Anti-CD45 radioimmunotherapy with 90Y but not 177Lu is effective treatment in a syngeneic murine leukemia model

• Published in: PloS one 2014, Vol.9 (12), p.e113601
• Main Authors: Orozco, Johnnie J, Balkin, Ethan R, Gooley, Ted A, Kenoyer, Aimee, Hamlin, Donald K, Wilbur, D Scott, Fisher, Darrell R, Hylarides, Mark D, Shadman, Mazyar, Green, Damian J, Gopal, Ajay K, Press, Oliver W, Pagel, John M
• Format: Article
• Language: English
• Subjects: Acute myeloid leukemia; Animals; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - therapeutic use; Antigens; Biology; Biology and Life Sciences; Bone marrow; Cancer therapies; CD45 antigen; Chemotherapy; Disease Models, Animal; Dosage; Dosimetry; Drug dosages; Hematology; Humans; Immunoglobulins; Iodine; Kidney - pathology; Kidney - radiation effects; Laboratory animals; Leukemia; Leukemia, Myeloid - immunology; Leukemia, Myeloid - pathology; Leukemia, Myeloid - radiotherapy; Leukocyte Common Antigens - antagonists & inhibitors; Leukocyte Common Antigens - immunology; Lutetium isotopes; Lymphoma; Medical research; Medicine and Health Sciences; Mice; Monoclonal antibodies; Myeloid leukemia; Myelosuppression; Nuclear medicine; Oncology; Physics; Radiation therapy; Radioimmunotherapy; Radioisotopes; Radionuclide Imaging; Spleen; Spleen - pathology; Spleen - radiation effects; Survival; Tissue Distribution - immunology; Tissue Distribution - radiation effects; Toxicity; Transplants & implants; Treatment Outcome; Yttrium isotopes; Yttrium Radioisotopes - adverse effects; Yttrium Radioisotopes - therapeutic use
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0113601

Radioimmunotherapy (RIT) for treatment of hematologic malignancies has primarily employed monoclonal antibodies (Ab) labeled with 131I or 90Y which have limitations, and alternative radionuclides are needed to facilitate wider adoption of RIT. We therefore compared the relative therapeutic efficacy and toxicity of anti-CD45 RIT employing 90Y and 177Lu in a syngeneic, disseminated murine myeloid leukemia (B6SJLF1/J) model. Biodistribution studies showed that both 90Y- and 177Lu-anti-murine CD45 Ab conjugates (DOTA-30F11) targeted hematologic tissues, as at 24 hours 48.8 ± 21.2 and 156 ± 14.6% injected dose per gram of tissue (% ID/g) of 90Y-DOTA-30F11 and 54.2 ± 9.5 and 199 ± 11.7% ID/g of 177Lu-DOTA-30F11 accumulated in bone marrow (BM) and spleen, respectively. However, 90Y-DOTA-30F11 RIT demonstrated a dose-dependent survival benefit: 60% of mice treated with 300 µCi 90Y-DOTA-30F11 lived over 180 days after therapy, and mice treated with 100 µCi 90Y-DOTA-30F11 had a median survival 66 days. 90Y-anti-CD45 RIT was associated with transient, mild myelotoxicity without hepatic or renal toxicity. Conversely, 177Lu- anti-CD45 RIT yielded no long-term survivors. Thus, 90Y was more effective than 177Lu for anti-CD45 RIT of AML in this murine leukemia model.