Development and evaluation of [¹⁸F]Flotaza for Aβ plaque imaging in postmortem human Alzheimer's disease brain

Positron emission tomographic (PET) studies of amyloid β (Aβ) accumulation in Alzheimer's disease (AD) have shown clinical utility. The aim of this study was to develop and evaluate the effectiveness of a new fluorine-18 radiotracer [¹⁸F]Flotaza (2-{2-[2-[¹⁸F]fluoroethoxy]ethoxy}ethoxy)-4'-N,N-dimethylaminoazobenzene), for Aβ plaque imaging. Nucleophilic [¹⁸F]fluoride was used in a one-step radiosynthesis for [¹⁸F]flotaza. Using post mortem human AD brain tissues consisting of anterior cingulate (AC) and corpus callosum (CC), binding affinity of Flotaza, Ki = 1.68 nM for human Aβ plaques and weak (>10^-5 M) for Tau protein. Radiosynthesis of [¹⁸F]Flotaza was very efficient in high radiochemical yields (>25%) with specific activities >74 GBq/μmol. Brain slices from all AD subjects were positively immunostained with anti-Aβ. Ratio of [¹⁸F]Flotaza in gray matter AC to white matter CC was >100 in all the 6 subjects. Very little white matter binding was seen. [¹⁸F]Flotaza binding in AC strongly correlated with anti-Aβ immunostains. [¹⁸F]Flotaza is therefore a suitable fluorine-18 PET radiotracer for PET imaging studies of human Aβ plaques.