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.