PET imaging of microglia by targeting macrophage colony-stimulating factor 1 receptor (CSF1R)
While neuroinflammation is an evolving concept and the cells involved and their functions are being defined, microglia are understood to be a key cellular mediator of brain injury and repair. The ability to measure microglial activity specifically and non-invasively would be a boon to the study of n...
Gespeichert in:
| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2019-01, Vol.116 (5), p.1686-1691 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1691 |
|---|---|
| container_issue | 5 |
| container_start_page | 1686 |
| container_title | Proceedings of the National Academy of Sciences - PNAS |
| container_volume | 116 |
| creator | Horti, Andrew G. Naik, Ravi Foss, Catherine A. Minn, Il Misheneva, Varia Du, Yong Wang, Yuchuan Mathews, William B. Wu, Yunkou Hall, Andrew LaCourse, Catherine Ahn, Hye-Hyun Nam, Hwanhee Lesniak, Wojciech G. Valentine, Heather Pletnikova, Olga Troncoso, Juan C. Smith, Matthew D. Calabresi, Peter A. Savonenko, Alena V. Dannals, Robert F. Pletnikov, Mikhail V. Pomper, Martin G. |
| description | While neuroinflammation is an evolving concept and the cells involved and their functions are being defined, microglia are understood to be a key cellular mediator of brain injury and repair. The ability to measure microglial activity specifically and non-invasively would be a boon to the study of neuroinflammation, which is involved in a wide variety of neuropsychiatric disorders including traumatic brain injury, demyelinating disease, Alzheimer’s disease (AD), and Parkinson’s disease, among others. We have developed [11C]CPPC [5-cyano-N-(4-(4-[11C]methylpiperazin-1-yl)-2-(piperidin-1-yl)phenyl)furan-2-carboxamide], a positron-emitting, high-affinity ligand that is specific for the macrophage colony-stimulating factor 1 receptor (CSF1R), the expression of which is essentially restricted to microglia within brain. [11C]CPPC demonstrates high and specific brain uptake in a murine and nonhuman primate lipopolysaccharide model of neuroinflammation. It also shows specific and elevated uptake in a murine model of AD, experimental allergic encephalomyelitis murine model of demyelination and in postmortem brain tissue of patients with AD. Radiation dosimetry in mice indicated [11C]CPPC to be safe for future human studies. [11C]CPPC can be synthesized in sufficient radiochemical yield, purity, and specific radioactivity and possesses binding specificity in relevant models that indicate potential for human PET imaging of CSF1R and the microglial component of neuroinflammation. |
| doi_str_mv | 10.1073/pnas.1812155116 |
| format | Article |
| fullrecord | <record><control><sourceid>jstor_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6358677</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><jstor_id>26580304</jstor_id><sourcerecordid>26580304</sourcerecordid><originalsourceid>FETCH-LOGICAL-c463t-2ddb7755c5f2ac7922a4812fc20805a8c9800c58882848e7d5fcb0d7720d0293</originalsourceid><addsrcrecordid>eNpdkc1L7DAUxYMoOk9du1IKbnRRvUmbj24EGcYPEBSdrYRMmtYObVOT9sH89y99o-PHKiHnl8s59yB0hOECA08uu1b5CywwwZRizLbQBEOGY5ZmsI0mAITHIiXpHvrj_RIAMipgF-0lwBKaYjJBr0-zeVQ1qqzaMrJF1FTa2bKuVLRYRb1ypelHpVHhuXtTpYm0rW27in1fNUOt_quF0r11EY6c0aYbr2fTlxv8fH6AdgpVe3P4ce6j-c1sPr2LHx5v76fXD7FOWdLHJM8XnFOqaUGU5hkhKg2ZCk1AAFVCZwJAUyEEEakwPKeFXkDOOYEcSJbso6v12G5YNCbXpu2dqmXnQjC3klZV8qfSVm-ytH9l2IJgnIcBZx8DnH0fjO9lU3lt6lq1xg5eEsyzJFgRLKCnv9ClHVwb0o0UY5kQdHR0uabC2rx3ptiYwSDH5uTYnPxqLvw4-Z5hw39WFYDjNbD0YcMbnbBQaQJp8g9bcZ24</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2176698859</pqid></control><display><type>article</type><title>PET imaging of microglia by targeting macrophage