Synthesis and characterization of a novel series of agonist compounds as potential radiopharmaceuticals for imaging dopamine D2/3 receptors in their high-affinity state

Jan Peter Van Wieringen, Vladimir Shalgunov, Henk M. Janssen, P. Michel Fransen, Anton G.M. Janssen, Martin C. Michel, Jan Booij (Corresponding author), Philip H. Elsinga

Research output: Contribution to journalArticleAcademicpeer-review

7 Citations (Scopus)

Abstract

Imaging of dopamine D2/3 receptors (D2/3R) can shed light on the nature of several neuropsychiatric disorders in which dysregulation of D2/3R signaling is involved. Agonist D2/3 tracers for PET/SPECT imaging are considered to be superior to antagonists because they are more sensitive to dopamine concentrations and may selectively label the high-affinity receptor state. Carbon-11-labeled D2/3R agonists have been developed, but these short-lived tracers can be used only in centers with a cyclotron. Here, we report the development of a series of novel D2R agonist compounds based on the 2-aminomethylchromane (AMC) scaffold that provides ample opportunities for the introduction of longer-lived [ 18F] or [123I]. Binding experiments showed that several AMC compounds have a high affinity and selectivity for D2/3R and act as agonists. Two fluorine-containing compounds were [18F]-labeled, and both displayed specific binding to striatal D2/3R in rat brain slices in vitro. These findings encourage further in vivo evaluations.

Original languageEnglish
Pages (from-to)391-410
Number of pages20
JournalJournal of Medicinal Chemistry
Volume57
Issue number2
DOIs
Publication statusPublished - 23 Jan 2014

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