In vivo CEST MR imaging of U87 mice brain tumor angiogenesis using targeted LipoCEST contrast agent at 7 T
Identifieur interne : 002322 ( Istex/Corpus ); précédent : 002321; suivant : 002323In vivo CEST MR imaging of U87 mice brain tumor angiogenesis using targeted LipoCEST contrast agent at 7 T
Auteurs : Julien Flament ; Françoise Geffroy ; Christelle Medina ; Caroline Robic ; Jean-François Mayer ; Sébastien Mériaux ; Julien Valette ; Philippe Robert ; Marc Port ; Denis Le Bihan ; Franck Lethimonnier ; Fawzi BoumezbeurSource :
- Magnetic Resonance in Medicine [ 0740-3194 ] ; 2013-01.
English descriptors
- KwdEn :
- Aime, Anb3, Anb3 receptors, Angew chem, Angiogenesis, Average interval, Body weight, Brain slices, Brain tissue, Brain tumor, Brain tumors, Castelli, Cest, Cest contrast, Cest effect, Cest images, Chem, Chemical exchange saturation transfer, Contrast agent, Contrast media, Controlateral, Controlateral rois, Dsat, First hour, Fluorescence microscopy, Imaging, Immunohistochemical staining, Intracerebral tumors, Intravenous, Intravenous injection, Lipocest, Liposome, Magn, Magn reson, Mice brain tumor, Molecular imaging, Mouse brain cortex, Mtrasym, Mtrasym values, Nanoparticles, Paracest, Paracest agents, Perfused, Proton, Receptor, Reson, Roi, Saturation, Saturation power, Second hour, Terreno, Third column, Time constants, Time point, Tumor angiogenesis, Tumor region, Vivo, Vivo detection, Zhang.
- Teeft :
- Aime, Anb3, Anb3 receptors, Angew chem, Angiogenesis, Average interval, Body weight, Brain slices, Brain tissue, Brain tumor, Brain tumors, Castelli, Cest, Cest contrast, Cest effect, Cest images, Chem, Chemical exchange saturation transfer, Contrast agent, Contrast media, Controlateral, Controlateral rois, Dsat, First hour, Fluorescence microscopy, Imaging, Immunohistochemical staining, Intracerebral tumors, Intravenous, Intravenous injection, Lipocest, Liposome, Magn, Magn reson, Mice brain tumor, Molecular imaging, Mouse brain cortex, Mtrasym, Mtrasym values, Nanoparticles, Paracest, Paracest agents, Perfused, Proton, Receptor, Reson, Roi, Saturation, Saturation power, Second hour, Terreno, Third column, Time constants, Time point, Tumor angiogenesis, Tumor region, Vivo, Vivo detection, Zhang.
Abstract
LipoCEST are liposome‐encapsulating paramagnetic contrast agents (CA) based on chemical exchange saturation transfer with applications in biomolecular MRI. Their attractive features include biocompatibility, subnanomolar sensitivity, and amenability to functionalization for targeting biomarkers. We demonstrate MR imaging using a targeted lipoCEST, injected intravenously. A lipoCEST carrying Tm(III)‐complexes was conjugated to RGD tripeptide (RGD‐lipoCEST), to target integrin ανβ3 receptors involved in tumor angiogenesis and was compared with an unconjugated lipoCEST. Brain tumors were induced in athymic nude mice by intracerebral injection of U87MG cells and were imaged at 7 T after intravenous injection of either of the two contrast agents (n = 12 for each group). Chemical exchange saturation transfer‐MSME sequence was applied over 2 h with an average acquisition time interval of 13.5 min. The chemical exchange saturation transfer signal was ∼1% in the tumor and controlateral regions, and decreased to ∼0.3% after 2 h; while RGD‐lipoCEST signal was ∼1.4% in the tumor region and persisted for up to 2 h. Immunohistochemical staining revealed a persistent colocalization of RGD‐lipoCEST with ανβ3 receptors in the tumor region. These results constitute an encouraging step toward in vivo MRI imaging of tumor angiogenesis using intravenously injected lipoCEST. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.
