Antibody-radionuclide conjugates as part of a myeloablative preparative regimen for marrow transplantation.
The behaviors of an anti-Ia antibody (7.2) and an antibody directed at a lymphocyte adhesion molecule (S.5) radiolabeled with 131I were studied in normal dogs. Antibody 7.2 localized to spleen and, to a lesser extent, to marrow and lymph nodes. Antibody S.5 rapidly localized to marrow and spleen, achieving tissue/blood ratios greater than 6:1 within three hours of injection that were maintained for at least 48 hours. Prior treatment with cyclophosphamide (CY) markedly altered the distribution of S.5 but had much less effect on the distribution of 7.2 and almost no effect on the distribution of a control antibody. When animals were treated with increasing doses of 131I labeled to S.5, lethal myelosuppression occurred when a dose of 6 mCi/kg was reached. At this dose, the otherwise lethal effects of 131I could be reversed with autologous marrow transplant support.
Appelbaum
F R
FR
Fred Hutchinson Cancer Research Center, Division of Clinical Research, Seattle, WA 98104.
Brown
P
P
Sandmaier
B
B
Badger
C
C
Schuening
F
F
Graham
T
T
Storb
R
R
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000032:analysis; D000954:Antigens, Surface / Q000276:immunology*; D001666:Binding Sites, Antibody; D001853:Bone Marrow / Q000276:immunology / Q000378:metabolism; D016026:Bone Marrow Transplantation; D015815:Cell Adhesion Molecules; D002460:Cell Line; D003520:Cyclophosphamide / Q000008:administration & dosage; D003602:Cytotoxicity, Immunologic; D004285:Dogs; D007166:Immunosuppressive Agents / Q000008:administration & dosage; D000922:Immunotoxins / Q000008:administration & dosage* / Q000032:analysis; D007457:Iodine Radioisotopes / Q000008:administration & dosage* / Q000032:analysis; D008214:Lymphocytes / Q000276:immunology; D011292:Premedication; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; D007166:Immunosuppressive Agents; D000922:Immunotoxins; D007457:Iodine Radioisotopes; D003520:Cyclophosphamide