Synthesis and biodistribution of [11C]procaterol, a β2-adrenoceptor agonist for positron emission tomography

The potent, subtype-selective radioligand (±)-erythro-5-(1-hydroxy-2-[11C]isopropyl-aminobutyl)-8-hydroxycarbostyril ([11C]procaterol) was synthesized and evaluated for visualization of pulmonary β2-adrenoceptors with positron emission tomography (PET). Procaterol was labelled by reductive alkylation of the desisopropyl precursor with [11C]acetone under the influence of NaCNBH3 and acetic acid. Synthesis and HPLC purification were performed in 34 min. Specific activities ranged from 26.5–39.3 TBq (about 700–1000 Ci)/mmol and the radiochemical yield was 2.4–8.6% (corrected for decay). Biodistribution studies were performed in male Wistar rats which were either untreated or predosed with (image,image)-propranolol hydrochloride (β-adrenoceptor antagonist, 2.5 mg/kg), ICI 118551 (β2-adrenoceptor antagonist, 0.15 mg/kg), CGP 20712A (β1-adrenoceptor antagonist, 0.15 mg/kg) or isoprenaline (β-adrenoceptor agonist, 15 mg/kg). Specific binding was observed in lungs, spleen and red blood cells, tissues known to contain β2-adrenoceptors. Pulmonary binding was blocked by propranolol, ICI 118551 and isoprenaline, but not by CGP 20712A. This binding pattern is consistent with the β2 selectivity of the adioligand. The clearance of [11C]procaterol was biphasic, with a rapid distribution phase (t1/2 0.17 min) representing 90% of the injected dose followed by an elimination phase (t1/2 18.1 min). About 45% of the plasma radioactivity was unmetabolized procaterol at 15 min postinjection. In a dynamic PET-study, the lungs of untreated control rats could barely be detected and total/non-specific binding ratios rose to only 1.2 at 20 min postinjection. Although labelling and administration of (-) erythro-procaterol, the most active of 4 stereoisomers, may produce better results, [11C]procaterol seems unsuitable for β-adrenoceptor imaging.