Development of tumor-targeting aza-vesamicol derivatives with high affinity for sigma receptors for cancer theranostics.

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.

SUBMITTER: Mishiro K 

PROVIDER: S-EPMC9384704 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature