^99Tc^m-c-myc mRNA反义肽核酸荷结肠癌裸鼠显像  

Experimental study on imaging of ^99Tc^m labeled c-myc mRNA antisense PNA in colorectal cancer tumor-bearing nude mice

作　　者：张召奇[1] 赵新明[1] 王建方[1] 张敬勉[1] 王颖晨[1] 孙莉[1] 戴春暖[1] 李德志[1] 江志华[1] 

机构地区：[1]河北医科大学第四医院核医学科,石家庄050011

出　　处：《中华核医学杂志》2008年第3期181-183,共3页Chinese Journal of Nuclear Medicine

基　　金：河北省自然科学基金（303515）;河北省普通高等学校强势特色学科肿瘤学科组课题（[2005]52） 志谢 本研究的核素标记得到北京师范大学陆浩博士大力协助

摘　　要：目的制备^99Tc^m-c-myc mRNA反义肽核酸（PNA）显像探针，通过反义显像研究^99Tc^m-c-myc mRNA反义PNA早期诊断结肠癌的可行性。方法利用化学合成法在c-myc mRNA反义PNA片段的5′端连上4个氨基酸[G-（D）-A—G—G]和1个氨基丁酸（Aba），再利用配体交换法对c-myc mRNA反义PNA行^99Tc^m标记。并用同样的方法制备^99Tc^m-c-myc mRNA无义PNA。进行人结肠癌LS174-T荷瘤裸小鼠显像。采用SAS 6．12软件进行统计学处理。结果^99Tc^m-c-myc mRNA反义PNA 6 h内标记率〉95％。血清孵育5h后标记率为91．1％。无义PNA的标记率与反义PNA基本一致。1h时反义组荷瘤裸鼠右后肢肿瘤部位可清晰显影，4h内未见明显变化。无义组肿瘤部位始终未见明显放射性摄取。注射^99Tc^m-c-myc mRNA反义PNA 1 h后，反义组与无义组肿瘤与对侧组织的放射性（T／N）比值分别为5．06±1．35和1．53±0．30，差异有统计学意义（t=4．47，P=0．04）。结论^99Tc^m-c-myc mRNA反义PNA可在荷瘤裸鼠活体内与高表达c-myc基因的人结肠癌LS174-T肿瘤组织特异结合，在肿瘤反义显像中有潜在的应用价值。Objective C-myc mRNA may become active before cancer development. The aim of this study was to explore the feasibility by using ^99Tc^m labeled c-myc mRNA antisense peptide nucleic acid （PNA） to early diagnose colorectal cancer. Methods Four amino acid [G（D）-A-G-G] and an Aba （ aminobutyric acid） were linked to the 5′ end of c-myc mRNA antisense PNA by chemical synthesize, then it was labeled with ^99Tc^m in ligands exchange method. ^99Tc^m labeled c-myc mRNA mismatch PNA was prepared in the same way as control. ^99Tc^m labeled c-myc mRNA antisense or mismatch PNA （37 MBq） was intravenously injected into nude mice bearing human colorectal LS174-T cell through tail vein. Radionuclide imaging was performed at 1,2 and 4 h postinjection. Statistical analysis was performed with SAS 6.12. Resuits The in vitro study showed that the labeling efficiency of ^99Tc^m labeled c-myc mRNA antisense PNA fragment was high （ 〉95% at 6 h）. The in vivo study showed that the tumor uptake of ^99Tc^m labeled c-myc mRNA antisense PNA was high from 1 h [ the radioactivity ratios of tumor to non-tumor （T/N） were 5.06 ± 1.35 and 1.53 ±0.30 in ^99Tc^m labeled c-myc mRNA antisense PNA group and ^99Tc^m labeled mRNA mismatch PNA group, respectively; t = 4. 47, P = 0.04 ] to 4 h after injection. In contrast, there was little ^99Tc^m labeled mRNA mismatch PNA accumulated in tumor within 4 h. Conclusions ^99Tc^m labeled c-myc mRNA antisense PNA exhibited high sensitivity and high specificity in binding with the colorectal LS174-T tumor tissue. The optimal imaging time for in vivo in the future may be at 4 h after injection.

关 键 词：结肠肿瘤 RNA 信使 RNA 反义 核酸探针 锝 放射性核素显像 小鼠 裸 

分 类 号：R686[医药卫生—骨科学]