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Anti-CD45 Monoclonal Antibody YAML568: A Promising Radioimmunoconjugate for Targeted Therapy of Acute Leukemia

¹ Department of Nuclear Medicine, University Ulm, Ulm, Germany; ² Department of Biometry and Medical Documentation, University Ulm, Ulm, Germany; ³ Sir William Dunn School of Pathology, Oxford, United Kingdom; and ⁴ Department of Internal Medicine III (Hematology/Oncology), University Ulm, Ulm, Germany

Correspondence: For correspondence or reprints contact: Gerhard Glatting, PhD, Abteilung Nuklearmedizin, Universität Ulm, D-89070 Ulm, Germany. E-mail: gerhard.glatting{at}uniklinik-ulm.de

The outcome of hematopoietic cell transplantation for hematologic malignancies may be improved by delivering targeted radiation to hematopoietic organs while relatively sparing nontarget organs. We evaluated the biodistribution of ¹¹¹In-labeled anti-CD45 antibody in humans using the rat IgG2a monoclonal antibody YAML568 that recognizes a common CD45 epitope present on all human leukocytes. Methods: Eight patients undergoing bone marrow transplantation received YAML568 labeled with 122 ± 16 MBq of ¹¹¹In intravenously followed by serial blood sampling, urine collection, and conjugated view planar -camera imaging up to 144 h after injection. Time–activity curves were obtained using region-of-interest analysis in the accumulating organs and residence times were calculated. An estimate for the radiation-absorbed doses for each organ per unit of administered activity of ⁹⁰Y was calculated using software for internal dose assessment. The first patient received no unlabeled antibody preloading. The second 2 patients received a preloading dose of 10 mg (0.15 mg/kg). The last 5 patients received a preloading dose of 30–47 mg (0.5 mg/kg). Results: No significant administration-related side effects were seen. The 3 patients receiving no antibody or low antibody preloading had an unfavorable biodistribution with a high initial accumulation of activity in the liver (37%) and the spleen (34%). For the patients receiving 0.5-mg/kg antibody preloading, the estimated radiation-absorbed doses for red bone marrow, spleen, liver, kidney, and total body were 6.4 ± 1.2, 19 ± 5, 3.9 ± 1.4, 1.1 ± 0.4, and 0.6 ± 0.1 mGy/MBq, respectively, demonstrating preferential red marrow targeting. A linear regression model showed that the amount of unlabeled antibody preloading per body weight has a strong influence on the estimated red marrow absorbed dose (P = 0.003, R² = 0.80). Conclusion: This study shows that the anti-CD45 monoclonal antibody YAML568 is suitable for delivering selectively radiation to hematopoietic tissues when labeled with ⁹⁰Y provided that a preloading dose of about 0.5 mg/kg unlabeled antibody is given.

Key Words: biodistribution • dosimetry • radiation-absorbed dose • radioimmunotherapy • anti-CD45