CLINICAL-EVALUATION OF CARBON-11-PHENYLEPHRINE - MAO-SENSITIVE MARKEROF CARDIAC SYMPATHETIC NEURONS

The sympathomimetic drug phenylephrine recently has been labeled with C-11 for use in PET studies of cardiac sympathetic innervation. Previo us reports using isolated perfused rat heart models indicate that phen ylephrine is metabolized by intraneuronal monoamine oxidase (MAO). Thi s report compares the imaging characteristics, neuronal selectivity an d kinetics of (-)-[C-11]phenylephrine (PHEN) to the structurally simil ar but MAO-resistant analog (-)-[C-11]-meta-hydroxyephedrine (HED), an established heart neuronal marker. Methods: Fourteen healthy voluntee rs were studied with PET and PHEN. Ten had paired studies with HED; fo ur of the 10 were scanned a second time with each tracer after oral ad ministration of desipramine, a selective neuronal transport blocker. H emodynamic and electrocardiographic responses were monitored. Blood le vels of intact radiotracer and radiolabeled metabolites were determine d from venous blood samples taken during the PET study. Myocardial ret ention indices for both tracers were calculated. Results: No hemodynam ic or electrocardiographic effects were observed with either tracer. P HEN showed reduced myocardial retention at 50 min compared to HED; how ever, image quality and uniformity of distribution were comparable. PH EN cleared from myocardium with a mean half-time of 59 +/- 5 min, whil e myocardial levels of HED remained constant. PHEN metabolites appeare d in the blood approximately three times faster than HED metabolites. Desipramine pretreatment markedly reduced (>60%) myocardial retention of both PHEN and HED. Conclusion: PHEN provides PET images of human he art comparable in quality and uniformity to HED. Like HED, PHEN locali zes in the sympathetic nerves of the heart. However, the more rapid ef flux of PHEN, that is likely mediated by MAO, may provide information on the functional status of cardiac sympathetic neurons unobtainable w ith HED.