Noninvasive imaging of the transcriptional activities of human telomerase promoter fragments in mice.
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.
Groot-Wassink
Thomas
T
Cancer Research United Kingdom Molecular Oncology Unit, Department of Imaging Sciences, Faculty of Medicine, Imperial College, Hammersmith Campus, London, United Kingdom.
Aboagye
Eric O
EO
Wang
Yaohe
Y
Lemoine
Nicholas R
NR
Keith
W Nicol
WN
Vassaux
Georges
G
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins; D005260:Female; D015870:Gene Expression; D005822:Genetic Vectors; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010051:Ovarian Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism / Q000821:virology; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism / Q000821:virology; D011401:Promoter Regions, Genetic / Q000235:genetics; D012313:RNA / Q000235:genetics; D019098:Telomerase / Q000096:biosynthesis / Q000235:genetics*; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed; D014158:Transcription, Genetic; D019076:Transgenes
D004268:DNA-Binding Proteins; D012313:RNA; D019098:Telomerase