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

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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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Acknowledgments

We thank all the staff at Cyclotron Radioisotope Center of Tohoku University for the HM-12 cyclotron operation. This study was supported by the Industrial Technology Research Grant Program of the NEDO in Japan (09E51025a), a Grant-in-Aid for Scientific Research (B) (25293259), and Health and Labour Sciences Research Grants from the Ministry of Health, Labour, and Welfare of Japan.

Conflict of Interest

Research funds for this study were provided by GE Healthcare, CLINO Co. Ltd., the SEI (Sumitomo Electric Industries, Ltd.) Group CSR Foundation. S. Furumoto, N. Okamura, and Y. Kudo are scientific consultants for the CLINO Co. Ltd.

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Correspondence to Shozo Furumoto.

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Tago, T., Furumoto, S., Okamura, N. et al. Preclinical Evaluation of [18F]THK-5105 Enantiomers: Effects of Chirality on Its Effectiveness as a Tau Imaging Radiotracer. Mol Imaging Biol 18, 258–266 (2016). https://doi.org/10.1007/s11307-015-0879-8

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  • DOI: https://doi.org/10.1007/s11307-015-0879-8

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