摘要
成纤维细胞激活蛋白(FAP)作为肿瘤特异性表达的泛癌靶点, 是放射性治疗药物研究的热点。该类药物能否成功实现临床转化需要跨学科的综合评价, 理想的药代动力学(PK)特征是其必要条件。该文总结了各种类型配体放射性治疗药物(如有机小分子、多肽中分子、非肽中分子和抗体大分子)的体内清除和转运, 细胞摄取和滞留的PK机制;基于非临床PK数据分析靶向FAP放射性治疗药物不同类型配体的优缺点;各类配体的多种修饰策略(如抗体片段化、白蛋白结合修饰、同异多聚化及点击化学共价反应基团修饰)对PK的影响;以及不同放射性治疗药物的临床PK数据对比, 以期为业内靶向FAP的放射性治疗药物研发提供参考。
Fibroblast activation protein(FAP)has attracted much attention as a pan-cancer target with tumor-specific expression.Successful translation of FAP-targeting radiotherapeutic drugs requires a multidisciplinary approach,in which ideal pharmacokinetic(PK)characteristics are essential.This paper summarizes the PK mechanisms governing systemic clearance,tissue distribution,cellular uptake,and intracellular retention of various ligands(such as organic small molecules,peptide mid-molecules,non-peptide mid-molecules,and antibody macromolecules),analyzes the advantages and disadvantages of FAP-targeting ligands based on non-clinical PK data,and reviews PK alterations following various modification strategies(such as antibody fragmentation,albumin binding,homo-or hetero-polymerization,and click chemistry modifications),as well as the comparison of clinical PK data of different FAP-targeting radiotherapeutic drugs.This review aims to provide references for the development of FAP-targeting radiotherapeutic drugs in the industry.
作者
张芝榕
张天宏
郝洺
颜洁
Zhang Zhirong;Zhang Tianhong;Hao Ming;Yan Jie(Qingdao Fengxi Pharmaceuticals Co.,Ltd.,Qingdao 266100,China)
出处
《中华核医学与分子影像杂志》
北大核心
2025年第9期566-570,共5页
Chinese Journal of Nuclear Medicine and Molecular Imaging
关键词
膜蛋白质类
放射性药物
药物疗法
药代动力学
FAP
发展趋势
Membrane proteins
Radiopharmaceuticals
Drug therapy
Pharmacokinetics
FAP
Trends D0I:10.3760/cma.j.cn321828-20241016-00351
