A ¹⁸F-labeled BF-227 derivative as a potential radioligand for imaging dense amyloid plaques by positron emission tomography

Purpose: The aims of this study were to evaluate the binding and pharmacokinetics of novel ¹⁸F-labeled ethenyl-benzoxazole derivatives (i.e., [¹⁸F] fluorinated amyloid imaging compound of Tohoku university ([¹⁸F]FACT)) as amyloid positron emission tomography (PET) tracers and to assess [¹⁸F]FACT efficacy in imaging of Alzheimer's disease (AD). Procedures: Binding assay was conducted using synthetic amyloid-β (Aβ) fibrils, fluorescence microscopy, and autoradiogram in three postmortem AD brains. Pharmacokinetics of [¹⁸F]FACT was assessed using 12 Crj:CD-1 (ICR) mice. In vivo binding ability with brain amyloid was investigated using amyloid precursor protein (APP) transgenic mouse. Clinical PET scanning using [¹⁸F]FACT was performed in ten healthy controls and ten mild cognitive impairment and ten AD patients. Results: [ ¹⁸F]FACT showed high binding affinity for synthetic Aβ fibrils, preferential binding to dense cored plaques in brain sections, and excellent brain uptake and rapid clearance in mice. Injection in APP mice resulted in specific in vivo labeling of amyloid deposits in the brain. PET scans of AD patients showed significantly higher [¹⁸F]FACT uptake in the neocortex compared to controls (P < 0.05, Kruskal-Wallis test). Conclusion: [¹⁸F]FACT is a promising agent for imaging dense Aβ plaques in AD.