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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aminopyridines / metabolism*
  • Benzofurans / metabolism
  • Female
  • Humans
  • Hydrocarbons, Fluorinated / metabolism
  • Indans / pharmacology*
  • Male
  • Monoamine Oxidase / metabolism*
  • Monoamine Oxidase Inhibitors / pharmacology*
  • Neurofibrillary Tangles / metabolism*
  • Positron-Emission Tomography
  • Quinolines / metabolism*
  • Radiopharmaceuticals / metabolism*
  • Supranuclear Palsy, Progressive / diagnostic imaging*
  • tau Proteins / metabolism*

Substances

  • AZD4694
  • Aminopyridines
  • Benzofurans
  • Hydrocarbons, Fluorinated
  • Indans
  • Monoamine Oxidase Inhibitors
  • Quinolines
  • Radiopharmaceuticals
  • THK5351
  • tau Proteins
  • rasagiline
  • Monoamine Oxidase