Binding of the PET radiotracer [¹⁸F]BF227 does not reflect the presence of alpha-synuclein aggregates in transgenic mice

Curr Alzheimer Res. 2014;11(10):955-60. doi: 10.2174/1567205011666141107154201.

Abstract

Alpha-synuclein (α-syn) aggregation is a neuropathological hallmark of many neurodegenerative diseases, collectively termed synucleinopathies. There is currently no pre-mortem diagnosis tool for these diseases. Although some compounds have been described as potential ligands for α-syn aggregates, no specific PET radiotracer of aggregated α-syn is currently available. Recently, [(18)F]BF227 has been proposed as an α-syn PET radiotracer in the absence of other specific candidates. We proposed here, for the first time, to use this radiotracer in an accelerated mouse model of synucleinopathy presenting α-syn depositions in brainstem and thalamus. Our in vivo and in vitro studies showed that [(18)F]BF227 does not bind to α-syn aggregates. These results highlight the fact that [(18)F]BF227 PET has no suitable characteristics for monitoring this experimental synucleinopathy, justifying the need to develop alternative α-syn PET radiotracers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzoxazoles* / chemistry
  • Brain Stem / diagnostic imaging
  • Brain Stem / pathology
  • Disease Models, Animal
  • Fluorodeoxyglucose F18*
  • Humans
  • Magnetic Resonance Imaging
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mutation / genetics
  • Positron-Emission Tomography*
  • Radioligand Assay
  • Tauopathies / diagnostic imaging*
  • Tauopathies / genetics
  • Thalamus / diagnostic imaging
  • Thalamus / pathology
  • Thiazoles* / chemistry
  • alpha-Synuclein / genetics
  • alpha-Synuclein / metabolism*

Substances

  • 2-(2-(2-dimethylaminothiazol-5-yl)ethenyl)-6-(2-(fluoro)ethoxy)benzoxazole
  • Benzoxazoles
  • Thiazoles
  • alpha-Synuclein
  • Fluorodeoxyglucose F18