colony-stimulating factor 1 receptor (CSF1R)</title><source>Jstor Complete Legacy</source><source>MEDLINE</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><source>Free Full-Text Journals in Chemistry</source><creator>Horti, Andrew G. ; Naik, Ravi ; Foss, Catherine A. ; Minn, Il ; Misheneva, Varia ; Du, Yong ; Wang, Yuchuan ; Mathews, William B. ; Wu, Yunkou ; Hall, Andrew ; LaCourse, Catherine ; Ahn, Hye-Hyun ; Nam, Hwanhee ; Lesniak, Wojciech G. ; Valentine, Heather ; Pletnikova, Olga ; Troncoso, Juan C. ; Smith, Matthew D. ; Calabresi, Peter A. ; Savonenko, Alena V. ; Dannals, Robert F. ; Pletnikov, Mikhail V. ; Pomper, Martin G.</creator><creatorcontrib>Horti, Andrew G. ; Naik, Ravi ; Foss, Catherine A. ; Minn, Il ; Misheneva, Varia ; Du, Yong ; Wang, Yuchuan ; Mathews, William B. ; Wu, Yunkou ; Hall, Andrew ; LaCourse, Catherine ; Ahn, Hye-Hyun ; Nam, Hwanhee ; Lesniak, Wojciech G. ; Valentine, Heather ; Pletnikova, Olga ; Troncoso, Juan C. ; Smith, Matthew D. ; Calabresi, Peter A. ; Savonenko, Alena V. ; Dannals, Robert F. ; Pletnikov, Mikhail V. ; Pomper, Martin G.</creatorcontrib><description>While neuroinflammation is an evolving concept and the cells involved and their functions are being defined, microglia are understood to be a key cellular mediator of brain injury and repair. The ability to measure microglial activity specifically and non-invasively would be a boon to the study of neuroinflammation, which is involved in a wide variety of neuropsychiatric disorders including traumatic brain injury, demyelinating disease, Alzheimer’s disease (AD), and Parkinson’s disease, among others. We have developed [11C]CPPC [5-cyano-N-(4-(4-[11C]methylpiperazin-1-yl)-2-(piperidin-1-yl)phenyl)furan-2-carboxamide], a positron-emitting, high-affinity ligand that is specific for the macrophage colony-stimulating factor 1 receptor (CSF1R), the expression of which is essentially restricted to microglia within brain. [11C]CPPC demonstrates high and specific brain uptake in a murine and nonhuman primate lipopolysaccharide model of neuroinflammation. It also shows specific and elevated uptake in a murine model of AD, experimental allergic encephalomyelitis murine model of demyelination and in postmortem brain tissue of patients with AD. Radiation dosimetry in mice indicated [11C]CPPC to be safe for future human studies. [11C]CPPC can be synthesized in sufficient radiochemical yield, purity, and specific radioactivity and possesses binding specificity in relevant models that indicate potential for human PET imaging of CSF1R and the microglial component of neuroinflammation.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.1812155116</identifier><identifier>PMID: 30635412</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Alzheimer Disease - metabolism ; Alzheimer's disease ; Animal models ; Animals ; Biological Sciences ; Brain ; Brain - metabolism ; Colonies ; Colony-stimulating factor ; Demyelinating diseases ; Demyelination ; Disease Models, Animal ; Dosimeters ; Dosimetry ; Experimental allergic encephalomyelitis ; Head injuries ; Inflammation ; Inflammation - metabolism ; Lipopolysaccharides ; Macrophage colony-stimulating factor ; Macrophage Colony-Stimulating Factor - metabolism ; Male ; Medical imaging ; Mental disorders ; Mice ; Mice, Inbred C57BL ; Microglia ; Microglia - metabolism ; Neuroimaging ; Parkinson's disease ; Physical Sciences ; Plaque, Amyloid - metabolism ; Positron emission ; Positron emission tomography ; Positron-Emission Tomography - methods ; Primates ; Radiation dosimetry ; Radioactivity ; Radiochemistry ; Radiopharmaceuticals - metabolism ; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor - metabolism ; Tomography ; Traumatic