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

• Published in: European journal of nuclear medicine and molecular imaging Vol. 48; no. 7; pp. 2110 - 2120
• Main Authors: Bischof, Gérard N, Dodich, Alessandra, Boccardi, Marina, van Eimeren, Thilo, Festari, Cristina, Barthel, Henryk, Hansson, Oskar, Nordberg, Agneta, Ossenkoppele, Rik, Sabri, Osama, Giovanni, B Frisoni G, Garibotto, Valentina, Drzezga, Alexander
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 2021; Springer Nature B.V
• Subjects: Alzheimer's disease; Basic Medicine; Biomarker-based diagnosis; Biomarkers; Cardiology; Context; Imaging; Mathematical analysis; Medical and Health Sciences; Medical diagnosis; Medicin och hälsovetenskap; Medicine; Medicine & Public Health; Medicinska och farmaceutiska grundvetenskaper; Neurodegenerative diseases; Neurology – Dementia; Neurosciences; Neurovetenskaper; Nuclear Medicine; Oncology; Orthopedics; Phases; Radiology; Review; Review Article; Second-generation tau PET tracers; Strategic roadmap; Tau protein; Tracers; Validity; Strategic roadmap; Alzheimer’s disease; Biomarker-based diagnosis; Second-generation tau PET tracers
• ISSN: 1619-7070; 1619-7089; 1619-7089
• DOI: 10.1007/s00259-020-05156-4

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.