中文摘要：

目的制备^99Tc^m-人端粒酶催化亚单位（hTERT）mRNA反义寡核苷酸（ASON）显像分子探针并验证其在荷MCF-7乳腺癌裸鼠早期诊断中的价值。方法采用双功能螯合剂法制备^99Tc^m-hTERT mRNA无义寡核苷酸（SON）、ASON探针。建立荷MCF-7乳腺癌裸鼠模型，运用阳离子脂质体介导法进行活体显像。采用SPSS12．0软件进行单因素方差分析。结果^99Tc^m-hTERT mRNA ASON标记率达到（76±5）％，放化纯〉96％，比活度达到1850kBq／μg。室温放置和健康人血清孵育24h后的放化纯均〉93％。SON与ASON的标记率基本一致。注射后4h反义组荷瘤裸鼠右上肢接种肿瘤部位可见放射性摄取，6～8h后显影清晰；无义组始终未见肿瘤部位放射性浓聚。反义组有和无脂质体介导的肿瘤／非肿瘤组织放射性（T／NT）比值分别为8．02±0．03和7．55±0．12，差异无统计学意义（t=-1．99，P〉0．05）；无义组有和无脂质体介导的T／NT比值分别为1．23±0．06和1．33±0．15，差异无统计学意义（t=0．42，P〉0．05）。但是分别比较反义组与无义组、脂质体介导组与无介导组间差异均有统计学意义（t=26．30和28．71，P均〈0．001）。结论^99Tc^m-hTERT mRNA ASON在荷瘤裸鼠活体内可与高表达hTERT基因的人乳腺癌MCF－7肿瘤组织特异靶向结合，在肿瘤分子功能显像中具有潜在应用价值。

英文摘要：

Objective Antisense imaging is one of the important modalities in the domain of molecular nuclear medicine. The purpose of this study was to design and synthesize an antisense oligonucleotide （ASON） molecular probe targeting human telomerase reverse transcriptase （hTERT） mRNA, and to validate the potential application value using animal model experimental study in early diagnosis of the tumor. Methods Antisense and sense molecular probes targeting hTERT mRNA were radiolabeled with ^99Tc^m through bifunctional chelator N-bydroxysuccinimidyl derivative of S-acetylmercaptoacetyltriglycine （S-Acetyl NHS-MAG3 ）. The BALB/c nu/nu nude mice were inoculated with MCF-7 mammary tumor cells in the right upper limbs. ^99Tc^m-hTERT mRNA ASON and ^99Tc^m-hTERT mRNA sense oligonucleotide （SON） with or without mediated by liposome was injected intravenously in mammary tumor-bearing BALB/c nude mice, respectively. Imaging in vivo was performed periodically. All data were analyzed by the statistic software of SPSS 12.0. Results The in vitro study showed that the labeling efficiencies of ^99Tc^m-hTERT mRNA ASON reached （76 ±5 ） %, with radiochemical purity greater than 96% and specific activity of 1850 kBq/μg. The stability of ^99Tc^m-hTERT mRNA ASON in room temperature and serum incubation after 24 h was still above 93%. The in vivo study showed that tumor uptake of ^99Tc^m-hTERT mRNA ASON was high from 4 to 8 h after injection. On the contrary, there was little ^99Tc^m-hTERT mRNA SON accumulated in tumor within 8 h. The radioactivity ratio of tumor-to-nontumor （T/NT） of antisense probe group with or without liposome mediation was 8.02 ± 0.03 and 7.55 ± 0.12, respectively （ t = - 1.99, P 〉 0.05 ）, and that of sense probe group with or without liposome mediation was 1.23± 0.06 and 1.33 ± 0. 15, respectively （ t = 0. 42, P 〉 0.05 ）. However, there was significant difference between antisense and sense probe groups with or without liposome mediation （ t = 26.30, 28.71, both P 〈 0. 001 ）