新型核素^64Cu标记硝基咪唑类肿瘤乏氧显像剂及正电子发射断层扫描显像研究  

Radio-labelling and Micro-PET Study of ^(64)Cu Labelled Pn AO-1-(2-nitroimidazole) for Hypoxia Imaging

作　　者：罗政[1,2] 朱华[1,2] 林新峰[1,2] 洪业[1,2] 肖绍文 张强[4] 褚泰伟[4] 杨志[1,2] 

机构地区：[1]北京大学肿瘤医院 [2]北京市肿瘤防治研究所核医学科,恶性肿瘤发病机制及转化研究教育部重点实验室,北京100142 [3]北京市肿瘤防治研究所放射治疗科,北京100142 [4]北京大学化学与分子工程学院,北京100871

出　　处：《高等学校化学学报》2015年第1期87-92,共6页Chemical Journal of Chinese Universities

基　　金：国家自然科学基金(批准号:81071198,81172083,81371592);北京市自然科学基金(批准号:7132040)资助~~

摘　　要：采用新型核素64Cu标记了含丙烯胺肟[Pn AO(3,3,9,9-Tetramethyl-4,8-diazaundecane-2,10-dione Dioxime)]结构的硝基咪唑类乏氧显像剂Pn AO-1-(2-nitroimidazole)[BMS181321],通过优化反应条件,于室温下反应10 min后即得到高放化纯度和高比活度的标记化合物64Cu-BMS181321.目标产物经放射性高效液相色谱检测验证和体外稳定性实验确认后,通过尾静脉注射到人源胰腺癌(PANC-1细胞系)裸鼠体内,分别于注射显像剂4和8 h后进行小动物正电子发射断层扫描显像(Micro-PET).结果表明,4 h左右肿瘤乏氧区域有良好的放射性浓聚.64Cu-BMS181321的合成及其分子显像研究开创了64Cu标记硝基咪唑类乏氧显像剂进行乏氧显像的先例,经进一步药物临床实验评价后,64Cu-BMS181321有望成为具有良好前景的PET乏氧显像药物.Monitoring hypoxia is very important for tumor treatment, the ideal hypoxia imaging agents should have a relatively long half-life and specific to hypoxic cells. However, such an ideal imaging agent has not been developed until now. In order to develop an ideal imaging agent for monitoring hypoxia, nitroimidazole imaging agent PnAO-1-（2-nitroimidazole）[BMS181321] was synthesized and radiolabeled with 64Cu for 64Cu- BMS181321 . The basic experimental process is as follows：the BMS181321 dissolved in sodium acetate buffer （pH=5. 5） was added to the eluent of 64CuCl2, and the solution was stirred and placed at room temperature for 10 min. The labelling efficiency and radiochemical purity of 64 Cu-BMS181321 were all over 99%, deter- mined by radio-HPLC. The 64 Cu-BMS181321 was stable in physiological saline for more than 15 h, which was a meaningful characteristic for clinical application. After quality control, 21. 8 MBq of 64 Cu-BMS181321 was injected into human pancreatic cancer xenograft mouse models via tale vein. Positron emission tomography （ PET） images were taken at 4 and 8 h after the injection. PET imaging in human tumor models was excellent compared with other PET hypoxia imaging agents. In brief, the research results suggest that 64 Cu-BMS181321 is potential for PET hypoxia imaging in clinical and should be further evaluated in clinic trial.

关 键 词：硝基咪唑 64Cu 正电子发射断层显像 乏氧显像 

分 类 号：O628[理学—有机化学] O652[理学—化学]