Development of a bioluminescent nitroreductase probe for preclinical imaging

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dc.contributor.author Vorobyeva, Anzhelika G.
dc.contributor.author Stanton, Michael
dc.contributor.author Godinat, Aurelien
dc.contributor.author Lund, Kjetil B.
dc.contributor.author Karateev, Grigory G.
dc.contributor.author Francis, Kevin P.
dc.contributor.author Allen, Elizabeth
dc.contributor.author Gelovani, Juri G.
dc.contributor.author McCormack, Emmet
dc.contributor.author Tangney, Mark
dc.contributor.author Dubikovskaya, Elena A.
dc.date.accessioned 2016-02-17T10:07:57Z
dc.date.available 2016-02-17T10:07:57Z
dc.date.issued 2015
dc.identifier.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
dc.identifier.volume 10 en
dc.identifier.issued 6 en
dc.identifier.issn 1932-6203
dc.identifier.uri http://hdl.handle.net/10468/2305
dc.identifier.doi 10.1371/journal.pone.0131037
dc.description.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. en
dc.description.sponsorship Intrace Medical SA, Switzerland (Industrial Grant 8421); Science Foundation Ireland/Enterprise Ireland (12/TIDA/B2437); Irish Health Research Board (PhD Scholars Programme in Cancer Biology HRA_POR/2010/138); Irish Cancer Society (PCI12TAN); European Commission (Seventh Framework Programme PIAP-GA-2013-612219-VIP) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Public Library of Science en
dc.rights © 2015 Vorobyeva et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited en
dc.rights.uri http://creativecommons.org/licenses/by/4.0/ en
dc.subject In vivo en
dc.subject Escherichia coli en
dc.subject Myeloperoxidase activity en
dc.subject Helicobacter pylori en
dc.subject Fluorescent probe en
dc.subject Prodrug therapy en
dc.subject Living subjects en
dc.subject Cancer therapy en
dc.subject Breast cancer en
dc.subject Reporter en
dc.title Development of a bioluminescent nitroreductase probe for preclinical imaging en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Mark Tangney, Cork Cancer Research Centre, University College Cork, Cork, Ireland. +353-21-490-3000 Email: m.tangney@ucc.ie en
dc.internal.availability Full text available en
dc.description.version Published Version en
dc.internal.wokid WOS:000356933800111
dc.contributor.funder Intrace Medical SA, Switzerland
dc.contributor.funder Bergen Research Foundation, Norway
dc.contributor.funder Norwegian Cancer Society
dc.contributor.funder Western Norway Regional Health Authority
dc.contributor.funder Science Foundation Ireland
dc.contributor.funder Enterprise Ireland
dc.contributor.funder Health Research Board
dc.contributor.funder Irish Cancer Society
dc.contributor.funder Seventh Framework Programme
dc.description.status Peer reviewed en
dc.identifier.journaltitle PLOS ONE en
dc.identifier.articleid e0131037


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© 2015 Vorobyeva et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited Except where otherwise noted, this item's license is described as © 2015 Vorobyeva et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
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