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Title: Imaging of Cerebral Amyloid Angiopathy with Bivalent 99m Tc-Hydroxamamide Complexes
Authors: Iikuni, Shimpei
Ono, Masahiro  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0002-2497-039X (unconfirmed)
Watanabe, Hiroyuki  kyouindb  KAKEN_id
Matsumura, Kenji
Yoshimura, Masashi
Kimura, Hiroyuki
Ishibashi-Ueda, Hatsue
Okamoto, Yoko
Ihara, Masafumi
Saji, Hideo
Author's alias: 小野, 正博
渡邊, 裕之
木村, 寛之
佐治, 英郎
Issue Date: 16-May-2016
Publisher: Nature Publishing Group
Journal title: Scientific Reports
Volume: 6
Thesis number: 25990
Abstract: Cerebral amyloid angiopathy (CAA), characterized by the deposition of amyloid aggregates in the walls of cerebral vasculature, is a major factor in intracerebral hemorrhage and vascular cognitive impairment and is also associated closely with Alzheimer's disease (AD). We previously reported 99m Tc-hydroxamamide (99m Tc-Ham) complexes with a bivalent amyloid ligand showing high binding affinity for β-amyloid peptide (Aβ(1-42)) aggregates present frequently in the form in AD. In this article, we applied them to CAA-specific imaging probes, and evaluated their utility for CAA-specific imaging. In vitro inhibition assay using Aβ(1-40) aggregates deposited mainly in CAA and a brain uptake study were performed for 99m Tc-Ham complexes, and all 99m Tc-Ham complexes with an amyloid ligand showed binding affinity for Aβ(1-40) aggregates and very low brain uptake. In vitro autoradiography of human CAA brain sections and ex vivo autoradiography of Tg2576 mice were carried out for bivalent 99m Tc-Ham complexes ([ 99m Tc]SB2A and [ 99m Tc]BT2B), and they displayed excellent labeling of Aβ depositions in human CAA brain sections and high affinity and selectivity to CAA in transgenic mice. These results may offer new possibilities for the development of clinically useful CAA-specific imaging probes based on the 99m Tc-Ham complex.
Rights: © 2016, Nature Publishing Group. All rights reserved. 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/
URI: http://hdl.handle.net/2433/215163
DOI(Published Version): 10.1038/srep25990
PubMed ID: 27181612
Appears in Collections:Journal Articles

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