As
sigma receptors are highly expressed on various
cancer cells, radiolabeled
sigma receptor ligands have been developed as imaging and therapeutic probes for
cancer. Previously, we synthesized and evaluated a radioiodinated
vesamicol derivative, 2-(4-[125I](4-iodophenyl)
piperidine)
cyclohexanol ((+)-[125I]pIV), and a radioiodinated aza-
vesamicol derivative, trans-2-(4-(3-[125I](4-iodophenyl)propyl)piperazin-1-yl)cyclohexan-1-ol ([125I]2), as
sigma-1 receptor-targeting probes. In order to obtain
sigma receptor-targeting probes with superior biodistribution characteristics, we firstly synthesized twelve
bromine-containing aza-
vesamicol derivatives and evaluated their affinity for
sigma receptors. One such derivative exhibited high selectivity for the
sigma-1 receptor and another exhibited high affinity for both the sigma-1 and
sigma-2 receptors. Thus, their
halogen-substituted
iodine- and radioiodine-containing compounds were prepared. The 125I-labeled compounds exhibited high uptake in
tumor and lower uptake in non-target tissues than the two previously developed and evaluated 125I-labeled
sigma receptor-targeting probes, [125I]pIV and [125I]2. Therefore, these novel radioiodine-labeled compounds should be promising as
sigma receptor-targeting probes.