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ACS Chem Neurosci. 2017 May 17;8(5):996-1003. doi: 10.1021/acschemneuro.6b00445. Epub 2017 Feb 27.

A Potential PET Radiotracer for the 5-HT2C Receptor: Synthesis and in Vivo Evaluation of 4-(3-[18F]fluorophenethoxy)pyrimidine.

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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.
Department of Nuclear Medicine, Seoul National University Bundang Hospital , Seongnam 13620, Republic of Korea.
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.
Department of Chemical & Molecular Engineering/Applied Chemistry, Hanyang University , Ansan, Gyeonggi-do 15588, Republic of Korea.


The serotonin 2C receptor subtype (5-HT2C) is an excitatory 5-HT receptor widely distributed throughout the central nervous system. As the 5-HT2C receptor displays multiple actions on various neurotransmitter systems including glutamate, dopamine, epinephrine, and γ-aminobutyric acid (GABA), abnormalities of the 5-HT2C receptor are associated with psychiatric diseases such as depression, schizophrenia, drug abuse, and anxiety. Up to date, three kinds of 5-HT2C PET 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-HT2C imaging 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-HT2C receptor 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-HT2C agonist, demonstrated that [18F]4 exhibits a high level of specific binding to 5-HT2C receptors in the rat brain.


5-HT2C receptor; PET radioligands; brain imaging; in vivo; psychiatric disorders

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