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Specific Detection and Imaging of Enzyme Activity by Signal‐Amplifiable Self‐Assembling 19 F MRI Probes
Author(s) -
Matsuo Kazuya,
Kamada Rui,
Mizusawa Keigo,
Imai Hirohiko,
Takayama Yuki,
Narazaki Michiko,
Matsuda Tetsuya,
Takaoka Yousuke,
Hamachi Itaru
Publication year - 2013
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201300817
Subject(s) - in vivo , nitroreductase , enzyme , ex vivo , chemistry , magnetic resonance imaging , matrix metalloproteinase , nuclear magnetic resonance spectroscopy , preclinical imaging , nuclear magnetic resonance , biophysics , in vitro , biochemistry , biology , medicine , stereochemistry , physics , microbiology and biotechnology , radiology
Abstract Specific turn‐on detection of enzyme activities is of fundamental importance in drug discovery research, as well as medical diagnostics. Although magnetic resonance imaging (MRI) is one of the most powerful techniques for noninvasive visualization of enzyme activity, both in vivo and ex vivo, promising strategies for imaging specific enzymes with high contrast have been very limited to date. We report herein a novel signal‐amplifiable self‐assembling 19 F NMR/MRI probe for turn‐on detection and imaging of specific enzymatic activity. In NMR spectroscopy, these designed probes are “silent” when aggregated, but exhibit a disassembly driven turn‐on signal change upon cleavage of the substrate part by the catalytic enzyme. Using these 19 F probes, nanomolar levels of two different target enzymes, nitroreductase (NTR) and matrix metalloproteinase (MMP), could be detected and visualized by 19 F NMR spectroscopy and MRI. Furthermore, we have succeeded in imaging the activity of endogenously secreted MMP in cultured media of tumor cells by 19 F MRI, depending on the cell lines and the cellular conditions. These results clearly demonstrate that our turn‐on 19 F probes may serve as a screening platform for the activity of MMPs.