Quantitative measurement of cerebral acetylcholinesterase using.
[11C]physostigmine, an acetylcholinesterase inhibitor, has been shown to be a promising positron emission tomography ligand to quantify the cerebral concentration of the enzyme in animals and humans in vivo. Here, a quantitative and noninvasive method to measure the regional acetylcholinesterase concentration in the brain is presented. The method is based on the observation that the ratio between regions rich in acetylcholinesterase and white matter, a region almost entirely deprived of this enzyme, was found to become 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 reference tissue model, with effectively one reversible tissue compartment and three parameters, was found to give a good description of the data in baboons. One of these parameters, the ratio between the total distribution volumes in the target and reference regions, showed a satisfactory correlation with the acetylcholinesterase concentration measured postmortem in two baboon brains. Eight healthy male subjects were also analyzed and the regional enzyme concentrations obtained again showed a good correlation with the known acetylcholinesterase concentrations measured in postmortem studies of human brain.
Blomqvist
G
G
INSERM U334, Service Hospitalier Frédéric Joliot, Orsay, France.
Tavitian
B
B
Pappata
S
S
Crouzel
C
C
Jobert
A
A
Doignon
I
I
Di Giamberardino
L
L
D000110:Acetylcholinesterase / Q000032:analysis* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000818:Animals; D001665:Binding Sites; D001812:Blood-Brain Barrier; D001921:Brain / Q000201:enzymology*; D002250:Carbon Radioisotopes; D002540:Cerebral Cortex / Q000201:enzymology; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010215:Papio; D010830:Physostigmine / Q000008:administration & dosage / Q000378:metabolism; D011149:Pons / Q000201:enzymology; D011699:Putamen / Q000201:enzymology; D013702:Temporal Lobe / Q000201:enzymology; D013788:Thalamus / Q000201:enzymology; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
D002250:Carbon Radioisotopes; D002800:Cholinesterase Inhibitors; D010830:Physostigmine; D000110:Acetylcholinesterase