文章基本信息

标题：Synthesis and in vivo characterization of 18F-labeled difluoroboron-curcumin derivative for β-amyloid plaque imaging
本地全文：下载
作者：Hyunjung Kim ; Young Hoon Im ; Jinhee Ahn 等
期刊名称：Scientific Reports
电子版ISSN：2045-2322
出版年度：2019
卷号：9
期号：1
页码：1-13
DOI：10.1038/s41598-019-43257-9
出版社：Springer Nature
摘要：Positron emission tomography imaging of β-amyloid (Aβ) plaques has proven useful in the diagnosis of Alzheimer's disease. A previous study from our group showed that 4'-O-[ 18 F]fluoropropylcurcumin has poor brain permeability, which is thought to be due to its rapid metabolism. In this study, we synthesized difluoroboron complexes of fluorine-substituted curcumin derivatives (1-4) and selected one of them based on the in vitro binding assays. The selected ligand 2 was found to distinctively stain Aβ plaques in APP/PS1 transgenic mouse brain sections. Radioligand [ 18 F]2 was synthesized via a two-step reaction consisting of [ 18 F]fluorination and subsequent aldol condensation. Biodistribution and metabolism studies indicated that radioligand [ 18 F]2 was converted to polar radioactive products and trapped in the normal mouse brain. In contrast, optical images of mice acquired after injection of 2 showed moderate fluorescence signal intensity in the mouse brain at 2 min with a decrease in the signal within 30 min. In the ex vivo optical images, the fluorescence signals in major tissues disappeared within 30 min. Taken together, these results suggest that [ 18 F]2 may be converted to polar 18 F-labeled blue-shifted fluorescent products. Further structural modifications are thus needed to render the radioligand metabolically stable.