Noninvasive imaging of the transcriptional activities of human telomerase promoter fragments in mice

被引:55
作者
Groot-Wassink, T
Aboagye, EO
Wang, YH
Lemoine, NR
Keith, WN
Vassaux, G
机构
[1] Univ London Imperial Coll Sci Technol & Med, Canc Res United Kingdom, Mol Oncol Unit, John Vane Sci Ctr,Barts & The London Sch Med & De, London EC1M 6BQ, England
[2] Univ London Imperial Coll Sci Technol & Med, Mol Oncol Grp, Dept Imaging Sci, Fac Med, London, England
[3] Univ Glasgow, Dept Med Oncol, Beatson Labs, Glasgow, Lanark, Scotland
关键词
D O I
10.1158/0008-5472.CAN-04-0426
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
We have assessed the feasibility of positron emission tomography (PET) and ex vivo gamma-counting to measure the pattern of expression of telomerase promoter fragments in vivo. Promoter fragments from either the RNA [human telomerase RNA (hTR)] or the catalytic components [human telomerase reverse transcriptase (hTERT)] of the telomerase genes were used to drive the expression of the sodium iodide symporter PET reporter gene in recombinant adenoviruses. Both promoter fragments provided cancer-selective expression that could be visualized and quantitated by PET. The transcriptional activity of the hTR promoter was found to be consistently stronger than that of the hTERT promoter. Both promoters appear therefore to be good candidates for safe use in gene therapy, and PET imaging can be used to assess the selectivity of promoters in vivo. Given that this methodology is directly scalable to humans, imaging gene expression using the sodium iodide symporter PET reporter gene could be applied to measure telomerase promoter activity in humans.
引用
收藏
页码:4906 / 4911
页数:6
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