Radiolabeled anti-CD45 monoclonal antibodies target lymphohematopoietic tissue in the macaque.
Despite bone marrow transplantation, many patients with advanced leukemia subsequently relapse. If an additional increment of radiation could be delivered to lymphohematopoietic tissues with relative specificity, the relapse rate may decrease without a marked increase in toxicity. We have examined the biodistribution of two 131I-labeled monoclonal antibodies reactive with the CD45 antigen in Macaca nemestrina. Three animals received 0.5 mg/kg BC8, an IgG1 of low avidity (6 x 10(7) L/mol). Three received 0.5 mg/kg AC8, an IgG2a of moderate avidity (5 x 10(8) L/mol), and two received 4.5 mg/kg AC8. Estimates of radiation absorbed dose demonstrated that these antibodies could deliver up to five times more radiation to lymph nodes, and up to 2.6 times more to bone marrow, than to lung or liver. The higher avidity AC8 antibody at 0.5 mg/kg was cleared more rapidly from blood and resulted in lower antibody uptake in lymph nodes than did BC8 at 0.5 mg/kg. Increasing the dose of AC8 to 4.5 mg/kg resulted in slower blood clearance and higher lymph node uptake. These studies suggest that radiolabeled anti-CD45 antibodies can deliver radiation with relative specificity to lymphohematopoietic tissues. This approach, in combination with marrow transplantation, may improve treatment of hematologic malignancies.
Matthews
D C
DC
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
Appelbaum
F R
FR
Eary
J F
JF
Hui
T E
TE
Fisher
D R
DR
Martin
P J
PJ
Durack
L D
LD
Nelp
W B
WB
Press
O W
OW
Badger
C C
CC
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D000915:Antibody Affinity; D015703:Antigens, CD / Q000276:immunology*; D001345:Autoradiography; D001853:Bone Marrow / Q000378:metabolism; D005434:Flow Cytometry; D006649:Histocompatibility Antigens / Q000276:immunology*; D007457:Iodine Radioisotopes; D007700:Kinetics; D017493:Leukocyte Common Antigens; D008198:Lymph Nodes / Q000378:metabolism; D008221:Lymphoid Tissue / Q000378:metabolism*; D008254:Macaca nemestrina; D008297:Male; D011829:Radiation Dosage; D016499:Radioimmunotherapy; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D006649:Histocompatibility Antigens; D007457:Iodine Radioisotopes; D017493:Leukocyte Common Antigens