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

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, radi oiodinated (+/-) 3'-IBVM distributed heterogenously in the rat brain follow ing a bolus IV injection, displaying high concentrations in the striatum an d moderate to low concentrations in the cortex and cerebellum, respectively . However, co injection of the radiotracer with the sigma ligand haloperido l resulted in significant reductions of radiotracer levels in all brain reg ions examined. Therefore, radioiodinated (+/-)-IBVM appears to bind to both VAChT and sigma receptors in vivo. NUCL MED BIOL 27;8:749-755, 2000. (C) 2 000 Elsevier Science Inc. All rights reserved.