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Open Access 01-12-2024 | Research

Head-to-head comparison of tau PET tracers [¹⁸F]PI-2620 and [¹⁸F]RO948 in non-demented individuals with brain amyloid deposition: the TAU-PET FACEHBI cohort

Authors: Matteo Tonietto, Oscar Sotolongo-Grau, Núria Roé-Vellvé, Santiago Bullich, Juan Pablo Tartari, Ángela Sanabria, Ainhoa García-Sánchez, Edilio Borroni, Christopher Galli, Esther Pérez-Martínez, Joan Castell-Conesa, Isabel Roca, Lluís Tárraga, Agustín Ruiz, Andrew W. Stephens, Mercè Boada, Gregory Klein, Marta Marquié, on behalf of the FACEHBI study group, on behalf of the AMYPAD consortium

Published in: Alzheimer's Research & Therapy | Issue 1/2024

Abstract

Background

Second-generation tau tracers for positron emission tomography (PET) show high affinity for paired helical filaments tau deposits characteristic of Alzheimer´s disease and low off-target binding. Differences in their chemical structure though may lead to variations in their regional tau uptake and off-target signal. In this work, we aimed to compare the in-vivo uptake of tau tracers [¹⁸F]PI-2620 and [¹⁸F]RO948 in the early stages of the AD continuum.

Methods

Data from the TAU-PET FACEHBI clinical trial (EUDRA-CT 2021–000473-83) were analyzed. All participants were non-demented and underwent tau imaging with [¹⁸F]PI-2620 and [¹⁸F]RO948 PET within 3 months, amyloid imaging with [¹⁸F]Florbetaben and brain magnetic resonance imaging. Tau PET standardized uptake values ratios (SUVR) were calculated in Braak and typical off-target regions using the inferior cerebellar cortex as a reference region.

Results

The cohort consisted of 18 individuals with subjective cognitive decline (n = 13) and mild cognitive impairment (n = 5), with centiloid values ranging from 17 to 159. Both tau tracers showed similar tau pathology distribution but presented a distinct off-target signal pattern on visual read. SUVR measurements for [¹⁸F]PI-2620 and [¹⁸F]RO948 were highly correlated in all Braak regions (R² range [0.65–0.80]). Regarding off-target signal, [¹⁸F]PI-2620 had higher SUVRs in vascular structures, and [¹⁸F]RO948 had higher SUVRs in the skull/meninges.

Conclusions

In a cohort of individuals at early stages of the AD continuum, tau PET tracers [¹⁸F]PI-2620 and [¹⁸F]RO948 showed similar in-vivo uptake in all Braak regions and distinct off-target signal. These preliminary results support the development of standardized quantification scales for tau deposition that are tracer-independent.

Trial registration

AEMPS EudraCT 2021–000473-83. Registered 30 December 2021.

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Title: Head-to-head comparison of tau PET tracers [18F]PI-2620 and [18F]RO948 in non-demented individuals with brain amyloid deposition: the TAU-PET FACEHBI cohort
Authors: Matteo Tonietto
Oscar Sotolongo-Grau
Núria Roé-Vellvé
Santiago Bullich
Juan Pablo Tartari
Ángela Sanabria
Ainhoa García-Sánchez
Edilio Borroni
Christopher Galli
Esther Pérez-Martínez
Joan Castell-Conesa
Isabel Roca
Lluís Tárraga
Agustín Ruiz
Andrew W. Stephens
Mercè Boada
Gregory Klein
Marta Marquié
on behalf of the FACEHBI study group
on behalf of the AMYPAD consortium
Publication date: 01-12-2024
Publisher: BioMed Central
Published in: Alzheimer's Research & Therapy / Issue 1/2024
Electronic ISSN: 1758-9193
DOI: https://doi.org/10.1186/s13195-024-01622-5

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