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

Area of Science:

• Neuroimaging
• Neurology
• Radiochemistry

Background:

• 4-repeat tauopathies, such as progressive supranuclear palsy (PSP) and cortical basal syndrome (CBS), are debilitating neurodegenerative diseases.
• Accurate quantification of tau pathology is crucial for diagnosis, monitoring disease progression, and evaluating treatment efficacy.
• The second-generation tau tracer 2-(2-([18F]fluoro)pyridin-4-yl)-9H-pyrrolo[2,3-b:4,5-c']dipyridine ([18F]PI-2620) shows promise for in vivo tau imaging.

Purpose of the Study:

• To develop and validate a data-driven methodology for identifying optimal reference regions for [18F]PI-2620 SUV ratio quantification.
• To assess the association of [18F]PI-2620 SUV ratios with clinical measures of disease severity and duration in patients with 4-repeat tauopathy.
• To establish the utility of [18F]PI-2620 for tracking disease progression in PSP and CBS.

Main Methods:

• A novel data-driven approach was employed to identify reference regions in the brain.
• Standardized uptake value (SUV) ratios were calculated using [18F]PI-2620 in patients with clinically diagnosed PSP or CBS.
• Statistical analyses were performed to correlate SUV ratios with clinical symptom severity and disease duration.

Main Results:

• The identified reference regions, specifically the fusiform gyrus and crus-cerebellum, significantly enhanced the quantification of [18F]PI-2620 SUV ratios.
• Calculated SUV ratios demonstrated a significant association with both symptom severity and disease duration in the studied patient cohort.
• The methodology successfully optimized reference regions for automated detection of brain imaging tracers, with potential applicability to other tracers.

Conclusions:

• This study establishes [18F]PI-2620 as a suitable tracer for monitoring disease progression in 4-repeat tauopathies, including PSP and CBS.
• The validated reference regions and methodology improve the clinical utility of [18F]PI-2620 for patient stratification and treatment trial monitoring.
• The data-driven approach for reference region identification offers a valuable tool for advancing brain imaging tracer quantification.