[(18)F]-labeled isoindol-1-one and isoindol-1,3-dione derivatives as potential PET imaging agents for detection of beta-amyloid fibrils

Bioorg Med Chem Lett. 2008 Oct 15;18(20):5701-4. doi: 10.1016/j.bmcl.2008.05.019. Epub 2008 May 7.

Abstract

In this study a novel series of isoindol-1-one and isoindol-1,3-dione derivatives for beta-amyloid-specific binding agents is described. Twelve compounds were synthesized and evaluated via a competitive binding assay with [(125)I]TZDM against beta-amyloid 1-42 (Abeta42) aggregates. Two new [(18)F]-labeled isoindole derivatives were synthesized and evaluated as potential beta-amyloid imaging probes based on the in vivo pharmacokinetic profiles. The preliminary results suggest that these [(18)F]18b and [(18)F]18c are promising positron emission tomography (PET) imaging probes for studying accumulation of Abeta fibrils in the brains of Alzheimer's disease (AD) patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid / chemistry*
  • Amyloid beta-Peptides / chemistry*
  • Animals
  • Binding, Competitive
  • Brain / drug effects
  • Chemistry, Pharmaceutical / methods*
  • Drug Design
  • Fluorine Radioisotopes / pharmacology*
  • Humans
  • Isoindoles / chemistry*
  • Kinetics
  • Mice
  • Models, Chemical
  • Plaque, Amyloid / drug effects
  • Positron-Emission Tomography / instrumentation*
  • Positron-Emission Tomography / methods

Substances

  • Amyloid
  • Amyloid beta-Peptides
  • Fluorine Radioisotopes
  • Isoindoles