title: In vivo CEST MR imaging of U87 mice brain tumor angiogenesis using targeted LipoCEST contrast agent at 7 T.
abstract: LipoCEST are liposome-encapsulating paramagnetic contrast agents (CA) based on chemical exchange saturation transfer with applications in biomolecular MRI. Their attractive features include biocompatibility, subnanomolar sensitivity, and amenability to functionalization for targeting biomarkers. We demonstrate MR imaging using a targeted lipoCEST, injected intravenously. A lipoCEST carrying Tm(III)-complexes was conjugated to RGD tripeptide (RGD-lipoCEST), to target integrin α(ν)β(3) receptors involved in tumor angiogenesis and was compared with an unconjugated lipoCEST. Brain tumors were induced in athymic nude mice by intracerebral injection of U87MG cells and were imaged at 7 T after intravenous injection of either of the two contrast agents (n = 12 for each group). Chemical exchange saturation transfer-MSME sequence was applied over 2 h with an average acquisition time interval of 13.5 min. The chemical exchange saturation transfer signal was ∼1% in the tumor and controlateral regions, and decreased to ∼0.3% after 2 h; while RGD-lipoCEST signal was ∼1.4% in the tumor region and persisted for up to 2 h. Immunohistochemical staining revealed a persistent colocalization of RGD-lipoCEST with α(ν)β(3) receptors in the tumor region. These results constitute an encouraging step toward in vivo MRI imaging of tumor angiogenesis using intravenously injected lipoCEST.
authors.affiliation: Neurospin, I2BM, Commissariat à l'Energie Atomique, Gif-sur-Yvette, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Flament
authors.forename: Françoise
authors.initials: F
authors.lastname: Geffroy
authors.forename: Christelle
authors.initials: C
authors.lastname: Medina
authors.forename: Caroline
authors.initials: C
authors.lastname: Robic
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Mayer
authors.forename: Sébastien
authors.initials: S
authors.lastname: Mériaux
authors.forename: Julien
authors.initials: J
authors.lastname: Valette
authors.forename: Philippe
authors.initials: P
authors.lastname: Robert
authors.forename: Marc
authors.initials: M
authors.lastname: Port
authors.forename: Denis
authors.initials: D
authors.lastname: Le Bihan
authors.forename: Franck
authors.initials: F
authors.lastname: Lethimonnier
authors.forename: Fawzi
authors.initials: F
authors.lastname: Boumezbeur
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000098:blood supply*; D045744:Cell Line, Tumor; D003287:Contrast Media; D008081:Liposomes; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic / Q000175:diagnosis*
chemical_list: D003287:Contrast Media; D008081:Liposomes; D058185:Magnetite Nanoparticles