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Evaluation of Cardiac ß-Adrenoreceptors in the Isolated Perfused Rat Heart Using (S)-¹¹C-CGP12388

¹ Nuklearmedizinische Klinik und Poliklinik der Technischen Universität München, Munich, Germany
² Department of Radiology, University of Michigan, Ann Arbor, Michigan
³ PET Center, Groningen University Hospital, Groningen, The Netherlands
⁴ Walther Straub für Pharmakologie und Toxikologie, Ludwig-Maximilians-Universität München, Munich, Germany

(S)-¹¹C-CGP12388 (¹¹C-CGP12388) was recently developed as an in vivo PET tracer for the evaluation of cardiac ß-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). ß-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 ß-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: ß-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.

Key Words: ¹¹C-CGP12388 • ß-adrenoreceptor density • isolated rat heart • Langendorff • PET