目的：探讨多巴胺D2受体显像剂131 I-nalepride （131 I-（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131 I-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131 I-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131 I-nalepride在小鼠纹状体中摄取最多，小鼠尾静脉注射131 I-nalepride 4 h后，纹状体与小脑比值即达111．87，12 h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131 I-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131 I-nalepride与多巴胺D2受体特异性结合很高；131 I-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131 I-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 131 I-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-[(1-ethyl-2-pyrrolidinyl) meth-yl]-2 ,3-dimethoxy-benzamide was used as the labeled precursor .The hydrogen peroxide method was adopted to label131 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 131 I-naleprid(P<0 .05) .These results indi-cated that 131 I-nalepride had specific binding to the dopamine D2 receptor .131 I-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 131 I-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 .
展开▼
