Anti-CD45 Radioimmunotherapy with .sup.90Y but Not .sup.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 .sup.131 I or .sup.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 .sup.90 Y and .sup.177 Lu in a syngeneic, disseminated murine myeloid leukemia (B6SJLF1/J) model. Biodistribution studies showed that both .sup.90 Y- and .sup.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 .sup.90 Y-DOTA-30F11 and 54.2±9.5 and 199±11.7% ID/g of .sup.177 Lu-DOTA-30F11 accumulated in bone marrow (BM) and spleen, respectively. However, .sup.90 Y-DOTA-30F11 RIT demonstrated a dose-dependent survival benefit: 60% of mice treated with 300 [micro]Ci .sup.90 Y-DOTA-30F11 lived over 180 days after therapy, and mice treated with 100 [micro]Ci .sup.90 Y-DOTA-30F11 had a median survival 66 days. .sup.90 Y-anti-CD45 RIT was associated with transient, mild myelotoxicity without hepatic or renal toxicity. Conversely, .sup.177 Lu- anti-CD45 RIT yielded no long-term survivors. Thus, .sup.90 Y was more effective than .sup.177 Lu for anti-CD45 RIT of AML in this murine leukemia model.