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

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 SUV_max 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.