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

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 Aβ42 aggregates. The new series of DPOD derivatives showed excellent affinity for Aβ aggregates with Ki values ranging from 4 to 47 nM. 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.

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