放射性核素示踪法对多肽VEGF125-136在家兔体内的药代动力学研究  

Pharmacokinetics of VEGF125-136 in rabbits by radionuclide tracing

作　　者：黄定德[1] 罗朝学[1] 刘广元[1] 郑磊[1] 陈杰[1] 李前伟[1] 程绍钧[1] 

机构地区：[1]第三军医大学西南医院核医学科,重庆400038

出　　处：《第三军医大学学报》2007年第18期1746-1748,共3页Journal of Third Military Medical University

基　　金：国家自然科学基金(30400114);第三军医大学科研基金(2004)~~

摘　　要：目的探讨VEGF125-136在家兔体内的药代动力学。方法采用放射性核素99Tcm对VEGF125-136进行间接标记。测定6只家兔静脉注射37MBq99Tcm-VEGF125-136后不同时间血浆中药物的放射性浓度,用DAS软件编制放射性浓度-时间曲线,并计算药代动力学参数。结果99Tcm-VEGF125-136的放射化学纯度大于97%,99Tcm-VEGF125-136在家兔体内的代谢符合三室模型,快分布相半衰期(t1/2α)为(5.327±2.351)min,慢分布相半衰期(t1/2β)为(26.446±6.502)min,消除相半衰期(t1/2γ)为(304.41±216.811)min,转运速率常数K10、K12、K21、K31及K13分别为(0.047±0.034)、(40.65±68.54)、(0.111±0.058)、(0.111±0.058)min-1及(0.002±0.004)min-1,清除率(CL)为(4.00±1.00)ml/min。结论VEGF125-136在家兔体内的药代动力学符合三室模型,且血液清除快而周边血管丰富的组织停留时间相对较长。Objective To investigate the pharmacokinetics of a 12-amino-acid residue peptide of vascular endothelial growth factor （VEGF, 125-136） in rabbits. Methods VEGF125-136 was indirectly labeled with 99Tern. After a single dose of 37 MBq of ^99Tc^m-VEGF125-136 was injected intravenously in 6 rabbits, the radioactive concentrations at different sampling times were determined. Then the plasma radioactive concentrationtime curve was drawn and pharmacokinetics parameters were calculated with DAS computer program. Results The radiochemistry purity of ^99Tc^m-VEGF125-136 was more than 97%, the radioactive concentrationtime curve of ^99Tc^m-VEGF125-136 was fitted to a three-compartment model with the main pharmacokinetic parameters as follows ： t1/2α, t1/2β and t1/2γ were （5. 327 ± 2.351 ）, （26. 446 ＋ 6. 502 ） and （ 304.41 ±216.811 ） min respectively. CL, K10, K12, K21, K31 and K13 were （4.00 ± 1.00） ml/min, （0. 047 ± 0. 034） min^-1, （40.65 ±68.54） min^-1, （0. 111 ±0.058） min^-1, （0. 111 ±0.058） min^-1 and （0.002 ±0.004） min^-1 respectively. Conclusion The pharmacokinetics is fitted to three compartment model in rabbits. VEGF125-136 can be cleared quickly from blood and its detention time in target tissue is long.

关 键 词：多肽 VEGF 锝放射性同位素 药代动力学 家兔 

分 类 号：R817[医药卫生—影像医学与核医学] R969.1[医药卫生—放射医学]