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 18 FPI-2620 as a potential substitute for 18 Ffluorodeoxyglucose ( 18 FFDG). 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 18 FPI-2620 tau-PET (0–60 min p.i.) and static 18 FFDG-PET (30–50 min p.i.). Regional standardized uptake value ratios of early-phase images (single frame SUVr) and the blood flow estimate (R 1 ) of 18 FPI-2620-PET were correlated with corresponding quantification of 18 FFDG-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 18 FPI-2620 tau-PET and 18 FFDG-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 18 FFDG-PET quantification was reached for 18 FPI-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 & R 1 ) displayed strong agreement in all cortical target regions for global mean (R SUVr 0.76, R R1  = 0.77) and cerebellar normalization (R SUVr 0.68, R R1  = 0.68). Visual interpretation revealed high regional correlations between early-phase tau-PET and 18 FFDG-PET. There were no relevant differences between more and less experienced readers. Conclusion Early-phase imaging of 18 FPI-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 18 FFDG-PET imaging by indexing both the distribution of tau and the extent of neuronal injury.