Tr. Degrado et al., EVALUATION OF (-)[F-18]FLUOROETHOXYBENZOVESAMICOL AS A NEW PET TRACEROF CHOLINERGIC NEURONS OF THE HEART, Nuclear medicine and biology, 21(2), 1994, pp. 189-195
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.