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

Tetsuro Tago, Shozo Furumoto, Nobuyuki Okamura, Ryuichi Harada, Hajime Adachi, Yoichi Ishikawa, Kazuhiko Yanai, Ren Iwata, Yukitsuka Kudo

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

Purpose: Noninvasive imaging of tau and amyloid-β pathologies would facilitate diagnosis of Alzheimer’s disease (AD). Recently, we have developed [18F]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 [18F]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)-[18F]THK-5105 has slower dissociation from tau than (R)-[18F]THK-5105. Biodistribution assays indicated that (S)-[18F]THK-5105 eliminated faster from the mouse brains and blood compared with (R)-[18F]THK-5105. Conclusion: (S)-[18F]THK-5105 could be more suitable than (R)-enantiomer for a tau imaging agent.

Original languageEnglish
Pages (from-to)258-266
Number of pages9
JournalMolecular Imaging and Biology
Volume18
Issue number2
DOIs
Publication statusPublished - 2016 Apr 1

Keywords

  • Alzheimer’s disease
  • Positron emission tomography
  • Stereoisomerism
  • Tau proteins

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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