IMPY, a potential beta-amyloid imaging probe for detection of prion deposits in scrapie-infected mice

Nucl Med Biol. 2008 Feb;35(2):197-201. doi: 10.1016/j.nucmedbio.2007.10.005. Epub 2007 Dec 20.

Abstract

Introduction: A potential single-photon emission computed tomography imaging agent for labeling of A beta plaques of Alzheimer's disease, IMPY (2-(4'-dimethylaminophenyl)-6-iodo-imidazo[1,2-a]pyridine), would be effective in detection of prion amyloid deposits in transmissible spongiform encephalopathies (TSEs).

Methods: In vitro autoradiographic studies were carried out with [125 I]IMPY on brain sections from scrapie-infected mice and age-matched controls. Competition study was performed to evaluate the prion deposit binding specificity with nonradioactive IMPY.

Results: Binding of [125 I]IMPY was observed in infected brain sections, while on age-matched control brain sections, there was no or very low labeling. Prion deposit binding was confirmed by histoblots with prion protein-specific monoclonal antibody 2D6. In the presence of nonradioactive IMPY, the binding of [125 I]IMPY was significantly inhibited in all regions studied.

Conclusions: These findings indicate that IMPY can detect the prion deposits in vitro in scrapie-infected mice. Labeled with 123 I, this ligand may be useful to quantitate prion deposit burdens in TSEs by in vivo imaging.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / pathology
  • Amyloid beta-Peptides / chemistry*
  • Animals
  • Antibodies, Monoclonal / chemistry
  • Autoradiography
  • Binding, Competitive
  • Brain / diagnostic imaging
  • Brain / pathology
  • Disease Models, Animal
  • Humans
  • Iodine Radioisotopes / pharmacokinetics
  • Isotope Labeling / methods*
  • Mice
  • Plaque, Amyloid / diagnostic imaging*
  • Plaque, Amyloid / pathology
  • Prions / chemistry*
  • Pyrazoles / pharmacokinetics*
  • Radionuclide Imaging
  • Radiopharmaceuticals / pharmacokinetics
  • Scrapie / diagnostic imaging*
  • Scrapie / pathology

Substances

  • Amyloid beta-Peptides
  • Antibodies, Monoclonal
  • Iodine Radioisotopes
  • Prions
  • Pyrazoles
  • Radiopharmaceuticals
  • 2,3-dihydro-1H-imidazo(1,2-b)pyrazole