Imaging of beta-adrenoceptors in the human thorax using (S)-[C-11]CGP12388 and positron emission tomography

We report positron emission tomography studies of beta -adrenoceptors in the human thorax with (S)-[C-11]CGP12388 (4-(3-(2'-[C-11]isopropylamino)-2-hydroxypropoxy)-2H-benzimidazol-2-one). beta -Adrenoceptors have previously been quantified using (S)-[C-11]CGP12177 (4-(3-tert-butylamino-2-hydroxypropoxy)-2H-benzimidazol-2[C-11]-one), but (S)-[C-11]CGP12388 is more easily prepared and therefore more suitable in a clinical setting. (S)-[C-11]CGP12388 was administered to five healthy volunteers on two separate days (control and pindolol block study). Arterial plasma samples were used to determine clearance, metabolites, and protein binding of the radioligand. Heart, lung and spleen showed high uptake of radioactivity, which was strongly suppressed (68-77%) by pindolol. Plasma clearance of (S)-[C-11]CGP 12388 was rapid, binding to plasma proteins was low (53 +/- 4%), and the radioligand was slowly metabolized. (S)-[C-11]CGP12388 produces high-quality images of the human thorax. Uptake of (S)-[C-11]CGP 12388 in heart, lung and spleen represents binding to beta -adrenoceptors. (S)-[C-11]CGP 12388 seems useful for imaging of beta -adrenoceptors in a clinical setting. (C) 2001 Elsevier Science B.V. All rights reserved