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Small-animal PET imaging of the type 1 and type 2 cannabinoid receptors in a photothrombotic stroke model

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

Abstract

Purpose

Recent ex vivo and pharmacological evidence suggests involvement of the endocannabinoid system in the pathophysiology of stroke, but conflicting roles for type 1 and 2 cannabinoid receptors (CB1 and CB2) have been suggested. The purpose of this study was to evaluate CB1 and CB2 receptor binding over time in vivo in a rat photothrombotic stroke model using PET.

Methods

CB1 and CB2 microPET imaging was performed at regular time-points up to 2 weeks after stroke using [18F]MK-9470 and [11C]NE40. Stroke size was measured using MRI at 9.4 T. Ex vivo validation was performed via immunostaining for CB1 and CB2. Immunofluorescent double stainings were also performed with markers for astrocytes (GFAP) and macrophages/microglia (CD68).

Results

[18F]MK-9470 PET showed a strong increase in CB1 binding 24 h and 72 h after stroke in the cortex surrounding the lesion, extending to the insular cortex 24 h after surgery. These alterations were consistently confirmed by CB1 immunohistochemical staining. [11C]NE40 did not show any significant differences between stroke and sham-operated animals, although staining for CB2 revealed minor immunoreactivity at 1 and 2 weeks after stroke in this model. Both CB +1 and CB +2 cells showed minor immunoreactivity for CD68.

Conclusion

Time-dependent and regionally strongly increased CB1, but not CB2, binding are early consequences of photothrombotic stroke. Pharmacological interventions should primarily aim at CB1 signalling as the role of CB2 seems minor in the acute and subacute phases of stroke.

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Acknowledgments

Merck & Co, Inc. is acknowledged for making available the [18F]MK-9470 precursor. The authors are grateful to Jeanine Santermans, Kimy Emonds and Ellen Devos for their help with the immunohistochemical stainings, and to Peter Vermaelen and Ann Van Santvoort for small-animal PET scanning. Tjibbe de Groot and Dominique Vanderghinste are gratefully acknowledged for the radiopharmaceutical preparations. Caroline Vandeputte, Daisy van Veghel and Nele Evens are doctoral fellows of the Institute for the Promotion of Innovation through Science and Technology in Flanders (IWT Vlaanderen). Cindy Casteels is a postdoctoral fellow of the Flemish Fund for Scientific Research (FWO Vlaanderen). Koen Van Laere is senior clinical research fellow for the FWO Vlaanderen. This work was funded by Leuven University grants: MoSAIC CoE (Molecular Small Animal Imaging Center, Center of Excellence): EF/05/008, and OT/05/58.

Conflicts of interest

None.

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Authors and Affiliations

  1. Division of Nuclear Medicine, KU Leuven, Leuven, Belgium

    Caroline Vandeputte, Cindy Casteels, Michel Koole, Anneleen Gerits & Koen Van Laere

  2. Molecular Small Animal Imaging Center, MoSAIC, KU Leuven, Leuven, Belgium

    Caroline Vandeputte, Cindy Casteels, Michel Koole, Daisy van Veghel, Nele Evens, Anneleen Gerits, Tom Dresselaers, Uwe Himmelreich, Guy Bormans & Koen Van Laere

  3. Laboratory of Histology, Biomedical Research Institute, Hasselt University, Hasselt, Belgium

    Tom Struys & Ivo Lambrichts

  4. Biomedical NMR Unit, KU Leuven, Leuven, Belgium

    Tom Struys, Tom Dresselaers & Uwe Himmelreich

  5. Laboratory of Radiopharmacy, KU Leuven, Leuven, Belgium

    Daisy van Veghel, Nele Evens & Guy Bormans

  6. Division of Nuclear Medicine, UZ Leuven, Herestraat 49, E901, 3000, Leuven, Belgium

    Koen Van Laere

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  1. Caroline Vandeputte
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Correspondence to Koen Van Laere.

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Vandeputte, C., Casteels, C., Struys, T. et al. Small-animal PET imaging of the type 1 and type 2 cannabinoid receptors in a photothrombotic stroke model. Eur J Nucl Med Mol Imaging 39, 1796–1806 (2012). https://doi.org/10.1007/s00259-012-2209-6

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  • DOI: https://doi.org/10.1007/s00259-012-2209-6

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