人端粒酶催化亚单位反义分子探针的药代动力学与急性毒性研究  

Study on pharmacokinetics and acute toxicity of human telomerase reverse transcriptase antisense oligonucleotide molecular probe

作　　者：王荣福[1] 刘萌[1] 张春丽[1] 闫平[1] 于明明[1] 崔永刚[1] 

机构地区：[1]北京大学第一医院核医学科,北京100034

出　　处：《中国临床药理学杂志》2009年第5期422-425,共4页The Chinese Journal of Clinical Pharmacology

基　　金：国家自然科学基金资助项目(39870241;30270410);国家重点基础研究发展计划基金-973计划基金资助项目(2006CB705705);北京大学985I期;II期基金资助项目(985-2-056)

摘　　要：目的分析放射性核素锝[99mTc]标记的人端粒酶催化亚单位反义分子探针的药代动力学与急性毒性作用。方法制备反义分子探针(99mTc-hTERT ASON),进行体内生物分布、药代动力学以及急性毒性实验。结果99mTc-hTERT ASON标记率为(76±5)%,放射性化学纯度达96%以上,比活度为1850kBq.μg-1;主要分布在肾脏、肝脏组织;体内分布符合三室模型;注射48h内,小鼠无不良反应与死亡。结论99mTc-hTERT ASON具有良好组织分布特点,无急性毒性作用;适合作为一种肿瘤分子显像剂应用于活体显像。Objective To study the pharmacokinetics and acute toxicity of human telomerase reverse transcriptase mRNA antisense oligonucleotide molecular probe labeled with technetium-99m （^99mTc-hTERT ASON）. Methods 99mTc-hTERT ASON was prepared. The biodistribution,pharmacokinetics,and the acute toxicity test of ^99mTc-hTERT mRNA ASON were performed. Results The labeling efficiencies of ^99mTc-hTERT mRNA ASON reached （76±5）%. The specific activity was up to 1 850 kBq·μg^-1,and the radiochemical purity was above 96%. ^99mTc- hTERT ASON accumulated mainly in liver and kidney, and was model. All Kunming mice were indicative of a three - compartment present well after injection of high dose of ^99mTc -hTERT mRNA ASON. Conclusion These results demonstrated that widespread tissue availability of ^99mTc - hTERT ASON and suggested its development as a potential tumor imaging agent.

关 键 词：反义寡核苷酸 体内生物分布 药代动力学 急性毒性 

分 类 号：R969.1[医药卫生—药理学] R817.33[医药卫生—药学]