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

Shimizu, Yoichi; Temma, Takashi; Hara, Isao; Makino, Akira; Kondo, Naoya; Ozeki, Ei-ichi; Ono, Masahiro; Saji, Hideo

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

Shimizu, Yoichi; Temma, Takashi; Hara, Isao et al.

Cancer Science, 2014, 105(8), 1056-1062

Permalink : https://hdl.handle.net/2115/57297

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アクセス権	open access
URI	https://hdl.handle.net/2115/57297
タイトル	In vivo imaging of membrane type-1 matrix metalloproteinase with a novel activatable near-infrared fluorescence probe
著者	Shimizu, Yoichi ; Temma, Takashi ; Hara, Isao ; Makino, Akira ; Kondo, Naoya ; Ozeki, Ei-ichi ; Ono, Masahiro ; Saji, Hideo
著者名 Shimizu, Yoichi
e-Rad_Researcher 90378787 著者名 Temma, Takashi
著者名 Hara, Isao
著者名 Makino, Akira
著者名 Kondo, Naoya
著者名 Ozeki, Ei-ichi
著者名 Ono, Masahiro
e-Rad_Researcher 40115853 著者名 Saji, Hideo
言語	英語
キーワード	Activatable probe
	membrane type-1 matrix metalloproteinase
	molecular imaging
	near-infrared
	optical
発行日	2014-08
出版者	Wiley-Blackwell
収録物名	Cancer Science
巻(号)	105(8)
ページ	1056-1062
抄録	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.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
権利情報	Creative Commons Attribution-NonCommercial 3.0 Unported
PISSN	1347-9032
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.1111/cas.12457