Synthesis and biological evaluation of radioiodinated 2,5-diphenyl-1,3,4-oxadiazoles for detecting -amyloid plaques in the brain.

ABSTRACT

This paper describes the synthesis and biological evaluation of a new series of 2,5-diphenyl-1,3,4-oxadiazole (1,3,4-DPOD) derivatives for detecting -amyloid plaques in Alzheimer's brains. The affinity for -amyloid plaques was assessed by an in vitro binding assay using pre-formed synthetic A42 aggregates. The new series of 1,3,4-DPOD derivatives showed affinity for A42 aggregates with Ki values ranging from 20 to 349 nM. The 1,3,4-DPOD derivatives clearly stained -amyloid plaques in an animal model of Alzheimer's disease, reflecting the affinity for A42 aggregates in vitro. Compared to 3,5-diphenyl-1,2,4-oxadiazole (1,2,4-DPOD) derivatives, they displayed good penetration of and fast washout from the brain in biodistribution experiments using normal mice. The novel radioiodinated 1,3,4-DPOD derivatives may be useful probes for detecting -amyloid plaques in the Alzheimer's brain.