Evaluation of Myelin Radiotracers in the Lysolecithin Rat Model of Focal Demyelination: Beware of Pitfalls!
The observation that amyloid radiotracers developed for Alzheimer’s disease bind to cerebral white matter paved the road to nuclear imaging of myelin in multiple sclerosis. The lysolecithin (lysophosphatidylcholine (LPC)) rat model of demyelination proved useful in evaluating and comparing candidate...
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| Veröffentlicht in: | Contrast media and molecular imaging 2019-01, Vol.2019 (2019), p.1-10 |
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| creator | Chauveau, Fabien Zimmer, Luc Bonnefoi, Frédéric Billard, Thierry Langlois, Jean-Baptiste Bolbos, Radu Bouillot, Caroline Hugon, Gaëlle Zhang, Min Li, Biao |
| description | The observation that amyloid radiotracers developed for Alzheimer’s disease bind to cerebral white matter paved the road to nuclear imaging of myelin in multiple sclerosis. The lysolecithin (lysophosphatidylcholine (LPC)) rat model of demyelination proved useful in evaluating and comparing candidate radiotracers to target myelin. Focal demyelination following stereotaxic LPC injection is larger than lesions observed in experimental autoimmune encephalitis models and is followed by spontaneous progressive remyelination. Moreover, the contralateral hemisphere may serve as an internal control in a given animal. However, demyelination can be accompanied by concurrent focal necrosis and/or adjacent ventricle dilation. The influence of these side effects on imaging findings has never been carefully assessed. The present study describes an optimization of the LPC model and highlights the use of MRI for controlling the variability and pitfalls of the model. The prototypical amyloid radiotracer [11C]PIB was used to show that in vivo PET does not provide sufficient sensitivity to reliably track myelin changes and may be sensitive to LPC side effects instead of demyelination as such. Ex vivo autoradiography with a fluorine radiotracer should be preferred, to adequately evaluate and compare radiotracers for the assessment of myelin content. |
| doi_str_mv | 10.1155/2019/9294586 |
| format | Article |
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O. ; Aage K O Alstrup</contributor><creatorcontrib>Chauveau, Fabien ; Zimmer, Luc ; Bonnefoi, Frédéric ; Billard, Thierry ; Langlois, Jean-Baptiste ; Bolbos, Radu ; Bouillot, Caroline ; Hugon, Gaëlle ; Zhang, Min ; Li, Biao ; Alstrup, Aage K. O. ; Aage K O Alstrup</creatorcontrib><description>The observation that amyloid radiotracers developed for Alzheimer’s disease bind to cerebral white matter paved the road to nuclear imaging of myelin in multiple sclerosis. The lysolecithin (lysophosphatidylcholine (LPC)) rat model of demyelination proved useful in evaluating and comparing candidate radiotracers to target myelin. Focal demyelination following stereotaxic LPC injection is larger than lesions observed in experimental autoimmune encephalitis models and is followed by spontaneous progressive remyelination. Moreover, the contralateral hemisphere may serve as an internal control in a given animal. However, demyelination can be accompanied by concurrent focal necrosis and/or adjacent ventricle dilation. The influence of these side effects on imaging findings has never been carefully assessed. The present study describes an optimization of the LPC model and highlights the use of MRI for controlling the variability and pitfalls of the model. The prototypical amyloid radiotracer [11C]PIB was used to show that in vivo PET does not provide sufficient sensitivity to reliably track myelin changes and may be sensitive to LPC side effects instead of demyelination as such. Ex vivo autoradiography with a fluorine radiotracer should be preferred, to adequately evaluate and compare radiotracers for the assessment of myelin content.</description><identifier>ISSN: 1555-4309</identifier><identifier>EISSN: 1555-4317</identifier><identifier>DOI: 10.1155/2019/9294586</identifier><identifier>PMID: 31281236</identifier><language>eng</language><publisher>Cairo, Egypt: Hindawi Publishing Corporation</publisher><subject>Amyloid ; Analgesics ; Automation ; Autoradiography ; Bioengineering ; Brain research ; Demyelination ; Encephalitis ; Experimental allergic encephalomyelitis ; Experiments ; Fluorine ; Imaging ; Laboratory animals ; Lesions ; Life Sciences ; Lysophosphatidylcholine ; Magnetic resonance imaging ; Medical imaging ; Medical research ; Multiple sclerosis ; Myelin ; Myelination ; Necrosis ; Neurons and Cognition ; NMR ; Nuclear magnetic resonance ; Nuclear medicine ; Optimization ; Radioactive tracers ; Side effects ; Studies ; Substantia alba ; Ventricle</subject><ispartof>Contrast media and molecular imaging, 2019-01, Vol.2019 (2019), p.1-10</ispartof><rights>Copyright © 2019 Min Zhang et al.