title: A Potential PET Radiotracer for the 5-HT2CReceptor: Synthesis and in Vivo Evaluation of 4-(3-[18F]fluorophenethoxy)pyrimidine.
abstract: The serotonin 2C receptor subtype (5-HT2C) is an excitatory 5-HT receptor widely distributed throughout the central nervous system. As the 5-HT2Creceptor displays multiple actions on various neurotransmitter systems including glutamate, dopamine, epinephrine, and γ-aminobutyric acid (GABA), abnormalities of the 5-HT2Creceptor are associated with psychiatric diseases such as depression, schizophrenia, drug abuse, and anxiety. Up to date, three kinds of 5-HT2CPET radiotracers such as [11C]N-methylated arylazepine (1), [11C]WAY-163909 (2), and [18F]fluorophenylcyclopropane (3) have been developed, but they may not be suitable for in vivo 5-HT2Cimaging study due to their modest specific binding. Herein, the synthesis and in vivo evaluation of 4-(3-[18F]fluorophenethoxy)pyrimidine [18F]4 as a potential PET radiotracer for the 5-HT2Creceptor is described. [18F]4 was synthesized by nucleophilic aromatic substitution of diaryliodonium precursor 17a with a 7.8 ± 2.7% (n = 6, decay corrected) radiochemical yield and over 99% radiochemical purity, showing an 89 ± 14 GBq/μmol specific radioactivity. The in vivo PET imaging studies of [18F]4 with or without lorcaserin, a U.S. Food and Drug Administration approved selective 5-HT2Cagonist, demonstrated that [18F]4 exhibits a high level of specific binding to 5-HT2Creceptors in the rat brain.
authors.affiliation: Center for Neuro-Medicine, Korea Institute of Science and Technology (KIST) , 5 Hwarangno 14-gil, Seongbuk-gu, Seoul 02792, Republic of Korea.|Department of Chemistry, Korea University , Seoul 02841, Republic of Korea.
authors.forename: Juhyeon
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Nuclear Medicine, Seoul National University Bundang Hospital , Seongnam 13620, Republic of Korea.
authors.forename: Byung Seok
authors.initials: BS
authors.lastname: Moon
authors.affiliation: Department of Nuclear Medicine, Seoul National University Bundang Hospital , Seongnam 13620, Republic of Korea.
authors.forename: Byung Chul
authors.initials: BC
authors.lastname: Lee
authors.affiliation: Department of Nuclear Medicine, Seoul National University Bundang Hospital , Seongnam 13620, Republic of Korea.
authors.forename: Ho-Young
authors.initials: HY
authors.lastname: Lee
authors.affiliation: Department of Chemistry, Korea University , Seoul 02841, Republic of Korea.
authors.forename: Hak-Joong
authors.identifier: 0000-0002-3213-2230
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Center for Neuro-Medicine, Korea Institute of Science and Technology (KIST) , 5 Hwarangno 14-gil, Seongbuk-gu, Seoul 02792, Republic of Korea.|Department of Biological Chemistry, Korea University of Science and Technology (UST) , 217 Gajungro, Yuseong-gu, Daejeon 34113, Republic of Korea.
authors.forename: Hyunah
authors.initials: H
authors.lastname: Choo
authors.affiliation: Department of Biological Chemistry, Korea University of Science and Technology (UST) , 217 Gajungro, Yuseong-gu, Daejeon 34113, Republic of Korea.|Convergence Research Center for Diagnosis, Treatment and Care System of Dementia, KIST , Seoul 02792, Republic of Korea.
authors.forename: Ae Nim
authors.initials: AN
authors.lastname: Pae
authors.affiliation: Center for Neuro-Medicine, Korea Institute of Science and Technology (KIST) , 5 Hwarangno 14-gil, Seongbuk-gu, Seoul 02792, Republic of Korea.|Department of Biological Chemistry, Korea University of Science and Technology (UST) , 217 Gajungro, Yuseong-gu, Daejeon 34113, Republic of Korea.
authors.forename: Yong Seo
authors.initials: YS
authors.lastname: Cho
authors.affiliation: Department of Chemical & Molecular Engineering/Applied Chemistry, Hanyang University , Ansan, Gyeonggi-do 15588, Republic of Korea.
authors.forename: Sun-Joon
authors.identifier: 0000-0003-0867-4416
authors.initials: SJ
authors.lastname: Min
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals / Q000138:chemical synthesis*; D051381:Rats; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism*
chemical_list: D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D044405:Receptor, Serotonin, 5-HT2C
keywords: 5-HT2C receptor; PET radioligands; brain imaging; in vivo; psychiatric disorders