^(99)Tc^m-REG的制备及其在正常小鼠体内分布和药代动力学研究  

Biodistribution characteristics and pharmacokinetics in normal mice and uptake of ^(99)Tc^m-REG

作　　者：谢文晖[1] 章斌[2] 刘慈懿[1] 常城[1] 雷贝[1] 王利华[1] 曾骏 吴翼伟[2] 

机构地区：[1]上海交通大学附属胸科医院核医学科,上海200030 [2]苏州大学附属第一医院核医学科,苏州215006 [3]无锡亿仁肿瘤医院,无锡214000

出　　处：《上海交通大学学报（医学版）》2014年第3期283-288,共6页Journal of Shanghai Jiao tong University:Medical Science

基　　金：上海市自然科学基金(11ZR1433700);上海市卫生局基金(2010066)~~

摘　　要：目的研究99Tcm-精氨酸-谷氨酸-甘氨酸(99Tcm-REG)与肺癌细胞结合及其在正常小鼠体内分布和药代动力学。方法采用99Tcm直接法标记REG,行99Tcm-REG与非小细胞肺癌细胞A549和H1299的结合实验。正常小鼠尾静脉注射99Tcm-REG后不同时间处死,取主要脏器或组织,测定其每克组织百分注射剂量率(%ID/g)。另取尾静脉注射99Tcm-REG后不同时间小鼠血液,测量放射性计数并计算药代动力学参数。尾静脉注射99Tcm-REG后,测定不同时间荷H1299细胞肿瘤裸鼠肿瘤%ID/g及肿瘤/肌肉比值。结果99Tcm直接标记REG的标记率为(92.90±2.86)%。99Tcm-REG与非小细胞肺癌细胞A549和H1299的最高结合率分别为(1.29±0.16)%和(2.32±0.31)%。体内分布提示99Tcm-REG在小鼠血液中清除迅速,2 h时放射性仅为注射5 min时的20.26%,肝脏内放射性浓聚较多,且呈缓慢下降,肾脏、心、肺放射性摄取随时间逐渐下降,其余组织放射性呈低水平。2 h肿瘤%ID/g为2.02±0.67,肿瘤/肌肉比值为3.50±1.27。结论99TcmREG具有亲肺癌细胞的特性,有可能成为一种亲肺癌肿瘤显像剂。Objective To investigate the uptake of 99Tcm labeled arginine-glutamic-glycine （REG） in human lung cancer cells and the biodistribution characteristics and pharmacokinetics of 99Tcm labeled REG in normal mice. Methods The REG was directly labeled by the 99Tcm and binding tests of 99 Tcm and non- small cell lung cancer cells A549 and H1299 were performed. Normal mice were killed at different time points after receiving tail intravenous injections of 99Tcm-REG. Major organs or tissues were excised for determining the percentage of the injected dose per gram of tissue mass （% ID/g）. The blood at different time points after mice had received tail intravenous injections of 99Tcm-REG was measured by the gamma counter and parameters of pharmacokinetics were calculated. The tumor % ID/g of H1299 tumor-bearing nude mice and tumor/muscle ratio were measured at different time points. Results The values of radiochemieal purity of 99Tcm-REG were （92.90± 2. 86）% . The binding rates of 99Tcm-REG and A549 cells, and 99Tcm-REG and H1299 cells were （1.29 ± 0. 16）% and （2.32 ±0.31）%, respectively. The biodistribution indicated that 99Tcm-REG in mouse blood was removed rapidly. The radioactivity at 2h after injection was only 20. 26% of the radioactivity at 5 rain after injection. The radioactivity was mainlyconcentrated in liver and slowly decreased with time. The radioactivity of kidneys, hearts, and lungs were decreased gradually with time and the levels of radioactivity of other tissues were low. The % ID/g of tumor was 2.02 ±0.67 and the tumor/muscle ratio was 3.50 ± 1.27 at 2h after itkiection. Conclusion 999Tc-REG can be uptaken by human lung cancer cells and may become a potential lung cancer imaging agent.

关 键 词：多肽 锝 肺癌 药代动力学 精氨酸-谷氨酸-甘氨酸 

分 类 号：R969.1[医药卫生—药理学]