Quantification of PET infusion studies without true equilibrium: A tissue clearance correction

Area of Science:

• Nuclear medicine
• Pharmacokinetics
• Biophysical modeling

Background:

• Positron emission tomography (PET) studies often use constant radioligand infusion to achieve equilibrium for accurate quantification.
• This method assumes uniform radioligand behavior, and deviations can introduce bias in total distribution volume (VT) measurements.
• True equilibrium may not be reached in all subjects, compromising quantitative accuracy.

Purpose of the Study:

• To develop and validate a correction method to reduce bias in PET quantification when true equilibrium is not present.
• To introduce the tissue clearance correction (TCC) to improve the accuracy of total distribution volume (VT) estimates.

Main Methods:

• Developed the tissue clearance correction (TCC) formula: VT = VT(A) / (1 - β/γ).
• Performed simulations to assess TCC robustness with imperfect parameter values (β, γ) and evaluate false positive rates.
• Validated TCC using human infusion PET data for [18F]FPEB, (-)-[18F]flubatine, and [11C]UCB-J.

Main Results:

• TCC successfully reduced bias in total distribution volume (VT) estimates across all tested radiotracers.
• Simulations confirmed TCC's robustness and its ability to reduce false positive rates.
• TCC significantly decreased intersubject variance in VT for [18F]FPEB in specific brain regions.

Conclusions:

• The tissue clearance correction (TCC) method enhances the accuracy of quantitative PET imaging during constant infusion studies.
• TCC addresses the challenge of achieving true equilibrium in all subjects, improving data reliability.
• This correction is crucial for precise quantification in PET studies utilizing radioligand infusions.