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

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 (18)F-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 (18)F-THK523 and (11)C-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 (18)F-THK523 and (11)C-PIB were estimated for all participants. Correlational analyses were performed between global and regional (18)F-THK523, (11)C-PIB, cognition and brain volumetrics.

RESULTS:

(18)F-THK523 presented with fast reversible kinetics. Significantly higher (18)F-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 (18)F-THK523 retention did not correlate with Aβ distribution as assessed by (11)C-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 (11)C-PIB, hippocampal (18)F-THK523 retention was correlated with several cognitive parameters and with hippocampal atrophy.

CONCLUSION:

(18)F-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 (18)F-THK523 retention in AD patients as well as the association of hippocampal (18)F-THK523 retention with cognitive parameters and hippocampal volume suggests (18)F-THK523 selectively binds to tau in AD patients. Unfortunately, the very high (18)F-THK523 retention in white matter precludes simple visual inspection of the images, preventing its use in research or clinical settings.

• 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
• Journal: European journal of nuclear medicine and molecular imaging (Eur J Nucl Med Mol Imaging) Vol. 41 Issue 5 Pg. 816-26 (May 2014) ISSN: 1619-7089 [Electronic] Germany
• PMID: 24514874 (Publication Type: Evaluation Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
• 2-(4-aminophenyl)-6-(2-fluoroethoxy)quinoline
• Amyloid beta-Peptides
• Aniline Compounds
• MAPT protein, human
• Quinolines
• Radiopharmaceuticals
• Thiazoles
• tau Proteins

Topics

• Aged
• Aged, 80 and over
• Alzheimer Disease (diagnostic imaging)
• Amyloid beta-Peptides (metabolism)
• Aniline Compounds (pharmacokinetics)
• Brain (diagnostic imaging)
• Case-Control Studies
• Female
• Frontotemporal Dementia (diagnostic imaging)
• Humans
• Male
• Middle Aged
• Positron-Emission Tomography
• Protein Binding
• Quinolines (pharmacokinetics)
• Radiopharmaceuticals (pharmacokinetics)
• Thiazoles (pharmacokinetics)
• Tissue Distribution
• tau Proteins (metabolism)