Quantitative measurement of cerebral acetylcholinesterase using [C-11]physostigmine and positron emission tomography

[C-11]physostigmine. an acetylcholinesterase inhibitor, has been shown to b e a promising positron emission tomography ligand to quantify the cerebral concentration of the enzyme in animals and humans in vivo. Here, a quantita tive and noninvasive method to measure the regional acetylcholinesterase as e concentration in the brain is presented. The method is based on the obser vation that the ratio between regions rich in acetylcholinesterase and whit e matter, a region almost entirely deprived of this enzyme, was found to be come approximately constant after 20 to 30 minutes, suggesting that at late time points the uptake mainly contains information about the distribution volume. Taking the white matter as the reference region, a simplified refer ence tissue model, with effectively one reversible tissue compartment and t hree parameters, was found to give a good description of the data in baboon s. One of these parameters. the ratio between the total distribution volume s in the target and reference regions, showed a satisfactory correlation wi th the acetylcholinesterase concentration measured postmortem in two baboon brains. Eight healthy male subjects were also analyzed and the regional en zyme concentrations obtained again showed a good correlation with the known acetylcholinesterase concentrations measured in postmortem studies of huma n brain.