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

Shalgunov, V., van Waarde, A., Booij, J., Michel, M. C., Dierckx, R. & Elsinga, P. H., May-2019, In : Medicinal research reviews. 39, 3, p. 1014-1052 39 p.

Research output: Contribution to journalReview articleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)1014-1052
Number of pages39
JournalMedicinal research reviews
Issue number3
Publication statusPublished - May-2019


  • agonist high-affinity state, experimental design, G-protein-coupled receptors, human brain, neurotransmitters, positron emission tomography, IN-VIVO BINDING, DOPAMINE D2(HIGH) RECEPTORS, TEST-RETEST REPRODUCIBILITY, ENDOGENOUS OPIOID RELEASE, BETA-ADRENERGIC-RECEPTOR, NONHUMAN PRIMATE BRAIN, D-2/3 AGONIST, 5-HT1A RECEPTORS, PET RADIOLIGAND, RAT-BRAIN

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