Rimota-Gd: Paramagnetic Probe for In Vivo MRI Studies of the Cannabinoid 1 Receptor Distribution in the Mouse Brain
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Date
2024-12-04
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Journal Article
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yes
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Abstract
The cannabinoid 1 receptor (CB1) is highly expressed in the central nervous system, where its physiological functions include the regulation of energy balance, pain, and addiction. Herein, we develop and validate a technique to use magnetic resonance imaging (MRI) to investigate the distribution of CB1 across mouse brains with high spatial resolution, expanding previously described in vitro studies and in vivo studies with positron emission tomography (PET). To support the MRI investigations, we developed a ligand that is specific for in vivo neuroimaging of CB1. By chemically conjugating the CB1 antagonist rimonabant acid to a gadolinium chelator, we obtained the paramagnetic probe Rimota-Gd. The specificity of binding of rimonabant acid to CB1 and the relaxation enhancement by the paramagnetic gadolinium permit MRI-based localization of CB1. We used Rimota-Gd to investigate the spatial distribution of CB1 across the mouse brain and compared the results with an investigation using the PET radioligand [F-18]MK-9470. Rimota-Gd opens the door for in vivo MRI imaging of CB1 and provides a roadmap for the study of other receptors by whole-brain images with high spatial and temporal resolution.
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published
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Journal / series
Volume
15 (23)
Pages / Article No.
4258 - 4266
Publisher
American Chemical Society
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Subject
molecular MRI; rimonabant; PET imaging; [F-18]MK9470; in vivo imaging; endocannabinoidsystem
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03129 - Wüthrich, Kurt / Wüthrich, Kurt