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

Area of Science:

• Nuclear medicine
• Neuroimaging
• Pharmacokinetics

Background:

• Accurate quantification of tau pathology using 18F-PI-2620 PET requires kinetic modeling and an input function.
• Total-body PET scanners offer enhanced sensitivity and data acquisition capabilities for dynamic imaging.

Purpose of the Study:

• To implement and validate a non-invasive image-derived input function (IDIF) for quantifying 18F-PI-2620 tau binding in the brain using total-body PET.
• To assess the impact of scan duration on the accuracy and stability of kinetic parameter quantification.

Main Methods:

• Dynamic total-body PET/CT data were acquired from 15 elderly participants using 18F-PI-2620.
• A subject-specific IDIF was derived from the descending aorta and applied to a two-tissue compartmental model (2TCM) for kinetic analysis.
• Kinetic parameters were estimated across various scan durations (10-90 minutes), and Logan graphical analysis was used to determine the total distribution volume (VT).

Main Results:

• Significant differences in kinetic parameters, including tracer delivery rate (K1), were observed between brain regions, with reduced K1 in the medial temporal lobe.
• Most kinetic parameters demonstrated stability after a 60-minute scan duration, and K1 showed stability after 30 minutes.
• Excellent correlation was found between VT values estimated using 2TCM and Logan analysis.

Conclusions:

• The study validates the utility of a non-invasive IDIF coupled with total-body PET for reliable quantification of 18F-PI-2620 brain kinetics.
• Optimal scan durations for stable kinetic parameter estimation were identified, suggesting potential for shorter scan times.
• This approach facilitates accurate assessment of tau pathology in neurodegenerative diseases.