond 16 years. Methods: The analysis set consisted of 495 patients with advanced, progressive, metastatic NENs treated with PRRT using 177Lu and/or 90Y labeled somatostatin analogs, and underwent dual-tracer imagine 68Ga-SSTR and 18F-FDG PET/CT at baseline. Results: Median age was 59 years. 382 (77.17%) patients were FDG-positive and 113 as FDG-negative before PRRT. The median follow-up time was 94mo (range 3-189 mo). For all patients, the median PFS and OS were 19.6 and 58.7 mo, respectively. A significant difference between FDG-positive and negative group was found for both PFS (18.5 v.s. 24.1 mo, p=0.0015) and OS (53.0 v.s .83.1 mo, p<0.0001). In pancreatic-NENs subgroup, a negative FDG scan predicted much higher OS (114.3 v.s. 52.8 mo, p=0.0006) than positive group. There was no direct correlation between 68Ga-SSTR SUVmax (single lesion) and OS (p>0.05). For those patients with a completely negative FDG scan, the median OS with SUVmax>15.0 and with ≤15.0 on 68Ga-SSTR PET were 108.3mo and 76.9mo, respectively. Conclusion: 18F-FDG PET imaging is an independent prognostic factor in patients with NEN treated with PRRT. It allows by using 18F-FDG, other than 68Ga-SSTR PET/CT, for predicting the prognosis of PRRT. High SSTR uptake combined with negative 18F-FDG is associated with a better long-term prognosis.
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Targeted Alpha Therapy of Recurrent Glia Tumors: Clinical Experience with 225Ac-Substance-P
Leszek Krolicki1, Frank Bruchertseifer2, Jolanta Kunikowska2, Bartosz Krolicki3, Maciej Jakucinski4, Dariusz Pawlak5, Onstantij Apostolidis6, Rafal Rola7, Adrian Merlo8, Alfred Morgenstern2
1Department of Nuclear Medicine, Medical University of Warsaw, 3Department of Neurosurgery, Institute of Oncology, 4Department of Diagnostic Imaging, Brodnowski Hospital, 7Department of Neurology, Military Institute of Aviation Medicine, Warsaw, 5Radioisotope Centre POLATOM, National Centre for Nuclear Research, Otwock, Poland, 2European Commission, Joint Research Centre, Directorate for Nuclear Safety and Security, Henryk Koziara, 6European Commission, Joint Research Centre, Directorate for Nuclear Safety and Security, Karlsruhe, Germany, 8Department of Neurosurgery, University of Basel, Basel, Switzerland
Regardless the histological grading gliomas are characterized by a high expression of receptor for Substance –P (SP). Therefore, SP labeled with alpha emitters could be used for local treatment of the tumour. Initially, 213 Bi was used for labeling of SP. Currently, 225Ac was introduced. It seems that a diverse range of energy, and longer T1/2 (10 days) should be favor for better distribution of the radiopharmaceutical into the tumor. The aim of study was to tolerability and overall survival assessment. Methods: 13 patients with histologically confirmed recurrence of the glia tumor grade II-IV were treated: group A – patients with grade II - III WHO (5 patients), group B – patients with grade IV (8 patients). All patients received a standard treatment (surgery + radio-chemo-therapy). On the time of recurrence/progression diagnosis, an intracavitary/intratumoral injection of 20-40 MBq 225Ac-DOTAGA-SP was applied every 2 months (1-7 injections). Results: In group A: PFS was 4.8 months, OS from primary diagnosis was 114.7 months, OS from diagnosis of recurrence – 38.0 months, and OS from start of radioisotopic treatment – 26.5 months. In group B: PFS was 3.0 months, OS from primary diagnosis was 21.3 months, OS from diagnosis of recurrence – 10.9 months, and OS from start of radioisotopic treatment – 5.0 months. Intracavitary/intratumoral injection of 225Ac-substance P was well tolerated only mild temporary adverse effects (edema, epileptic seizures, aphasia) were observed in 3 patients. Conclusion: It seems that local injection of 225Ac-DOTAGA-SP is promising option treatment for different grade glia tumors, especially grade II and III. This observation requires further clinical trials.
