Rimota-Gd:\nParamagnetic Probe for In Vivo MRI Studies\nof the Cannabinoid 1 Receptor Distribution in the Mouse Brain

The cannabinoid 1 receptor (CB1) is highly expressed\nin the central\nnervous system, where its physiological functions include the regulation\nof energy balance, pain, and addiction. Herein, we develop and validate\na technique to use magnetic resonance imaging (MRI) to investigate\nthe distribution of CB1 across mouse brains with high spatial resolution,\nexpanding previously described in vitro studies and in vivo studies\nwith positron emission tomography (PET). To support the MRI investigations,\nwe developed a ligand that is specific for in vivo neuroimaging of\nCB1. By chemically conjugating the CB1 antagonist rimonabant acid\nto a gadolinium chelator, we obtained the paramagnetic probe Rimota-Gd.\nThe specificity of binding of rimonabant acid to CB1 and the relaxation\nenhancement by the paramagnetic gadolinium permit MRI-based localization\nof CB1. We used Rimota-Gd to investigate the spatial distribution\nof CB1 across the mouse brain and compared the results with an investigation\nusing the PET radioligand [<sup>18</sup>F]MK-9470. Rimota-Gd opens\nthe door for in vivo MRI imaging of CB1 and provides a roadmap for\nthe study of other receptors by whole-brain images with high spatial\nand temporal resolution.