</rights><rights>Copyright © 2019 Min Zhang et al. This is an open access article distributed under the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. http://creativecommons.org/licenses/by/4.0</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><rights>Copyright © 2019 Min Zhang et al. 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c505t-a43288b81135ac5fc5c890cbc70e8ce74733ebc670697358f2dd254ffd97ca203</citedby><cites>FETCH-LOGICAL-c505t-a43288b81135ac5fc5c890cbc70e8ce74733ebc670697358f2dd254ffd97ca203</cites><orcidid>0000-0001-5812-9518 ; 0000-0002-2937-9523 ; 0000-0002-4177-741X ; 0000-0001-7127-4250 ; 0000-0001-8468-3205 ; 0000-0002-2805-7098</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6594279/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6594279/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53770,53772</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31281236$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-02278818$$DView record in HAL$$Hfree_for_read</backlink></links><search><contributor>Alstrup, Aage K. O.</contributor><contributor>Aage K O Alstrup</contributor><creatorcontrib>Chauveau, Fabien</creatorcontrib><creatorcontrib>Zimmer, Luc</creatorcontrib><creatorcontrib>Bonnefoi, Frédéric</creatorcontrib><creatorcontrib>Billard, Thierry</creatorcontrib><creatorcontrib>Langlois, Jean-Baptiste</creatorcontrib><creatorcontrib>Bolbos, Radu</creatorcontrib><creatorcontrib>Bouillot, Caroline</creatorcontrib><creatorcontrib>Hugon, Gaëlle</creatorcontrib><creatorcontrib>Zhang, Min</creatorcontrib><creatorcontrib>Li, Biao</creatorcontrib><title>Evaluation of Myelin Radiotracers in the Lysolecithin Rat Model of Focal Demyelination: Beware of Pitfalls!</title><title>Contrast media and molecular imaging</title><addtitle>Contrast Media Mol Imaging</addtitle><description>The observation that amyloid radiotracers developed for Alzheimer’s disease bind to cerebral white matter paved the road to nuclear imaging of myelin in multiple sclerosis. The lysolecithin (lysophosphatidylcholine (LPC)) rat model of demyelination proved useful in evaluating and comparing candidate radiotracers to target myelin. Focal demyelination following stereotaxic LPC injection is larger than lesions observed in experimental autoimmune encephalitis models and is followed by spontaneous progressive remyelination. Moreover, the contralateral hemisphere may serve as an internal control in a given animal. However, demyelination can be accompanied by concurrent focal necrosis and/or adjacent ventricle dilation. The influence of these side effects on imaging findings has never been carefully assessed. The present study describes an optimization of the LPC model and highlights the use of MRI for controlling the variability and pitfalls of the model. The prototypical amyloid radiotracer [11C]PIB was used to show that in vivo PET does not provide sufficient sensitivity to reliably track myelin changes and may be sensitive to LPC side effects instead of demyelination as such. Ex vivo autoradiography with a fluorine radiotracer should be preferred, to adequately evaluate and compare radiotracers for the assessment of myelin content.</description><subject>Amyloid</subject><subject>Analgesics</subject><subject>Automation</subject><subject>Autoradiography</subject><subject>Bioengineering</subject><subject>Brain research</subject><subject>Demyelination</subject><subject>Encephalitis</subject><subject>Experimental allergic encephalomyelitis</subject><subject>Experiments</subject><subject>Fluorine</subject><subject>Imaging</subject><subject>Laboratory animals</subject><subject>Lesions</subject><subject>Life Sciences</subject><subject>Lysophosphatidylcholine</subject><subject>Magnetic resonance imaging</subject><subject>Medical imaging</subject><subject>Medical research</subject><subject>Multiple sclerosis</subject><subject>Myelin</subject><subject>Myelination</subject><subject>Necrosis</subject><subject>Neurons and Cognition</subject><subject>NMR</subject><subject>Nuclear magnetic resonance</subject><subject>Nuclear medicine</subject><subject>Optimization</subject><subject>Radioactive tracers</subject><subject>Side effects</subject><subject>Studies</subject><subject>Substantia