Durable donor engraftment after radioimmunotherapy using α-emitter astatine-211-labeled anti-CD45 antibody for conditioning in allogeneic hematopoietic cell transplantation

Blood. 2012 Feb 2;119(5):1130-8. doi: 10.1182/blood-2011-09-380436. Epub 2011 Dec 1.


To reduce toxicity associated with external γ-beam radiation, we investigated radioimmunotherapy with an anti-CD45 mAb labeled with the α-emitter, astatine-211 ((211)At), as a conditioning regimen in dog leukocyte antigen-identical hematopoietic cell transplantation (HCT). Dose-finding studies in 6 dogs treated with 100 to 618 μCi/kg (211)At-labeled anti-CD45 mAb (0.5 mg/kg) without HCT rescue demonstrated dose-dependent myelosuppression with subsequent autologous recovery, and transient liver toxicity in dogs treated with (211)At doses less than or equal to 405 μCi/kg. Higher doses of (211)At induced clinical liver failure. Subsequently, 8 dogs were conditioned with 155 to 625 μCi/kg (211)At-labeled anti-CD45 mAb (0.5 mg/kg) before HCT with dog leukocyte antigen-identical bone marrow followed by a short course of cyclosporine and mycophenolate mofetil immunosuppression. Neutropenia (1-146 cells/μL), lymphopenia (0-270 cells/μL), and thrombocytopenia (1500-6560 platelets/μL) with prompt recovery was observed. Seven dogs had long-term donor mononuclear cell chimerism (19%-58%), whereas 1 dog treated with the lowest (211)At dose (155 μCi/kg) had low donor mononuclear cell chimerism (5%). At the end of follow-up (18-53 weeks), only transient liver toxicity and no renal toxicity had been observed. In conclusion, conditioning with (211)At-labeled anti-CD45 mAb is safe and efficacious and provides a platform for future clinical trials of nonmyeloablative transplantation with radioimmunotherapy-based conditioning.

Publication types

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

MeSH terms

  • Alpha Particles / therapeutic use
  • Animals
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / metabolism
  • Antibodies, Monoclonal / therapeutic use*
  • Astatine / chemistry
  • Astatine / pharmacokinetics
  • Astatine / therapeutic use*
  • Blood Donors
  • Boron Compounds / chemistry
  • Cells, Cultured
  • Dogs
  • Dose-Response Relationship, Drug
  • Graft Survival* / immunology
  • Graft Survival* / radiation effects
  • Hematologic Neoplasms / blood
  • Hematologic Neoplasms / immunology
  • Hematologic Neoplasms / radiotherapy
  • Hematologic Neoplasms / therapy*
  • Hematopoietic Stem Cell Transplantation* / methods
  • Leukocyte Common Antigens / immunology*
  • Radioimmunotherapy / adverse effects
  • Radioimmunotherapy / methods*
  • Transplantation Conditioning / methods*
  • Transplantation, Homologous


  • Antibodies, Monoclonal
  • Boron Compounds
  • dodecaborate
  • Leukocyte Common Antigens
  • Astatine