Preclinical Evaluation of a Fibroblast Activation Protein and a Prostate-Specific Membrane Antigen Dual-Targeted Probe for Noninvasive Prostate Cancer Imaging

Prostate-specific membrane antigen (PSMA) is a prostate cancer target that plays a crucial role in prostate cancer diagnosis and therapy. Herein, a novel dual-targeted imaging probe, [⁶⁸Ga]Ga-FAPI-PSMA, was prepared by radiolabeling conjugated DOTA-FAPI-PSMA with the short half-life radionuclide gallium-68 (⁶⁸Ga), which is dedicated to prostate cancer diagnostic imaging. In vitro, [⁶⁸Ga]Ga-FAPI-PSMA had higher affinity for the PSMA and FAP high-expressing cell lines 22Rv1 and U87 MG with IC₅₀ values of 4.73 and 2.10 nM, respectively, than in the corresponding negative expression cell lines PC₃ and A549, and significant differences in cell uptake were also observed. In vivo, [⁶⁸Ga]Ga-FAPI-PSMA was rapidly cleared from the body, and the estimated radiation dose was relatively low compared with several other FAPI probes. In 22Rv1 and U87 MG tumor xenografts, [⁶⁸Ga]Ga-FAPI-PSMA rapidly accumulated in tumors after administration, and the best images can be obtained at 1 h postinjection. In conclusion, the dual-targeted probe [⁶⁸Ga]Ga-FAPI-PSMA was successfully prepared for in vivo prostate cancer PET/CT imaging.