Advanced Clinical Research Center, Fukushima Global Medical Science Center, Fukushima Medical University, Fukushima, 960-1295, Japan.
Department of Nuclear Medicine, Fukushima Medical University, Fukushima, 960-1295, Japan.
Sci Rep. 2020 Apr 22;10(1):6810. doi: 10.1038/s41598-020-63557-9.
To explore stem-cell-targeted radioimmunotherapy with α-particles in acute myelogenous leukemia (AML), pharmacokinetics and dosimetry of the At-labeled anti-C-X-C chemokine receptor type 4 monoclonal antibody (At-CXCR4 mAb) were conducted using tumor xenografted mice. The biological half-life of At-CXCR4 mAb in blood was 15.0 h. The highest tumor uptake of 5.05%ID/g with the highest tumor-to-muscle ratio of 8.51 ± 6.14 was obtained at 6 h. Radiation dosimetry estimated with a human phantom showed absorbed doses of 0.512 mGy/MBq in the bone marrow, 0.287 mGy/MBq in the kidney, and <1 mGy/MBq in other major organs except bone. Sphere model analysis revealed 22.8 mGy/MBq in a tumor of 10 g; in this case, the tumor-to-bone marrow and tumor-to-kidney ratios were 44.5 and 79.4, respectively. The stem-cell-targeted α-particle therapy using At-CXCR4 mAb for AML appears possible and requires further therapeutic studies.
为了探索急性髓系白血病（AML）中基于干细胞的α粒子放射免疫治疗，我们使用肿瘤异种移植小鼠进行了放射性标记的抗 C-X-C 趋化因子受体 4 单克隆抗体（At-CXCR4 mAb）的药代动力学和剂量学研究。At-CXCR4 mAb 在血液中的生物学半衰期为 15.0 小时。在 6 小时时，获得了最高的肿瘤摄取量 5.05%ID/g 和最高的肿瘤与肌肉比 8.51±6.14。用人体模型进行的辐射剂量学估计显示，骨髓中的吸收剂量为 0.512 mGy/MBq，肾脏中的吸收剂量为 0.287 mGy/MBq，除骨骼外其他主要器官的吸收剂量均小于 1 mGy/MBq。球体模型分析显示，在 10g 的肿瘤中为 22.8 mGy/MBq；在这种情况下，肿瘤与骨髓和肿瘤与肾脏的比值分别为 44.5 和 79.4。使用 At-CXCR4 mAb 进行 AML 的基于干细胞的α粒子治疗似乎是可行的，需要进一步的治疗研究。
