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Imaging of the brain serotonin transporters (SERT) with 18F-labelled fluoromethyl-McN5652 and PET in humans

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

[11C]DASB is currently the most frequently used highly selective radiotracer for visualization and quantification of central SERT. Its use, however, is hampered by the short half-life of 11C, the moderate cortical test–retest reliability, and the lack of quantifying endogenous serotonin. Labelling with 18F allows in principle longer acquisition times for kinetic analysis in brain tissue and may provide higher sensitivity. The aim of our study was to firstly use the new highly SERT-selective 18F-labelled fluoromethyl analogue of (+)-McN5652 ((+)-[18F]FMe-McN5652) in humans and to evaluate its potential for SERT quantification.

Methods

The PET data from five healthy volunteers (three men, two women, age 39 ± 10 years) coregistered with individual MRI scans were semiquantitatively assessed by volume-of-interest analysis using the software package PMOD. Rate constants and total distribution volumes (V T) were calculated using a two-tissue compartment model and arterial input function measurements were corrected for metabolite/plasma data. Standardized uptake region-to-cerebellum ratios as a measure of specific radiotracer accumulation were compared with those of a [11C]DASB PET dataset from 21 healthy subjects (10 men, 11 women, age 38 ± 8 years).

Results

The two-tissue compartment model provided adequate fits to the data. Estimates of total distribution volume (V T) demonstrated good identifiability based on the coefficients of variation (COV) for the volumes of interest in SERT-rich and cortical areas (COV V T <10%). Compared with [11C]DASB PET, there was a tendency to lower mean uptake values in (+)-[18F]FMe-McN5652 PET; however, the standard deviation was also somewhat lower. Altogether, cerebral (+)-[18F]FMe-McN5652 uptake corresponded well with the known SERT distribution in humans.

Conclusion

The results showed that (+)-[18F]FMe-McN5652 is also suitable for in vivo quantification of SERT with PET. Because of the long half-life of 18F, the widespread use within a satellite concept seems feasible.

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Acknowledgments

We would like to thank all the volunteers who participated in this trial. This work was partially supported by the German Federal Ministry of Education and Research (BMBF), Germany, FKZ: 01EO1001. We also thank the anonymous reviewers for their helpful criticisms and comments that significantly improved the manuscript.

Conflicts of interest

None.

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Authors and Affiliations

  1. Department of Nuclear Medicine, University of Leipzig, Leipzig, Germany

    Swen Hesse, Georg-Alexander Becker, Marianne Patt, Anita Seese, Dietlind Sorger, Philipp M. Meyer, Bernd Habermann, Julia Luthardt, Anke Bresch & Osama Sabri

  2. AdiposityDiseases, Leipzig University Medical Center, Leipzig, Germany

    Swen Hesse

  3. Institute of Radiopharmacy, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany

    Peter Mäding, Jörg Zessin, Frank Füchtner & Jörg Steinbach

  4. Institute of Radiopharmacy, Research Site Leipzig, Helmholtz-Zentrum Dresden-Rossendorf, Leipzig, Germany

    Peter Brust & Jörg Steinbach

  5. Department of Neuroradiology, University of Leipzig, Leipzig, Germany

    Donald Lobsien

  6. Department of Anaesthesiology and Intensive Care, University of Leipzig, Leipzig, Germany

    Sven Laudi

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  1. Swen Hesse
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Correspondence to Swen Hesse.

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Hesse, S., Brust, P., Mäding, P. et al. Imaging of the brain serotonin transporters (SERT) with 18F-labelled fluoromethyl-McN5652 and PET in humans. Eur J Nucl Med Mol Imaging 39, 1001–1011 (2012). https://doi.org/10.1007/s00259-012-2078-z

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  • DOI: https://doi.org/10.1007/s00259-012-2078-z

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