靶向成纤维细胞激活蛋白分子影像的临床研究与应用进展  

Clinical research and application progress of fibroblast activation protein targeted molecular imaging

作　　者：付浩 陈皓鋆[1] 吴华[1] FU Hao;CHEN Haojun;WU Hua(Department of Nuclear Medicine,Minnan PET Center,The First Affiliated Hospital of Xiamen University,Xiamen 361003,China)

机构地区：[1]厦门大学附属第一医院核医学科,闽南PET中心,福建厦门361003

出　　处：《厦门大学学报（自然科学版）》2024年第5期917-932,共16页Journal of Xiamen University：Natural Science

基　　金：国家自然科学基金青年基金(82102094)。

摘　　要：[背景]肿瘤微环境中的肿瘤相关成纤维细胞(CAF)在肿瘤生物行为中起重要作用,成纤维细胞激活蛋白(FAP)作为CAF的特异性标志物,在90%的上皮肿瘤中均有表达.近年来,FAP抑制剂(FAPI)正电子发射断层成像(PET)在肿瘤疾病与非肿瘤疾病中的临床研究和应用进展迅速,成为领域内的前沿热点.[进展]FAPI PET/计算机断层扫描(CT)在包括头颈部肿瘤、肺癌、消化系统肿瘤、肉瘤等多种肿瘤的诊断评价中显示出克服其氟代脱氧葡萄糖(FDG)PET/CT的不足、显著提升诊断效能的优点.同时,以FAPI为载体的放射性核素诊疗一体化研究也引起关注.本文对FAPI PET/CT在肿瘤与非肿瘤疾病的临床研究和应用进展以及基于FAPI的放射性核素诊疗一体化研究动向进行综述.[展望]未来随着FAPI分子探针药动学的进一步提升,更多前瞻性大样本量的临床研究系统性评价FAPI分子影像在肿瘤疾病和非肿瘤疾病中的价值,以及不同治疗方式的联合,FAP有望成为重要的诊疗一体化靶点,为肿瘤治疗提供全新的策略.[Background]Cancer-associated fibroblasts(CAFs)are a major component of the tumor microenvironment(TME)and secrete growth factors,inflammatory ligands,and extracellular matrix(ECM),which promote tumor proliferation,therapy resistance,and immune exclusion.Fibroblast activation protein(FAP)is overexpressed on the cell membrane and in the stroma of CAFs in approximately 90%of epithelial neoplasms.However,it is not expressed in normal fibroblasts,normal epithelial cells,or the stroma of benign epithelial tumors.Therefore,FAP has emerged as a novel cancer target due to its wide distribution across numerous cancer types.[Progress]FAP-targeted imaging with radioiodine-labeled monoclonal antibody F19 was the first step in moving the concept of FAP-directed tumor stromal targeting from the preclinical phase to in vivo evaluation.FAP-targeting has been reported using a variety of approaches,including vaccines,chimeric antigen receptor(CAR)T cells,and peptide drug complexes.FAP inhibitors(FAPIs)with high selectivity and chemical stability,represent promising strategies for the development of FAPIs.Studies conducted using FAPIs,which have favorable radiopharmacokinetics,have initiated to the clinical application of FAP-targeted theranostics in various tumors.18 F-fluorode-oxyglucose(18 F-FDG)is the most widely used tracer for positron emission tomography(PET)imaging in the field of oncology.However,nonspecific and physiological radiotracer uptake in crucial organs reduces diagnostic accuracy in many cases,which has substantial disadvantages for various applications.FAPI PET is independent of glucose metabolism,leading to a low background signal in the brain,liver,nasopharyngeal,oral mucosa,and gastrointestinal tract.Additionally,FAPI PET can be used without any dietary preparation and provides stable tracer uptake from 10 min to 3 h after administration.Consequently,the clinical interest in FAPI imaging has shown an explosive increase,and FAPI imaging has been explored for various purposes in different clinical settings,yiel

关 键 词：成纤维细胞激活蛋白 分子影像 正电子发射断层成像 肿瘤疾病 非肿瘤疾病 放射性核素诊疗 

分 类 号：R44[医药卫生—诊断学]