brain injury</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2019-01, Vol.116 (5), p.1686-1691</ispartof><rights>Volumes 1–89 and 106–116, copyright as a collective work only; author(s) retains copyright to individual articles</rights><rights>Copyright National Academy of Sciences Jan 29, 2019</rights><rights>2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c463t-2ddb7755c5f2ac7922a4812fc20805a8c9800c58882848e7d5fcb0d7720d0293</cites><orcidid>0000-0002-7776-6472</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/26580304$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/26580304$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27901,27902,53766,53768,57992,58225</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30635412$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Horti, Andrew G.</creatorcontrib><creatorcontrib>Naik, Ravi</creatorcontrib><creatorcontrib>Foss, Catherine A.</creatorcontrib><creatorcontrib>Minn, Il</creatorcontrib><creatorcontrib>Misheneva, Varia</creatorcontrib><creatorcontrib>Du, Yong</creatorcontrib><creatorcontrib>Wang, Yuchuan</creatorcontrib><creatorcontrib>Mathews, William B.</creatorcontrib><creatorcontrib>Wu, Yunkou</creatorcontrib><creatorcontrib>Hall, Andrew</creatorcontrib><creatorcontrib>LaCourse, Catherine</creatorcontrib><creatorcontrib>Ahn, Hye-Hyun</creatorcontrib><creatorcontrib>Nam, Hwanhee</creatorcontrib><creatorcontrib>Lesniak, Wojciech G.</creatorcontrib><creatorcontrib>Valentine, Heather</creatorcontrib><creatorcontrib>Pletnikova, Olga</creatorcontrib><creatorcontrib>Troncoso, Juan C.</creatorcontrib><creatorcontrib>Smith, Matthew D.</creatorcontrib><creatorcontrib>Calabresi, Peter A.</creatorcontrib><creatorcontrib>Savonenko, Alena V.</creatorcontrib><creatorcontrib>Dannals, Robert F.</creatorcontrib><creatorcontrib>Pletnikov, Mikhail V.</creatorcontrib><creatorcontrib>Pomper, Martin G.</creatorcontrib><title>PET imaging of microglia by targeting macrophage colony-stimulating factor 1 receptor (CSF1R)</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>While neuroinflammation is an evolving concept and the cells involved and their functions are being defined, microglia are understood to be a key cellular mediator of brain injury and repair. The ability to measure microglial activity specifically and non-invasively would be a boon to the study of neuroinflammation, which is involved in a wide variety of neuropsychiatric disorders including traumatic brain injury, demyelinating disease, Alzheimer’s disease (AD), and Parkinson’s disease, among others. We have developed [11C]CPPC [5-cyano-N-(4-(4-[11C]methylpiperazin-1-yl)-2-(piperidin-1-yl)phenyl)furan-2-carboxamide], a positron-emitting, high-affinity ligand that is specific for the macrophage colony-stimulating factor 1 receptor (CSF1R), the expression of which is essentially restricted to microglia within brain. [11C]CPPC demonstrates high and specific brain uptake in a murine and nonhuman primate lipopolysaccharide model of neuroinflammation. It also shows specific and elevated uptake in a murine model of AD, experimental allergic encephalomyelitis murine model of demyelination and in postmortem brain tissue of patients with AD. Radiation dosimetry in mice indicated [11C]CPPC to be safe for future human studies. [11C]CPPC can be synthesized in sufficient radiochemical yield, purity, and specific radioactivity and possesses binding specificity in relevant models that indicate potential for human PET imaging of CSF1R and the microglial component of neuroinflammation.