Radiosynthesis of novel carbon-11-labeled triaryl ligands for cannabinoid-type 2 receptor

doi:10.1016/j.bmcl.2010.01.074

Bioorganic & Medicinal Chemistry Letters

Volume 20, Issue 5, 1 March 2010, Pages 1565-1568

https://doi.org/10.1016/j.bmcl.2010.01.074 Get rights and content

Abstract

Two novel triaryl ligands 2 and 5 with potent in vitro binding affinities for the cannabinoid subtype-2 (CB2) receptor were labeled with a positron-emitting radioactive nuclide ¹¹C. Radioligands [¹¹C]2, [¹¹C]5, and their analogs [¹¹C]3 and [¹¹C]4 were synthesized by O-[¹¹C]methylation of their corresponding phenol precursors with [¹¹C]CH₃I. [¹¹C]2–5 had relatively high uptakes (>1.2% injected dose/g tissue) in mouse brains.

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Acknowledgements

This study was supported in part by Grants-in-Aid for Scientific Research for the Molecular Imaging Program from the Ministry of Education, Culture, Sports, Science and Technology, Government of Japan.

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The endocannabinoid system (ECS) is a ubiquitous modulatory neurotransmission system in the brain. It consists of a family of naturally occurring lipids, the endocannabinoids, of transport and degradation proteins, and of cannabinoid receptors. Experimental evidence points towards an important role of the type 1 cannabinoid (CB₁) receptor in the pathogenesis of Huntington’s disease (HD) in multiple disease domains, including motor, cognitive, and behavioral aspects. Also, the type 2 cannabinoid (CB₂) receptor is part of an endogenous mechanism of defense that is involved in neuroinflammation. In this chapter, we provide an overview of the role of the ECS in the pathophysiology of HD. We focus on molecular imaging using PET for visualization and quantitative assessment of CB₁ and CB₂ receptors.

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Radiosynthesis of novel carbon-11-labeled triaryl ligands for cannabinoid-type 2 receptor

Abstract

Graphical abstract

Section snippets

Acknowledgements

Neuroimage

Nucl. Med. Biol.

Nucl. Med. Biol.

Nucl. Med. Biol.

Nature

Nature

J. Pharmcol. Exp. Ther.

Neuropsychobiology

J. Neurochem.