title: Antibody-based PET imaging of amyloid beta in mouse models of Alzheimer's disease.
abstract: Owing to their specificity and high-affinity binding, monoclonal antibodies have potential as positron emission tomography (PET) radioligands and are currently used to image various targets in peripheral organs. However, in the central nervous system, antibody uptake is limited by the blood-brain barrier (BBB). Here we present a PET ligand to be used for diagnosis and evaluation of treatment effects in Alzheimer's disease. The amyloid β (Aβ) antibody mAb158 is radiolabelled and conjugated to a transferrin receptor antibody to enable receptor-mediated transcytosis across the BBB. PET imaging of two different mouse models with Aβ pathology clearly visualize Aβ in the brain. The PET signal increases with age and correlates closely with brain Aβ levels. Thus, we demonstrate that antibody-based PET ligands can be successfully used for brain imaging.
authors.affiliation: Department of Public Health and Caring Sciences/Geriatrics, Uppsala University, Rudbeck Laboratory, 75185 Uppsala, Sweden.
authors.forename: Dag
authors.identifier: http://orcid.org/0000-0002-9430-3859
authors.initials: D
authors.lastname: Sehlin
authors.affiliation: Department of Public Health and Caring Sciences/Geriatrics, Uppsala University, Rudbeck Laboratory, 75185 Uppsala, Sweden.
authors.forename: Xiaotian T
authors.initials: XT
authors.lastname: Fang
authors.affiliation: Department of Public Health and Caring Sciences/Geriatrics, Uppsala University, Rudbeck Laboratory, 75185 Uppsala, Sweden.
authors.forename: Linda
authors.initials: L
authors.lastname: Cato
authors.affiliation: Department of Medicinal Chemistry, Preclinical PET Platform, Uppsala University, 75123 Uppsala, Sweden.|PET Centre, Uppsala University Hospital, 75185 Uppsala, Sweden.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Antoni
authors.affiliation: Department of Public Health and Caring Sciences/Geriatrics, Uppsala University, Rudbeck Laboratory, 75185 Uppsala, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Lannfelt
authors.affiliation: Department of Public Health and Caring Sciences/Geriatrics, Uppsala University, Rudbeck Laboratory, 75185 Uppsala, Sweden.
authors.forename: Stina
authors.initials: S
authors.lastname: Syvänen
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D049268:Positron-Emission Tomography / Q000379:methods*; D011859:Radiography
chemical_list: D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal