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

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)F]PI-2620 as a potential substitute for [(18)F]fluorodeoxyglucose ([(18)F]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 [(18)F]PI-2620 tau-PET (0–60 min p.i.) and static [(18)F]FDG-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)F]PI-2620-PET were correlated with corresponding quantification of [(18)F]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 [(18)F]PI-2620 tau-PET and [(18)F]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 [(18)F]FDG-PET quantification was reached for [(18)F]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 & 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)F]FDG-PET. There were no relevant differences between more and less experienced readers. CONCLUSION: Early-phase imaging of [(18)F]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 [(18)F]FDG-PET imaging by indexing both the distribution of tau and the extent of neuronal injury. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00259-020-04788-w) contains supplementary material, which is available to authorized users.