Ecstasy-induced reduction of the availability of the brain serotonin transporter as revealed by [11C](+)McN5652-PET and the multi-linear reference tissue model: loss of transporters or artifact of tracer kinetic modelling?

Abstract

In a previous positron emission tomography (PET) study with the serotonin transporter (SERT) ligand [11C](+)McN5652, we found protracted reduction of the availability of the brain SERT in users of the drug ecstasy. However, the multi-linear reference tissue method for the quantification of SERT availability used in this study is prone to effects of altered levels of statistical noise that c`ould simulate reduction of SERT. The aim of the present study was to take into account this confound by re-evaluation of the data now using a modelling approach that is rather insensitive to alterations in the level of statistical noise. A total of 116 subjects (30 current, 29 former ecstasy users, 29 drug-naive, 28 polydrug controls) in whom [ 11C](+)McN5652-PET had been performed previously were re-evaluated. The equilibrium specific-to-non-specific partition coefficient V" 3 was obtained voxel-wise by application of the simplified reference tissue method (SRTM), which provides quite unbiased results up to rather large noise levels. Voxel-based comparisons between the groups were performed using statistical parametric mapping. V"3 was reduced in the striatum and in the thalamus in current ecstasy users. This was confirmed by volume-of-interest-based analysis. This result suggests that the ecstasy-induced reduction of SERT availability in SERT-rich brain regions reported previously indicates reduced SERT binding potential rather than being an artifact of tracer kinetic modelling. SRTM analysis did not confirm previous findings in neocortical brain areas.