PDF file - 99K, Materials and methods of CytoCy5S synthesis, purification, spectral and structural characterization in addition to NTR/CytoCy5S enzymatic reaction conditions and western blots.

PDF file - 402K, Synthesis, mechanism and spectral characteristics of CytoCy5S.

PDF file - 314K, In vivo characterization of NTR/CytoCy5S fluorescence and fluorescence lifetime distributions in NB4NTR+GFP+ subcutaneous tumors, NCI-H460NTR+Luc+GFP+ orthotopic xenografts and gastrointestinal tract.

Abstract The ability to visualize reporter gene expression in vivo has revolutionized all facets of biologic 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 squarine 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 noninvasive monitoring of disease progression in orthotopic xenografts of disseminated leukemia, lung, and metastatic breast cancer. This methodology facilitated therapeutic evaluation of NTR gene–directed enzymatic prodrug therapy with conventional metronidazole antibiotics. These studies show NTR/CytoCy5S as a near-infrared gene reporter system with broad preclinical and prospective clinical applications within imaging, and gene therapy, of cancer. Cancer Res; 73(4); 1276–86. ©2012 AACR.

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PDF file - 718K, In vitro viability of NB4 and MDA-MB-231 cells � NTR � MTZ.

PDF file - 358K, In vitro viability of NB4, NCI-H460 and MDA-MB-231 cells NTR CytoCy5S.