Chelator Optimization and Therapeutic Potential of (188)Re-FAPI for FAP-Targeted Radionuclide Therapy

螯合剂优化及(188)Re-FAPI在FAP靶向放射性核素治疗中的治疗潜力

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Abstract

Fibroblast activation protein (FAP) has emerged as a highly promising molecular target for cancer theranostics, with current research prioritizing the optimization of FAP-targeted radiopharmaceutical pharmacokinetics. The development of diverse FAP inhibitor (FAPI) probes conjugated with therapeutic radionuclides has significantly advanced the field of FAP-targeted radionuclide therapy (FAP-TRT). Among available radionuclides, rhenium-188 has emerged as a particularly valuable theranostic radionuclide, offering the rare combination of economical availability, therapeutic β(-) emissions (E (max) = 2.12 MeV), and γ emissions suitable for SPECT imaging (155 keV, 15% abundance). The strategic development of (188)Re-labeled FAPI compounds represents a promising approach to enhance the efficacy and clinical translation of FAP-targeted radionuclide therapy. A recent study has developed and evaluated four novel (188)Re-labeled FAP inhibitors through rational structure optimization, which provided a cost-effective viable alternative to established therapeutic radionuclides in clinical oncology.

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