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

Adenosine A2A receptor (A2AR) is thought to interact with dopamine D2 receptor. Selective A2AR antagonists have attracted attention as the treatment of Parkinson\u27s disease. In this study, we investigated the distribution of the A2ARs in the living human brain using positron emission tomography (PET) and [7-methyl-11C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([11C]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 K1, k2, k3, and k4 between metabolite-corrected plasma and tissue time activity of [11C]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). [11C]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 [11C]TMSX was relatively larger in the thalamus to compare with other mammals. To date, [11C]TMSX is the only promising PET ligand, which is available to clinical use for mapping the A2ARs in the living human brain

Aging effect on adenosine A1 receptors in human putamen -A MPDX PET study-

16th Annual Meeting of the Organization for Human Brain Mapping 201

Low density of sigma1 receptors in early Alzheimer\u27s disease

Objective: The sigma1 receptor is considered to be involved in cognitive function. A postmortem study reported that the sigma1 receptors were reduced in the hippocampus in Alzheimer\u27s disease (AD). However, in vivo imaging of sigma1 receptors in the brain of AD patients has not been reported. The aim of this study is to investigate the mapping of sigma1 receptors in AD using [11C]SA4503 positron emission tomography (PET). Methods: We studied fi ve AD patients and seven elderly volunteers. A dynamic series of decay-corrected PET data acquisition was performed for 90 min starting at the time of the injection of 500 MBq of [11C]SA4503. A twotissue three-compartment model was used to estimate K1, k2, k3, k4, and the delay between metabolite-corrected plasma and tissue time activity using a Gauss-Newton algorithm. The ratio of k3 to k4 was computed as the binding potential (BP), which is linearly related to the density of sigma1 receptors. Unpaired t tests were used to compare K1 and BP in patients with AD and normal subjects.Results: As compared with normals, BP in the AD was signifi cantly lower in the frontal, temporal, and occipital lobe, cerebellum and thalamus, whereas K1 was signifi - cantly lower in the parietal lobe.Conclusions: [11C]SA4503 PET can demonstrate that the density of cerebral and cerebellar sigma1 receptors is reduced in early AD