Alzheimer's disease (AD) is pathologically characterized by the accumulation of amyloid plaques and neurofibrillary tangles in the brain, and thus, the in vivo imaging of plaques and tangles would be beneficial for the early diagnosis of AD. It has been suggested that 5-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,4,6-heptatrien-3-one (curcumin) may be responsible for low age-adjusted prevalence of AD in India. In the present study, eight novel derivatives of curcumin and 4-(4-hydroxy-3-methoxyphenyl)-3-buten-2-one (dehydrozingerone) were synthesized and their binding affinities for β-amyloid (Aβ) aggregates were measured. Of these ligands, fluoropropyl-substituted curcumin (8) showed the highest binding affinity (K_i = 0.07 nM), and therefore, 8 was radiolabeled and evaluated as a potential probe for Aβ plaque imaging. Partition coefficient measurement and biodistribution in normal mice demonstrated that [¹⁸F]8 has a suitable lipophilicity and reasonable initial brain uptake. Metabolism studies also indicated that [¹⁸F]8 is metabolically stable in the brain. These results suggest that [¹⁸F]8 is a suitable radioligand for Aβ plaque imaging.