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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?

Department of Nuclear Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany, buchert{at}uke.uni-hamburg.de

Frank Thiele

Philips Research Laboratories Aachen, Aachen, Germany

Rainer Thomasius

Department of Psychiatry and Psychotherapy, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany

Florian Wilke

Department of Nuclear Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany

Kay Petersen

Department of Psychiatry and Psychotherapy, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany

Winfried Brenner

Department of Nuclear Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany

Janos Mester

Department of Nuclear Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany

Lothar Spies

Philips Research Laboratories Aachen, Aachen, Germany

Malte Clausen

Department of Nuclear Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany

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.

Key Words: ecstasy • serotonin transporter • PET • (+)McN5652 • simplified reference tissue method • multi-linear reference tissue method

This version was published on August 1, 2007

Journal of Psychopharmacology, Vol. 21, No. 6, 628-634 (2007)
DOI: 10.1177/0269881106071975


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