In VivoPET Imaging of Adenosine 2A Receptors in Neuroinflammatory and Neurodegenerative Disease

Abstract

Adenosine receptors are G-protein coupled P1 purinergic receptors that are broadly expressed in the peripheral immune system, vasculature, and the central nervous system (CNS). Within the immune system, adenosine 2A (A2A) receptor-mediated signaling exerts a suppressive effect on ongoing inflammation. In healthy CNS,A2Areceptors are expressed mainly within the neurons of the basal ganglia. Alterations inA2Areceptor function and expression have been noted in movement disorders, and in Parkinson’s disease pharmacologicalA2Areceptor antagonism leads to diminished motor symptoms. AlthoughA2Areceptors are expressed only at a low level in the healthy CNS outside striatum, pathological challenge or inflammation has been shown to lead to upregulation ofA2Areceptors in extrastriatal CNS tissue, and this has been successfully quantitated usingin vivopositron emission tomography (PET) imaging andA2Areceptor-binding radioligands. Several radioligands for PET imaging ofA2Areceptors have been developed in recent years, andA2Areceptor-targeting PET imaging may thus provide a potential additional tool to evaluate various aspects of neuroinflammationin vivo. This review article provides a brief overview ofA2Areceptors in healthy brain and in a selection of most important neurological diseases and describes the recent advances inA2Areceptor-targeting PET imaging studies.