Design of a multivalent bifunctional chelator for diagnostic 64Cu PET imaging in Alzheimer's disease

Herein, we report a Cu-64 positron emission tomography (PET) imaging agent that shows appreciable in vivo brain uptake and exhibits high specific affinity for beta-amyloid (A beta) 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 A beta interacting fragments that dramatically improves the A beta-binding affinity and lipophilicity for favorable blood-brain barrier penetration, while the use of optimized-length spacers between the Cuchelating group and the A beta-interacting fragments further improves the in vivo A beta-binding specificity and brain uptake of the corresponding Cu-64 PET imaging agent.