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. 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)), a novel radiolabeled sst receptor antagonist with a high affinity for the sst2 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 68Ga-OPS202, compared with the reference compound, 68Ga-DOTATOC (an sst receptor agonist), in PET imaging. Methods: Patients received a single 150-MBq intravenous injection of 68Ga-DOTATOC (15 μg of peptide) and 2 single 150-MBq intravenous injections of 68Ga-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. Results: 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 68Ga-OPS202 scans than for the 68Ga-DOTATOC scan: the median of the mean tumor-to-background SUVmax ratios were significantly higher for 15 and 50 μg of 68Ga-OPS202 (5.3 and 4.3, with interquartile ranges of 2.9-5.7 and 3.4-6.3 and P values of 0.004 and 0.008) than for 68Ga-DOTATOC (1.9, with an interquartile range of 1.4-2.9). The higher tumor-to-background ratio of 68Ga-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 68Ga-DOTATOC: 94% and 88% for 50 and 15 μg of 68Ga-OPS202, respectively, and 59% for 15 μg of 68Ga-DOTATOC (P < 0.001). Positive predictive values for 68Ga-OPS202 PET/CT and 68Ga-DOTATOC PET/CT were similar (∼98%). There were no significant differences in image contrast, sensitivity, or positive predictive values between the 2 68Ga-OPS202 peptide doses, indicating a high reproducibility. Conclusion: Preliminary diagnostic efficacy data from this phase II study indicate that 68Ga-OPS202 has high sensitivity for the detection of gastroenteropancreatic NETs. Further studies in larger patient populations are warranted.