脑乙酰胆碱酯酶的PET显像剂[^(11)C]4-乙酰氧基-N-甲基哌啶在大鼠体内分布的研究  

The Distribution of[^(11)C]MP4A-a PET Imaging Agent for Brain Acetylcholinesterase Activity in Rat

作　　者：周玲[1] 管一晖[2] 薛方平 张政伟[2] 刘平[2] 丁正同[1,3] 蒋雨平[1,3] 

机构地区：[1]复旦大学上海医学院神经病学系,200032 [2]复旦大学PET中心,200235 [3]复旦大学附属华山医院神经内科,200040

出　　处：《中国临床神经科学》2008年第6期580-584,共5页Chinese Journal of Clinical Neurosciences

基　　金：上海市经济委员会资助(编号:05JYYY-49)项目负责人蒋雨平

摘　　要：目的:研究脑乙酰胆碱酯酶(AChE)活性的正电子断层扫描(PET)诊断显像剂[^(11)C]4-乙酰氧基-N-甲基哌啶([^(11)C] MP4A)在大鼠体内的摄取和分布。方法:正常雌性SD大鼠尾静脉注射[^(11)C]MP4A,按注射后5、15、25、35、45和60 min时间点分组后断头处死动物,迅速取血,分离脏器和脑(大脑皮质、小脑和脑干),用自动γ放射性计数仪计算经衰变校正后不同时间点各脏器放射性摄取率,以%ID/g表示。结果:一次剂量的[^(11)C]MP4A静脉注射后,血中5 min时%ID/g为(13.44±1.88),清除迅速,60 min时接近于基线水平;各脏器组织中%ID/g 15～25 min达到稳态;大脑皮质5 min%ID/g为(2.26±0.29)。脑内各区域的摄取在注射后15～25 min达到稳态。皮质的平均%ID/g>小脑,两者比值范围为1.13～2.08;60min时小脑、脑干和皮质的%ID/g与其最高峰相比分别下降了77%、80%和40%;皮质放射活性清除最慢。结论:[^(11)C]MP4A血中清除迅速。脑各区域摄取在短时达到稳态,提示[^(11)C]MP4A有较好的脂溶性,易透过血脑屏障;皮质摄取比小脑高但清除慢,表明[^(11)C]MP4A能更好反映皮质AChE活性,适合作为脑AChE活性的PET诊断显像剂。Aim： To study the uptake and distribution of the N-[^11C]methyl-4-piperidyl acetate （[^11C]MP4A）, a tracer for in vivo measurement brain acetylcholinesterase （ACHE） activity using positron emission tomography （PET） in rats. Method：[^11C]MP4A were administered intravenously in SD rats. At 5,15,25,35,45,60 min after injection, rats were decapitated. Blood, organ tissue and brain （cerebral cortex, cerebellum and brainstem） samples were obtained. The samples were weighted and the radioactivity was measured. The radioactivity was expressed as %ID/g. Results： The blood showed rapid and high uptake and rapid elimination of radioactivity after injection ： the %ID/g was 13.44 ± 1.88 at 5 min and almost base level at 60 min. The organ uptakes were almost constant between 15-25 min. The average %ID/g in kidney was highest. The %ID/g in cerebral cortex was 2.26 ± 0.29 at 5 min after injection of [^11C]MP4A. The uptakes of all the regions in brain were also constant between 15-25 min. The average %ID/g in cortex was higher than that in cerebellum and the radioactivity ratio of cortex/cerebellum was 1.13-2.08. The %ID/g in cerebellum, brainstem and cerebral cortex at 60rain after injection reduced by 77%, 80% and 40% differently contrast to their highest %ID/g values. Conclusion： The uptake in blood was rapid and highest after injection at once. Each region uptake of brain reached constant in short time. These showed [^11C]MP4A had a better liposolubility to reach through blood-brain barrier. The uptake in cortex was higher and the elimination was slower, so the [^11C]MP4A can well image the activity of AChE in cortex. [^11C]MP4A is a suitable agent for in vivo measurement brain AChE activity in the further study.

关 键 词：乙酰胆碱酯酶 正电子发射断层扫描 [^11C]4-乙酰氧基-N-甲基哌啶 分布 

分 类 号：R749.1[医药卫生—神经病学与精神病学] R817.4[医药卫生—临床医学]