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Purpose <p>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 [<sup>18</sup>F]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 [<sup>18</sup>F]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.</p> Methods <p>Dynamic [<sup>18</sup>F]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 (<i>n</i> = 54), HC (<i>n</i> = 18), and disease controls (α-synucleinopathies, <i>n</i> = 21; Alzheimer’s disease (AD, <i>n</i> = 22) using VT-ratios (VTr) and 20-40min static standardized uptake value ratios (SUVr).</p> Results <p>Using the data-driven temporo-orbital WM reference, PSP patients showed significantly higher basal ganglia [<sup>18</sup>F]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 [<sup>18</sup>F]PI-2620 showed significant associations with clinical disease severity exclusively when using the novel temporo-orbital WM reference.</p> Conclusions <p> A data-driven temporo-orbital WM reference optimizes [<sup>18</sup>F]PI-2620 PET assessment for PSP diagnosis, outperforming conventional cerebellar references used in tau-PET imaging.</p>

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Developing a novel reference region for [18F]PI-2620-PET imaging to facilitate the assessment of 4-repeat tauopathies

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年6月10日

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  • Lukas Frontzkowski,
  • Johannes Gnörich,
  • Mattes Gross,
  • Amir Dehsarvi,
  • Sebastian N. Roemer-Cassiano,
  • Carla Palleis,
  • Sabrina Katzdobler,
  • Anna Dewenter,
  • Anna Steward,
  • Davina Biel,
  • Fabian Hirsch,
  • Zeyu Zhu,
  • Johannes Levin,
  • Andrew W. Stephens,
  • Andre Müller,
  • Norman Koglin,
  • Gérard N. Bischof,
  • Gabor G. Kovacs,
  • Günter U. Höglinger,
  • Matthias Brendel,
  • Nicolai Franzmeier

摘要

Purpose

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.

Methods

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).

Results

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.

Conclusions

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.