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European Journal of Nuclear Medicine and Molecular Imaging

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01.05.2014 | Original Article

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

verfasst von: Victor L. Villemagne, 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

Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging | Ausgabe 5/2014

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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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Titel: In vivo evaluation of a novel tau imaging tracer for Alzheimer’s disease
verfasst von: Victor L. Villemagne
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
Publikationsdatum: 01.05.2014
Verlag: Springer Berlin Heidelberg
Erschienen in: European Journal of Nuclear Medicine and Molecular Imaging / Ausgabe 5/2014
Print ISSN: 1619-7070
Elektronische ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-013-2681-7

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusion

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