Safety, Biodistribution, and Radiation Dosimetry of ^sup 68^Ga-OPS202 in Patients with Gastroenteropancreatic Neuroendocrine Tumors: A Prospective Phase I Imaging Study

• Published in: The Journal of nuclear medicine (1978) Vol. 59; no. 6; p. 909
• Main Authors: Nicolas, Guillaume P, Beykan, Seval, Bouterfa, Hakim, Kaufmann, Jens, Bauman, Andreas, Lassmann, Michael, Reubi, Jean Claude, Rivier, Jean EF, Maecke, Helmut R, Fani, Melpomeni, Wild, Damian
• Format: Journal Article
• Language: English
• Published: New York Society of Nuclear Medicine 01.06.2018
• Subjects: Acetic acid; Bladder; Blood; Computed tomography; Dosimeters; Dosimetry; Growth hormones; Injection; Intravenous administration; Kidneys; Lesions; Liver; Medical imaging; Neuroendocrine tumors; Organs; Patients; Pharmaceutical sciences; Pharmacokinetics; Pharmacology; Positron emission; Positron emission tomography; Radiation; Radiation dosimetry; Safety; Somatostatin; Spleen; Tomography; Tumors; Urinalysis; Urinary bladder; Urine; Windows (intervals)
• ISSN: 0161-5505; 1535-5667

Preclinical and preliminary clinical evidence indicates that radiolabeled somatostatin (sst) receptor antagonists perform better than agonists in detecting neuroendocrine tumors (NETs). We performed a prospective phase I/II study to evaluate the sst receptor antagonist 68Ga-OPS202 (68Ga-NODAGA-JR11; NODAGA = 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid and JR11 = Cpa-c(DCys-Aph(Hor)-DAph(Cbm)-Lys-Thr-Cys)-DTyr-NH2)) for PET imaging. Here, we report the results of phase I of the study. Methods: Patients received 2 single 150-MBq intravenous injections of 68Ga-OPS202 3–4 wk apart (15 μg of peptide at visit 1 and 50 μg at visit 2). At visit 1, a dynamic PET/CT scan over the kidney was obtained during the first 30 min after injection, and static whole-body scans were obtained at 0.5, 1, 2, and 4 h after injection; at visit 2, a static whole-body scan was obtained at 1 h. Blood samples and urine were collected at regular intervals to determine 68Ga-OPS202 pharmacokinetics. Safety, biodistribution, radiation dosimetry, and the most appropriate imaging time point for 68Ga-OPS202 were assessed. Results: Twelve patients with well-differentiated gastroenteropancreatic (GEP) NETs took part in the study. 68Ga-OPS202 cleared rapidly from the blood, with a mean residence time of 2.4 ± 1.1 min/L. The organs with the highest mean dose coefficients were the urinary bladder wall, kidneys, and spleen. The calculated effective dose was 2.4E−02 ± 0.2E−02 mSv/MBq, corresponding to 3.6 mSv, for a reference activity of 150 MBq. Based on total numbers of detected malignant lesions, the optimal time window for the scan was between 1 and 2 h. For malignant liver lesions, the time point at which most patients had the highest mean tumor contrast was 1 h. 68Ga-OPS202 was well tolerated; adverse events were grade 1 or 2, and there were no signals of concern from laboratory blood or urinalysis tests. Conclusion: 68Ga-OPS202 showed favorable biodistribution and imaging properties, with optimal tumor contrast between 1 and 2 h after injection. Dosimetry analysis revealed that the dose delivered by 68Ga-OPS202 to organs is similar to that delivered by other 68Ga-labeled sst analogs. Further evaluation of 68Ga-OPS202 for PET/CT imaging of NETs is therefore warranted.