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The serotonin 2C receptor subtype (5-HT 2C ) is an excitatory 5-HT receptor widely distributed throughout the central nervous system. As the 5-HT 2C receptor displays multiple actions on various neurotransmitter systems including glutamate, dopamine, epinephrine, and γ-aminobutyric acid (GABA), abnormalities of the 5-HT 2C receptor are associated with psychiatric diseases such as depression, schizophrenia, drug abuse, and anxiety. Up to date, three kinds of 5-HT 2C PET radiotracers such as [ 11 C]N-methylated arylazepine (1), [ 11 C]WAY-163909 (2), and [ 18 F]fluorophenylcyclopropane (3) have been developed, but they may not be suitable for in vivo 5-HT 2C imaging study due to their modest specific binding. Herein, the synthesis and in vivo evaluation of 4-(3-[ 18 F]fluorophenethoxy)pyrimidine [ 18 F]4 as a potential PET radiotracer for the 5-HT 2C receptor is described. [ 18 F]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 [ 18 F]4 with or without lorcaserin, a U.S. Food and Drug Administration approved selective 5-HT 2C agonist, demonstrated that [ 18 F]4 exhibits a high level of specific binding to 5-HT 2C receptors in the rat brain.

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

A Potential PET Radiotracer for the 5-HT_2C Receptor: Synthesis and in Vivo Evaluation of 4-(3-[¹⁸F]fluorophenethoxy)pyrimidine