title: 2-Nitroimidazole-tricarbocyanine conjugate as a near-infrared fluorescent probe for in vivo imaging of tumor hypoxia.
abstract: We developed a novel near-infrared (NIR) fluorescent probe, GPU-167, for in vivo 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. In vivo fluorescence imaging specifically detected GPU-167 in tumors 24 h after administration. Ex vivo 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 in vivo optical imaging probe for tumor hypoxia.
authors.affiliation: Laboratory of Pharmaceutical and Medicinal Chemistry, Gifu Pharmaceutical University, Gifu 501-1196, Japan.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Okuda
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Okabe
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kadonosono
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ueno
authors.forename: Bahaa G M
authors.initials: BG
authors.lastname: Youssif
authors.forename: Shinae
authors.initials: S
authors.lastname: Kizaka-Kondoh
authors.forename: Hideko
authors.initials: H
authors.lastname: Nagasawa
mesh_terms: D000818:Animals; D002232:Carbocyanines / Q000737:chemistry*; D015687:Cell Hypoxia; D005456:Fluorescent Dyes / Q000737:chemistry*; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000473:pathology*; D009593:Nitroimidazoles / Q000737:chemistry*; D019265:Spectroscopy, Near-Infrared / Q000379:methods*
chemical_list: D002232:Carbocyanines; D005456:Fluorescent Dyes; C573827:GPU-167; D009593:Nitroimidazoles