Institute for Frontier Science Initiative, Kanazawa University, Kakuma-machi, Kanazawa, 920-1192, Japan.
Graduate School of Medical Sciences, Kanazawa University, Kakuma-machi, Kanazawa, 920-1192, Japan.
Sci Rep. 2020 Jul 17;10(1):11917. doi: 10.1038/s41598-020-68846-x.
[Ra]RaCl is the first alpha-particle emitting radiopharmaceutical to be used for castration-resistant prostate cancer patients with bone metastases because of its excellent therapeutic effects. [Ra]RaCl is excreted via the intestine into feces, and some is absorbed from the intestine into the blood, which may be undesirable in terms of the exposure to radiation. Recently, we showed that a complex of myo-inositol-hexakisphosphate (InsP6) with zinc is a useful decorporation agent against radiostrontium. In this study, we hypothesized that Zn-InsP6 could bind to not only strontium but also to radium, and could inhibit the absorption of radium from the intestine. In in vitro binding experiments, Zn-InsP6 showed a high binding affinity for radium. In in vivo biodistribution experiments by intravenous injection of [Ra]RaCl after treatment of Zn-InsP6, mice treated with Zn-InsP6 showed significantly lower bone accumulation of radioactivity (34.82 ± 1.83%Dose/g) than the mice in the non-treatment control group (40.30 ± 2.78%Dose/g) at 48 h postinjection. These results indicate that Zn-InsP6 bound radium in the intestine and inhibited the absorption of radium into the blood. Therefore, the insoluble Zn-InsP6 complex has high potential to decrease the side effects of [Ra]RaCl.
[Ra]RaCl 是第一种用于有骨转移的去势抵抗性前列腺癌患者的α粒子发射放射性药物，因为其具有极好的治疗效果。[Ra]RaCl 通过肠道排泄到粪便中，一些从肠道吸收到血液中，这在辐射暴露方面可能不理想。最近，我们表明肌醇六磷酸（InsP6）与锌的复合物是一种对抗放射性锶的有用的脱放射性药物。在这项研究中，我们假设 Zn-InsP6 不仅可以与锶结合，还可以与镭结合，并可以抑制镭从肠道的吸收。在体外结合实验中，Zn-InsP6 对镭表现出高的结合亲和力。在静脉注射[Ra]RaCl 后的体内生物分布实验中，在用 Zn-InsP6 处理后，与未处理的对照组（40.30 ± 2.78%Dose/g）相比，用 Zn-InsP6 处理的小鼠在注射后 48 小时时骨骼中放射性的积累明显更低（34.82 ± 1.83%Dose/g）。这些结果表明，Zn-InsP6 在肠道中结合了镭，并抑制了镭被吸收到血液中。因此，不溶性 Zn-InsP6 复合物具有降低[Ra]RaCl 副作用的高潜力。
