SPECIFIC BETA-ADRENERGIC-RECEPTOR BINDING OF CARAZOLOL MEASURED WITH PET

Carazolol is a promising high-affinity beta-adrenergic receptor ligand for the noninvasive determination of beta receptor status using PET. Earlier investigations demonstrated specific receptor binding of caraz olol in mice. These PET studies with S(-)--[2''-C-11]carazolol in pigs were performed to explore the utility of the tracer for PET receptor studies. Methods: Tracer uptake in the heart and lung was measured by PET as a function of time. Receptors were blocked with propranolol and different doses of ICI 118,551 to estimate specific binding. Fluorine -18-1''-Fluorocarazolol and the less active R-enantiomer of [C-11]-car azolol were also studied. Results: Specific receptor binding was 75% o f the total uptake in the heart, preventable and displaceable by propr anolol. Dose-dependent competition showed that carazolol binds in vivo to beta(1) and to beta(2) subtypes. Uptake of the labeled R(+) enanti omer of carazolol was not receptor-specific. Conclusions: Carazolol la beled with C-11 or F-18 is a strong candidate for use in receptor esti mation with PET. The in vivo observations were consistent with its kno wn high affinity and slow receptor dissociation rate. Its high specifi c receptor uptake and low metabolism allow existing kinetic models to be applied for receptor measurements. The C-11 label is convenient for repeated administrations, though F-18 allowed the long observation pe riods necessary for measurement of the receptor dissociation rate. If needed, nonspecific uptake can be estimated without pharmacologic inte rvention by using the labeled R enantiomer.