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

Abstract

We previously investigated 213Bi-labeled anti-CD45 antibody to replace total body irradiation as conditioning for hematopoietic cell transplantation in a canine model. While this allowed sustained engraftment of marrow, limited availability and high cost of 213Bi led to a preliminary investigation in mice of 211At-labeled antibody for the same application. To gain an understanding of the differences between the two radionuclides, biodistribution and myelosuppression/toxicity studies were conducted with 213Bi- and 211At-labeled rat anti-murine CD45 antibody, 30F11, conjugates. After injecting mice with 2-50 μCi on 10 μg 30F11 conjugate or 20 μCi on 2 or 40 μg conjugate, biodistributions, myelosuppression and non-hematological toxicities were evaluated. Biodistribution studies showed that the spleen had the highest concentration of radioactivity, ranging from167-417 % injected dose/gram (%ID/g) at 24 h after injection in the 211At studies and 45-166 %ID/g at 3 h after injection in the 213Bi studies. The higher concentrations observed for 211At-labeled 30F11 was likely due to its longer half-life which, permitted more localization of antibody to the spleen before decay. 211At was more effective at myelosuppression for the same (mCi) quantity of injected radioactivity. Injection of only 20 or 50 μCi 211At resulted in lethal myeloablation. There was severe reversible acute hepatic toxicitymore » with 50 μCi 213Bi, but not with lower doses or any dose of 211At. No significant renal toxicity occurred with either radionuclide. The data suggested that considerably lower quantities of 211At-labeled anti-CD45 antibody than 213Bi-labeled antibody might be effective for myelosuppression.« less

Authors:
; ; ; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
952901
Report Number(s):
PNNL-SA-63030
Journal ID: ISSN 0008-5472; CNREA8; 600306000; TRN: US0902583
DOE Contract Number:  
AC05-76RL01830
Resource Type:
Journal Article
Journal Name:
Cancer Research, 69(6):2408-2415
Additional Journal Information:
Journal Volume: 69; Journal Issue: 6; Journal ID: ISSN 0008-5472
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRONMENTAL POLLUTANT EFFECTS ON LIVING ORGANISMS AND BIOLOGICAL MATERIALS; ASTATINE 211; BISMUTH 213; HALF-LIFE; IRRADIATION; MICE; SPLEEN; TOXICITY; ANTIBODIES; LABELLED COMPOUNDS; RADIONUCLIDE KINETICS

Citation Formats

Nakamae, Hirohisa, Wilbur, D Scott, Hamlin, Donald K, Thakar, Monica S, Santos, E B, Fisher, Darrell R, Kenoyer, Aimee L, Pagel, John M, Press, Oliver W, Storb, Rainer, and Sandmaier, B M. Biodistributions, Myelosuppression, and Toxicities in Mice Treated with an Anti-CD45 Antibody Labeled with the alpha-Emitting Radionuclides Bismuth-213 or Astatine-211. United States: N. p., 2009. Web. doi:10.1158/0008-5472.CAN-08-4363.
Nakamae, Hirohisa, Wilbur, D Scott, Hamlin, Donald K, Thakar, Monica S, Santos, E B, Fisher, Darrell R, Kenoyer, Aimee L, Pagel, John M, Press, Oliver W, Storb, Rainer, & Sandmaier, B M. Biodistributions, Myelosuppression, and Toxicities in Mice Treated with an Anti-CD45 Antibody Labeled with the alpha-Emitting Radionuclides Bismuth-213 or Astatine-211. United States. https://doi.org/10.1158/0008-5472.CAN-08-4363
Nakamae, Hirohisa, Wilbur, D Scott, Hamlin, Donald K, Thakar, Monica S, Santos, E B, Fisher, Darrell R, Kenoyer, Aimee L, Pagel, John M, Press, Oliver W, Storb, Rainer, and Sandmaier, B M. 2009. "Biodistributions, Myelosuppression, and Toxicities in Mice Treated with an Anti-CD45 Antibody Labeled with the alpha-Emitting Radionuclides Bismuth-213 or Astatine-211". United States. https://doi.org/10.1158/0008-5472.CAN-08-4363.
@article{osti_952901,
title = {Biodistributions, Myelosuppression, and Toxicities in Mice Treated with an Anti-CD45 Antibody Labeled with the alpha-Emitting Radionuclides Bismuth-213 or Astatine-211},
author = {Nakamae, Hirohisa and Wilbur, D Scott and Hamlin, Donald K and Thakar, Monica S and Santos, E B and Fisher, Darrell R and Kenoyer, Aimee L and Pagel, John M and Press, Oliver W and Storb, Rainer and Sandmaier, B M},
abstractNote = {We previously investigated 213Bi-labeled anti-CD45 antibody to replace total body irradiation as conditioning for hematopoietic cell transplantation in a canine model. While this allowed sustained engraftment of marrow, limited availability and high cost of 213Bi led to a preliminary investigation in mice of 211At-labeled antibody for the same application. To gain an understanding of the differences between the two radionuclides, biodistribution and myelosuppression/toxicity studies were conducted with 213Bi- and 211At-labeled rat anti-murine CD45 antibody, 30F11, conjugates. After injecting mice with 2-50 μCi on 10 μg 30F11 conjugate or 20 μCi on 2 or 40 μg conjugate, biodistributions, myelosuppression and non-hematological toxicities were evaluated. Biodistribution studies showed that the spleen had the highest concentration of radioactivity, ranging from167-417 % injected dose/gram (%ID/g) at 24 h after injection in the 211At studies and 45-166 %ID/g at 3 h after injection in the 213Bi studies. The higher concentrations observed for 211At-labeled 30F11 was likely due to its longer half-life which, permitted more localization of antibody to the spleen before decay. 211At was more effective at myelosuppression for the same (mCi) quantity of injected radioactivity. Injection of only 20 or 50 μCi 211At resulted in lethal myeloablation. There was severe reversible acute hepatic toxicity with 50 μCi 213Bi, but not with lower doses or any dose of 211At. No significant renal toxicity occurred with either radionuclide. The data suggested that considerably lower quantities of 211At-labeled anti-CD45 antibody than 213Bi-labeled antibody might be effective for myelosuppression.},
doi = {10.1158/0008-5472.CAN-08-4363},
url = {https://www.osti.gov/biblio/952901}, journal = {Cancer Research, 69(6):2408-2415},
issn = {0008-5472},
number = 6,
volume = 69,
place = {United States},
year = {Sun Mar 15 00:00:00 EDT 2009},
month = {Sun Mar 15 00:00:00 EDT 2009}
}