Pharmacokinetics of radiolabeled monoclonal antibody B6.2 in patients with metastatic breast cancer.
Thirteen patients with metastatic breast carcinoma were given injections of 50-1593 micrograms of 131I-monoclonal antibody (MAb) B6.2 immunoglobulin G and F(ab')2 for pharmacokinetic evaluation and radioimmunoimaging. Blood clearance of the 131I-MAb-B6.2 was biphasic. The mean half-times (t 1/2 alpha, t 1/2 beta) for the immunoglobulin G were 3.5 +/- 1.7 and 20.9 +/- 11.0 h, respectively. The t 1/2 alpha for the F(ab')2 was 1.7 +/- 1.3 h, and the t 1/2 beta was 31.0 +/- 5.7 h. The percentage of protein bound 131I for the immunoglobulin G and for the F(ab')2 at 72 h was 73.7 +/- 11.4% and 58.2 +/- 14.5%, respectively. In vitro reactivity of MAb B6.2 with granulocytes isolated from normal subjects and patients was demonstrated by cytofluorometric and radioimmunoassays. MAb B6.2 was shown to bind with normal cross-reacting antigen, a cell surface antigen known to be expressed on normal human granulocytes. Reactivity with normal cross-reacting antigen on granulocytes is consistent with the skeletal images obtained during immunoscintigraphy of all 13 patients. A specific tumor image was observed in one patient. No toxicity was encountered. In spite of extensive preclinical data suggesting that 131I-MAb B6.2 would be a useful agent for radioimmunoimaging, the clinical utility of this reagent is probably limited because of the reactivity with granulocytes.
Hayes
D F
DF
Zalutsky
M R
MR
Kaplan
W
W
Noska
M
M
Thor
A
A
Colcher
D
D
Kufe
D W
DW
D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal; D001943:Breast Neoplasms / Q000000981:diagnostic imaging / Q000276:immunology / Q000378:metabolism*; D003429:Cross Reactions; D005260:Female; D006098:Granulocytes / Q000276:immunology; D006207:Half-Life; D006801:Humans; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G / Q000378:metabolism; D007457:Iodine Radioisotopes; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011877:Radionuclide Imaging
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D007457:Iodine Radioisotopes