Molecular imaging of inflammation in the ApoE -/- mouse model of atherosclerosis with IodoDPA

Biochem Biophys Res Commun. 2015 May 22;461(1):70-5. doi: 10.1016/j.bbrc.2015.03.171. Epub 2015 Apr 6.

Abstract

Background: Atherosclerosis is a common and serious vascular disease predisposing individuals to myocardial infarction and stroke. Intravascular plaques, the pathologic lesions of atherosclerosis, are largely composed of cholesterol-laden luminal macrophage-rich infiltrates within a fibrous cap. The ability to detect those macrophages non-invasively within the aorta, carotid artery and other vessels would allow physicians to determine plaque burden, aiding management of patients with atherosclerosis.

Methods and results: We previously developed a low-molecular-weight imaging agent, [(125)I]iodo-DPA-713 (iodoDPA), which selectively targets macrophages. Here we use it to detect both intravascular macrophages and macrophage infiltrates within the myocardium in the ApoE -/- mouse model of atherosclerosis using single photon emission computed tomography (SPECT). SPECT data were confirmed by echocardiography, near-infrared fluorescence imaging and histology. SPECT images showed focal uptake of radiotracer at the aortic root in all ApoE -/- mice, while the age-matched controls were nearly devoid of radiotracer uptake. Focal radiotracer uptake along the descending aorta and within the myocardium was also observed in affected animals.

Conclusions: IodoDPA is a promising new imaging agent for atherosclerosis, with specificity for the macrophage component of the lesions involved.

Keywords: Arteriosclerosis; Coronary artery disease; Macrophages; TSPO imaging; oxLDL.

Publication types

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

MeSH terms

  • Acetamides / pharmacokinetics*
  • Animals
  • Apolipoproteins E / genetics
  • Atherosclerosis / diagnostic imaging*
  • Atherosclerosis / metabolism*
  • Macrophages / diagnostic imaging*
  • Macrophages / metabolism*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Molecular Imaging / methods*
  • Pyrimidines / pharmacokinetics*
  • Radiopharmaceuticals / pharmacokinetics
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Tomography, Emission-Computed, Single-Photon / methods
  • Vasculitis / diagnostic imaging
  • Vasculitis / metabolism

Substances

  • Acetamides
  • Apolipoproteins E
  • Pyrimidines
  • Radiopharmaceuticals
  • N,N-diethyl-2-(2-(3-iodo-4-methoxyphenyl)-5,7-dimethylpyrazolo(1,5-a)pyrimidin-3-yl)acetamide