New Enzyme-Activated Solubility-Switchable Contrast Agent for Magnetic Resonance Imaging: From Synthesis to in Vivo Imaging
We designed and synthesized a novel contrast agent (CA) to image the activity of matrix metalloproteinase-2 (MMP-2) in a tumor, noninvasively using magnetic resonance imaging (MRI). We exploited the concept of solubility-switchable CAs in the design of a protease-modulated CA (PCA), referred to as P...
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| Veröffentlicht in: | Journal of medicinal chemistry 2009-03, Vol.52 (6), p.1576-1581 |
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| container_title | Journal of medicinal chemistry |
| container_volume | 52 |
| creator | Jastrzȩbska, Beata Lebel, Réjean Therriault, Hélène McIntyre, J. Oliver Escher, Emanuel Guérin, Brigitte Paquette, Benoit Neugebauer, Witold A Lepage, Martin |
| description | We designed and synthesized a novel contrast agent (CA) to image the activity of matrix metalloproteinase-2 (MMP-2) in a tumor, noninvasively using magnetic resonance imaging (MRI). We exploited the concept of solubility-switchable CAs in the design of a protease-modulated CA (PCA), referred to as PCA2-switch. This PCA contains a paramagnetic gadolinium chelate (Gd-DOTA), which was attached to the N-terminus of a MMP-2 cleavable peptide sequence via a hydrophobic chain. The aqueous solubility of the CA depends on the presence of a polyethylene glycol chain (PEG) on the C-terminus of the peptide. Upon proteolytic cleavage of the peptide by MMP-2, the PEG chain is detached from the CA, which becomes less water soluble. This compound and control compounds were successfully tested in an animal model bearing two tumors with different levels of MMP-2 activity. |
| doi_str_mv | 10.1021/jm801411h |
| format | Article |
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Oliver ; Escher, Emanuel ; Guérin, Brigitte ; Paquette, Benoit ; Neugebauer, Witold A ; Lepage, Martin</creator><creatorcontrib>Jastrzȩbska, Beata ; Lebel, Réjean ; Therriault, Hélène ; McIntyre, J. Oliver ; Escher, Emanuel ; Guérin, Brigitte ; Paquette, Benoit ; Neugebauer, Witold A ; Lepage, Martin</creatorcontrib><description>We designed and synthesized a novel contrast agent (CA) to image the activity of matrix metalloproteinase-2 (MMP-2) in a tumor, noninvasively using magnetic resonance imaging (MRI). We exploited the concept of solubility-switchable CAs in the design of a protease-modulated CA (PCA), referred to as PCA2-switch. This PCA contains a paramagnetic gadolinium chelate (Gd-DOTA), which was attached to the N-terminus of a MMP-2 cleavable peptide sequence via a hydrophobic chain. The aqueous solubility of the CA depends on the presence of a polyethylene glycol chain (PEG) on the C-terminus of the peptide. Upon proteolytic cleavage of the peptide by MMP-2, the PEG chain is detached from the CA, which becomes less water soluble. This compound and control compounds were successfully tested in an animal model bearing two tumors with different levels of MMP-2 activity.</description><identifier>ISSN: 0022-2623</identifier><identifier>EISSN: 1520-4804</identifier><identifier>DOI: 10.1021/jm801411h</identifier><identifier>PMID: 19228016</identifier><identifier>CODEN: JMCMAR</identifier><language>eng</language><publisher>Columbus, OH: American Chemical Society</publisher><subject>Animals ; Biological and medical sciences ; Contrast Media ; Contrast media. Radiopharmaceuticals ; Heterocyclic Compounds ; Magnetic Resonance Imaging ; Matrix Metalloproteinase 2 - metabolism ; Medical sciences ; Mice ; Neoplasms, Experimental - enzymology ; Organometallic Compounds ; Pharmacology. Drug treatments ; Solubility ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization</subject><ispartof>Journal of medicinal chemistry, 2009-03, Vol.52 (6), p.1576-1581</ispartof><rights>Copyright © 2009 American Chemical Society</rights><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a343t-6ba7d3f289aad57dcc19c66493fc3f0175efd5b75498e1bf129a0dd0ef0bee873</citedby><cites>FETCH-LOGICAL-a343t-6ba7d3f289aad57dcc19c66493fc3f0175efd5b75498e1bf129a0dd0ef0bee873</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/jm801411h$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jm801411h$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,776,780,2752,27053,27901,27902,56713,56763</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21284691$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19228016$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jastrzȩbska, Beata</creatorcontrib><creatorcontrib>Lebel, Réjean</creatorcontrib><creatorcontrib>Therriault, Hélène</creatorcontrib><creatorcontrib>McIntyre, J. Oliver</creatorcontrib><creatorcontrib>Escher, Emanuel</creatorcontrib><creatorcontrib>Guérin, Brigitte</creatorcontrib><creatorcontrib>Paquette, Benoit</creatorcontrib><creatorcontrib>Neugebauer, Witold A</creatorcontrib><creatorcontrib>Lepage, Martin</creatorcontrib><title>New Enzyme-Activated Solubility-Switchable