Development and clinical potential of F-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 Ga-labeled PSMA compounds are widely used, F-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 biodistribution. This led to the development of F-PSiMA, a SiFA-based radiotracer with an optimized linker exhibiting favorable PSMA potency (IC = 154 ± 47 nM in LNCaP cells). F-PSiMA radiosynthesis with low to high concentrations of F and precursor achieved molar activities ( ) of 10.9-82.5 GBq μmol and showed a 24-38% increase in tumor uptake in LNCaP tumors (SUV 1.56 ± 0.18; 7.23 ± 0.75% ID per g at lower and SUV 1.90 ± 0.29; 9.62 ± 1.29% ID per g at higher ) compared to our previous lead, F-SiFA-Asp-PEG-PSMA. PSMA specificity was confirmed by a 20 ± 10% reduction in SUV upon co-injection with DCFPyl. These promising and results support further clinical translation of F-PSiMA for prostate cancer PET imaging.