两种^(125)I-β-CIT的动物体内分布研究

Comparative study on biodistribution of domestic and imported ^(125)I-β-CIT

目的 研究国内研制的1 2 5I 甲基 3 β ( 4 碘苯基 )托烷 2 β 羧酸甲基脂 ( β CIT)动物体内分布情况 ,并与RBI公司的1 2 5I β CIT进行对比。 方法 1 2 5I β CIT制备采用Iodogen标记法 ;行兔血药清除动力学实验、小鼠体内分布实验和SD大鼠放射自显影实验。结果 1 2 5I β CIT标记率为 ( 91.10±8 0 9) %。兔血液时间 放射性曲线符合血液动力学二室模型 ,拟合曲线方程为 :C =0 .3 44 8e- 1 1 .1 57t+0 172 4e- 0 .2 38t。国内研制的1 2 5I β CIT在正常小鼠体内分布与RBI公司的1 2 5I β CIT基本一致 ,主要分布在纹状体 ,额叶、顶叶、颞叶、枕叶皮质、海马、脑干等亦摄取。1 2 5I β CIT注射后 2h纹状体摄取最大值达3 1.88%ID g ,大脑皮质、海马、脑干均于 45min内达摄取高峰 ,小脑 5min达摄取高峰。全脑于1 2 5I β CIT注射后 3 0min摄取值最大 ,为 6.11%ID。1 2 5I β CIT在体内肺摄取量最大 ,为 3 0 .6%ID g ,其次为肝、肾、脾、肠道、心脏、胃。纹状体的特异摄取率 6h最大 ,为 17.43 ,2 4h为 5 .76,大脑皮质、海马、脑干的特异性摄取率均低于 4。放射自显影示国内研制的1 2 5I β CIT主要分布在纹状体区。 结论国内研制的β CIT有望成为一种多巴胺受体显像剂 。

Objective To characterize the kinetics and biodistribution of a domestically synthesized 125I-2β-carbomethoxy-3β-4-iodopheny1tropane (β-CIT ) and to compare it with that of 125I-β-CIT imported from RBI company. Methods ①The biodistribution of domestic and RBI company produced 125I-β-CIT in KM mice. Twenty groups of mice (group of 5) were injected into the tail vein with either one of 125I-β-CIT products. Each group of both products was killed at 5,15,30 and 45 min, and 1,2,4,6,8 and 24 h. ② Autoradiography was performed on the brain of SD rats at 2 h after injection. Results Domestic 125I-β-CIT was primarily uptaked in the striatum, also in areas rich in 5-HTT such as the brain stem, frontal cortex, parietal cortex, temporal cortex, occipital cortex and hippocampus. Striatal uptake peaked at 2 h postinjection of 125I-β-CIT. The ratio of specific to nonspecific binding in striatum peaked at 6 h. The highest radioactivity was in the lungs and the less radioactivity was in the liver, kidney, spleen and intestine. Autoradiography confirmed that 125I-β-CIT primarily bound to striatum and lower room temperature significantly reduced the binding of the agent. Conclusion The domestic 125I-β-CIT binds primarily to dopamine transporters in the striatum in mice and rats and the maximum uptake is in the lungs.