Evaluation of distribution of adenosine A2A receptors in normal human brain measured with [11C]TMSX PET

被引:52
作者
Mishina, Masahiro
Ishiwata, Kiichi
Kimura, Yuichi
Naganawa, Mika
Oda, Keiichi
Kobayashi, Shiro
Katayama, Yasuo
Ishii, Kenji
机构
[1] Chiba Hokusoh Hosp, Nippon Med Sch, Neurol Inst, Imba, Chiba 2701694, Japan
[2] Tokyo Metropolitan Inst Gerontol, Positron Med Ctr, Itabashi Ku, Tokyo 1730022, Japan
[3] Nippon Med Sch, Dept Internal Med 2, Bunkyo Ku, Tokyo 1138602, Japan
关键词
adenosine A(2A) receptor; positron emission tomography; (11)C]TMSX; human brain; Parkinson's disease;
D O I
10.1002/syn.20423
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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. (c) 2007 Wiley-Liss, Inc.
引用
收藏
页码:778 / 784
页数:7
相关论文
共 38 条
[11]   Parametric imaging of ligand-receptor binding in PET using a simplified reference region model [J].
Gunn, RN ;
Lammertsma, AA ;
Hume, SP ;
Cunningham, VJ .
NEUROIMAGE, 1997, 6 (04) :279-287
[12]   Randomized trial of the adenosine A2A receptor antagonist istradefylline in advanced PD [J].
Hauser, RA ;
Hubble, JP ;
Truong, DD .
NEUROLOGY, 2003, 61 (03) :297-303
[13]   First visualization of adenosine A2A receptors in the human brain by positron emission tomography with [11C]TMSX [J].
Ishiwata, K ;
Mishina, M ;
Kimura, Y ;
Oda, K ;
Sasaki, T ;
Ishii, K .
SYNAPSE, 2005, 55 (02) :133-136
[14]   Further characterization of a CNS adenosine A2a receptor ligand [11C]KF18446 with in vitro autoradiography and in vivo tissue uptake [J].
Ishiwata, K ;
Ogi, N ;
Shimada, J ;
Nonaka, H ;
Tanaka, A ;
Suzuki, F ;
Senda, M .
ANNALS OF NUCLEAR MEDICINE, 2000, 14 (02) :81-89
[15]   Preclinical studies on [11C]TMSX for mapping adenosine A2A receptors by positron emission tomography [J].
Ishiwata, K ;
Wang, WF ;
Kimura, Y ;
Kawamura, K ;
Ishii, K .
ANNALS OF NUCLEAR MEDICINE, 2003, 17 (03) :205-211
[16]   Adenosine A2A receptor imaging with [11C]KF18446 PET in the rat brain after quinolinic acid lesion:: Comparison with the dopamine receptor imaging [J].
Ishiwata, K ;
Ogi, N ;
Hayakawa, N ;
Oda, K ;
Nagaoka, T ;
Toyama, H ;
Suzuki, F ;
Endo, K ;
Tanaka, A ;
Senda, M .
ANNALS OF NUCLEAR MEDICINE, 2002, 16 (07) :467-475
[17]   Synthesis and preliminary evaluation of [C-11]KF17837, a selective adenosine A(2A) antagonist [J].
Ishiwata, K ;
Noguchi, J ;
Toyama, H ;
Sakiyama, Y ;
Koike, N ;
Ishii, S ;
Oda, K ;
Endo, K ;
Suzuki, F ;
Senda, M .
APPLIED RADIATION AND ISOTOPES, 1996, 47 (5-6) :507-511
[18]  
Ishiwata K, 2000, J NUCL MED, V41, P345
[19]   New aspects of physiological and pathophysiological functions of adenosine A2A receptor in basal ganglia [J].
Kase, H .
BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY, 2001, 65 (07) :1447-1457
[20]   An increase of sigma1 receptors in the aged monkey brain [J].
Kawamura, K ;
Kimura, Y ;
Tsukada, H ;
Kobayashi, T ;
Nishiyama, S ;
Kakiuchi, T ;
Ohba, H ;
Harada, N ;
Matsuno, K ;
Ishii, K ;
Ishiwata, K .
NEUROBIOLOGY OF AGING, 2003, 24 (05) :745-752