Noninvasive Imaging of Human Telomerase Reverse Transcriptase (hTERT) Messenger RNA with 99mTc-Radiolabeled Antisense Probes in Malignant Tumors

Journal of Nuclear Medicine

Feng Qin Guo¹  Chun Li Zhang¹  Ping Yan¹  Li Juan Di¹  Meng Liu¹  Hong Jie Liu¹  Rong Fu Wang¹  Ming Ming Yu¹ 

[1] Department of Nuclear Medicine, Peking University First Hospital, West District, Beijing, China Department of Nuclear Medicine, Peking University First Hospital, West District, Beijing, China Department of Nuclear Medicine, Peking University First Hospital, West District, Beijing, China

关键词: ^99mTc;    antisense;    molecular imaging;    human telomerase reverse transcriptase;    hTERT;    biodistribution;   

DOI  :  10.2967/jnumed.107.042622

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 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 99mTc-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 99mTc 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. 99mTc-MAG3-ASON or 99mTc-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 99mTc-MAG3-ASON/SON reached 76% ± 5% (n = 5) within 15–30 min at room temperature, the specific activity was up to 1,850 kBq/μg, and the radiochemical purity was >96% after purification. 99mTc-MAG3-ASON showed complete stability at room temperature and in fresh 37°C human serum. In comparison with 99mTc-MAG3-SON, 99mTc-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 99mTc-MAG3-ASON, whereas the xenografts were not imaged at any time after injection of 99mTc-MAG3-SON. Conclusion: This in vivo study provides evidence that 99mTc-MAG3-ASON targeting hTERT mRNA can be used as a potential candidate for visualization of hTERT expression in carcinomas.

【 授权许可】

Unknown