A NOVEL BETA-ADRENOCEPTOR LIGAND FOR POSITRON-EMISSION-TOMOGRAPHY - EVALUATION IN EXPERIMENTAL-ANIMALS

Myocardial and pulmonary beta-adrenoceptors can be imaged and quantifi ed with the antagonist ypropoxy]-1,3-dihydro-2H-benzimidazol-2-[C-11]- one (S-[C-11]CGP-12177). The synthesis of this ligand (based on the re action of a precursor with [C-11]phosgene) is laborious and in many ce nters the final product has a low and variable specific activity. This prevents widespread use of S-[C-11]CGP-12177 for studies in patients. We prepared S-[C-11]CGP-12388, the isopropyl analogue of CGP-12177, b y a reliable one-pot procedure and evaluated the radiopharmaceutical f or beta-adrenoceptor imaging. Blocking experiments with subtype-select ive beta-adrenergic drugs showed that myocardial and pulmonary uptake of S-[C-11]CGP-12388 in anesthetized rats reflects ligand binding to b eta(1)- and beta(2)-adrenoceptors. In this animal model, clearance, me tabolism and tissue/plasma ratios of S-[C-11]CGP-12388 were similar to those of S-[C-11]CGP-12177. A [F-18]fluoroisopropyl analogue of CGP-1 2177 showed less favorable characteristics. S-[C-11]CGP-12388 was ther efore selected for evaluation in humans and it may become the tracer o f choice for clinical studies since it is easily prepared. (C) 1998 El sevier Science B.V.