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Test–retest reproducibility of [11C]PBR28 binding to TSPO in healthy control subjects

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Abstract

Purpose

The PET radioligand [11C]PBR28 binds to the translocator protein (TSPO), a marker of brain immune activation. We examined the reproducibility of [11C]PBR28 binding in healthy subjects with quantification on a regional and voxel-by-voxel basis. In addition, we performed a preliminary analysis of diurnal changes in TSPO availability.

Methods

Twelve subjects were examined using a high-resolution research tomograph and [11C]PBR28, six in the morning and afternoon of the same day, and six in the morning on two separate days. Regional volumes of distribution (V T) were derived using a region-of-interest based two-tissue compartmental analysis (2TCM), as well as a parametric approach. Metabolite-corrected arterial plasma was used as input function.

Results

For the whole sample, the mean absolute variability in V T in the grey matter (GM) was 18.3 ± 12.7 %. Intraclass correlation coefficients in GM regions ranged from 0.90 to 0.94. Reducing the time of analysis from 91 to 63 min yielded a variability of 16.9 ± 14.9 %. There was a strong correlation between the parametric and 2TCM-derived GM values (r = 0.99). A significant increase in GM V T was observed between the morning and afternoon examinations when using secondary methods of quantification (p = 0.028). In the subjects examined at the same time of the day, the absolute variability was 15.9 ± 12.2 % for the 91-min 2TCM data.

Conclusion

V T of [11C]PBR28 binding showed medium reproducibility and high reliability in GM regions. Our findings support the use of parametric approaches for determining [11C]PBR28 V T values, and indicate that the acquisition time could be shortened. Diurnal changes in TSPO binding in the brain may be a potential confounder in clinical studies and should be investigated further.

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Acknowledgments

We thank Ruyji Nakao for his diligent work with metabolite analyses, and Martin Schain for his generous help in calculating the ICCs. We also thank the other members of the PET group for their close assistance during this study.

Compliance with ethical standards

ᅟ

Funding

The research leading to these results received funding from the Swedish Research Council (VR 09114), the European Union’s Seventh Framework Programme (FP7/2007-2013) under grant agreement no. HEALTH-F2-2011-278850 (INMIND), Karolinska Institutet and PRIMA Barn och vuxenpsykiatri AB. The contribution of I.Y. was supported by MindView (Multimodal Imaging of Neurological Disorders; project reference 603002), and the European Commission's Framework Programme FP7-HEALTH.

Conflicts of interest

L.F. is employed part time at the AstraZeneca Translational Science Center at Karolinska Institutet. S.C. has received grant support from AstraZeneca as coinvestigator, and has served as a one-off speaker for Roche and Otsuka Pharmaceuticals. A.V. has received funding from CHDI Foundations Inc. All other authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the principles of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Authors and Affiliations

  1. Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden

    K. Collste, A. Forsberg, A. Varrone, N. Amini, I. Yakushev, C. Halldin, L. Farde & S. Cervenka

  2. Department of Clinical Neuroscience, Neuroimmunology Unit, Karolinska Institutet, Stockholm, Sweden

    S. Aeinehband

  3. Department of Nuclear Medicine and TUM Neuroimaging Center (TUM-NIC), Technische Universität München, Munich, Germany

    I. Yakushev

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  1. K. Collste
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Correspondence to K. Collste.

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Collste, K., Forsberg, A., Varrone, A. et al. Test–retest reproducibility of [11C]PBR28 binding to TSPO in healthy control subjects. Eur J Nucl Med Mol Imaging 43, 173–183 (2016). https://doi.org/10.1007/s00259-015-3149-8

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  • DOI: https://doi.org/10.1007/s00259-015-3149-8

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