Nitroreductase, a Near-Infrared Reporter Platform for In Vivo Time-Domain Optical Imaging of Metastatic Cancer

Institute of Medicine/Section of Hematology, University of Bergen.
Cancer Research (Impact Factor: 9.33). 12/2012; 73(4). DOI: 10.1158/0008-5472.CAN-12-2649
Source: PubMed


The ability to visualize reporter gene expression in vivo has revolutionized all facets of biological investigation and none more so than imaging applications in oncology. Near-infrared reporter gene imaging may facilitate more accurate evaluation of chemotherapeutic response in preclinical models of orthotopic and metastatic cancers. We report the development of a cell permeable, quenched cyanine probe (CytoCy5S), which is reduced by Escherichia coli nitroreductase (NTR) resulting in a near-infrared fluorescent product. Time-domain molecular imaging of NTR/CytoCy5S reporter platform permitted non-invasive monitoring of disease progression in orthotopic xenografts of disseminated leukemia, lung and metastatic breast cancer. This methodology facilitated therapeutic evaluation of nitroreductase gene-directed enzymatic prodrug therapy with conventional metronidazole antibiotics. These studies demonstrate NTR/CytoCy5S as a near-infrared gene reporter system with broad preclinical and prospective clinical applications within imaging, and gene therapy, of cancer.

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