Gastrin-releasing peptide receptor (GRPR) is overexpressed in most prostate cancers (PCa) and is a potential target in diagnosis and treatment. In this study, based on the previously reported GRPR antagonist RM26 and novel chelating agent Dar derivatives, we designed and evaluated two radiopharmaceuticals, [68Ga]Ga-Dar-C5-P2-RM26 and [68Ga]Ga-Dar-P2-RM26. Both radiotracers were easily prepared at room temperature and showed high radiochemical stability in phosphate-buffered saline (PBS) and fetal bovine serum (FBS). Cellular and animal experiments indicated that the two radiotracers exhibited specific tumor uptakes in PC-3 xenograft mice models. Specifically, [68Ga]Ga-Dar-C5-P2-RM26 and [68Ga]Ga-Dar-P2-RM26 displayed 6.617 ± 0.245 % ID/g and 5.973 ± 1.261 % ID/g tumor uptake, respectively. Positron emission tomography/ computer tomography (PET/CT) imaging results indicated that these two radiotracers showed excellent tumor-to-background contrast at 0.5 h, 1 h, and 2 h post intravenous injection (p.i.). In summary, [68Ga]Ga-Dar-C5-RM26 and [68Ga]Ga-Dar-RM26 are GRPR-targeted radiotracers with high potential for clinical translation in tumor-targeted imaging.
