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.