Optical imaging of matrix metalloproteinase-2 activity in tumors: feasibility study in a mouse model.

TitleOptical imaging of matrix metalloproteinase-2 activity in tumors: feasibility study in a mouse model.
Publication TypeJournal Article
Year of Publication2001
AuthorsBremer C, Bredow S, Mahmood U, Weissleder R, Tung CH
JournalRadiology
Volume221
Issue2
Pagination523-9
Date Published2001 Nov
ISSN0033-8419
KeywordsAnimals, Chemistry Techniques, Analytical, Feasibility Studies, Matrix Metalloproteinase 2, Mice, Mice, Nude, Neoplasms, Experimental, Spectrum Analysis
Abstract

PURPOSE: To develop an optical imaging method to determine the expression level of tumoral matrix metalloproteinase-2 (MMP-2) in vivo.

MATERIALS AND METHODS: An optical contrast agent was developed that was highly activatable by means of MMP-2-induced conversion. Signal characteristics of the probe were quantified ex vivo with a recombinant enzyme. Animal tumor models were established with MMP-2-positive (human fibrosarcoma cell line, n = 4) and MMP-2-negative (well-differentiated mammary adenocarcinoma, n = 4) tumor cell lines. Both tumors were implanted into nude mice and were optically imaged after intravenous administration of the MMP-2-sensitive probe.

RESULTS: The MMP-2-sensitive probe was activated by MMP-2 in vitro, producing up to an 850% increase in near-infrared fluorescent signal intensity. This activation could be blocked by MMP-2 inhibitors. MMP-2-positive tumors were easily identified as high-signal-intensity regions as early as 1 hour after intravenous injection of the MMP-2 probe, while contralateral MMP-2-negative tumors showed little to no signal intensity. A nonspecific control probe showed little to no activation in MMP-2-positive tumors.

CONCLUSION: It is feasible to image MMP-2 enzyme activity in vivo by using near-infrared optical imaging technology and "smart" matrix metalloproteinase-sensitive probes.

DOI10.1148/radiol.2212010368
Alternate JournalRadiology
PubMed ID11687699
Grant ListR21/R33 CA088365 / CA / NCI NIH HHS / United States
Related Institute: 
Molecular Imaging Innovations Institute (MI3)

Weill Cornell Medicine
Department of Radiology
525 East 68th Street New York, NY 10065