Anti-CD45 monoclonal antibody YAML568: A promising radioimmunoconjugate for targeted therapy of acute leukemia.
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.
Glatting
Gerhard
G
Department of Nuclear Medicine, University Ulm, Ulm, Germany. gerhard.glatting@uniklinik-ulm.de
Müller
Marguerite
M
Koop
Bernd
B
Hohl
Kathrin
K
Friesen
Claudia
C
Neumaier
Bernd
B
Berrie
Eleanor
E
Bird
Pru
P
Hale
Geoffrey
G
Blumstein
Norbert M
NM
Waldmann
Herman
H
Bunjes
Donald
D
Reske
Sven N
SN
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
D000911:Antibodies, Monoclonal; C513680:YAML568 monoclonal antibody; D017493:Leukocyte Common Antigens