In Vivo Near-Infrared Fluorescence Imaging Selective for Soluble Amyloid Aggregates Using y-Shaped BODIPY Derivative

Soluble amyloid beta (A beta) aggregates, suggested to be the most toxic forms of A beta, draw attention as therapeutic targets and biomarkers of Alzheimer's disease (AD). As soluble A beta aggregates are transient and diverse, imaging their diverse forms in vivo is expected to have a marked impact on research and diagnosis of AD. Herein, we report a near-infrared fluorescent (NIRF) probe, BAOP-16, targeting diverse soluble A beta aggregates. BAOP-16, whose molecular shape resembles "y", showed a marked selective increase in fluorescence intensity upon binding to soluble A beta aggregates in the near-infrared region and a high binding affinity for them. Additionally, BAOP-16 could detect A beta oligomers in the brains of A beta-inoculated model mice. In an in vivo fluorescence imaging study of BAOP-16, brains of AD model mice displayed significantly higher fluorescence signals than those of wild-type mice. These results indicate that BAOP-16 could be useful for the in vivo NIRF imaging of diverse soluble A beta aggregates.