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 beta-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 beta-amyloid plaques was assessed by an in vitro-binding assay using pre-formed synthetic A beta 42 aggregates. The new series of DPOD derivatives showed excellent affinity for Ab aggregates with K-i values ranging from 4 to 47 nM. In biodistribution experiments using normal mice, [I-125]12, [I-125]13, [I-125]14, and [I-125]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 modi. cations are necessary to improve the uptake and rapid clearance of non-specifically bound radiotracers, the DPOD pharmacophore with high-binding affinity for Ab aggregates may be useful as a backbone structure to develop novel beta-amyloid imaging agents. (c) 2008 Elsevier Ltd. All rights reserved.