Luo Yihui, Fu Haitian, Yu Chunjing
Wuxi School of Medicine, Jiangnan University, Wuxi, China.
Department of Nuclear Medicine, Affiliated Hospital of Jiangnan University, Wuxi, China.
Front Pharmacol. 2025 May 14;16:1593380. doi: 10.3389/fphar.2025.1593380. eCollection 2025.
The discovery of biomarkers for malignant tumors is driving the development of new radiopharmaceuticals in nuclear medicine. The development and optimization of novel radiopharmaceuticals to occupy an increasingly important role in tumor diagnosis and treatment. In recent years, fibroblast activation protein (FAP) has gained attention as a promising tumor target due to its widespread expression across various tumors. FAP inhibitor (FAPI) radiopharmaceuticals are considered to be the most promising to be developed for targeting FAP due to their rapid and specific tumor targeting. This review briefly outlines the developmental history of FAP-targeted small-molecule enzyme activity inhibitors, highlighting the effective role of targeting molecules, linkers, and certain functional groups in the delivery of radioisotopes to cancerous tissues. These development strategies will serve as a reference for the further development and application of relevant radiopharmaceuticals. This review also delineates the progress on clinical FAPI as a radioisotope delivery vehicle for the targeted radioligand therapy of tumors and introduces the latest combination therapy involving FAPI radiopharmaceutical for tumor treatment. The findings provide novel therapeutic insights into the targeted radioligand therapy of tumors.
恶性肿瘤生物标志物的发现推动了核医学中新放射性药物的发展。新型放射性药物的研发与优化在肿瘤诊断和治疗中发挥着越来越重要的作用。近年来，成纤维细胞活化蛋白（FAP）因其在各种肿瘤中广泛表达而成为有前景的肿瘤靶点，受到关注。FAP抑制剂（FAPI）放射性药物因其快速且特异性的肿瘤靶向性，被认为是最有开发前景的靶向FAP的药物。本文综述简要概述了FAP靶向小分子酶活性抑制剂的发展历程，强调了靶向分子、连接体和某些官能团在将放射性同位素递送至癌组织中的有效作用。这些发展策略将为相关放射性药物的进一步研发和应用提供参考。本文综述还阐述了临床FAPI作为肿瘤靶向放射性配体治疗的放射性同位素递送载体的进展，并介绍了涉及FAPI放射性药物用于肿瘤治疗的最新联合治疗方法。这些发现为肿瘤靶向放射性配体治疗提供了新的治疗思路。
