title: αVβ3 integrin-targeted microSPECT/CT imaging of inflamed atherosclerotic plaques in mice.
abstract: BACKGROUND
  αVβ3-integrin is expressed by activated endothelial cells and macrophages in atherosclerotic plaques and may represent a valuable marker of high-risk plaques. We evaluated (99m)Tc-maraciclatide, an integrin-specific tracer, for imaging vascular inflammation in atherosclerotic lesions in mice.
  
  
  METHODS
  Apolipoprotein E-negative (ApoE(-/-)) mice on a Western diet (n = 10) and normally fed adult C57BL/6 control mice (n = 4) were injected with (99m)Tc-maraciclatide (51.8 ± 3.7 MBq). A blocking peptide was infused in three ApoE(-/-) mice; this condition served as another control. After 90 min, the animals were imaged via single-photon emission computed tomography (SPECT). While maintained in the same position, the mice were transferred to computed tomography (CT) to obtain contrast-enhanced images of the aortic arch. Images from both modalities were fused, and signal was quantified in the aortic arch and in the vena cava for subtraction of blood-pool activity. The aorta was carefully dissected after imaging for gamma counting, autoradiography, and histology.
  
  
  RESULTS
  Tracer uptake was significantly higher in ApoE(-/-) mice than in both groups of control mice (1.56 ± 0.33 vs. 0.82 ± 0.24 vs. 0.98 ± 0.11, respectively; P = 0.006). Furthermore, higher tracer activity was detected via gamma counting in the aorta of hypercholesterolemic mice than in both groups of control mice (1.52 ± 0.43 vs. 0.78 ± 0.19 vs. 0.47 ± 0.31 (99m)Tc-maraciclatide %ID/g, respectively; P = 0.018). Autoradiography showed significantly higher tracer uptake in the atherosclerotic aorta than in the control aorta (P = 0.026). Finally, in the atherosclerotic aorta, immunostaining indicated that the integrin signal came predominantly from macrophages and was correlated with the macrophage CD68 immunomarker (r = 0.73).
  
  
  CONCLUSIONS
  (99m)Tc-maraciclatide allows in vivo detection of inflamed atherosclerotic plaques in mice and may represent a non-invasive approach for identifying high-risk plaques in patients.
authors.affiliation: Pôle de Recherche Cardiovasculaire (CARD), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, Brussels, Belgium. david.vancraeynest@uclouvain.be.|Division of Cardiology, Cliniques Universitaires St-Luc, Avenue Hippocrate, 10-2881, B-1200, Brussels, Belgium. david.vancraeynest@uclouvain.be.
authors.forename: David
authors.initials: D
authors.lastname: Vancraeynest
authors.affiliation: Pôle d'Imagerie Médicale, Radiothérapie et Oncologie (MIRO), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Véronique
authors.initials: V
authors.lastname: Roelants
authors.affiliation: IREC Imaging Platform, Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Caroline
authors.initials: C
authors.lastname: Bouzin
authors.affiliation: Pôle d'Imagerie Médicale, Radiothérapie et Oncologie (MIRO), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, Brussels, Belgium.
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Hanin
authors.affiliation: Pôle d'Imagerie Médicale, Radiothérapie et Oncologie (MIRO), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Stephan
authors.initials: S
authors.lastname: Walrand
authors.affiliation: Pôle d'Imagerie Médicale, Radiothérapie et Oncologie (MIRO), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Vanesa
authors.initials: V
authors.lastname: Bol
authors.affiliation: Pôle d'Imagerie Médicale, Radiothérapie et Oncologie (MIRO), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, Brussels, Belgium.
authors.forename: Anne
authors.initials: A
authors.lastname: Bol
authors.affiliation: Pôle de Recherche Cardiovasculaire (CARD), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, Brussels, Belgium.|Division of Cardiology, Cliniques Universitaires St-Luc, Avenue Hippocrate, 10-2881, B-1200, Brussels, Belgium.
authors.forename: Anne-Catherine
authors.initials: AC
authors.lastname: Pouleur
authors.affiliation: Pôle de Recherche Cardiovasculaire (CARD), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, Brussels, Belgium.|Division of Cardiology, Cliniques Universitaires St-Luc, Avenue Hippocrate, 10-2881, B-1200, Brussels, Belgium.
authors.forename: Agnès
authors.initials: A
authors.lastname: Pasquet
authors.affiliation: Pôle de Recherche Cardiovasculaire (CARD), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, Brussels, Belgium.|Division of Cardiology, Cliniques Universitaires St-Luc, Avenue Hippocrate, 10-2881, B-1200, Brussels, Belgium.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Gerber
authors.affiliation: INSERM UMR_S 1166, Integrative Biology of Atherosclerosis Team, Université Pierre et Marie Curie-Paris6 and institute of Cardiometabolism and Nutrition (ICAN), Pitié-Salpêtrière Hospital, 75013, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Lesnik
authors.affiliation: INSERM UMR_S 1166, Integrative Biology of Atherosclerosis Team, Université Pierre et Marie Curie-Paris6 and institute of Cardiometabolism and Nutrition (ICAN), Pitié-Salpêtrière Hospital, 75013, Paris, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Huby
authors.affiliation: Pôle d'Imagerie Médicale, Radiothérapie et Oncologie (MIRO), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, Brussels, Belgium.
authors.forename: François
authors.initials: F
authors.lastname: Jamar
authors.affiliation: Pôle de Recherche Cardiovasculaire (CARD), Institut de Recherche Expérimentale et Clinique (IREC), Université Catholique de Louvain, Brussels, Belgium.|Division of Cardiology, Cliniques Universitaires St-Luc, Avenue Hippocrate, 10-2881, B-1200, Brussels, Belgium.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Vanoverschelde
keywords: Maraciclatide; SPECT imaging; Vulnerable atherosclerotic plaque; αVβ3 integrin