Biodistribution of yttrium-90-labeled anti-CD45 antibody in a nonhuman primate model

Eneida Nemecek, Donald K. Hamlin, Darrell R. Fisher, Kenneth Krohn, John M. Pagel, Frederick R. Appelbaum, Oliver W. Press, Dana C. Matthews

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Purpose: Radioimmunotherapy may improve the outcome of hematopoietic cell transplantation for hematologic malignancies by delivering targeted radiation to hematopoietic organs while relatively sparing nontarget organs. We evaluated the organ localization of yttrium-90-labeled anti-CB45 (90Y-anti- CD45) antibody in macaques, a model that had previously predicted iodine-131-labeled anti-CB45 (131I-anti-CB45) antibody biodistribution in humans. Experimental Design: Twelve Macaca nemestrina primates received anti-CB45 antibody labeled with 1 to 2 mCi of 90Y followed by serial blood sampling and marrow and lymph node biopsies, and necropsy. The content of 90Y per gram of tissue was determined by liquid scintillation spectrometry. Time-activity curves were constructed using average isotope concentrations in each tissue at measured time points to yield the fractional residence time and estimate radiation absorbed doses for each organ per unit of administered activity. The biodistribution of 90Y-anti-CD45 antibody was then compared with that previously obtained with 131I-anti-CD45 antibody in macaques. Results: The spleen received 2,120, marrow 1,060, and lymph nodes 315 cGy/mCi of 90Y injected. The liver and lungs were the nontarget organs receiving the highest radiation absorbed doses (440 and 285 cGy/mCi, respectively). Ytrrium-90-labeled anti-CD45 antibody delivered 2.5- and 3.7-fold more radiation to marrow than to liver and lungs, respectively. The ratios previously observed with 131I-anti-CD45 antibody were 2.5-and 2.2-fold more radiation to marrow than to liver and lungs, respectively. Conclusions: This study shows that 90Y-anti-CD45 antibody can deliver relatively selective radiation to hematopoietic tissues, with similar ratios of radiation delivered to target versus nontarget organs, as compared with the 131I immunoconjugate in the same animal model.

Original languageEnglish (US)
Pages (from-to)787-794
Number of pages8
JournalClinical Cancer Research
Volume11
Issue number2 I
StatePublished - Jan 15 2005
Externally publishedYes

Fingerprint

Yttrium
Primates
Anti-Idiotypic Antibodies
Radiation
Bone Marrow
Macaca
Lung
Liver
Lymph Nodes
Macaca nemestrina
Immunoconjugates
Radioimmunotherapy
Cell Transplantation
Hematologic Neoplasms
Isotopes
Iodine
Spectrum Analysis
Research Design
Spleen
Animal Models

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Nemecek, E., Hamlin, D. K., Fisher, D. R., Krohn, K., Pagel, J. M., Appelbaum, F. R., ... Matthews, D. C. (2005). Biodistribution of yttrium-90-labeled anti-CD45 antibody in a nonhuman primate model. Clinical Cancer Research, 11(2 I), 787-794.

Biodistribution of yttrium-90-labeled anti-CD45 antibody in a nonhuman primate model. / Nemecek, Eneida; Hamlin, Donald K.; Fisher, Darrell R.; Krohn, Kenneth; Pagel, John M.; Appelbaum, Frederick R.; Press, Oliver W.; Matthews, Dana C.

In: Clinical Cancer Research, Vol. 11, No. 2 I, 15.01.2005, p. 787-794.

Research output: Contribution to journalArticle

Nemecek, E, Hamlin, DK, Fisher, DR, Krohn, K, Pagel, JM, Appelbaum, FR, Press, OW & Matthews, DC 2005, 'Biodistribution of yttrium-90-labeled anti-CD45 antibody in a nonhuman primate model', Clinical Cancer Research, vol. 11, no. 2 I, pp. 787-794.
Nemecek E, Hamlin DK, Fisher DR, Krohn K, Pagel JM, Appelbaum FR et al. Biodistribution of yttrium-90-labeled anti-CD45 antibody in a nonhuman primate model. Clinical Cancer Research. 2005 Jan 15;11(2 I):787-794.
Nemecek, Eneida ; Hamlin, Donald K. ; Fisher, Darrell R. ; Krohn, Kenneth ; Pagel, John M. ; Appelbaum, Frederick R. ; Press, Oliver W. ; Matthews, Dana C. / Biodistribution of yttrium-90-labeled anti-CD45 antibody in a nonhuman primate model. In: Clinical Cancer Research. 2005 ; Vol. 11, No. 2 I. pp. 787-794.
@article{b2326f6b4840494b8c79d60b69962f3a,
title = "Biodistribution of yttrium-90-labeled anti-CD45 antibody in a nonhuman primate model",
abstract = "Purpose: Radioimmunotherapy may improve the outcome of hematopoietic cell transplantation for hematologic malignancies by delivering targeted radiation to hematopoietic organs while relatively sparing nontarget organs. We evaluated the organ localization of yttrium-90-labeled anti-CB45 (90Y-anti- CD45) antibody in macaques, a model that had previously predicted iodine-131-labeled anti-CB45 (131I-anti-CB45) antibody biodistribution in humans. Experimental Design: Twelve Macaca nemestrina primates received anti-CB45 antibody labeled with 1 to 2 mCi of 90Y followed by serial blood sampling and marrow and lymph node biopsies, and necropsy. The content of 90Y per gram of tissue was determined by liquid scintillation spectrometry. Time-activity curves were constructed using average isotope concentrations in each tissue at measured time points to yield the fractional residence time and estimate radiation absorbed doses for each organ per unit of administered activity. The biodistribution of 90Y-anti-CD45 antibody was then compared with that previously obtained with 131I-anti-CD45 antibody in macaques. Results: The spleen received 2,120, marrow 1,060, and lymph nodes 315 cGy/mCi of 90Y injected. The liver and lungs were the nontarget organs receiving the highest radiation absorbed doses (440 and 285 cGy/mCi, respectively). Ytrrium-90-labeled anti-CD45 antibody delivered 2.5- and 3.7-fold more radiation to marrow than to liver and lungs, respectively. The ratios previously observed with 131I-anti-CD45 antibody were 2.5-and 2.2-fold more radiation to marrow than to liver and lungs, respectively. Conclusions: This study shows that 90Y-anti-CD45 antibody can deliver relatively selective radiation to hematopoietic tissues, with similar ratios of radiation delivered to target versus nontarget organs, as compared with the 131I immunoconjugate in the same animal model.",
author = "Eneida Nemecek and Hamlin, {Donald K.} and Fisher, {Darrell R.} and Kenneth Krohn and Pagel, {John M.} and Appelbaum, {Frederick R.} and Press, {Oliver W.} and Matthews, {Dana C.}",
year = "2005",
month = "1",
day = "15",
language = "English (US)",
volume = "11",
pages = "787--794",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "2 I",

