In vivo characterization of myocardium muscarinic receptors by positron emission tomography

The feasibility of studying myocardium muscarinic receptors, non invasively, in a “live” being can be demonstrated using positron emission tomography (PET) and a ligand labelled by carbon 11, an externally detectable short lived radionuclide. Criteria necessary for in vitro characterization of muscarinic receptors by a specific ligand were verified in vivo by this method. This demonstration was carried out after injecting in a baboon, high specific activity 11 C-MQNB (the methiodide salt of quinuclidinyl benzylate) a muscarinic antagonist drug, and displacing the radioactive ligand by increasing amounts of atropine. Displacement was proportionnal to the dose of atropine and a correlation was observed between displacement and pharmacological activity (increase of heart rate). Stereospecificity of the binding was also demonstrated by using two stereoisomers of benzetimide : dexetimide and levetimide.