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

Abstract

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 hydrophllic 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 matrlx-metalloproteinase 7 (MMP-7) in living, tumorbearing mice. Control experiments were performed using an agent that was not claavsd 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 (gadoliniumdiethylenetriamlnepentaacetic acid). PCA7-sw)tch 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. © 2007 BC Decker Inc.