99Tcm-c-myc mRNA反义肽核酸荷结肠癌裸鼠显像 |
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引用本文: | 张召奇,赵新明,王建方,张敬勉,王颖晨,孙莉,戴春暖,李德志,江志华. 99Tcm-c-myc mRNA反义肽核酸荷结肠癌裸鼠显像[J]. 中华核医学杂志, 2008, 28(3) |
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作者姓名: | 张召奇 赵新明 王建方 张敬勉 王颖晨 孙莉 戴春暖 李德志 江志华 |
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作者单位: | 河北医科大学第四医院核医学科,石家庄,050011 |
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基金项目: | 河北省自然科学基金,河北省普通高等学校强势特色学科肿瘤学科组课题 |
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摘 要: | 目的 制备99Tcm-c-myc mRNA反义肽核酸(PNA)显像探针,通过反义显像研究99Tcm-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99Tcm标记.并用同样的方法制备99Tcm-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 99Tcm-c-myc mRNA反义PNA 6h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99Tcm-c-myc mRN反义PNA 1h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 99Tcm-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.
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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 |
Experimental study on imaging of 99Tcm labeled c-myc mRNA antisense PNA in colorectal cancer tumor-bearing nude mice |
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Abstract: | Objective C-myc mRNA may become active before cancer development. The aim of this study was to explore the feasibility by using 99Tcm 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 99Tcm in ligands exchange method. 99Tcm labeled c-myc mRNA mismatch PNA was prepared in the same way as control. 99Tcm labeled c-myc mRNA antisense or mismatch PNA (37MBq) was intravenously injected into nude mice bearing human colorectal LS174-T cell through tail vein. Radionuclide imaging was performed at 1,2 and 4h postinjection. Statistical analysis was performed with SAS 6.12. Results The in vitro study showed that the labeling efficiency of 99Tcm labeled c-myc mRNA antisense PNA fragment was high (>95% at 6h). The in vivo study showed that the tumor uptake of 99Tcm labeled c-mycmRNA antisense PNA was high from 1h [the radioactivity ratios of tumor to non-tumor (T/N) were 5.06±1.35 and 1.53±0.30 in 99Tcm labeled c-myc mRNA antisense PNA group and 99Tcm labeled mRNA mismatch PNA group, respectively; t=4.47, P=0.04] to 4h after injection. In contrast, there was little 99Tcm labeled mRNA mismatch PNA accumulated in tumor within 4h. Conclusions 99Tcm 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 4h after injection. |
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Keywords: | Colonic neoplasms RNA messenger RNA antisense Nucleic acid probes Technetium Radionuclide imaging Mice nude |
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