一种靶向TGR5的胆汁酸类化合物的^(18)F标记与初步评价  

Synthesis and Preliminary Evaluation of ^(18)F-Labeled Bile Acid Compound for TGR5

作　　者：贾丽娜[1,2] 江大卫[1,2] 程登峰[3] 张岚[1] 

机构地区：[1]中国科学院上海应用物理研究所放射化学与工程技术部,上海201800 [2]中国科学院大学,北京100049 [3]复旦大学附属中山医院,上海200032

出　　处：《核化学与放射化学》2014年第4期247-252,共6页Journal of Nuclear and Radiochemistry

基　　金：国家自然科学基金资助项目(No.10875163)

摘　　要：G-蛋白偶联受体(TGR5)是一类位于细胞膜上的胆汁酸受体,与体内的糖代谢、能量代谢和胰高血糖素样多肽-1的分泌密切相关。相对于正常组织,TGR5在多种肿瘤组织中过量表达,并与患者的预后相关,是肿瘤诊断、治疗和预后评估的一个潜在靶点。因此,利用点击化学的方法简单高效的制备了一种靶向TGR5的18F-PET探针[18F]FEA-LCA。该探针具有较高的放射化学产率(66%~74%)、比活度(大于300PBq/mol)和放射化学纯度(大于99%)。[18F]FEA-LCA具有其母体化合物LCA相似的亲脂性,并具有良好的体外稳定性。本工作为进一步研究[18F]FEA-LCA作为TGR5过量表达的肿瘤的PET探针奠定了良好的基础。G protein-coupled receptor （TGR5） is a cell-surface bile acid receptor which is closely related to glucose metabolism, energy expenditure and the secretion of glucagon-like peptide-1. TGR5 is a potential target for diagnosis, treatment and prognosis evaluation of the tumors, whose expression is strongly upregulated in many tumors compared to expres- sion levels in normal tissues and is associated with the prognosis of the patients. Therefore, the 18F-PET probe [18F]FEA-LCA was prepared with the simply and efficiency click chemis- try method with a high radiochemical yield （66%-74%）, high radiochemical purity （〉99%）, and high specific activity （〉300 PBq/mol）. [18F]FEA-LCA has a similar lipophilicity to the parental bile acid lithocholic acid and a high metabolic stability in vitro.This work make a solid foundation for further study the [18F]FEA-LCA as the PET probe tO the tumors of TGRS-overexpression.

关 键 词：胆汁酸 TGR5 ^18F 石胆酸 PET显像 

分 类 号：R817[医药卫生—影像医学与核医学]