5-羟色胺转运体显像剂[^(125)I]-ADAM的合成以及初步生物学分布

Synthesis and evaluation of serotonin transporter imaging agent [^(125)I]-ADAM

完成了5-羟色胺转运体显像剂[125I]-2-((2-((二甲基氨基)甲基)苯基)巯基)5-碘苯胺([125I]-2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine,[125I]ADAM)的制备和初步生物学特性的评价。以2,5-二溴-硝基苯和2-巯基苯甲酸为起始原料,合成标记前体5-三丁基锡-2-[2-(二甲基氨基甲基苯基巯基)]苯胺,采用双氧水标记法标记;并进行了大鼠体内和脑内的初步生物分布研究。合成标记前体5-三丁基锡-2-[2-(二甲基氨基甲基苯基巯基)]苯胺的总产率为42%,用[125I]NaI标记后,TLC测放射化学纯度(RCP)大于95%;125I-ADAM大鼠脑摄取高,在富含5-羟色胺转运蛋白的丘脑中的摄取随时间延长而增加,滞留时间长,其特异结合在注射后60min、120min和240min分别为3.38,3.62和4.36。本合成方法总收率高,标记方法简便,放射化学纯度高,125I-ADAM初始进脑量高,与SERT结合特异,可望用于研究脑内SERT功能。

Synthsis of a new ligand： 2-（（2-（（Dimethylamino）methyl）phenyl）thio）-5-iodophenylamine（^125I-ADAM） as a serotonin imaging agent is reported. The radioiodinated ligand was prepared by iododestannylation reaction using hydrogen peroxide. The chemical structure of the labeling precursor （5-（tributylstannyl）-2-（（2-（（dimethylamino） methyl）phenyl）thio）phenylamine） and all intermediates were verified by IR, HNMR and MS. The radiochemical purity of ^125I-ADAM was above 95% determined by TLC. Biodistribution studies in rats showed that the initial uptake of ^125I-ADAM in the brain was high, and consistently the highest binding appeared in hypothalamus, a region with the highest density of SERT. The specific binding （（T/CB）-I） of ^125I-ADAM in hypothalamus were 3.38, 3.62 and 4.36 at 60 min, 120 min and 240 min postinjection, respectively. These data suggest that ^125I-ADAM may be useful for SPECT imaging of SERT binding sites in the brain.