5-HT_(1A)受体显像剂^(131)I-MPPI的合成和动物试验  

Synthesis and Biodistribution of ^(131)I-MPPI as 5-HT_(1A) Imaging Agent

作　　者：陆春雄[1] 吴春英[1] 蒋泉福[1] 邹美芬[1] 陈正平[1] 王颂佩[1] 张同兴[1] 李晓敏[1] 

机构地区：[1]江苏省原子医学研究所,江苏无锡214063

出　　处：《核化学与放射化学》2006年第3期183-187,共5页Journal of Nuclear and Radiochemistry

基　　金：江苏省"135"医学重点人才基金(RC2002068);江苏省"六大人才高峰"基金资助(2003-07)

摘　　要：为了找到适合123I标记的5-羟色胺(5-HT1A)受体显像剂,合成了4-三正丁基锡-N-[2-[1-(2-甲氧基苯基)]-1-哌嗪基]乙基-N-2-吡啶基-苯甲酰胺(MPPBu3Sn,标记前体),并采用双氧水标记法进行131I标记,得到标记物131I-MPPI,标记率大于90%,放化纯大于99%。初步动物实验结果显示,131I-MPPI在大鼠海马中摄取最多,30 min时,海马与小脑的摄取率比值为2.90,说明131I-MPPI浓集在海马中,与5-HT1A受体在脑中的分布一致;放射自显影结果显示,在注射8-OH-DPAT后,海马(CA3区)与小脑的光密度比值从13.98±0.87降至1.96±0.46,与阻断前差异显著,说明131I-MPPI与5-HT1A受体结合具有特异性;注射后5 min和120 min,甲状腺的摄取率分别为(0.069±0.020)%和(0.128±0.026)%,表明脱碘是其主要代谢途径;131I-MPPI对5-HT1A受体具有高度亲和性和特异性,可作为筛选其他化合物对5-HT1A受体亲和大小的工具药。The synthesis and biological evaluation of serotonin（5-HT1A） imaging agent [^131I]- 4-iodo-N-[- 2-[- 1-（ 2-methoxyphenyl ） ]-l-piperazinyl ] ethyl-N-2-pridinyl-benzami-de （^131I-MPPI）were reported. The chemical structure of aimed compound and intermediates were confirmed by IR, ^1H NMR and MS. Radiochemical purity is above 99% determined by TLC. Biodistribution of ^131I-MPPI in rats displayed high uptake in hippocampus and low uptake in cerebellum. The ratio of the uptake of ^131I-MPPI in hippocampus to cerebellum is 2. 90 at 30 min post-injection. Autoradiography of brain section displayed significant decrease of radioactivity in hippocampus when rats were pretreated with 8-OH-DPAT, a selective 5-HT1A agonist, compared with control. The uptake ratios of thyroid are（0. 069 ±0. 020）% and （0.128±0.026）% at 5 min and 120 min, respectively, and they are increased with time, suggesting that in vivo deiodination may be the major route of metabolism. These findings strongly suggested that ^131I-MPPI could be used as an in vivo marker for studies of the pharmacology of the 5-HT1A receptor system in animal.

关 键 词：5-HT1A受体 ^131I-MPPI 合成 显像剂 生物分布 

分 类 号：R817[医药卫生—影像医学与核医学]