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  18F-PI2620 Tau-PET in progressive supranuclear palsy: A multi-center evaluation

Brendel, M., Barthel, H., van Eimeren, T., Marek, K., Beyer, L., Song, M., et al. (2019). 18F-PI2620 Tau-PET in progressive supranuclear palsy: A multi-center evaluation. Journal of Nuclear Medicine, 60(Suppl. 1): 54.

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 Creators:
Brendel, Matthias1, Author
Barthel, Henryk1, Author
van Eimeren, Thilo1, Author
Marek, Kenneth1, Author
Beyer, Leonie1, Author
Song, Mengmeng1, Author
Palleis, Carla1, Author
Hammes, Jochen1, Author
Saur, Dorothee1, Author
Schroeter, Matthias L.2, Author           
Rumpf, Jost-Julian1, Author
Rullmann, Michael1, Author
Schildan, Andreas1, Author
Patt, Marianne1, Author
Madonia, Jennifer1, Author
Russell, David1, Author
Stephens, Andrew1, Author
Roeber, Sigrun1, Author
Levin, Johannes1, Author
Classen, Joseph1, Author
Hoeglinger, Guenter1, AuthorBartenstein, Peter1, AuthorDrzezga, Alexander1, AuthorSeibyl, John1, AuthorSabri, Osama1, Author more..
Affiliations:
1External Organizations, ou_persistent22              
2Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_634549              

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 Abstract: Background: Progressive supranuclear palsy (PSP) is a 4-repeat (4R) tauopathy and region-specific tau deposits establish the neuropathological diagnosis of “definite PSP” post mortem. Future interventional trials against tau in PSP would strongly benefit from biomarkers to validate the specific presence of the target and to monitor the target’s magnitude during therapy. First generation tau positron-emission-tomography (PET) ligands such as 18F-THK5351 or 18F-AV1451 were somewhat able to distinguish PSP patients from healthy controls (HC) or from patients with other neurodegenerative diseases, but relevant fractions of the PET signal in PSP may have been related to concomitant monoamine-oxidase (MAO) increases. The novel second generation tau-PET ligand 18F-PI2620 proved absent off-target binding to MAO and high affinity to 3/4R tau in Alzheimer’s disease (AD). The aim of this multicenter-evaluation was to investigate 18F-PI2620 in patients with suspected 4R tau pathology in clinically diagnosed PSP. Methods: Seventeen patients (70±7 y, n=8 female) with probable or possible PSP Richardson syndrome according to MDS-PSP criteria underwent 18F-PI2620 PET at four different centers together with ten HC and seven disease controls (Multi-system atrophy, Parkinson’s disease, and AD). PET scans were acquired 0-60 min p.i. followed by coregistration to a 18F-PI2620 template in the MNI space. Standardized uptake value ratios (SUVr) of predefined brain regions in the basal ganglia were generated using cerebellar scaling of a 30-60 min p.i. frame after inspection of the full dynamic range. SUVr data were compared between PSP, HC, and disease controls by an ANOVA including Bonferroni post hoc correction. Statistical parametric mapping (SPM, V12) was performed between PSP and HC (t-test). SUVr and SPM data were corrected for different centers. Additionally, disease severity measured by the PSP rating scale (PSPRS) was correlated with PET findings. An in vitro pilot autoradiography using 18F-PI2620 incubation of brain slices was performed for the globus pallidus of a single PSP patient and compared to the cortical binding in a specimen from an AD patient. Results: Our study indicates significantly elevated mean 18F-PI2620 SUVr in PSP patients (PSPRS: 40±17; range 13-71) in the globus pallidus (1.34±0.16; p = 0.001; d = 1.68) and the substantia nigra (1.33±0.14; p = 0.003; d = 1.49) when compared to HC (1.12±0.09 / 1.15±0.08). Disease controls showed a similar signal in the globus pallidus (1.11±0.06; p = n.s.) and a slight elevation in the substantia nigra (1.23±0.09; p = n.s.) when compared to HC. A voxel-wise analysis SPM revealed elevated 18F-PI2620 uptake in the globus pallidus, the substantia nigra as well as in the frontal and parietal cortex (all p < 0.001, uncorrected) as compared to controls. There was no correlation between 18F-PI2620 SUVr in the globus pallidus and the substantia nigra with PSPRS in any region (all p > 0.2). Subjects with low disease severity (PSPRS &#8804; 30; n=4) already had a significantly elevated 18F-PI2620 uptake in the globus pallidus when compared to HC (1.38±0.13 vs. 1.12±0.09; p = 0.001; d = 2.32). Preliminary in vitro autoradiography showed distinguishable 18F-PI2620 binding in the globus pallidus of a PSP patient which was however far lower when compared to cortical binding in AD. Conclusions: The results of this preliminary multi-center evaluation indicate a value of 18F-PI2620 to diagnose and differentiate suspected PSP patients in vivo. The magnitude of tracer binding between patients seems to be variably expressed but not correlated with disease severity. These results indicate that 18F-PI2620 may show potential as a biomarker to assess tau pathology in PSP patients and that it may be helpful to establish earlier and more reliable diagnosis of PSP.

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 Dates: 2019-05-01
 Publication Status: Published online
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Title: Annual Meeting of the Society-of-Nuclear-Medicine-and-Molecular-Imaging (SNMMI)
Place of Event: Anaheim, CA, USA
Start-/End Date: 2019-06-22 - 2019-06-25

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Title: Journal of Nuclear Medicine
Source Genre: Journal
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Publ. Info: New York : Society of Nuclear Medicine
Pages: - Volume / Issue: 60 (Suppl. 1) Sequence Number: 54 Start / End Page: - Identifier: ISSN: 0161-5505
CoNE: https://pure.mpg.de/cone/journals/resource/991042725914954