RT Journal Article
SR Electronic
T1 Anti-CD45 Monoclonal Antibody YAML568: A Promising Radioimmunoconjugate for Targeted Therapy of Acute Leukemia
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 1335
OP 1341
VO 47
IS 8
A1 Gerhard Glatting
A1 Marguerite Müller
A1 Bernd Koop
A1 Kathrin Hohl
A1 Claudia Friesen
A1 Bernd Neumaier
A1 Eleanor Berrie
A1 Pru Bird
A1 Geoffrey Hale
A1 Norbert M. Blumstein
A1 Herman Waldmann
A1 Donald Bunjes
A1 Sven N. Reske
YR 2006
UL http://jnm.snmjournals.org/content/47/8/1335.abstract
AB 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 γ-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.