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

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 specifi...

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Bibliographic Details
Published in:European journal of medicinal chemistry 2022-12, Vol.243, p.114764-114764, Article 114764
Main Authors: Alluri, Santosh, Eisenberg, Seth M., Grisanti, Laurel A., Tanner, Miles, Volkow, Nora D., Kim, Sung Won, Kil, Kun-Eek
Format: Article
Language:English
Subjects:
Adrenergic receptors
Alpha-2c
Brain imaging
PET imaging
Small-molecule radiotracer
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Summary: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 labeled 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. [Display omitted] •Synthesis and C-11 radiolabeling of benzo-1,4-dioxane-based α2C-AR ligands.•In vitro binding potency and in vivo evaluation of BBB permeability in rat brain.•Investigate the influence of brain efflux pumps on BBB permeability.
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2022.114764