Cardiac beta-adrenergic receptor density measured in vivo using PET, CGP 12177, and a new graphical method.

The in vivo quantification of myocardial beta-adrenergic receptor has been obtained in five closed-chest dogs using positron emission tomography (PET). The ligand was racemic (+/-)[11C] CGP 12177, a very potent hydrophilic antagonist of the beta-adrenergic receptor. A kinetic method appeared unsuitable because of the presence of metabolites which made the input function difficult to measure and also inaccurate. Therefore, a graphical method, based on a particular protocol, was proposed. The animals were injected with a trace amount of (+/-)[11C]CGP 12177, which was followed 40 min later by a second injection of radioligand with a low-specific activity. An additional injection of an excess of unlabeled CGP 12177 was administered after 90 min and allowed for the estimation of the dissociation rate constant. The main advantage of this graphical approach is that the results are obtained without having to measure the input function and therefore without estimating the metabolites. The average value of Bmax was 31 +/- 4 pmole/ml of tissue and the dissociation constant was 0.014 +/- 0.002 min-1.