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J Nucl Med. 2008; 49 (Supplement 1):104P
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Oncology-Basic Science: Basic Science

New Targets

Detection of hTERT mRNA with 99mTc-radiolabeled antisense probe in malignant tumors in vivo

Rong Fu Wang1, Meng Liu1, Chun Li Zhang1, Ping Yan1, Ming Ming Yu1 and Feng Qin Guo1

1 Nuclear Medicine, Beijing University 1st Hospital, Beijing, China

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Objectives: The aim of this study was to evaluate whether 99mTc radiolabeled antisense probe targeting human telomerase reverse transcriptase(hTERT) mRNA can be used for imaging of hTERT expression in vivo.

Methods: One 18mer uniformly phosphorothioate-modified oligonucleotide targeting hTERT mRNA was radiolabeled with 99mTc through bifunctional chelator. The radiolabeled probe was characterized in vitro. RT-PCR was performed to assay the mRNA level after cells had been incubated with probes. 99mTc-MAG3-ASON/SON was injected intravenously in tumor-bearing nude mice. Biodistribution and imaging in vivo was performed periodically.

Results: The labeling efficiencies of 99mTc-MAG3-ASON/SON reached 76%±5%, the specific activity was up to 1850 kBq/µg, and the radiochemical purity was above 96% after purification. 99mTc-MAG3-ASON showed stable at room temperature and in fresh human serum. In comparison with 99mTc-MAG3-SON, 99mTc-MAG3-ASON preserved the capacity to bind living hTERT-expressing cells specifically and inhibit the expression of hTERT mRNA significantly as well as ASON. In nude mice bearing tumor, tumor radioactivity uptake of 99mTc-MAG3-ASON was significantly higher than that of 99mTc-MAG3-SON. The xenografts were clearly imaged at 4h till 8h noninvasively after injection of 99mTc-MAG3-ASON, while the xenografts were not imaged at any time after injection of 99mTc-MAG3-SON.

Conclusions: 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 carcinoma.

Research Support: This study was supported by grants from the National Natural Science Foundation of China (NSFC 30470498 and 30670583), the National Basic Research Program (973 Program, 2006CB705705-1) and the second phase of National Education Ministry "985" Project (985-2-056).





This Article
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Right arrow Articles by Guo, F. Q.
PubMed
Right arrow Articles by Wang, R. F.
Right arrow Articles by Guo, F. Q.