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

Sci Rep. 2020 Apr 22;10(1):6810. doi: 10.1038/s41598-020-63557-9.

Abstract

To explore stem-cell-targeted radioimmunotherapy with α-particles in acute myelogenous leukemia (AML), pharmacokinetics and dosimetry of the 211At-labeled anti-C-X-C chemokine receptor type 4 monoclonal antibody (211At-CXCR4 mAb) were conducted using tumor xenografted mice. The biological half-life of 211At-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 211At-CXCR4 mAb for AML appears possible and requires further therapeutic studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use*
  • Astatine / therapeutic use*
  • Humans
  • Iodine Radioisotopes
  • Leukemia, Myeloid, Acute / immunology*
  • Leukemia, Myeloid, Acute / pathology
  • Leukemia, Myeloid, Acute / therapy*
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Muscles / pathology
  • Neoplastic Stem Cells / pathology*
  • Organ Specificity
  • Radiation Dosage
  • Radioimmunotherapy*
  • Receptors, CXCR4 / immunology*
  • Tissue Distribution
  • U937 Cells
  • Xenograft Model Antitumor Assays

Substances

  • Antibodies, Monoclonal
  • Astatine-211
  • CXCR4 protein, human
  • Iodine Radioisotopes
  • Receptors, CXCR4
  • Iodine-125
  • Astatine