title: Potential Therapeutic Applications of Adenosine A2AReceptor Ligands and Opportunities for A2AReceptor Imaging.
abstract: Adenosine A2Areceptors (A2ARs) are highly expressed in the human striatum, and at lower densities in the cerebral cortex, the hippocampus, and cells of the immune system. Antagonists of these receptors are potentially useful for the treatment of motor fluctuations, epilepsy, postischemic brain damage, or cognitive impairment, and for the control of an immune checkpoint during immunotherapy of cancer. A2AR agonists may suppress transplant rejection and graft-versus-host disease; be used to treat inflammatory disorders such as asthma, inflammatory bowel disease, and rheumatoid arthritis; be locally applied to promote wound healing and be employed in a strategy for transient opening of the blood-brain barrier (BBB) so that therapeutic drugs and monoclonal antibodies can enter the brain. Increasing A2AR signaling in adipose tissue is also a potential strategy to combat obesity. Several radioligands for positron emission tomography (PET) imaging of A2ARs have been developed in recent years. This review article presents a critical overview of the potential therapeutic applications of A2AR ligands, the use of A2AR imaging in drug development, and opportunities and limitations of PET imaging in future research.
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, 1, 9713 GZ, Groningen, The Netherlands.
authors.forename: Aren
authors.initials: A
authors.lastname: van Waarde
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, 1, 9713 GZ, Groningen, The Netherlands.|Department of Nuclear Medicine, University Hospital, Ghent University, De Pintelaan 185, 9000, Ghent, Belgium.
authors.forename: Rudi A J O
authors.initials: RAJO
authors.lastname: Dierckx
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, 1, 9713 GZ, Groningen, The Netherlands.
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Zhou
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, 1, 9713 GZ, Groningen, The Netherlands.
authors.forename: Shivashankar
authors.initials: S
authors.lastname: Khanapur
authors.affiliation: Central Research Laboratory, Hamamatsu Photonics K.K., Hamakita, Hamamatsu, Shizuoka 434-8601, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Tsukada
authors.affiliation: Research Institute of Cyclotron and Drug Discovery Research, Southern TOHOKU Research Institute for Neuroscience, 7-115 Yatsuyamada, Koriyama, 963-8052, Japan.|Department of Biofunctional Imaging, Fukushima Medical University, 1 Hikarigaoka, Fukushima, 960-1295, Japan.|Research Team for Neuroimaging, Tokyo Metropolitan Institute of Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo, 173-0015, Japan.
authors.forename: Kiichi
authors.initials: K
authors.lastname: Ishiwata
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, 1, 9713 GZ, Groningen, The Netherlands.
authors.forename: Gert
authors.initials: G
authors.lastname: Luurtsema
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, 1, 9713 GZ, Groningen, The Netherlands.
authors.forename: Erik F J
authors.initials: EFJ
authors.lastname: de Vries
authors.affiliation: University of Groningen, University Medical Center Groningen, Department of Nuclear Medicine and Molecular Imaging, 1, 9713 GZ, Groningen, The Netherlands.
authors.forename: Philip H
authors.initials: PH
authors.lastname: Elsinga
mesh_terms: D058908:Adenosine A2 Receptor Agonists / Q000494:pharmacology*; D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D006801:Humans; D008024:Ligands; D049268:Positron-Emission Tomography; D011869:Radioligand Assay; D043705:Receptor, Adenosine A2A / Q000032:analysis / Q000378:metabolism
chemical_list: D058908:Adenosine A2 Receptor Agonists; D058917:Adenosine A2 Receptor Antagonists; D008024:Ligands; D043705:Receptor, Adenosine A2A
keywords: Positron emission tomography (PET) imaging; adenosine A2A receptors; agonists; antagonists; drug development