Kinetic analysis of regional (S)(-)11C-nicotine binding in normal and Alzheimer brains--in vivo assessment using positron emission tomography.
A compartment model has been developed and validated for the kinetic analysis of (S)(-)11C-nicotine binding in the brain including a compensation for the influence of regional cerebral blood flow (rCBF). The model was applied to eight patients with Alzheimer disease (AD) and three age-matched healthy volunteers who received intravenous injections of (S)(-)11C-nicotine and 11C-butanol. The uptake and time course of radioactivity in different brain regions were assessed by positron emission tomography (PET). The rate constant k2* was formulated by dividing the K2 rate constant for 11C-nicotine with the K1 rate constant for 11C-butanol and thereby minimizing the influence of CBF on the quantitated binding of 11C-nicotine. The rate constant k2* for 11C-nicotine giving a quantitative measure of binding in the brain tissue was significantly higher in the temporal and frontal cortices as well as in the hippocampus of AD brains as compared with controls, indicating deficits in specific nicotinic binding in these brain areas of AD patients. A significant and negative correlation was obtained between cognitive function (Mini-Mental State Examination) and k2* of 11C-nicotine in the temporal and frontal cortices as well as in the hippocampus. The described kinetic model allowed in vivo quantification of nicotinic receptor binding in brain, which will be of importance in the future for evaluation of diagnosis, progress of disease, as well as the therapeutic effects in the treatment of AD.
Nordberg
A
A
Department of Clinical Neuroscience and Family Medicine, Karolinska Institute, Huddinge University Hospital, Sweden.
Lundqvist
H
H
Hartvig
P
P
Lilja
A
A
Långström
B
B
D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000235:genetics / Q000503:physiopathology; D001783:Blood Flow Velocity / Q000502:physiology; D001921:Brain / Q000000981:diagnostic imaging* / Q000503:physiopathology; D005260:Female; D005625:Frontal Lobe / Q000000981:diagnostic imaging / Q000503:physiopathology; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000493:pharmacokinetics*; D011978:Receptors, Nicotinic / Q000235:genetics / Q000502:physiology*; D012016:Reference Values; D012039:Regional Blood Flow / Q000502:physiology; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology*; D013702:Temporal Lobe / Q000000981:diagnostic imaging / Q000503:physiopathology; D014055:Tomography, Emission-Computed
D011978:Receptors, Nicotinic; D009538:Nicotine