title: Small unilamellar vesicles: a platform technology for molecular imaging of brain tumors.
abstract: Molecular imaging enables the non-invasive investigation of cellular and molecular processes. Although there are challenges to overcome, the development of targeted contrast agents to increase the sensitivity of molecular imaging techniques is essential for their clinical translation. In this study, spontaneously forming, small unilamellar vesicles (sULVs) (30 nm diameter) were used as a platform to build a bimodal (i.e., optical and magnetic resonance imaging (MRI)) targeted contrast agent for the molecular imaging of brain tumors. sULVs were loaded with a gadolinium (Gd) chelated lipid (Gd-DPTA-BOA), functionalized with targeting antibodies (anti-EGFR monoclonal and anti-IGFBP7 single domain), and incorporated a near infrared dye (Cy5.5). The resultant sULVs were characterized in vitro using small angle neutron scattering (SANS), phantom MRI and dynamic light scattering (DLS). Antibody targeted and nontargeted Gd loaded sULVs labeled with Cy5.5 were assessed in vivo in a brain tumor model in mice using time domain optical imaging and MRI. The results demonstrated that a spontaneously forming, nanosized ULVs loaded with a high payload of Gd can selectively target and image, using MR and optical imaging, brain tumor vessels when functionalized with anti-IGFBP7 single domain antibodies. The unique features of these targeted sULVs make them promising molecular MRI contrast agents.
authors: Institute for Biological Sciences, National Research Council of Canada, Ottawa, ON, Canada.
authors: Umar
authors: U
authors: Iqbal
authors: Homam
authors: H
authors: Albaghdadi
authors: Mu-Ping
authors: MP
authors: Nieh
authors: Ursula I
authors: UI
authors: Tuor
authors: Zoltan
authors: Z
authors: Mester
authors: Danica
authors: D
authors: Stanimirovic
authors: John
authors: J
authors: Katsaras
authors: Abedelnasser
authors: A
authors: Abulrob
mesh_terms: D000818:Animals; D000906:Antibodies / Q000737:chemistry; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002614:Chelating Agents / Q000494:pharmacology; D003287:Contrast Media / Q000494:pharmacology; D003952:Diagnostic Imaging / Q000379:methods*; D005682:Gadolinium; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins / Q000737:chemistry; D008027:Light; D008055:Lipids / Q000737:chemistry; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice; D004369:Pentetic Acid / Q000494:pharmacology; D019047:Phantoms, Imaging; D012542:Scattering, Radiation
chemical_list: D000906:Antibodies; D002614:Chelating Agents; D003287:Contrast Media; D018969:Insulin-Like Growth Factor Binding Proteins; D008055:Lipids; C102529:insulin-like growth factor binding protein-related protein 1; D004369:Pentetic Acid; D005682:Gadolinium