Technetium-99m labeled pyridyl benzofuran derivatives as single photon emission computed tomography imaging probes for β-amyloid plaques in Alzheimer's brains

J Med Chem. 2012 Mar 8;55(5):2279-86. doi: 10.1021/jm201513c. Epub 2012 Feb 24.

Abstract

Three novel (99m)Tc-labeled pyridyl benzofuran derivatives were tested as potential probes for imaging β-amyloid plaques using single photon emission computed tomography (SPECT). The (99m)Tc and corresponding rhenium complexes were synthesized with bis(aminoethanethiol) (BAT) as a chelating ligand. All Re complexes showed affinity for Aβ(1-42) aggregates (K(i) = 13.6-149.6 nM). Biodistribution experiments in normal mice revealed that the (99m)Tc-labeled derivatives displayed sufficient uptake in the brain (1.41-1.80% ID/g at 2 min postinjection). Notably, [(99m)Tc]BAT-Bp-2 showed a good initial uptake (1.80% ID/g at 2 min) and a reasonable washout from the brain (0.79% ID/g at 60 min). Ex vivo autoradiography with [(99m)Tc]BAT-Bp-2 revealed substantial labeling of β-amyloid plaques in sections of brain tissue from Tg2576 transgenic mice but not in the age-matched controls. [(99m)Tc]BAT-Bp-2 may be a potential SPECT probe for imaging β-amyloid plaques in Alzheimer's brains.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / diagnostic imaging*
  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides / metabolism
  • Animals
  • Benzofurans / chemical synthesis*
  • Benzofurans / chemistry
  • Benzofurans / pharmacokinetics
  • Brain / diagnostic imaging*
  • Brain / metabolism
  • Chelating Agents / chemical synthesis
  • Chelating Agents / chemistry
  • Coordination Complexes / chemical synthesis*
  • Coordination Complexes / chemistry
  • Coordination Complexes / pharmacokinetics
  • Mice
  • Mice, Transgenic
  • Molecular Imaging
  • Plaque, Amyloid / diagnostic imaging*
  • Plaque, Amyloid / metabolism
  • Pyridines / chemical synthesis*
  • Pyridines / chemistry
  • Pyridines / pharmacokinetics
  • Radiopharmaceuticals / chemical synthesis*
  • Radiopharmaceuticals / chemistry
  • Radiopharmaceuticals / pharmacokinetics
  • Rhenium
  • Structure-Activity Relationship
  • Technetium*
  • Tissue Distribution
  • Tomography, Emission-Computed, Single-Photon

Substances

  • Amyloid beta-Peptides
  • Benzofurans
  • Chelating Agents
  • Coordination Complexes
  • Pyridines
  • Radiopharmaceuticals
  • Rhenium
  • Technetium