title: Positron emission tomography imaging of fibrillar parenchymal and vascular amyloid-β in TgCRND8 mice.
abstract: Few quantitative diagnostic and monitoring, tools are available to clinicians treating patients with Alzheimer's disease. Further, many of the promising quantitative imaging tools under development lack clear specificity toward different types of Amyloid-β (Aβ) pathology such as vascular or oligomeric species. Antibodies offer an opportunity to image specific types of Aβ pathology because of their excellent specificity. In this study, we developed a method to translate a panel of anti-Aβ antibodies, which show excellent histological performance, into live animal imaging contrast agents. In the TgCRND8 mouse model of Alzheimer's disease, we tested two antibodies, M64 and M116, that target parenchyma aggregated Aβ plaques and one antibody, M31, that targets vascular Aβ. All three antibodies were administered intravenously after labeling with both poly(ethylene glycol) to enhance circulation and (64)Cu to allow detection via positron emission tomography (PET) imaging. We were clearly able to differentiate TgCRND8 mice from wild type controls by PET imaging using either M116, the anti-Aβ antibody targeting parenchymal Aβ or M31, the antivascular Aβ antibody. To confirm the validity of the noninvasive imaging of specific Aβ pathology, brains were examined after imaging and showed clear evidence of binding to Aβ plaques.
authors.affiliation: Department of Chemical Engineering and Applied Chemistry, University of Toronto, Toronto, Ontario M5S 3E5, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: McLean
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Cooke
authors.forename: Ricardo
authors.initials: R
authors.lastname: Albay
authors.forename: Charles
authors.initials: C
authors.lastname: Glabe
authors.forename: Molly S
authors.initials: MS
authors.lastname: Shoichet
mesh_terms: D016229:Amyloid beta-Peptides / Q000097:blood* / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000098:blood supply* / Q000000981:diagnostic imaging*; D051379:Mice; D057507:Mice, 129 Strain; D008822:Mice, Transgenic; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging* / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods*; D011485:Protein Binding / Q000502:physiology; D019275:Radiopharmaceuticals / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D019275:Radiopharmaceuticals