[18F]-FDDNP was synthesized and characterized as a positron-emitting probe to identify Alzheimer’s disease (AD) in transgenic mouse models (Tg2576 and dE9) expressing the AD pathology. We observed in in vitro, in vivo, and ex vivo studies that [18F]-FDDNP accumulated specifically in the Ab-overexpressing brain regions and that this accumulation was significantly reduced by co-incubation with non-radioactive FDDNP. In ex vivo and in vivo studies of brain sections, the retention of radioactivity was more specific in Tg2576 mice than in dE9 mice. Using in vitro, ex vivo, in vivo, and ELISA analyses, we characterized the utility of [18F]-FDDNP in mapping b-amyloid in the Tg2576 mouse brain, to assess its potential application in imaging strategies.