Url:
DOI: 10.1002/mrm.24217
Links to Exploration step
ISTEX:9DE7EA85B10661F7FA906761CD80C2196F91AF01Le document en format XML
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unit="page-count">9</biblScope><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2013-01">2013-01</date></imprint><idno type="ISSN">0740-3194</idno></series></biblStruct></sourceDesc><seriesStmt><idno type="ISSN">0740-3194</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aime</term><term>Anb3</term><term>Anb3 receptors</term><term>Angew chem</term><term>Angiogenesis</term><term>Average interval</term><term>Body weight</term><term>Brain slices</term><term>Brain tissue</term><term>Brain tumor</term><term>Brain tumors</term><term>Castelli</term><term>Cest</term><term>Cest contrast</term><term>Cest effect</term><term>Cest images</term><term>Chem</term><term>Chemical exchange saturation transfer</term><term>Contrast agent</term><term>Contrast media</term><term>Controlateral</term><term>Controlateral rois</term><term>Dsat</term><term>First hour</term><term>Fluorescence microscopy</term><term>Imaging</term><term>Immunohistochemical staining</term><term>Intracerebral tumors</term><term>Intravenous</term><term>Intravenous injection</term><term>Lipocest</term><term>Liposome</term><term>Magn</term><term>Magn reson</term><term>Mice brain tumor</term><term>Molecular imaging</term><term>Mouse brain cortex</term><term>Mtrasym</term><term>Mtrasym values</term><term>Nanoparticles</term><term>Paracest</term><term>Paracest agents</term><term>Perfused</term><term>Proton</term><term>Receptor</term><term>Reson</term><term>Roi</term><term>Saturation</term><term>Saturation power</term><term>Second hour</term><term>Terreno</term><term>Third column</term><term>Time constants</term><term>Time point</term><term>Tumor angiogenesis</term><term>Tumor region</term><term>Vivo</term><term>Vivo detection</term><term>Zhang</term></keywords><keywords scheme="Teeft" xml:lang="en"><term>Aime</term><term>Anb3</term><term>Anb3 receptors</term><term>Angew chem</term><term>Angiogenesis</term><term>Average interval</term><term>Body weight</term><term>Brain slices</term><term>Brain tissue</term><term>Brain tumor</term><term>Brain tumors</term><term>Castelli</term><term>Cest</term><term>Cest contrast</term><term>Cest effect</term><term>Cest images</term><term>Chem</term><term>Chemical exchange saturation transfer</term><term>Contrast agent</term><term>Contrast media</term><term>Controlateral</term><term>Controlateral rois</term><term>Dsat</term><term>First hour</term><term>Fluorescence microscopy</term><term>Imaging</term><term>Immunohistochemical staining</term><term>Intracerebral tumors</term><term>Intravenous</term><term>Intravenous injection</term><term>Lipocest</term><term>Liposome</term><term>Magn</term><term>Magn reson</term><term>Mice brain tumor</term><term>Molecular imaging</term><term>Mouse brain cortex</term><term>Mtrasym</term><term>Mtrasym values</term><term>Nanoparticles</term><term>Paracest</term><term>Paracest agents</term><term>Perfused</term><term>Proton</term><term>Receptor</term><term>Reson</term><term>Roi</term><term>Saturation</term><term>Saturation power</term><term>Second hour</term><term>Terreno</term><term>Third column</term><term>Time constants</term><term>Time point</term><term>Tumor angiogenesis</term><term>Tumor region</term><term>Vivo</term><term>Vivo detection</term><term>Zhang</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">LipoCEST are liposome‐encapsulating paramagnetic contrast agents (CA) based on chemical exchange saturation transfer with applications in biomolecular MRI. Their attractive features include biocompatibility, subnanomolar sensitivity, and amenability to functionalization for targeting biomarkers. We demonstrate MR imaging using a targeted lipoCEST, injected intravenously. A lipoCEST carrying Tm(III)‐complexes was conjugated to RGD tripeptide (RGD‐lipoCEST), to target integrin ανβ3 receptors involved in tumor angiogenesis and was compared with an unconjugated lipoCEST. Brain tumors were induced in athymic nude mice by intracerebral injection of U87MG cells and were imaged at 7 T after intravenous injection of either of the two contrast agents (n = 12 for each group). Chemical exchange saturation transfer‐MSME sequence was applied over 2 h with an average acquisition time interval of 13.5 min. The chemical exchange saturation transfer signal was ∼1% in the tumor and controlateral regions, and decreased to ∼0.3% after 2 h; while RGD‐lipoCEST signal was ∼1.4% in the tumor region and persisted for up to 2 h. Immunohistochemical staining revealed a persistent colocalization of RGD‐lipoCEST with ανβ3 receptors in the tumor region. These results constitute an encouraging step toward in vivo MRI imaging of tumor angiogenesis using intravenously injected lipoCEST. