Uptake of radioligands by rat heart and lung in vivo: CGP 12177 does and CGP 26505 does not reflect binding to β-adrenoceptors

Abstract The biodistribution of (-)-4-(3-t-butylamino-2-hydroxypropoxy)-[5,7-3H-benzimidazol-2-one (CGP12177, a non-selective β-adrenoceptor antagonist) and 1-[2-(3-carbamoyl-4-hydroxy)-(5- 3 H-phenoxy)]-2-propanol methanesuifonate, (CGP26505, a β-tadrenoceptor antagonist) was studied in rats pretreated with various α- and β-adrenoceptor blocking drugs (5 min before 3 H injection, in dosages at which the drugs demonstrated the expected selectivity). Cardiac and pulmonary radioactivity were measured after 10 min, when specific binding was maximal. Uptake of [ 3 H]CGP12177 was linked to binding to β-adrenoceptors since it was not affected by prazosin or yohimbine, and was equally well inhibited by propranolol, unlabelled CGP12177 and isoprenaline. Moreover, atenolol and CGP20712A inhibited [ 3 H]CGP12177 uptake in heart (predominantly β 1 -adrenoceptors) more potently than ICI 118,551, while in lungs (predominantly β 2 -adrenoceptors) ICI 118,551 was more potent than atenolol or CGP20712A. In contrast, [ 3 HICGP26505 uptake in the target organs was equally effectively inhibited by propranolol and ICI 118,551, and significantly lowered by α-adrenoceptor antagonists. We conclude that [ 11 C]CGP12177, but not [ 11 C]CGP26505 will be suitable for positron emission tomography imaging of β-adrenoceptors in animals.