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In vivo imaging of membrane type-1 matrix metalloproteinase with a novel activatable near-infrared fluorescence probe

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Title: In vivo imaging of membrane type-1 matrix metalloproteinase with a novel activatable near-infrared fluorescence probe
Authors: Shimizu, Yoichi Browse this author
Temma, Takashi Browse this author →KAKEN DB
Hara, Isao Browse this author
Makino, Akira Browse this author
Kondo, Naoya Browse this author
Ozeki, Ei-ichi Browse this author
Ono, Masahiro Browse this author
Saji, Hideo Browse this author →KAKEN DB
Keywords: Activatable probe
membrane type-1 matrix metalloproteinase
molecular imaging
Issue Date: Aug-2014
Publisher: Wiley-Blackwell
Journal Title: Cancer Science
Volume: 105
Issue: 8
Start Page: 1056
End Page: 1062
Publisher DOI: 10.1111/cas.12457
Abstract: Membrane type-1 matrix metalloproteinase (MT1-MMP) is a protease activating MMP-2 that mediates cleavage of extracellular matrix components and plays pivotal roles in tumor migration, invasion and metastasis. Because in vivo noninvasive imaging of MT1-MMP would be useful for tumor diagnosis, we developed a novel near-infrared (NIR) fluorescence probe that can be activated following interaction with MT1-MMP in vivo. MT1-hIC7L is an activatable fluorescence probe comprised of anti-MT1-MMP monoclonal antibodies conjugated to self-assembling polymer micelles that encapsulate NIR dyes (IC7-1, em: 858nm) at concentrations sufficient to cause fluorescence self-quenching. In aqueous buffer, MT1-hIC7L fluorescence was suppressed to background levels and increased approximately 35.5-fold in the presence of detergent. Cellular uptake experiments revealed that in MT1-MMP positive C6 glioma cells, MT1-hIC7L showed significantly higher fluorescence that increased with time as compared to hIC7L, a negative control probe lacking the anti-MT1-MMP monoclonal antibody. In MT1-MMP negative MCF-7 breast adenocarcinoma cells, both MT1-hIC7L and hIC7L showed no obvious fluorescence. In addition, the fluorescence intensity of C6 cells treated with MT1-hIC7L was suppressed by pre-treatment with an MT1-MMP endocytosis inhibitor (P<0.05). In vivo optical imaging using probes intravenously administered to tumor-bearing mice showed that MT1-hIC7L specifically visualized C6 tumors (tumor-to-background ratios: 3.8 +/- 0.3 [MT1-hIC7L] vs 3.1 +/- 0.2 [hIC7L] 48h after administration, P<0.05), while the probes showed similarly low fluorescence in MCF-7 tumors. Together, these results show that MT1-hIC7L would be a potential activatable NIR probe for specifically detecting MT1-MMP-expressing tumors.
Type: article
Appears in Collections:アイソトープ総合センター (Central Institute of Isotope Science) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 志水 陽一

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