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Antibody-based PET imaging of amyloid beta in mouse models of Alzheimer's disease

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 ba...

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Autores principales: Sehlin, Dag, Fang, Xiaotian T., Cato, Linda, Antoni, Gunnar, Lannfelt, Lars, Syvänen, Stina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4762893/
https://www.ncbi.nlm.nih.gov/pubmed/26892305
http://dx.doi.org/10.1038/ncomms10759
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author Sehlin, Dag
Fang, Xiaotian T.
Cato, Linda
Antoni, Gunnar
Lannfelt, Lars
Syvänen, Stina
author_facet Sehlin, Dag
Fang, Xiaotian T.
Cato, Linda
Antoni, Gunnar
Lannfelt, Lars
Syvänen, Stina
author_sort Sehlin, Dag
collection PubMed
description 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.
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spelling pubmed-47628932016-03-04 Antibody-based PET imaging of amyloid beta in mouse models of Alzheimer's disease Sehlin, Dag Fang, Xiaotian T. Cato, Linda Antoni, Gunnar Lannfelt, Lars Syvänen, Stina Nat Commun Article 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. Nature Publishing Group 2016-02-19 /pmc/articles/PMC4762893/ /pubmed/26892305 http://dx.doi.org/10.1038/ncomms10759 Text en Copyright © 2016, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Sehlin, Dag
Fang, Xiaotian T.
Cato, Linda
Antoni, Gunnar
Lannfelt, Lars
Syvänen, Stina
Antibody-based PET imaging of amyloid beta in mouse models of Alzheimer's disease
title Antibody-based PET imaging of amyloid beta in mouse models of Alzheimer's disease
title_full Antibody-based PET imaging of amyloid beta in mouse models of Alzheimer's disease
title_fullStr Antibody-based PET imaging of amyloid beta in mouse models of Alzheimer's disease
title_full_unstemmed Antibody-based PET imaging of amyloid beta in mouse models of Alzheimer's disease
title_short Antibody-based PET imaging of amyloid beta in mouse models of Alzheimer's disease
title_sort antibody-based pet imaging of amyloid beta in mouse models of alzheimer's disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4762893/
https://www.ncbi.nlm.nih.gov/pubmed/26892305
http://dx.doi.org/10.1038/ncomms10759
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