Alzheimer’s Research & Therapy (Nov 2024)

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

  • 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

DOI
https://doi.org/10.1186/s13195-024-01622-5
Journal volume & issue
Vol. 16, no. 1
pp. 1 – 13

Abstract

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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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