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Several exploratory studies have demonstrated the feasibility of cholecystokinin-2 receptor (CCK2R) targeting in patients with medullary thyroid carcinoma (MTC) and other neuroendocrine tumors (NETs). We report the results of a prospective phase I/IIA pilot study (clinicaltrials.gov NCT06155994) conducted at our center with the 68 Ga-labeled peptide analog DOTA-DGlu-Ala-Tyr-Gly-Trp-(N-Me)Nle-Asp-1-Nal-Phe-NH 2 ( 68 Ga-DOTA-MGS5). Methods: Six patients with advanced MTC and 6 patients with gastroenteropancreatic and bronchopulmonary NETs confirmed by previous PET/CT imaging with other PET tracers received a single dose of 180 MBq of 68 Ga-DOTA-MGS5. The first 6 patients enrolled in the study were included in the dosimetry evaluation, and safety was assessed in all 12 patients. PET/CT imaging was performed at different time points after injection to perform dosimetric calculations and to determine the optimal imaging time window. In addition, blood and urine samples were collected for pharmacokinetic assessments. Results: The administration of 68 Ga-DOTA-MGS5 was well tolerated, with minor adverse drug reactions occurring only in 3 patients. 68 Ga-DOTA-MGS5 was cleared rapidly from the blood, with less than 21% of the injected activity present in blood 215 ± 10 min after injection. Tracer elimination occurred mainly through the kidneys, with a cumulative urinary excretion greater than 40% 3 h after injection. A high percentage of intact radiopeptide was confirmed in plasma. The highest absorbed dose was found for the urinary bladder wall, the stomach wall, and the kidneys, with an effective dose of 0.023 ± 0.007 mSv/MBq. The time points of 1 and 2 h after injection proved to be optimal for PET/CT imaging. In the 6 patients included in the dosimetry evaluation, local metastasis was confirmed in 2 patients with advanced MTC, whereas only 1 of 4 patients with gastroenteropancreatic NETs was positive in 68 Ga-DOTA-MGS5 PET/CT. Conclusion: Besides confirming the safety of administration, within the phase I part of the prospective clinical trial, an acceptable effective whole-body dose, an overall favorable biodistribution, and the feasibility of cholecystokinin-2 receptor imaging could be shown for 68 Ga-DOTA-MGS5., (© 2025 by the Society of Nuclear Medicine and Molecular Imaging.)