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European Journal of Nuclear Medicine and Molecular Imaging

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Open Access 01-07-2018 | Original Article

Dual tracer tau PET imaging reveals different molecular targets for ¹¹C-THK5351 and ¹¹C-PBB3 in the Alzheimer brain

Authors: Konstantinos Chiotis, Per Stenkrona, Ove Almkvist, Vladimir Stepanov, Daniel Ferreira, Ryosuke Arakawa, Akihiro Takano, Eric Westman, Andrea Varrone, Nobuyuki Okamura, Hitoshi Shimada, Makoto Higuchi, Christer Halldin, Agneta Nordberg

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 9/2018

Abstract

Purpose

Several tau PET tracers have been developed, but it remains unclear whether they bind to the same molecular target on the heterogeneous tau pathology. In this study we evaluated the binding of two chemically different tau-specific PET tracers (¹¹C-THK5351 and ¹¹C-PBB3) in a head-to-head, in vivo, multimodal design.

Methods

Nine patients with a diagnosis of mild cognitive impairment or probable Alzheimer’s disease and cerebrospinal fluid biomarker evidence supportive of the presence of Alzheimer’s disease brain pathology were recruited after thorough clinical assessment. All patients underwent imaging with the tau-specific PET tracers ¹¹C-THK5351 and ¹¹C-PBB3 on the same day, as well as imaging with the amyloid-beta-specific tracer ¹¹C-AZD2184, a T1-MRI sequence, and neuropsychological assessment.

Results

The load and regional distribution of binding differed between ¹¹C-THK5351 and ¹¹C-PBB3 with no statistically significant regional correlations observed between the tracers. The binding pattern of ¹¹C-PBB3, but not that of ¹¹C-THK5351, in the temporal lobe resembled that of ¹¹C-AZD2184, with strong correlations detected between ¹¹C-PBB3 and ¹¹C-AZD2184 in the temporal and occipital lobes. Global cognition correlated more closely with ¹¹C-THK5351 than with ¹¹C-PBB3 binding. Similarly, cerebrospinal fluid tau measures and entorhinal cortex thickness were more closely correlated with ¹¹C-THK5351 than with ¹¹C-PBB3 binding.

Conclusion

This research suggests different molecular targets for these tracers; while ¹¹C-PBB3 appeared to preferentially bind to tau deposits with a close spatial relationship to amyloid-beta, the binding pattern of ¹¹C-THK5351 fitted the expected distribution of tau pathology in Alzheimer’s disease better and was more closely related to downstream disease markers.

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Title: Dual tracer tau PET imaging reveals different molecular targets for 11C-THK5351 and 11C-PBB3 in the Alzheimer brain
Authors: Konstantinos Chiotis
Per Stenkrona
Ove Almkvist
Vladimir Stepanov
Daniel Ferreira
Ryosuke Arakawa
Akihiro Takano
Eric Westman
Andrea Varrone
Nobuyuki Okamura
Hitoshi Shimada
Makoto Higuchi
Christer Halldin
Agneta Nordberg
Publication date: 01-07-2018
Publisher: Springer Berlin Heidelberg
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 9/2018
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-018-4012-5

At a glance: The STEP trials

Springer Medicine

Dual tracer tau PET imaging reveals different molecular targets for ¹¹C-THK5351 and ¹¹C-PBB3 in the Alzheimer brain

Abstract

Purpose

Methods

Results

Conclusion

At a glance: The STEP trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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