Preclinical Evaluation of [(18)F]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 proper...

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Publicado en:Molecular Imaging & Biology Vol. 18; no. 2; pp. 258 - 267
Autores principales: Tago, Tetsuro, Furumoto, Shozo, Okamura, Nobuyuki, Harada, Ryuichi, Adachi, Hajime, Ishikawa, Yoichi, Yanai, Kazuhiko, Iwata, Ren, Kudo, Yukitsuka
Formato: research Journal Article
Publicado: Springer Nature Apr2016
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Apr2016
      vid: 18
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      pub: Springer Nature
      place: New York, New York
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        atl: Preclinical Evaluation of [(18)F]THK-5105 Enantiomers: Effects of Chirality on Its Effectiveness as a Tau Imaging Radiotracer.
      aug:
        au:
          Tago, Tetsuro
          Furumoto, Shozo
          Okamura, Nobuyuki
          Harada, Ryuichi
          Adachi, Hajime
          Ishikawa, Yoichi
          Yanai, Kazuhiko
          Iwata, Ren
          Kudo, Yukitsuka
        affil: Department of Pharmacology, Tohoku University School of Medicine, Sendai Japan
      sug:
        subj:
          Quinolines Analysis
          Radioisotopes
          Tomography, Emission-Computed Methods
          Amines Analysis
          Nerve Tissue Proteins Analysis
          Quinolines
          Amines
          Chemistry
          Human
          Radioactivity
          Animal Studies
          Mice
          Male
          Radiography
          Brain
          Alzheimer's Disease Metabolism
          Brain Metabolism
          Chromatography, High Pressure Liquid
          Nerve Tissue Proteins Metabolism
          Alzheimer's Disease
          Alzheimer's Disease Blood
          Metabolism
          Validation Studies
          Comparative Studies
          Evaluation Research
          Multicenter Studies
          Male
      ab: 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 assayResults: 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.
      pubtype: Academic Journal
      doctype:
        research
        Journal Article
      ougenre: Article
    language: English
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