Early-phase [18F]PI-2620 tau-PET imaging as a surrogate marker of neuronal 
injury

Beyer, Leonie; Nitschmann, Alexander; Barthel, Henryk; van Eimeren, Thilo; Unterrainer, Marcus; Sauerbeck, Julia; Marek, Ken; Song, Mengmeng; Palleis, Carla; Respondek, Gesine; Hammes, Jochen; Barbe, Michael T.; Onur, Özgür; Jessen, Frank; Saur, Dorothee; Schroeter, Matthias L.; Rumpf, Jost-Julian; Rullmann, Michael; Schildan, Andreas; Patt, Marianne; Neumaier, Bernd; Barret, Olivier; Madonia, Jennifer; Russell, David S.; Stephens, Andrew W.; Roeber, Sigrun; Herms, Jochen; Bötzel, Kai; Levin, Johannes; Classen, Joseph; Höglinger, Günter U.; Bartenstein, Peter; Villemagne, Victor; Drzezga, Alexander; Seibyl, John; Sabri, Osama; Brendel, Matthias

doi:10.1007/s00259-020-04788-w

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Early-phase [18F]PI-2620 tau-PET imaging as a surrogate marker of neuronal injury

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Schroeter, Matthias L.
Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society;

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Citation

Beyer, L., Nitschmann, A., Barthel, H., van Eimeren, T., Unterrainer, M., Sauerbeck, J., et al. (2020). Early-phase [18F]PI-2620 tau-PET imaging as a surrogate marker of neuronal injury. European Journal of Nuclear Medicine and Molecular Imaging, 47(12), 2911-2922. doi:10.1007/s00259-020-04788-w.

Cite as: https://hdl.handle.net/21.11116/0000-0006-59D2-9

Abstract

Purpose

Second-generation tau radiotracers for use with positron emission tomography (PET) have been developed for visualization of tau deposits in vivo. For several β-amyloid and first-generation tau-PET radiotracers, it has been shown that early-phase images can be used as a surrogate of neuronal injury. Therefore, we investigated the performance of early acquisitions of the novel tau-PET radiotracer [18F]PI-2620 as a potential substitute for [18F]fluorodeoxyglucose ([18F]FDG).
Methods

Twenty-six subjects were referred with suspected tauopathies or overlapping parkinsonian syndromes (Alzheimer’s disease, progressive supranuclear palsy, corticobasal syndrome, multi-system atrophy, Parkinson’s disease, multi-system atrophy, Parkinson's disease, frontotemporal dementia) and received a dynamic [18F]PI-2620 tau-PET (0–60 min p.i.) and static [18F]FDG-PET (30–50 min p.i.). Regional standardized uptake value ratios of early-phase images (single frame SUVr) and the blood flow estimate (R1) of [18F]PI-2620-PET were correlated with corresponding quantification of [18F]FDG-PET (global mean/cerebellar normalization). Reduced tracer uptake in cortical target regions was also interpreted visually using 3-dimensional stereotactic surface projections by three more and three less experienced readers. Spearman rank correlation coefficients were calculated between early-phase [18F]PI-2620 tau-PET and [18F]FDG-PET images for all cortical regions and frequencies of disagreement between images were compared for both more and less experienced readers.
Results

Highest agreement with [18F]FDG-PET quantification was reached for [18F]PI-2620-PET acquisition from 0.5 to 2.5 min p.i. for global mean (lowest R = 0.69) and cerebellar scaling (lowest R = 0.63). Correlation coefficients (summed 0.5–2.5 min SUVr & R1) displayed strong agreement in all cortical target regions for global mean (RSUVr 0.76, RR1 = 0.77) and cerebellar normalization (RSUVr 0.68, RR1 = 0.68). Visual interpretation revealed high regional correlations between early-phase tau-PET and [18F]FDG-PET. There were no relevant differences between more and less experienced readers.
Conclusion

Early-phase imaging of [18F]PI-2620 can serve as a surrogate biomarker for neuronal injury. Dynamic imaging or a dual time-point protocol for tau-PET imaging could supersede additional [18F]FDG-PET imaging by indexing both the distribution of tau and the extent of neuronal injury.