中华核医学杂志
中華覈醫學雜誌
중화핵의학잡지
CHINESE JOURNAL OF NUCLEAR MEDICINE
2009年
2期
109-112
,共4页
闫瑾%管一晖%薛方平%张政伟%刘平%林祥通
閆瑾%管一暉%薛方平%張政偉%劉平%林祥通
염근%관일휘%설방평%장정위%류평%림상통
HupA%碳放射性同位素%药代动力学%大鼠
HupA%碳放射性同位素%藥代動力學%大鼠
HupA%탄방사성동위소%약대동역학%대서
HupA%Carbon radioisotopes%Pharmacokinetics%Rats
目的 利用自制的11C-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11C-HupA,分别于5,15,30,60和90 min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"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SPSS 11.5软件.组间比较采用方差分析.结果 11C-HupA进入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±O.01)ml·min-1·kg-1,经肝胆系统代谢,肾是"C-HupA的主要排泄器官,在注射后15 min达到高峰,为(3.56±0.36)%ID/g,之后呈逐渐下降的趋势;肝在15 min为(2.55±0.34)%ID/g,60 min之前放射性分布维持在较高的水平.11C-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-1.11C-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 11C-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.
目的 利用自製的11C-石杉堿甲(HupA)研究治療阿爾茨海默病(AD)的有效藥物HupA在正常大鼠體內的生物學分佈及藥代動力學特徵.方法 經SD大鼠尾靜脈註射11C-HupA,分彆于5,15,30,60和90 min測量血液及各主要組織器官的放射性,計算每剋組織百分註射劑量率(%ID/g).經大鼠尾靜脈取血進行藥代動力學分析;25隻SD大鼠尾靜脈註射"C-HupA後,于上述不同時間點分彆將各組(每組5隻)大鼠斷頭處死,迅速解剖取腦,分離額葉、頂葉、顳葉、枕葉、小腦、海馬、紋狀體、丘腦、腦榦等腦區,計算%ID/g.採用SPSS 11.5軟件.組間比較採用方差分析.結果 11C-HupA進入大鼠體內具有血液清除快的特點,半衰期(T1/2)為(14.61±1.77)min,藥物自體內總清除率(CL)為(0.12±O.01)ml·min-1·kg-1,經肝膽繫統代謝,腎是"C-HupA的主要排洩器官,在註射後15 min達到高峰,為(3.56±0.36)%ID/g,之後呈逐漸下降的趨勢;肝在15 min為(2.55±0.34)%ID/g,60 min之前放射性分佈維持在較高的水平.11C-HupA在肌肉、皮膚等組織放射性分佈較少.大鼠血時間.放射性濃度麯線符閤藥代動力學一室模型,麯線下麵積(AUC)0-∞.為(167.57±12.39)kBq·ml-1·min-1.11C-HupA在各腦區放射性分佈差異有統計學意義(F=9.96,8.72,26.28,9.33,8.48.P均<0.001),大腦皮質、海馬、丘腦及腦榦分佈較多.結論 11C-HupA藥代動力學研究簡便、快速,特異性好,靈敏度高,可定量觀測髒器功能.其在大鼠腦內分佈特點為治療AD提供瞭一定的依據.
목적 이용자제적11C-석삼감갑(HupA)연구치료아이자해묵병(AD)적유효약물HupA재정상대서체내적생물학분포급약대동역학특정.방법 경SD대서미정맥주사11C-HupA,분별우5,15,30,60화90 min측량혈액급각주요조직기관적방사성,계산매극조직백분주사제량솔(%ID/g).경대서미정맥취혈진행약대동역학분석;25지SD대서미정맥주사"C-HupA후,우상술불동시간점분별장각조(매조5지)대서단두처사,신속해부취뇌,분리액협、정협、섭협、침협、소뇌、해마、문상체、구뇌、뇌간등뇌구,계산%ID/g.채용SPSS 11.5연건.조간비교채용방차분석.결과 11C-HupA진입대서체내구유혈액청제쾌적특점,반쇠기(T1/2)위(14.61±1.77)min,약물자체내총청제솔(CL)위(0.12±O.01)ml·min-1·kg-1,경간담계통대사,신시"C-HupA적주요배설기관,재주사후15 min체도고봉,위(3.56±0.36)%ID/g,지후정축점하강적추세;간재15 min위(2.55±0.34)%ID/g,60 min지전방사성분포유지재교고적수평.11C-HupA재기육、피부등조직방사성분포교소.대서혈시간.방사성농도곡선부합약대동역학일실모형,곡선하면적(AUC)0-∞.위(167.57±12.39)kBq·ml-1·min-1.11C-HupA재각뇌구방사성분포차이유통계학의의(F=9.96,8.72,26.28,9.33,8.48.P균<0.001),대뇌피질、해마、구뇌급뇌간분포교다.결론 11C-HupA약대동역학연구간편、쾌속,특이성호,령민도고,가정량관측장기공능.기재대서뇌내분포특점위치료AD제공료일정적의거.
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.
