Novel ¹⁸F-labeled dibenzylideneacetone derivatives as potential positron emission tomography probes for in vivo imaging of β-amyloid plaques

Eur J Med Chem. 2014 Sep 12:84:628-38. doi: 10.1016/j.ejmech.2014.07.070. Epub 2014 Jul 21.

Abstract

A series of dibenzylideneacetones were synthesized and evaluated as imaging probes for β-amyloid plaques. They displayed high binding affinity to Aβ(1-42) aggregates (K(i) = 6.4 for 8, K(i) = 3.0 for 9), and the high binding were confirmed by in vitro autoradiography with AD human and transgenic mouse brain sections. Two of them were selected for (18)F-labeling directly on the benzene ring. In biodistribution experiments, [(18)F]8 and [(18)F]9 displayed high initial uptakes (9.29 ± 0.41 and 5.38 ± 0.68% ID/g) and rapid washouts from the normal brain (brain(2 min)/brain(60 min) ratios of 21.6 and 13.4). These preliminary results suggest that [(18)F]8 and [(18)F]9 may be used as potential PET imaging agents for the detection of Aβ plaques in the brain.

Keywords: AD; Aβ plaques; Dibenzylideneacetone derivatives; PET imaging agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / analysis
  • Amyloid beta-Peptides / metabolism*
  • Animals
  • Brain / metabolism
  • Brain / pathology
  • Fluorescent Dyes / chemical synthesis
  • Fluorescent Dyes / chemistry
  • Fluorine Radioisotopes
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Molecular Imaging*
  • Molecular Structure
  • Pentanones* / chemical synthesis
  • Pentanones* / chemistry
  • Peptide Fragments / analysis
  • Peptide Fragments / metabolism*
  • Positron-Emission Tomography*
  • Staining and Labeling

Substances

  • Amyloid beta-Peptides
  • Fluorescent Dyes
  • Fluorine Radioisotopes
  • Pentanones
  • Peptide Fragments
  • amyloid beta-protein (1-42)