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

We previously investigated the potential of targeted radiotherapy using a bismuth-213 (²¹³Bi)–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 ²¹³Bi induced us to investigate an alternative α-emitting radionuclide, astatine-211 (²¹¹At), for the same application. Biodistribution and toxicity studies were conducted with conjugates of the anti-murine CD45 antibody 30F11 with either ²¹³Bi or ²¹¹At. Mice were injected with 2 to 50 μCi on 10 μg or 20 μCi on 2 or 40 μg 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 ²¹¹At conjugate and 45 ± 9% to 166 ± 11% ID/g after injection of the ²¹³Bi conjugate. The higher concentrations observed for ²¹¹At-labeled 30F11 were due to its longer half-life, which permitted better localization of isotope to the spleen before decay. ²¹¹At was more effective at producing myelosuppression for the same quantity of injected radioactivity. All mice injected with 20 or 50 μCi ²¹¹At, but none with the same quantities of ²¹³Bi, had lethal myeloablation. Severe reversible acute hepatic toxicity occurred with 50 μCi ²¹³Bi, but not with lower doses of ²¹³Bi or with any dose of ²¹¹At. No renal toxicity occurred with either radionuclide. The data suggest that smaller quantities of ²¹¹At-labeled anti-CD45 antibody are sufficient to achieve myelosuppression and myeloablation with less nonhematologic toxicity compared with ²¹³Bi-labeled antibody. [Cancer Res 2009;69(6):2408–15]