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Head-to-head comparison of 11C-PBR28 and 11C-ER176 for quantification of the translocator protein in the human brain

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Abstract

Introduction

11C-ER176 is a new PET tracer to quantify the translocator protein (TSPO), a biomarker for inflammation. The aim of this study was to perform a head-to-head comparison between 11C-ER176 and the widely used 11C-PBR28.

Methods

Seven healthy volunteers had a 90-min PET scan and metabolite-corrected arterial input function with 11C-PBR28 in the morning and 11C-ER176 in the afternoon. Binding was quantified at the regional level in terms of VT with a two-tissue compartmental model. By using VND values from the literature obtained with pharmacological blockade, we derived the binding potential BPND for both tracers.

Results

11C-ER176 was more stable in arterial blood than 11C-PBR28 (the percentages of unmetabolized parent in plasma at 90 min were 29.0 ± 8.3% and 8.8 ± 2.9% respectively). The brain time–activity curves for both tracers were well fitted by the two-tissue model, but 11C-ER176 had higher VT values than 11C-PBR28 (5.74 ± 1.54 vs 4.43 ± 1.99 ml/cm3) and a lower coefficient of variation. The BPND of 11C-ER176 was more than 4 times larger than that of 11C-PBR28 for high-affinity binders, and more than 9 times larger for mixed-affinity binders.

Conclusion

11C-ER176 displays a higher binding potential and a smaller variability of VT values. Thanks to these characteristics, clinical studies performed with 11C-ER176 are expected to have higher statistical power and thus require fewer subjects.

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Funding

This study was partially funded by the Harrison, Chao, Graham, and Nantz Funds of the Houston Methodist Foundation.

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Authors and Affiliations

  1. Nantz National Alzheimer Center and Houston Methodist Research Neurological Institute, and Weill Cornell Medicine, 6670 Bertner Ave, Houston, TX, 77030, USA

    Paolo Zanotti-Fregonara, Belen Pascual, Meixiang Yu, David Beers, Stanley H. Appel & Joseph C. Masdeu

  2. Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK

    Mattia Veronese

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  1. Paolo Zanotti-Fregonara
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  2. Belen Pascual
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Correspondence to Paolo Zanotti-Fregonara.

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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 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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

Conflict of interest

Joseph Masdeu is on a General Electric Healthcare advisory board and receives research support from GE, Eli Lilly, Biogen, Abbvie, and Novartis. The other authors declare no conflict of interest.

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Zanotti-Fregonara, P., Pascual, B., Veronese, M. et al. Head-to-head comparison of 11C-PBR28 and 11C-ER176 for quantification of the translocator protein in the human brain. Eur J Nucl Med Mol Imaging 46, 1822–1829 (2019). https://doi.org/10.1007/s00259-019-04349-w

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  • DOI: https://doi.org/10.1007/s00259-019-04349-w

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