TY  - JOUR
AU  - Frontzkowski, Lukas
AU  - Gnoerich, Johannes
AU  - Gross, Mattes
AU  - Dehsarvi, Amir
AU  - Roemer-Cassiano, Sebastian N
AU  - Palleis, Carla
AU  - Katzdobler, Sabrina
AU  - Dewenter, Anna
AU  - Steward, Anna
AU  - Biel, Davina
AU  - Hirsch, Fabian
AU  - Zhu, Zeyu
AU  - Levin, Johannes
AU  - Stephens, Andrew W
AU  - Müller, Andre
AU  - Koglin, Norman
AU  - Bischof, Gérard N
AU  - Kovacs, Gabor G
AU  - Höglinger, Günter U
AU  - Brendel, Matthias
AU  - Franzmeier, Nicolai
TI  - Developing a novel reference region for [18F]PI-2620-PET imaging to facilitate the assessment of 4-repeat tauopathies.
JO  - European journal of nuclear medicine and molecular imaging
VL  - 52
IS  - 13
SN  - 1619-7070
CY  - Heidelberg [u.a.]
PB  - Springer-Verl.
M1  - DZNE-2025-01427
SP  - 5098 - 5112
PY  - 2025
AB  - 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.
KW  - Four-repeat tauopathies (Other)
KW  - Progressive supranuclear palsy (Other)
KW  - Reference region (Other)
KW  - Tau (Other)
KW  - [18F]PI-2620 (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:40490537
C2  - pmc:PMC12589379
DO  - DOI:10.1007/s00259-025-07396-8
UR  - https://pub.dzne.de/record/282975
ER  -