The Current Status of Radionuclide Tumor Targeting Diagnosis and Therapy Based on FAP-2286: From Preclinical Studies to Clinical Application

In recent years, fibroblast activation protein (FAP) has demonstrated significant potential in oncology, and the development of FAP-targeted therapeutic agents has increasingly become a key research focus in the fields of molecular imaging and radionuclide therapy. Among these, FAP inhibitor (FAPI)-based small molecules have demonstrated favorable pharmacokinetics and imaging potential, showing promising potential in the diagnosis and treatment of tumors. As a peptide-based radiopharmaceutical derived from structural optimization of FAPI, FAP-2286 consists of a FAP-specific binding peptide conjugated to a DOTA chelator. It not only preserves the high affinity and favorable imaging characteristics of small-molecule FAPI tracers but also markedly prolongs tumor retention, thereby enabling both diagnostic and therapeutic applications. Preclinical and early clinical studies have shown encouraging results, characterized by prolonged in vivo retention and a favorable safety profile, supporting its use as a theranostic agent. This review provides a comprehensive overview of the current literature on FAP-2286, from preclinical development to clinical translation, highlighting its diagnostic value, the status of FAP-targeted radionuclide therapy, and the challenges and opportunities in advancing FAP-based theranostics.