Abstract
Prostate-specific membrane antigen (PSMA) is a key target for diagnosing prostate cancer through positron emission tomography (PET). While (68)Ga-labeled PSMA compounds are widely used, (18)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 in vivo biodistribution. This led to the development of (18)F-PSiMA, a SiFA-based radiotracer with an optimized linker exhibiting favorable PSMA potency (IC(50) = 154 ± 47 nM in LNCaP cells). (18)F-PSiMA radiosynthesis with low to high concentrations of (18)F 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 (SUV(60min) 1.56 ± 0.18; 7.23 ± 0.75% ID per g at lower A (m) and SUV(60min) 1.90 ± 0.29; 9.62 ± 1.29% ID per g at higher A (m)) compared to our previous lead, (18)F-SiFA-Asp(2)-PEG(3)-PSMA. PSMA specificity was confirmed by a 20 ± 10% reduction in SUV(60min) upon co-injection with DCFPyl. These promising in vitro and in vivo results support further clinical translation of (18)F-PSiMA for prostate cancer PET imaging.