Novel 2,5-diphenylthiophene derivatives were synthesized and structure activity relationship with regard to Abeta plaque binding was studied. Binding affinities of these compounds were found to range from 3.9 to >1000 nM, depending on the substitution patterns on the phenyl ring. The fluoroethyl-substituted thiophene derivatives showed excellent binding affinities. These compounds may be useful for the development of novel PET tracers for the imaging of beta-amyloid plaques in the brain of patients with Alzheimer's disease.