Hunting for the high-affinity state of G-protein-coupled receptors with agonist tracers: Theoretical and practical considerations for positron emission tomography imaging

Vladimir Shalgunov, Aren van Waarde*, Jan Booij, Martin C Michel, Rudi Dierckx, Philip H. Elsinga

*Bijbehorende auteur voor dit werk

Onderzoeksoutputpeer review

12 Citaten (Scopus)
127 Downloads (Pure)


The concept of the high-affinity state postulates that a certain subset of G-protein-coupled receptors is primarily responsible for receptor signaling in the living brain. Assessing the abundance of this subset is thus potentially highly relevant for studies concerning the responses of neurotransmission to pharmacological or physiological stimuli and the dysregulation of neurotransmission in neurological or psychiatric disorders. The high-affinity state is preferentially recognized by agonists in vitro. For this reason, agonist tracers have been developed as tools for the noninvasive imaging of the high-affinity state with positron emission tomography (PET). This review provides an overview of agonist tracers that have been developed for PET imaging of the brain, and the experimental paradigms that have been developed for the estimation of the relative abundance of receptors configured in the high-affinity state. Agonist tracers appear to be more sensitive to endogenous neurotransmitter challenge than antagonists, as was originally expected. However, other expectations regarding agonist tracers have not been fulfilled. Potential reasons for difficulties in detecting the high-affinity state in vivo are discussed.

Originele taal-2English
Pagina's (van-tot)1014-1052
Aantal pagina's39
TijdschriftMedicinal research reviews
Nummer van het tijdschrift3
StatusPublished - mei-2019

Citeer dit