alba</subject><subject>Ventricle</subject><issn>1555-4309</issn><issn>1555-4317</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>RHX</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNqNkU1vEzEQhi1ERUvbG2e0iAuoDfXHem33UKn0gyKlKkJwthzvLHFx1sXeTZV_X2-SBtoTJ49nnnk94xehNwR_IoTzI4qJOlJUlVxWL9BOTvFRyYh4uYmx2kavU7rFuCyZYq_QNiNUEsqqHfT7Ym58bzoX2iI0xfUCvGuL76Z2oYvGQkxFvndTKMaLFDxY102XQFdchxr80HQZrPHFOcyWzUut4-Iz3JsIQ_mb6xrjfXq3h7ZykGB_fe6in5cXP86uRuObL1_PTscjyzHvRqZkVMqJJIRxY3ljuZUK24kVGKQFUQrGYGIrgSslGJcNrWvKy6aplbCGYraLTla6d_1kBrWFNq_i9V10MxMXOhinn1ZaN9W_wlxXXJVUqCzwcSUwfdZ2dTrWQw5TKqQkck4y-2H9WAx_ekidnrlkwXvTQuiTppQzmf-7GuZ6_wy9DX1s81csKUKIZFWmDleUjSGlCM1mAoL14LgeHNdrxzP-9t9lN_CjxRk4WC_j2trcu_-Ug8xAY_7ShGEmMXsAkQC8Vg</recordid><startdate>20190101</startdate><enddate>20190101</enddate><creator>Chauveau, Fabien</creator><creator>Zimmer, Luc</creator><creator>Bonnefoi, Frédéric</creator><creator>Billard, Thierry</creator><creator>Langlois, Jean-Baptiste</creator><creator>Bolbos, Radu</creator><creator>Bouillot, Caroline</creator><creator>Hugon, Gaëlle</creator><creator>Zhang, Min</creator><creator>Li, Biao</creator><general>Hindawi Publishing Corporation</general><general>Hindawi</general><general>Hindawi Limited</general><general>Wiley</general><scope>ADJCN</scope><scope>AHFXO</scope><scope>RHU</scope><scope>RHW</scope><scope>RHX</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QO</scope><scope>7QP</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>BYOGL</scope><scope>CCPQU</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>1XC</scope><scope>VOOES</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-5812-9518</orcidid><orcidid>https://orcid.org/0000-0002-2937-9523</orcidid><orcidid>https://orcid.org/0000-0002-4177-741X</orcidid><orcidid>https://orcid.org/0000-0001-7127-4250</orcidid><orcidid>https://orcid.org/0000-0001-8468-3205</orcidid><orcidid>https://orcid.org/0000-0002-2805-7098</orcidid></search><sort><creationdate>20190101</creationdate><title>Evaluation of Myelin Radiotracers in the Lysolecithin Rat Model of Focal Demyelination: Beware of Pitfalls!</title><author>Chauveau, Fabien ; 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O.</au><au>Aage K O Alstrup</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evaluation of Myelin Radiotracers in the Lysolecithin Rat Model of Focal Demyelination: Beware of Pitfalls!</atitle><jtitle>Contrast media and molecular imaging</jtitle><addtitle>Contrast Media Mol Imaging</addtitle><date>2019-01-01</date><risdate>2019</risdate><volume>2019</volume><issue>2019</issue><spage>1</spage><epage>10</epage><pages>1-10</pages><issn>1555-4309</issn><eissn>1555-4317</eissn><abstract>The observation that amyloid radiotracers developed for Alzheimer’s disease bind to cerebral white matter paved the road to nuclear imaging of myelin in multiple sclerosis. The lysolecithin (lysophosphatidylcholine (LPC)) rat model of demyelination proved useful in evaluating and comparing candidate radiotracers to target myelin. Focal demyelination following stereotaxic LPC injection is larger than lesions observed in experimental autoimmune encephalitis models and is followed by spontaneous progressive remyelination. Moreover, the contralateral hemisphere may serve as an internal control in a given animal. However, demyelination can be accompanied by concurrent focal necrosis and/or adjacent ventricle dilation. The influence of these side effects on imaging findings has never been carefully assessed. The present study describes an optimization of the LPC model and highlights the use of MRI for controlling the variability and pitfalls of the model. The prototypical amyloid radiotracer [11C]PIB was used to show that in vivo PET does not provide sufficient sensitivity to reliably track myelin changes and may be sensitive to LPC side effects instead of demyelination as such. 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| subjects | Amyloid Analgesics Automation Autoradiography Bioengineering Brain research Demyelination Encephalitis Experimental allergic encephalomyelitis Experiments Fluorine Imaging Laboratory animals Lesions Life Sciences Lysophosphatidylcholine Magnetic resonance imaging Medical imaging Medical research Multiple sclerosis Myelin Myelination Necrosis Neurons and Cognition NMR Nuclear magnetic resonance Nuclear medicine Optimization Radioactive tracers Side effects Studies Substantia alba Ventricle |
| title | Evaluation of Myelin Radiotracers in the Lysolecithin Rat Model of Focal Demyelination: Beware of Pitfalls! |
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