^(131)I-c(RGD)_2的药代动力学及急性毒性研究  

Pharmacokinetics and Acute Toxicity Study of ^(131)I-c( RGD)_2

作　　者：马欢[1] 郝攀[1] 马超[2] 闫平[1] 刘敏[1] 王荣福[1] 陈雪祺[1] 张春丽[1] 

机构地区：[1]北京大学第一医院核医学科,北京100034 [2]厦门大学附属中山医院核医学科,福建厦门361004

出　　处：《标记免疫分析与临床》2016年第1期71-73,共3页Labeled Immunoassays and Clinical Medicine

基　　金：北京市自然科学基金(7112129)

摘　　要：目的用131I标记二硫键成环的RGD肽二聚体c(RGD)2,探讨其在裸鼠体内的药代动力学参数、急性毒性反应和死亡情况,评价其应用的安全性。方法选取5只裸鼠为实验对象,每只经尾静脉注射131I-c(RGD)2(7.4 MBq/200μL),分别于注射后3、6、10、15、30、45、60、120、180及360min断尾取血5μL,测量血液的放射性计数,采用PKSolver软件进行药代动力学分析。另取裸鼠10只随机分为实验组及对照组,实验组每只经尾静脉注射131I-c(RGD)2(7.4 MB/60μL);对照组经尾静脉注射生理盐水60μL,观察注射后72 h内裸鼠的不良反应和死亡情况。结果血液药–时曲线符合权重系数为1/CC的开放性二房室分布模型,其中分布相半衰期(t1/2α)为15.364 min,消除相半衰期(t1/2β)为123.125 min。注射131I-c(RGD)2后72 h内,裸鼠无不良反应与死亡。结论 c(RGD)2具有理想的药代动力学特点,且无明显毒性作用,这些均有利于其作为新药应用于临床。Objective To evaluate the safety, pharmacokinetics and acute toxicity of 131I-c（RGD）2in nude mice. Methods Five nude mice were injected with 131I-c（RGD）2 via tail vein（7.4 MBq in 200 μL/mouse） and blood samples（5 μL）were collected by cutting down the tail end at 3,6, 10, 15,30,45,60,120,180 and 360 rain after administration. The radioactive accounts of blood samples were measured using a γ- counter and the pharmacokinetics data was calculated by the PKSolver software. 10 nude mice were randomly divided into 2 groups,the experimental group and the control group,for the acute toxicity study. The experimental mice were injected with 131I-c（RGD）2 via tail vein（7.4 MBq in 60 pJ_/mouse）and the control mice were injected with saline （60 μL/mouse）to observe the adverse reaction. Results The blood dynamics of 131I-c（RGD）2 in nude mice conformed to the two-compartment model with the weight of 1/CC, and t1/2α and t1/2β were 15. 364 rain and 123. 125 min respectively. No adverse reaction was observed within 72 h after injection. Conclusion The ideal pharmacokinetic characteristics and tissue tolerance of 131 I-C（ RGD）2 suggest it to be a potential-agent in clinical practice.

关 键 词：药代动力学 RGD肽 急性毒性 

分 类 号：R965[医药卫生—药理学] R811[医药卫生—药学]