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submitted on 04.06.2020 and posted on 05.06.2020by Hong-Jun Cho, Truc T. Huynh, Buck E. Rogers, Liviu M. Mirica
Herein, we report to the best of our knowledge the
first 64Cu 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 WT mice.
The employed approach uses a bifunctional chelator with two Aβ-interacting
fragments that dramatically improves the Aβ-binding affinity and lipophilicity
for favorable BBB 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 64Cu PET imaging agent.