TY - JOUR
T1 - Clinical validity of increased cortical binding of tau ligands of the THK family and PBB3 on PET as biomarkers for Alzheimer’s disease in the context of a structured 5-phase development framework
AU - Chiotis, Konstantinos
AU - Dodich, Alessandra
AU - Boccardi, Marina
AU - Festari, Cristina
AU - Drzezga, Alexander
AU - Hansson, Oskar
AU - Ossenkoppele, Rik
AU - Frisoni, Giovanni
AU - Garibotto, Valentina
AU - Nordberg, Agneta
N1 - Funding Information: This work was supported by the Swiss National Science Foundation (grant n. IZSEZ0_188355), by the Alzheimer?s Association, by the OsiriX Foundation, and by the APRA (Association Suisse pour la Recherche sur l?Alzheimer). We wish to thank the Swedish Foundation for Strategic Research (SSF; RB13-0192), the Swedish Research Council (projects 05817, 2017-0295, and 2017-06086), the Center for Innovative Medicine (CIMED; Region Stockholm and Karolinska Institutet), the Regional Agreement on Medical Training and Clinical Research (ALF) for Region Stockholm, the Swedish Society for Medical Research, the Loo and Hans Osterman Foundation for Medical Research, the Foundation for Geriatric Diseases at Karolinska Institutet, the Magnus Bergvalls Foundation, the Tore Nilson Foundation for Medical Research, the Sigurd and Elsa Golje Memorial, the Eva och Oscar Ahr?n Research Foundation Stockholm, the Foundation for Old Servants, the Axel Linder Foundation, the ?hl?n Foundation, the Gun and Bertil Stohne Foundation, the Karolinska Institutet Foundations, the Swedish Brain Foundation, the Swedish Alzheimer?s Foundation, the Swedish Dementia Association, and the EU FW7 large-scale integrating project INMiND (http://www.uni-muenster.de/INMiND) for financial support. Konstantinos Chiotis was supported by Region Stockholm (clinical postdoctorial appointment). V. Garibotto was supported by the Swiss National Science Foundation (projects 320030_169876 and 320030_185028) and by the Velux foundation (project 1123). Funding Information: This work was supported by the Swiss National Science Foundation (grant n. IZSEZ0_188355), by the Alzheimer’s Association, by the OsiriX Foundation, and by the APRA (Association Suisse pour la Recherche sur l’Alzheimer). Funding Information: We wish to thank the Swedish Foundation for Strategic Research (SSF; RB13-0192), the Swedish Research Council (projects 05817, 2017-0295, and 2017-06086), the Center for Innovative Medicine (CIMED; Region Stockholm and Karolinska Institutet), the Regional Agreement on Medical Training and Clinical Research (ALF) for Region Stockholm, the Swedish Society for Medical Research, the Loo and Hans Osterman Foundation for Medical Research, the Foundation for Geriatric Diseases at Karolinska Institutet, the Magnus Bergvalls Foundation, the Tore Nilson Foundation for Medical Research, the Sigurd and Elsa Golje Memorial, the Eva och Oscar Ahrén Research Foundation Stockholm, the Foundation for Old Servants, the Axel Linder Foundation, the Åhlén Foundation, the Gun and Bertil Stohne Foundation, the Karolinska Institutet Foundations, the Swedish Brain Foundation, the Swedish Alzheimer’s Foundation, the Swedish Dementia Association, and the EU FW7 large-scale integrating project INMiND ( http://www.uni-muenster.de/INMiND ) for financial support. Konstantinos Chiotis was supported by Region Stockholm (clinical postdoctorial appointment). Funding Information: V. Garibotto was supported by the Swiss National Science Foundation (projects 320030_169876 and 320030_185028) and by the Velux foundation (project 1123). Publisher Copyright: © 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/7
Y1 - 2021/7
N2 - Purpose: The research community has focused on defining reliable biomarkers for the early detection of the pathological hallmarks of Alzheimer’s disease (AD). In 2017, the Geneva AD Biomarker Roadmap initiative adapted the framework for the systematic validation of oncological biomarkers to AD, with the aim to accelerate their development and implementation in clinical practice. The aim of this work was to assess the validation status of tau PET ligands of the THK family and PBB3 as imaging biomarkers for AD, based on the Biomarker Roadmap methodology. Methods: A panel of experts in AD biomarkers convened in November 2019 at a 2-day workshop in Geneva. The level of clinical validity of tau PET ligands of the THK family and PBB3 was assessed based on the 5-phase development framework before the meeting and discussed during the workshop. Results: PET radioligands of the THK family discriminate well between healthy controls and patients with AD dementia (phase 2; partly achieved) and recent evidence suggests an accurate diagnostic accuracy at the mild cognitive impairment (MCI) stage of the disease (phase 3; partly achieved). The phases 2 and 3 were considered not achieved for PBB3 since no evidence exists about the ligand’s diagnostic accuracy. Preliminary evidence exists about the secondary aims of each phase for all ligands. Conclusion: Much work remains for completing the aims of phases 2 and 3 and replicating the available evidence. However, it is unlikely that the validation process for these tracers will be completed, given the presence of off-target binding and the development of second-generation tracers with improved binding and pharmacokinetic properties.
AB - Purpose: The research community has focused on defining reliable biomarkers for the early detection of the pathological hallmarks of Alzheimer’s disease (AD). In 2017, the Geneva AD Biomarker Roadmap initiative adapted the framework for the systematic validation of oncological biomarkers to AD, with the aim to accelerate their development and implementation in clinical practice. The aim of this work was to assess the validation status of tau PET ligands of the THK family and PBB3 as imaging biomarkers for AD, based on the Biomarker Roadmap methodology. Methods: A panel of experts in AD biomarkers convened in November 2019 at a 2-day workshop in Geneva. The level of clinical validity of tau PET ligands of the THK family and PBB3 was assessed based on the 5-phase development framework before the meeting and discussed during the workshop. Results: PET radioligands of the THK family discriminate well between healthy controls and patients with AD dementia (phase 2; partly achieved) and recent evidence suggests an accurate diagnostic accuracy at the mild cognitive impairment (MCI) stage of the disease (phase 3; partly achieved). The phases 2 and 3 were considered not achieved for PBB3 since no evidence exists about the ligand’s diagnostic accuracy. Preliminary evidence exists about the secondary aims of each phase for all ligands. Conclusion: Much work remains for completing the aims of phases 2 and 3 and replicating the available evidence. However, it is unlikely that the validation process for these tracers will be completed, given the presence of off-target binding and the development of second-generation tracers with improved binding and pharmacokinetic properties.
KW - Alzheimer’s disease
KW - Biomarker-based diagnosis
KW - PBB3
KW - Strategic roadmap
KW - THK
KW - Tau PET
UR - http://www.scopus.com/inward/record.url?scp=85102426162&partnerID=8YFLogxK
U2 - https://doi.org/10.1007/s00259-021-05277-4
DO - https://doi.org/10.1007/s00259-021-05277-4
M3 - Review article
C2 - 33723628
SN - 1619-7070
VL - 48
SP - 2086
EP - 2096
JO - European journal of nuclear medicine and molecular imaging
JF - European journal of nuclear medicine and molecular imaging
IS - 7
ER -