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Biodistributions, Myelosuppression and Toxicities in Mice Treated with an Anti-CD45 Antibody Labeled with the α-Emitting Radionuclides Bismuth-213 or Astatine-211

Nakamae, Hirohisa and Wilbur, D. Scott and Hamlin, Donald K. and Thakar, Monica S. and Santos, Erlinda B. and Fisher, Darrell R. and Kenoyer, Aimee L. and Pagel, John M. and Press, Oliver W. and Storb, Rainer and Sandmaier, Brenda M. (2009) Biodistributions, Myelosuppression and Toxicities in Mice Treated with an Anti-CD45 Antibody Labeled with the α-Emitting Radionuclides Bismuth-213 or Astatine-211. Cancer Research, 69 (6). pp. 2408-2415. ISSN 0008-5472

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We previously investigated the potential of targeted radiotherapy using a bismuth-213- labeled anti-CD45 antibody to replace total body irradiation as conditioning for hematopoietic cell transplantation in a canine model. While this approach allowed sustained marrow engraftment, limited availability, high cost and short half-life of bismuth-213 induced us to investigate an alternative α-emitting radionuclide, astatine-211, for the same application. Biodistribution and toxicity studies were conducted with conjugates of the anti-murine CD45 antibody 30F11 with either bismuth-213 or astatine-211. Mice were injected with 2-50 μCi on 10 μg or 20 μCi on 2 or 40 μg 30F11 conjugate. Biodistribution studies showed that the spleen contained the highest concentration of radioactivity, ranging from 167±23 to 417±109 % injected dose/gram (%ID/g) after injection of the astatine-211 conjugate and 45±9 to 166±11 %ID/g after injection of the bismuth-213 conjugate. The higher concentrations observed for astatine-211- labeled 30F11 were due to its longer half-life, which permitted better localization of isotope to the spleen before decay. Astatine-211 was more effective at producing myelosuppression for the same quantity of injected radioactivity. All mice injected with 20 or 50 μCi astatine-211 but none with the same quantities of bismuth-213 had lethal myeloablation. Severe reversible acute hepatic toxicity occurred with 50 μCi bismuth-213, but not with lower doses of bismuth-213 or with any dose of astatine-211. No renal toxicity occurred with either radionuclide. The data suggest that smaller quantities of astatine-211-labeled anti-CD45 antibody are sufficient to achieve myelosuppression and myeloablation with less non-hematological toxicity compared with bismuth-213-labeled antibody.

Item Type: Article or Abstract
Additional Information: This article is available to subscribers only via the URL above for the first 12 months post-publication.
DOI: 10.1158/0008-5472.CAN-08-4363
PubMed ID: 19244101
PMCID: PMC2657815
Grant Numbers: R01 CA118940-03, P30 CA015704-34, R01 CA109663-04, K08 CA095448-05
Keywords or MeSH Headings: * Alpha Particles * Animals * Antibodies, Monoclonal/immunology* * Antigens, CD45/immunology* * Astatine/pharmacokinetics* * Astatine/toxicity * Bismuth/pharmacokinetics* * Bismuth/toxicity * Female * Immunotoxins/immunology * Immunotoxins/pharmacokinetics* * Immunotoxins/toxicity * Isotope Labeling * Kidney Diseases/etiology * Liver Diseases/etiology * Mice * Mice, Inbred BALB C * Radiation Injuries, Experimental/etiology * Radioimmunotherapy/adverse effects * Radioimmunotherapy/methods * Radioisotopes/pharmacokinetics* * Radioisotopes/toxicity * Rats * Tissue Distribution
Subjects: Therapeutics > Radiotherapy
Therapeutics > Transplantation > Stem Cell transplantation
Depositing User: Library Staff
Date Deposited: 17 Dec 2008 00:40
Last Modified: 14 Feb 2012 14:42

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