中文摘要：

目的通过荷瘤裸鼠体内实验研究验证hTERT反义分子探针（^99mTc-hTERT ASON）作为新型分子显像剂的可行性,探讨其在整体动物水平上的应用价值。方法以双功能螯合剂法制备放射性核素^99mTc标记的反义分子探针（^99mTc-hTERT ASON）。建立荷MCF-7乳腺癌动物模型,进行体内生物分布与显像实验。所有结果通过统计学软件SPSS12.0进行分析。结果^99mTc-hTERT ASON标记率达到76%±5%（n=5）,放射性化学纯度达到96%以上,比活度为1850kBq/μg。^99mTc-hTERT ASON主要分布在肾脏与肝脏组织;^99mTc-hTERT ASON的肿瘤摄取率与肿瘤/非肿瘤比值（T/NT）均高于对照组（P〈0.05）;6h时^99mTc-hTERT ASON的肿瘤/血液比值（T/B）与肿瘤/肌肉比值（T/M）分别为2.02与8.85。在注射^99mTc-hTERT ASON后4～8h,荷瘤裸鼠肿瘤部位出现明显放射性浓聚。结论^99mTc-hTERT ASON能特异性地聚集于肿瘤组织中,且T/NT比值较高,有望应用于肿瘤的基因显像研究。

英文摘要：

Objective To validate hTERT antisense imaging agent as a novel molecular probe in nude mice bearing tumor, and to evaluate the potential application value. Methods Antisense and sense molecular probes targeting hTERT mRNA was radiolabeled with technetium-99m. The BALB/c nu/nu nude mice were inoculated with MCF-7 mammary tumor cells in the right upper limbs. Antisense or sense molecular probe was injected intravenously in nude mice bearing tumor. Biodistribution and imaging in vivo was performed periodically. All data were analyzed by the statistic software of SPSS 12.0. Resuits The labeling efficiencies of molecular probe reached 76%±5%, the specific activity was up to 1850 kBq/μg, and the radiochemical purity was above 96 % after purification. The molecular probe accumulated mostly in the kidney and liver. In comparison with radioactivity concentration in tumor tissue and the tumor to-nontumor （T/NT） ratio of antisense molecular probe, those of sense molecular probe were significantly lower （P〈0. 05）. After injection of antisense molecular probe, the ratio of tumor-to-muscle （T/M） exceeded 8.8, and that of tumor to-blood （T/B） reached 2.0 at 6 h. As for imaging in vivo, all nude mice possessed substantial abdomen radioactivity accumulation after injection of molecular probe. The hTERT- expressing xenografts were clearly imaged at 4 h till 8 b after administration of antisense molecular probe. On the contrary, the tumors were not clearly imaged at any time after injection of sense molecular probe. Conclusion This in vivo study provided evidence that antisense molecular probe targeting hTERT mRNA could be used as a potential candidate for visualization of hTERT expression in carcinomas.