Development of a bioluminescent nitroreductase probe for preclinical imaging
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Date
2015
Authors
Vorobyeva, Anzhelika G.
Stanton, Michael
Godinat, Aurelien
Lund, Kjetil B.
Karateev, Grigory G.
Francis, Kevin P.
Allen, Elizabeth
Gelovani, Juri G.
McCormack, Emmet
Tangney, Mark
Journal Title
Journal ISSN
Volume Title
Publisher
Public Library of Science
Published Version
Abstract
Bacterial nitroreductases (NTRs) have been widely utilized in the development of novel antibiotics, degradation of pollutants, and gene-directed enzyme prodrug therapy (GDEPT) of cancer that reached clinical trials. In case of GDEPT, since NTR is not naturally present in mammalian cells, the prodrug is activated selectively in NTR-transformed cancer cells, allowing high efficiency treatment of tumors. Currently, no bioluminescent probes exist for sensitive, non-invasive imaging of NTR expression. We therefore developed a "NTR caged luciferin" (NCL) probe that is selectively reduced by NTR, producing light proportional to the NTR activity. Here we report successful application of this probe for imaging of NTR in vitro, in bacteria and cancer cells, as well as in vivo in mouse models of bacterial infection and NTR-expressing tumor xenografts. This novel tool should significantly accelerate the development of cancer therapy approaches based on GDEPT and other fields where NTR expression is important.
Description
Keywords
In vivo , Escherichia coli , Myeloperoxidase activity , Helicobacter pylori , Fluorescent probe , Prodrug therapy , Living subjects , Cancer therapy , Breast cancer , Reporter
Citation
Vorobyeva AG, Stanton M, Godinat A, Lund KB, Karateev GG, Francis KP, et al. (2015) Development of a Bioluminescent Nitroreductase Probe for Preclinical Imaging. PLoS ONE 10(6): e0131037. doi:10.1371/journal.pone.0131037