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

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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 [ 18 F]PI-2620 and [ 18 F]RO948 in the early stages of the AD continuum. 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 [ 18 F]PI-2620 and [ 18 F]RO948 PET within 3 months, amyloid imaging with [ 18 F]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. 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 [ 18 F]PI-2620 and [ 18 F]RO948 were highly correlated in all Braak regions (R 2 range [0.65–0.80]). Regarding off-target signal, [ 18 F]PI-2620 had higher SUVRs in vascular structures, and [ 18 F]RO948 had higher SUVRs in the skull/meninges. In a cohort of individuals at early stages of the AD continuum, tau PET tracers [ 18 F]PI-2620 and [ 18 F]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. AEMPS EudraCT 2021–000473-83. Registered 30 December 2021.

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