{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T10:16:29Z","timestamp":1753870589234,"version":"3.41.2"},"reference-count":24,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2019,3,23]],"date-time":"2019-03-23T00:00:00Z","timestamp":1553299200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Synapse"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>A positron emission tomography (PET) radioligand, [<jats:sup>18<\/jats:sup>F]FMH3, has been developed to interrogate histamine receptor subtype 3 (H3R), where dysfunction at this site is linked with obesity, sleep abnormality, and cognitive disorders. [<jats:sup>18<\/jats:sup>F]FMH3 was evaluated for imaging central H3R sites in non\u2010human primates through test\u2013retest (TRT) and dose\u2010receptor occupancy studies with two selective H3R antagonists in order to support clinical investigations. Two adult female baboons underwent [<jats:sup>18<\/jats:sup>F]FMH3 PET brain scans in the HR+, at repeated baseline (<jats:italic>n<\/jats:italic>\u00a0=\u00a07) and following administration of escalating doses of ABT\u2010239 (0.003\u20130.1m\/kg, <jats:italic>n<\/jats:italic>\u00a0=\u00a04) and ciproxifan (0.5\u20132.1\u00a0mg\/kg, <jats:italic>n<\/jats:italic>\u00a0=\u00a07). Volume of distribution (<jats:italic>V<\/jats:italic><jats:sub>T<\/jats:sub>) in brain regions was estimated using the 2\u2010tissue compartment model. TRT variability of <jats:italic>V<\/jats:italic><jats:sub>T<\/jats:sub> across repeated baseline scans was reported as % coefficient of variation (COV). ABT\u2010239 and ciproxifan occupancy at H3R was estimated using the occupancy plot, and the relationship of occupancy with dose and plasma levels was determined. In baboons, distribution of [<jats:sup>18<\/jats:sup>F]FMH3 was high in the striatum, intermediate in cortical regions, and low in the brain stem. COV of baseline <jats:italic>V<\/jats:italic><jats:sub>T<\/jats:sub> was 7.0\u00a0\u00b1\u00a03.5%, averaged across regions and animals. Dose\u2010dependent effects of ABT\u2010239 and ciproxifan measured the brain. ED50 and EC50, respectively, were 0.011\u00a0mg\/kg and 0.942\u00a0ng\/ml for ABT\u2010239 and 0.73\u00a0mg\/kg and 208.3\u00a0ng\/ml for ciproxifan. [<jats:sup>18<\/jats:sup>F]FMH3 demonstrated high TRT reliability and can be used to measure occupancy of H3R\u2010targeted drugs. Validation in non\u2010human primates support [<jats:sup>18<\/jats:sup>F]FMH3 PET studies toward clinical investigations of H3R.<\/jats:p>","DOI":"10.1002\/syn.22096","type":"journal-article","created":{"date-parts":[[2019,3,6]],"date-time":"2019-03-06T01:56:01Z","timestamp":1551837361000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Imaging histamine H3 receptors with [<sup>18<\/sup>F]FMH3: Test\u2013retest and occupancy studies in the non\u2010human primate"],"prefix":"10.1002","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7490-2494","authenticated-orcid":false,"given":"Christine M.","family":"Sandiego","sequence":"first","affiliation":[{"name":"Invicro, a Konica Minolta Company New Haven Connecticut"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olivier","family":"Barret","sequence":"additional","affiliation":[{"name":"Invicro, a Konica Minolta Company New Haven Connecticut"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hsiaoju","family":"Lee","sequence":"additional","affiliation":[{"name":"Invicro, a Konica Minolta Company New Haven Connecticut"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Alagille","sequence":"additional","affiliation":[{"name":"Invicro, a Konica Minolta Company New Haven Connecticut"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy","family":"Amenta","sequence":"additional","affiliation":[{"name":"Invicro, a Konica Minolta Company New Haven Connecticut"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krista","family":"Fowles","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Radiology Yale University New Haven Connecticut"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Holden","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Radiology Yale University New Haven Connecticut"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John P.","family":"Seibyl","sequence":"additional","affiliation":[{"name":"Invicro, a Konica Minolta Company New Haven Connecticut"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gilles","family":"Tamagnan","sequence":"additional","affiliation":[{"name":"XingImaging, LLC New Haven Connecticut"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,3,23]]},"reference":[{"issue":"7","key":"e_1_2_8_2_1","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.2967\/jnumed.109.071753","article-title":"Evaluation of 11C\u2010GSK189254 as a novel radioligand for the H3 receptor in humans using PET","volume":"51","author":"Ashworth S.","year":"2010","journal-title":"Journal of Nuclear Medicine: Official Publication, Society of Nuclear 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