Kinetic models for estimating occupancy from single-scan PET displacement studies.

Area of Science:

• Nuclear medicine
• Pharmacology
• Biophysics

Background:

• Traditional PET target engagement studies require multiple scans, increasing radiation exposure and costs.
• Existing kinetic models assume steady-state conditions, which are not met during drug displacement scans.

Purpose of the Study:

• To develop and validate kinetic models for analyzing PET drug displacement data.
• To enable accurate target engagement assessment using a single, in-scan drug administration approach.

Main Methods:

• Modified existing PET compartment models to account for time-variant occupancy during in-scan drug administration.
• Developed approximate and numerical solutions for the resulting differential equations.
• Validated the models using simulations and applied them to PET data from pigs undergoing [11C]UCB-J displacement with brivaracetam.

Main Results:

• Simulations demonstrated unbiased and accurate occupancy estimation at relatively high levels.
• The developed models accurately estimated the dose-occupancy relationship in pigs.
• Results showed good agreement with traditional methods like the Lassen plot.

Conclusions:

• The proposed kinetic models offer a robust framework for determining target occupancy from single PET displacement scans.
• This approach reduces radiation exposure and costs associated with PET target engagement studies.
• The findings support the adoption of PET displacement studies as a more efficient alternative.