Development of novel β-amyloid probes based on 3,5-diphenyl-1,2,4-oxadiazole.

ABSTRACT
In the search for novel probes for the imaging in vivo of β-amyloid plaques in Alzheimer's disease (AD) brain, we have synthesized and evaluated a series of 3,5-diphenyl-1,2,4-oxadiazole (DPOD) derivatives. The affinity for　β-amyloid plaques was assessed by an in vitro-binding assay using pre-formed synthetic Abeta42 aggregates. The new series of DPOD derivatives showed excellent affinity for Aβ aggregates with K_i values ranging from 4 to 47nM. In biodistribution experiments using normal mice, [¹²⁵I]12, [¹²⁵I]13, [¹²⁵I]14, and [¹²⁵I]15 examined displayed sufficient uptake for imaging, ranging from 2.2 to 3.3% ID/g. But the washout of the four ligands from the brain was relatively slow. Although additional modifications are necessary to improve the uptake and rapid clearance of non-specifically bound radiotracers, the DPOD pharmacophore with high-binding affinity for Aβ aggregates may be useful as a backbone structure to develop novel β-amyloid imaging agents.