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

Abstract

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). 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. 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 (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 [¹⁸F]FDG-PET. There were no relevant differences between more and less experienced readers. 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.