Development of a bioluminescent nitroreductase probe for preclinical imaging

Anzhelika G. Vorobyeva, Michael Stanton, Aurélien Godinat, Kjetil B. Lund, Grigory G. Karateev, Kevin P. Francis, Elizabeth Allen, Juri G. Gelovani, Emmet McCormack, Mark Tangney, Elena A. Dubikovskaya

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

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.

Original languageEnglish
Article numbere0131037
JournalPLoS One
Volume10
Issue number6
DOIs
Publication statusPublished - 25 Jun 2015
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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