11^C-HupA在正常大鼠体内的分布及药代动力学特征

目的利用自制的11^C-石杉碱甲（HupA）研究治疗阿尔茨海默病（AD）的有效药物HupA在正常大鼠体内的生物学分布及药代动力学特征。方法经SD大鼠尾静脉注射11^C-HupA,分别于5,15,30,60和90min测量血液及各主要组织器官的放射性,计算每克组织百分注射剂量率（％ID／g）。经大鼠尾静脉取血进行药代动力学分析;25只SD大鼠尾静脉注射11^C-HupA后,于上述不同时间点分别将各组（每组5只）大鼠断头处死,迅速解剖取脑,分离额叶、顶叶、颞叶、枕叶、小脑、海马、纹状体、丘脑、脑干等脑区,计算％ID／g。采用SPSS11．5软件,组间比较采用方差分析。结果11^C-HupA进人大鼠体内具有血液清除快的特点,半衰期（T1/2）为（14．61±1．77）min,药物自体内总清除率（CL）为（0．12±0．01）ml·min^-1·k^-1,经肝胆系统代谢,肾是11^C-HupA的主要排泄器官,在注射后15min达到高峰,为（3．56±0．36）％ID／g,之后呈逐渐下降的趋势;肝在15min为（2．55±0．34）％ID／g,60min之前放射胜分布维持在较高的水平。11^C-HupA在肌肉、皮肤等组织放射性分布较少。大鼠血时间-放射性浓度曲线符合药代动力学一室模型,曲线下面积（AUC）0-∞为（167．57±12．39）kBq·ml^-1·min^-1。11^C—HupA在各脑区放射性分布差异有统计学意义（F=9．96,8．72,26．28,9．33,8．48,P均〈0．001）,大脑皮质、海马、丘脑及脑干分布较多。结论11^C—HupA药代动力学研究简便、快速,特异性好,灵敏度高,可定量观测脏器功能。其在大鼠脑内分布特点为治疗AD提供了一定的依据。

Pharmacokinetics and biodistribution of 11C-HupA in the normal animal

Objective HupA is one of the potential drugs which can be used to treat Alzheimer's disease(AD).The aim of this study was to explore the pharmacokinetics and biodistribution of HupA in vivo by using 11C-HupA.Methods A total of 25 SD rats were studied.They were divided into 5 groups (5 rats in each group).All had intravenous injection of 22 MBq(in0.2 ml)11C-HupA through tail vein.Dynamic im-aging Was acquired from 5 to 90 minutes after injection.Venous blood and organ activities were collected at 5,15,30,60.and 90 minutes after injection.Percentage activity of injected dose per gram of tissue(%ID/g)was calculated to characterize the biodistribution of tracer in different brain regions: frontal,apical, temporal,occipital,cerebellum,hippocampus,striatum,thalamencephalon, and brain stem, Variance analysis using SPSS 11.5 software was performed and compared among the study groups.Results 11C-HupA was character-istic for its quick clearance from blood,with half time T1/2 of (14.61±1.77) min,and clearance rate (CL)macokinetics of 11C-HupA in rats corresponded to a one-compartment model.with an activity curve(area 11C-HupA distribution in different brain regions,being greater in cerebral cortex,hippocampus,hypothala-mus and brain stem. Conclusions Pharmacokinetic study of 11C-HupA in brain was fast.convenient and showed high specificity and sensitivity.Its ability to quantitatively evaluate brain function and its character-istic distribution in mice provided some evidence for monitoring therapy in AD patients.