Age differences in muscarinic cholinergic receptors assayed with (+)N-[11C]methyl-3-piperidyl benzilate in the brains of conscious monkeys

Abstract

Age-related changes in muscarinic cholinergic receptors were evaluated with the novel ligand (+)N-[11C]methyl-3-piperidyl benzilate ((+)3-MPB) in the living brains of young (5.9 ± 1.8 years old) and aged (19.0 ± 3.3 years old) monkeys (Macaca mulatta) in the conscious state using high-resolution positron emission tomography (PET). For quantitative analysis of receptor binding in vivo, metabolite-corrected arterial plasma radioactivity curves were obtained as an input function into the brain, and kinetic analyses using the three-compartment model and graphical Logan plot analysis were applied. Kinetic analyses of [11C](+)3-MPB indicated a regionally specific decrease in the receptor binding in vivo determined as binding potential (BP) = k3/k4 in aged animals compared with young animals. Thus, the frontal and temporal cortices as well as the striatum showed age-related reduction of muscarinic cholinergic receptors in vivo, reflecting the reduced receptor density (Bmax) determined by Scatchard plot analysis in vivo. In the hippocampus, although BP of [11C](+)3-MPB indicated no significant age-related changes, it showed an inverse correlation with individual cortisol levels in plasma. When the graphical Logan plot analysis was applied, all regions assayed showed significant age-related decrease of [11C](+)3-MPB binding. These results demonstrate the usefulness of kinetic three-compartment model analysis of [11C](+)3-MPB with metabolite-corrected arterial plasma input as an indicator for the aging process of the cortical muscarinic cholinergic receptors in vivo as measured by PET. © 2001 Wiley-Liss, Inc.