Quantification of Tau Load Using [¹⁸F]AV1451 PET.

Area of Science:

• Neuroimaging
• Radiochemistry
• Nuclear Medicine

Background:

• Alzheimer's disease (AD) is characterized by tau pathology.
• [¹⁸F]AV1451 (flortaucipir) is a positron emission tomography (PET) tracer for imaging tau accumulation.
• Standardized uptake value ratios (SUVr) from static scans are commonly used but may be flow-dependent, necessitating validation with quantitative methods, especially for longitudinal studies.

Purpose of the Study:

• To identify the optimal tracer kinetic model for quantifying tau load using [¹⁸F]AV1451 PET.
• To validate quantitative approaches against traditional SUVr measurements.
• To assess the influence of tau burden on model selection.

Main Methods:

• Dynamic 130-minute PET scans with [¹⁸F]AV1451 were performed in 5 AD patients and 5 controls after intravenous injection.
• Arterial blood sampling was used to generate a metabolite-corrected plasma input function.
• Regional time-activity curves were analyzed using various pharmacokinetic models, including single (1T2k_V_B) and two (2T4k_V_B) tissue compartment models, and the simplified reference tissue model (SRTM).

Main Results:

• The reversible single tissue compartment model (1T2k_V_B) was preferred in controls, while the reversible two tissue compartmental model (2T4k_V_B) was favored in AD patients.
• Simplified reference tissue model (SRTM) derived binding potential (BP_ND) correlated well with indirect plasma input binding (DVR-1) in both groups.
• Standardized uptake value ratios (80-100 min) showed strong correlations with distribution volume ratio (DVR) and SRTM-derived BP_ND.

Conclusions:

• [¹⁸F]AV1451 kinetic model preference is influenced by subject status and tau burden (V_T), with higher tau loads potentially requiring a two-compartment model.
• Consistent results can be achieved using the 2T4k_V_B model for AD patients.
• SRTM provides a reliable method for deriving binding potential (BP_ND) for [¹⁸F]AV1451 tau imaging.