MITIGATE-NeoBOMB1, a Phase I/IIa Study to Evaluate Safety, Pharmacokinetics, and Preliminary Imaging of 68 Ga-NeoBOMB1, a Gastrin-Releasing Peptide Receptor Antagonist, in GIST Patients.

Autor: Gruber L; Department of Radiology, Medical University Innsbruck, Innsbruck, Austria., Jiménez-Franco LD; Medical Radiation Physics/Radiation Protection, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany., Decristoforo C; Department of Nuclear Medicine, Medical University Innsbruck, Innsbruck, Austria., Uprimny C; Department of Nuclear Medicine, Medical University Innsbruck, Innsbruck, Austria., Glatting G; Medical Radiation Physics/Radiation Protection, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.; Medical Radiation Physics, Department of Nuclear Medicine, Ulm University, Ulm, Germany., Hohenberger P; Division of Surgical Oncology and Thoracic Surgery, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany., Schoenberg SO; Institute of Clinical Radiology and Nuclear Medicine, University Medical Center Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany., Reindl W; Klinikum Mannheim II, Medizinische Klinik, Mannheim, Germany; and., Orlandi F; Advanced Accelerator Applications, a Novartis Company, Colleretto Giacosa TO, Italy., Mariani M; Advanced Accelerator Applications, a Novartis Company, Colleretto Giacosa TO, Italy., Jaschke W; Department of Radiology, Medical University Innsbruck, Innsbruck, Austria., Virgolini I; Department of Nuclear Medicine, Medical University Innsbruck, Innsbruck, Austria Irene.Virgolini@i-med.ac.at.
Jazyk: angličtina
Zdroj: Journal of nuclear medicine : official publication, Society of Nuclear Medicine [J Nucl Med] 2020 Dec; Vol. 61 (12), pp. 1749-1755. Date of Electronic Publication: 2020 Apr 24.
DOI: 10.2967/jnumed.119.238808
Abstrakt: Gastrin-releasing peptide receptors (GRPRs) are potential molecular imaging targets in a variety of tumors. Recently, a 68 Ga-labeled antagonist to GRPRs, NeoBOMB1, was developed for PET. We report on the outcome of a phase I/IIa clinical trial (EudraCT 2016-002053-38) within the EU-FP7 project Closed-loop Molecular Environment for Minimally Invasive Treatment of Patients with Metastatic Gastrointestinal Stromal Tumors ('MITIGATE') (grant agreement no. 602306) in patients with oligometastatic gastrointestinal stromal tumors (GIST). Methods: The main objectives were evaluation of safety, biodistribution, dosimetry, and preliminary tumor targeting of 68 Ga-NeoBOMB1 in patients with advanced tyrosine-kinase inhibitors-treated GIST using PET/CT. Six patients with histologically confirmed GIST and unresectable primary lesion or metastases undergoing an extended protocol for detailed pharmacokinetic analysis were included. 68 Ga-NeoBOMB1 was prepared using a kit procedure with a licensed 68 Ge/ 68 Ga generator. 68 Ga-NeoBOMB1 (3 MBq/kg of body weight) was injected intravenously, and safety parameters were assessed. PET/CT included dynamic imaging at 5, 11, and 19 min as well as static imaging at 1, 2, and 3-4 h after injection for dosimetry calculations. Venous blood samples and urine were collected for pharmacokinetic analysis. Tumor targeting was assessed on a per-lesion and per-patient basis. Results: 68 Ga-NeoBOMB1 (50 μg) was prepared with high radiochemical purity (yield > 97%). Patients received 174 ± 28 MBq of the radiotracer, which was well tolerated in all patients over a follow-up period of 4 wk. Dosimetry calculations revealed a mean effective dose of 0.029 ± 0.06 mSv/MBq, with the highest organ dose to the pancreas (0.274 ± 0.099 mSv/MBq). Mean plasma half-life was 27.3 min with primarily renal clearance (mean 25.7% ± 5.4% of injected dose 4 h after injection). Plasma metabolite analyses revealed high stability; metabolites were detected only in the urine. In 3 patients, a significant uptake with increasing maximum SUVs (SUV max at 2 h after injection: 4.3-25.9) over time was found in tumor lesions. Conclusion: This phase I/IIa study provides safety data for 68 Ga-NeoBOMB1, a promising radiopharmaceutical for targeting GRPR-expressing tumors. Safety profiles and pharmacokinetics are suitable for PET imaging, and absorbed dose estimates are comparable to those of other 68 Ga-labeled radiopharmaceuticals used in clinical routine.
(© 2020 by the Society of Nuclear Medicine and Molecular Imaging.)
Databáze: MEDLINE
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