Head-to-Head Comparison of 68Ga-NODAGA-JR11 and 68Ga-DOTATATE PET/CT in Patients with Metastatic, Well-Differentiated Neuroendocrine Tumors: Interim Analysis of a Prospective Bicenter Study.

The current study aimed to compare 68Ga-NODAGA-Cpa-cyclo(d-Cys-amino-Phe-hydroorotic acid-d-4-amino-Phe(carbamoyl)-Lys-Thr-Cys)-d-Tyr-NH2 (JR11) and 68Ga-DOTATATE PET/CT in patients with metastatic, well-differentiated neuroendocrine tumors. Methods: A prospective bicenter study aimed at enrolling 100 patients with histologically proven, metastatic or unresectable, well-differentiated neuroendocrine tumors was conducted. The first 48 patients represented the study cohort. Each patient received 68Ga-DOTATATE on the first day and 68Ga-NODAGA-JR11 on the second day. Whole-body PET/CT scans were performed at 40-60 min after injection. Normal-organ uptake, lesion numbers, lesion uptake, and sensitivity were compared. The potential impact on clinical management was also determined. Results: Overall, 68Ga-NODAGA-JR11 demonstrated lower background uptake in normal organs. Compared with 68Ga-DOTATATE, 68Ga-NODAGA-JR11 detected significantly more liver lesions (673 vs. 584, P = 0.002). The target-to-background ratio of liver lesions was significantly higher on 68Ga-NODAGA-JR11 (6.4 ± 8.7 vs. 3.1 ±2.6, P = 0.000). Comparable uptake was observed for primary tumors, bone lesions, and lymph node metastases. In total, 180 lesions were detected on conventional imaging in 15 patients; 165 and 139 lesions of them were positive on 68Ga-NODAGA-JR11 and 68Ga-DOTATATE, leading to a sensitivity of 91.7% and 77.2%, respectively. In 14.5% (7/48) of patients, 68Ga-NODAGA-JR11 PET might have a potential impact on clinical management. Conclusion: 68Ga-NODAGA-JR11 shows better sensitivity and a higher target-to-background ratio than 68Ga-DOTATATE. The detection of more lesions by the antagonist may have a potential impact on clinical management in a subgroup of patients.

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

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 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 the results of phase I of the study. Methods: Patients received 2 single 150-MBq intravenous injections of 68Ga-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 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 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. 68Ga-OPS202 was well tolerated; adverse events were grade 1 or 2, and there were no signals of concern from laboratory blood or urinalysis tests. Conclusion:68Ga-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 68Ga-OPS202 to organs is similar to that delivered by other 68Ga-labeled sst analogs. Further evaluation of 68Ga-OPS202 for PET/CT imaging of NETs is therefore warranted.

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 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.