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

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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 c...