Anti-CD45 pretargeted radioimmunotherapy using bismuth-213: high rates of complete remission and long-term survival in a mouse myeloid leukemia xenograft model

Blood. 2011 Jul 21;118(3):703-11. doi: 10.1182/blood-2011-04-347039. Epub 2011 May 25.


Pretargeted radioimmunotherapy (PRIT) using an anti-CD45 antibody (Ab)-streptavidin (SA) conjugate and DOTA-biotin labeled with β-emitting radionuclides has been explored as a strategy to decrease relapse and toxicity. α-emitting radionuclides exhibit high cytotoxicity coupled with a short path length, potentially increasing the therapeutic index and making them an attractive alternative to β-emitting radionuclides for patients with acute myeloid leukemia. Accordingly, we have used (213)Bi in mice with human leukemia xenografts. Results demonstrated excellent localization of (213)Bi-DOTA-biotin to tumors with minimal uptake into normal organs. After 10 minutes, 4.5% ± 1.1% of the injected dose of (213)Bi was delivered per gram of tumor. α-imaging demonstrated uniform radionuclide distribution within tumor tissue 45 minutes after (213)Bi-DOTA-biotin injection. Radiation absorbed doses were similar to those observed using a β-emitting radionuclide ((90)Y) in the same model. We conducted therapy experiments in a xenograft model using a single-dose of (213)Bi-DOTA-biotin given 24 hours after anti-CD45 Ab-SA conjugate. Among mice treated with anti-CD45 Ab-SA conjugate followed by 800 μCi of (213)Bi- or (90)Y-DOTA-biotin, 80% and 20%, respectively, survived leukemia-free for more than 100 days with minimal toxicity. These data suggest that anti-CD45 PRIT using an α-emitting radionuclide may be highly effective and minimally toxic for treatment of acute myeloid leukemia.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / pharmacology*
  • Biotin / analogs & derivatives
  • Biotin / pharmacology
  • Bismuth / pharmacology*
  • Cell Line, Tumor
  • Disease Models, Animal
  • Dose-Response Relationship, Immunologic
  • Dose-Response Relationship, Radiation
  • Female
  • Humans
  • Leukemia, Myeloid, Acute / immunology
  • Leukemia, Myeloid, Acute / radiotherapy*
  • Leukocyte Common Antigens / antagonists & inhibitors*
  • Leukocyte Common Antigens / immunology
  • Mice
  • Mice, Inbred BALB C
  • Organometallic Compounds / pharmacology
  • Radioimmunotherapy / methods*
  • Radioisotopes / pharmacology*
  • Remission Induction
  • Streptavidin / pharmacology
  • Survival Rate
  • Xenograft Model Antitumor Assays


  • Antibodies
  • DOTA-biotin
  • Organometallic Compounds
  • Radioisotopes
  • Biotin
  • Streptavidin
  • Leukocyte Common Antigens
  • PTPRC protein, human
  • Bismuth