Pharmacokinetics of radiolabeled monoclonal antibody B6.2 in patients with metastatic breast cancer

Cancer Res. 1986 Jun;46(6):3157-63.

Abstract

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.

MeSH terms

  • Adult
  • Aged
  • Animals
  • Antibodies, Monoclonal*
  • Breast Neoplasms / diagnostic imaging
  • Breast Neoplasms / immunology
  • Breast Neoplasms / metabolism*
  • Cross Reactions
  • Female
  • Granulocytes / immunology
  • Half-Life
  • Humans
  • Immunoglobulin Fab Fragments
  • Immunoglobulin G / metabolism
  • Iodine Radioisotopes
  • Kinetics
  • Mice
  • Mice, Inbred BALB C
  • Middle Aged
  • Neoplasm Metastasis
  • Radionuclide Imaging

Substances

  • Antibodies, Monoclonal
  • Immunoglobulin Fab Fragments
  • Immunoglobulin G
  • Iodine Radioisotopes