Preclinical Evaluation of [18F]THK-5105 Enantiomers: Effects of Chirality on Its Effectiveness as a Tau Imaging Radiotracer

Purpose Noninvasive imaging of tau and amyloid-β pathologies would facilitate diagnosis of Alzheimer’s disease (AD). Recently, we have developed [ 18 F]THK-5105 for selective detection of tau pathology by positron emission tomography (PET). The purpose of this study was to clarify biological properties of optically pure [ 18 F]THK-5105 enantiomers. Procedures Binding for tau aggregates in AD brain section was evaluated by autoradiography (ARG). In vitro binding assays were performed to evaluate the binding properties of enantiomers for AD brain homogenates. The pharmacokinetics in the normal mouse brains was assessed by ex vivo biodistribution assay Results The ARG of enantiomers showed the high accumulation of radioactivity corresponding to the distribution of tau deposits. In vitro binding assays revealed that ( S )-[ 18 F]THK-5105 has slower dissociation from tau than ( R )-[ 18 F]THK-5105. Biodistribution assays indicated that ( S )-[ 18 F]THK-5105 eliminated faster from the mouse brains and blood compared with ( R )-[ 18 F]THK-5105. Conclusion ( S )-[ 18 F]THK-5105 could be more suitable than ( R )-enantiomer for a tau imaging agent.