Neuronal injury assessment with early-phases of [18F]PI-2620 tau-PET versus [18F]flutemetamol β-amyloid-PET recordings

Abstract

Abstract Purpose Characteristic features of β-amyloid-PET (A), tau-PET (T) and FDG-PET (N) can serve for the A/T/N classification of neurodegenerative diseases. Recent studies showed that the early, perfusion-weighted phases of β-amyloid- or tau-PET recordings serve as surrogates for cerebrometabolic deficits to FDG-PET, therefore indicate neuronal injury. As such, two channels of diagnostic information can be obtained in the setting of a single PET scan. However, there has hitherto been no comparison of early-phase β-amyloid- and tau-PET as surrogates for deficits in perfusion/metabolism. Therefore, we undertook to compare [18F]flutemetamol β-amyloid-PET and [18F]PI-2620 tau-PET as “one-stop shop” dual purpose tracers for detection of neurodegenerative disease. Methods We obtained early-phase PET recordings with [18F]PI-2620 (0.5–2.5 min p.i.) and [18F]flutemetamol (0–10 min p.i.) in 66 patients with suspected neurodegenerative disease. We contrasted global mean normalized images (SUVr) in the patients with a normal cohort of 15 volunteers without evidence of increased pathology to β-amyloid- and tau-PET examinations. Regional group differences of tracer uptake (z-scores) of 246 Brainnetome volumes-of-interest were calculated for both tracers, and the correlations of the z-scores were evaluated using Spearman’s rank correlation coefficient. Lobar compartments, regions with significant neuronal injury (z-scores < -3) and patients with different neurodegenerative disease entities (e.g., Alzheimer’s disease or 4R-tauopathies) served for subgroup analysis. Additionally, we used partial regression to correlate regional neuronal injury with clinical tests. Results The z-scores of perfusion-weighted images of both tracers showed high correlations across brain, especially in the frontal and parietal lobes, which were the brain regions with pronounced neuronal injury (R = 0.83 ± 0.08; range: 0.61–0.95). Z-scores of individual patients correlated well by region (R = 0.57 ± 0.15; range: 0.16–0.90), notably when significant neuronal injury was present (R = 0.66 ± 0.15; range: 0.28–0.90). Conclusion The early perfusion phases of tau- and β-amyloid-PET are roughly equivalent indices of perfusion defect indicative of regional and lobar neuronal injury in patients with various neurodegenerative diseases. As such, either tracer may serve as a comparable diagnostic channel in the A/T/N classification framework.