{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T12:41:49Z","timestamp":1763037709095,"version":"3.41.2"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T00:00:00Z","timestamp":1638403200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01EB021155"],"award-info":[{"award-number":["R01EB021155"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007270","name":"University of Michigan","doi-asserted-by":"publisher","award":["Department of Radiology"],"award-info":[{"award-number":["Department of Radiology"]}],"id":[{"id":"10.13039\/100007270","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:p>Mutations in the huntingtin gene (HTT) triggers aggregation of huntingtin protein (<jats:italic>m<\/jats:italic>HTT), which is the hallmark pathology of neurodegenerative Huntington\u2019s disease (HD). Development of a high affinity <jats:sup>18<\/jats:sup>F radiotracer would enable the study of Huntington\u2019s disease pathology using a non-invasive imaging modality, positron emission tomography (PET) imaging. Herein, we report the first synthesis of fluorine-18 imaging agent, 6-(5-((5-(2,2-difluoro-2-(fluoro-<jats:sup>18<\/jats:sup>F)ethoxy)pyridin-2-yl)methoxy)benzo[<jats:italic>d<\/jats:italic>]oxazol-2-yl)-2-methylpyridazin-3(2<jats:italic>H<\/jats:italic>)-one ([<jats:sup>18<\/jats:sup>F]1), a radioligand for HD and its preclinical evaluation <jats:italic>in vitro<\/jats:italic> (autoradiography of post-mortem HD brains) and <jats:italic>in vivo<\/jats:italic> (rodent and non-human primate brain PET). [<jats:sup>18<\/jats:sup>F]1 was synthesized in a 4.1% RCY (decay corrected) and in an average molar activity of 16.5 \u00b1 12.5 GBq\/\u03bcmol (445 \u00b1 339 Ci\/mmol). [<jats:sup>18<\/jats:sup>F]1 penetrated the blood-brain barrier of both rodents and primates, and specific saturable binding in post-mortem brain slices was observed that correlated to <jats:italic>m<\/jats:italic>HTT aggregates identified by immunohistochemistry.<\/jats:p>","DOI":"10.3389\/fnins.2021.766176","type":"journal-article","created":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T14:32:24Z","timestamp":1638455544000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":14,"title":["Synthesis and Evaluation of a Fluorine-18 Radioligand for Imaging Huntingtin Aggregates by Positron Emission Tomographic Imaging"],"prefix":"10.3389","volume":"15","author":[{"given":"Tanpreet","family":"Kaur","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allen F.","family":"Brooks","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex","family":"Lapsys","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy J.","family":"Desmond","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jenelle","family":"Stauff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janna","family":"Arteaga","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wade P.","family":"Winton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter J. 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