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Preclinical evaluation of new C-11 labeled benzo-1,4-dioxane PET radiotracers for brain α2C adrenergic receptors

European Journal of Medicinal Chemistry. 2022-09; 
Santosh Alluri,Seth M. Eisenberg,Laurel A. Grisanti,Miles Tanner,Nora D. Volkow,Sung Won Kim,Kun-Eek Kil
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Abstract

As one of the nine subtypes of adrenergic receptors (ARs) in the brain, α2C-ARs play essential roles in emotion and memory, and are implicated in neuropsychiatric disorders, including depression, Alzheimer's disease, substance use disorder, and schizophrenia. A recently developed α2C-AR specific positron emission tomography (PET) radiotracer, [11C]ORM-13070, showed promise for imaging α2C-ARs in the brain. Herein, we prepared highly potent C-11 labelled benzo-1,4-dioxane derivatives and compared them with [11C]ORM-13070, aiming to improve the specific binding signal, as evaluated by in vivo rodent brain PET imaging.© 2022 Elsevier Inc. All rights reserved.

Keywords

Adrenergic receptorsAlpha-2cBrain imagingSmall-molecule radiotracerPET imaging