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.</div></front></TEI><istex><corpusName>wiley</corpusName><keywords><teeft><json:string>lipocest</json:string><json:string>cest</json:string><json:string>mtrasym</json:string><json:string>paracest</json:string><json:string>magn</json:string><json:string>magn reson</json:string><json:string>reson</json:string><json:string>controlateral</json:string><json:string>anb3</json:string><json:string>liposome</json:string><json:string>cest contrast</json:string><json:string>chem</json:string><json:string>angiogenesis</json:string><json:string>intravenous injection</json:string><json:string>intravenous</json:string><json:string>tumor region</json:string><json:string>aime</json:string><json:string>dsat</json:string><json:string>cest 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tumors</json:string><json:string>saturation</json:string><json:string>vivo</json:string><json:string>mouse brain cortex</json:string><json:string>average interval</json:string><json:string>time point</json:string><json:string>third column</json:string><json:string>vivo detection</json:string><json:string>fluorescence microscopy</json:string><json:string>molecular imaging</json:string><json:string>cest effect</json:string><json:string>saturation power</json:string><json:string>brain tumor</json:string><json:string>contrast media</json:string><json:string>anb3 receptors</json:string><json:string>contrast agent</json:string><json:string>proton</json:string></teeft></keywords><author><json:item><name>Julien Flament</name><affiliations><json:string>Neurospin, I2BM, Commissariat à l'Energie Atomique, Gif‐sur‐Yvette, France</json:string></affiliations></json:item><json:item><name>Françoise Geffroy</name><affiliations><json:string>Neurospin, I2BM, Commissariat à l'Energie Atomique, Gif‐sur‐Yvette, France</json:string></affiliations></json:item><json:item><name>Christelle Medina</name><affiliations><json:string>Guerbet, Research Division, BP 57400, 95943 Roissy‐Charles de Gaulle Cedex, France</json:string></affiliations></json:item><json:item><name>Caroline Robic</name><affiliations><json:string>Guerbet, Research Division, BP 57400, 95943 Roissy‐Charles de Gaulle Cedex, France</json:string></affiliations></json:item><json:item><name>Jean‐François Mayer</name><affiliations><json:string>Guerbet, Research Division, BP 57400, 95943 Roissy‐Charles de Gaulle Cedex, France</json:string></affiliations></json:item><json:item><name>Sébastien Mériaux</name><affiliations><json:string>Neurospin, I2BM, Commissariat à l'Energie Atomique, Gif‐sur‐Yvette, France</json:string></affiliations></json:item><json:item><name>Julien Valette</name><affiliations><json:string>Neurospin, I2BM, Commissariat à l'Energie Atomique, Gif‐sur‐Yvette, France</json:string></affiliations></json:item><json:item><name>Philippe Robert</name><affiliations><json:string>Guerbet, Research Division, BP 57400, 95943 Roissy‐Charles de Gaulle Cedex, France</json:string></affiliations></json:item><json:item><name>Marc Port</name><affiliations><json:string>Guerbet, Research Division, BP 57400, 95943 Roissy‐Charles de Gaulle Cedex, France</json:string></affiliations></json:item><json:item><name>Denis Le Bihan</name><affiliations><json:string>Neurospin, I2BM, Commissariat à l'Energie Atomique, Gif‐sur‐Yvette, France</json:string></affiliations></json:item><json:item><name>Franck Lethimonnier</name><affiliations><json:string>Neurospin, I2BM, Commissariat à l'Energie Atomique, Gif‐sur‐Yvette, France</json:string></affiliations></json:item><json:item><name>Fawzi Boumezbeur</name><affiliations><json:string>Neurospin, I2BM, Commissariat à l'Energie Atomique, Gif‐sur‐Yvette, France</json:string><json:string>Ph.D., NeuroSpin, IBM, CEA, Centre de Saclay, Bât. 145, 91191 Gif‐sur‐Yvette Cedex, France===</json:string></affiliations></json:item></author><subject><json:item><lang><json:string>eng</json:string></lang><value>molecular MRI</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>CEST</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>lipoCEST contrast agents</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>tumor angiogenesis</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>ανβ3 imaging</value></json:item><json:item><lang><json:string>eng</json:string></lang><value>U87MG</value></json:item></subject><articleId><json:string>MRM24217</json:string></articleId><language><json:string>eng</json:string></language><originalGenre><json:string>article</json:string></originalGenre><abstract>LipoCEST