Possibility Of Cancer-Stem-Cell-Targeted Radioimmunotherapy For Acute Myelogenous Leukemia Using At-211-Cxcr4 Monoclonal Antibody

To explore stem-cell-targeted radioimmunotherapy with alpha-particles in acute myelogenous leukemia (AML), pharmacokinetics and dosimetry of the At-211-labeled anti-C-X-C chemokine receptor type 4 monoclonal antibody (At-211-CXCR4 mAb) were conducted using tumor xenografted mice. The biological half-life of At-211-CXCR4 mAb in blood was 15.0h. The highest tumor uptake of 5.05%ID/g with the highest tumor-to-muscle ratio of 8.51 +/- 6.14 was obtained at 6h. 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 10g; in this case, the tumor-to-bone marrow and tumor-to-kidney ratios were 44.5 and 79.4, respectively. The stem-cell-targeted alpha-particle therapy using At-211-CXCR4 mAb for AML appears possible and requires further therapeutic studies.