KINETIC-ANALYSIS OF REGIONAL (S)(-)C-11-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)(-)C-11-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)(-)C-11-nicotine and C-11-butanol. The uptake and time course of radioactivity in different brain regions were assessed by positron emission tomography (PET). The rate constant k(2)* was formulated by dividing the K-2 rate constant for C-11-nicotine with the K-1 rate constant for C-11-butanol and thereby minimizing the influence of CBF on the quantitated binding of C-11-nicotine. The rate constant k(2)* for C-11-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 k(2)* of C-11-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.