title: Atherosclerotic plaque uptake of a novel integrin tracer ¹⁸F-Flotegatide in a mouse model of atherosclerosis.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Siemens Molecular Imaging, 6140 Bristol Parkway, Culver City, CA, USA.
authors.forename: Helen
authors.initials: H
authors.lastname: Su
authors.forename: Natalia
authors.initials: N
authors.lastname: Gorodny
authors.forename: Luis Felipe
authors.initials: LF
authors.lastname: Gomez
authors.forename: Umesh B
authors.initials: UB
authors.lastname: Gangadharmath
authors.forename: Fanrong
authors.initials: F
authors.lastname: Mu
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Walsh
authors.forename: Katrin
authors.initials: K
authors.lastname: Szardenings
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Berman
authors.forename: Hartmuth C
authors.initials: HC
authors.lastname: Kolb
authors.forename: Balaji K
authors.initials: BK
authors.lastname: Tamarappoo
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000000981:diagnostic imaging* / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D057054:Molecular Imaging / Q000379:methods*; D009842:Oligopeptides / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D001057:Apolipoproteins E; D015415:Biomarkers; D005462:Fluorine Radioisotopes; D039302:Integrin alphaVbeta3; D009842:Oligopeptides; D019275:Radiopharmaceuticals; C047981:arginyl-glycyl-aspartic acid