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Review
. 2021 Jul;48(7):2086-2096.
doi: 10.1007/s00259-021-05277-4. Epub 2021 Mar 15.

Clinical validity of increased cortical binding of tau ligands of the THK family and PBB3 on PET as biomarkers for Alzheimer's disease in the context of a structured 5-phase development framework

Konstantinos Chiotis  1   2 , Alessandra Dodich  3   4 , Marina Boccardi  5 , Cristina Festari  6 , Alexander Drzezga  7   8   9 , Oskar Hansson  10   11 , Rik Ossenkoppele  12   13 , Giovanni Frisoni  5   14 , Valentina Garibotto  4   15 , Agneta Nordberg  16   17
Affiliations
Review

Clinical validity of increased cortical binding of tau ligands of the THK family and PBB3 on PET as biomarkers for Alzheimer's disease in the context of a structured 5-phase development framework

Konstantinos Chiotis et al. Eur J Nucl Med Mol Imaging. 2021 Jul.

Abstract

Purpose: The research community has focused on defining reliable biomarkers for the early detection of the pathological hallmarks of Alzheimer's disease (AD). In 2017, the Geneva AD Biomarker Roadmap initiative adapted the framework for the systematic validation of oncological biomarkers to AD, with the aim to accelerate their development and implementation in clinical practice. The aim of this work was to assess the validation status of tau PET ligands of the THK family and PBB3 as imaging biomarkers for AD, based on the Biomarker Roadmap methodology.

Methods: A panel of experts in AD biomarkers convened in November 2019 at a 2-day workshop in Geneva. The level of clinical validity of tau PET ligands of the THK family and PBB3 was assessed based on the 5-phase development framework before the meeting and discussed during the workshop.

Results: PET radioligands of the THK family discriminate well between healthy controls and patients with AD dementia (phase 2; partly achieved) and recent evidence suggests an accurate diagnostic accuracy at the mild cognitive impairment (MCI) stage of the disease (phase 3; partly achieved). The phases 2 and 3 were considered not achieved for PBB3 since no evidence exists about the ligand's diagnostic accuracy. Preliminary evidence exists about the secondary aims of each phase for all ligands.

Conclusion: Much work remains for completing the aims of phases 2 and 3 and replicating the available evidence. However, it is unlikely that the validation process for these tracers will be completed, given the presence of off-target binding and the development of second-generation tracers with improved binding and pharmacokinetic properties.

Keywords: Alzheimer’s disease; Biomarker-based diagnosis; PBB3; Strategic roadmap; THK; Tau PET.

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Figures

Fig. 1
Fig. 1
Synopsis of the clinical validity of tau PET ligands of the THK family as adapted from an oncology framework [2, 4]
Fig. 2
Fig. 2
Synopsis of the clinical validity of PBB3 PET as adapted from an oncology framework [2, 4]
See this image and copyright information in PMC

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