title: Evaluation of distribution of adenosine A2A receptors in normal human brain measured with [11C]TMSX PET.
abstract: Adenosine A(2A) receptor (A2AR) is thought to interact with dopamine D(2) receptor. Selective A2AR antagonists have attracted attention as the treatment of Parkinson's disease. In this study, we investigated the distribution of the A2ARs in the living human brain using positron emission tomography (PET) and [7-methyl-(11)C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([(11)C]TMSX). We recruited five normal male subjects. A dynamic series of PET scans was performed for 60 min, and the arterial blood was sampled during the scan to measure radioactivity of the parent compound and labeled metabolites. Circular regions of interest of 10-mm diameter were placed in the PET images over the cerebellum, brainstem, thalamus, head of caudate nucleus, anterior and posterior putamen, frontal lobe, temporal lobe, parietal lobe, occipital lobe, and posterior cingulate gyrus for each subject. A two-tissue, three-compartment model was used to estimate K(1), k(2), k(3), and k(4) between metabolite-corrected plasma and tissue time activity of [(11)C]TMSX. The binding potential (BP) was the largest in the anterior (1.25) and posterior putamen (1.20), was next largest in the head of caudate nucleus (1.05) and thalamus (1.03), and was small in the cerebral cortex, especially frontal lobe (0.46). [(11)C]TMSX PET showed the largest BP in the striatum in which A2ARs were enriched as in postmortem and nonhuman studies reported, but that the binding of [(11)C]TMSX was relatively larger in the thalamus to compare with other mammals. To date, [(11)C]TMSX is the only promising PET ligand, which is available to clinical use for mapping the A2ARs in the living human brain.
authors.affiliation: Neurological Institute, Nippon Medical School Chiba-Hokusoh Hospital, Imba-gun, Chiba-ken 270-1694, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Mishina
authors.forename: Kiichi
authors.initials: K
authors.lastname: Ishiwata
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kimura
authors.forename: Mika
authors.initials: M
authors.lastname: Naganawa
authors.forename: Keiichi
authors.initials: K
authors.lastname: Oda
authors.forename: Shiro
authors.initials: S
authors.lastname: Kobayashi
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Katayama
authors.forename: Kenji
authors.initials: K
authors.lastname: Ishii
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects*; D001931:Brain Mapping; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007700:Kinetics; D008279:Magnetic Resonance Imaging; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods*; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D013997:Time Factors; D014018:Tissue Distribution / Q000187:drug effects; D014970:Xanthines / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D002250:Carbon Radioisotopes; C405422:KF18446; D043705:Receptor, Adenosine A2A; D014970:Xanthines