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. 2021 Nov;48(12):3872-3885.
doi: 10.1007/s00259-021-05391-3. Epub 2021 May 22.

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

Mengmeng Song #  1 , Maximilian Scheifele #  1 , Henryk Barthel  2 , Thilo van Eimeren  3   4   5   6 , Leonie Beyer  1 , Ken Marek  7   8 , Florian Eckenweber  1 , Carla Palleis  9 , Lena Kaiser  1 , Anika Finze  1 , Maike Kern  1 , Alexander Nitschmann  1 , Gloria Biechele  1 , Sabrina Katzdobler  9 , Gèrard Bischof  4 , Jochen Hammes  4   10 , Frank Jessen  6   11   12 , Dorothee Saur  13 , Matthias L Schroeter  13   14   15   16 , Jost-Julian Rumpf  13 , Michael Rullmann  2 , Andreas Schildan  2 , Marianne Patt  2 , Bernd Neumaier  17   18 , Andrew W Stephens  19 , Boris-Stephan Rauchmann  20   21 , Robert Perneczky  20   22   23   24 , Johannes Levin  9   23   24 , Joseph Classen  13 , Günter U Höglinger  11   23   24   25 , Peter Bartenstein  1   24 , Guido Boening  1 , Sibylle Ziegler  1   24 , Victor Villemagne  26   27   28 , Alexander Drzezga  4   6 , John Seibyl  7   8 , Osama Sabri  2 , Matthias Brendel  29 ; German Imaging Initiative for Tauopathies (GII4T)
Affiliations

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

Mengmeng Song et al. Eur J Nucl Med Mol Imaging. 2021 Nov.

Abstract

Purpose: Dynamic 60-min 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). This study investigated if truncated acquisition and static time windows can be used for [18F]PI-2620 tau-PET imaging of PSP.

Methods: Thirty-seven patients with PSP Richardson syndrome (PSP-RS) were evaluated together with ten HCs. [18F]PI-2620 PET was performed by a dynamic 60-min scan. Distribution volume ratios (DVRs) were calculated using full and truncated scan durations (0-60, 0-50, 0-40, 0-30, and 0-20 min p.i.). Standardized uptake value ratios (SUVrs) were obtained 20-40, 30-50, and 40-60 min 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, area under the curve (AUC), multi-region classifier).

Results: 0-50 and 0-40 DVR showed equivalent effect sizes as 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 static acquisition windows (averaged Cohen's d: 0.99). The globus pallidus internus discriminated patients with PSP-RS and HCs 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%.

Conclusion: Truncated and static imaging windows can be used for [18F]PI-2620 PET imaging of PSP. 0-40 min dynamic scanning offers the best balance between accuracy and economic scanning.

Keywords: Progressive supranuclear palsy; Tau-PET; Time window; [18F]PI-2620.

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Conflict of interest statement

M.B. received speaker honoraria from GE healthcare and LMI and is an advisor of LMI. M.T.B. received speaker’s honoraria from Medtronic, Boston Scientific, Abbott (formerly St. Jude), GE Medical, UCB, Bial and research funding from the Felgenhauer-Stiftung, Forschungspool Klinische Studien (University of Cologne), H2020, Medtronic and Boston Scientific. C.P. received research funding from Lüneburg heritage. G.U.H. received research support from GE Healthcare and Neuropore; has ongoing research collaborations with Orion and Prothena; serves as a consultant for AbbVie, AlzProtect, Asceneuron, Biogen, Biohaven, Lundbeck, Novartis, Roche, Sanofi, and UCB; received honoraria for scientific presentations from AbbVie, Biogen, Roche, Teva, UCB, and Zambon; and holds a patent on PERK Activation for the Treatment of Neurodegenerative Diseases (PCT/EP2015/068734). G.R. received honoraria for scientific presentations from Biogen. O.S. receives research support from LMI. All other authors do not report a conflict of interest.

Figures

Fig. 1
Fig. 1
Representative [18F]PI-2620 images for different dynamic and static imaging windows. Axial slices upon an MRI standard template of a patient with PSP Richardson syndrome (PSP-RS; female, 69 years, PSP rating scale: 34) and a healthy control (HC; female, 70 years) show distribution volume ratios (DVR) and standardized uptake value ratios (SUVr)
Fig. 2
Fig. 2
Effect sizes (Cohen’s d) in all brain regions for different dynamic and static [18F]PI-2620 imaging windows. DVR, distribution volume ratio; SUVr, standardized uptake value ratio; GPe, globus pallidus externus; GPi, globus pallidus internus; PUT, putamen; STN, subthalamic nucleus; SN, substantia nigra; DMB, dorsal midbrain; MPFC, medial prefrontal cortex; DLPFC, dorsolateral prefrontal cortex; DN, dentate nucleus. Negative Cohen’s d values were multiplied by −1 for comparability purposes
Fig. 3
Fig. 3
Receiver-operating characteristic (ROC) curve analysis in the globus pallidus internus. ROC curves show the discrimination of patients with progressive supranuclear palsy Richardson syndrome and healthy controls by globus pallidus internus quantification in different dynamic and static [18F]PI-2620 imaging windows. DVR, distribution volume ratio; SUVr, standardized uptake value ratio
Fig. 4
Fig. 4
Multi-region classifier in comparison of dynamic and static imaging windows. Semi-quantitative classification (red, positive; green, negative) of PSP target regions was performed by applying a mean value (MV) + 2 standard deviations (SD) threshold as obtained from the healthy control (HC) data. One single region defined the scan as global positive, and only the global read-out is shown. Bottom rows provide the number of positive classified scans relative to the analyzed scans. PSP, progressive supranuclear palsy; RS, Richardson syndrome; DVR, distribution volume ratio; SUVr, standardized uptake value ratio
Fig. 5
Fig. 5
Representative [18F]PI-2620 images for 0–60 DVR, 0–40 DVR, and 20–40 SUVr in Alzheimer’s disease (AD) and α-synucleinopathies. Axial slices upon an MRI standard template show distribution volume ratios (DVR) and the standardized uptake value ratio (SUVr) of a patient with AD (female, 66 years, MMSE: 20), a patient with PD (female, 57 years, MoCA: 28, UPDRS: 25), and a patient with MSA-C (male, 55 years, MoCA: 26, UPDRS: 28)
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