Age differences in muscarinic cholinergic receptors assayed with (+)N-[(11)C]methyl-3-piperidyl benzilate in the brains of conscious monkeys.
Age-related changes in muscarinic cholinergic receptors were evaluated with the novel ligand (+)N-[(11)C]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 [(11)C](+)3-MPB indicated a regionally specific decrease in the receptor binding in vivo determined as binding potential (BP) = k(3)/k(4) 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 (B(max)) determined by Scatchard plot analysis in vivo. In the hippocampus, although BP of [(11)C](+)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 [(11)C](+)3-MPB binding. These results demonstrate the usefulness of kinetic three-compartment model analysis of [(11)C](+)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.
Tsukada
H
H
Central Research Laboratory, Hamamatsu Photonics K. K., Hamakita, Shizuoka 434-8601, Japan. tsukada@crl.hpk.co.jp
Kakiuchi
T
T
Nishiyama
S
S
Ohba
H
H
Sato
K
K
Harada
N
N
Takahashi
K
K
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001561:Benzilates / Q000493:pharmacokinetics*; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D002250:Carbon Radioisotopes; D003243:Consciousness; D006213:Hallucinogens / Q000493:pharmacokinetics*; D006854:Hydrocortisone / Q000145:classification; D008253:Macaca mulatta; D008279:Magnetic Resonance Imaging; D008297:Male; D011869:Radioligand Assay; D011976:Receptors, Muscarinic / Q000378:metabolism*; D014055:Tomography, Emission-Computed
D001561:Benzilates; D002250:Carbon Radioisotopes; D006213:Hallucinogens; D011976:Receptors, Muscarinic; C001966:N-methyl-3-piperidyl benzilate; D006854:Hydrocortisone