Increased streptavidin uptake in tumors pretargeted with biotinylated antibody using a conjugate of streptavidin-fab fragment.
Radiolabeled streptavidin accumulated in tumors pretargeted with biotinylated antibody. However, the absolute delivery of radioactivity was limited. To increase the tumor uptake of radioactivity further, we conjugated streptavidin with a mouse monoclonal antibody (MAb) fragment, OST6Fab, which recognizes antigen on human osteosarcoma. Another mouse MAb, OST7, which also reacts with the same tumor but recognizes an epitope different from the OST6 epitope, was biotinylated. The radioiodinated streptavidin-OST6Fab conjugate was administered to tumor-bearing mice after the biotinylated OST7 pretargeting. The uptake of the conjugate in tumors pretargeted with the biotinylated antibody was significantly higher than that of streptavidin and that of the conjugate of streptavidin and irrelevant Fab fragment. Renal uptake of radioactivity was decreased markedly, and the blood clearance was retarded by the conjugation with Fab fragment. In conclusion, the conjugate of streptavidin with specific Fab fragment increased the accumulation of radioactivity in tumors pretargeted with biotinylated antibody.
Yao
Z
Z
Department of Nuclear Medicine, Faculty of Medicine, Kyoto University, Japan. yao@kuhp.kyoto-u.ac.jp
Zhang
M
M
Sakahara
H
H
Saga
T
T
Kobayashi
H
H
Nakamoto
Y
Y
Toyama
S
S
Konishi
J
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D000918:Antibody Specificity; D001665:Binding Sites; D001710:Biotin / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology*; D004347:Drug Interactions; D006801:Humans; D018796:Immunoconjugates / Q000378:metabolism / Q000494:pharmacology*; D007128:Immunoglobulin Fragments / Q000378:metabolism; D007202:Indicators and Reagents / Q000378:metabolism / Q000493:pharmacokinetics*; D007457:Iodine Radioisotopes; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D012516:Osteosarcoma / Q000378:metabolism*; D019809:Streptavidin / Q000378:metabolism / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D018796:Immunoconjugates; D007128:Immunoglobulin Fragments; D007202:Indicators and Reagents; D007457:Iodine Radioisotopes; D001710:Biotin; D019809:Streptavidin