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. <b>Methods:</b> 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 (SUV_max/SUV_mean) of normal tissue and lesions judged malignant was compared with standard PET imaging (number of lesions, uptake per lesion). <b>Results:</b> When compared with standard imaging, ⁶⁸Ga-DOTA-MGS5 showed significantly increased blood-pool activity (<i>P</i> ≤ 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 SUV_max of 7.2 at 1 h and 2 h after injection versus 4.7 with ¹⁸F-DOPA (<i>P</i> < 0.001). In the 2 patients with MTC imaged with ⁶⁸Ga-DOTATOC and ⁶⁸Ga-DOTA-MGS5, the same total number of lesions (<i>n</i> = 14) was detected (mean SUV_max, 24.3 vs. 17.4 and 18.7 at 1 and 2 h after injection, respectively; <i>P</i> > 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. <b>Conclusion:</b> 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.