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Development of a PET radioligand for potassium channels to image CNS demyelination
Central nervous system (CNS) demyelination represents the pathological hallmark of multiple sclerosis (MS) and contributes to other neurological conditions. Quantitative and specific imaging of demyelination would thus provide critical clinical insight. Here, we investigated the possibility of targe...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5766510/ https://www.ncbi.nlm.nih.gov/pubmed/29330383 http://dx.doi.org/10.1038/s41598-017-18747-3 |
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author | Brugarolas, Pedro Sánchez-Rodríguez, Jorge E. Tsai, Hsiu-Ming Basuli, Falguni Cheng, Shih-Hsun Zhang, Xiang Caprariello, Andrew V. Lacroix, Jerome J. Freifelder, Richard Murali, Dhanabalan DeJesus, Onofre Miller, Robert H. Swenson, Rolf E. Chen, Chin-Tu Herscovitch, Peter Reich, Daniel S. Bezanilla, Francisco Popko, Brian |
author_facet | Brugarolas, Pedro Sánchez-Rodríguez, Jorge E. Tsai, Hsiu-Ming Basuli, Falguni Cheng, Shih-Hsun Zhang, Xiang Caprariello, Andrew V. Lacroix, Jerome J. Freifelder, Richard Murali, Dhanabalan DeJesus, Onofre Miller, Robert H. Swenson, Rolf E. Chen, Chin-Tu Herscovitch, Peter Reich, Daniel S. Bezanilla, Francisco Popko, Brian |
author_sort | Brugarolas, Pedro |
collection | PubMed |
description | Central nervous system (CNS) demyelination represents the pathological hallmark of multiple sclerosis (MS) and contributes to other neurological conditions. Quantitative and specific imaging of demyelination would thus provide critical clinical insight. Here, we investigated the possibility of targeting axonal potassium channels to image demyelination by positron emission tomography (PET). These channels, which normally reside beneath the myelin sheath, become exposed upon demyelination and are the target of the MS drug, 4-aminopyridine (4-AP). We demonstrate using autoradiography that 4-AP has higher binding in non-myelinated and demyelinated versus well-myelinated CNS regions, and describe a fluorine-containing derivative, 3-F-4-AP, that has similar pharmacological properties and can be labeled with (18)F for PET imaging. Additionally, we demonstrate that [(18)F]3-F-4-AP can be used to detect demyelination in rodents by PET. Further evaluation in Rhesus macaques shows higher binding in non-myelinated versus myelinated areas and excellent properties for brain imaging. Together, these data indicate that [(18)F]3-F-4-AP may be a valuable PET tracer for detecting CNS demyelination noninvasively. |
format | Online Article Text |
id | pubmed-5766510 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-57665102018-01-17 Development of a PET radioligand for potassium channels to image CNS demyelination Brugarolas, Pedro Sánchez-Rodríguez, Jorge E. Tsai, Hsiu-Ming Basuli, Falguni Cheng, Shih-Hsun Zhang, Xiang Caprariello, Andrew V. Lacroix, Jerome J. Freifelder, Richard Murali, Dhanabalan DeJesus, Onofre Miller, Robert H. Swenson, Rolf E. Chen, Chin-Tu Herscovitch, Peter Reich, Daniel S. Bezanilla, Francisco Popko, Brian Sci Rep Article Central nervous system (CNS) demyelination represents the pathological hallmark of multiple sclerosis (MS) and contributes to other neurological conditions. Quantitative and specific imaging of demyelination would thus provide critical clinical insight. Here, we investigated the possibility of targeting axonal potassium channels to image demyelination by positron emission tomography (PET). These channels, which normally reside beneath the myelin sheath, become exposed upon demyelination and are the target of the MS drug, 4-aminopyridine (4-AP). We demonstrate using autoradiography that 4-AP has higher binding in non-myelinated and demyelinated versus well-myelinated CNS regions, and describe a fluorine-containing derivative, 3-F-4-AP, that has similar pharmacological properties and can be labeled with (18)F for PET imaging. Additionally, we demonstrate that [(18)F]3-F-4-AP can be used to detect demyelination in rodents by PET. Further evaluation in Rhesus macaques shows higher binding in non-myelinated versus myelinated areas and excellent properties for brain imaging. Together, these data indicate that [(18)F]3-F-4-AP may be a valuable PET tracer for detecting CNS demyelination noninvasively. Nature Publishing Group UK 2018-01-12 /pmc/articles/PMC5766510/ /pubmed/29330383 http://dx.doi.org/10.1038/s41598-017-18747-3 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Brugarolas, Pedro Sánchez-Rodríguez, Jorge E. Tsai, Hsiu-Ming Basuli, Falguni Cheng, Shih-Hsun Zhang, Xiang Caprariello, Andrew V. Lacroix, Jerome J. Freifelder, Richard Murali, Dhanabalan DeJesus, Onofre Miller, Robert H. Swenson, Rolf E. Chen, Chin-Tu Herscovitch, Peter Reich, Daniel S. Bezanilla, Francisco Popko, Brian Development of a PET radioligand for potassium channels to image CNS demyelination |
title | Development of a PET radioligand for potassium channels to image CNS demyelination |
title_full | Development of a PET radioligand for potassium channels to image CNS demyelination |
title_fullStr | Development of a PET radioligand for potassium channels to image CNS demyelination |
title_full_unstemmed | Development of a PET radioligand for potassium channels to image CNS demyelination |
title_short | Development of a PET radioligand for potassium channels to image CNS demyelination |
title_sort | development of a pet radioligand for potassium channels to image cns demyelination |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5766510/ https://www.ncbi.nlm.nih.gov/pubmed/29330383 http://dx.doi.org/10.1038/s41598-017-18747-3 |
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