TY - JOUR T1 - Serotonin transporter (SERT) occupancy by oral sibutramine in the living human brain using 11C-DASB PET JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 487 LP - 487 VL - 50 IS - supplement 2 AU - Peter Talbot AU - Stefan Bradley AU - Cyril Clarke AU - Kola Babalola AU - Andrew Philipp AU - Gavin Brown AU - Adam McMahon AU - Julian Matthews Y1 - 2009/05/01 UR - http://jnm.snmjournals.org/content/50/supplement_2/487.abstract N2 - 487 Objectives We present the first PET study of central SERT inhibition by the appetite suppressant drug sibutramine (SIB) in humans. Methods 12 healthy males completed a double-blind, placebo-controlled, within-subject crossover investigation of central SERT occupancy (using 11C-DASB) by 15 mg/day of SIB at steady state. Correlations were measured between occupancy and i) plasma concentrations of SIB and its active metabolites M1 and M2; ii) food intake. PET scans were performed on the HRRT. Binding potentials (BPND) on placebo and SIB were calculated by Logan reference tissue (cerebellum) method. Results Baseline (placebo) BPND values were: brainstem 0.60±0.09; caudate 0.82±0.24; putamen 1.22±0.32; thalamus 1.25±0.31. Mean SERT occupancy was 30.0%±10.2% (range ~ 10%-50%). Occupancy was positively correlated (p=0.09) with plasma concentration of M2, but not with SIB or M1. All subjects with significant appetite suppression (n = 5) had occupancy in the upper range (~ 25-50%). Non-responders (n = 7) had occupancy across the whole range. Conclusions Our data support that: i) SERT occupancy by clinical doses of SIB can be measured accurately by 11C-DASB PET and is of modest magnitude; ii) SERT occupancy is predominantly mediated by M2 in humans; iii) SERT occupancy may be necessary but not sufficient for SIB's efficacy in humans, supporting preclinical data suggesting that the hypophagic effect requires the co-inhibition of both SERT and norepinephrine transporters. ER -