}

TY - JOUR

T1 - Biodistribution of yttrium-90-labeled anti-CD45 antibody in a nonhuman primate model

AU - Nemecek, Eneida

AU - Hamlin, Donald K.

AU - Fisher, Darrell R.

AU - Krohn, Kenneth

AU - Pagel, John M.

AU - Appelbaum, Frederick R.

AU - Press, Oliver W.

AU - Matthews, Dana C.

PY - 2005/1/15

Y1 - 2005/1/15

N2 - Purpose: Radioimmunotherapy may improve the outcome of hematopoietic cell transplantation for hematologic malignancies by delivering targeted radiation to hematopoietic organs while relatively sparing nontarget organs. We evaluated the organ localization of yttrium-90-labeled anti-CB45 (90Y-anti- CD45) antibody in macaques, a model that had previously predicted iodine-131-labeled anti-CB45 (131I-anti-CB45) antibody biodistribution in humans. Experimental Design: Twelve Macaca nemestrina primates received anti-CB45 antibody labeled with 1 to 2 mCi of 90Y followed by serial blood sampling and marrow and lymph node biopsies, and necropsy. The content of 90Y per gram of tissue was determined by liquid scintillation spectrometry. Time-activity curves were constructed using average isotope concentrations in each tissue at measured time points to yield the fractional residence time and estimate radiation absorbed doses for each organ per unit of administered activity. The biodistribution of 90Y-anti-CD45 antibody was then compared with that previously obtained with 131I-anti-CD45 antibody in macaques. Results: The spleen received 2,120, marrow 1,060, and lymph nodes 315 cGy/mCi of 90Y injected. The liver and lungs were the nontarget organs receiving the highest radiation absorbed doses (440 and 285 cGy/mCi, respectively). Ytrrium-90-labeled anti-CD45 antibody delivered 2.5- and 3.7-fold more radiation to marrow than to liver and lungs, respectively. The ratios previously observed with 131I-anti-CD45 antibody were 2.5-and 2.2-fold more radiation to marrow than to liver and lungs, respectively. Conclusions: This study shows that 90Y-anti-CD45 antibody can deliver relatively selective radiation to hematopoietic tissues, with similar ratios of radiation delivered to target versus nontarget organs, as compared with the 131I immunoconjugate in the same animal model.

AB - Purpose: Radioimmunotherapy may improve the outcome of hematopoietic cell transplantation for hematologic malignancies by delivering targeted radiation to hematopoietic organs while relatively sparing nontarget organs. We evaluated the organ localization of yttrium-90-labeled anti-CB45 (90Y-anti- CD45) antibody in macaques, a model that had previously predicted iodine-131-labeled anti-CB45 (131I-anti-CB45) antibody biodistribution in humans. Experimental Design: Twelve Macaca nemestrina primates received anti-CB45 antibody labeled with 1 to 2 mCi of 90Y followed by serial blood sampling and marrow and lymph node biopsies, and necropsy. The content of 90Y per gram of tissue was determined by liquid scintillation spectrometry. Time-activity curves were constructed using average isotope concentrations in each tissue at measured time points to yield the fractional residence time and estimate radiation absorbed doses for each organ per unit of administered activity. The biodistribution of 90Y-anti-CD45 antibody was then compared with that previously obtained with 131I-anti-CD45 antibody in macaques. Results: The spleen received 2,120, marrow 1,060, and lymph nodes 315 cGy/mCi of 90Y injected. The liver and lungs were the nontarget organs receiving the highest radiation absorbed doses (440 and 285 cGy/mCi, respectively). Ytrrium-90-labeled anti-CD45 antibody delivered 2.5- and 3.7-fold more radiation to marrow than to liver and lungs, respectively. The ratios previously observed with 131I-anti-CD45 antibody were 2.5-and 2.2-fold more radiation to marrow than to liver and lungs, respectively. Conclusions: This study shows that 90Y-anti-CD45 antibody can deliver relatively selective radiation to hematopoietic tissues, with similar ratios of radiation delivered to target versus nontarget organs, as compared with the 131I immunoconjugate in the same animal model.

UR - http://www.scopus.com/inward/record.url?scp=12344309103&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=12344309103&partnerID=8YFLogxK

M3 - Article

C2 - 15701869

AN - SCOPUS:12344309103

VL - 11

SP - 787

EP - 794

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 2 I

ER -