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Biodistribution of Yttrium-90–Labeled Anti-CD45 Antibody in a Nonhuman Primate Model

¹ Division of Clinical Research, Fred Hutchinson Cancer Research Center; Departments of ² Pediatrics, ³ Medicine, ⁴ Radiology, and ⁵ Radiation Oncology, University of Washington, Seattle, Washington; and ⁶ Pacific Northwest National Laboratories, Richland, Washington

Requests for reprints: Eneida R. Nemecek, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, P. O. Box 19024, MS D5-280, Seattle, WA 98109. Phone: 206-667-1816; Fax: 206-667-5899; E-mail: enemecek{at}fhcrc.org.

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

Experimental Design: Twelve Macaca nemestrina primates received anti-CD45 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.

Key Words: radioimmunotherapy • anti-CD45 antibody • iodine-131 • leukemia

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