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

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