Tetsuro Tago1,2, Shozo Furumoto3,4,5, Nobuyuki Okamura6, Ryuichi Harada7, Hajime Adachi1,2, Yoichi Ishikawa1, Kazuhiko Yanai6, Ren Iwata1, Yukitsuka Kudo7. 1. Division of Radiopharmaceutical Chemistry, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan. 2. Department of Radiopharmaceutical Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan. 3. Division of Radiopharmaceutical Chemistry, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan. furumoto@cyric.tohoku.ac.jp. 4. Department of Radiopharmaceutical Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan. furumoto@cyric.tohoku.ac.jp. 5. Cyclotron and Radioisotope Center (CYRIC), Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai, 980-8578, Japan. furumoto@cyric.tohoku.ac.jp. 6. Department of Pharmacology, Tohoku University School of Medicine, Sendai, Japan. 7. Division of Neuro-Imaging, Institute of Development, Aging and Cancer, Sendai, Japan.
Abstract
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.
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.
Entities:
Keywords:
Alzheimer’s disease; Positron emission tomography; Stereoisomerism; Tau proteins
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