Mishiro Kenji, Wang Mengfei, Hirata Saki, Fuchigami Takeshi, Shiba Kazuhiro, Kinuya Seigo, Ogawa Kazuma
Institute for Frontier Science Initiative, Kanazawa University Kakuma-machi Kanazawa Ishikawa 920-1192 Japan
Graduate School of Pharmaceutical Sciences, Kanazawa University Kakuma-machi Kanazawa Ishikawa 920-1192 Japan.
RSC Med Chem. 2022 Jun 30;13(8):986-997. doi: 10.1039/d2md00099g. eCollection 2022 Aug 17.
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-Ipiperidine)cyclohexanol ((+)-[I]IV), and a radioiodinated aza-vesamicol derivative, -2-(4-(3-Ipropyl)piperazin-1-yl)cyclohexan-1-ol ([I]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 I-labeled compounds exhibited high uptake in tumor and lower uptake in non-target tissues than the two previously developed and evaluated I-labeled sigma receptor-targeting probes, [I]IV and [I]2. Therefore, these novel radioiodine-labeled compounds should be promising as sigma receptor-targeting probes.
由于σ受体在各种癌细胞上高度表达，放射性标记的σ受体配体已被开发为癌症的成像和治疗探针。此前，我们合成并评估了一种放射性碘化维库溴铵衍生物，2-(4-I哌啶)环己醇((+)-[I]IV)，以及一种放射性碘化氮杂维库溴铵衍生物，-2-(4-(3-I丙基)哌嗪-1-基)环己醇([I]2)，作为靶向σ-1受体的探针。为了获得具有优异生物分布特性的靶向σ受体的探针，我们首先合成了十二种含溴的氮杂维库溴铵衍生物，并评估了它们对σ受体的亲和力。其中一种衍生物对σ-1受体表现出高选择性，另一种对σ-1和σ-2受体均表现出高亲和力。因此，制备了它们的卤素取代的含碘和放射性碘的化合物。与之前开发并评估的两种放射性碘化靶向σ受体的探针[I]IV和[I]2相比，I标记的化合物在肿瘤中的摄取较高，而在非靶组织中的摄取较低。因此，这些新型放射性碘标记的化合物有望成为靶向σ受体的探针。
