%0 Conference Paper
%A Frontzkowski, Lukas
%A Gross, Mattes
%A Roemer-Cassiano, Sebastian
%A Palleis, Carla
%A Dehsarvi, Amir
%A Katzdobler, Sabrina
%A Dewenter, Anna
%A Steward, Anna
%A Biel, Davina
%A Hirsch, Fabian
%A Gnoerich, Johannes
%A Levin, Johannes
%A Stephens, Andrew W.
%A Mueller, Andre
%A Koglin, Norman
%A Bischof, Gérard N
%A Kovacs, Gabor G.
%A Höglinger, Günter U
%A Brendel, Matthias
%A Franzmeier, Nicolai
%T Developing a Novel Reference Region for PI‐2620‐PET Imaging to Facilitate Assessment of 4‐Repeat Tauopathies
%J Alzheimer's and dementia
%V 21
%N S2
%@ 1552-5260
%M DZNE-2026-00036
%P e104777
%D 2025
%X Neurodegenerative 4-repeat (4R) tauopathies commonly manifest as progressive supranuclear palsy (PSP). PSP patients show elevated PI-2620-PET in subcortical 4R tau predilection sites (e.g., globus pallidus), suggesting PI-2620-PET as a promising 4R tau neuroimaging candidate. However, optimal quantification of PI-2620-PET in 4R tauopathies remains challenging, as conventional cerebellar tau-PET reference regions also accumulate 4R tau. We aimed to use unbiased image-derived input function (IDIF) PET data to determine an optimized PET reference region for in vivo quantification of 4R tau.We obtained 60-minute dynamic PI-2620-PET in 54 PSP Richardson Syndrome (PSP-RS) patients and 19 healthy controls (HC), applying IDIF-modeling using carotid timeseries to assess unbiased PI-2620-PET binding and determine total distribution volume (VT). Through an iterative approach, we intensity-normalized VT-images against white-matter regions in the Hammers brain atlas, identifying regions where intensity-normalized pallidum PET values showed the largest PSP-RS vs. HC differences. White-matter regions with strongest PSP-RS vs. HC differences surviving multiple-comparison correction were summarized into a single reference region spanning bilateral temporo-orbital white-matter. This ROI was then used to determine SUVRs using conventional 20-40 minute PI-2620-PET data in PSP-RS, a PSP-non-RS validation sample (n = 63), as well as non-tau disease controls (i.e., alpha-synucleinopathies, n = 20; Alzheimer's disease, n = 23).Using PI-2620 SUVRs obtained with the temporo-orbital white-matter reference, we detected strong PSP-RS vs. HC group differences in basal ganglia SUVRs using voxel-wise comparisons (p <0.001, FWE-cluster corrected). Similar basal ganglia differences were detected for PSP-non-RS vs. HC, but not for alpha-syn (no group differences) or AD vs. HC (cortical AD-like group differences). In contrast, minimal group differences were found using a conventional inferior cerebellar grey matter reference region.Our findings strongly suggest temporo-orbital white-matter is superior to inferior cerebellum as a reference region for PI-2620-PET imaging in 4R tauopathies, due to increased sensitivity and purported specificity for 4R tau.
%B Alzheimer’s Association International Conference
%C 27 Jul 2025 - 31 Jul 2025, Toronto (Canada)
Y2 27 Jul 2025 - 31 Jul 2025
M2 Toronto, Canada
%K Humans
%K Positron-Emission Tomography
%K Supranuclear Palsy, Progressive: diagnostic imaging
%K Supranuclear Palsy, Progressive: metabolism
%K Male
%K Female
%K tau Proteins: metabolism
%K Aged
%K Biomarkers: metabolism
%K Middle Aged
%K Brain: diagnostic imaging
%K Brain: metabolism
%K Tauopathies: diagnostic imaging
%K Tauopathies: metabolism
%K Neuroimaging
%K tau Proteins (NLM Chemicals)
%K Biomarkers (NLM Chemicals)
%F PUB:(DE-HGF)1 ; PUB:(DE-HGF)16
%9 AbstractJournal Article
%R 10.1002/alz70856_104777
%U https://pub.dzne.de/record/283140