title: PET/CT imaging of integrin αvβ3 expression in human carotid atherosclerosis.
abstract: OBJECTIVE
  The goal of this study was to evaluate the feasibility of [(18)F]Galacto-RGD positron emission tomography (PET)/computed tomography (CT) imaging of αvβ3 expression in human carotid plaques.
  
  
  BACKGROUND
  The integrin αvβ3 is expressed by macrophages and angiogenic endothelial cells in atherosclerotic lesions and thus is a marker of plaque inflammation and, potentially, of plaque vulnerability. [(18)F]Galacto-RGD is a PET tracer binding specifically to αvβ3. Therefore, [(18)F]Galacto-RGD PET/CT imaging of αvβ3 expression in human carotid plaques might provide a novel noninvasive biomarker of plaque vulnerability.
  
  
  METHODS
  [(18)F]Galacto-RGD PET/CT imaging was performed in 10 patients with high-grade carotid artery stenosis scheduled for carotid endarterectomy. Tracer uptake was measured in the stenotic areas of the carotid arteries, as well as on the contralateral side, and was corrected for blood pool activity, measured in the distal common carotid artery (target-to-background [TB] ratio). TB ratio was correlated with immunohistochemistry of αvβ3 expression (LM609), macrophage density (CD68), and microvessel density (CD31) of the surgical specimen. In addition, ex vivo autoradiography of the surgical specimen with [(18)F]Galacto-RGD and competition experiments with an unlabeled αvβ3-specific RGD peptide were performed.
  
  
  RESULTS
  [(18)F]Galacto-RGD PET/CT showed significantly higher TB ratios in stenotic areas compared with nonstenotic areas (p = 0.01). TB ratios correlated significantly with αvβ3 expression (R = 0.787, p = 0.026) and intensity of ex vivo autoradiography (R = 0.733, p = 0.038). Binding to atherosclerotic plaques was efficiently blocked in ex vivo competition experiments. A weak-to-moderate correlation was found with macrophage density (R = 0.367, p = 0.299) and microvessel density (R = 0.479, p = 0.176), which did not reach statistical significance.
  
  
  CONCLUSIONS
  [(18)F]Galacto-RGD PET/CT shows specific tracer accumulation in human atherosclerotic carotid plaques, which correlates with αvβ3 expression. Based on these initial data, larger prospective studies are now warranted to evaluate the potential of molecular imaging of αvβ3 expression for assessment of plaque inflammation in patients.
authors.affiliation: Department of Nuclear Medicine, Technische Universität München, Munich, Germany. Electronic address: ambros.beer@tum.de.
authors.forename: Ambros J
authors.initials: AJ
authors.lastname: Beer
authors.affiliation: Department of Vascular Surgery, Technische Universität München, Munich, Germany.
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Pelisek
authors.affiliation: Department of Vascular Surgery, Technische Universität München, Munich, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Heider
authors.affiliation: Turku PET Centre and Department of Cardiology, Turku, Finland.
authors.forename: Antti
authors.initials: A
authors.lastname: Saraste
authors.affiliation: Department of Vascular Surgery, Technische Universität München, Munich, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Reeps
authors.affiliation: Department of Radiology, Technische Universität München, Munich, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Metz
authors.affiliation: Department of Pathology, Helmholtz Zentrum München, Neuherberg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Seidl
authors.affiliation: Institute for Advanced Study and Center of Integrated Protein Science, Technische Universität München, Department Chemie, Garching, Germany; Chemistry Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
authors.forename: Horst
authors.initials: H
authors.lastname: Kessler
authors.affiliation: Chair of Pharmaceutical Radiochemistry, Technische Universität München, Garching, Germany.
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Wester
authors.affiliation: Department of Vascular Surgery, Technische Universität München, Munich, Germany.
authors.forename: Hans Henning
authors.initials: HH
authors.lastname: Eckstein
authors.affiliation: Department of Nuclear Medicine, Technische Universität München, Munich, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Schwaiger
mesh_terms: D000368:Aged; D001345:Autoradiography; D015415:Biomarkers / Q000032:analysis; D002339:Carotid Arteries / Q000737:chemistry / Q000000981:diagnostic imaging; D002340:Carotid Artery Diseases / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000378:metabolism; D005240:Feasibility Studies; D005260:Female; D005690:Galactose / Q000031:analogs & derivatives; D006801:Humans; D007150:Immunohistochemistry; D039302:Integrin alphaVbeta3 / Q000032:analysis*; D008264:Macrophages / Q000737:chemistry / Q000000981:diagnostic imaging; D008297:Male; D055806:Microvessels / Q000737:chemistry / Q000000981:diagnostic imaging; D008875:Middle Aged; D057054:Molecular Imaging / Q000379:methods*; D064847:Multimodal Imaging / Q000379:methods*; D010456:Peptides, Cyclic; D049268:Positron-Emission Tomography; D011237:Predictive Value of Tests; D019275:Radiopharmaceuticals; D012720:Severity of Illness Index; D014057:Tomography, X-Ray Computed; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D039302:Integrin alphaVbeta3; D010456:Peptides, Cyclic; D019275:Radiopharmaceuticals; C423503:fluorogalacto-RGD; D005690:Galactose
keywords: biomarker; carotid stenosis; imaging; molecular imaging; plaque