title: Specific somatostatin receptor II expression in arterial plaque: (68)Ga-DOTATATE autoradiographic, immunohistochemical and flow cytometric studies in apoE-deficient mice.
abstract: BACKGROUND
  The rupture of atherosclerotic plaques is triggered by inflammation. Specific detection of inflammation is therefore the focus of many investigations. Noninvasive imaging methods, such as positron emission tomography (PET), also are suited for this purpose. (68)Ga-DOTATATE is a (68)Ga-labeled radiotracer with specific affinity to somatostatin receptor subtype-2 (SSTR-2). SSTR-2 was found specifically expressed on human macrophages/monocytes.
  
  
  OBJECTIVE
  We aimed to confirm the distribution of SSTR-2 in inflammatory plaques, and to assess its co-localization with macrophages within the plaques. We also assessed (68)Ga-DOTATATE uptakes in plaques by autoradiography.
  
  
  METHODS
  Apolipoprotein E (ApoE)-/- mice on a high-cholesterol diet were injected with (68)Ga-DOTATATE. The animals were sacrificed and aorta sections were examined using autoradiography and immunohistochemistry. Furthermore, expression of SSTR-2 was analyzed by flow cytometry. Western blot was conducted to assess SSTR-2 regulation in basal and lipopolysaccharide (LPS)-activated state. To evaluate the specificity of the (68)Ga-DOTATATE, the sections were pre-incubated with monoclonal SSTR-2 antibody before autoradiography.
  
  
  RESULTS
  Autoradiographic imaging showed uptake of (68)Ga-DOTATATE co-localized with the macrophage-rich plaques by immunohistochemical examination. A high expression of SSTR-2 on macrophages was found by flow cytometry and western blot. Stimulation with lipopolysaccharide did not alter expression of SSTR-2 in macrophages.
  
  
  CONCLUSIONS
  Due to its specific binding to macrophages, (68)Ga-DOTATATE might be a suitable radiotracer for the evaluation of inflammatory activity in unstable plaques.
authors: Department of Nuclear Medicine, University of Wuerzburg, Germany.
authors: Xiang
authors: X
authors: Li
authors: Wolfgang
authors: W
authors: Bauer
authors: Michael C
authors: MC
authors: Kreissl
authors: Johannes
authors: J
authors: Weirather
authors: Elisabeth
authors: E
authors: Bauer
authors: Ina
authors: I
authors: Israel
authors: Dominik
authors: D
authors: Richter
authors: Gabriele
authors: G
authors: Riehl
authors: Andreas
authors: A
authors: Buck
authors: Samuel
authors: S
authors: Samnick
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis; D002469:Cell Separation; D005260:Female; D005434:Flow Cytometry; D005710:Gallium Radioisotopes / Q000737:chemistry*; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D007249:Inflammation; D008264:Macrophages / Q000166:cytology; D051379:Mice; D008822:Mice, Transgenic; D009000:Monocytes / Q000166:cytology; D058226:Plaque, Atherosclerotic / Q000378:metabolism*; D049268:Positron-Emission Tomography; D017481:Receptors, Somatostatin / Q000235:genetics / Q000378:metabolism*
chemical_list: D001057:Apolipoproteins E; D005710:Gallium Radioisotopes; D017481:Receptors, Somatostatin; C492049:Sstr2 protein, mouse
keywords: (68)Ga-DOTATATE; Atherosclerosis; Autoradiography; Inflammation; Somatostatin receptor subtype2