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[Cancer Research 64, 4906-4911, July 15, 2004]
© 2004 American Association for Cancer Research


Regular Articles

Noninvasive Imaging of the Transcriptional Activities of Human Telomerase Promoter Fragments in Mice

Thomas Groot-Wassink1, Eric O. Aboagye2, Yaohe Wang1, Nicholas R. Lemoine1, W. Nicol Keith3 and Georges Vassaux1

1 Cancer Research United Kingdom Molecular Oncology Unit and 2 Molecular Therapy Group, Department of Imaging Sciences, Faculty of Medicine, Imperial College, Hammersmith Campus, London, United Kingdom, and 3 Cancer Research United Kingdom, Department of Medical Oncology, University of Glasgow, Beatson Laboratories, Glasgow, United Kingdom

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.




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