In vivo optical imaging of membrane-type matrix metalloproteinase (MT-MMP) activity.
Herein we demonstrate for the first time that a fluorogenic probe can be used as an in vivo imaging agent for visualizing activities of membrane-tethered, membrane-type matrix metalloproteinases (MT-MMPs). An MT-MMP fluorogenic probe that consisted of an MT1-MMP (MMP-14) substrate and near-infrared (NIR) dye-quencher pair exhibited rapid, efficient boosts in fluorescence upon cleavage by MT1-MMP in tumor-bearing mice. In particular, unlike similar fluorogenic probes designed to target extracellular, soluble-type MMPs (EC-MMPs)--which can be cleared from the bloodstream after activation--the fluorescence signals activated by MT1-MMP enable clear visualization of MT1-MMP-positive tumors in animal models for up to 24 h. The results indicate that a simple form of a fluorogenic probe that is less effective in EC-MMP imaging is an effective probe for imaging MT-MMP activities in vivo. These findings can be widely applied to designing probes and to applications targeting various membrane-anchored proteases in vivo.
Laboratory of Molecular Imaging and Nanomedicine, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, Maryland 20892, United States.
Lei
L
Zhu
Fan
F
Zhang
Ying
Y
Ma
Gang
G
Liu
Kwangmeyung
K
Kim
Xuexun
X
Fang
Seulki
S
Lee
Xiaoyuan
X
Chen
D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D005456:Fluorescent Dyes; D053504:Matrix Metalloproteinases, Membrane-Associated / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D057054:Molecular Imaging; D009369:Neoplasms / Q000201:enzymology
D005456:Fluorescent Dyes; D053504:Matrix Metalloproteinases, Membrane-Associated