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Multicenter Retrospective Analysis of 68Ga-DOTA-TOC/TATE and 18F-FDG-Positron Emission Tomography/Computed Tomography in Neuroendocrine Tumor Patients Retreated with Peptide Receptor Radionuclide Therapy: First Results
Margarida Rodrigues1, Diana Paez2, Michael Hofmann3, Harvey Turner4, Dale Bailey5, Alexander Haug6, Jukka Kemppainen7, Richard Baum8, Hojjat Hojjat Ahmadzadehfar9, Vikas Prasad10, Cs Bal11, Partha Choudhury12, Giovanni Paganelli13, Chiara Maria Grana14, Akram Al-Ibraheem15, Mike Sathekge16, Levent Kabasakal17, Omar Alonso18, Irene Virgolini1
1Department of Nuclear Medicine, Medical University Innsbruck, Tyrol, Austria, 2Nuclear Medicine and Diagnostic Imaging Section, International Atomic Energy Agency, Vienna International Center, 6Division of Nuclear Medicine, Department of Biomedical Imaging and Image Guided Therapy, Medical University of Vienna, Vienna, Austria, 3Molecular Imaging and Nuclear Medicine Therapeutics Peter Maccaccum Centre and Sir Maccaccum Department of Oncology, The University of Melbourne UIC, Australia, 4Department of Nuclear Medicine, The University of Western Australia, 5Department of Nuclear Medicine, Royal North Shore Hospital, Sydney, New South Wales, Australia, 7Docrates Cancer Center and University of Turku, Turku, Finland, 8Zentralklinik, Bad Berka, 9Department of Nuclear Medicine, University Hospital Bonn, Sigmund, Bonn, Germany, 10Department of Nuclear Medicine, University of Ulm, Albert-Einstein-Allee, Ulm, Germany, 11All India of Institute of Medical Science, New Delhi, 12Rajiv Gandhi Cancer Institute and Research Centre, Delhi, India, 13Nuclear Medicine Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Forli-Cesena, Italy, 14Division of Nuclear Medicine, IEO, European Institute of Oncology IRCCS, Milan, Italy, 15King Hussein Cancer Center, Amman, Jordan,16Department of Nuclear Medicine, Steve Biko Academic Hospital, University of Pretoria, Private Bag X169, Pretoria, South Africa, 17Istanbul University-Cerrahpasa, Cerrahpasa School of Medicine, Department of Nuclear Medicine, Fatih, Istanbul, Turkey, 18Clinical Hospital of the University of Uruguay, Uruguay
Peptide receptor radionuclide therapy (PRRT) employing the radiolabeled somatostatin analogues 177Lu/90Y-labeled DOTA-TOC/TATE/lanreotide has been used as a systemic treatment approach in inoperable or metastatic somatostatin receptors (SSTR)-positive tumors. SSTR positivity is evaluated by SSTR-imaging with 68Ga-DOTA-TOC/TATE/NOC/ lanreotide PET/CT or 99mTc-HYNIC-TOC/111In-DOTA-TOC/lanreotide scintigraphy. 68Ga-DOTA-TOC PET was found with a significantly higher detection rate compared with conventional SSTR scintigraphy and diagnostic CT. 18F-FDG-PET/CT assesses glycolytic metabolism, and its higher uptake was found to be associated with tumor aggressiveness. Aim: The primary objective of this retrospective multicenter study was to determine and compare the value of 68Ga-DOTA-TOC/TATE and 18F-FDG-PET/CT for initial and follow-up evaluation of NET patients retreated with PRRT. Methods: A retrospective evaluation of a cohort of about 200 patients who had histologically proven NET and underwent both PRRT and combined 68Ga-DOTA-TOC/TATE and 18F-FDG-PET/CT studies before PRRT and during follow-up after first full PRRT and PRRT retreatment was performed. Patients’ information was collected from several institutions in different countries. Results: Demographic data and first results concerning primary tumor and metastases localizations, tumor grades (ENET criteria), extent of tumor disease evaluated with 68Ga-PET, 18FDG-PET, CT and MRI, among others, PRRT activities applied, efficiency of PRRT and disease course (in terms of progressive disease, stable disease, partial remission or complete remission) will be presented and discussed.
