title: Anti-CD45 monoclonal antibody YAML568: A promising radioimmunoconjugate for targeted therapy of acute leukemia.
abstract: 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 gamma-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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Nuclear Medicine, University Ulm, Ulm, Germany. gerhard.glatting@uniklinik-ulm.de
authors.forename: Gerhard
authors.initials: G
authors.lastname: Glatting
authors.forename: Marguerite
authors.initials: M
authors.lastname: Müller
authors.forename: Bernd
authors.initials: B
authors.lastname: Koop
authors.forename: Kathrin
authors.initials: K
authors.lastname: Hohl
authors.forename: Claudia
authors.initials: C
authors.lastname: Friesen
authors.forename: Bernd
authors.initials: B
authors.lastname: Neumaier
authors.forename: Eleanor
authors.initials: E
authors.lastname: Berrie
authors.forename: Pru
authors.initials: P
authors.lastname: Bird
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Hale
authors.forename: Norbert M
authors.initials: NM
authors.lastname: Blumstein
authors.forename: Herman
authors.initials: H
authors.lastname: Waldmann
authors.forename: Donald
authors.initials: D
authors.lastname: Bunjes
authors.forename: Sven N
authors.initials: SN
authors.lastname: Reske
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000627:therapeutic use; D016026:Bone Marrow Transplantation; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000628:therapy*; D017493:Leukocyte Common Antigens / Q000096:biosynthesis / Q000737:chemistry*; D008297:Male; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000628:therapy*; D016499:Radioimmunotherapy / Q000379:methods*; D033581:Stem Cell Transplantation; D014184:Transplantation, Homologous
chemical_list: D000911:Antibodies, Monoclonal; C513680:YAML568 monoclonal antibody; D017493:Leukocyte Common Antigens