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

Kaide, Sho; Ono, Masahiro; Watanabe, Hiroyuki; Shimizu, Yoichi; Nakamoto, Yuji; Togashi, Kaori; Yamaguchi, Aiko; Hanaoka, Hirofumi; Saji, Hideo.
Bioorg Med Chem; 26(12): 3352-3358, 2018 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-29751990
In the amyloid cascade hypothesis, ß-amyloid (Aß) 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, [18F]4-dimethylamino-4'-fluoro-chalcone ([18F]DMFC) and [18F]4'-fluoro-4-methylamino-chalcone ([18F]FMC), as Aß imaging probes. The conversion of iodine directly introduced to the chalcone backbone into fluorine was successfully carried out by 18F-labeling via the corresponding boronate precursors, achieving the direct introduction of fluorine-18 into the chalcone backbone to prepare [18F]DMFC and [18F]FMC. In a biodistribution study using normal mice, [18F]DMFC and [18F]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 Aß imaging agent ([18F]Florbetapir), meaning the improvement of the probability of detecting Aß plaques and the reduction of non-specific binding in the brain. In the in vitro binding studies using aggregates of recombinant Aß peptides, [18F]DMFC and [18F]FMC showed high binding affinity to recombinant Aß aggregates at the Kd values of 4.47 and 6.50 nM, respectively. In the in vitro autoradiography (ARG) experiment with AD brain sections, [18F]DMFC and [18F]FMC markedly accumulated only in a region with abundant Aß plaques, indicating that they clearly recognized human Aß plaques in vitro. These encouraging results suggest that [18F]DMFC and [18F]FMC may be promising PET probes for the detection of an amyloid pathology and the early diagnosis of AD with marked accuracy.
Selo DaSilva