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.
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2017 Oct 12 [Epub]
Guillaume P Nicolas, Seval Beykan, Hakim Bouterfa, Jens Kaufmann, Andreas Bauman, Michael Lassmann, Jean Claude Reubi, Jean E F Rivier, Helmut R Maecke, Melpomeni Fani, Damian Wild
Division of Nuclear Medicine, University Hospital Basel, Basel, Switzerland., Department of Nuclear Medicine, University Hospital Würzburg, Würzburg, Germany., OctreoPharm Sciences GmbH, Ipsen Group, Berlin, Germany., Division of Radiopharmaceutical Chemistry, University Hospital Basel, Basel, Switzerland., Cell Biology and Experimental Cancer Research, University of Berne, Berne, Switzerland., Clayton Foundation Laboratories for Peptide Biology, Salk Institute, La Jolla, California; and., Department of Nuclear Medicine, University Hospital Freiburg, Freiburg, Germany., Division of Nuclear Medicine, University Hospital Basel, Basel, Switzerland .