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

Alzheimers Res Ther. 2024 Nov 28;16(1):257. doi: 10.1186/s13195-024-01622-5.

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.

Keywords: Alzheimer; FACEHBI; Mild cognitive impairment; Positron emission tomography; Subjective cognitive decline; Tau; [18F]PI-2620; [18F]RO948.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / metabolism
  • Aniline Compounds
  • Brain* / diagnostic imaging
  • Brain* / metabolism
  • Cohort Studies
  • Female
  • Fluorine Radioisotopes / pharmacokinetics
  • Humans
  • Male
  • Middle Aged
  • Positron-Emission Tomography* / methods
  • Pyridines
  • Radiopharmaceuticals / pharmacokinetics
  • Stilbenes
  • tau Proteins* / metabolism

Substances

  • tau Proteins
  • ((18)F)PI-2620
  • 4-(N-methylamino)-4'-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)stilbene
  • Fluorine Radioisotopes
  • Radiopharmaceuticals
  • Aniline Compounds
  • Pyridines
  • Stilbenes