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, 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. NUCL MED BIOL 27;8:749-755, 2000. (C) 2000 Elsevier Science Inc. All rights reserved.