Kinetic modeling of 18F-PI-2620 binding in the brain using an image-derived input function with total-body PET

Accurate quantification of tau binding from 18F-PI-2620 PET requires kinetic modeling and an input function. Here, we implemented a non-invasive Image-derived input function (IDIF) derived using the state-of-the-art total-body uEXPLORER PET/CT scanner to quantify tau binding and tracer delivery rate from 18F-PI-2620 in the brain. Additionally, we explored the impact of scan duration on the quantification of kinetic parameters. Total-body PET dynamic data from 15 elderly participants were acquired. Time-activity curves from the grey matter regions of interest (ROIs) were fitted to the two-tissue compartmental model (2TCM) using a subject-specific IDIF derived from the descending aorta. ROI-specific kinetic parameters were estimated for different scan durations ranging from 10 to 90 minutes. Logan graphical analysis was also used to estimate the total distribution volume (VT). Differences in kinetic parameters were observed between ROIs, including significant reduction in tracer delivery rate (K1) in the medial temporal lobe. All kinetic parameters remained relatively stable after the 60-minute scan window across all ROIs, with K1 showing high stability after 30 minutes of scan duration. Excellent correlation was observed between VT estimated using 2TCM and Logan plot analysis. This study demonstrated the utility of IDIF with total-body PET in investigating 18F-PI-2620 kinetics in the brain.