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靶向成纤维细胞活化蛋白放射性探针研究进展

Research progress of radioprobes targeting fibroblast activating protein

  • 摘要: 成纤维细胞活化蛋白(FAP)是癌症相关成纤维细胞和活化成纤维细胞的重要生物标志物,在许多肿瘤和纤维化组织的活化成纤维细胞上高表达,而在正常组织和非恶性肿瘤中基本不表达。因此,FAP已经成为肿瘤等疾病的诊断和治疗的优良靶标。基于FAP抑制剂(FAPI)的PET显像和内放射疗法已成为包括癌症、纤维化等多种疾病在内的新型诊疗手段,以介绍FAP介导疾病发生发展的机制及其作为靶标的诊疗意义为开端,对125I、68Ga、64Cu等多种放射性核素标记靶向FAP探针的结构演进、显像、体内生物分布及其药代动力学性质进行了系统总结,归纳了改善探针的药代动力学性质和靶标亲和力的相关策略,包括采用方酰胺连接子、使用白蛋白结合剂加以修饰、开发双靶向探针,对未来靶向FAP新型放射性探针的开发和经典探针的临床应用提出了一些参考建议。

     

    Abstract: Fibroblast activating protein (FAP) is an important biomarker of cancer associated fibroblasts and activated fibroblasts, which is highly expressed in activated fibroblasts of many tumor and fibrotic tissues, but not in normal tissues and non malignant lesions. Therefore, FAP has become an excellent target for diagnosis and treatment of tumors and other diseases. PET imaging and internal radiotherapy based on FAP inhibitor (FAPI) have been used in the diagnosis and treatment of many diseases, such as cancer and fibrosis. We first introduce the mechanism of disease occurrence and progression mediated by FAP and its clinical significance as a therapeutic target.Then,we systematically summarize the FAP probes labeled with 125I, 68Ga, 64Cu and other radionuclides, including their structural evolution, imaging, biodistribution and pharmacokinetic properties.After that, the reported strategies to improve the pharmacokinetic properties and target affinity of probes are summarized, including the use of squaramide linkers,modification with albumin binding agent,the development of dual-targeting probes.Finally, some suggestions for the future development of novel radioactive probes targeting FAP and the clinical application of classical probes are proposed.

     

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