Development of a Bioluminescent Nitroreductase Probe for Preclinical Imaging.

Vorobyeva AG; Stanton M; Godinat A; Lund KB; Karateev GG; Francis KP; Allen E; Gelovani JG; McCormack E; Tangney M; Dubikovskaya EA

doi:10.1371/journal.pone.0131037

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Journal article

Development of a Bioluminescent Nitroreductase Probe for Preclinical Imaging.

Vorobyeva AG School of Basic Sciences, Institute of Chemical Sciences and Engineering, Swiss Federal Institute of Technology of Lausanne, Lausanne, Switzerland.
Stanton M Cork Cancer Research Centre, University College Cork, Cork, Ireland.
Godinat A School of Basic Sciences, Institute of Chemical Sciences and Engineering, Swiss Federal Institute of Technology of Lausanne, Lausanne, Switzerland.
Lund KB Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Internal Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway.
Karateev GG School of Basic Sciences, Institute of Chemical Sciences and Engineering, Swiss Federal Institute of Technology of Lausanne, Lausanne, Switzerland.
Francis KP PerkinElmer, Hopkinton, Massachusetts, United States of America.
Allen E School of Life Sciences, Swiss Institute for Experimental Cancer Research (ISREC), Swiss Federal Institute of Technology of Lausanne, Lausanne, Switzerland.
Gelovani JG Department of Biomedical Engineering, College of Engineering and School of Medicine, Wayne State University, Detroit, Michigan, United States of America.
McCormack E Department of Clinical Science, University of Bergen, Bergen, Norway; Department of Internal Medicine, Hematology Section, Haukeland University Hospital, Bergen, Norway.
Tangney M Cork Cancer Research Centre, University College Cork, Cork, Ireland.
Dubikovskaya EA School of Basic Sciences, Institute of Chemical Sciences and Engineering, Swiss Federal Institute of Technology of Lausanne, Lausanne, Switzerland.

2015-06-26

Published in:

PloS one. - 2015

English 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.

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