At-211 Production using the CYPRIS MP-30

Washiyama, Kohshin; Oda, Takashi; Shigenori, Sasaki; Aoki, Miho; Gomez, Francisco L. Guerra; Taniguchi, Manami; Nishijima, Ken‐ichi; Takahashi, Kazuhiro

doi:10.1016/j.jmir.2019.11.133

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“…Production and purification of 211 At. 211 At was produced by 209 Bi(α, 2n) 211 At nuclear reaction using a MP-30 cyclotron (Sumitomo Heavy Industries Ltd. Tokyo, Japan) in our facility 34 . A schematic diagram of production, separation, and preparation of 211 At for the radiolabeling of anti-CXCR4 mAb is shown in Fig.…”

Section: Cell Line and Xenograft Model The Human Aml Cell Line U937 mentioning

confidence: 99%

Possibility of cancer-stem-cell-targeted radioimmunotherapy for acute myelogenous leukemia using 211At-CXCR4 monoclonal antibody

Oriuchi

Aoki

Ukon

et al. 2020

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to explore stem-cell-targeted radioimmunotherapy with α-particles in acute myelogenous leukemia (AML), pharmacokinetics and dosimetry of the 211 At-labeled anti-C-X-C chemokine receptor type 4 monoclonal antibody ( 211 At-CXCR4 mAb) were conducted using tumor xenografted mice. The biological half-life of 211 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 211 At-CXCR4 mAb for AML appears possible and requires further therapeutic studies.Targeted α-particle therapy (TAT) has great potential for the treatment of cancer based on the specific delivery of a high radiation dose from α-particles emitting radionuclides to tumors while minimizing systemic toxic effects, and it may lead to additional treatment options for many types of advanced or refractory cancer 1 . The high level of radiobiological effectiveness of α-particles, in comparison with β-particles emissions, requires fewer radiation tracks to induce cell death. The short path length of α-particles radiation confines its cytotoxic effect to the target tissue and the surrounding tumor microenvironment while limiting toxic effects to non-neoplastic tissues.Following the successful clinical TAT with 223 Ra dichloride for the treatment of metastatic castration-resistant prostate cancer with bone metastases and the clinical experience with 213 Bi-and 225 Ac-labeled compounds 2-4 , there has been an increased interest in new applications of TAT for many tumor types. Among the α-particles-emitting radionuclides for TAT, 211 At can be produced using a cyclotron with an α-particle beam, and its separation and purification from the target has been established after decades of continuous research. After a branch decay with a half-life of 7.21 h, 211 At completely emits α-particles with 100% probability. A few clinical applications of 211 At for the treatment of malignant neoplasms have been reported 5,6 .The failure of medical and radiological anti-cancer therapies is partially attributable to the heterogeneity of cancer. One of the mechanisms explaining cancer heterogeneity is the existence of cancer stem cells (CSCs) 7 . CSCs exhibit self-renewal activity and long-term proliferating capability 8 . The concept of neoplastic stem cells may explain the failure of various therapies to achieve long-lasting responses in patients 9 , because CSCs are suggested as a potential source of resistance to different types of anti-neoplastic drug. Anti-neoplastic drugs are considered to act on mature neoplastic cells rather than on CSCs in many neoplastic tissues. This is partially owing to th...

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Section: Cell Line and Xenograft Model The Human Aml Cell Line U937 mentioning

confidence: 99%