title: Anti-CD45 radioimmunotherapy with 90Y but not 177Lu is effective treatment in a syngeneic murine leukemia model.
abstract: 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.
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America; Hematology Division, University of Washington, Seattle, WA, United States of America.
authors.forename: Johnnie J
authors.initials: JJ
authors.lastname: Orozco
authors.affiliation: Radiation Oncology, University of Washington, Seattle, WA, United States of America.
authors.forename: Ethan R
authors.initials: ER
authors.lastname: Balkin
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America.
authors.forename: Ted A
authors.initials: TA
authors.lastname: Gooley
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America.
authors.forename: Aimee
authors.initials: A
authors.lastname: Kenoyer
authors.affiliation: Radiation Oncology, University of Washington, Seattle, WA, United States of America.
authors.forename: Donald K
authors.initials: DK
authors.lastname: Hamlin
authors.affiliation: Radiation Oncology, University of Washington, Seattle, WA, United States of America.
authors.forename: D Scott
authors.initials: DS
authors.lastname: Wilbur
authors.affiliation: Dade Moeller Health Group, Richland, WA, United States of America.
authors.forename: Darrell R
authors.initials: DR
authors.lastname: Fisher
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Hylarides
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America; Hematology Division, University of Washington, Seattle, WA, United States of America.
authors.forename: Mazyar
authors.initials: M
authors.lastname: Shadman
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America; Medical Oncology, University of Washington, Seattle, WA, United States of America.
authors.forename: Damian J
authors.initials: DJ
authors.lastname: Green
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America; Medical Oncology, University of Washington, Seattle, WA, United States of America.
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Gopal
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America; Medical Oncology, University of Washington, Seattle, WA, United States of America.
authors.forename: Oliver W
authors.initials: OW
authors.lastname: Press
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America; Medical Oncology, University of Washington, Seattle, WA, United States of America.
authors.forename: John M
authors.initials: JM
authors.lastname: Pagel
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D004195:Disease Models, Animal; D006801:Humans; D007668:Kidney / Q000473:pathology / Q000528:radiation effects; D007951:Leukemia, Myeloid / Q000276:immunology* / Q000473:pathology / Q000532:radiotherapy*; D017493:Leukocyte Common Antigens / Q000037:antagonists & inhibitors / Q000276:immunology*; D051379:Mice; D016499:Radioimmunotherapy; D011877:Radionuclide Imaging; D013154:Spleen / Q000473:pathology / Q000528:radiation effects; D014018:Tissue Distribution / Q000276:immunology / Q000528:radiation effects; D016896:Treatment Outcome; D015021:Yttrium Radioisotopes / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D015021:Yttrium Radioisotopes; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human