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Decreased in vivo availability of the cannabinoid type 2 receptor in Alzheimer’s disease

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

Abstract

Purpose

The cannabinoid type 2 receptor (CB2R) is expressed by immune cells such as monocytes and macrophages. In the brain, CB2R is primarily found on microglia. CB2R upregulation has been reported in animal models of Alzheimer’s disease, with a preferential localization near amyloid beta (Aβ) plaques, and in patients post mortem. We performed in vivo brain imaging and kinetic modelling of the CB2R tracer [11C]NE40 in healthy controls (HC) and in patients with Alzheimer’s disease (AD) to investigate whether higher CB2R availability regionally colocalized to Aβ deposits is present in vivo.

Methods

Dynamic 90-min [11C]NE40 PET scans were performed in eight HC and nine AD patients with full kinetic modelling using arterial sampling and metabolite correction and partial volume correction. All AD patients received a static [11C]PIB scan 40 min after injection. In four HC, a retest scan with [11C]NE40 PET was performed within 9 weeks to investigate test–retest characteristics.

Results

[11C]NE40 was metabolized quickly leading to 50 % of intact tracer 20 min after injection and 20 % at 90 min. A two-tissue kinetic model fitted most of the time–activity curves best; both binding potential (BPND) and distribution volume (V T) parameters could be used. Brain uptake was generally low with an average K 1 value of 0.07 ml/min/ml tissue. V T and BPND were in the range of 0.7 – 1.8 and 0.6 – 1.6, respectively. Test values in HC were about 30 % for V T and BPND. AD patients showed overall significantly lower CB2R binding. No relationship was found between regional or global amyloid load and CB2R availability.

Conclusion

Kinetic modelling of [11C]NE40 is possible with a two-tissue reversible model. In contrast to preclinical and post-mortem data, [11C]NE40 PET shows lower CB2R availability in vivo in AD patients, with no relationship to Aβ plaques. A possible explanation for these findings is that [11C]NE40 binds to CB2R with lower affinity and/or selectivity than to CB1R.

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Acknowledgments

We thank Prof. Dr. Wim Vandenberghe for revising the manuscript. We also thank Mr. Kwinten Porters, Mrs. Mieke Steukers and Ms. Hannelore Bels, as well as the clinical PET radiopharmacy team (especially Mrs. Marva Bex and Dr. Pharm. Kim Serdons), for their contribution to the execution of the study. K.V.L. is Senior Research Fellow for the Flemish Scientific Research Foundation, Belgium (FWO Vlaanderen). This research was partially sponsored by EU FP7 grant FP7/2007-2013, INMiND, grant agreement no. 278850.

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Author notes

    Authors and Affiliations

    1. Department of Imaging & Pathology, Nuclear Medicine and Molecular Imaging, KU Leuven and University Hospitals Leuven, Leuven, Belgium

      Rawaha Ahmad, Andrey Postnov & Koen Van Laere

    2. Division of Nuclear Medicine, University Hospital Leuven, Herestraat 49 E901, 3000, Leuven, Belgium

      Rawaha Ahmad & Koen Van Laere

    3. National Research Nuclear University MEPhI, Moscow, Russia

      Andrey Postnov

    4. Laboratory for Radiopharmacy, KU Leuven, Leuven, Belgium

      Guy Bormans

    5. Department of Neurology, University Hospital Brussels, Brussels, Belgium

      Jan Versijpt

    6. Old Age Psychiatry, Department of Psychiatry, KU Leuven and University Hospitals Leuven, Leuven, Belgium

      Mathieu Vandenbulcke

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    Correspondence to Rawaha Ahmad.

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    All procedures performed in this study 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.

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

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    Rawaha Ahmad and Andrey Postnov contributed equally to this work.

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    Ahmad, R., Postnov, A., Bormans, G. et al. Decreased in vivo availability of the cannabinoid type 2 receptor in Alzheimer’s disease. Eur J Nucl Med Mol Imaging 43, 2219–2227 (2016). https://doi.org/10.1007/s00259-016-3457-7

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    • DOI: https://doi.org/10.1007/s00259-016-3457-7

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