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

(S)-¹¹C-CGP12388 (¹¹C-CGP12388) was recently developed as an in vivo PET tracer for the evaluation of cardiac β-adrenergic receptors. The purpose of this study was to evaluate the myocardial kinetics of ¹¹C-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). β-Adrenergic-blocking studies were also done using propranolol (blocking: n = 6). Two bolus injections of ¹¹C-CGP12388 were administered at a 25-min interval, and time-activity curves were measured using bismuth germanate detectors. The β-adrenergic receptor density (B _max) and total distribution volume (DV_tot) were estimated using compartmental modeling. After the experiment, B_max in vitro was measured for all hearts using ³H-CGP12177, and the values were compared with the B_max estimated in isolated hearts. Results: DV _tot was significantly lower in the blocking group than in the high-flow group (P < 0.01), and there was no significant difference in DV_tot between the high-and the low-flow groups. B_max values estimated from ¹¹C-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 (r² = 0.69; P < 0.001). Conclusion: β-Adrenoreceptor density in the isolated rat heart can be quantified using ¹¹C-CGP12388 and a 2-injection protocol. The binding of the tracer was flow independent, with low nonspecific binding. These results suggest that ¹¹C-CGP12388 is a promising PET tracer that may be applicable to human studies.