This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pagel, J. M. Articles by Press, O. W. Search for Related Content PubMed PubMed Citation Articles by Pagel, J. M. Articles by Press, O. W.

Pretargeted Radioimmunotherapy Using Anti-CD45 Monoclonal Antibodies to Deliver Radiation to Murine Hematolymphoid Tissues and Human Myeloid Leukemia

¹ Fred Hutchinson Cancer Research Center; Departments of ² Medicine, ³ Radiation Oncology, and ⁴ Pediatrics, University of Washington, Seattle, Washington; and ⁵ Pacific Northwest National Laboratories, Richland, Washington

Requests for reprints: John Pagel, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N, M/S D5-380, Seattle, WA 98109. Phone: 206-667-1868; Fax: 206-667-4111; E-mail: jpagel{at}fhcrc.org.

Key Words: radioimmunotherapy • CD45 • leukemia

Radioimmunotherapy (RIT) for treatment of hematologic malignancies frequently fails because of disease recurrence. We therefore conducted pretargeted (P)RIT studies to augment the efficacy in mice of therapy using a pretargeted anti-human (h)CD45 antibody (Ab)-streptavidin (SA) conjugate followed by a biotinylated clearing agent and radiolabeled 1,4,7,10-tetraazacylodode cane N,N',N'',N'''-tetraacetic (DOTA)-biotin. Tumor-to-blood ratios at 24 hours were 20:1 using pretargeted anti-hCD45 RIT and <1:1 with conventional RIT. In vivo imaging studies confirmed that the PRIT approach provided high-contrast tumor images with minimal blood-pool activity, whereas directly labeled anti-hCD45 Ab produced distinct tumor images but the blood pool retained a large amount of labeled Ab for a prolonged time. Therapy experiments showed that ⁹⁰Y-DOTA-biotin significantly prolonged survival of mice treated with pretargeted anti-hCD45 Ab-SA compared with mice treated with conventional RIT using ⁹⁰Y-labeled anti-hCD45 Ab at 200 µCi. Because human CD45 antigens are confined to xenograft tumor cells in this model, and all murine tissues are devoid of hCD45 and will not bind anti-hCD45 Ab, we also compared one-step and PRIT using an anti-murine (m)CD45 Ab where the target antigen is present on normal hematopoietic tissues. After 24 h, 27.3% ± 2.8% of the injected dose of activity was delivered per gram (% ID/g) of lymph node using ¹³¹I-A20-Ab compared with 40.0 ± 5.4% ID/g for pretargeted ¹¹¹In-DOTA-biotin. These data suggest that pretargeted methods for delivering RIT may be superior to conventional RIT when targeting CD45 for the treatment of leukemia and may allow for the intensification of therapy, while minimizing toxicities. [Cancer Res 2009;69(1):185–92]

This article has been cited by other articles:

				D. J. Green, J. M. Pagel, E. R. Nemecek, Y. Lin, A. Kenoyer, A. Pantelias, D. K. Hamlin, D. S. Wilbur, D. R. Fisher, J. G. Rajendran, et al. Pretargeting CD45 enhances the selective delivery of radiation to hematolymphoid tissues in nonhuman primates Blood, August 6, 2009; 114(6): 1226 - 1235. [Abstract] [Full Text] [PDF]