A fluoro-analogue of the potent narcotic antagonist, naltrexone, was synthesized and shown to bind with high affinity to opiate receptors in vitro. 3-[fluorine-18]acetylcyclofoxy was prepared via a one-step triflate displacement reaction with the positron emitting fluorine-18 ion from tetraethylammonium [fluorine-18]fluoride. [Fluorine-18] 3-Acetylcyclofoxy accumulation in opiate receptor rich brain regions of both rat and baboon was shown to be completely displaced by the active enantiomer of naloxone ((-)-naloxone) while the identical dose of the pharmacologically inert (+)-naloxone has no detectable effect. Moreover, both rat and baboon brain showed the well documented, typical opiate receptor distribution so that basal ganglia and thalamus are clearly visible in the living baboon brain up to 95 min after intravenous injection of 3-[fluorine-18] acetylcyclofoxy. We expect that 3-[fluorine-18)acetylcyclofoxy will be a useful probe for visualizing opiate receptors in living humans.
