Biodistribution of 99mTc-labeled anti-human epidermal growth factor receptor (EGF-R) humanized monoclonal antibody h-R3 in a xenograft model of human lung adenocarcinoma.
The anti-human epidermal growth factor receptor (EGF-R) humanized monoclonal antibody (MAb) h-R3 is an (IgG1), which binds to an extracellular domain of EGF-R. It was used to evaluate the biodistribution on nude mice xenografted with H-125 human lung adenocarcinoma cell line. Results were compared with its murine version of the MAb ior-egf/r3. Twenty-one athymic female 4NMRI nu/nu mice were injected intraperitoneally with 10 microg/100 muCi of 99mTc-labeled MAbs. Immunoreactivity of 99mTc-labeled MAbs were measured by enzyme-linked immunosorbent assay (ELISA) on H-125 cell line and the immunoreactive fractions was determined by the Lindmo method. Among all organs, significant accumulation was found in serum (27.05 +/- 2.08 %ID/g) and tumor (3.903 +/- 0.89 %ID/g) at 4 h after injection. These values decreased to 5.03 +/- 0.50 %ID/g and 2.19 +/- 0.56 %ID/g for serum and tumor, respectively. The immunoreactive fraction was found to be 0.70, with a correlation coefficient r = 0.9984. With the good biodistribution and tumor uptake of the 99mTc-labeled humanized antibody h-R3, a phase I diagnostic clinical trial of tumor with epithelial origin should be pursued.
Morales-Morales
A
A
Center of Molecular Immunology, Havana, Cuba.
Ducongé
J
J
Caballero-Torres
I
I
Núñez-Gandolff
G
G
Fernández
E
E
Iznaga-Escobar
N
N
D000230:Adenocarcinoma / Q000378:metabolism*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000493:pharmacokinetics; D066246:ErbB Receptors / Q000276:immunology*; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000737:chemistry / Q000493:pharmacokinetics*; D007553:Isotope Labeling; D008175:Lung Neoplasms / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D015609:Organotechnetium Compounds / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D013667:Technetium; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D018796:Immunoconjugates; D015609:Organotechnetium Compounds; D013667:Technetium; D066246:ErbB Receptors