^(99)Tc^m标记小干扰RNA探针的干扰活性及其在荷瘤鼠体内的生物分布  

In-vitro Inhibitory Activity and In-vivo Biodistribution of ^(99)Tc^m Radiolabeled Small Interference RNA

作　　者：康磊[1] 王荣福[1] 闫平[1] 张春丽[1] 刘萌[1] 徐小洁[2] 

机构地区：[1]北京大学第一医院核医学科,北京100034 [2]军事医学科学院生物工程研究所,北京100850

出　　处：《同位素》2011年第2期65-71,共7页Journal of Isotopes

基　　金：国家自然科学基金资助项目(30870729;30900374);国家重点基础研究发展计划("973"计划)资助项目(2006CB705705);教育部教育振兴行动计划特殊专项("九八五"工程:Ⅱ期)资助项目(985-2-056)

摘　　要：使用双功能螯合剂NHS-MAG3和氯化亚锡还原法构建99Tcm标记的小干扰RNA(Small InterferenceRNA,si RNA)探针。将标记和未标记的端粒逆转录酶(Human Telomerase Reverse Trancriptase,hTERT)靶向si RNA转染至肝癌HepG2细胞,72 h后,蛋白印迹法显示两者具有相近的蛋白抑制率(约76.7%)。标记物在荷HepG肿瘤裸鼠体内的生物分布显示,肾脏分布最高,其次为肝脏。注射hTERT靶向探针后1~6 h内,肿瘤分布由(0.82±0.16)%ID/g增加至(0.97±0.15)%ID/g,肿瘤与血液和肿瘤与肌肉的放射性摄取比(T/NT)分别为2.62±0.70和6.02±0.52,显著高于对照组(P<0.05)。以上结果提示,99Tcm-si RNA探针对活体肿瘤示踪具有良好的研究前景和潜在的应用价值。Small interference RNA（siRNA） was radiolabeled by using the bifunctional chelator of NHS-MAG3 and SnCl2·2H2O.After transfected into Hepatocarcinoma HepG2 cells,labeled and unlabeled hTERT-targeted siRNA had the similar inhibitory rate about 76.7% measured by western blotting method.In the biodistribution study,the radio-active accumulation was primarily found in the kidneys,and then in liver.The radioactivity of hTERT-targeted siRNA in tumor increased from（0.82 ± 0.16） %ID/g to（0.97 ± 0.15） %ID/g from 1 to 6 hours after the administration.The uptake ratio of tumor to blood and tumor to muscle were 2.62 ± 0.70 and 6.02 ± 0.52,respectively,significantly higher than that of the control group（P0.05）.These results indicated that 99Tcm radiolabeled hTERT-targeted siRNA allows for prospective future and potential application value in the noninvasive visualization of tumor telomerase in vivo.

关 键 词：99Tcm 小干扰RNA 干扰活性 生物分布 

分 类 号：R817.4[医药卫生—影像医学与核医学]