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Clinical validity of increased cortical uptake of [18F]flortaucipir on PET as a biomarker for Alzheimer’s disease in the context of a structured 5-phase biomarker development framework

Wolters, E. E. ; Dodich, A. ; Boccardi, M. ; Corre, J. ; Drzezga, A. ; Hansson, O. LU orcid ; Nordberg, A. ; Frisoni, G. B. ; Garibotto, V. and Ossenkoppele, R. LU (2021) In European Journal of Nuclear Medicine and Molecular Imaging 48(7). p.2097-2109
Abstract

Purpose: In 2017, the Geneva Alzheimer’s disease (AD) Biomarker Roadmap initiative adapted the framework of the systematic validation of oncological diagnostic biomarkers to AD biomarkers, with the aim to accelerate their development and implementation in clinical practice. With this work, we assess the maturity of [18F]flortaucipir PET and define its research priorities. Methods: The level of maturity of [18F]flortaucipir was assessed based on the AD Biomarker Roadmap. The framework assesses analytical validity (phases 1–2), clinical validity (phases 3–4), and clinical utility (phase 5). Results: The main aims of phases 1 (rationale for use) and 2 (discriminative ability) have been achieved.... (More)

Purpose: In 2017, the Geneva Alzheimer’s disease (AD) Biomarker Roadmap initiative adapted the framework of the systematic validation of oncological diagnostic biomarkers to AD biomarkers, with the aim to accelerate their development and implementation in clinical practice. With this work, we assess the maturity of [18F]flortaucipir PET and define its research priorities. Methods: The level of maturity of [18F]flortaucipir was assessed based on the AD Biomarker Roadmap. The framework assesses analytical validity (phases 1–2), clinical validity (phases 3–4), and clinical utility (phase 5). Results: The main aims of phases 1 (rationale for use) and 2 (discriminative ability) have been achieved. [18F]Flortaucipir binds with high affinity to paired helical filaments of tau and has favorable kinetic properties and excellent discriminative accuracy for AD. The majority of secondary aims of phase 2 were fully achieved. Multiple studies showed high correlations between ante-mortem [18F]flortaucipir PET and post-mortem tau (as assessed by histopathology), and also the effects of covariates on tracer binding are well studied. The aims of phase 3 (early detection ability) were only partially or preliminarily achieved, and the aims of phases 4 and 5 were not achieved. Conclusion: Current literature provides partial evidence for clinical utility of [18F]flortaucipir PET. The aims for phases 1 and 2 were mostly achieved. Phase 3 studies are currently ongoing. Future studies including representative MCI populations and a focus on healthcare outcomes are required to establish full maturity of phases 4 and 5.

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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Alzheimer’s disease, Biomarker-based diagnosis, PET, Strategic roadmap, [F]flortaucipir
in
European Journal of Nuclear Medicine and Molecular Imaging
volume
48
issue
7
pages
13 pages
publisher
Springer
external identifiers
  • pmid:33547556
  • scopus:85100597518
ISSN
1619-7070
DOI
10.1007/s00259-020-05118-w
language
English
LU publication?
yes
id
98405667-81dd-4a1c-a171-3a21f3f797b1
date added to LUP
2021-02-25 09:10:50
date last changed
2025-04-18 13:35:02
@article{98405667-81dd-4a1c-a171-3a21f3f797b1,
  abstract     = {{<p>Purpose: In 2017, the Geneva Alzheimer’s disease (AD) Biomarker Roadmap initiative adapted the framework of the systematic validation of oncological diagnostic biomarkers to AD biomarkers, with the aim to accelerate their development and implementation in clinical practice. With this work, we assess the maturity of [<sup>18</sup>F]flortaucipir PET and define its research priorities. Methods: The level of maturity of [<sup>18</sup>F]flortaucipir was assessed based on the AD Biomarker Roadmap. The framework assesses analytical validity (phases 1–2), clinical validity (phases 3–4), and clinical utility (phase 5). Results: The main aims of phases 1 (rationale for use) and 2 (discriminative ability) have been achieved. [<sup>18</sup>F]Flortaucipir binds with high affinity to paired helical filaments of tau and has favorable kinetic properties and excellent discriminative accuracy for AD. The majority of secondary aims of phase 2 were fully achieved. Multiple studies showed high correlations between ante-mortem [<sup>18</sup>F]flortaucipir PET and post-mortem tau (as assessed by histopathology), and also the effects of covariates on tracer binding are well studied. The aims of phase 3 (early detection ability) were only partially or preliminarily achieved, and the aims of phases 4 and 5 were not achieved. Conclusion: Current literature provides partial evidence for clinical utility of [<sup>18</sup>F]flortaucipir PET. The aims for phases 1 and 2 were mostly achieved. Phase 3 studies are currently ongoing. Future studies including representative MCI populations and a focus on healthcare outcomes are required to establish full maturity of phases 4 and 5.</p>}},
  author       = {{Wolters, E. E. and Dodich, A. and Boccardi, M. and Corre, J. and Drzezga, A. and Hansson, O. and Nordberg, A. and Frisoni, G. B. and Garibotto, V. and Ossenkoppele, R.}},
  issn         = {{1619-7070}},
  keywords     = {{Alzheimer’s disease; Biomarker-based diagnosis; PET; Strategic roadmap; [F]flortaucipir}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{7}},
  pages        = {{2097--2109}},
  publisher    = {{Springer}},
  series       = {{European Journal of Nuclear Medicine and Molecular Imaging}},
  title        = {{Clinical validity of increased cortical uptake of [<sup>18</sup>F]flortaucipir on PET as a biomarker for Alzheimer’s disease in the context of a structured 5-phase biomarker development framework}},
  url          = {{http://dx.doi.org/10.1007/s00259-020-05118-w}},
  doi          = {{10.1007/s00259-020-05118-w}},
  volume       = {{48}},
  year         = {{2021}},
}