Synthesis and biological characterization of stable and radioiodinated (±)-trans-2-hydroxy-3-P{4-(3-iodophenyl)piperidyl}-1,2,3,4-tetrahyd ronaphthalene (3′-IBVM)

The vesamicol analogue (±)-trans-2-Hydroxy-3-{4-(3-iodophenyl)piperidyl}-1,2,3,4-tetrahydr onaphthalene (3′-IBVM), a potent ligand for the vesicular acetylcholine transporter (VAChT), was evaluated as a potential radiotracer for studying VAChT density in vivo. In radioligand binding experiments, 3′-IBVM displays subnanomolar affinity for VAChT and 100-fold selectivity for VAChT over σ1 and σ2 receptors. Consistent with this profile, radioiodinated (±)-3′-IBVM distributed heterogenously in the rat brain following a bolus IV injection, displaying high concentrations in the striatum and moderate to low concentrations in the cortex and cerebellum, respectively. However, co-injection of the radiotracer with the sigma ligand haloperidol resulted in significant reductions of radiotracer levels in all brain regions examined. Therefore, radioiodinated (±)-IBVM appears to bind to both VAChT and sigma receptors in vivo.