多巴胺D2受体显像剂^(131)I-nalepride的制备和动物体内研究  

Preparation and animal in vivo study of ^(131)I-nalepride as a dopamine D2 receptor imaging agent

作　　者：王立振[1] 杨敏[1] 徐宇平[1] 潘栋辉[1] 陈飞[1] 

机构地区：[1]江苏省原子医学研究所/卫生部核医学重点实验室/江苏省分子核医学重点实验室,江苏无锡214063

出　　处：《重庆医学》2014年第2期129-131,135,共4页Chongqing medicine

基　　金：国家自然科学基金资助项目(30670714;81171339;81101077);中国博士后科学基金(2013M531389);江苏省博士后基金(1301165C);江苏省自然科学基金项目(BK2008108;BK201116;BE2012622;BL2012031);江苏省高技术研究计划(BG2006604)

摘　　要：目的探讨多巴胺D2受体显像剂131I-nalepride(131I-(s)-(-)-N-[(1-烯丙基-2-吡咯烷基)甲基]-2,3-二甲氧基-5-三丁基锡苯甲酰胺)的制备以及在小动物体内的性质,评价其在神经精神疾病诊断应用中的可行性。方法以(s)-(-)-N-[(1-烯丙基-2-吡咯烷基)甲基]-2,3-二甲氧基-5-三丁基锡苯甲酰胺为标记前体,用双氧水法进行131I-nalepride的标记,行ICR小鼠生物分布特性实验,并对SD大鼠进行阻断实验和脑部放射自显影研究。结果 131I-nalepride标记率和放化纯均大于95%;ICR小鼠生物分布特性研究结果显示131I-nalepride在小鼠纹状体中摄取最多,小鼠尾静脉注射131I-nalepride 4h后,纹状体与小脑比值即达111.87,12h后达到最高,为416.97;SD大鼠阻断实验和脑部放射自显影结果显示,在注射131I-nalepride后,纹状体与小脑的光密度比值从7.43±0.86降至1.07±0.18,与阻断前比较差异有统计学意义(P<0.05),说明131I-nalepride与多巴胺D2受体特异性结合很高;131I-nalepride进入血液后迅速被组织摄取,其中以肝、肾的早期摄取最高,肝为(14.82±3.88)%ID/g,肾为(10.28±1.65)%ID/g,各脏器的清除均较快。结论 131I-nalepride对多巴胺D2受体具有高度亲和性和特异性,可作为多巴胺D2受体的单光子发射计算机断层成像术显像剂并作为工具药筛选、评价其他抗精神病药物对多巴胺D2受体的亲和力。Objective To study the preparation of 131I-nalepride and its characters in small animal in vivo,and to evaluate the feasibility for its application in diagnosing neuropsychiatric disease. Methods s-5-（tributyltin）- N E（1-ethyl-2 pyrrolidinyl） meth yl]-2,3-dimethoxy-benzamide was used as the labeled precursor. The hydrogen peroxide method was adopted to labeP31 I-nalepride.The bio-distribution character test in ICR mice was performed. SD rats were performed the blocking experiment and the cerebral au- toradiography. Results The radiolabeled yield and radiochemical purity were over 95 ~. The results of the bio distribution character test showed that the striatum had the highest uptake. The striatum to cerebellum uptake radio（ST/CB） reached 111.87 at 4 h after injection and the maximum ST/CB value of 416.97 at 12 h after injection. Regional brain autoradiography showed that the optical densities were significantly decreased from 7.43±0.86 to 1.07±0.18 after injection of 1311-naleprid（P〈0.05）. These results indi- cated that 1811 nalepride had specific binding to the dopamine D2 receptor. 1311 nalepride was rapidly uptaken by organs after injec- tion. The initial uptake in liver and kidney were higher and the % ID/g values were 14.82±3.88 and 10.28±1.65 receptively. The tracer was cleared out from the organ quite rapidly. Conclusion 131i_nalepride has the high affinity and specificity to dopamine D2 receptor,which could be used as the EPECT imaging agent of dopamine D2 receptors and as a tool drug to screen and evaluate the affinity of other antipsychotic agents to dopamine D2 receptors.

关 键 词：受体 多巴胺D2 131I-nalepride 显像剂 生物分布 

分 类 号：R943[医药卫生—药剂学]