Conversion of iodine to fluorine-18 based on iodinated chalcone and evaluation for β-amyloid PET imaging.

In the amyloid cascade hypothesis, β-amyloid (Aβ) plaques is one of the major pathological biomarkers in the Alzheimer's disease (AD) brain. We report the synthesis and evaluation of novel radiofluorinated chalcones, [18 F]4-dimethylamino-4'-fluoro-chalcone ([18 F]DMFC) and [18 F]4'-fluoro-4-methylamino-chalcone ([18 F]FMC), as Aβ imaging probes. The conversion of iodine directly introduced to the chalcone backbone into fluorine was successfully carried out by 18 F-labeling via the corresponding boronate precursors, achieving the direct introduction of fluorine-18 into the chalcone backbone to prepare [18 F]DMFC and [18 F]FMC. In a biodistribution study using normal mice, [18 F]DMFC and [18 F]FMC showed a higher initial uptake (4.43 and 5.47% ID/g at 2 min postinjection, respectively) into and more rapid clearance (0.52 and 0.66% ID/g at 30 min postinjection, respectively) from the brain than a Food and Drug Administration (FDA)-approved Aβ imaging agent ([18 F]Florbetapir), meaning the improvement of the probability of detecting Aβ plaques and the reduction of non-specific binding in the brain. In the in vitro binding studies using aggregates of recombinant Aβ peptides, [18 F]DMFC and [18 F]FMC showed high binding affinity to recombinant Aβ aggregates at the Kd values of 4.47 and 6.50 nM, respectively. In the in vitro autoradiography (ARG) experiment with AD brain sections, [18 F]DMFC and [18 F]FMC markedly accumulated only in a region with abundant Aβ plaques, indicating that they clearly recognized human Aβ plaques in vitro. These encouraging results suggest that [18 F]DMFC and [18 F]FMC may be promising PET probes for the detection of an amyloid pathology and the early diagnosis of AD with marked accuracy.