Development and clinical potential of 18F-PSiMA for prostate cancer PET imaging.

Prostate-specific membrane antigen (PSMA) is a key target for diagnosing prostate cancer through positron emission tomography (PET). While 68Ga-labeled PSMA compounds are widely used, 18F-labeled PSMA inhibitors have gained traction for clinical tumor imaging. We previously investigated PSMA-targeting compounds based on the Lys-urea-Glu motif, incorporating a silicon fluoride-acceptor (SiFA) and chemical auxiliaries to enhance in vivo biodistribution. This led to the development of 18F-PSiMA, a SiFA-based radiotracer with an optimized linker exhibiting favorable PSMA potency (IC50 = 154 ± 47 nM in LNCaP cells). 18F-PSiMA radiosynthesis with low to high concentrations of 18F and precursor achieved molar activities (A m) of 10.9-82.5 GBq μmol-1 and showed a 24-38% increase in tumor uptake in LNCaP tumors (SUV60min 1.56 ± 0.18; 7.23 ± 0.75% ID per g at lower A m and SUV60min 1.90 ± 0.29; 9.62 ± 1.29% ID per g at higher A m) compared to our previous lead, 18F-SiFA-Asp2-PEG3-PSMA. PSMA specificity was confirmed by a 20 ± 10% reduction in SUV60min upon co-injection with DCFPyl. These promising in vitro and in vivo results support further clinical translation of 18F-PSiMA for prostate cancer PET imaging.