Reduction of SERT binding in Ecstasy users: Reproducibility of PET studies

Abstract

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Objectives: Carbon-11-labeled-McN-5652 and Carbon-11-labeled-DASB have both recently been highlighted as tracers which detect reduction of the serotonin transporter (SERT) in ecstasy users. This finding has been confirmed by different image processing techniques applied to identical datasets but not to different study populations. We tested the control-user differences of the binding parameters between tracers as well as studies for reproducibility. Methods: To test between-tracer reproducibility, PET studies were obtained with both MCN and DASB in 42 subjects (19 controls, 23 users). To test between-study reproducibility, PET studies with DASB obtained in the same 42 subjects were compared to PET studies obtained in a new set of 32 subjects (16 controls, 16 users). Using compartmental modeling the total tissue distribution volume (DV) was calculated. Correction for nonspecific binding was achieved both by subtracting the cerebellar DV from the regional DV (=DVspec) and by dividing regional DV by cerebellar DV (=DVR). Reduction of binding was calculated from the percent difference between controls and users. Reproducibility was tested by rank correlation, linear correlation, and by factor analysis. Results: Between tracer reproducibility (r) of DV, DVspec and DVR was 0.481, 0.910 and 0.522, respectively. The between study reproducibility (r) of the same three parameters was 0.786, 0.924, and 0.806. Factor analysis showed that 87% of variance can be ascribed to two factors. The reductions of DVspec for both comparisons and both tracers showed high loads on factor 1, while reductions of DVR showed high loads on factor 2. The factorial assignment of DV reductions was less consistent. Conclusions: The results indicate outstanding between-tracer as well as between-study reproducibility of DVspec and excellent between study reproducibility of DV and DVR. These results may assist design and interpretation of PET studies of the SERT in the future.