{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T15:06:41Z","timestamp":1770736001789,"version":"3.49.0"},"reference-count":39,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2015,10,16]],"date-time":"2015-10-16T00:00:00Z","timestamp":1444953600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>We investigated [<jats:sup>18<\/jats:sup>F]fluoroethyl\u2010harmol ([<jats:sup>18<\/jats:sup>F]<jats:styled-content style=\"fixed-case\">FEH<\/jats:styled-content>) as a reversible and selective ligand for positron emission tomography (<jats:styled-content style=\"fixed-case\">PET<\/jats:styled-content>) studies of monoamine oxidase A (<jats:styled-content style=\"fixed-case\">MAO<\/jats:styled-content>\u2010A). Binding of [<jats:sup>18<\/jats:sup>F]<jats:styled-content style=\"fixed-case\">FEH<\/jats:styled-content> in rat brain cryostat sections indicated high affinity (<jats:styled-content style=\"fixed-case\"><jats:italic>K<\/jats:italic><jats:sub>D<\/jats:sub><\/jats:styled-content>\u00a0=\u00a03 <jats:styled-content style=\"fixed-case\">nM<\/jats:styled-content>), and density (<jats:italic>B<\/jats:italic><jats:sub>max<\/jats:sub>; 600\u00a0pmol\/g). The plasma free fraction was 45%, and untransformed parent constituted only 13% of plasma radioactivity at 10\u00a0min after injection. Compartmental analysis of <jats:styled-content style=\"fixed-case\">PET<\/jats:styled-content> recordings in pargyline\u2010treated rats showed high permeability to brain (<jats:italic>K<\/jats:italic><jats:sub>1<\/jats:sub>; 0.32\u00a0mL\/g\/min) and slow washout (<jats:italic>k<\/jats:italic><jats:sub>2<\/jats:sub>; 0.024\/min), resulting in a uniformly high equilibrium distribution volume (<jats:styled-content style=\"fixed-case\"><jats:italic>V<\/jats:italic><jats:sub>D<\/jats:sub><\/jats:styled-content>; 20\u00a0mL\/g). Using this <jats:styled-content style=\"fixed-case\"><jats:italic>V<\/jats:italic><jats:sub>D<\/jats:sub><\/jats:styled-content> to estimate unbound ligand in brain of untreated rats, the binding potential ranged from 4.2 in cerebellum to 7.2 in thalamus. We also calculated maps of rats receiving [<jats:sup>18<\/jats:sup>F]<jats:styled-content style=\"fixed-case\">FEH<\/jats:styled-content> at a range of specific activities, and then estimated saturation binding parameters in the living brain. In thalamus, striatum and frontal cortex <jats:styled-content style=\"fixed-case\"><jats:italic>K<\/jats:italic><jats:sub>D<\/jats:sub><\/jats:styled-content> was globally close to 300 <jats:styled-content style=\"fixed-case\">nM<\/jats:styled-content> and <jats:italic>B<\/jats:italic><jats:sub>max<\/jats:sub> was close to 1600\u00a0pmol\/g; the 100\u2010fold discrepancy in affinity suggests a very low free fraction for [<jats:sup>18<\/jats:sup>F]<jats:styled-content style=\"fixed-case\">FEH<\/jats:styled-content> in the living brain. Based on a synthesis of findings, we calculate the endogenous dopamine concentration to be 0.4\u00a0\u03bcM in the striatal compartment containing <jats:styled-content style=\"fixed-case\">MAO<\/jats:styled-content>\u2010A, thus unlikely to exert competition against [<jats:sup>18<\/jats:sup>F]<jats:styled-content style=\"fixed-case\">FEH<\/jats:styled-content> binding <jats:italic>in\u00a0vivo<\/jats:italic>. In summary, [<jats:sup>18<\/jats:sup>F]<jats:styled-content style=\"fixed-case\">FEH<\/jats:styled-content> has good properties for the detection of <jats:styled-content style=\"fixed-case\">MAO<\/jats:styled-content>\u2010A in the rat brain by <jats:styled-content style=\"fixed-case\">PET<\/jats:styled-content>, and may present logistic advantages for clinical research at centers lacking a medical cyclotron.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc13370-fig-0006-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\nWe made a compartmental analysis of [<jats:sup>18<\/jats:sup>F]fluoroethylharmol ([<jats:sup>18<\/jats:sup>F]FEH) binding to monoamine oxidase A (MAO\u2010A) in living rat brain and estimated the saturation binding parameters from the binding potential (BP<jats:sub>ND<\/jats:sub>). The <jats:italic>B<\/jats:italic><jats:sub>max<\/jats:sub> was of comparable magnitude to that <jats:italic>in\u00a0vitro<\/jats:italic>, but with apparent affinity (300\u00a0nM), it was 100\u2010fold lower <jats:italic>in\u00a0vivo<\/jats:italic>. PET imaging with [<jats:sup>18<\/jats:sup>F]FEH is well suited for quantitation of MAO\u2010A in living brain.