成纤维细胞激活蛋白靶向药物及其用于疾病显像和治疗的研究进展

Research progress of fibroblast activation protein targeting drugs and their application in disease imaging and therapy

成纤维细胞激活蛋白(FAP)在90%以上的上皮性肿瘤的癌症相关成纤维细胞(CAFs)中高丰度表达,具有特异性和广谱性,是肿瘤微环境靶向显像和治疗的研究热点。FAP靶向抗体、小分子抑制剂和多肽作为配体,通过偶联核素以及荧光探针用于肿瘤靶向显像、治疗、精准手术导航,并通过二聚体化以及新剂型构建(如白蛋白、纳米递送系统等)优化FAP靶向药物的生物分布,进而增加其在肿瘤内的滞留时间和增强生物学作用,推动其用于肿瘤靶向内放射性治疗和光热治疗。除了肿瘤,FAP也可为炎性疾病的显像和治疗提供有价值的靶点。笔者就近年来FAP在肿瘤和非肿瘤性疾病中的显像和治疗的研究进展进行综述。

Fibroblast activation protein(FAP)is highly expressed in cancer-associated fibroblasts(CAFs)of more than 90%epithelial tumors with specificity and broad spectrum.FAP ligands,such as targeted antibodies,small molecule inhibitors and peptides,are used in tumor targeted imaging,therapy and precise surgical navigation by coupling radionuclides and fluorescent probes.Moreover,through dimerization,construction of new dosage forms such as albumin,nano-delivery system and other means to optimize the biological distribution of FAP targeted drug to increase its retention and biological effects in tumor and promote its use in tumor targeted internal radiation therapy and photothermal therapy.In addition to neoplastic diseases,FAP can also provide valuable targets for imaging and therapy of inflammatory disease.This article reviews the research progress of imaging and therapy of FAP in tumor and non-tumor diseases in recent years.