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Radiolabeled RGD, an Important Theranostic Ligand for Targeting Angiogenesis: Bench to Bedside
Rakhee Vatsa1, Jaya Shukla1, Ashwin Singh Parihar1, Sudipta Chakraborty2, Ashutosh Dash2, Bhagwant Rai Mittal1
1Department of Nuclear Medicine, Postgraduate Institute of Medical Education and Research, Chandigarh, 2Bhabha Atomic Research Centre, Mumbai, Maharashtra, India
Background: Angiogenesis, an essential phenomenon for tumor growth, invasion and metastasis is known to be associated with integrin αvβ3. Over-expression of this integrin have been observed on endothelial cells of neovasculature and in various malignancies. The present study aims to explore the potential of Ga-68 and Lu-177 labeled RGD tripeptide in breast, lung and TENIS patients. Methods: Reaction parameters were optimised in-house for radiolabeling of RGD with Ga-68 and Lu-177. Post quality control tests, biodistribution studies were performed in normal sprague dwaley rats. A total of 100 patients (n=80 and 5 for Breast and lung cancer respectively, and n=15 TENIS) have undergone Ga-68 RGD PET/CT scan. Two patents with TENIS have undergone Lu-177 RGD therapy. Results: Radiolabeling yield of >95% and RCP of >99% was achieved under optimised conditions. The final preparation was observed to be sterile and the endotoxin content was found to less than 4 EU/ml and 15 EU/ml in Ga-68-RGD and Lu-177 RGD preparations respectively. Animal study revealed maximum counts in liver and spleen with excretion through kidneys at 45 min. Physiological uptake was observed in bilateral brain ventricles, liver, spleen with variable uptake in intestine at 45 min. Excretion was observed mainly via kidneys. Variable uptake (SUVmax 1.02-20.8) was observed in primary lesion.Good uptake of Lu-177 RGD was observed in primary and metastatic lesions. The tracer was well tolerated by the patients. Conclusion: The study suggested the radiolabled RGD peptide has immense potential for becoming a theranostic agent for tumors expressing integrin αvβ3.
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SPECT-Computed Tomography with New 99mTC-Prostate-Specific Membrane Antigen-T4 Tracer in Patients with Recurrent Prostate Cancer
Sonya Sergieva1, Radoslav Mangaldjiev1, Milena Dimcheva1, Bozhil Robev1
Department of Nuclear Medicine, Sofia Cancer Center, Sofia, Bulgaria
Introduction: Prostate-specific membrane antigen (PSMA) is a cell surface glycoprotein with a large extracellular domain with overexpression of the prostatic tumor cells. A lot of small molecules of PSMA ligands or inhibitors binding to active site of PSMA were developed. 99mTc-PSMA-T4 is a new radiopharmaceutical (Polatom) for imaging of loco-regional metastases and/or local relapse in patients with prostate cancer. Imaging Protocol: Whole-body imaging examinations with subsequent target SPECT-CT studies of the pelvis, abdomen and/or chest and were carried out 1–3 hrs. post i.v. administration of 99mTc-PSMA-T4 in 18 patients with prostate cancer. The average activity dose, injected i.v. was 6.3MBq/kg in a man of 70 kg. SPECT-CT gamma camera Symbia T2, Siemens, was used for topographic localization and morphological substratum of “hot” abnormal foci. Double-head SPECT acquisition included 64 projections, 25 s/projection, matrix 256x256. Low dose CT scanning was performed in the helical mode. Acquisition parameters included settings at 130 KeV; 30 mA; 3–5 mm slice thickness. The images were interpreted based on all other clinical and radiological data. Patients: Eighteen patients with prostate carcinoma were included were studied during the period January-March 2019. Seventeen of them were studied after radical treatment (total prostatectomy or definitive radiotherapy of the tumor) and one - after tru-cut biopsy and cytoreductive radiotherapy. All patients were with biochemical progression and clinical data for recurrence of the disease, they were studied for restaging. Results: Normal biodistribution of the radiopharmaceutical with high activity background was observed in the liver, spleen, kidneys, salivary glands, bowels and urinary bladder. In 11 patients positive local recurrence, lymph node and/or bone metastases with intensive tracer uptake were imaged; in one of them lung mets were visualised and in another - adrenal suprarenal met was established; there was suspicious for local recurrence in 4 patients with negative MRT study who will be followed up. In one case with local recurrence with intensive uptake, bone mets were negative - without tracer uptake due to therapy with X-geva and hormonotherapy.There was one patient with negative result. Conclusion: In conclusion oncotropic SPECT-CT tracer as 99mTc-PSMA can help in selecting the right therapeutic strategy for a single patient with prostate cancer:
- To follow-up of patients after complex therapy and biochemical recurrence for re-staging
- For imaging of local recurrence and/or metastases after therapy in order to perform SRT (salvage radiation therapy) or target radiotherapy
- To monitor therapeutic effect after treatment – to detect progressive / active lesions or to report full/ partial response
- To assess PSMA expression before Radio Ligand Therapy (RLT) with Lu-PSMA/Ac-PSMA.
