%0 Journal Article
%A Frontzkowski, Lukas
%A Gnoerich, Johannes
%A Gross, Mattes
%A Dehsarvi, Amir
%A Roemer-Cassiano, Sebastian N
%A Palleis, Carla
%A Katzdobler, Sabrina
%A Dewenter, Anna
%A Steward, Anna
%A Biel, Davina
%A Hirsch, Fabian
%A Zhu, Zeyu
%A Levin, Johannes
%A Stephens, Andrew W
%A Müller, 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 [18F]PI-2620-PET imaging to facilitate the assessment of 4-repeat tauopathies.
%J European journal of nuclear medicine and molecular imaging
%V 52
%N 13
%@ 1619-7070
%C Heidelberg [u.a.]
%I Springer-Verl.
%M DZNE-2025-01427
%P 5098 - 5112
%D 2025
%X Progressive supranuclear palsy (PSP) is a fatal 4-repeat (4R) tauopathy with progressive movement phenotypes. In-vivo 4R tau biomarkers are therefore crucial for PSP diagnosis, monitoring, and treatment evaluation. The tau-PET tracer [18F]PI-2620 binds to 4R tau and shows increased uptake in PSP-associated regions (e.g., globus pallidus), and is therefore a candidate 4R tau biomarker. However, commonly used cerebellar tau-PET reference regions show regional proximity to cerebellar 4R tau deposits in PSP, confounding semiquantitative [18F]PI-2620 assessments. Therefore, we employed bias-free image-derived input function (IDIF) PET quantification to identify an optimized data-driven reference region for assessing 4R tau in PSP.Dynamic [18F]PI-2620 PET (60 min) was acquired in 58 PSP-Richardson Syndrome (PSP-RS) and 18 healthy controls (HC). IDIF-modelling with carotid timeseries derived total distribution volume (VT). Iteratively normalizing VT images to atlas-based white matter (WM), we identified reference candidates maximizing PSP-RS vs. HC pallidum differences. The best-performing WM references were combined to a temporo-orbital WM reference, validated in PSP-nonRS (n = 54), HC (n = 18), and disease controls (α-synucleinopathies, n = 21; Alzheimer’s disease (AD, n = 22) using VT-ratios (VTr) and 20-40min static standardized uptake value ratios (SUVr).Using the data-driven temporo-orbital WM reference, PSP patients showed significantly higher basal ganglia [18F]PI-2620 signal vs. HC compared to cerebellar normalization. Receiver operating curve (ROC) analysis confirmed higher diagnostic accuracy using the temporo-orbital WM reference. Pallidum [18F]PI-2620 showed significant associations with clinical disease severity exclusively when using the novel temporo-orbital WM reference.A data-driven temporo-orbital WM reference optimizes [18F]PI-2620 PET assessment for PSP diagnosis, outperforming conventional cerebellar references used in tau-PET imaging.The online version contains supplementary material available at 10.1007/s00259-025-07396-8.
%K Four-repeat tauopathies (Other)
%K Progressive supranuclear palsy (Other)
%K Reference region (Other)
%K Tau (Other)
%K [18F]PI-2620 (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:40490537
%2 pmc:PMC12589379
%R 10.1007/s00259-025-07396-8
%U https://pub.dzne.de/record/282975