Sensitivity Comparison of ⁶⁸Ga-OPS202 and ⁶⁸Ga-DOTATOC PET/CT in Patients with Gastroenteropancreatic Neuroendocrine Tumors: A Prospective Phase II Imaging Study

Abstract

Radiolabeled somatostatin (sst) receptor agonists are integral to the diagnosis of gastroenteropancreatic neuroendocrine tumors (NETs), but detection rates, especially of liver metastases, remain limited even with PET/CT. 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)), a novel radiolabeled sst receptor antagonist with a high affinity for the sst receptor, has the potential to perform better than sst receptor agonists. Here, we present the results of the phase II component of a phase I/II study that evaluated the sensitivity of Ga-OPS202, compared with the reference compound,Ga-DOTATOC (an sst receptor agonist), in PET imaging. Patients received a single 150-MBq intravenous injection ofGa-DOTATOC (15 μg of peptide) and 2 single 150-MBq intravenous injections of Ga-OPS202 (15 μg of peptide at visit 1 and 50 μg at visit 2). Whole-body PET/CT acquisitions were performed 1 h after injection on the same calibrated PET/CT scanner. Diagnostic efficacy measures were compared against contrast medium-enhanced CT or MRI as the gold standard. Two independent masked experts read the scans, and both outcomes were combined for analysis. Twelve consecutive patients with low- or intermediate-grade gastroenteropancreatic NETs took part in this prospective study. Image contrast for matched malignant liver lesions was significantly higher for the Ga-OPS202 scans than for theGa-DOTATOC scan: the median of the mean tumor-to-background SUV ratios were significantly higher for 15 and 50 μg of Ga-OPS202 (5.3 and 4.3, with interquartile ranges of 2.9-5.7 and 3.4-6.3 and values of 0.004 and 0.008) than for Ga-DOTATOC (1.9, with an interquartile range of 1.4-2.9). The higher tumor-to-background ratio ofGa-OPS202 resulted not only in a higher detection rate of liver metastases but also in a significantly higher lesion-based overall sensitivity with the antagonist than with Ga-DOTATOC: 94% and 88% for 50 and 15 μg ofGa-OPS202, respectively, and 59% for 15 μg of Ga-DOTATOC ( < 0.001). Positive predictive values for Ga-OPS202 PET/CT andGa-DOTATOC PET/CT were similar (∼98%). There were no significant differences in image contrast, sensitivity, or positive predictive values between the 2 Ga-OPS202 peptide doses, indicating a high reproducibility. Preliminary diagnostic efficacy data from this phase II study indicate that Ga-OPS202 has high sensitivity for the detection of gastroenteropancreatic NETs. Further studies in larger patient populations are warranted.

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

“…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. 41 The effective dose of 68 Ga-OPS202 (0.024 ± 0.002 mSv/MBq, Table 2) was at a similar level to that of the agonists 68 Ga-DOTA-TOC and 68 Ga-DOTA-TATE (0.021 ± 0.003 mSv/MBq). 54 Organs receiving the highest dose were the urinary bladder wall, kidneys, and spleen.…”

“…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 . The effective dose of 68 Ga‐OPS202 (0.024 ± 0.002 mSv/MBq, Table ) was at a similar level to that of the agonists 68 Ga‐DOTA‐TOC and 68 Ga‐DOTA‐TATE (0.021 ± 0.003 mSv/MBq) .…”

“…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.…”