| Autor: |
Drake LR; Department of Medicinal Chemistry , University of Michigan , Ann Arbor , Michigan 48109 , United States., Pham JM; Department of Radiology , University of Michigan , Ann Arbor , Michigan 48109 , United States., Desmond TJ; Department of Radiology , University of Michigan , Ann Arbor , Michigan 48109 , United States., Mossine AV; Department of Radiology , University of Michigan , Ann Arbor , Michigan 48109 , United States., Lee SJ; Department of Radiology , University of Michigan , Ann Arbor , Michigan 48109 , United States., Kilbourn MR; Department of Radiology , University of Michigan , Ann Arbor , Michigan 48109 , United States., Koeppe RA; Department of Radiology , University of Michigan , Ann Arbor , Michigan 48109 , United States., Brooks AF; Department of Radiology , University of Michigan , Ann Arbor , Michigan 48109 , United States., Scott PJH; Department of Medicinal Chemistry , University of Michigan , Ann Arbor , Michigan 48109 , United States.; Department of Radiology , University of Michigan , Ann Arbor , Michigan 48109 , United States. |
| Abstrakt: |
[ 18 F]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 [ 18 F]AV-1451 and MAO through (i) enzyme inhibition assays, (ii) autoradiography with postmortem tissue samples, and (iii) nonhuman primate PET imaging. We confirm that [ 18 F]AV-1451 is a weak inhibitor of MAO-A and -B and that MAO inhibitors can alter binding of [ 18 F]AV-1451 in autoradiography and in vivo PET imaging. |