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Prognostic Value of Baseline 18F-FDG Positron Emission Tomography/Computed Tomography Metabolic Parameters in Pediatric Lymphoma
Yeye Zhou1, Bin Zhang1, Shibiao Sang1, Yiwei Wu1, Shengming Deng1
1Department of Nuclear Medicine, The First Affiliated Hospital of Soochow University, Suzhou, China
Objectives: To investigate the prognostic value of metabolic parameters tMTV, TLG and SUVmax measured on baseline 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) in pediatric Lymphoma. Methods: From March 2013 to February 2019. 37 patients (28 males and 9 females, average age 14.95 years) with pediatric Lymphoma who underwent 18F-FDG PET/CT scan prior to treatment were retrospectively included in this study. Maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were recorded. Survival curve were calculated according to the Kaplan-Meier curves and log-rank test. Mann-Whitney U-test was used to assess differences in metabolic parameters between different clinical outcomes. Results: The median follow-up time was 37 months (range 6-71 months). The 2-year progression-free survival (PFS) of the lower and higher TLG group was 94.1% (16/17) and 55% (11/20), respectively (p=0.006). TLG and tMTV were significantly higher in patients with progression-free compared to progression group. Univariate analysis showed that B symptoms (p=0.015), tMTV (p=0.012), TLG (p=0.006) were the predictive factors for PFS; multivariate analysis revealed TLG was the only independent prognostic factor for PFS (HR=10.471, 95%CI=1.322-86.948, p=0.026). Conclusion: TLG of baseline 18F-FDG PET/CT was an independent prognostic factor for PFS in patients with pediatric lymphoma.
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Radachlorin-Gallium-68 Labeled Pharmaceutical: A New Theranostic Agent for the Integration of Photodynamic Therapy and Nuclear Imaging
Yousef Fazaeli1, Fatemeh Yari2
1Nuclear Medicine Research Group, Agricultural, Medical and Industrial Research School, Nuclear Science and Technology Research Institute (NSTRI), Karaj, Iran, 2Department of Nuclear Engineering, Science and Research Branch, Islamic Azad University, Tehran, Iran
The cyclic tetrapyrrolic compounds, such as porphyrins, have an important role to play in medical research due to their vital role in the body of living beings, the ability to accumulate in a variety of human cancer cells, as well as having distinct physical, magnetic, and optical properties. Therefore, they are very useful in the design of anticancer pharmaceuticals and photodynamic therapy. Due to the prominent properties of gallium -68 and the targeted accumulation of radachlorin anticancer drug, the radiopharmaceutical complex of this porphyrin is synthesized with gallium -68 radionuclide and its biological information such as ,partition coefficient and biodistribution studies in wild type and tumor bearing rats were studied. High accumulation of the complex in the tumor, rapid washout from the body and lower radiation doses to patients were observed using this labeled compound. In this study combining the excellent reactivity of gallium -68 with flat-lipophilic ligands with neutral electrical charge, such as radachlorin, the potential for beta-excretion for PET and the use of radachlorin in PDT for therapeutic purposes, a new PET / PDT imaging agent was Introduced.
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