A novel beta-adrenoceptor ligand for positron emission tomography: Evaluation in experimental animals

Myocardial and pulmonary beta-adrenoceptors can be imaged and quantified with the antagonist (S)-4-[3[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-1,3-dihydro-2H-benzimidazol-2-[C-11]-one (S-[C-11]CGP-12177). The synthesis of this ligand (based on the reaction of a precursor with [C-11]phosgene) is laborious and in many centers 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, by a reliable one-pot procedure and evaluated the radiopharmaceutical for beta-adrenoceptor imaging. Blocking experiments with subtype-selective beta-adrenergic drugs showed that myocardial and pulmonary uptake of S-[C-11]CGP-12388 in anesthetized rats reflects ligand binding to beta(1)- and beta(2)-adrenoceptors. In this animal model, clearance, metabolism 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-12177 showed less favorable characteristics. S-[C-11]CGP-12388 was therefore selected for evaluation in humans and it may become the tracer of choice for clinical studies since it is easily prepared. (C) 1998 Elsevier Science B.V