Synthesis and evaluation of copper-64 labeled benzofuran derivatives targeting β-amyloid aggregates.

In vivo imaging of β-amyloid (Aβ) aggregates consisting of Aβ(1-40) and Aβ(1-42) peptides by positron emission tomography (PET) contributes to the diagnosis and therapy for Alzheimer's disease (AD). Because (64)Cu (t1/2=12.7h) is a radionuclide for PET with a longer physical half-life than (11)C (t1/2=20min) and (18)F (t1/2=110min), it is an attractive radionuclide for the development of Aβ imaging probes that are suitable for routine use. In the present study, we designed and synthesized two novel (64)Cu labeled benzofuran derivatives and evaluated their utility as PET imaging probes for Aβ aggregates. In an in vitro binding assay, 6 and 8 showed binding affinity for Aβ(1-42) aggregates with a Ki value of 33 and 243nM, respectively. In addition, these probes bound to Aβ plaques deposited in the brain of an AD model mouse in vitro. In a biodistribution experiment using normal mice, these probes showed low brain uptake (0.33% and 0.36% ID/g) at 2min post-injection. Although refinement to enhance brain uptake is needed, [(64)Cu]6 and [(64)Cu]8 demonstrated the feasibility of developing novel PET probes for imaging Aβ aggregates.