Synthesis and biological characterization of stable and radioiodinated (+/-)-trans-2-hydroxy-3-P[4-(3-iodophenyl)piperidyl]-1,2,3,4-tetrahydronaphthalene (3'-IBVM)

Abstract

The vesamicol analogue (+/-)-trans-2-Hydroxy-3-[4-(3-iodophenyl)piperidyl]-1,2,3,4-tetrahydronaphthalene (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 sigma1 and sigma2 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.