2-Nitroimidazole-Tricarbocyanine Conjugate as a Near-Infrared Fluorescent Probe for <i>in Vivo</i> Imaging of Tumor Hypoxia

We developed a novel near-infrared (NIR) fluorescent probe, GPU-167, for <i>in vivo</i> imaging of tumor hypoxia. GPU-167 comprises a tricarbocyanine dye as an NIR fluorophore and two 2-nitroimidazole moieties as exogenous hypoxia markers that undergo bioreductive activation and then selective entrapment in hypoxic cells. After treatment with GPU-167, tumor cells contained significantly higher levels of fluorescence in hypoxia than in normoxia. <i>In vivo</i> fluorescence imaging specifically detected GPU-167 in tumors 24 h after administration. <i>Ex vivo</i> analysis revealed that fluorescence showed a strong correlation with hypoxia inducible factor (HIF)-1 active hypoxic regions. These data suggest that GPU-167 is a promising <i>in vivo</i> optical imaging probe for tumor hypoxia