Specific detection and imaging of enzyme activity by signal-amplifiable self-assembling 19Fa MRI probes

Kazuya Matsuo, Rui Kamada, Keigo Mizusawa, Hirohiko Imai, Yuki Takayama, Michiko Narazaki, Tetsuya Matsuda, Yousuke Takaoka, Itaru Hamachi

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)

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 19Fa 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 19F probes, nanomolar levels of two different target enzymes, nitroreductase (NTR) and matrix metalloproteinase (MMP), could be detected and visualized by 19Fa NMR spectroscopy and MRI. Furthermore, we have succeeded in imaging the activity of endogenously secreted MMP in cultured media of tumor cells by 19Fa MRI, depending on the cell lines and the cellular conditions. These results clearly demonstrate that our turn-on 19F probes may serve as a screening platform for the activity of MMPs. MR imaging probes: New signal-amplifiable self-assembling 19Fa NMR/MRI probes for turn-on detection and imaging of specific enzymatic activity are reported. The probes are "silent" when aggregated, but exhibit a disassembly-driven turn-on signal change upon cleavage of their substrate part by nanomolar concentrations of the enzyme. These turn-on probes can be used to visualize the activity of endogenously secreted matrix metalloproteinases from tumor cells (see graphic).

Original languageEnglish
Pages (from-to)12875-12883
Number of pages9
JournalChemistry - A European Journal
Volume19
Issue number38
DOIs
Publication statusPublished - 2013 Sep 16
Externally publishedYes

Keywords

  • NMR spectroscopy
  • enzyme activity
  • imaging agents
  • magnetic resonance imaging
  • self-assembly
  • signal amplification

ASJC Scopus subject areas

  • Catalysis
  • Organic Chemistry

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