Journal
RADIOLOGY
Volume 221, Issue 2, Pages 523-529Publisher
RADIOLOGICAL SOC NORTH AMERICA
DOI: 10.1148/radiol.2212010368
Keywords
animals; enzymes; experimental study; molecular analysis; neoplasms, experimental studies
Funding
- NCI NIH HHS [R21/R33 CA088365] Funding Source: Medline
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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.
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