Biodistribution of yttrium-90-labeled anti-CD45 antibody in a nonhuman primate model.
OBJECTIVE
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-CD45 ((90)Y-anti-CD45) antibody in macaques, a model that had previously predicted iodine-131-labeled anti-CD45 ((131)I-anti-CD45) antibody biodistribution in humans.


METHODS
Twelve Macaca nemestrina primates received anti-CD45 antibody labeled with 1 to 2 mCi of (90)Y followed by serial blood sampling and marrow and lymph node biopsies, and necropsy. The content of (90)Y 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 (90)Y-anti-CD45 antibody was then compared with that previously obtained with (131)I-anti-CD45 antibody in macaques.


RESULTS
The spleen received 2,120, marrow 1,060, and lymph nodes 315 cGy/mCi of (90)Y injected. The liver and lungs were the nontarget organs receiving the highest radiation absorbed doses (440 and 285 cGy/mCi, respectively). Yttrium-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 (131)I-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 (90)Y-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 (131)I immunoconjugate in the same animal model.
Nemecek
Eneida R
ER
Division of Clinical Research, Fred Hutchinson Cancer Research Center, University of Washington, 1100 Fairview Avenue North, Seattle, WA 98109, USA. enemecek@fhcrc.org
Hamlin
Donald K
DK
Fisher
Darrell R
DR
Krohn
Kenneth A
KA
Pagel
John M
JM
Appelbaum
Frederick R
FR
Press
Oliver W
OW
Matthews
Dana C
DC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects; D004195:Disease Models, Animal; D018796:Immunoconjugates / Q000493:pharmacokinetics*; D017493:Leukocyte Common Antigens / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects; D008254:Macaca nemestrina; D008297:Male; D011829:Radiation Dosage; D013154:Spleen / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects; D014018:Tissue Distribution; D015021:Yttrium Radioisotopes / Q000493:pharmacokinetics*
D000911:Antibodies, Monoclonal; D018796:Immunoconjugates; D015021:Yttrium Radioisotopes; D017493:Leukocyte Common Antigens