Enhancement of monoclonal antibody uptake in human colon tumor xenografts following irradiation.
Indium-111-labeled AUA1 tumor-associated monoclonal antibody raised against an antigen of colon adenocarcinoma was used to evaluate the effect of ionizing radiation on antibody uptake by the LoVo adenocarcinoma cell line grown as a xenograft in nude mice. Tumors were exposed to single doses of external X-irradiation of between 400 and 1600 cGy followed, 24 h later, by administration of specific or nonspecific antibody. Animals were sacrificed 3 days after antibody administration. At doses higher than 400 cGy, tumor uptake with both specific and nonspecific antibody was significantly increased. No difference in changes in tumor volume was observed between the groups receiving irradiation and the controls. Specific antibody uptake by tumors was always significantly higher than nonspecific having an approximate 4-fold binding advantage. Vascular permeability and the vascular volume of irradiated and control tumors was measured 24 and 72 h after irradiation, using iodine-125-labeled nonspecific antibody and labelling of the red blood cells in vivo with 99mTcO4. At doses higher than 400 cGy, vascular permeability in the tumor 24 h after irradiation was significantly increased (P less than 0.05), while the vascular volume decreased (P less than 0.001) compared to control values. However at 72 h after irradiation there was no difference between treated and control groups. The results obtained in this study suggest a potential value of external irradiation to increase monoclonal antibody uptake by tumors governed mainly by the increased vascular permeability of the tumor vasculature soon after the irradiation exposure.
Kalofonos
H
H
Imperial Cancer Research Fund Oncology Group, Royal Postgraduate Medical School, Hammsersmith Hospital, London, England.
Rowlinson
G
G
Epenetos
A A
AA
D000230:Adenocarcinoma / Q000276:immunology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis / Q000493:pharmacokinetics*; D000937:Antigen-Antibody Reactions / Q000528:radiation effects*; D000951:Antigens, Neoplasm / Q000032:analysis; D000954:Antigens, Surface / Q000032:analysis; D001692:Biological Transport / Q000528:radiation effects*; D003110:Colonic Neoplasms / Q000276:immunology*; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D007124:Immunoenzyme Techniques; D007074:Immunoglobulin G; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D014965:X-Rays
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D007074:Immunoglobulin G