Specific marrow localization of an 131I-labeled anti-myeloid antibody in normal dogs: effects of a "cold" antibody pretreatment dose on marrow localization.
Tumor recurrence and regimen-related toxicity remain major obstacles in the successful use of marrow transplantation as therapy for hematologic malignancies. By attaching radionuclides to monoclonal antibodies (MoAbs) targeted at myeloid-associated antigenic determinants, a more effective and directed delivery of therapy may be possible without increasing toxicity. We investigated the biodistribution over time of an anti-myeloid antibody (DM-5) labeled with trace amounts of 131I in normal dogs. This study demonstrates the ability to target marrow with a high degree of selectivity, achieving marrow/blood ratios of 25-30:1 with the greatest concentration in any other organ being a tissue/blood ratio of 1.4:1 for stomach at 48 h. A pretreatment dose of unlabeled antibody effectively reduced early hepatic uptake by 80%, resulting in improved marrow localization with an estimated 58.6% of the injected dose localized in marrow within 2 h following infusion, compared to 32.8% without pretreatment. The marrow concentration clearance curve for the radioimmunoconjugate revealed an initial short half-life (4.75 h), suggesting rapid internalization, digestion, and release of free iodine (dehalogenation). This view was supported by a corresponding rise in trichloroacetic acid-non-precipitable activity during this period. Methods aimed at decreasing dehalogenation may result in longer residence time of the radionuclide within the marrow space, resulting in more effective tumor cell kill. This approach may provide a way to improve upon the current results obtained with marrow transplantation as treatment for patients with leukemia and other hematologic malignancies.
Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.
J A
JA
Bianco
B
B
Sandmaier
P A
PA
Brown
C
C
Badger
I
I
Bernstein
J
J
Eary
L
L
Durack
F
F
Schuening
R
R
Storb
F
F
Appelbaum
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000493:pharmacokinetics*; D001853:Bone Marrow / Q000276:immunology*; D001854:Bone Marrow Cells; D004285:Dogs; D006098:Granulocytes / Q000276:immunology; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008657:Metabolic Clearance Rate; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal