Successful Design of a Multivalent Bifunctional Chelator for Diagnostic 64Cu PET Imaging in Alzheimer’s Disease

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.