Discovery and development of brain-penetrant ¹⁸F-labeled radioligands for neuroimaging of the sigma-2 receptors.

ABSTRACT: We have discovered and synthesized a series of indole-based derivatives as novel sigma-2 (σ ₂) receptor ligands. Two ligands with high σ ₂ receptor affinity and subtype selectivity were then radiolabeled with F-18 in good radiochemical yields and purities, and evaluated in rodents. In biodistribution studies in male ICR mice, radioligand [¹⁸F]9, or 1-(4-(5,6-dimethoxyisoindolin-2-yl)butyl)-4-(2-[¹⁸F]fluoroethoxy)-1H-indole, was found to display high brain uptake and high brain-to-blood ratio. Pretreatment of animals with the selective σ ₂ receptor ligand CM398 led to significant reductions in both brain uptake (29%-54%) and brain-to-blood ratio (60%-88%) of the radioligand in a dose-dependent manner,

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC9069315 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature