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Noninvasive imaging of human telomerase reverse transcriptase (hTERT) messenger RNA with (99)mTc-radiolabeled antisense probes in malignant tumors
Men Liu; Ron-Fu Wang; Chun Li Zhang; Ping Yan; Ming Ming, Yu; Li Juan Di; Hong Jie Liu; Feng Qin Guo
关键词Tc-99m antisense molecular imaging human telomerase reverse transcriptase hTERT biodistribution
刊名JOURNAL OF NUCLEAR MEDICINE
2007-12-01
DOI10.2967/jnumed.107.042622
48期:12页:2028-2036
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Radiology, Nuclear Medicine & Medical Imaging
研究领域[WOS]Radiology, Nuclear Medicine & Medical Imaging
关键词[WOS]IN-VITRO ; GENE-EXPRESSION ; CANCER ; CELLS ; THERAPY ; PEPTIDE ; OLIGONUCLEOTIDES ; CULTURE ; MICE
英文摘要

The expression of human telomerase reverse transcriptase (hTERT) is present in most malignant cells (>85%) but is undetectable in most normal somatic cells. Visualization of hTERT expression using radionuclide targeting can provide important diagnostic information in malignant tumors. The overall aim of this study was to evaluate whether Tc-99m-radiolabeled antisense oligonucleotide (ASON) targeting hTERT messenger RNA (mRNA) can be used for imaging of hTERT expression in vivo. Methods: One 18-mer antisense or sense uniformly phosphorothioate-modified oligonucleotide targeting hTERT mRNA was radiolabeled with Tc-99m through the bifunctional chelator N-hydroxysuccinimidyl derivative of S-acetylmercaptoacetyltriglycine (S-acetyl NHS-MAG3). Then the radiolabeled probe was characterized in vitro. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to assay the mRNA level after proliferating cells had been incubated with the antisense and sense probes. Tc-99m-MAG3-ASON or Tc-99m-MAG3-SON was injected intravenously in mammary tumor-bearing BALB/c nude mice. Biodistribution and in vivo imaging was performed periodically. All data were analyzed by statistical software. Results: The labeling efficiencies of Tc-99m-MAG3-ASON/SON reached 76% +/- 5% (n = 5) within 15-30 min at room temperature, the specific activity was up to 1,850 kBq/mu g, and the radiochemical purity was >96% after purification. Tc-99m-MAG3-ASON showed complete stability at room temperature and in fresh 37 degrees C human serum. In comparison with Tc-99m-MAG3-SON, Tc-99m-MAG3-ASON preserved the capacity to bind living hTERT-expressing cells specifically and to inhibit the expression of hTERT mRNA significantly as well as ASON. In nude mice bearing hTERT-expressing MCF-7 xenografts, tumor radioactivity uptake of 99mTc-MAG3-ASON after injection was significantly higher than that of 99mTc-MAG3-SON after injection (P < 0.05). The hTERT-expressing xenografts were clearly imaged at 4-8 h noninvasively after injection of Tc-99m-MAG3-ASON, whereas the xenografts were not imaged at any time after injection of Tc-99m-MAG3-SON. Conclusion: This in vivo study provides evidence that Tc-99m-MAG3-ASON targeting hTERT mRNA can be used as a potential candidate for visualization of hTERT expression in carcinomas.

语种英语
WOS记录号WOS:000252895100022
引用统计
被引频次:24[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/61286
专题北京大学第一临床医学院_核医学科
作者单位Peking Univ, First Hosp, Dept Nucl Med, Beijing, Peoples R China
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Men Liu,Ron-Fu Wang,Chun Li Zhang,et al. Noninvasive imaging of human telomerase reverse transcriptase (hTERT) messenger RNA with (99)mTc-radiolabeled antisense probes in malignant tumors[J]. JOURNAL OF NUCLEAR MEDICINE,2007,48(12):2028-2036.
APA Men Liu.,Ron-Fu Wang.,Chun Li Zhang.,Ping Yan.,Ming Ming, Yu.,...&Feng Qin Guo.(2007).Noninvasive imaging of human telomerase reverse transcriptase (hTERT) messenger RNA with (99)mTc-radiolabeled antisense probes in malignant tumors.JOURNAL OF NUCLEAR MEDICINE,48(12),2028-2036.
MLA Men Liu,et al."Noninvasive imaging of human telomerase reverse transcriptase (hTERT) messenger RNA with (99)mTc-radiolabeled antisense probes in malignant tumors".JOURNAL OF NUCLEAR MEDICINE 48.12(2007):2028-2036.
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