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

Significance Metal radiotracers exhibit beneficial properties that can improve in vivo positron emission tomography (PET) imaging over traditional radionuclides, such as longer half-lives, facile last-stage radiolabeling steps, and the potential for dual imaging-therapy applications. Among such radionuclides, 64 Cu exhibits a longer half-life (t 1/2 = 12.7 h) that allows for later PET imaging times and the ability to distribute 64 Cu imaging agents to facilities that do not have an on-site cyclotron. Herein, we report a 64 Cu PET imaging agent that shows appreciable in vivo brain uptake and exhibits high specific affinity for beta-amyloid aggregates, leading to the successful PET imaging of amyloid plaques in the brains of 5xFAD mice versus those of wild-type mice.