Design of a bioreductively-activated fluorescent pH probe for tumor hypoxia imaging

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-fluoresce...

Full description

Saved in:
Bibliographic Details
Published in:Bioorganic & medicinal chemistry 2009-10, Vol.17 (19), p.6952-6958
Main Authors: Nakata, Eiji, Yukimachi, Yoshihiro, Kariyazono, Hirokazu, Im, Seongwang, Abe, Chiaki, Uto, Yoshihiro, Maezawa, Hiroshi, Hashimoto, Toshihiro, Okamoto, Yasuko, Hori, Hitoshi
Format: Article
Language:English
Subjects:
Animals
Benzopyrans - chemistry
Bioreductive activation
Cell Hypoxia
Cell Line
Diagnostic Imaging - methods
Dinitrobenzenes - chemistry
Drug Design
Fluorescent Dyes
Fluorescent imaging
Fluorescent pH probe
Humans
Hydrogen-Ion Concentration
Microsomes, Liver
Neoplasms - metabolism
Neoplasms - pathology
Nitro reduction
Oxidation-Reduction
Tumor hypoxia
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0968-0896
1464-3391
DOI:10.1016/j.bmc.2009.08.037