Clinical validity of second-generation tau PET tracers as biomarkers for Alzheimer’s disease in the context of a structured 5-phase development framework

G. rard N. Bischof*, Alessandra Dodich, Marina Boccardi, Thilo van Eimeren, Cristina Festari, Henryk Barthel, Oskar Hansson, Agneta Nordberg, Rik Ossenkoppele, Osama Sabri, B. Frisoni G. Giovanni, Valentina Garibotto, Alexander Drzezga

*Corresponding author for this work

Research output: Contribution to journalReview articleAcademicpeer-review

Abstract

Purpose: In 2017, the Geneva Alzheimer’s disease (AD) strategic biomarker roadmap initiative proposed a framework of the systematic validation AD biomarkers to harmonize and accelerate their development and implementation in clinical practice. Here, we use this framework to examine the translatability of the second-generation tau PET tracers into the clinical context. Methods: All available literature was systematically searched based on a set of search terms that related independently to analytic validity (phases 1–2), clinical validity (phase 3–4), and clinical utility (phase 5). The progress on each of the phases was determined based on scientific criteria applied for each phase and coded as fully, partially, preliminary achieved or not achieved at all. Results: The validation of the second-generation tau PET tracers has successfully passed the analytical phase 1 of the strategic biomarker roadmap. Assay definition studies showed evidence on the superiority over first-generation tau PET tracers in terms of off-target binding. Studies have partially achieved the primary aim of the analytical validity stage (phase 2), and preliminary evidence has been provided for the assessment of covariates on PET signal retention. Studies investigating of the clinical validity in phases 3, 4, and 5 are still underway. Conclusion: The current literature provides overall preliminary evidence on the establishment of the second-generation tau PET tracers into the clinical context, thereby successfully addressing some methodological issues from the tau PET tracer of the first generation. Nevertheless, bigger cohort studies, longitudinal follow-up, and examination of diverse disease population are still needed to gauge their clinical validity.
Original languageEnglish
Pages (from-to)2110-2120
Number of pages11
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Volume48
Issue number7
Early online date2021
DOIs
Publication statusE-pub ahead of print - 2021

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