Developing a Novel Reference Region for PI-2620-PET Imaging to Facilitate Assessment of 4-Repeat Tauopathies

Sep 30, 2026

Neurodegenerative 4-repeat (4R) tauopathies often present as progressive supranuclear palsy (PSP), with elevated PI-2620-PET signal in subcortical predilection sites such as the globus pallidus. Quantifying PI-2620-PET in vivo is difficult because conventional cerebellar tau-PET reference regions also accumulate 4R tau. The study uses unbiased IDIF-PET modeling and an image-derived optimization strategy to establish a temporo-orbital white-matter reference region for improved 4R tau assessment.

LanguageEnglish

CategoryHealthcare

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Pages4

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Abstract

Background

Methods

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DOI: 10. 1002/alz70856_104777 BIOMARKERS POSTER PRESENTATION NEUROIMAGING Developing a Novel Reference Region for PI-2620-PET Imaging to Facilitate Assessment of 4-Repeat Tauopathies Lukas Frontzkowski1, 2 Mattes Gross3 Sebastian Roemer-Cassiano 1, 4, 5 Carla Palleis6, 7, 8, 9, 10 Amir Dehsarvi 1 Sabrina Katzdobler 11, 12, 13, 14 Anna Dewenter 1 Anna Steward 1, 15 Davina Biel 1 Fabian Hirsch 1 Johannes Gnörich9, 16 Johannes Levin 13, 14, 17, 18, 19 Andrew W. Stephens20 Andre Mueller20 Norman Koglin20 Gérard N Bischof20 Gabor G. Kovacs21, 22, 23 Günter U Höglinger6, 11, 24 Matthias Brendel2, 6, 11 Nicolai Franzmeier25, 26 1 Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Bavaria, Germany 2 Department of Nuclear Medicine, University Hospital, LMU Munich, Munich, Bavaria, Germany 3 Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Bavaria, Germany 4 Department of Neurology, University Hospital, LMU Munich, Munich, Bavaria, Germany 5 Max Planck School of Cognition, Leipzig, Sachsen, Germany 6 German Center for Neurodegenerative Diseases (DZNE), Munich, Germany 7 University Hospital, Ludwig-Maximilians-Universität, Munich, Germany 8 Department of Neurology, Klinikum der Ludwig-Maximilians Universität München, Munich, Bavaria, Germany 9 University Hospital, LMU Munich, Munich, Germany 10 Munich Cluster for Systems Neurology (SyNergy), Munich, Germany 11 Munich Cluster for Systems Neurology (SyNergy), Munich, Bavaria, Germany 12 Department of Neurology, University Hospital, LMU, Munich, Germany 13 University Hospital, LMU Munich, Munich, Bavaria, Germany Abstract Background: 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 asa 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. Methods: 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). This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2025 The Alzheimer’s Association. Alzheimer’s & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer’s Association. Alzheimer’s Dement. 2025;21(Suppl. 2):e104777. [https://doi.org/10.1002/alz70856_104777](https://doi.org/10.1002/alz70856_104777) wi[leyonlinelibrary.com/journal/alz](leyonlinelibrary.com/journal/alz) 1of4 BIOMARKERS 14 German Center for Neurodegenerative Diseases (DZNE), Munich, Bavaria, Germany 15 Institute for Stroke and Dementia Research, LMU, Munich, Munich, Germany

FAQs

Why is selecting a PI-2620-PET reference region challenging in 4-repeat tauopathies?

Conventional cerebellar tau-PET reference regions can also accumulate 4R tau, which complicates accurate quantification of PI-2620-PET binding.

How did the study optimize the PI-2620-PET reference region?

The work used unbiased image-derived input function (IDIF) PET data and an iterative, intensity-normalized comparison of candidate regions to identify areas showing the largest PSP-Rich vs. healthy control differences.

Which reference region performed better in PI-2620-PET imaging results?

Temporo-orbital white-matter produced stronger PSP-RS vs. healthy control differences in basal ganglia SUVRs than a conventional inferior cerebellar grey matter reference region.

Sep 30, 2026

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