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

Santosh Alluri; Seth M Eisenberg; Laurel A Grisanti; Miles Tanner; Nora D Volkow; Sung Won Kim; Kun-Eek Kil

doi:10.1016/j.ejmech.2022.114764

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

Eur J Med Chem. 2022 Dec 5:243:114764. doi: 10.1016/j.ejmech.2022.114764. Epub 2022 Sep 17.

Authors

Santosh Alluri¹, Seth M Eisenberg², Laurel A Grisanti³, Miles Tanner³, Nora D Volkow⁴, Sung Won Kim⁵, Kun-Eek Kil⁶

Affiliations

¹ University of Missouri Research Reactor, University of Missouri, Columbia, MO, 65211, USA.
² Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, MD, 20892-1013, USA.
³ Department of Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, MO, 65211, USA.
⁴ Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, MD, 20892-1013, USA; National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, 20892-1013, USA.
⁵ Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, MD, 20892-1013, USA. Electronic address: [email protected].
⁶ University of Missouri Research Reactor, University of Missouri, Columbia, MO, 65211, USA; Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, MO, 65211, USA. Electronic address: [email protected].

PMID: 36272201
DOI: 10.1016/j.ejmech.2022.114764

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 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.

Keywords: Adrenergic receptors; Alpha-2c; Brain imaging; PET imaging; Small-molecule radiotracer.

Published by Elsevier Masson SAS.

MeSH terms

Brain / diagnostic imaging
Brain / metabolism
Carbon Radioisotopes / metabolism
Piperazines* / metabolism
Positron-Emission Tomography
Receptors, Adrenergic, alpha-2* / metabolism

Substances

1,4-dioxane
Carbon-11
Carbon Radioisotopes
Receptors, Adrenergic, alpha-2
Piperazines