</description><subject>Alzheimer Disease - metabolism</subject><subject>Alzheimer's disease</subject><subject>Animal models</subject><subject>Animals</subject><subject>Biological Sciences</subject><subject>Brain</subject><subject>Brain - metabolism</subject><subject>Colonies</subject><subject>Colony-stimulating factor</subject><subject>Demyelinating diseases</subject><subject>Demyelination</subject><subject>Disease Models, Animal</subject><subject>Dosimeters</subject><subject>Dosimetry</subject><subject>Experimental allergic encephalomyelitis</subject><subject>Head injuries</subject><subject>Inflammation</subject><subject>Inflammation - metabolism</subject><subject>Lipopolysaccharides</subject><subject>Macrophage colony-stimulating factor</subject><subject>Macrophage Colony-Stimulating Factor - metabolism</subject><subject>Male</subject><subject>Medical imaging</subject><subject>Mental disorders</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Microglia</subject><subject>Microglia - metabolism</subject><subject>Neuroimaging</subject><subject>Parkinson's disease</subject><subject>Physical Sciences</subject><subject>Plaque, Amyloid - metabolism</subject><subject>Positron emission</subject><subject>Positron emission tomography</subject><subject>Positron-Emission Tomography - methods</subject><subject>Primates</subject><subject>Radiation dosimetry</subject><subject>Radioactivity</subject><subject>Radiochemistry</subject><subject>Radiopharmaceuticals - metabolism</subject><subject>Receptors, Granulocyte-Macrophage Colony-Stimulating Factor - metabolism</subject><subject>Tomography</subject><subject>Traumatic brain injury</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkc1L7DAUxYMoOk9du1IKbnRRvUmbj24EGcYPEBSdrYRMmtYObVOT9sH89y99o-PHKiHnl8s59yB0hOECA08uu1b5CywwwZRizLbQBEOGY5ZmsI0mAITHIiXpHvrj_RIAMipgF-0lwBKaYjJBr0-zeVQ1qqzaMrJF1FTa2bKuVLRYRb1ypelHpVHhuXtTpYm0rW27in1fNUOt_quF0r11EY6c0aYbr2fTlxv8fH6AdgpVe3P4ce6j-c1sPr2LHx5v76fXD7FOWdLHJM8XnFOqaUGU5hkhKg2ZCk1AAFVCZwJAUyEEEakwPKeFXkDOOYEcSJbso6v12G5YNCbXpu2dqmXnQjC3klZV8qfSVm-ytH9l2IJgnIcBZx8DnH0fjO9lU3lt6lq1xg5eEsyzJFgRLKCnv9ClHVwb0o0UY5kQdHR0uabC2rx3ptiYwSDH5uTYnPxqLvw4-Z5hw39WFYDjNbD0YcMbnbBQaQJp8g9bcZ24</recordid><startdate>20190129</startdate><enddate>20190129</enddate><creator>Horti, Andrew G.</creator><creator>Naik, Ravi</creator><creator>Foss, Catherine A.</creator><creator>Minn, Il</creator><creator>Misheneva, Varia</creator><creator>Du, Yong</creator><creator>Wang, Yuchuan</creator><creator>Mathews, William B.</creator><creator>Wu, Yunkou</creator><creator>Hall, Andrew</creator><creator>LaCourse, Catherine</creator><creator>Ahn, Hye-Hyun</creator><creator>Nam, Hwanhee</creator><creator>Lesniak, Wojciech G.</creator><creator>Valentine, Heather</creator><creator>Pletnikova, Olga</creator><creator>Troncoso, Juan C.</creator><creator>Smith, Matthew D.</creator><creator>Calabresi, Peter A.</creator><creator>Savonenko, Alena V.</creator><creator>Dannals, Robert F.</creator><creator>Pletnikov, Mikhail V.</creator><creator>Pomper, Martin G.</creator><general>National Academy of Sciences</general><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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-7776-6472</orcidid></search><sort><creationdate>20190129</creationdate><title>PET imaging of microglia by targeting macrophage colony-stimulating factor 1 receptor (CSF1R)</title><author>Horti, Andrew G. ; Naik, Ravi ; Foss, Catherine A. ; Minn, Il ; Misheneva, Varia ; Du, Yong ; Wang, Yuchuan ; Mathews, William B. ; Wu, Yunkou ; Hall, Andrew ; LaCourse, Catherine ; Ahn, Hye-Hyun ; Nam, Hwanhee ; Lesniak, Wojciech G. ; Valentine, Heather ; Pletnikova, Olga ; Troncoso, Juan C. ; Smith, Matthew D. ; Calabresi, Peter A. ; Savonenko, Alena V. ; Dannals, Robert F. ; Pletnikov, Mikhail V. ; Pomper, Martin G.