title: Nanoparticles functionalised with an anti-platelet human antibody for in vivo detection of atherosclerotic plaque by magnetic resonance imaging.
abstract: Atherosclerosis is an inflammatory disease associated with the formation of atheroma plaques likely to rupture in which platelets are involved both in atherogenesis and atherothrombosis. The rupture is linked to the molecular composition of vulnerable plaques, causing acute cardiovascular events. In this study we propose an original targeted contrast agent for molecular imaging of atherosclerosis. Versatile USPIO (VUSPIO) nanoparticles, enhancing contrast in MR imaging, were functionalised with a recombinant human IgG4 antibody, rIgG4 TEG4, targeting human activated platelets. The maintenance of immunoreactivity of the targeted VUSPIO against platelets was confirmed in vitro by flow cytometry, transmission electronic and optical microscopy. In the atherosclerotic ApoE(-/-) mouse model, high-resolution ex vivo MRI demonstrated the selective binding of TEG4-VUSPIO on atheroma plaques. It is noteworthy that the rationale for targeting platelets within atherosclerotic lesions is highlighted by our targeted contrast agent using a human anti-αIIbβ3 antibody as a targeting moiety.
  
  
  BACKGROUND
  Current clinical assessment of atherosclerotic plagues is suboptimal. The authors in the article designed functionalized superparamagnetic iron oxide nanoparticles with TEG4, a recombinant human antibody, to target activated platelets. By using MRI, these nanoparticles can be utilized to study the process of atheroma pathogenesis.
authors: CNRS, UMR5536, CRMSB, Centre de Résonance Magnétique des Systèmes Biologiques, Université Bordeaux, Bordeaux, France; Plateforme Technologique et d'Innovation Biomédicale, Pessac, France.
authors: Marie-Josée
authors: MJ
authors: Jacobin-Valat
authors: CNRS, UMR5536, CRMSB, Centre de Résonance Magnétique des Systèmes Biologiques, Université Bordeaux, Bordeaux, France; Plateforme Technologique et d'Innovation Biomédicale, Pessac, France.
authors: Jeanny
authors: J
authors: Laroche-Traineau
authors: CNRS, UMR5536, CRMSB, Centre de Résonance Magnétique des Systèmes Biologiques, Université Bordeaux, Bordeaux, France; Plateforme Technologique et d'Innovation Biomédicale, Pessac, France.
authors: Mélusine
authors: M
authors: Larivière
authors: CNRS, UPR9048, Université de Bordeaux, Institut de Chimie de la Matière Condensée de Bordeaux, Pessac, France.
authors: Stéphane
authors: S
authors: Mornet
authors: CNRS, UMR5536, CRMSB, Centre de Résonance Magnétique des Systèmes Biologiques, Université Bordeaux, Bordeaux, France; Plateforme Technologique et d'Innovation Biomédicale, Pessac, France.
authors: Stéphane
authors: S
authors: Sanchez
authors: CNRS, UMR5536, CRMSB, Centre de Résonance Magnétique des Systèmes Biologiques, Université Bordeaux, Bordeaux, France.
authors: Marc
authors: M
authors: Biran
authors: CNRS, UPS3044, "Baculovirus et thérapie", St Christol-Les-Alez, France.
authors: Caroline
authors: C
authors: Lebaron
authors: CNRS, UPR9048, Université de Bordeaux, Institut de Chimie de la Matière Condensée de Bordeaux, Pessac, France.
authors: Julien
authors: J
authors: Boudon
authors: Bordeaux Imaging Center, Université Bordeaux, Bordeaux, France.
authors: Sabrina
authors: S
authors: Lacomme
authors: CNRS, UPS3044, "Baculovirus et thérapie", St Christol-Les-Alez, France.
authors: Martine
authors: M
authors: Cérutti
authors: CNRS, UMR5536, CRMSB, Centre de Résonance Magnétique des Systèmes Biologiques, Université Bordeaux, Bordeaux, France; Plateforme Technologique et d'Innovation Biomédicale, Pessac, France. Electronic address: gisele.clofent-sanchez@rmsb.u-bordeaux2.fr.
authors: Gisèle
authors: G
authors: Clofent-Sanchez
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000494:pharmacology*; D001792:Blood Platelets; D003287:Contrast Media / Q000737:chemistry / Q000494:pharmacology*; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D057054:Molecular Imaging / Q000379:methods*; D053758:Nanoparticles / Q000737:chemistry*; D058226:Plaque, Atherosclerotic / Q000378:metabolism / Q000473:pathology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex
chemical_list: D000911:Antibodies, Monoclonal; D003287:Contrast Media; D019039:Platelet Glycoprotein GPIIb-IIIa Complex
keywords: Atherosclerosis; Human antibody; MRI contrast agents; Nanoparticles; Platelets