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

Abstract

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 Ga-OPS202 (Ga-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-NH)) for PET imaging. Here, we report the results of phase I of the study. Patients received 2 single 150-MBq intravenous injections ofGa-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 Ga-OPS202 pharmacokinetics. Safety, biodistribution, radiation dosimetry, and the most appropriate imaging time point forGa-OPS202 were assessed. Twelve patients with well-differentiated gastroenteropancreatic (GEP) NETs took part in the study.Ga-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. Ga-OPS202 was well tolerated; adverse events were grade 1 or 2, and there were no signals of concern from laboratory blood or urinalysis tests.Ga-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 Ga-OPS202 to organs is similar to that delivered by otherGa-labeled sst analogs. Further evaluation of Ga-OPS202 for PET/CT imaging of NETs is therefore warranted.

Comparative evaluation of 68Ga-labelled TATEs: the impact of chelators on imaging

“…It may also be a potential source of the differences observed in the PK values of the two tracers. NODAGA (1,4,7-triazacyclononane,1glutaric acid-4,7-acetic acid) is also a good dualfunctional chelating agent for 68 Ga. 68 Ga-OPS202 (an SSTR antagonist), also called 68 Ga-NODAGA-JR11 (JR11 = Cpa-c( D Cys-Aph(Hor)-D Aph(Cbm)-Lys-Thr-Cys)-D Tyr-NH2), is a radiolabelled antagonist that may recognize more SST receptor binding sites [14,15] and has the potential to improve SST receptor PET/CT imaging. The half inhibitory concentration (IC 50 ) of 68 Ga-OPS202 (antagonist) on SSTR2 is 1.2 ± 0.2, and the half inhibitory concentration (IC 50 ) of 68 Ga-DOTA-TATE (agonist) on SSTR2 is 0.2 ± 0.04, indicating that both have a high affinity for SSTR2 [16].…”

Design and development of the theranostic pair 177Lu‐OPS201/68Ga‐OPS202 for targeting somatostatin receptor expressing tumors

“…Regarding the diagnostic compound, 68 Ga‐DOTA‐JR11 demonstrated rapid tumor uptake, high tumor‐to‐background ratios, and rapid blood clearance in patients with metastatic NETs . In agreement with clinical data obtained using 68 Ga‐OPS202, 68 Ga‐OPS201 showed low liver background, considered to be advantageous for the detection of liver metastases, while its effective dose (0.022 ± 0.003 mSv/MBq, Table ) is similar to 68 Ga‐OPS202 and compares favorably with published data for 68 Ga‐DOTA‐TATE and 68 Ga‐DOTA‐TOC.…”

“…68 Ga‐satoreotide trizoxetan ( 68 Ga‐OPS202) was evaluated using two microdose levels (15 and 50 μg) and compared with 68 Ga‐DOTA‐TOC PET/CT in a prospective phase 1/2 study (NCT02162446) involving 12 low‐ or intermediate‐grade gastroenteropancreatic NETs (GEP‐NET) patients . Both doses of 68 Ga‐OPS202 showed increased image contrast compared with 68 Ga‐DOTA‐TOC because of lower hepatic, intestinal, and pancreatic uptake.…”

“…gastroenteropancreatic NETs (GEP-NET) patients. 41,53 Both doses of 68 Ga-OPS202 showed increased image contrast compared with 68 Ga-DOTA-TOC because of lower hepatic, intestinal, and pancreatic uptake. This resulted in a substantially higher sensitivity and diagnostic accuracy (overall and specifically for detection of liver metastases) of 68 Ga-OPS202 than 68 Ga-DOTA-TOC PET/CT for staging well to moderately differentiated GEP-NET patients.…”

Reply: Advantages and Limits of Targeted Radionuclide Therapy with Somatostatin Antagonists

“…In our opinion, and based on our recent findings, the administration of an appropriate peptide mass is a key parameter for optimal imaging and therapy of somatostatin receptor-expressing tumors. We herein take the opportunity to respond to the valuable questions raised by Hindié et al, in addition to the already addressed points in our recent articles (1,3,4).…”