First visualization of adenosine A 2A receptors in the human brain by positron emission tomography with [ 11 C]TMSX

[ 11 C]TMSX is a new positron emission tomography (PET) radioligand that provides visualization of adenosine A 2A receptors (A 2A Rs) in the brain, heart and skeletal muscle. Here we report on the first visualization of the A 2A Rs in the human brain by PET and [ 11 C]TMSX in a male healthy volunteer, compared with the adenosine A 1 receptors (A 1 Rs) and dopamine D 2 receptors (D 2 Rs) which were measured by PET with [ 11 C]MPDX and [ 11 C]raclopride, respectively. The distribution volume (DV) of [ 11 C]TMSX in the baseline was relatively high in the head of caudate nucleus, putamen, and thalamus and relatively low in the cortical regions. Infusion of theophylline, a nonselective A 2A R antagonist (K i for A 2A Rs = 16000 nM for theophylline vs 5.9 nM for TMSX), slightly reduced the DVs in the head of caudate nucleus (8.0% reduction) and putamen (4.5% reduction), but not in the other regions having much lower levels of A 2A Rs, demonstrating the A 2A R‐specific binding of [ 11 C]TMSX. On the other hand, the A 1 Rs were widely distributed in the whole brain except for the cerebellum, while the binding potential of [ 11 C]raclopride was predominantly high in the striatum. We concluded that [ 11 C]TMSX is an applicable PET ligand for mapping the A 2A Rs in the caudate nucleus and putamen in clinical studies because of no availability of other radioligands until now. The [ 11 C]TMSX PET is of great interest for studying the pathophysiology of neurological and psychiatric disorders together with the [ 11 C]raclopride PET for D 2 Rs evaluation and/or the [ 11 C]MPDX PET for A 1 Rs evaluation. Synapse 55:133–136, 2005. © 2004 Wiley‐Liss, Inc.