Development and evaluation of [18F]Flotaza for Aβ plaque imaging in postmortem human Alzheimer's disease brain

Bioorg Med Chem Lett. 2021 Aug 15:46:128164. doi: 10.1016/j.bmcl.2021.128164. Epub 2021 Jun 1.

Abstract

Positron emission tomographic (PET) studies of amyloid β (Aβ) accumulation in Alzheimer's disease (AD) have shown clinical utility. The aim of this study was to develop and evaluate the effectiveness of a new fluorine-18 radiotracer [18F]Flotaza (2-{2-[2-[18F]fluoroethoxy]ethoxy}ethoxy)-4'-N,N-dimethylaminoazobenzene), for Aβ plaque imaging. Nucleophilic [18F]fluoride was used in a one-step radiosynthesis for [18F]flotaza. Using post mortem human AD brain tissues consisting of anterior cingulate (AC) and corpus callosum (CC), binding affinity of Flotaza, Ki = 1.68 nM for human Aβ plaques and weak (>10-5 M) for Tau protein. Radiosynthesis of [18F]Flotaza was very efficient in high radiochemical yields (>25%) with specific activities >74 GBq/μmol. Brain slices from all AD subjects were positively immunostained with anti-Aβ. Ratio of [18F]Flotaza in gray matter AC to white matter CC was >100 in all the 6 subjects. Very little white matter binding was seen. [18F]Flotaza binding in AC strongly correlated with anti-Aβ immunostains. [18F]Flotaza is therefore a suitable fluorine-18 PET radiotracer for PET imaging studies of human Aβ plaques.

Keywords: Alzheimer’s disease; Human Aβ plaques; PET imaging; [(18)F]Flotaza.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / diagnosis*
  • Alzheimer Disease / metabolism
  • Brain / diagnostic imaging*
  • Drug Development*
  • Humans
  • Molecular Structure
  • Plaque, Amyloid / chemistry*
  • Positron-Emission Tomography