Evaluation of Cardiac -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 -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). -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 -adrenergic receptor density (Bmax) and total distribution volume (DVtot) were estimated using compartmental modeling. After the experiment, Bmax in vitro was measured for all hearts using 3HCGP12177, and the values were compared with the Bmax 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 highand the low-flow groups. Bmax values estimated from 11CCGP12388 kinetics were 5.05 0.90 pmol/g under the highflow model and 5.20 0.63 pmol/g under the low-flow model. The Bmax results in isolated hearts correlated significantly with the measured in vitro Bmax values (r2 0.69; P 0.001). Conclusion: -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.