Noninvasive detection of matrix metalloproteinase activity in vivo using a novel magnetic resonance imaging contrast agent with a solubility switch.

Lepage M, Dow WC, Melchior M, You Y, Fingleton B, Quarles CC, P├ępin C, Gore JC, Matrisian LM, McIntyre JO
Mol Imaging. 2007 6 (6): 393-403

PMID: 18053410

We have developed novel proteinase-modulated contrast agents (PCAs) to detect the activity of proteinases in vivo using magnetic resonance imaging. The PCAs are based on the concept of a solubility switch, from hydrophilic to hydrophobic, that significantly modifies the pharmacokinetic properties of the agent as revealed by the slow efflux kinetics from the activity site. Our compound PCA7-switch detects the activity of the secreted matrix-degrading proteinase matrix-metalloproteinase 7 (MMP-7) in living, tumor-bearing mice. Control experiments were performed using an agent that was not cleaved by MMP-7 (PCA7-scrambled), an agent that could be cleaved by MMP-7 but lacked the solubility switch (PCA7-B), and a standard contrast agent (gadolinium-diethylenetriaminepentaacetic acid). PCA7-switch detected a reduction in MMP-7 activity in tumor-bearing mice treated with a synthetic MMP inhibitor, demonstrating its effectiveness in noninvasive functional imaging of proteolytic activity in vivo.

MeSH Terms (12)

Animals Contrast Media Humans Magnetic Resonance Imaging Matrix Metalloproteinase 7 Matrix Metalloproteinases Mice Mice, Nude Models, Biological Neoplasm Transplantation Solubility Tumor Cells, Cultured

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