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

Journal of Nuclear Medicine

Markus Schwaiger¹  Frank M. Bengel¹  Philip H. Elsinga¹  Joerg Remien¹  Ngoc Nguyen¹  David M. Raffel¹  Mitsuru Momose¹  Hans-Jürgen Wester¹  Sybille Reder¹  Petra Watzlowik¹ 

关键词: ¹¹C-CGP12388;    β-adrenoreceptor density;    isolated rat heart;    Langendorff;    PET;   

DOI  :  

学科分类：医学（综合）

来源: Society of Nuclear Medicine

【 摘 要 】

(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 (Bmax) and total distribution volume (DVtot) were estimated using compartmental modeling. After the experiment, Bmax in vitro was measured for all hearts using 3H-CGP12177, 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 high- and the low-flow groups. Bmax 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 Bmax results in isolated hearts correlated significantly with the measured in vitro Bmax 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.

【 授权许可】

Unknown