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Beyer, Leonie; Nitschmann, Alexander; Barthel, Henryk; Eimeren, Thilo van; Drzezga, Alexander; Seibyl, John; Sabri, Osama; Unterrainer, Marcus; Sauerback, Julia; Marek, Ken; Song, Mengmeng; Palleis, Carla; Respondek, Gesine; Hammes, Jochen; Barbe, Michael T.; Onur, Ozgur A.; 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; Brendel, Matthias (2020): Early-phase 18FPI-2620 tau-PET imaging as a surrogate marker of neuronal injury. In: European journal of nuclear medicine and molecular imaging, Vol. 47: pp. 2911-2922
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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 \textgreekb-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 18FPI-2620 as a potential substitute for 18Ffluorodeoxyglucose (18FFDG). 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 18FPI-2620 tau-PET (0-60~min p.i.) and static 18FFDG-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 18FPI-2620-PET were correlated with corresponding quantification of 18FFDG-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 18FPI-2620 tau-PET and 18FFDG-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 18FFDG-PET quantification was reached for 18FPI-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 18FFDG-PET. There were no relevant differences between more and less experienced readers. CONCLUSION Early-phase imaging of 18FPI-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 18FFDG-PET imaging by indexing both the distribution of tau and the extent of neuronal injury.