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Published online before print October 1, 2001, 10.1148/radiol.2212010368
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(Radiology. 2001;221:523-529.)
© RSNA, 2001

Experimental Studies

Optical Imaging of Matrix Metalloproteinase–2 Activity in Tumors: Feasibility Study in a Mouse Model1

Christoph Bremer, MD, Sebastian Bredow, PhD2, Umar Mahmood, MD, PhD, Ralph Weissleder, MD, PhD and Ching-Hsuan Tung, PhD

1 From the Center for Molecular Imaging Research, Massachusetts General Hospital, Bldg 149, 13th St, Rm 5406, Charlestown, MA 02129. Received January 25, 2001; revision requested March 6; revision received April 2; accepted May 21. Supported in part by National Institutes of Health grant R21/R33 CA088365. C.H.T. supported by a 1999 RSNA Seed Grant 1. C.B. supported by the German Research Foundation (DFG). Address correspondence to C.H.T. (e-mail: tung@helix.mgh.harvard.edu).

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.

Index terms: Animals • Enzymes • Experimental study • Molecular analysis • Neoplasms, experimental studies, **.323




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