Age-related alterations of serotonin (5-hydroxytryptamine; 5-HT) type 2A receptors (5-HT2A) in the living brains of young (6.0+/-1.3 years old) and aged (19.2+/-3.0 years old) monkeys (Macaca mulatta) were evaluated with [C-11]MDL100,907 in the conscious state using high-resolution positron emission tomography (PET). For quantitative analysis of 5-HT2A binding in vivo, PET scan of [C-11]MDL100,907 was performed with arterial blood sampling in each animal, and the metabolic-corrected arterial input function was used for Logan graphical analysis. Higher cerebral binding of [C-11]MDL100,907 was observed in the hippocampus, cingulate gyrus, frontal, temporal and occipital cortices, regions known to contain high densities of 5-HT2A, by in vitro assay. Binding was intermediate in the striatum and thalamus, and lower in the pens and cerebellum in both young and aged monkeys. The age-related decrease in [C-11]MDL100,907 binding to 5-HT2A receptors was prominent in the hippocampus, cingulate gyrus, frontal, temporal and occipital cortices, but not in the striatum, thalamus and pens. These observation demonstrated the usefulness of [C-11]MDL100,907 as an labeled compound for assessment of the aging process of the cortical 5-HT2A measured by PET. (C) 2000 Elsevier Science B.V. All rights reserved.