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PET imaging of brain acetylcholinesterase using [ 11 C]CP‐126,998, a brain selective enzyme inhibitor
Author(s) -
Bencherif B.,
Endres C.J.,
Musachio J.L.,
Villalobos A.,
Hilton J.,
Scheffel U.,
Dannals R.F.,
Williams S.,
Frost J.J.
Publication year - 2002
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.10072
Subject(s) - acetylcholinesterase , donepezil , hippocampus , aché , basal ganglia , thalamus , cerebellum , chemistry , cholinergic , amygdala , medicine , endocrinology , neuroscience , central nervous system , enzyme , psychology , biochemistry , disease , dementia
PET and [ 11 C]CP‐126,998, an N ‐benzylpiperidinebenzisoxazole, were used to image brain acetylcholinesterase (AChE) distribution in healthy controls before and after administration of 5 mg donepezil p.o., a reversible AChE inhibitor. Logan plots were used to compute distribution volumes ( V T ). The V T of [ 11 C]CP‐126,998 was highest in the basal ganglia and cerebellum and lowest in the cerebral cortex, thalamus, amygdala, and hippocampus. The regional V T values correlated well with AChE concentration measured in vitro. Donepezil, given 4 h before PET scanning, induced a substantial inhibition of [ 11 C]CP‐126,998 binding (43–62%) in all brain regions when compared to the baseline PET study. The results of this study indicate that PET imaging of [ 11 C]CP‐126,998 may be useful in quantifying the distribution of regional brain AChE. This new PET radiotracer may potentially be employed in the diagnosis and treatment of patients with disorders of cholinergic neurotransmission, such as Alzheimer's disease. Synapse 45:1–9, 2002. © 2002 Wiley‐Liss, Inc.