title: Anti-amyloid-β-mediated positron emission tomography imaging in Alzheimer's disease mouse brains.
abstract: Antibody-mediated imaging of amyloid β (Aβ) in Alzheimer's disease (AD) offers a promising strategy to detect and monitor specific Aβ species, such as oligomers, that have important pathological and therapeutic relevance. The major current limitation of antibodies as a diagnostic and imaging device is poor blood-brain-barrier permeability. A classical anti-Aβ antibody, 6E10, is modified with 10 kDa polyethylene glycol (PEG) and a positron emitting isotope, Copper-64 (t(½) = 12.7 h), and intravenously delivered to the TgCRND8 mouse model of Alzheimer's disease. Modification of 6E10 with PEG (6E10-PEG) increases accumulation of 6E10 in brain tissue in both TgCRND8 and wild type control animals. 6E10-PEG differentiates TgCRND8 animals from wild type controls using positron emission tomography (PET) and provides a framework for using antibodies to detect pathology using non-invasive medical imaging techniques.
authors.affiliation: Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: McLean
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Cooke
authors.forename: Yuanfei
authors.initials: Y
authors.lastname: Wang
authors.forename: David
authors.initials: D
authors.lastname: Green
authors.forename: Paul E
authors.initials: PE
authors.lastname: Fraser
authors.forename: Peter St
authors.initials: PS
authors.lastname: George-Hyslop
authors.forename: Molly S
authors.initials: MS
authors.lastname: Shoichet
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D000906:Antibodies / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D001812:Blood-Brain Barrier / Q000473:pathology; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D009997:Osmotic Pressure; D049268:Positron-Emission Tomography; D011485:Protein Binding; D011817:Rabbits
chemical_list: D016229:Amyloid beta-Peptides; D000906:Antibodies; D007074:Immunoglobulin G