Abstract
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.