Clinical Evaluation of Carbon-11-Phenylephrine: MAO-Sensitive Marker of Cardiac Sympathetic Neurons

The sympathomimetic drug phenylephrine recently has been labeled with 11 C for use in PET studies of cardiac sympathetic innervation. Previous reports using isolated perfused rat heart models indicate that phenylephrine is metabolized by intraneuronal monoamine oxidase (MAO). This report compares the imaging characteristics, neuronal selectivity and kinetics of (-)-[ 11 C]phenylephrine (PHEN) to the structurally similar but MAO-resistant analog (-)-[ 11 C]-meta-hydroxyephedrine (HED), an established heart neuronal marker. Methods : Fourteen healthy volunteers were studied with PET and PHEN. Ten had paired studies with HED ; four of the 10 were scanned a second time with each tracer after oral administration of desipramine, a selective neuronal transport blocker. Hemodynamic and electrocardiographic responses were monitored. Blood levels of intact radiotracer and radiolabeled metabolites were determined from venous blood samples taken during the PET study. Myocardial retention indices for both tracers were calculated. Results : No hemodynamic or electrocardiographic effects were observed with either tracer. PHEN showed reduced myocardial retention at 50 min compared to HED ; however, image quality and uniformity of distribution were comparable. PHEN cleared from myocardium with a mean half-time of 59 ± 5 min, while myocardial levels of HED remained constant. PHEN metabolites appeared 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 heart comparable in quality and uniformity to HED. Like HED, PHEN localizes in the sympathetic nerves of the heart. However, the more rapid efflux of PHEN, that is likely mediated by MAO, may provide information on the functional status of cardiac sympathetic neurons unobtainable with HED.