are liposome‐encapsulating paramagnetic contrast agents (CA) based on chemical exchange saturation transfer with applications in biomolecular MRI. Their attractive features include biocompatibility, subnanomolar sensitivity, and amenability to functionalization for targeting biomarkers. We demonstrate MR imaging using a targeted lipoCEST, injected intravenously. A lipoCEST carrying Tm(III)‐complexes was conjugated to RGD tripeptide (RGD‐lipoCEST), to target integrin ανβ3 receptors involved in tumor angiogenesis and was compared with an unconjugated lipoCEST. Brain tumors were induced in athymic nude mice by intracerebral injection of U87MG cells and were imaged at 7 T after intravenous injection of either of the two contrast agents (n = 12 for each group). Chemical exchange saturation transfer‐MSME sequence was applied over 2 h with an average acquisition time interval of 13.5 min. The chemical exchange saturation transfer signal was ∼1% in the tumor and controlateral regions, and decreased to ∼0.3% after 2 h; while RGD‐lipoCEST signal was ∼1.4% in the tumor region and persisted for up to 2 h. Immunohistochemical staining revealed a persistent colocalization of RGD‐lipoCEST with ανβ3 receptors in the tumor region. These results constitute an encouraging step toward in vivo MRI imaging of tumor angiogenesis using intravenously injected lipoCEST. 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xml:id="author-0000"><persName><forename type="first">Julien</forename><surname>Flament</surname></persName><affiliation>Neurospin, I2BM, Commissariat à l'Energie Atomique, Gif‐sur‐Yvette, France<address><country key="FR"></country></address></affiliation></author><author xml:id="author-0001"><persName><forename type="first">Françoise</forename><surname>Geffroy</surname></persName><affiliation>Neurospin, I2BM, Commissariat à l'Energie Atomique, Gif‐sur‐Yvette, France<address><country key="FR"></country></address></affiliation></author><author xml:id="author-0002"><persName><forename type="first">Christelle</forename><surname>Medina</surname></persName><affiliation>Guerbet, Research Division, BP 57400, 95943 Roissy‐Charles de Gaulle Cedex, France<address><country key="FR"></country></address></affiliation></author><author xml:id="author-0003"><persName><forename type="first">Caroline</forename><surname>Robic</surname></persName><affiliation>Guerbet, Research Division, BP 57400, 95943 Roissy‐Charles de Gaulle Cedex, France<address><country key="FR"></country></address></affiliation></author><author xml:id="author-0004"><persName><forename type="first">Jean‐François</forename><surname>Mayer</surname></persName><affiliation>Guerbet, Research Division, BP 57400, 95943 Roissy‐Charles de Gaulle Cedex, France<address><country key="FR"></country></address></affiliation></author><author xml:id="author-0005"><persName><forename type="first">Sébastien</forename><surname>Mériaux</surname></persName><affiliation>Neurospin, I2BM, Commissariat à l'Energie Atomique, Gif‐sur‐Yvette, France<address><country key="FR"></country></address></affiliation></author><author xml:id="author-0006"><persName><forename type="first">Julien</forename><surname>Valette</surname></persName><affiliation>Neurospin, I2BM, Commissariat à l'Energie Atomique, Gif‐sur‐Yvette, France<address><country key="FR"></country></address></affiliation></author><author xml:id="author-0007"><persName><forename type="first">Philippe</forename><surname>Robert</surname></persName><affiliation>Guerbet, Research Division, BP 57400, 95943 Roissy‐Charles de Gaulle Cedex, France<address><country key="FR"></country></address></affiliation></author><author xml:id="author-0008"><persName><forename type="first">Marc</forename><surname>Port</surname></persName><affiliation>Guerbet, Research Division, BP 57400, 95943 Roissy‐Charles de Gaulle Cedex, France<address><country key="FR"></country></address></affiliation></author><author xml:id="author-0009"><persName><forename type="first">Denis</forename><surname>Le Bihan</surname></persName><affiliation>Neurospin, I2BM, Commissariat à l'Energie Atomique, Gif‐sur‐Yvette, France<address><country key="FR"></country></address></affiliation></author><author xml:id="author-0010"><persName><forename type="first">Franck</forename><surname>Lethimonnier</surname></persName><affiliation>Neurospin, I2BM, Commissariat à l'Energie Atomique, Gif‐sur‐Yvette, France<address><country key="FR"></country></address></affiliation></author><author xml:id="author-0011" role="corresp"><persName><forename