Synthesis and Preclinical Evaluation of Dual-Mode Fluorescent 18F-PET Tracers Targeting PSMA

Dual-mode fluorescent PET tracers for imaging prostate cancer hold promise for coordinating preoperative PET imaging with intraoperative surgical imaging applications. Here, we disclose two PET tracers containing three key design elements: (1) an organotrifluoroborate for one-step radiofluorination at Curie levels of [¹⁸F] fluoride in good yields and high molar activity (A_m) values: 42–167 GBq/μmol, (2) two fluorescein moieties (FAM and FITC) for fluorescent visualization, and (3) two pharmacophores based on clinically validated scaffolds PSMA-617 and PSMA-1007. These tracers are the first-ever examples of dual-mode PSMA-targeting agents that are labeled with both fluorescein and fluorine-18. Both were evaluated using LNCaP and 22Rv1 xenografts and show high tumor uptake (7–17% ID/g), strong fluorescent visualization on cultured LNCaP and 22Rv1 cells, and fluorescence detection ex vivo. These results highlight the potential of PSMA-targeting dual-mode tracers for clinical translation in PET imaging, surgical navigation, fluorescence-guided surgery (FGS), and radioguided surgery (RGS).