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Background: S-(−)[11C]CGP-12177 is reported to be a useful PET ligand for β-adrenoreceptor in the heart and lung. Its pharmacokinetic properties, however, have not been fully examined due to difficulty in S-(−)[11C]CGP-12177 production. Recently, we have developed a simple and improved synthesis of S-(−)[11C]CGP-12177 with high yields and high specific activity. The aim of this study is to determine pharmacokinetic properties of high specific activity S-(−)[11C]CGP-12177 in vitro and in vivo using rats. Methods: In vitro studies: S-(−)[11C]CGP-12177 (final concentration, 1 nM) with various concentrations of (±)CGP-12177, (±)propranolol, or (−)timolol was added in vitro to rat myocardial slices (n=4 in each condition). Incubation was performed at 30 °C for 90 min. The radioactivity in the myocardial slices was determined at the end of incubation. In vivo studies: Control and (±)propranolol-pretreated (7 μmol/kg, i.v., 5 min prior to S-(−)[11C]CGP-12177 injection) rats (n=4 in each group) were given S-(−)[11C]CGP-12177 (0.4 nmol/kg) intravenously. Radioactivity in tissues was measured at 20 min after injection of S-(−)[11C]CGP-12177. Results: In vitro studies: Uptake of S-(−)[11C]CGP-12177 in the myocardial slices was significantly decreased, depending on the concentration of the β-adrenoreceptor antagonists. S-(−)[11C]CGP-12177 uptake was 26%, 31%, and 36% of the control value, respectively, at 5×10−6 M (±)CGP-12177, (±)propranolol, and (−)timolol. In vivo studies: In the control group, uptake of S-(−)[11C]CGP-12177 was highest in the lung (10.3±0.5% ID/g), followed in decreasing order by the heart (2.4±0.1 %ID/g), kidneys, and liver. Pretreatment with (±)propranolol significantly reduced S-(−)[11C]CGP-12177 uptake in the lung and heart, to 11% and 17% of the control value, respectively (p |
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