药物动力学解空间及其在多巴胺转运蛋白显像剂^18F—FECNT中的应用  

Solution space of pharmacokinetics and its application on mice brain with ^18F-FECNT

作　　者：曹国宪[1] 陈正平[1] 周杏琴[1] 

机构地区：[1]江苏省原子医学研究所、卫生部核医学重点实验室、江苏省分子核医学重点实验室,江苏省无锡市214063

出　　处：《中华核医学杂志》2011年第4期255-258,共4页Chinese Journal of Nuclear Medicine

基　　金：国家自然科学基金（30970844）;江苏省自然科学基金（BK2008111）

摘　　要：目的提出药物动力学解空间概念，以研究放射性药物在各种脏器组织中的药物动力学。方法在药物动力学微分方程组特解基础上，利用其相互间线性无关的特性，构作解空间，用以表达药物在体内的动力学行为。正常小鼠尾静脉注射0．2ml（7．4MBq）^18F-N-（2-氟乙基）-2B-甲酯基-3B-（4-氯苯基）去甲基托烷（FECNT），分别于给药后5，15，30，60，120，180min处死，取各脑组织，测质量及放射性计数。用解空间理论进行动力学研究。结果基于微分方程组的药物动力学模型的解存在于该解空间中，并可用解空间的基线性表示药物在各种脏器和组织中的动力学解，当解空间的维数小于三维时，能用坐标图直观表示。用该理论获得的^18F—FECNT小鼠脑内各种组织的药物动力学方程所描述的药物量随时间变化的规律与实验事实相符，对应于纹状体、额叶、颞叶、枕叶、顶叶、海马，小脑等脑组织的解空间坐标分别为（10．13，1．49）、（4．27，0．84）、（4．48，0．81）、（2．89，0．98）、（3．65，0．83）、（3．55，0．98）和（2．03、1．25）。对应于各脑组织的分布相系数与比值、消除相系数与比值能定量描述各脑组织中的药物量差别及变化趋势。结论药物动力学解空间理论能研究药物在各种脏器和组织中的动力学行为，该理论推广应用至普药的动力学研究值得探索。Objective To forward the concept of solution space of pharmacokinetics for studying radiopharmaceutical distributions in animal models. Methods On the basis of special solutions of differential equations of pharmacokinetics, the solution space was established using the characteristics of linearly independent particular solutions and used to express the pharmacokinetics of pharmaceuticals in vivo. 0. 2 ml （7.4 MBq） 2β-carbomethoxy-3β- （4-corophenyl）-8-（2-^18Ffluoroethyl） nortropane （^18FFECNT） was injected through tail vein into normal mice. The mice were sacrificed by decapitation at 5, 15, 30, 60, 120 and 180 min post-injection. Brain tissues were removed and weighed, and radioactivity was counted with the γ-counter. The solution space theory was used to study pharmacokineties of 18 F-FECNT in brain tissues of mice. Results The result showed that all solutions of pharmacokinetics models, based on differential equations, were included in the solution space. The solution of any organ or tissue could be linearly expressed by bases of the solution space. When the dimension number of the solution space was no more than 3, the solution could be directly expressed with coordinate picture. By this rule in our theory, the quantity of ^18F-FECNT in brain tissues of mice changed with time, which was accorded with the experiment. The coordinates of striatum, frontal cortex, temporal cortex, occipital cortex, parietal cortex, hippocampus and cerebellum in the solution space were （10.13, 1.49）, （4.27,0.84）, （4.48, 0.81）, （2.89, 0.98）, （3.65, 0.83）, （ 3.55, 0. 98 ） and （ 2.03, 1.25 ）, respectively. Conclusion The theory of solution space could be used to study pharmacokineties of 18F-FECNT in mice brain.

关 键 词：药代动力学 FECNT 氟放射性同位素 多巴胺质膜转运蛋白质类 

分 类 号：R96[医药卫生—药理学]