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

Juhyeon Kim, Byung Seok Moon, Byung Chul Lee, Ho Young Lee, Hak Joong Kim, Hyunah Choo, Ae Nim Pae, Yong Seo Cho, Sun Joon Min

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)996-1003
Number of pages8
JournalACS Chemical Neuroscience
Volume8
Issue number5
DOIs
Publication statusPublished - 2017 May 17

Fingerprint

Receptor, Serotonin, 5-HT2C
Serotonin 5-HT2 Receptor Agonists
Aminobutyrates
Imaging techniques
Serotonin Receptors
Radioactivity
Neurology
United States Food and Drug Administration
Epinephrine
Substance-Related Disorders
Neurotransmitter Agents
Psychiatry
Rats
Glutamic Acid
Dopamine
Brain
Schizophrenia
Substitution reactions
Anxiety
Central Nervous System

Keywords

  • 5-HT receptor
  • brain imaging
  • in vivo
  • PET radioligands
  • psychiatric disorders

ASJC Scopus subject areas

  • Physiology
  • Biochemistry
  • Cognitive Neuroscience
  • Cell Biology

Cite this

A Potential PET Radiotracer for the 5-HT2C Receptor : Synthesis and in Vivo Evaluation of 4-(3-[18F]fluorophenethoxy)pyrimidine. / Kim, Juhyeon; Moon, Byung Seok; Lee, Byung Chul; Lee, Ho Young; Kim, Hak Joong; Choo, Hyunah; Pae, Ae Nim; Cho, Yong Seo; Min, Sun Joon.

In: ACS Chemical Neuroscience, Vol. 8, No. 5, 17.05.2017, p. 996-1003.

Research output: Contribution to journalArticle

Kim, Juhyeon ; Moon, Byung Seok ; Lee, Byung Chul ; Lee, Ho Young ; Kim, Hak Joong ; Choo, Hyunah ; Pae, Ae Nim ; Cho, Yong Seo ; Min, Sun Joon. / A Potential PET Radiotracer for the 5-HT2C Receptor : Synthesis and in Vivo Evaluation of 4-(3-[18F]fluorophenethoxy)pyrimidine. In: ACS Chemical Neuroscience. 2017 ; Vol. 8, No. 5. pp. 996-1003.
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abstract = "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.",
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AU - Kim, Hak Joong

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