A novel 18F-labeled pyridyl benzofuran derivative for imaging of β-amyloid plaques in Alzheimer's brains

Bioorg Med Chem Lett. 2010 Oct 15;20(20):6141-4. doi: 10.1016/j.bmcl.2010.08.016. Epub 2010 Aug 8.

Abstract

A potential probe for PET targeting β-amyloid plaques in Alzheimer's disease (AD) brain, FPYBF-1 (5-(5-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)benzofuran-2-yl)-N,N-dimethylpyridin-2-amine), was synthesized and evaluated. In experiments in vitro, FPYBF-1 displayed high affinity for Aβ(1-42) aggregates (K(i)=0.9 nM), and substantial labeling of β-amyloid plaques in sections of postmortem AD brains but not control brains. In experiments in vivo, [(18)F]FPYBF-1 displayed good initial uptake (5.16%ID/g at 2 min postinjection) and rapid washout from the brain (2.44%ID/g at 60 min postinjection) in normal mice, and excellent binding to β-amyloid plaques in a murine model of AD. Furthermore, the specific labeling of plaques labeling was observed in autoradiographs of autopsied AD brain sections. [(18)F]FPYBF-1 may be a useful probe for imaging β-amyloid plaques in living brain tissue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / diagnostic imaging*
  • Amyloid beta-Peptides / analysis
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Autopsy
  • Autoradiography
  • Benzofurans* / chemistry
  • Brain / diagnostic imaging*
  • Brain / pathology
  • Fluorine Radioisotopes* / chemistry
  • Humans
  • Male
  • Mice
  • Mice, Transgenic
  • Plaque, Amyloid / diagnostic imaging*
  • Positron-Emission Tomography / methods*
  • Radiopharmaceuticals* / chemistry

Substances

  • Amyloid beta-Peptides
  • Benzofurans
  • Fluorine Radioisotopes
  • Radiopharmaceuticals
  • benzofuran