Journal Article

DZNE-2025-01427

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Developing a novel reference region for [18F]PI-2620-PET imaging to facilitate the assessment of 4-repeat tauopathies.

Frontzkowski, L. ; Gnoerich, J.Extern* ; Gross, M. ; Dehsarvi, A. ; Roemer-Cassiano, S. N. ; Palleis, C.DZNE* ; Katzdobler, S.Extern* ; Dewenter, A. ; Steward, A. ; Biel, D. ; Hirsch, F. ; Zhu, Z. ; Levin, J.DZNE* ; Stephens, A. W. ; Müller, A. ; Koglin, N. ; Bischof, G. N. ; Kovacs, G. G. ; Höglinger, G. U.DZNE* ; Brendel, M. (Last author)DZNE* ; Franzmeier, N.

2025
Springer-Verl. Heidelberg [u.a.]

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Please use a persistent id in citations: doi:10.1007/s00259-025-07396-8

Abstract: 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.

Keyword(s): Four-repeat tauopathies ; Progressive supranuclear palsy ; Reference region ; Tau ; [18F]PI-2620

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Contributing Institute(s):

1. Molecular Neurodegeneration (AG Haass)
2. Clinical Research (Munich) (Clinical Research (Munich))
3. Clinical Neurodegeneration (AG Levin)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)
2. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2025

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Database coverage:
; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; DEAL Springer ; DEAL Springer ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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