5-HT_(1A)受体显像剂^(18)F-MPPF的制备及其生物学特性评价  

Preparation and biological evaluation of ^(18)F-MPPF as a 5-HT_(1A) imaging agent

作　　者：吴春英[1] 林祥通[1] 陆春雄[2] 邹美芬[2] 张政伟[1] 刘平[1] 薛方平[1] 陈正平[2] 蒋泉福[2] 傅榕赓[2] 王颂佩[2] 张同兴[2] 李晓敏[2] 朱钧清[2] 

机构地区：[1]复旦大学附属华山医院核医学科PET中心,上海现在200235 [2]江苏省原子医学研究所

出　　处：《中华核医学杂志》2004年第2期121-123,i001,共4页Chinese Journal of Nuclear Medicine

基　　金：江苏省 1 35医学重点人才基金资助项目 (RC2 0 0 2 0 68) ;江苏省"六大人才高峰"基金资助项目

摘　　要：目的　探讨 5 羟色胺 (5 HT1A)受体显像剂 4 1 8F N 2 [1 (2 甲氧基苯基 ) 1 哌嗪基乙基 ] N 2 吡啶基 苯甲酰胺 (1 8F MPPF)的1 8F标记方法及其生物学特性。方法　以氟化聚铵 (kryptofix K+ 1 8F)为亲核试剂 ,在二甲亚砜 (DMSO)溶液中与 4 (2′ 甲氧基 苯基 ) 1 [2′ (正 2″ 吡啶基 ) 对硝基苯甲酰胺 ] 乙基哌嗪 (MPPNO2 )进行氟代亲核置换反应 ,用HPLC检测放射化学纯度 (RCP) ;进行1 8F MPPF大鼠脑内分布和阻断实验、大鼠脑放射自显影及异常毒性实验。结果　HPLC检测示1 8F MPPF与杂质分离好 ,RCP >95 % ;大鼠脑内分布实验表明 ,放射性在脑内不同区域的清除速率不同 ,小脑清除最快 ,海马最慢 ,海马每克组织百分注射剂量率 (%ID g)在注药后 2 ,30和 6 0min分别为 0 86 2 ,0 196和 0 0 4 8,注药后 30min ,海马特异结合 [(T CB) - 1]可达 2 70 ;预先给予 8 羟基 2 N ,N′ (双正丙基 )氨基四氢萘(8 OH DPAT)、4 (2′ 甲氧基 苯基 ) 1 [2′ (正 2″ 吡啶基 ) 环己烷碳酰胺 ] 乙基哌嗪 (WAY10 0 6 35 )和螺环哌啶酮 (Spiperone)后 ,海马 (T CB) - 1分别降至 0 89,0 74和 1 93;放射自显影示 ,1 31 I 4 (2′ 甲氧基 苯基 ) 1 [2′ (正 2″ 吡啶基 ) 对碘苯甲酰胺 ] 乙基哌嗪Objective To develop and evaluate 4- 18 F-fluoro- N -2-[1-(2-methoxyphenyl)-1-piperazinyl]ethyl- N -2-pridinyl-benzamide ( 18 F-MPPF) as a 5-hydroxytryptamine (5-HT 1A ) imaging agent. Methods Nucleophilic substitution of fluoro replacement reaction was proceeding in dimethyl sulfoxide (DMSO) solution by oil-bath heating. Radiochemical purity (RCP) was determined by high pressure liquid chromatography (HPLC). Biological evaluations were performed in rats and mice. Results RCP determined by HPLC was over 95% and were stable within 3 h. Biodistribution studies in rats showed that the initial uptake of 18 F-MPPF in the brain was high [(0.621±0.010) %ID/organ at 2 min]. The specific binding in hippocampus reaches its peak value of 2.70 at 30 min postinjection. (T/CB)-1 in hippocampus were significantly reduced to 0.89,0.74 and 1.93 by pretreatment with 8-hydroxy-2- N,N -(di- n -propyl) aminotetralin (8-OH-DPAT),4-(2′-methoxy-phenyl)-1-[2′-( n -2″-pyridinyl)-cyclohexanecarboxamido]-ethyl-piperazine (WAY100635) and spiperone at 30 min postinjection,respectively. The rat brain autoradiography and analysis showed that there was high 131 I-4-(2′-methoxy-phenyl)-1-[2′-( n -2″-pyridinyl)- p -iodobenzamido]-ethyl piperazine (MPPI) upake in hippocampus,the hippocampus/cerebellum ratio was significantly reduced from 13.98±0.87 to 1.96±0.46 by pretreatment with 8-OH-DPAT at 30 min postinjection. Conclusions 18 F-MPPF can be specifically accumulated in hippocampus. It suggests that 18 F-MPPF might be a useful imaging agent for the studies of localization,function and modulation of 5-HT 1A receptor in the brain.

关 键 词：5-HT1A受体 显像剂 ^18F-MPPF 制备 生物学特性 评价 药代动力学 

分 类 号：R817[医药卫生—影像医学与核医学]