Evaluation of cardiac β-adrenoreceptors in the isolated perfused rat heart using (S)-11C-CGP12388

(S)-C-11-CGP12388 (C-11-CGP12388) was recently developed as an in vivo PET tracer for the evaluation of cardiac beta-adrenergic receptors. The purpose of this study was to evaluate the myocardial kinetics of C-11-CGP12388 using the perfused rat heart model. Methods: Normal rat hearts were cannulated for retrograde perfusion according to the Langendorff method. Studies were performed using constant coronary flow rates of 12 mL/min (high flow: n = 6) and 6 mL/min (low flow: n = 6). beta-Adrenergic-blocking studies were also done using propranolol (blocking: n = 6). Two bolus injections of C-11-CGP12388 were administered at a 25-min interval, and time-activity curves were measured using bismuth germanate detectors. The beta-adrenergic receptor density (B-max) and total distribution volume (DVtot) were estimated using compartmental modeling. After the experiment, B-max in vitro was measured for all hearts using H-3-CGP12177, and the values were compared with the B-max estimated in isolated hearts. Results: DVtot was significantly lower in the blocking group than in the high-flow group (P < 0.01), and there was no significant difference in DVtot between the high- and the low-flow groups. B-max values estimated from C-11-CGP12388 kinetics were 5.05 +/- 0.90 pmol/g under the high-flow model and 5.20 +/- 0.63 pmol/g under the low-flow model. The B-max results in isolated hearts correlated significantly with the measured in vitro B-max values (r(2) = 0.69; P < 0.001). Conclusion: beta-Adrenoreceptor density in the isolated rat heart can be quantified using C-11-CGP12388 and a 2-injection protocol. The binding of the tracer was flow independent, with low nonspecific binding. These results suggest that C-11-CGP12388 is a promising PET tracer that may be applicable to human studies.