EVALUATION OF (-)[F-18]FLUOROETHOXYBENZOVESAMICOL AS A NEW PET TRACEROF CHOLINERGIC NEURONS OF THE HEART

F-18-labeled (-)fluoroethoxybenzovesamicol [(-)FEOBV] is a novel PET t racer which binds to the vesicular acetylcholine transporter of cholin ergic neurons. To evaluate the in vivo binding specificity and kinetic properties of (-)FEOBV, studies were performed in isolated working ra t hearts. External gamma,gamma-coincidence monitoring of hearts indica ted high extraction of radiotracer by the myocardium and rapid wash-ou t of unbound tracer (> 90% of maximal accumulation) within 5 min. Incl usion of (-)vesamicol (10 mu M) throughout perfusion decreased the ret ention of (-)FEOBV by 71% (P < 0.005) and 76% (P < 0.005) in atria and ventricles, respectively. However, the initial uptake rate of the tra cer was unaffected. Additional experiments showed the inactive stereoi somer, (+)FEOBV, to have a lower retention than the (-)FEOBV isomer in ventricles, indicating stereospecificity of the binding process that is consistent with structure-activity relationships of vesamicol conge ners. The results indicate (-)FEOBV to be a moderately specific probe of vesamicol-sensitive binding in cholinergic neurons of the heart in experimental conditions that assure adequate washout of unbound tracer . However, the utility of the radiotracer for in vivo studies with PET is likely to be limited by the low rate of specific binding in myocar dium consistent with the low density of cholinergic neurons in the hea rt.