Abstract
Preclinical and preliminary clinical evidence indicates that radiolabeled somatostatin receptor (sst) antagonists perform better than agonists in terms of detecting neuroendocrine tumors (NETs). This prospective phase I/II study is the first to evaluate an sst 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 results of the phase I component of the study. Methods: Patients received two single intravenous injections of 150 MBq 68Ga-OPS202 three to 4 weeks apart (15 µg peptide at visit 1 and 50 µg at visit 2). At visit 1, a dynamic PET/CT scan was performed over the kidney during the first 30 min post-injection and static whole-body scans at 0.5, 1, 2, and 4 h p.i; at visit 2, a static whole-body scan was performed 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 rapidly cleared from the blood; the mean residence time in the blood was 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 for laboratory blood or urinalysis tests. Conclusion: 68Ga-OPS202 shows favorable biodistribution and imaging properties with optimal tumor contrast between 1 and 2 h post-injection. Dosimetry analysis revealed that 68Ga-OPS202 delivers a similar dose to organs as other 68Ga-labeled somatostatin analogs. Further evaluation of 68Ga-OPS202 for PET/CT imaging of NETs is therefore warranted.
- Neuroendocrine
- PET/CT
- Radiopharmaceuticals
- 68Ga-NODAGA-JR11
- 68Ga-OPS202
- dosimetry
- neuroendocrine tumors
- somatostatin receptor antagonist
- Copyright © 2017 by the Society of Nuclear Medicine and Molecular Imaging, Inc.