Noninvasive Detection of Matrix Metalloproteinase Activity In Vivo using a Novel Magnetic Resonance Imaging Contrast Agent with a Solubility Switch | Zendy

Martin Lepage | Zendy; William C. Dow | Zendy; Marco Melchior | Zendy; Ying You | Zendy; Barbara Fingleton | Zendy; C. Chad Quarles | Zendy; C.A. Pepin | Zendy; John C. Gore | Zendy; Lynn M. Matrisian | Zendy; J. Oliver McIntyre | Zendy

Open Access

Noninvasive Detection of Matrix Metalloproteinase Activity In Vivo using a Novel Magnetic Resonance Imaging Contrast Agent with a Solubility Switch

Author(s) -

Martin Lepage,

William C. Dow,

Marco Melchior,

Ying You,

Barbara Fingleton,

C. Chad Quarles,

C.A. Pepin,

John C. Gore,

Lynn M. Matrisian,

J. Oliver McIntyre

Publication year - 2007

Publication title -

molecular imaging

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 0.815

H-Index - 60

eISSN - 1536-0121

pISSN - 1535-3508

DOI - 10.2310/7290.2007.00035

Subject(s) - in vivo , matrix metalloproteinase , gadolinium , chemistry , magnetic resonance imaging , matrix metalloproteinase inhibitor , solubility , biophysics , matrix (chemical analysis) , biochemistry , medicine , chromatography , biology , radiology , microbiology and biotechnology , organic chemistry

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

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