Diagnostic Performance of the 68Ga-Labeled Minigastrin Analog DOTA-MGS5 in Patients with Advanced Medullary Thyroid Cancer and Other Neuroendocrine Tumors

A prospective phase 1/2a pilot study (NCT06155994) was performed at our center to compare the diagnostic performance of cholecystokinin-2 receptor (CCK2R) PET/CT imaging with the 68Ga-labeled peptide analog DOTA-DGlu-Ala-Tyr-Gly-Trp-(N-Me)Nle-Asp-1-Nal-Phe-NH2 (68Ga-DOTA-MGS5) with that of the reference standard PET/CT. Methods: Six patients with advanced medullary thyroid cancer (MTC) and 6 patients with other neuroendocrine tumors (NETs)-4 with gastroenteropancreatic (GEP) NETs and 2 with bronchopulmonary (BP) NETs-were included in the study. All patients had known metastases, documented by 68Ga-DOTATOC and 18F-DOPA PET/CT. Intensity of tracer accumulation (SUVmax/SUVmean) of normal tissue and lesions judged malignant was compared with standard PET imaging (number of lesions, uptake per lesion). Results: When compared with standard imaging, 68Ga-DOTA-MGS5 showed significantly increased blood-pool activity (P ≤ 0.009), with improved lesion contrast at 2 h after injection compared with 1 h after injection. Four of 6 patients with MTC had positive lesions on 68Ga-DOTA-MGS5 PET/CT. Fifty-one lesions were detected with 18F-DOPA versus 48 with 68Ga-DOTA-MGS5, with a significantly higher mean SUVmax of 7.2 at 1 h and 2 h after injection versus 4.7 with 18F-DOPA (P < 0.001). In the 2 patients with MTC imaged with 68Ga-DOTATOC and 68Ga-DOTA-MGS5, the same total number of lesions (n = 14) was detected (mean SUVmax, 24.3 vs. 17.4 and 18.7 at 1 and 2 h after injection, respectively; P > 0.5). In patients with non-MTC NETs, 26 CCK2R-positive lesions were confirmed for 2 patients with BP-NETs compared with 45 lesions visualized with 68Ga-DOTATOC. In the 4 patients with GEP-NETs, only 1 of 21 lesions displaying positive uptake on 68Ga-DOTATOC PET/CT was visualized with 68Ga-DOTA-MGS5 (an ileal NET), whereas the lesions in the other 3 patients were negative on 68Ga-DOTA-MGS5 PET/CT. Conclusion: CCK2R PET/CT using 68Ga-DOTA-MGS5 showed a high tumor lesion detection rate in patients with MTC, with lesion uptake values comparable to those with 18F-DOPA and 68Ga-DOTATOC. In patients with non-MTC NETs, 68Ga-DOTA-MGS5 PET/CT showed possible applicability in patients with BP-NETs, which needs to be verified in a larger patient cohort. In contrast, 68Ga-DOTA-MGS5 PET/CT seemed to be of limited value in patients with GEP-NETs.