Noninvasive Detection of Matrix Metalloproteinase Activity In Vivo using a Novel Magnetic Resonance Imaging Contrast Agent with a Solubility Switch
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...
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| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2007-11-01
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| Series: | Molecular Imaging |
| Online Access: | https://doi.org/10.2310/7290.2007.00035 |
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| _version_ | 1846097841823416320 |
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| author | Martin Lepage William C. Dow Marco Melchior Ying You Barbara Fingleton C. Chad Quarles Claude Pépin John C. Gore Lynn M. Matrisian J. Oliver McIntyre |
| author_facet | Martin Lepage William C. Dow Marco Melchior Ying You Barbara Fingleton C. Chad Quarles Claude Pépin John C. Gore Lynn M. Matrisian J. Oliver McIntyre |
| author_sort | Martin Lepage |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-9e994925d1524712bfd45a3008b4ca0f |
| institution | Kabale University |
| issn | 1536-0121 |
| language | English |
| publishDate | 2007-11-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Molecular Imaging |
| spelling | doaj-art-9e994925d1524712bfd45a3008b4ca0f2025-01-02T02:59:18ZengSAGE PublishingMolecular Imaging1536-01212007-11-01610.2310/7290.2007.0003510.2310_7290.2007.00035Noninvasive Detection of Matrix Metalloproteinase Activity In Vivo using a Novel Magnetic Resonance Imaging Contrast Agent with a Solubility SwitchMartin LepageWilliam C. DowMarco MelchiorYing YouBarbara FingletonC. Chad QuarlesClaude PépinJohn C. GoreLynn M. MatrisianJ. Oliver McIntyreWe 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.https://doi.org/10.2310/7290.2007.00035 |
| spellingShingle | Martin Lepage William C. Dow Marco Melchior Ying You Barbara Fingleton C. Chad Quarles Claude Pépin John C. Gore Lynn M. Matrisian J. Oliver McIntyre Noninvasive Detection of Matrix Metalloproteinase Activity In Vivo using a Novel Magnetic Resonance Imaging Contrast Agent with a Solubility Switch Molecular Imaging |
| title | Noninvasive Detection of Matrix Metalloproteinase Activity In Vivo using a Novel Magnetic Resonance Imaging Contrast Agent with a Solubility Switch |
| title_full | Noninvasive Detection of Matrix Metalloproteinase Activity In Vivo using a Novel Magnetic Resonance Imaging Contrast Agent with a Solubility Switch |
| title_fullStr | Noninvasive Detection of Matrix Metalloproteinase Activity In Vivo using a Novel Magnetic Resonance Imaging Contrast Agent with a Solubility Switch |
| title_full_unstemmed | Noninvasive Detection of Matrix Metalloproteinase Activity In Vivo using a Novel Magnetic Resonance Imaging Contrast Agent with a Solubility Switch |
| title_short | Noninvasive Detection of Matrix Metalloproteinase Activity In Vivo using a Novel Magnetic Resonance Imaging Contrast Agent with a Solubility Switch |
| title_sort | noninvasive detection of matrix metalloproteinase activity in vivo using a novel magnetic resonance imaging contrast agent with a solubility switch |
| url | https://doi.org/10.2310/7290.2007.00035 |
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