99Tcm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

使用双功能螯合剂NHS MAG3和氯化亚锡还原法构建99Tcm标记的小干扰RNA（Small Interference RNA，siRNA）探针。将标记和未标记的端粒逆转录酶（Human Telomerase Reverse Trancriptase，hTERT）靶向siRNA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，⁹⁹Tc^m-siRNA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。

In-vitro Inhibitory Activity and In-vivo Biodistribution of 99Tcm Radiolabeled Small Interference RNA

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(P<0.05).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.