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


CONCLUSIONS
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.
Momose
Mitsuru
M
Nuklearmedizinische Klinik und Poliklinik der Technischen Universität München, Munich, Germany.
Reder
Sybille
S
Raffel
David M
DM
Watzlowik
Petra
P
Wester
Hans-Jürgen
HJ
Nguyen
Ngoc
N
Elsinga
Philip H
PH
Bengel
Frank M
FM
Remien
Joerg
J
Schwaiger
Markus
M
D000818:Animals; D001562:Benzimidazoles / Q000493:pharmacokinetics*; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D003198:Computer Simulation; D006321:Heart / Q000000981:diagnostic imaging*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate; D008955:Models, Cardiovascular; D009206:Myocardium / Q000378:metabolism*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
D001562:Benzimidazoles; D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; D011943:Receptors, Adrenergic, beta; C109239:CGP 12388