Possibility of cancer-stem-cell-targeted radioimmunotherapy for acute myelogenous leukemia using 211At-CXCR4 monoclonal antibody.
Possibility of cancer-stem-cell-targeted radioimmunotherapy for acute myelogenous leukemia using 211At-CXCR4 monoclonal antibody.
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使用 211At-CXCR4 单克隆抗体对急性髓性白血病进行癌症干细胞靶向放射免疫治疗的可能性。
DOI：
10.1038/s41598-020-63557-9
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发表时间：
2020
期刊：
影响因子：
--
通讯作者：
Oriuchi N
中科院分区：
文献类型：
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作者：
Mizoguchi N;Kano K;Shima S;Tsuchida K;Takakusagi Y;Serizawa I;Akahane K;Kawahara M;Yoshida M;Kitani Y;Hashimoto K;Furukawa M;Kamada T;Katoh H;Yoshida D;Shirai K.;Yoshinori Sakurai;Oriuchi N
为探讨α粒子放射免疫治疗急性髓性白血病（AML）的靶向作用，采用211 At-CXCR 4单克隆抗体（211 At-CXCR 4 mAb）进行肿瘤移植小鼠的药代动力学和剂量学研究。211 At-CXCR 4 mAb在血液中的生物半衰期为15.0 h。6 h时肿瘤摄取最高为5.05%ID/g，肿瘤/肌肉比值最高为8.51 ± 6.14。用人体模体估计的辐射剂量学显示，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，除骨外的其他主要器官中的吸收剂量<1 mGy/MBq。球体模型分析显示，10 g肿瘤中的剂量为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。211 At-CXCR 4 mAb用于AML的干细胞靶向α粒子治疗似乎是可能的，需要进一步的治疗研究。
To explore stem-cell-targeted radioimmunotherapy with α-particles in acute myelogenous leukemia (AML), pharmacokinetics and dosimetry of the211At-labeled anti-C-X-C chemokine receptor type 4 monoclonal antibody (211At-CXCR4 mAb) were conducted using tumor xenografted mice. The biological half-life of211At-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 using211At-CXCR4 mAb for AML appears possible and requires further therapeutic studies.