title: A Novel Liposomal Nanoparticle for the Imaging of Amyloid Plaque by Magnetic Resonance Imaging.
abstract: Amyloid binding molecules with greater hydrophilicity than existing ligands were synthesized. The lead candidate ET6-21 bound amyloid fibrils, and amyloid deposits in dog brain and human brain tissue ex vivo. The ligand was used to prepare novel amyloid-targeted liposomal nanoparticles. The preparation was tested in the Tg2576 and TetO/APP mouse models of amyloid deposition. Gd chelates and Indocyanine green were included in the particles for visualization by MRI and near-infrared microscopy. Upon intravenous injection, the particles successfully traversed the blood-brain barrier in these mice, and bound to the plaques. Magnetic resonance imaging (T1-MRI) conducted 4 days after injection demonstrated elevated signal in the brains of mice with amyloid plaques present. No signal was observed in amyloid-negative mice, or in amyloid-positive mice injected with an untargeted version of the same agent. The MRI results were confirmed by immunohistochemical and fluorescent microscopic examination of mouse brain sections, showing colocalization of the fluorescent tags and amyloid deposits.
authors.affiliation: Texas Children's Hospital, Houston, TX, USA.|Baylor College of Medicine, Houston, TX, USA.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Tanifum
authors.affiliation: Texas Children's Hospital, Houston, TX, USA.|Baylor College of Medicine, Houston, TX, USA.
authors.forename: Ketan
authors.initials: K
authors.lastname: Ghaghada
authors.affiliation: University of Houston, Houston, TX, USA.
authors.forename: Craig
authors.initials: C
authors.lastname: Vollert
authors.affiliation: University of Kentucky, Lexington, KY, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Head
authors.affiliation: University of Houston, Houston, TX, USA.
authors.forename: Jason L
authors.initials: JL
authors.lastname: Eriksen
authors.affiliation: Texas Children's Hospital, Houston, TX, USA.|Baylor College of Medicine, Houston, TX, USA.
authors.forename: Ananth
authors.initials: A
authors.lastname: Annapragada
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging; D008081:Liposomes / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D053758:Nanoparticles / Q000378:metabolism*; D059906:Neuroimaging / Q000379:methods; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging*
chemical_list: D008081:Liposomes
keywords: Alzheimer’s disease; amyloid angiopathy; amyloid plaque; gadolinium; imaging; liposome; magnetic resonance imaging; molecular imaging; nanoparticle