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

Abstract

Assessment of an antidepressant's occupancy at the serotonin transporter (SERT) in vivo using PET scans represents a demanding procedure. We evaluated novel approaches for SERT quantification to simplify the occupancy calculation. [¹¹C]DASB PET/MRI scans with bolus plus constant infusion were performed twice in 47 healthy controls and 31 patients with major depressive disorder with intravenous application of 8 mg citalopram or saline solution (randomized, cross-over, double-blind). Binding potentials (BP_P and BP_ND) were estimated over time and within two radioligand equilibrium periods (before and after drug challenge). Reference occupancy was calculated as the relative decrease in post-drug BP_P between the placebo and citalopram scans. We introduced three methods for estimating SERT occupancy. Method 1 replaced the arterial blood sampling (BP_P) by reference region modeling during equilibrium timeframes (BP_ND). Method 2 replaced the post-dose placebo equilibrium period with the pre-dose citalopram equilibrium period. Method 3 integrated aspects of both Methods 1 and 2, utilizing BP_ND and the pre-dose citalopram equilibrium phase. The results showed equivalent occupancy values (p < 0.05) for the majority of VOIs and high agreement (max R² = 0.89) between the reference (utilizing arterial blood sampling, along with the placebo and citalopram scan) and the proposed methods, indicating that they are a promising solution for simplifying occupancy estimation.