Biodistributions, myelosuppression, and toxicities in mice treated with an anti-CD45 antibody labeled with the alpha-emitting radionuclides bismuth-213 or astatine-211. Cancer Res 2009 Mar 15;69(6):2408-15
Date
02/27/2009Pubmed ID
19244101Pubmed Central ID
PMC2657815DOI
10.1158/0008-5472.CAN-08-4363Scopus ID
2-s2.0-65549097348 (requires institutional sign-in at Scopus site) 52 CitationsAbstract
We previously investigated the potential of targeted radiotherapy using a bismuth-213 ((213)Bi)-labeled anti-CD45 antibody to replace total body irradiation as conditioning for hematopoietic cell transplantation in a canine model. Although this approach allowed sustained marrow engraftment, limited availability, high cost, and short half-life of (213)Bi induced us to investigate an alternative alpha-emitting radionuclide, astatine-211 ((211)At), for the same application. Biodistribution and toxicity studies were conducted with conjugates of the anti-murine CD45 antibody 30F11 with either (213)Bi or (211)At. Mice were injected with 2 to 50 muCi on 10 microg or 20 muCi on 2 or 40 microg of 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 (211)At conjugate and 45 +/- 9% to 166 +/- 11% ID/g after injection of the (213)Bi conjugate. The higher concentrations observed for (211)At-labeled 30F11 were due to its longer half-life, which permitted better localization of isotope to the spleen before decay. (211)At was more effective at producing myelosuppression for the same quantity of injected radioactivity. All mice injected with 20 or 50 muCi (211)At, but none with the same quantities of (213)Bi, had lethal myeloablation. Severe reversible acute hepatic toxicity occurred with 50 muCi (213)Bi, but not with lower doses of (213)Bi or with any dose of (211)At. No renal toxicity occurred with either radionuclide. The data suggest that smaller quantities of (211)At-labeled anti-CD45 antibody are sufficient to achieve myelosuppression and myeloablation with less nonhematologic toxicity compared with (213)Bi-labeled antibody.
Author List
Nakamae H, Wilbur DS, Hamlin DK, Thakar MS, Santos EB, Fisher DR, Kenoyer AL, Pagel JM, Press OW, Storb R, Sandmaier BMMESH terms used to index this publication - Major topics in bold
Alpha ParticlesAnimals
Antibodies, Monoclonal
Astatine
Bismuth
Female
Immunotoxins
Isotope Labeling
Kidney Diseases
Leukocyte Common Antigens
Liver Diseases
Mice
Mice, Inbred BALB C
Radiation Injuries, Experimental
Radioimmunotherapy
Radioisotopes
Rats
Tissue Distribution
