In vitro evaluation of iodine-125-labeled monoclonal antibody (MAb 425) in human high-grade glioma cells.
Human high-grade glioma cell lines (A1207, U-87MG, U-373MG, and F39) with high levels of epidermal growth factor receptor (EGF-R) expression were incubated for 2-48 h with 1 microCi/ml of the EGF-R-specific 125I-MAb 425 and measured for surface-bound, cytoplasmic, and nuclear radioactivity. The A1207 and U-373MG cell lines showed the highest surface-bound radioactivity with 215.9 +/- 8.7 nCi (30 h) and 287.8 +/- 23.2 nCi (24 h)/10(6) cells, respectively, whereas the U-87MG and the F39 cell lines bound significantly less antibody (48.8 +/- 5.4 nCi [48 h] and 31.1 +/- 0.7 nCi [24 h]). Surface-bound antibody was efficiently internalized into the cytoplasm. The U-373MG, U-87MG, and A1207 cell lines achieved 19.8% +/- 2.1 internalization of the surface-bound antibody in contrast to > 40% for the F39 cell line. Only the A1207 cell line showed significant nuclear radioactivity. There was no correlation between the reported EGF-R number and amount of antibody bound or internalized. We conclude that binding and uptake of the 125I-MAb 425 is specific for human glioma cells and shows saturation kinetics independent of receptor density.
Emrich
J G
JG
Department of Radiation Oncology and Nuclear Medicine, Allegheny University of the Health Sciences, Philadelphia, Pennsylvania 19102, USA.
Bender
H
H
Class
R
R
Eshleman
J
J
Miyamoto
C
C
Brady
L W
LW
D000911:Antibodies, Monoclonal / Q000378:metabolism*; D001345:Autoradiography; D015153:Blotting, Western; D002277:Carcinoma / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005069:Evaluation Studies as Topic; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000378:metabolism*; D006801:Humans; D018796:Immunoconjugates / Q000493:pharmacokinetics*; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics*; D012967:Sodium Dodecyl Sulfate; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D018796:Immunoconjugates; D007457:Iodine Radioisotopes; D012967:Sodium Dodecyl Sulfate; D066246:ErbB Receptors