Simplified methods for SERT occupancy estimation measured with [11C]DASB PET bolus plus infusion

Area of Science:

• Neuroscience
• Radiopharmacology
• Molecular Imaging

Background:

• Assessing antidepressant occupancy at the serotonin transporter (SERT) in vivo using PET scans is complex.
• Novel quantification methods are needed to simplify SERT occupancy calculations.

Purpose of the Study:

• To evaluate simplified methods for estimating SERT occupancy using [11C]DASB PET/MRI scans.
• To compare novel occupancy estimation methods with a reference method involving arterial blood sampling.

Main Methods:

• Utilized [11C]DASB PET/MRI scans in healthy controls and MDD patients under placebo and citalopram conditions.
• Estimated binding potentials (BPp and BPnd) and calculated reference occupancy.
• Developed and tested three novel methods to simplify occupancy estimation, including reference region modeling and alternative equilibrium periods.

Main Results:

• The proposed methods yielded equivalent SERT occupancy values compared to the reference method (p < 0.05).
• High agreement (max R² = 0.89) was observed between the reference and simplified methods.
• The novel methods successfully simplified occupancy estimation without compromising accuracy.

Conclusions:

• The developed methods offer a promising and simplified approach for estimating SERT occupancy.
• These novel methods can reduce the procedural demands of in vivo antidepressant occupancy assessment.
• Simplified SERT occupancy estimation can facilitate clinical research and drug development for depression.