期刊
ACS CHEMICAL NEUROSCIENCE
卷 10, 期 8, 页码 3839-3846出版社
AMER CHEMICAL SOC
DOI: 10.1021/acschemneuro.9b00326
关键词
positron emission tomography (PET) imaging; tau PET; Alzheimer's disease; monoamine oxidase (MAO); flortaucipir
资金
- NIH (NIGMS: Pharmacological Sciences Training Program) [T32-GM07767]
- MICH-R Pilot Grant [UL1TR002240]
[F-18]AV-1451 is one of the most widely used radiotracers for positron emission tomography (PET) imaging of tau protein aggregates in neurodegenerative disorders. While the radiotracer binds with high affinity to tau neurofibrillary tangles, extensive clinical studies have simultaneously revealed off-target tracer accumulation in areas of low tau burden such as the basal ganglia and choroid plexus. Though there are a number of possible reasons for this accumulation, it is often attributed to off-target binding to monoamine oxidase (MAO). In this paper, we investigate the association between [F-18]AV-1451 and MAO through (i) enzyme inhibition assays, (ii) autoradiography with postmortem tissue samples, and (iii) nonhuman primate PET imaging. We confirm that [F-18]AV-1451 is a weak inhibitor of MAO-A and -B and that MAO inhibitors can alter binding of [F-18]AV-1451 in autoradiography and in vivo PET imaging.
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