Synthesis and in vivo characterization of 18 F-labeled difluoroboron-curcumin derivative for β-amyloid plaque imaging

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.