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Neuroimage Clin. 2019;24:102091. doi: 10.1016/j.nicl.2019.102091. Epub 2019 Nov 13.

Rasagiline, a monoamine oxidase B inhibitor, reduces in vivo [18F]THK5351 uptake in progressive supranuclear palsy.

Author information

1
Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, 6825 Boulevard LaSalle, Verdun, Montreal, QC H4H 1R3, Canada; Alzheimer's Disease Research Unit, Douglas Hospital, McGill University, Montreal, Canada; Department of Neurology, National Neuroscience Institute, Singapore.
2
Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, 6825 Boulevard LaSalle, Verdun, Montreal, QC H4H 1R3, Canada; Alzheimer's Disease Research Unit, Douglas Hospital, McGill University, Montreal, Canada.
3
Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, 6825 Boulevard LaSalle, Verdun, Montreal, QC H4H 1R3, Canada; Reference Center for Biological Markers of Dementia (BIODEM), University of Antwerp, Antwerp, Belgium.
4
McConnell Brain Imaging Centre, McGill University, 3801 University Street, Montreal, Québec H3A 2B4, Canada.
5
Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, 6825 Boulevard LaSalle, Verdun, Montreal, QC H4H 1R3, Canada; Alzheimer's Disease Research Unit, Douglas Hospital, McGill University, Montreal, Canada; Montreal Neurological Institute, 3801 University Street, Montreal, Québec H3A 2B4, Canada; Department of Neurology and Neurosurgery, McGill University, 3801 University Street, Montreal, Québec H3A 2B4, Canada.
6
Translational Neuroimaging Laboratory, The McGill University Research Centre for Studies in Aging, 6825 Boulevard LaSalle, Verdun, Montreal, QC H4H 1R3, Canada; Alzheimer's Disease Research Unit, Douglas Hospital, McGill University, Montreal, Canada. Electronic address: serge.gauthier@mcgill.ca.

Abstract

BACKGROUND:

[18F]THK5351 is a tau positron emission tomography tracer that has shown promise in quantifying tau distribution in tauopathies such as Alzheimer's disease (AD) and progressive supranuclear palsy (PSP). However, the interpretation of [18F]THK5351 uptake has been shown to be confounded by high monoamine oxidase B (MAO-B) availability across the brain in AD.

OBJECTIVES:

To test the hypothesis that the MAO-B inhibitor, rasagiline reduces [18F]THK5351 uptake in PSP.

METHODS:

Six individuals (4: PSP; 2: cognitively unimpaired, CU) underwent [18F]THK5351 and [18F]AZD4694 to quantify baseline tau and amyloid deposition, respectively. Following a 10-day course of 1 mg rasagiline, all participants received a post-challenge [18F]THK5351 scan. The baseline and post-rasagiline challenge standardized uptake value (SUV) were generated normalized for patient weight and injected radioactivity.

RESULTS:

The post-rasagiline regional SUV was reduced on average by 69-89% in PSP, and 53-81% in CU. The distributions of post-rasagiline [18F]THK5351 SUV among PSP individuals were not consistent with the typical pattern of tau aggregates in PSP.

CONCLUSIONS:

Similar to AD, the interpretation of [18F]THK5351 uptake in PSP is likely confounded by off-target binding to MAO-B binding sites. [18F]THK5351 is not sufficient in quantifying tau aggregates in PSP using the proposed rasagiline dosing regimen.

KEYWORDS:

Monoamine oxidase-B; Positron emission tomography; Progressive Supranuclear Palsy; Rasagiline; [(18)F]THK5351 tau tracer

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