Measurement of Acetylcholinesterase(AChE)Activity in Living Brain by Positron Emission Tomography(PET).
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Accession number;99A1042712
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| Title;Measurement of Acetylcholinesterase(AChE)Activity in Living Brain by Positron Emission Tomography(PET). |
| Author;
IRIE TOSHIAKI
(National Inst. of Radiological Sciences)
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Journal Title;NIRS-M (Natl Inst Radiol Sci)
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Journal Code:Z0881A
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ISSN:
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VOL.;NO.132;PAGE.23-31(1999)
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| Figure&Table&Reference;FIG.5, TBL.1, REF.11 |
| Pub. Country;Japan |
| Language;Japanese |
| Abstract;Central cholinergic neuronal system has been known to be related to learning and memory, and its deficit is found in the brain of Alzheimer's disease(AD) and other degenerative disorders. Postmortem studies have shown that acetylcholinesterase(AChE), one of biochemical markers of central cholinergic nerve system, is consistently reduced in the cerebral cortex of patients with Alzheimer's disease(AD). Non-invasive mapping and/or measuring AChE activity in the living brain by positron emission tomography(PET) would be a useful tool for assessment of cholinergic dysfunction in AD and other disorders, and provide a direct method for validation of therapeutic efficacy of drugs, AChE inhibitors. We have challenged to measure AChE activity using tracers of subustrate type, radiolabeled acetylcholine analogs, which are lipophilic enough to go across blood brain barrier and are metabolically trapped by AChE in the brain. The analogs designed, N-methylpiperidyl esters, were evaluated in terms of their metabolic rate and specificity against AChE. Studies examining the response to AChE activity showed metabolic accumulation of some analogs responded well to changes in cortical AChE activity in an animal model of AD. The study was further applied to living human by PET using [11C]N-methylpiperidyl-4-acetate (MP4A), which was chosen on the basis of its reactivity and specificity suitable for the human cortical AChE. Regional cerebral metabolic rate of MP4A reflecting AChE activity was quantitatively determined using three compartment model analysis of dynamic PET data and the arterial input function obtained by TLC-radioluminography of plasma samples. The kinetic analyses showed that AChE activities estimated were well agree with those of postmortem examination in cerebral cortices and thalamus in healthy subjects, and that there was significant reduction of cortical AChE activity in patients with AD.... (author abst.) |
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