{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:07:52Z","timestamp":1753891672040,"version":"3.41.2"},"reference-count":18,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,26]],"date-time":"2021-11-26T00:00:00Z","timestamp":1637884800000},"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","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:p>The serotonin 5-HT<jats:sub>2<\/jats:sub><jats:sub><jats:italic>C<\/jats:italic><\/jats:sub> receptor (5-HT<jats:sub>2<\/jats:sub><jats:sub><jats:italic>C<\/jats:italic><\/jats:sub>R) is abundantly expressed throughout the central nervous system, and involved in a variety of neuroendocrine and neurobehavioral processes. The development of a selective radioligand that will enable <jats:italic>in vivo<\/jats:italic> imaging and quantification of 5-HT<jats:sub>2<\/jats:sub><jats:sub><jats:italic>C<\/jats:italic><\/jats:sub>R densities represents a significant technological advancement in understanding both the normal function and pathophysiology of the 5-HT<jats:sub>2<\/jats:sub><jats:sub><jats:italic>C<\/jats:italic><\/jats:sub>R. Four 7-halogen-2-phenyl isoindolones (7-F, Cl, Br, I) were synthesized and displayed high affinities for 5-HT<jats:sub>2<\/jats:sub><jats:sub><jats:italic>C<\/jats:italic><\/jats:sub>R and high selectivity over 5-HT<jats:sub>2<\/jats:sub><jats:sub><jats:italic>A<\/jats:italic><\/jats:sub> and 5-HT<jats:sub>2<\/jats:sub><jats:sub><jats:italic>B<\/jats:italic><\/jats:sub>. [<jats:sup>11<\/jats:sup>C]7-Chloro-2-[4-methoxy-3-[2-(4-methylpiperidin-1-yl)ethoxy]phenyl]isoindolin-1-one (<jats:bold>6<\/jats:bold>) and [<jats:sup>11<\/jats:sup>C]7-iodo-2-[4-methoxy-3-[2-(4-methylpiperidin-1-yl)ethoxy]phenyl]isoindolin-1-one (<jats:bold>9<\/jats:bold>) were synthesized in high radiochemical yield of 37\u201344% [<jats:italic>n<\/jats:italic> = 10, decay corrected from end of (<jats:sup>11<\/jats:sup>C)CH<jats:sub>3<\/jats:sub>I synthesis] with high radiochemical purity <jats:italic>via O<\/jats:italic>-methylation with [<jats:sup>11<\/jats:sup>C]CH<jats:sub>3<\/jats:sub>I, respectively. MicroPET imaging studies in male rats with or without 5-HT<jats:sub>2<\/jats:sub><jats:sub><jats:italic>C<\/jats:italic><\/jats:sub> antagonist SB-242084 showed that [<jats:sup>11<\/jats:sup>C]<jats:bold>6<\/jats:bold> and [<jats:sup>11<\/jats:sup>C]<jats:bold>9<\/jats:bold> display specific bindings to 5-HT<jats:sub>2<\/jats:sub><jats:sub><jats:italic>C<\/jats:italic><\/jats:sub>R in the choroid plexus and hippocampus. <jats:italic>In vivo<\/jats:italic> microPET brain imaging studies in rhesus monkeys demonstrated that [<jats:sup>11<\/jats:sup>C]<jats:bold>6<\/jats:bold> and [<jats:sup>11<\/jats:sup>C]<jats:bold>9<\/jats:bold> exhibit excellent blood-brain barrier penetration. The contrast of bindings to the choroid plexus and hippocampus compared to the cerebellum peaked at 2.7 and 1.6, respectively, for [<jats:sup>11<\/jats:sup>C]<jats:bold>6<\/jats:bold>, and 3.7 and 2.7, respectively, for [<jats:sup>11<\/jats:sup>C]<jats:bold>9<\/jats:bold>, which were reduced by administration of a dose of SB-242084. Our results support the candidacy of [<jats:sup>11<\/jats:sup>C]<jats:bold>6<\/jats:bold> and [<jats:sup>11<\/jats:sup>C]<jats:bold>9<\/jats:bold> for further study as radioligands for <jats:italic>in vivo<\/jats:italic> quantitation of 5-HT<jats:sub>2<\/jats:sub><jats:sub><jats:italic>C<\/jats:italic><\/jats:sub> sites by PET.<\/jats:p>","DOI":"10.3389\/fnins.2021.766320","type":"journal-article","created":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T06:14:29Z","timestamp":1638339269000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Synthesis and Evaluation of [11C]7-Halogen-2-Phenyl Isoindolone Derivatives: Potential PET Radioligands for in vivo Imaging of 5-HT2C Receptors"],"prefix":"10.3389","volume":"15","author":[{"given":"Fanxing","family":"Zeng","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathon A.","family":"Nye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronald J.","family":"Voll","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiyoung","family":"Mun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark M.","family":"Goodman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,11,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.1016\/s0028-3908(99)00010-6","article-title":"A review of central 5-HT receptors and their function.","volume":"38","author":"Barnes","year":"1999","journal-title":"Neuropharmacology"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1177\/0269881117725915","article-title":"Serotonin and brain function: a tale of two receptors.","volume":"31","author":"Carhart-Harris","year":"2017","journal-title":"J. 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