type="first">Fawzi</forename><surname>Boumezbeur</surname></persName><email>fawzi.boumezbeur@cea.fr</email><affiliation>Neurospin, I2BM, Commissariat à l'Energie Atomique, Gif‐sur‐Yvette, France<address><country key="FR"></country></address></affiliation><affiliation>Ph.D., NeuroSpin, I2BM, CEA, Centre de Saclay, Bât. 145, 91191 Gif‐sur‐Yvette Cedex, France===</affiliation></author><idno type="istex">9DE7EA85B10661F7FA906761CD80C2196F91AF01</idno><idno type="ark">ark:/67375/WNG-4XBB1TBH-T</idno><idno type="DOI">10.1002/mrm.24217</idno><idno type="unit">MRM24217</idno><idno type="toTypesetVersion">file:MRM.MRM24217.pdf</idno></analytic><monogr><title level="j" type="main">Magnetic Resonance in Medicine</title><title level="j" type="alt">MAGNETIC RESONANCE IN MEDICINE</title><idno type="pISSN">0740-3194</idno><idno type="eISSN">1522-2594</idno><idno type="book-DOI">10.1002/(ISSN)1522-2594</idno><idno type="book-part-DOI">10.1002/mrm.v69.1</idno><idno type="product">MRM</idno><imprint><biblScope unit="vol">69</biblScope><biblScope unit="issue">1</biblScope><biblScope unit="page" from="179">179</biblScope><biblScope unit="page" to="187">187</biblScope><biblScope unit="page-count">9</biblScope><publisher>Wiley Subscription Services, Inc., A Wiley Company</publisher><pubPlace>Hoboken</pubPlace><date type="published" when="2013-01"></date></imprint></monogr></biblStruct></sourceDesc></fileDesc><profileDesc><abstract xml:lang="en" style="main"><head>Abstract</head><p>LipoCEST are liposome‐encapsulating paramagnetic contrast agents (CA) based on chemical exchange saturation transfer with applications in biomolecular MRI. Their attractive features include biocompatibility, subnanomolar sensitivity, and amenability to functionalization for targeting biomarkers. We demonstrate MR imaging using a targeted lipoCEST, injected intravenously. A lipoCEST carrying Tm(III)‐complexes was conjugated to RGD tripeptide (RGD‐lipoCEST), to target integrin α<hi rend="subscript">ν</hi>β<hi rend="subscript">3</hi> receptors involved in tumor angiogenesis and was compared with an unconjugated lipoCEST. Brain tumors were induced in athymic nude mice by intracerebral injection of U87MG cells and were imaged at 7 T after intravenous injection of either of the two contrast agents (<hi rend="italic">n</hi> = 12 for each group). Chemical exchange saturation transfer‐MSME sequence was applied over 2 h with an average acquisition time interval of 13.5 min. The chemical exchange saturation transfer signal was ∼1% in the tumor and controlateral regions, and decreased to ∼0.3% after 2 h; while RGD‐lipoCEST signal was ∼1.4% in the tumor region and persisted for up to 2 h. Immunohistochemical staining revealed a persistent colocalization of RGD‐lipoCEST with α<hi rend="subscript">ν</hi>β<hi rend="subscript">3</hi> receptors in the tumor region. These results constitute an encouraging step toward in vivo MRI imaging of tumor angiogenesis using intravenously injected lipoCEST. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.</p></abstract><textClass><keywords xml:lang="en"><term xml:id="kwd1">molecular MRI</term><term xml:id="kwd2">CEST</term><term xml:id="kwd3">lipoCEST contrast agents</term><term xml:id="kwd4">tumor angiogenesis</term><term xml:id="kwd5">α<hi rend="subscript">ν</hi>β<hi rend="subscript">3</hi> imaging</term><term xml:id="kwd6">U87MG</term></keywords><keywords rend="articleCategory"><term>Full Paper</term></keywords><keywords rend="tocHeading1"><term>Preclinical and Clinical Imaging—Full paper</term></keywords></textClass><langUsage><language ident="en"></language></langUsage></profileDesc></teiHeader></istex:fulltextTEI><json:item><extension>txt</extension><original>false</original><mimetype>text/plain</mimetype><uri>https://api.istex.fr/document/9DE7EA85B10661F7FA906761CD80C2196F91AF01/fulltext/txt</uri></json:item></fulltext><metadata><istex:metadataXml wicri:clean="Wiley, elements deleted: body"><istex:xmlDeclaration>version="1.0" 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Immunohistochemical staining revealed a persistent colocalization of RGD‐lipoCEST with α<sub>ν</sub>β<sub>3</sub> receptors in the tumor region. These results constitute an encouraging step toward in vivo MRI imaging of tumor angiogenesis using intravenously injected lipoCEST. 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Immunohistochemical staining revealed a persistent colocalization of RGD‐lipoCEST with ανβ3 receptors in the tumor region. These results constitute an encouraging step toward in vivo MRI imaging of tumor angiogenesis using intravenously injected lipoCEST. 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