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OBJECTIVE To validate an in vivo method for mapping acetylcholinesterase (AChE) activity in human brain, preparatory to monitoring inhibitor therapy in AD. BACKGROUND AChE activity is decreased in postmortem AD brain. Lacking a reliable in vivo measure, little is known about central activity in early AD, when the disease is commonly targeted by AChE(More)
N-[11C]Methylpiperidin-4-yl propionate ([11C]PMP) is a substrate for hydrolysis by acetylcholinesterase (AChE). This work evaluates kinetic analysis alternatives for estimation of relative AChE activity using dynamic positron emission tomography (PET) studies of [11C]PMP. The PET studies were performed on three groups of subjects: (1) 12 normal volunteer(More)
Although the inhibition of acetylcholinesterase remains the primary treatment of Alzheimer's disease, little is known of the results of increased acetylcholine levels on muscarinic receptor occupancy or function. Using N-(2-[18F]fluoroethyl)-4-piperidyl benzilate ([18F]FEPB), a moderate affinity (Ki = 1.7 nmol/L) nonsubtype-selective muscarinic receptor(More)
Microglial activation in crossing white matter tracts is a hallmark of noncystic periventricular leukomalacia (PVL), the leading pathology underlying cerebral palsy in prematurely born infants. Recent studies indicate that neuroinflammation within an early time window can produce long-lasting defects in oligodendroglial maturation, myelination deficit, as(More)
Two esters, N-[11C]methylpiperidyl acetate ([11C]AMP) and N-[11C]methylpiperidyl propionate ([11C]PMP), were synthesized in no-carrier-added forms and evaluated as in vivo substrates for brain acetylcholinesterase (AChE). After peripheral injection in mice, each ester showed rapid penetration into the brain and a regional retention of radioactivity(More)
There is currently great interest in developing radiolabeled substrates for acetylcholinesterase and butyrylcholinesterase that would be useful in the in vivo imaging of patients with Alzheimer's disease. Using a simple in vitro spectrophotometric assay for determination of enzymatic cleavage rates, the structure-activity relationship for a short series of(More)
The ability to study multiple physiologic processes of the brain simultaneously within the same subject would provide a new means to explore the interactions between neurotransmitter systems in vivo. Currently, examination of two distinct neuropharmacologic measures with positron emission tomography (PET) necessitates performing two separate scans spaced in(More)
There exists a spatial organization of receptive fields and a modular organization of the flexion withdrawal reflex system. However, the three dimensional location and organization of interneurons interposed in flexion reflex pathways has not been systematically examined. We determined the anatomical locations of spinal neurons involved in the hindlimb(More)
(E)-N-[(11)C]Methyl-4-(3-pyridinyl)-3-butene-1-amine ([(11)C]metanicotine), a high affinity (K(i) = 16 nM) CNS-selective nicotinic agonist, was prepared by the [(11)C]alkylation of the desmethyl precursor with [(11)C]methyl trifluoromethanesulfonate. In vivo distribution studies in mice demonstrated good blood brain permeability but essentially uniform(More)
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