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

Research output: Contribution to journalReview article


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.


External organisations
  • University of Geneva
  • University of Trento
  • German Center for Neurodegenerative Diseases (DZNE), Bonn
  • University of Cologne
  • Jülich Research Centre
  • Skåne University Hospital
  • Karolinska Institutet
  • Geneva University Hospital
  • Vrije Universiteit Amsterdam
  • Amsterdam UMC - Vrije Universiteit Amsterdam
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurology


  • Alzheimer’s disease, Biomarker-based diagnosis, PET, Strategic roadmap, [F]flortaucipir
Original languageEnglish
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Publication statusE-pub ahead of print - 2021 Feb 6
Publication categoryResearch