Atherosclerotic plaque uptake of a novel integrin tracer ¹⁸F-Flotegatide in a mouse model of atherosclerosis

J Nucl Cardiol. 2014 Jun;21(3):553-62. doi: 10.1007/s12350-014-9879-3. Epub 2014 Mar 14.

Abstract

Introduction: Rupture of unstable atherosclerotic plaque that leads to stroke and myocardial infarction may be induced by macrophage infiltration and neovessel formation. A tracer that selectively binds to integrin αvβ3 a protein expressed by macrophages and neovascular endothelium may identify rupture prone plaque.

Methods: (18)F-labeled "R-G-D" containing tripeptide (Flotegatide), a click chemistry derived radiotracer that binds to integrin αvβ3 was injected in ApoE knockout mice fed a high fat diet. Uptake of Flotegatide by atherosclerotic plaque was visualized by micro-PET, autoradiography, and correlated to histologic markers of inflammation and angiogenesis.

Results: We found that Flotegatide preferentially binds to aortic plaque in an ApoE knockout mouse model of atherosclerosis. The tracer's uptake is strongly associated with presence of histologic markers for macrophage infiltration and integrin expression. There is a weaker but detectable association between Flotegatide uptake and presence of an immunohistochemical marker for neovascularization.

Discussion: We hypothesize that Flotegatide may be a useful tracer for visualization of inflamed plaque in clinical subjects with atherosclerosis and may have potential for detecting vulnerable plaque.

Publication types

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

MeSH terms

  • Animals
  • Apolipoproteins E / genetics
  • Atherosclerosis / diagnostic imaging*
  • Atherosclerosis / metabolism*
  • Biomarkers / metabolism
  • Disease Models, Animal*
  • Female
  • Fluorine Radioisotopes / pharmacokinetics
  • Integrin alphaVbeta3 / metabolism*
  • Mice
  • Mice, Knockout
  • Molecular Imaging / methods*
  • Oligopeptides / pharmacokinetics*
  • Positron-Emission Tomography / methods
  • Radiopharmaceuticals / pharmacokinetics
  • Reproducibility of Results
  • Sensitivity and Specificity

Substances

  • Apolipoproteins E
  • Biomarkers
  • Fluorine Radioisotopes
  • Integrin alphaVbeta3
  • Oligopeptides
  • Radiopharmaceuticals
  • arginyl-glycyl-aspartic acid