Molecular imaging of atherosclerotic plaques with technetium-99m-labelled antisense oligonucleotides

Eur J Nucl Med Mol Imaging. 2005 Jan;32(1):6-14. doi: 10.1007/s00259-004-1700-0. Epub 2004 Nov 26.

Abstract

Purpose: The purpose of this study was to visualise experimental atherosclerotic lesions using radiolabelled antisense oligonucleotides (ASONs).

Methods: Atherosclerosis was induced in New Zealand White rabbits fed 1% cholesterol for approximately 60 days. In vivo and ex vivo imaging was performed in atherosclerotic rabbits and normal control rabbits after i.v. injection of 92.5+/-18.5 MBq (99m)Tc-labelled ASON or (99m)Tc-labelled sense oligonucleotides. Immediately after the in vivo imaging, the animals were sacrificed and ex vivo imaging of the aortic specimens was performed. Biodistribution of radiolabelled c-myc ASON was evaluated in vivo in atherosclerotic rabbits.

Results: Planar imaging revealed accumulation of (99m)Tc-labelled c-myc ASON in atherosclerotic lesions along the artery wall. Ex vivo imaging further demonstrated that the area of activity accumulation matched the area of atherosclerotic lesions. In contrast, no atherosclerotic lesions were found in the vessel wall and no positive imaging results were obtained in animals of the control group.

Conclusion: This molecular imaging approach has potential for non-invasive imaging of atherosclerotic plaques at an early stage.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arteriosclerosis / diagnostic imaging*
  • Arteriosclerosis / metabolism*
  • Genes, myc / genetics
  • Male
  • Metabolic Clearance Rate
  • Molecular Biology / methods
  • Oligonucleotides, Antisense / genetics
  • Oligonucleotides, Antisense / pharmacokinetics*
  • Organ Specificity
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Rabbits
  • Radionuclide Imaging
  • Radiopharmaceuticals / pharmacokinetics
  • Technetium / pharmacokinetics*
  • Tissue Distribution

Substances

  • Oligonucleotides, Antisense
  • Proto-Oncogene Proteins c-myc
  • Radiopharmaceuticals
  • Technetium