18^F-AlF-NOTA-G-TMTP1的合成及对高转移潜能肝癌细胞荷瘤鼠的显像研究  

Synthesis and preliminary evaluation of 18^F-AlF-NOTA-G-TMTP1 for PET imaging on nude mice bearing high-metastatic potential hepatoma cells

作　　者：李业森[1] 张德良[2] 张现忠[2] 彭添兴[1] 范文博[1] 颜和平[1] 吴华[1] 

机构地区：[1]厦门大学附属第一医院核医学科,361003 [2]厦门大学分子影像暨转化医学研究中心

出　　处：《中华核医学与分子影像杂志》2015年第5期351-354,共4页Chinese Journal of Nuclear Medicine and Molecular Imaging

基　　金：基金项目：国家自然科学基金（81471684）

摘　　要：目的合成18^F-AlF-NOTA-G-TMTP1，并在高转移潜能肝癌细胞荷瘤裸鼠体内评价其生物学性质。方法通过固相法合成NOTA—G—TMTP1，利用18^F标记制得PET探针18^F-AlF-NOTA-G-TMTP1。分别用低转移潜能肝癌细胞株HCC97L和高转移潜能肝癌细胞株HCCLM3建立荷瘤裸鼠模型，并进行microPET／CT显像及生物分布研究。结果18^F-AlF-NOTA-G-TMTP1标记产率为（25±6）％（n=5），放化纯大于95％，比活度大于11．1GBq／I．~mol，脂水分配系数为一3．166＋_0．022。注射后35min的microPET／CT显像结果显示，18^F-AlF-NOTA-G-TMTP1在HCC97L和HCCLM3荷瘤裸鼠模型中的肿瘤／肌肉比值分别为1．8＋0．4和4．7±0．2。竞争性抑制实验结果显示，共注射G-TMTPl可将HCCLM3肿瘤对18^F-AlF-NOTA-G-TMTP1的摄取降低61．4％。结论成功合成的”F—A1F．NOTA．G．TMTPl可特异性靶向由高转移潜能肝癌细胞构建的瘤体。Objective To synthesize 18^F-AlF-NOTA-G-TMTP1 and evaluate its potential for PET imaging on nude mice bearing high-metastatic potential hepatoma cells. Methods NOTA-G-TMTP1 was synthesized by the standard Fmoc-solid phase synthetic protocols and radiolabeled with lSF using NOTA-A1F chelation method. The nude mice models bearing low-metastatic potential HCC97L and high-metastatic poten- tial HCCLM3 xenografts were established separately. The tumor-targeting characteristics of 18^F-AlF-NOTA-G-TMTP1 were assessed by microPET/CT and biodistribution assay. Results NOTA-G-TMTP1 was labeled with l8^F in one step with （25±6）% labeling yield （n= 5）. The radiochemical purity of 18^F-AlF-NOTA-G-TMTP1 was more than 95% with a specific activity more than 11.1 GBq/μmol. The octanol/water partition coefficient （logP） for ISF-A1F-NOTA-G-TMTP1 was -3.166±0.022. The tumor to muscle ratios were 1.8±0. 4 and 4.7±0.2 at 35 min post injection for HCC97L and HCCLM3, respectively. The uptake of 18^F-AlF-NOTA-G-TMTP1 in HCCLM3 tumor was inhibited （61.4%） by unlabeled G-TMTP1. Conclusion is 18^F-AlF-NOTA-G-TMTP1 has been successfully synthesized. It shows specific uptake by tumor induced by the high-metastatic potential hepatoma cells.

关 键 词：肝肿瘤 A1F-NOTA-G-TMTPl 氟放射性同位素 化学合成 体层摄影术 发射型计算机 小鼠 裸 

分 类 号：R735.7[医药卫生—肿瘤]