Feasibility of short imaging protocols for [18F]PI‐2620 tau‐PET in progressive supranuclear palsy

Mengmeng Song,Matthias L Schroeter,Gloria Biechele,Lena Kaiser,Henryk Barthel,Jost‐Julian Rumpf,Matthias Brendel,Sabrina Katzdobler,Dorothee Saur,Alexander Nitschmann,Frank Jessen,Guido Boening,Osama Sabri,Maike Kern,Robert Perneczky,Maximilian Scheifele,Bernd Neumaier,Boris‐Stephan Rauchmann,Thilo Van Eimeren,Andreas Schildan,Johannes Levin,Jochen Hammes,Florian Eckenweber,Anika Finze,Marianne Patt,Carla Palleis,Alexander Drzezga,Peter Bartenstein,Leonie Beyer,Sibylle Ziegler,Michael Rullmann,Andrew Stephens ,John Seibyl ,Victor L Villemagne ,Kenneth Marek ,Joseph Claßen ,Gérard N Bischof ,Günter U Höglinger

doi:10.1002/alz.052563

Abstract

AbstractBackgroundDynamic 60‐minute positron‐emission‐tomography (PET) imaging with the novel tau radiotracer [18F]PI‐2620 facilitated accurate discrimination between patients with progressive supranuclear palsy (PSP) and healthy controls (HCs). We now aimed to investigate if shorter acquisition and static time windows of [18F]PI‐2620 tau‐PET can be used for imaging of patients with PSP.MethodWe evaluated 37 patients at five different centers with probable or possible PSP Richardson syndrome (PSP‐RS) together with ten HCs. [18F]PI‐2620 PET was performed by a dynamic 60 minute scan. Distribution volume ratios (DVRs, multilinear reference tissue model 2, cerebellar reference) were calculated using full and truncated scan durations (0‐60, 0‐50, 0‐40, 0‐30, and 0‐20 minutes p.i.). Standardized uptake value ratios (SUVrs, cerebellar reference) were obtained from static imaging windows with 20 minutes duration (20‐40, 30‐50, and 40‐60 minutes p.i.). All DVR and SUVr data were compared with regard to their potential to discriminate patients with PSP‐RS from HCs in predefined subcortical and cortical target regions (effect size, receiver operating area under the curve (AUC), multi‐region classifier). Finally, we tested if shorter [18F]PI‐2620 PET imaging can also be applied to patients with Alzheimer’s disease (n=11).ResultThe effect size of 0‐50 and 0‐40 DVR was equivalent to 0‐60 DVR (averaged Cohen’s d: 1.22 and 1.16 vs. 1.26), whereas the performance dropped for 0‐30 or 0‐20 DVR. The 20‐40 SUVr indicated the best performance of all short static acquisition windows (averaged Cohen’s d: 0.99). The globus pallidus internus discriminated patients with PSP and healthy controls at a similarly high level for 0‐60 DVR (AUC: 0.96), 0‐40 DVR (AUC: 0.96), and 20‐40 SUVr (AUC: 0.94). The multi‐region classifier sensitivity of these time windows was consistently 86%. 0‐40 DVR showed similar performance in Alzheimer’s disease when compared to 0‐60 DVR.ConclusionShort dynamic acquisition and static imaging windows can be used for [18F]PI‐2620 PET imaging of PSP. 0‐40 minute dynamic scanning offers the best balance between accuracy and economic scanning and is may also be suitable for [18F]PI‐2620 PET imaging of Alzheimer’s disease.

Highlights

Progressive supranuclear palsy (PSP) is a neurodegenerative movement disorder characterized by pathological aggregation of hyperphosphorylated microtubule-associated four repeat (4R) isoform tau-protein in neurons and glial cells of the brain [1].Clinical diagnosis of progressive supranuclear palsy (PSP) only shows limited sensitivity and moderate specificity in early disease stages as revealed by recent autopsy-controlled data [2]
This study investigated if truncated acquisition and static time windows can be used for [18F]PI2620 tau-PET imaging of PSP
All Distribution volume ratios (DVRs) and Standardized uptake value ratios (SUVrs) data were compared with regard to their potential to discriminate patients with PSP Richardson syndrome (PSP-RS) from healthy controls (HCs) in predefined subcortical and cortical target regions (effect size, area under the curve (AUC), multi-region classifier)

Summary

Introduction

Clinical diagnosis of PSP only shows limited sensitivity and moderate specificity in early disease stages as revealed by recent autopsy-controlled data [2]. Since the development of tau targeting therapies is progressing at a high pace, the identification of specific biomarkers that would allow for early detection of tau pathology in PSP becomes crucial. An ideal biomarker would ensure that tau targeting therapies could be initiated as early as possible which proves to be critical in neurodegenerative diseases [3]. While current tau targeting trials in PSP include patients in later disease stages, a validated PSP tau biomarker could allow the inclusion of early stage patients without loss of specificity. Dynamic [18F]PI-2620 imaging over one hour already proved a high sensitivity to detect patients with PSP at a high specificity towards healthy controls and tau-negative neurodegeneration disorders [5]

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