title: Feasibility of [18F]-RGD for ex vivo imaging of atherosclerosis in detection of αvβ3 integrin expression.
abstract: BACKGROUND
  Inflammation and angiogenesis play an important role in atherosclerotic plaque rupture. Therefore, molecular imaging of these processes could be used for determination of rupture-prone atherosclerotic plaques. αvβ3 integrin is involved in the process of angiogenesis. Targeted imaging of αvβ3 integrin has been shown to be possible in previous studies on tumor models, using radiolabeled arginine-glycine-aspartate (RGD). Our aim was to investigate feasibility of ex vivo detection of αvβ3 integrin in carotid endarterectomy (CEA) specimens.
  
  
  RESULTS
  Nineteen CEA specimens were incubated in 5 MBq [18F]-RGD-K5 for 1 hour followed by 1 hour emission microPET scan. The results were quantified in 4 mm wide segments as percent incubation dose per gram (%Inc/g). Segmental-to-total ratio was calculated and presence of αvβ3 integrin and endothelial cells in each segment was confirmed by immunohistochemical staining for CD31 and αvβ3 integrin, respectively. [18F]-RGD-K5 uptake was heterogeneously distributed across CEA specimens and was localized within the vessel wall. Significant correlations were observed between segmental-to-total ratio with αvβ3 integrin staining score (r = 0.58, P = .038) and CD31 staining score (ρ = 0.67, P < .002).
  
  
  CONCLUSIONS
  This study showed the feasibility of integrin imaging by determination of αvβ3 integrin expression in human atherosclerotic plaques.
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, P.O. Box 30001, 9700 RB, Groningen, The Netherlands. reza.golestani@yale.edu.|Cardiovascular Medicine Section, Department of Internal Medicine, Yale University, New Haven, CT, USA. reza.golestani@yale.edu.
authors.forename: Reza
authors.initials: R
authors.lastname: Golestani
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, P.O. Box 30001, 9700 RB, Groningen, The Netherlands.
authors.forename: Leila
authors.initials: L
authors.lastname: Mirfeizi
authors.affiliation: Division of Vascular Surgery, Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Clark J
authors.initials: CJ
authors.lastname: Zeebregts
authors.affiliation: Department of Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Johanna
authors.initials: J
authors.lastname: Westra
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, P.O. Box 30001, 9700 RB, Groningen, The Netherlands.
authors.forename: Hans J
authors.initials: HJ
authors.lastname: de Haas
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, P.O. Box 30001, 9700 RB, Groningen, The Netherlands.
authors.forename: Andor W J M
authors.initials: AW
authors.lastname: Glaudemans
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, P.O. Box 30001, 9700 RB, Groningen, The Netherlands.
authors.forename: Michel
authors.initials: M
authors.lastname: Koole
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, P.O. Box 30001, 9700 RB, Groningen, The Netherlands.
authors.forename: Gert
authors.initials: G
authors.lastname: Luurtsema
authors.affiliation: Department of Cardiology, Thorax Center, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: René A
authors.initials: RA
authors.lastname: Tio
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, P.O. Box 30001, 9700 RB, Groningen, The Netherlands.|Department of Nuclear Medicine, Ghent University Hospital, Ghent, Belgium.
authors.forename: Rudi A J O
authors.initials: RA
authors.lastname: Dierckx
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, P.O. Box 30001, 9700 RB, Groningen, The Netherlands.|Department of Clinical and Hospital Pharmacy, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Hendrikus H
authors.initials: HH
authors.lastname: Boersma
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, P.O. Box 30001, 9700 RB, Groningen, The Netherlands.
authors.forename: Philip H
authors.initials: PH
authors.lastname: Elsinga
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Hanzeplein 1, P.O. Box 30001, 9700 RB, Groningen, The Netherlands.|Faculty of Science and Technology, Biomedical Photonic Imaging, University of Twente, Enschede, The Netherlands.
authors.forename: Riemer H J A
authors.initials: RH
authors.lastname: Slart
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D002340:Carotid Artery Diseases / Q000000981:diagnostic imaging* / Q000378:metabolism*; D005240:Feasibility Studies; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics*; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods; D057054:Molecular Imaging / Q000379:methods*; D009842:Oligopeptides / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D015415:Biomarkers; D039302:Integrin alphaVbeta3; D009842:Oligopeptides; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18; C047981:arginyl-glycyl-aspartic acid
keywords: MicroPET imaging; RGD; ex vivo; imaging; integrin; vulnerable atherosclerotic plaque