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

  • Victor L. VillemagneEmail author
  • Shozo Furumoto
  • Michelle T. Fodero-Tavoletti
  • Rachel S. Mulligan
  • John Hodges
  • Ryuichi Harada
  • Paul Yates
  • Olivier Piguet
  • Svetlana Pejoska
  • Vincent Doré
  • Kazuhiko Yanai
  • Colin L. Masters
  • Yukitsuka Kudo
  • Christopher C. Rowe
  • Nobuyuki Okamura
Original Article

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.

Keywords

Alzheimer’s disease Tau imaging Aβ Imaging Neurodegeneration Brain 

Notes

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.

Supplementary material

259_2013_2681_MOESM1_ESM.pdf (1.1 mb)
ESM 1 (PDF 1123 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Victor L. Villemagne
    • 1
    • 2
    • 8
    Email author
  • Shozo Furumoto
    • 3
  • Michelle T. Fodero-Tavoletti
    • 1
    • 2
  • Rachel S. Mulligan
    • 1
  • John Hodges
    • 4
    • 5
  • Ryuichi Harada
    • 3
  • Paul Yates
    • 1
  • Olivier Piguet
    • 4
    • 5
  • Svetlana Pejoska
    • 1
  • Vincent Doré
    • 1
    • 6
  • Kazuhiko Yanai
    • 3
  • Colin L. Masters
    • 2
  • Yukitsuka Kudo
    • 7
  • Christopher C. Rowe
    • 1
  • Nobuyuki Okamura
    • 3
  1. 1.Centre for PETAustin HealthMelbourneAustralia
  2. 2.The Mental Health Research InstituteMelbourneAustralia
  3. 3.Department of PharmacologyTohoku University School of MedicineSendaiJapan
  4. 4.Neuroscience Research AustraliaSydneyAustralia
  5. 5.The University of New South WalesSydneyAustralia
  6. 6.Preventative Health FlagshipCSIRO ICTBrisbaneAustralia
  7. 7.Innovation of New Biomedical Engineering CenterTohoku UniversitySendaiJapan
  8. 8.Department of Nuclear Medicine and Centre for PETAustin HealthHeidelbergAustralia

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