title: Design of a bioreductively-activated fluorescent pH probe for tumor hypoxia imaging.
abstract: We have designed and evaluated UTX-12 as a novel fluorescent pH probe for tumor hypoxia imaging. UTX-12 consists of a p-nitro benzyl moiety, which is a latent hypoxia-selective leaving group activated by nitro reduction, directly linked to SNARF. Although UTX-12 itself is colorless and non-fluorescent in aqueous solution, nitro reduction triggers the release of SNARF which has well-characterized long wavelength absorption and fluorescence that is sensitive to pH. The resultant SNARF, released intracellularly by enzymatic reduction of UTX-12, allows measurement of pH by pH-dependent dual emission shifts. UTX-12 showed clear differences in fluorescence behavior between hypoxic and aerobic conditions in liver microsomes and inside V79 cells. These data are confirmation that UTX-12 is biologically reduced inside tumor cells and the released SNARF should monitor intracellular pH of tumor cells selectively with reduced background signal.
authors.affiliation: Department of Life System, Institute of Technology and Science, Graduate School, The University of Tokushima, Minamijosanjimacho 2, Tokushima 770-8506, Japan. nakata@bio.tokushima-u.ac.jp
authors.forename: Eiji
authors.initials: E
authors.lastname: Nakata
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yukimachi
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kariyazono
authors.forename: Seongwang
authors.initials: S
authors.lastname: Im
authors.forename: Chiaki
authors.initials: C
authors.lastname: Abe
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Uto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Maezawa
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Hashimoto
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Okamoto
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Hori
mesh_terms: D000818:Animals; D001578:Benzopyrans / Q000737:chemistry*; D015687:Cell Hypoxia; D002460:Cell Line; D003952:Diagnostic Imaging / Q000379:methods*; D004136:Dinitrobenzenes / Q000737:chemistry*; D015195:Drug Design; D005456:Fluorescent Dyes; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008862:Microsomes, Liver; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D010084:Oxidation-Reduction
chemical_list: D001578:Benzopyrans; D004136:Dinitrobenzenes; D005456:Fluorescent Dyes; C063917:SNARF dye