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Alzheimer’s disease biomarker roadmap 2020: Second‐generation tau PET tracers
Author(s) -
Bischof Gerard N.,
Dodich Alessandra,
Ashton Nicholas J,
Boccardi Marina,
Barthel Henryk,
Carrillo Maria C.,
Chiotis Konstantinos,
Corre Julie,
Démonet JeanFrançois,
Gietl Anton F.,
Johnson Keith A.,
Hansson Oskar,
Leuzy Antoine,
Lorenzi Marco,
Nordberg Agneta K,
Ossenkoppele Rik,
Rabinovici Gil D.,
Ratib Osman,
Sabri Osama,
Treyer Valerie,
Unschuld Paul G.,
Villemagne Victor L.L.,
Wolters Emma E.,
Winblad Bengt,
Frisoni Giovanni B.,
Garibotto Valentina,
Drzezga Alexander
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.039556
Subject(s) - biomarker , context (archaeology) , positron emission tomography , medicine , oncology , psychology , nuclear medicine , neuroscience , chemistry , biology , biochemistry , paleontology
Background Selective positron emission tomography (PET) tracers to target neurofibrillary tangles of the second generation have indicated to overcome some of the methodological issues observed with the tau‐tracers of the first generation. How these second‐generation tau tracers may be better suitable for clinical practice was assessed in the context of the Geneva Biomarker Roadmap Initiative during and prior to a two‐day workshop (Geneva, November 2019). Method Guided by a framework for systematic validation of oncological diagnostic biomarkers adapted for the implementation of biomarker quantifying the pathological hallmarks of Alzheimer’s Disease (AD), we evaluated the performance of the tau‐selective tracers of the second generation. Subsequently we defined research priorities focusing on the advancement of the framework, with the goal for implementation of these PET tracers in clinical practice. Result All tracers identified as second generation, have provided evidence for in vitro binding to tau tangles in tissue samples of patients with and without Alzheimer’s disease. Additionally, in vivo pharmacokinetic modeling has been successfully achieved for some (e.g., 18F‐MK‐6240, 18F‐PI‐2620) but not all second‐generation tau tracers (e.g., GTP‐1, 18F‐JNJ‐067). Overall, observational cross‐sectional studies have provided preliminary evidence on the diminished extent of off‐target binding, high discriminatory ability between healthy and diseased populations and sensitivity in clinically diverse samples (e.g., 18F‐RO‐948, 18F‐MK‐6240, 18F‐PI‐2620). Conclusion A readily implementation of the tau tracer of the second‐generation in clinical practice is limited by the scarcity of comprehensive data analysis with bigger samples sizes and by the overall lack of end‐of‐life studies. However, the goal of the second‐generation tau tracers to overcome some of the methodological issues raised by the first generation tau tracers is partially achieved. Finally, the adaptation of the oncological diagnostic framework to the clinical validity of biomarkers measuring AD pathology has proven most useful in formulating new practical research goals to advance the clinical utility of the second generation tau tracer.