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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

Chiotis, Konstantinos ; Dodich, Alessandra ; Boccardi, Marina ; Festari, Cristina ; Drzezga, Alexander ; Hansson, Oskar LU orcid ; Ossenkoppele, Rik LU ; Frisoni, Giovanni ; Garibotto, Valentina and Nordberg, Agneta (2021) In European Journal of Nuclear Medicine and Molecular Imaging 48(7). p.2086-2096
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... (More)

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.

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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer’s disease, Biomarker-based diagnosis, PBB3, Strategic roadmap, Tau PET, THK
in
European Journal of Nuclear Medicine and Molecular Imaging
volume
48
issue
7
pages
11 pages
publisher
Springer
external identifiers
  • pmid:33723628
  • scopus:85102426162
ISSN
1619-7070
DOI
10.1007/s00259-021-05277-4
language
English
LU publication?
yes
id
7957188b-2b09-41e1-bf4c-82daa8905860
date added to LUP
2021-12-10 11:56:04
date last changed
2022-08-12 02:09:56
@article{7957188b-2b09-41e1-bf4c-82daa8905860,
  abstract     = {{<p>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.</p>}},
  author       = {{Chiotis, Konstantinos and Dodich, Alessandra and Boccardi, Marina and Festari, Cristina and Drzezga, Alexander and Hansson, Oskar and Ossenkoppele, Rik and Frisoni, Giovanni and Garibotto, Valentina and Nordberg, Agneta}},
  issn         = {{1619-7070}},
  keywords     = {{Alzheimer’s disease; Biomarker-based diagnosis; PBB3; Strategic roadmap; Tau PET; THK}},
  language     = {{eng}},
  number       = {{7}},
  pages        = {{2086--2096}},
  publisher    = {{Springer}},
  series       = {{European Journal of Nuclear Medicine and Molecular Imaging}},
  title        = {{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}},
  url          = {{http://dx.doi.org/10.1007/s00259-021-05277-4}},
  doi          = {{10.1007/s00259-021-05277-4}},
  volume       = {{48}},
  year         = {{2021}},
}