Contrast Agent for Magnetic Resonance Imaging: From Synthesis to in Vivo Imaging</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>We designed and synthesized a novel contrast agent (CA) to image the activity of matrix metalloproteinase-2 (MMP-2) in a tumor, noninvasively using magnetic resonance imaging (MRI). We exploited the concept of solubility-switchable CAs in the design of a protease-modulated CA (PCA), referred to as PCA2-switch. This PCA contains a paramagnetic gadolinium chelate (Gd-DOTA), which was attached to the N-terminus of a MMP-2 cleavable peptide sequence via a hydrophobic chain. The aqueous solubility of the CA depends on the presence of a polyethylene glycol chain (PEG) on the C-terminus of the peptide. Upon proteolytic cleavage of the peptide by MMP-2, the PEG chain is detached from the CA, which becomes less water soluble. This compound and control compounds were successfully tested in an animal model bearing two tumors with different levels of MMP-2 activity.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Contrast Media</subject><subject>Contrast media. Radiopharmaceuticals</subject><subject>Heterocyclic Compounds</subject><subject>Magnetic Resonance Imaging</subject><subject>Matrix Metalloproteinase 2 - metabolism</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Neoplasms, Experimental - enzymology</subject><subject>Organometallic Compounds</subject><subject>Pharmacology. Drug treatments</subject><subject>Solubility</subject><subject>Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpt0EtPGzEQwHGroioh5dAvUPlSJA7b-rHP3qKIlwRUalquq1nvOHG0a4PtTZT2y7OIABdOc_nNjPQn5Atn3zkT_Me6LxlPOV99IBOeCZakJUsPyIQxIRKRC3lIjkJYM8YkF_ITOeSVEONKPiH_b3FLz-y_XY_JTEWzgYgtXbhuaExn4i5ZbE1UK2g6pHNno4cQ6WyJNlLtPL2BpcVoFP2NwVmwCulVD0tjlz_puXc9XexsXGEwgUZHjaV3ZuNeyGfyUUMX8Hg_p-Tv-dmf-WVy_eviaj67TkCmMiZ5A0UrtSgrgDYrWqV4pfI8raRWUjNeZKjbrCmytCqRN5qLCljbMtSsQSwLOSUnz3fvvXsYMMS6N0Fh14FFN4Q6L1gqskyO8PQZKu9C8Kjre2968Luas_qpdP1aerRf90eHpsf2Te7TjuDbHkBQ0Gk_1jHh1QkuyjSv-JsDFeq1G7wdW7zz8BHlNJNu</recordid><startdate>20090326</startdate><enddate>20090326</enddate><creator>Jastrzȩbska, Beata</creator><creator>Lebel, Réjean</creator><creator>Therriault, Hélène</creator><creator>McIntyre, J. Oliver</creator><creator>Escher, Emanuel</creator><creator>Guérin, Brigitte</creator><creator>Paquette, Benoit</creator><creator>Neugebauer, Witold A</creator><creator>Lepage, Martin</creator><general>American Chemical Society</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20090326</creationdate><title>New Enzyme-Activated Solubility-Switchable Contrast Agent for Magnetic Resonance Imaging: From Synthesis to in Vivo Imaging</title><author>Jastrzȩbska, Beata ; Lebel, Réjean ; Therriault, Hélène ; McIntyre, J. Oliver ; Escher, Emanuel ; Guérin, Brigitte ; Paquette, Benoit ; Neugebauer, Witold A ; Lepage, Martin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a343t-6ba7d3f289aad57dcc19c66493fc3f0175efd5b75498e1bf129a0dd0ef0bee873</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Contrast Media</topic><topic>Contrast media. Radiopharmaceuticals</topic><topic>Heterocyclic Compounds</topic><topic>Magnetic Resonance Imaging</topic><topic>Matrix Metalloproteinase 2 - metabolism</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Neoplasms, Experimental - enzymology</topic><topic>Organometallic Compounds</topic><topic>Pharmacology. Drug treatments</topic><topic>Solubility</topic><topic>Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jastrzȩbska, Beata</creatorcontrib><creatorcontrib>Lebel, Réjean</creatorcontrib><creatorcontrib>Therriault, Hélène</creatorcontrib><creatorcontrib>McIntyre, J. 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This PCA contains a paramagnetic gadolinium chelate (Gd-DOTA), which was attached to the N-terminus of a MMP-2 cleavable peptide sequence via a hydrophobic chain. The aqueous solubility of the CA depends on the presence of a polyethylene glycol chain (PEG) on the C-terminus of the peptide. Upon proteolytic cleavage of the peptide by MMP-2, the PEG chain is detached from the CA, which becomes less water soluble. This compound and control compounds were successfully tested in an animal model bearing two tumors with different levels of MMP-2 activity.</abstract><cop>Columbus, OH</cop><pub>American Chemical Society</pub><pmid>19228016</pmid><doi>10.1021/jm801411h</doi><tpages>6</tpages></addata></record> |
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| subjects | Animals Biological and medical sciences Contrast Media Contrast media. Radiopharmaceuticals Heterocyclic Compounds Magnetic Resonance Imaging Matrix Metalloproteinase 2 - metabolism Medical sciences Mice Neoplasms, Experimental - enzymology Organometallic Compounds Pharmacology. Drug treatments Solubility Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization |
| title | New Enzyme-Activated Solubility-Switchable Contrast Agent for Magnetic Resonance Imaging: From Synthesis to in Vivo Imaging |
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