Improved Tau PET SUVR Quantification in 4-Repeat Tau Phenotypes with [¹⁸F]PI-2620

We used a new data-driven methodology to identify a set of reference regions that enhanced the quantification of the SUV ratio of the second-generation tau tracer 2-(2-([¹⁸F]fluoro)pyridin-4-yl)-9H-pyrrolo[2,3-b:4,5-c']dipyridine ([¹⁸F]PI-2620) in a group of patients clinically diagnosed with 4-repeat tauopathy, specifically progressive supranuclear palsy or cortical basal syndrome. The study found that SUV ratios calculated using the identified reference regions (i.e., fusiform gyrus and crus-cerebellum) were significantly associated with symptom severity and disease duration. This establishes, for the first time to our knowledge, the suitability of [¹⁸F]PI-2620 for tracking disease progression in this 4-repeat disease population. This is an important step toward increased clinical utility, such as patient stratification and monitoring in disease-modifying treatment trials. Additionally, the applied methodology successfully optimized reference regions for automated detection of brain imaging tracers. This approach may also hold value for other brain imaging tracers.