title: Preclinical Evaluation of [(18)F]THK-5105 Enantiomers: Effects of Chirality on Its Effectiveness as a Tau Imaging Radiotracer.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  (S)-[(18)F]THK-5105 could be more suitable than (R)-enantiomer for a tau imaging agent.
authors.affiliation: Division of Radiopharmaceutical Chemistry, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan.|Department of Radiopharmaceutical Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Tago
authors.affiliation: Division of Radiopharmaceutical Chemistry, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan. furumoto@cyric.tohoku.ac.jp.|Department of Radiopharmaceutical Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan. furumoto@cyric.tohoku.ac.jp.|Cyclotron and Radioisotope Center (CYRIC), Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai, 980-8578, Japan. furumoto@cyric.tohoku.ac.jp.
authors.forename: Shozo
authors.initials: S
authors.lastname: Furumoto
authors.affiliation: Department of Pharmacology, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Okamura
authors.affiliation: Division of Neuro-Imaging, Institute of Development, Aging and Cancer, Sendai, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Harada
authors.affiliation: Division of Radiopharmaceutical Chemistry, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan.|Department of Radiopharmaceutical Chemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Adachi
authors.affiliation: Division of Radiopharmaceutical Chemistry, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ishikawa
authors.affiliation: Department of Pharmacology, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yanai
authors.affiliation: Division of Radiopharmaceutical Chemistry, Cyclotron and Radioisotope Center, Tohoku University, Sendai, Japan.
authors.forename: Ren
authors.initials: R
authors.lastname: Iwata
authors.affiliation: Division of Neuro-Imaging, Institute of Development, Aging and Cancer, Sendai, Japan.
authors.forename: Yukitsuka
authors.initials: Y
authors.lastname: Kudo
mesh_terms: D000544:Alzheimer Disease / Q000097:blood / Q000000981:diagnostic imaging / Q000378:metabolism; D000814:Aniline Compounds / Q000032:analysis* / Q000737:chemistry*; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D008297:Male; D055442:Metabolome; D051379:Mice; D049268:Positron-Emission Tomography / Q000379:methods*; D011804:Quinolines / Q000032:analysis* / Q000737:chemistry*; D011849:Radioactive Tracers; D011851:Radioactivity; D013237:Stereoisomerism; D016875:tau Proteins / Q000032:analysis* / Q000378:metabolism
chemical_list: D000814:Aniline Compounds; D011804:Quinolines; D011849:Radioactive Tracers; C000590971:THK5105; D016875:tau Proteins
keywords: Alzheimer’s disease; Positron emission tomography; Stereoisomerism; Tau proteins