Anti-CD45 Radioimmunotherapy with 90Y but Not 177Lu Is Effective Treatment in a Syngeneic Murine Leukemia Model

Radioimmunotherapy (RIT) for treatment of hematologic malignancies has primarily employed monoclonal antibodies (Ab) labeled with I-131 or Y-90 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 Y-90 and Lu-177 in a syngeneic, disseminated murine myeloid leukemia (B6SJLF1/J) model. Biodistribution studies showed that both Y-90- and Lu-177-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 Y-90-DOTA-30F11 and 54.2 +/- 9.5 and 199 +/- 11.7% ID/g of Lu-177-DOTA-30F11 accumulated in bone marrow (BM) and spleen, respectively. However, Y-90-DOTA-30F11 RIT demonstrated a dose-dependent survival benefit: 60% of mice treated with 300 mu Ci Y-90-DOTA-30F11 lived over 180 days after therapy, and mice treated with 100 mu Ci Y-90-DOTA-30F11 had a median survival 66 days. Y-90-anti-CD45 RIT was associated with transient, mild myelotoxicity without hepatic or renal toxicity. Conversely, Lu-177-anti-CD45 RIT yielded no long-term survivors. Thus, Y-90 was more effective than Lu-177 for anti-CD45 RIT of AML in this murine leukemia model.