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

作者：Pei Wang, Shuai Wang, Futao Liu, Yanan Ren, Qian Guo, Qian Zhang, Xingguo Hou, Yuan Yao, Hua Zhu, Zhi Yang · 发表于：Molecular Pharmaceutics · 年份：2023 · DOI：10.1021/acs.molpharmaceut.2c01000 · 被引用次数：34 · 研究领域：Peptidase Inhibition and Analysis、Radiopharmaceutical Chemistry and Applications、Prostate Cancer Treatment and Research

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, [ 68 Ga]Ga-FAPI-PSMA, was prepared by radiolabeling conjugated DOTA-FAPI-PSMA with the short half-life radionuclide gallium-68 ( 68 Ga), which is dedicated to prostate cancer diagnostic imaging. In vitro, [ 68 Ga]Ga-FAPI-PSMA had higher affinity for the PSMA and FAP high-expressing cell lines 22Rv1 and U87 MG with IC 50 values of 4.73 and 2.10 nM, respectively, than in the corresponding negative expression cell lines PC 3 and A549, and significant differences in cell uptake were also observed. In vivo, [ 68 Ga]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, [ 68 Ga]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 [ 68 Ga]Ga-FAPI-PSMA was successfully prepared for in vivo prostate cancer PET/CT imaging.