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c463t-2ddb7755c5f2ac7922a4812fc20805a8c9800c58882848e7d5fcb0d7720d0293</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Alzheimer Disease - metabolism</topic><topic>Alzheimer's disease</topic><topic>Animal models</topic><topic>Animals</topic><topic>Biological Sciences</topic><topic>Brain</topic><topic>Brain - metabolism</topic><topic>Colonies</topic><topic>Colony-stimulating factor</topic><topic>Demyelinating diseases</topic><topic>Demyelination</topic><topic>Disease Models, Animal</topic><topic>Dosimeters</topic><topic>Dosimetry</topic><topic>Experimental allergic encephalomyelitis</topic><topic>Head injuries</topic><topic>Inflammation</topic><topic>Inflammation - metabolism</topic><topic>Lipopolysaccharides</topic><topic>Macrophage colony-stimulating factor</topic><topic>Macrophage Colony-Stimulating Factor - metabolism</topic><topic>Male</topic><topic>Medical imaging</topic><topic>Mental disorders</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Microglia</topic><topic>Microglia - metabolism</topic><topic>Neuroimaging</topic><topic>Parkinson's disease</topic><topic>Physical Sciences</topic><topic>Plaque, Amyloid - metabolism</topic><topic>Positron emission</topic><topic>Positron emission tomography</topic><topic>Positron-Emission Tomography - methods</topic><topic>Primates</topic><topic>Radiation dosimetry</topic><topic>Radioactivity</topic><topic>Radiochemistry</topic><topic>Radiopharmaceuticals - metabolism</topic><topic>Receptors, Granulocyte-Macrophage Colony-Stimulating Factor - metabolism</topic><topic>Tomography</topic><topic>Traumatic brain injury</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Horti, Andrew G.</creatorcontrib><creatorcontrib>Naik, Ravi</creatorcontrib><creatorcontrib>Foss, Catherine A.</creatorcontrib><creatorcontrib>Minn, Il</creatorcontrib><creatorcontrib>Misheneva, Varia</creatorcontrib><creatorcontrib>Du, Yong</creatorcontrib><creatorcontrib>Wang, Yuchuan</creatorcontrib><creatorcontrib>Mathews, William B.</creatorcontrib><creatorcontrib>Wu, Yunkou</creatorcontrib><creatorcontrib>Hall, Andrew</creatorcontrib><creatorcontrib>LaCourse, Catherine</creatorcontrib><creatorcontrib>Ahn, Hye-Hyun</creatorcontrib><creatorcontrib>Nam, Hwanhee</creatorcontrib><creatorcontrib>Lesniak, Wojciech G.</creatorcontrib><creatorcontrib>Valentine, Heather</creatorcontrib><creatorcontrib>Pletnikova, Olga</creatorcontrib><creatorcontrib>Troncoso, Juan C.</creatorcontrib><creatorcontrib>Smith, Matthew D.</creatorcontrib><creatorcontrib>Calabresi, Peter A.</creatorcontrib><creatorcontrib>Savonenko, Alena V.</creatorcontrib><creatorcontrib>Dannals, Robert F.</creatorcontrib><creatorcontrib>Pletnikov, Mikhail V.</creatorcontrib><creatorcontrib>Pomper, Martin G.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Horti, Andrew G.</au><au>Naik, Ravi</au><au>Foss, Catherine A.</au><au>Minn, Il</au><au>Misheneva, Varia</au><au>Du, Yong</au><au>Wang, Yuchuan</au><au>Mathews, William B.</au><au>Wu, Yunkou</au><au>Hall, Andrew</au><au>LaCourse, Catherine</au><au>Ahn, Hye-Hyun</au><au>Nam, Hwanhee</au><au>Lesniak, Wojciech G.</au><au>Valentine, Heather</au><au>Pletnikova, Olga</au><au>Troncoso, Juan C.</au><au>Smith, Matthew D.</au><au>Calabresi, Peter A.</au><au>Savonenko, Alena V.</au><au>Dannals, Robert F.</au><au>Pletnikov, Mikhail V.</au><au>Pomper, Martin G.