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 Blood, 15 February 2008, Vol. 111, No. 4, pp. 2261-2268.
Prepublished online as a Blood First Edition Paper on November 27, 2007; DOI 10.1182/blood-2007-06-097451.

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NEOPLASIA

Eradication of disseminated leukemia in a syngeneic murine leukemia model using pretargeted anti-CD45 radioimmunotherapy

John M. Pagel1,2, Nathan Hedin1, Lacey Drouet1, Brent L. Wood1, Anastasia Pantelias1, Yukang Lin1, Donald K. Hamlin3, D. Scott Wilbur3, Ajay K. Gopal1,2, Damian Green1,2, Frederick R. Appelbaum1,2, and Oliver W. Press1,2

1 Fred Hutchinson Cancer Research Center, Seattle, WA; and the Departments of2 Medicine and 3 Radiation Oncology, University of Washington, Seattle

We describe the use of pretargeted radioimmunotherapy (PRIT) using an anti–murine CD45 antibody-streptavidin (SA) conjugate followed by radiobiotin to deliver radiation selectively to murine hematolymphoid tissues, which may potentially augment the efficacy and decrease the toxicity of radioimmunotherapy for disseminated murine leukemia. Biodistribution and therapeutic results demonstrated high target organ to nontarget organ ratios of radioactivity and significant long-term survival in leukemic mice using PRIT. These data suggest that anti-CD45 PRIT using an anti–CD45-SA conjugate in a syngeneic murine model of disseminated leukemia may be more effective and less toxic than directly labeled monoclonal antibodies.


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R. M. Sharkey, H. Karacay, S. Litwin, E. A. Rossi, W. J. McBride, C.-H. Chang, and D. M. Goldenberg
Improved Therapeutic Results by Pretargeted Radioimmunotherapy of Non-Hodgkin's Lymphoma with a New Recombinant, Trivalent, Anti-CD20, Bispecific Antibody
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