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


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2014-02-11

AUTHORS

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

ABSTRACT

PurposeDiagnosis 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.MethodsTen 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.Results18F-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.Conclusion18F-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. More... »

PAGES

816-826

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00259-013-2681-7

DOI

http://dx.doi.org/10.1007/s00259-013-2681-7

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1052642973

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/24514874


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Turtle is a human-readable linked data format.

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29 schema:description PurposeDiagnosis 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.MethodsTen 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.Results18F-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.Conclusion18F-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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