文章基本信息

标题：Design of a multivalent bifunctional chelator for diagnostic 64Cu PET imaging in Alzheimer’s disease
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作者：Hong-Jun Cho ; Truc T. Huynh ; Buck E. Rogers 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2020
卷号：117
期号：49
页码：30928-30933
DOI：10.1073/pnas.2014058117
出版社：The National Academy of Sciences of the United States of America
摘要：Herein, we report a 64 Cu positron emission tomography (PET) imaging agent that shows appreciable in vivo brain uptake and exhibits high specific affinity for beta-amyloid (Aβ) aggregates, leading to the successful PET imaging of amyloid plaques in the brains of 5xFAD mice versus those of wild-type mice. The employed approach uses a bifunctional chelator with two Aβ-interacting fragments that dramatically improves the Aβ-binding affinity and lipophilicity for favorable blood–brain barrier penetration, while the use of optimized-length spacers between the Cu-chelating group and the Aβ-interacting fragments further improves the in vivo Aβ-binding specificity and brain uptake of the corresponding 64 Cu PET imaging agent.
关键词：Alzheimer’s disease ; positron emission tomography imaging ; blood–brain barrier ; amyloid beta (Aβ) peptide ; multivalent effect