11C-labelled PIB analogues as potential tracer agents for in vivo imaging of amyloid beta in Alzheimer's disease

Eur J Med Chem. 2009 Apr;44(4):1415-26. doi: 10.1016/j.ejmech.2008.09.038. Epub 2008 Oct 7.

Abstract

Pittsburgh Compound-B (PIB) is currently being evaluated clinically for in vivo visualization of amyloid plaques in patients with Alzheimer's disease (AD). We have synthesized three structural isomers of 6-hydroxy-2-(4'-aminophenyl)-1,3-benzothiazole, performed radiolabelling with carbon-11 and investigated their in vivo and in vitro properties. Specific binding to amyloid plaques was demonstrated in vitro using post-mortem brain homogenates of AD patients, transgenic AD mice brain sections and post-mortem human AD brain sections. In normal mice, initial brain uptake (at 2 min p.i.) was high and was followed by a fast wash-out. The three structural analogues have a high potential as tracer agents for in vivo visualization of amyloid plaques in AD patients.

MeSH terms

  • Alzheimer Disease / metabolism*
  • Amyloid beta-Peptides / analysis*
  • Amyloid beta-Peptides / metabolism
  • Aniline Compounds / chemical synthesis
  • Aniline Compounds / chemistry*
  • Aniline Compounds / metabolism
  • Animals
  • Benzothiazoles / chemistry
  • Benzothiazoles / metabolism
  • Brain / metabolism
  • Carbon Radioisotopes / chemistry
  • Fluorine Radioisotopes / chemistry
  • Humans
  • Hydroxides / chemistry
  • Isomerism
  • Mice
  • Radioactive Tracers
  • Staining and Labeling
  • Thiazoles / chemical synthesis
  • Thiazoles / chemistry*
  • Thiazoles / metabolism

Substances

  • 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
  • Amyloid beta-Peptides
  • Aniline Compounds
  • Benzothiazoles
  • Carbon Radioisotopes
  • Fluorine Radioisotopes
  • Hydroxides
  • Radioactive Tracers
  • Thiazoles
  • hydroxide ion
  • benzothiazole