Abstract
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 [(18)F]Flotaza (2-{2-[2-[(18)F]fluoroethoxy]ethoxy}ethoxy)-4'-N,N-dimethylaminoazobenzene), for Aβ plaque imaging. Nucleophilic [(18)F]fluoride was used in a one-step radiosynthesis for [(18)F]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 [(18)F]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 [(18)F]Flotaza in gray matter AC to white matter CC was >100 in all the 6 subjects. Very little white matter binding was seen. [(18)F]Flotaza binding in AC strongly correlated with anti-Aβ immunostains. [(18)F]Flotaza is therefore a suitable fluorine-18 PET radiotracer for PET imaging studies of human Aβ plaques.