一种靶向TGR5的胆汁酸类化合物的~(18)F标记与初步评价

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。

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

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 glucagons-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 expression 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 chemistry 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 TGR5-overexpression.