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

被引：50

作者：

Lepage, Martin ^{[1
,2
,3
,4
]}

Dow, William C. ^{[1
,2
,3
,4
]}

Melchior, Marco ^{[1
,2
,3
,4
]}

You, Ying ^{[1
,2
,3
,4
]}

Fingleton, Barbara ^{[1
,2
,3
,4
]}

Quarles, C. Chad ^{[1
,2
,3
,4
]}

Pepin, Claude ^{[1
,2
,3
,4
]}

Gore, John C. ^{[1
,2
,3
,4
]}

Matrisian, Lynn M. ^{[1
,2
,3
,4
]}

McIntyre, J. Oliver ^{[1
,2
,3
,4
]}

机构：

[1] Univ Sherbrooke, Sherbrooke Mol Imaging Ctr, Sherbrooke, PQ J1H 5N4, Canada

[2] Vanderbilt Univ, Vanderbilt Univ Inst Imaging Sci, Dept Canc Biol, Nashville, TN USA

[3] Vanderbilt Univ, Vanderbilt Univ Inst Imaging Sci, Vanderbilt Ingram Canc Ctr, Nashville, TN USA

[4] Alerion Biomed Inc, San Diego, CA USA

来源：

MOLECULAR IMAGING | 2007年 / 6卷 / 06期

关键词：

D O I：

10.2310/7290.2007.00035

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：393 / 403

页数：11

共 35 条

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