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

Purpose: To develop an optical imaging method to determine the expression l evel of tumoral matrix metalloproteinase-2 (MMP-2) in vivo. Materials and methods: An optical contrast agent was developed that was hig hly activatable by means of MMP-2-induced conversion. Signal characteristic s of the probe were quantified ex vivo with a recombinant enzyme. Animal tu mor models were established with MMP-2-positive (human fibrosarcoma cell li ne, n=4) and MMP-2-negative (well-differentiated mammary adenocarcinoma, n= 4) tumor cell lines. Both tumors were implanted into nude mice and were opt ically imaged after intravenous administration of the MMP-2-sensitive probe . Results: The MMP-2-sensitive probe was activated by MMP-2 in vitro, produci ng up to an 850% increase in near-infrared fluorescent signal intensity. Th is activation could be blocked by MMP-2 inhibitors. MMP-2-positive tumors w ere easily identified as high-signal-intensity regions as early as 1 hour a fter intravenous injection of the MMP-2 probe, while contralateral MMP-2-ne gative tumors showed little to no signal intensity. A nonspecific control p robe 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 metalloproteina se-sensitive probes.