Positron emission tomography imaging of the γ-aminobutyric acid system

• Published in: Neuroscience letters 2019-01, Vol.691, p.35-43
• Main Authors: Andersson, Jan D., Matuskey, David, Finnema, Sjoerd J.
• Format: Article
• Language: English
• Subjects: [11C]flumazenil; [11C]Ro15-4513; [11C]RO6899880; GABA; PET imaging
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2018.08.010

•This review summarizes the recent development of positron emission tomography (PET) radioligands for γ-aminobutyric acid A (GABAA) receptors.•Clinical and translational applications of GABA PET radioligands are highlighted.•The importance and challenge of radioligands with increased sensitivity to efficiently measure GABA release are also discussed.•We conclude that PET tracers with increased GABA sensitivity will have broad applications across several brain disorders. In this review, we summarize the recent development of positron emission tomography (PET) radioligands for γ-aminobutyric acid A (GABAA) receptors and their potential to measure changes in endogenous GABA levels and highlight the clinical and translational applications of GABA-sensitive PET radioligands. We review the basic physiology of the GABA system with a focus on the importance of GABAA receptors in the brain and specifically the benzodiazepine binding site. Challenges for the development of central nervous system radioligands and particularly for radioligands with increased GABA sensitivity are outlined, as well as the status of established benzodiazepine site PET radioligands and agonist GABAA radioligands. We underline the challenge of using allosteric interactions to measure GABA concentrations and review the current state of PET imaging of changes in GABA levels. We conclude that PET tracers with increased GABA sensitivity are required to efficiently measure GABA release and that such a tool could be broadly applied to assess GABA transmission in vivo across several disorders.