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In vivo evaluation of a novel tau imaging tracer for Alzheimer’s disease

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Diagnosis of tauopathies such as Alzheimer’s disease (AD) still relies on post-mortem examination of the human brain. A non-invasive method of determining brain tau burden in vivo would allow a better understanding of the pathophysiology of tauopathies. The purpose of the study was to evaluate 18F-THK523 as a potential tau imaging tracer.

Methods

Ten healthy elderly controls, three semantic dementia (SD) and ten AD patients underwent neuropsychological examination, MRI as well as 18F-THK523 and 11C-Pittsburgh compound B (PIB) positron emission tomography (PET) scans. Composite memory and non-memory scores, global and hippocampal brain volume, and partial volume-corrected tissue ratios for 18F-THK523 and 11C-PIB were estimated for all participants. Correlational analyses were performed between global and regional 18F-THK523, 11C-PIB, cognition and brain volumetrics.

Results

18F-THK523 presented with fast reversible kinetics. Significantly higher 18F-THK523 retention was observed in the temporal, parietal, orbitofrontal and hippocampi of AD patients when compared to healthy controls and SD patients. White matter retention was significantly higher than grey matter retention in all participants. The pattern of cortical 18F-THK523 retention did not correlate with Aβ distribution as assessed by 11C-PIB and followed the known distribution of tau in the AD brain, being higher in temporal and parietal areas than in the frontal region. Unlike 11C-PIB, hippocampal 18F-THK523 retention was correlated with several cognitive parameters and with hippocampal atrophy.

Conclusion

18F-THK523 does not bind to Aβ in vivo, while following the known distribution of paired helical filaments (PHF)-tau in the brain. Significantly higher cortical 18F-THK523 retention in AD patients as well as the association of hippocampal 18F-THK523 retention with cognitive parameters and hippocampal volume suggests 18F-THK523 selectively binds to tau in AD patients. Unfortunately, the very high 18F-THK523 retention in white matter precludes simple visual inspection of the images, preventing its use in research or clinical settings.

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Acknowledgements

We thank Prof. Michael Woodward, Dr. John Merory, Dr. Gordon Chan, Dr. Kenneth Young, Dr. David Darby, Ms. Fiona Lamb and the Brain Research Institute for their assistance with this study. The study was partially supported by an Alzheimer Drug Discovery Foundation Research Grant (20101208 AFTD) and by a National Health and Medical Research Council of Australia Project Grant 1044361. The funding sources had no input into the design and conduct of the study; collection, management, analysis and interpretation of the data; and in the preparation, review, approval or decision to submit the manuscript for publication.

Conflicts of interest

None.

Author information

Authors and Affiliations

  1. Centre for PET, Austin Health, Melbourne, Australia

    Victor L. Villemagne, Michelle T. Fodero-Tavoletti, Rachel S. Mulligan, Paul Yates, Svetlana Pejoska, Vincent Doré & Christopher C. Rowe

  2. The Mental Health Research Institute, Melbourne, Australia

    Victor L. Villemagne, Michelle T. Fodero-Tavoletti & Colin L. Masters

  3. Department of Pharmacology, Tohoku University School of Medicine, Sendai, Japan

    Shozo Furumoto, Ryuichi Harada, Kazuhiko Yanai & Nobuyuki Okamura

  4. Neuroscience Research Australia, Sydney, Australia

    John Hodges & Olivier Piguet

  5. The University of New South Wales, Sydney, Australia

    John Hodges & Olivier Piguet

  6. Preventative Health Flagship, CSIRO ICT, Brisbane, Australia

    Vincent Doré

  7. Innovation of New Biomedical Engineering Center, Tohoku University, Sendai, Japan

    Yukitsuka Kudo

  8. Department of Nuclear Medicine and Centre for PET, Austin Health, 145 Studley Rd, Heidelberg, VIC, 3084, Australia

    Victor L. Villemagne

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  1. Victor L. Villemagne
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Corresponding author

Correspondence to Victor L. Villemagne.

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Authors’ contributions

Dr. Villemagne had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis

Drs. Villemagne, Furumoto, Fodero-Tavoletti, Kudo, Rowe and Okamura participated in the design, acquisition, analysis and interpretation of the data and writing of this manuscript.

Study concept and design: Villemagne, Okamura, Kudo, Rowe

Acquisition of data: Villemagne, Rowe, Fodero-Tavoletti, Pejoska, Yates, Piguet, Mulligan

Analysis and interpretation of data: Villemagne, Doré, Rowe, Okamura

Drafting of the manuscript: Villemagne, Okamura

Critical revision of the manuscript for important intellectual content: Villemagne, Furumoto, Rowe, Harada, Fodero-Tavoletti, Piguet, Hodges, Yanai, Masters, Kudo, Okamura

Statistical analysis: Villemagne, Okamura

Study supervision: Villemagne, Okamura

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Villemagne, V.L., Furumoto, S., Fodero-Tavoletti, M.T. et al. In vivo evaluation of a novel tau imaging tracer for Alzheimer’s disease. Eur J Nucl Med Mol Imaging 41, 816–826 (2014). https://doi.org/10.1007/s00259-013-2681-7

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  • DOI: https://doi.org/10.1007/s00259-013-2681-7

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