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>PET imaging of microglia by targeting macrophage colony-stimulating factor 1 receptor (CSF1R)</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2019-01-29</date><risdate>2019</risdate><volume>116</volume><issue>5</issue><spage>1686</spage><epage>1691</epage><pages>1686-1691</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>While neuroinflammation is an evolving concept and the cells involved and their functions are being defined, microglia are understood to be a key cellular mediator of brain injury and repair. The ability to measure microglial activity specifically and non-invasively would be a boon to the study of neuroinflammation, which is involved in a wide variety of neuropsychiatric disorders including traumatic brain injury, demyelinating disease, Alzheimer’s disease (AD), and Parkinson’s disease, among others. We have developed [11C]CPPC [5-cyano-N-(4-(4-[11C]methylpiperazin-1-yl)-2-(piperidin-1-yl)phenyl)furan-2-carboxamide], a positron-emitting, high-affinity ligand that is specific for the macrophage colony-stimulating factor 1 receptor (CSF1R), the expression of which is essentially restricted to microglia within brain. [11C]CPPC demonstrates high and specific brain uptake in a murine and nonhuman primate lipopolysaccharide model of neuroinflammation. It also shows specific and elevated uptake in a murine model of AD, experimental allergic encephalomyelitis murine model of demyelination and in postmortem brain tissue of patients with AD. Radiation dosimetry in mice indicated [11C]CPPC to be safe for future human studies. [11C]CPPC can be synthesized in sufficient radiochemical yield, purity, and specific radioactivity and possesses binding specificity in relevant models that indicate potential for human PET imaging of CSF1R and the microglial component of neuroinflammation.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>30635412</pmid><doi>10.1073/pnas.1812155116</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0002-7776-6472</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0027-8424 |
| ispartof | Proceedings of the National Academy of Sciences - PNAS, 2019-01, Vol.116 (5), p.1686-1691 |
| issn | 0027-8424 1091-6490 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6358677 |
| source | Jstor Complete Legacy; MEDLINE; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Alzheimer Disease - metabolism Alzheimer's disease Animal models Animals Biological Sciences Brain Brain - metabolism Colonies Colony-stimulating factor Demyelinating diseases Demyelination Disease Models, Animal Dosimeters Dosimetry Experimental allergic encephalomyelitis Head injuries Inflammation Inflammation - metabolism Lipopolysaccharides Macrophage colony-stimulating factor Macrophage Colony-Stimulating Factor - metabolism Male Medical imaging Mental disorders Mice Mice, Inbred C57BL Microglia Microglia - metabolism Neuroimaging Parkinson's disease Physical Sciences Plaque, Amyloid - metabolism Positron emission Positron emission tomography Positron-Emission Tomography - methods Primates Radiation dosimetry Radioactivity Radiochemistry Radiopharmaceuticals - metabolism Receptors, Granulocyte-Macrophage Colony-Stimulating Factor - metabolism Tomography Traumatic brain injury |
| title | PET imaging of microglia by targeting macrophage colony-stimulating factor 1 receptor (CSF1R) |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-08T08%3A25%3A22IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-jstor_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=PET%20imaging%20of%20microglia%20by%20targeting%20macrophage%20colony-stimulating%20factor%201%20receptor%20(CSF1R)&rft.jtitle=Proceedings%20of%20the%20National%20Academy%20of%20Sciences%20-%20PNAS&rft.au=Horti,%20Andrew%20G.&rft.date=2019-01-29&rft.volume=116&rft.issue=5&rft.spage=1686&rft.epage=1691&rft.pages=1686-1691&rft.issn=0027-8424&rft.eissn=1091-6490&rft_id=info:doi/10.1073/pnas.1812155116&rft_dat=%3Cjstor_pubme%3E26580304%3C/jstor_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2176698859&rft_id=info:pmid/30635412&rft_jstor_id=26580304&rfr_iscdi=true |