Background: The goal of this research was to investigate the feasibility of 64Cu labeling in prostate-specific membrane antigen imaging and therapy (PSMA I&T) for PSMA positron emission tomography (PET) imaging and biodistribution evaluation. Materials and Methods: PSMA I&T was labeled with 64Cu, and stability in human and mouse sera was evaluated. Prostate cancer cell lines were used for specific uptake assays (22RV1 for PSMA-positive, PC-3 for -negative). Both PC-3 and 22RV1 cells were transplanted into the left and right thighs in a mouse for PET/computed tomography (CT) imaging. Biodistribution was performed using 22RV1 tumor models. Results: Labeling yield (decay corrected) of 64Cu-PSMA I&T was more than 95% compared to the free 64Cu peak. The serum stability of 64Cu-PSMA I&T was maintained at more than 90% until 60 h. Regarding the specific binding of 64Cu-PSMA I&T was 7.5-fold higher to 22RV1 cells than PC-3 cells (p < 0.001). On PET/CT imaging, more specific 64Cu-PSMA I&T uptake was observed to 22RV1 tumors than to PC-3 tumors. In the PSMA blocking study using 2-phosphonomethoxypropyl adenine (2-PMPA), the 64Cu-PSMA I&T signal significantly decreased in the 22RV1 tumor region. In the biodistribution study, the kidney uptake was the highest among all organs at 2 h (52.6 ± 20.8%ID/g) but sharply decreased at 24 and 48 h. Also, the liver showed similar uptake over time (range, 10-12%ID/g). On the contrary, 64Cu-PSMA I&T uptake of the tumors increased with time and peaked at 48 h (5.6 ± 0.1%ID/g). Conclusions: PSMA I&T labeled with 64Cu showed the feasibility of the PSMA specific PET imaging through in vitro and in vivo studies. Furthermore, 64Cu-PSMA I&T might be considered as the candidate of future clinical trial.
Keywords: 64Cu; PET imaging; PSMA; PSMA I&T.