Age-related reduction of [11C]MDL100,907 binding to central 5-HT(2A) receptors: PET study in the conscious monkey brain.
Age-related alterations of serotonin (5-hydroxytryptamine; 5-HT) type 2A receptors (5-HT(2A)) 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 [11C]MDL100,907 in the conscious state using high-resolution positron emission tomography (PET). For quantitative analysis of 5-HT(2A) binding in vivo, PET scan of [11C]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 [11C]MDL100, 907 was observed in the hippocampus, cingulate gyrus, frontal, temporal and occipital cortices, regions known to contain high densities of 5-HT(2A), by in vitro assay. Binding was intermediate in the striatum and thalamus, and lower in the pons and cerebellum in both young and aged monkeys. The age-related decrease in [11C]MDL100,907 binding to 5-HT(2A) receptors was prominent in the hippocampus, cingulate gyrus, frontal, temporal and occipital cortices, but not in the striatum, thalamus and pons. These observation demonstrated the usefulness of [11C]MDL100,907 as an labeled compound for assessment of the aging process of the cortical 5-HT(2A) measured by PET.
Kakiuchi
T
T
Central Research Laboratory, Hamamatsu Photonics K.K., 5000 Hirakuchi, Hamakita, 434-8601, Shizuoka, Japan.
Nishiyama
S
S
Sato
K
K
Ohba
H
H
Nakanishi
S
S
Tsukada
H
H
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D002250:Carbon Radioisotopes; D005464:Fluorobenzenes / Q000378:metabolism*; D008253:Macaca mulatta; D008297:Male; D010880:Piperidines / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000378:metabolism*; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
D002250:Carbon Radioisotopes; D005464:Fluorobenzenes; D010880:Piperidines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C079049:volinanserin