Syntheses and preclinical evaluations of ¹¹C-labeled radioligands for imaging brain orexin-1 and orexin-2 receptors with positron emission tomography.

ABSTRACT: Despite their importance in regulating several functions in the brain, there is no effective radioligand for in vivo imaging of brain orexin-1 (OX₁R) or orexin-2 receptors (OX₂R) with positron emission tomography (PET). In a search for radioligand candidates, we identified GSK1059865 (1) as a highly potent and selective inhibitor for OX₁R (K _i = 5.0 nM for OX₁R, ∼80-fold selective over OX₂R) and similarly ET1 (2) for OX₂R (IC₅₀ = 0.8 nM for OX₂R, ∼3000-fold selective over OX₁R) with each possessing many physicochemical properties conducive for good brain permeability. We labeled compound 1 and compound 2 with carbon-11 (t _1/2 = 20.4 min) in high isol

SUBMITTER: Jana S 

PROVIDER: S-EPMC12180406 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature