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000282975 1001_ $$00000-0001-9321-956X$$aFrontzkowski, Lukas$$b0
000282975 245__ $$aDeveloping a novel reference region for [18F]PI-2620-PET imaging to facilitate the assessment of 4-repeat tauopathies.
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000282975 520__ $$aProgressive 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.
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000282975 650_7 $$2Other$$aFour-repeat tauopathies
000282975 650_7 $$2Other$$aProgressive supranuclear palsy
000282975 650_7 $$2Other$$aReference region
000282975 650_7 $$2Other$$aTau
000282975 650_7 $$2Other$$a[18F]PI-2620
000282975 7001_ $$0P:(DE-2719)9001652$$aGnoerich, Johannes$$b1$$udzne
000282975 7001_ $$aGross, Mattes$$b2
000282975 7001_ $$aDehsarvi, Amir$$b3
000282975 7001_ $$aRoemer-Cassiano, Sebastian N$$b4
000282975 7001_ $$0P:(DE-2719)9000852$$aPalleis, Carla$$b5$$udzne
000282975 7001_ $$0P:(DE-2719)9001160$$aKatzdobler, Sabrina$$b6$$udzne
000282975 7001_ $$aDewenter, Anna$$b7
000282975 7001_ $$aSteward, Anna$$b8
000282975 7001_ $$aBiel, Davina$$b9
000282975 7001_ $$aHirsch, Fabian$$b10
000282975 7001_ $$aZhu, Zeyu$$b11
000282975 7001_ $$0P:(DE-2719)2811659$$aLevin, Johannes$$b12$$udzne
000282975 7001_ $$aStephens, Andrew W$$b13
000282975 7001_ $$aMüller, Andre$$b14
000282975 7001_ $$aKoglin, Norman$$b15
000282975 7001_ $$0P:(DE-2719)9002485$$aBischof, Gérard N$$b16
000282975 7001_ $$aKovacs, Gabor G$$b17
000282975 7001_ $$0P:(DE-2719)2811373$$aHöglinger, Günter U$$b18$$udzne
000282975 7001_ $$0P:(DE-2719)9001539$$aBrendel, Matthias$$b19$$eLast author$$udzne
000282975 7001_ $$aFranzmeier, Nicolai$$b20
000282975 773__ $$0PERI:(DE-600)2098375-X$$a10.1007/s00259-025-07396-8$$gVol. 52, no. 13, p. 5098 - 5112$$n13$$p5098 - 5112$$tEuropean journal of nuclear medicine and molecular imaging$$v52$$x1619-7070$$y2025
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