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01-04-2016 | Research Article

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

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

Published in: Molecular Imaging and Biology | Issue 2/2016

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.

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Title: Preclinical Evaluation of [18F]THK-5105 Enantiomers: Effects of Chirality on Its Effectiveness as a Tau Imaging Radiotracer
Authors: Tetsuro Tago
Shozo Furumoto
Nobuyuki Okamura
Ryuichi Harada
Hajime Adachi
Yoichi Ishikawa
Kazuhiko Yanai
Ren Iwata
Yukitsuka Kudo
Publication date: 01-04-2016
Publisher: Springer US
Published in: Molecular Imaging and Biology / Issue 2/2016
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI: https://doi.org/10.1007/s11307-015-0879-8

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

Abstract

Purpose

Procedures

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Procedures

Results

Conclusion

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