摘要
目的探讨新型分子探针99 mTc-RRL的药代动力学及急性毒性作用。方法用一步法制备分子探针99 mTc-RRL,在健康小鼠体内进行99 mTc-RRL的生物分布特性研究及小鼠体内急性毒性实验,以及在健康白兔体内进行99 mTc-RRL的药代动力学。结果99 mTc-RRL标记率为(76.9±4.5)%,放射性化学纯度达96%以上,比活度达1480 k Bq·mg-1以上。示踪剂体内分布符合权重为1/c2的三室模型,快分布相半衰期、慢分布相半衰期及消除相半衰期分别为(2.04±1.53)、(19.50±7.07)、(361.30±187.90)min,清除率为(2.03±0.41)m L·min-1。示踪剂在血液中清除迅速,主要通过肾排泄,其余组织器官放射性均随时间逐渐降低,注射99 mTc-RRL 48 h内,小鼠无不良反应与死亡发生。结论99 mTc-RRL具有理想的组织分布特点,无急性毒性作用,是一种用于人体比较理想的肿瘤分子显像剂。
Objective To evaluate the pharmacokinetics and acute toxicity of RRL（ Arg- Arg- Leu） molecular probe labeled with technetium- 99 m（^99mTc- RRL）. Methods ^99mTc- RRL was prepared by one- step method. Biodistribution,and the acute toxicity test of ^99mTc- RRL in mice and pharmacokinetics in health rabbits were performed.Results Labeling efficiencies of ^99mTc- RRL reached（ 76. 9 ± 4. 5） %.The radiochemical purity was above 96%,and the specific activity was up to 1480 k Bq·mg^- 1. Its dynamics in rabbits conformed to the three-compartment model with the weight of 1 / c2,and the main parameters were as follows： fast distribution phase half- life,slow distribution and elimination half- life phase half- life were（ 2. 04 ± 1. 53）,（ 19. 50 ± 7. 07） and（ 361. 30 ± 187. 90） min respectively,clearance was（ 2. 03 ± 0. 41） mL·min^- 1. The pharmacokinetics and distribution results showed that the peptide could be quickly cleared from blood in healthy animals and distributed more in the kidney,and the other organs and tissue were decreased gradually. Conclusion The results demonstrated that ^99mTc- RRL had a ideal tissue distribution and no acute toxicity,suggesting its development as a potential tumor imaging agent.
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2015年第16期1610-1612,共3页
The Chinese Journal of Clinical Pharmacology
基金
国家"十二五"支撑项目基金资助项目(2014BAA03B03)
国家自然科学基金资助项目(81071183)
国家重大科学仪器设备开发专项基金资助项目(2011YQ03011409)
