Low density of sigma1 receptors in early Alzheimer’s disease

• Published in: Annals of nuclear medicine Vol. 22; no. 3; pp. 151 - 156
• Main Authors: Mishina, Masahiro, Ohyama, Masashi, Ishii, Kenji, Kitamura, Shin, Kimura, Yuichi, Oda, Kei-ichi, Kawamura, Kazunori, Sasaki, Toru, Kobayashi, Shiro, Katayama, Yasuo, Ishiwata, Kiichi
• Format: Journal Article
• Language: English
• Published: Japan Springer Japan 01.04.2008; Springer Nature B.V
• Subjects: Aged; Alzheimer Disease - diagnostic imaging; Alzheimer Disease - pathology; Alzheimer's disease; Brain Chemistry; Carbon Radioisotopes - pharmacokinetics; Cerebellum - diagnostic imaging; Cerebellum - pathology; Cerebral Cortex - diagnostic imaging; Cerebral Cortex - pathology; Female; Humans; Imaging; Male; Medicine; Medicine & Public Health; Nuclear Medicine; Original Article; Piperazines - pharmacokinetics; Positron-Emission Tomography; Radiology; Radiopharmaceuticals - pharmacokinetics; Receptors, sigma - analysis; Receptors, sigma - chemistry; Thalamus - diagnostic imaging; Thalamus - pathology; Tissue Distribution; Cerebellum; receptor; Alzheimer’s disease; Positron emission tomography; Sigma; Cortex
• ISSN: 0914-7187; 1864-6433
• DOI: 10.1007/s12149-007-0094-z

Objective The sigma 1 receptor is considered to be involved in cognitive function. A postmortem study reported that the sigma 1 receptors were reduced in the hippocampus in Alzheimer’s disease (AD). However, in vivo imaging of sigma 1 receptors in the brain of AD patients has not been reported. The aim of this study is to investigate the mapping of sigma 1 receptors in AD using [ 11 C]SA4503 positron emission tomography (PET). Methods We studied five 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 [ 11 C]SA4503. A two-tissue three-compartment model was used to estimate K 1 , k 2 , k 3 , k 4 , and the delay between metabolite-corrected plasma and tissue time activity using a Gauss-Newton algorithm. The ratio of k 3 to k 4 was computed as the binding potential (BP), which is linearly related to the density of sigma 1 receptors. Unpaired t tests were used to compare K 1 and BP in patients with AD and normal subjects. Results As compared with normals, BP in the AD was significantly lower in the frontal, temporal, and occipital lobe, cerebellum and thalamus, whereas K 1 was significantly lower in the parietal lobe. Conclusions [ 11 C]SA4503 PET can demonstrate that the density of cerebral and cerebellar sigma 1 receptors is reduced in early AD.