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.13370","type":"journal-article","created":{"date-parts":[[2015,9,19]],"date-time":"2015-09-19T12:37:03Z","timestamp":1442666223000},"page":"908-917","source":"Crossref","is-referenced-by-count":16,"title":["Specific binding of [<sup>18<\/sup>F]fluoroethyl\u2010harmol to monoamine oxidase A in rat brain cryostat sections, and compartmental analysis of binding in living brain"],"prefix":"10.1111","volume":"135","author":[{"given":"Simone","family":"Maschauer","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Imaging and Radiochemistry Department of Nuclear Medicine Friedrich Alexander University Erlangen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adelina","family":"Haller","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Imaging and Radiochemistry Department of Nuclear Medicine Friedrich Alexander University Erlangen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick J.","family":"Riss","sequence":"additional","affiliation":[{"name":"Department of Chemistry Universitetet i Oslo &amp; Norsk Medisinisk Syklotronsenter AS Oslo Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Torsten","family":"Kuwert","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Imaging and Radiochemistry Department of Nuclear Medicine Friedrich Alexander University Erlangen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olaf","family":"Prante","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Imaging and Radiochemistry Department of Nuclear Medicine Friedrich Alexander University Erlangen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Cumming","sequence":"additional","affiliation":[{"name":"Department of Neuroscience and Pharmacology Copenhagen University Copenhagen Denmark"},{"name":"Department of Neuropsychiatry and Psychosomatic Medicine OUS\u2010Rikshospitalet Oslo Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2015,10,16]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/archgenpsychiatry.2011.82"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1006982732681"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0969-8051(97)00013-9"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/jlcr.1519"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/0278-5846(89)90147-4"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/jn\/128.12.2512"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1990.tb01918.x"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2013.297"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2003.10.021"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1017\/CBO9780511575853"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/syn.20916"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.1992.tb11026.x"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004647-199711000-00014"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2396(199911)34:2<124::AID-SYN5>3.0.CO;2-O"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2014.63"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/syn.21785"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-010-0537-x"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2867601"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2009.09.048"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2001.00649.x"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nucmedbio.2003.10.003"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/jlcr.3247"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2014.82"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0404.1986.tb04618.x"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jcbfm.9600493"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2396(199701)25:1<30::AID-SYN4>3.0.CO;2-G"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/syn.20258"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm701378e"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00228974"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/0378-8741(84)90003-5"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.13001"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apradiso.2015.01.002"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(96)00074-4"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2011.184"},{"key":"e_1_2_7_36_1","first-page":"1612","article-title":"In vivo evaluation of pegylated [18F]harmine derivatives: selective reversible MAO\u2010A inhibitors","volume":"53","author":"Schieferstein H.","year":"2012","journal-title":"J. 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