(S)-(11)C-CGP12388 ((11)C-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 (11)C-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 (11)C-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 (DV(tot)) were estimated using compartmental modeling. After the experiment, B(max) in vitro was measured for all hearts using (3)H-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 (11)C-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 (11)C-CGP12388 and a 2-injection protocol. The binding of the tracer was flow independent, with low nonspecific binding. These results suggest that (11)C-CGP12388 is a promising PET tracer that may be applicable to human studies.