Synthesis and evaluation of ¹⁸F-labeled styryltriazole and resveratrol derivatives for β-amyloid plaque imaging

J Med Chem. 2012 Jan 26;55(2):883-92. doi: 10.1021/jm201400q. Epub 2012 Jan 11.

Abstract

In the present study, a styryltriazole and four resveratrol derivatives were synthesized as candidates for β-amyloid (Aβ) plaque imaging. On the basis of their binding affinities to Aβ(1-42) aggregates, the styryltriazole (1, K(i) = 12.8 nM) and one resveratrol derivative (5, K(i) = 0.49 nM) were labeled with (18)F. In normal mice, tissue distribution of [(18)F]5 showed good initial brain uptake (3.26% ID/g at 2 min) but slow wash-out from brains (2-to-60 min uptake ratio: 2.9). Furthermore, it underwent in vivo metabolic defluorination (1.88% ID/g at 2 min and 9.73% ID/g at 60 min). In contrast, [(18)F]1 displayed high initial brain uptake (5.38% ID/g at 2 min) with rapid wash-out from brains (0.52% ID/g at 60 min; 2-to-60 min uptake ratio: 10.3). These results indicate that [(18)F]1 has in vivo kinetics comparable to PET radiopharmaceuticals currently under commercial development, demonstrating that [(18)F]1 is a desirable PET radioligand for Aβ plaque imaging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid beta-Peptides / metabolism*
  • Aniline Compounds / chemical synthesis*
  • Aniline Compounds / chemistry
  • Aniline Compounds / pharmacokinetics
  • Animals
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Fluorine Radioisotopes
  • Male
  • Mice
  • Mice, Inbred ICR
  • Peptide Fragments / metabolism
  • Plaque, Amyloid / metabolism*
  • Radioligand Assay
  • Radionuclide Imaging
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / chemistry
  • Radiopharmaceuticals / pharmacokinetics
  • Resveratrol
  • Stereoisomerism
  • Stilbenes / chemical synthesis*
  • Stilbenes / chemistry
  • Stilbenes / pharmacokinetics
  • Structure-Activity Relationship
  • Styrenes / chemical synthesis*
  • Styrenes / chemistry
  • Styrenes / pharmacokinetics
  • Tissue Distribution
  • Triazoles / chemical synthesis*
  • Triazoles / chemistry
  • Triazoles / pharmacokinetics
  • Triazoles / pharmacology

Substances

  • 1-(2-fluoroethyl)-4-(4-N,N-dimethylaminostyryl)-1H-1,2,3-triazole
  • 1-(4-(3-fluoropropoxy)styryl)-3,5-dimethoxybenzene
  • Amyloid beta-Peptides
  • Aniline Compounds
  • Fluorine Radioisotopes
  • Peptide Fragments
  • Radiopharmaceuticals
  • Stilbenes
  • Styrenes
  • Triazoles
  • amyloid beta-protein (1-42)
  • Resveratrol