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

TitleRasagiline, a monoamine oxidase B inhibitor, reduces in vivo [F]THK5351 uptake in progressive supranuclear palsy.
Publication TypeJournal Article
Year of Publication2019
AuthorsNg KPin, Therriault J, Kang MSu, Struyfs H, Pascoal TA, Mathotaarachchi S, Shin M, Benedet AL, Massarweh G, Soucy J-P, Rosa-Neto P, Gauthier S
JournalNeuroimage Clin
Date Published2019

BACKGROUND: [F]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 [F]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 [F]THK5351 uptake in PSP.METHODS: Six individuals (4: PSP; 2: cognitively unimpaired, CU) underwent [F]THK5351 and [F]AZD4694 to quantify baseline tau and amyloid deposition, respectively. Following a 10-day course of 1 mg rasagiline, all participants received a post-challenge [F]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 [F]THK5351 SUV among PSP individuals were not consistent with the typical pattern of tau aggregates in PSP.CONCLUSIONS: Similar to AD, the interpretation of [F]THK5351 uptake in PSP is likely confounded by off-target binding to MAO-B binding sites. [F]THK5351 is not sufficient in quantifying tau aggregates in PSP using the proposed rasagiline dosing regimen.

Alternate JournalNeuroimage Clin
PubMed ID31795034
PubMed Central IDPMC6889764