Relationship between in vitro binding activity and in vivo tumor accumulation of radiolabeled monoclonal antibodies.
The relationship between in vitro cell binding and in vivo tumor accumulation of radiolabeled antibodies was studied using 125I- and 111In-labeled monoclonal antibodies to human osteosarcoma, and a human osteosarcoma xenograft (KT005) in nude mice. Three monoclonal antibodies--OST6, OST7, and OST15--raised against human osteosarcoma recognize the same antigen molecule. Although the binding of both 125I- and 111In-labeled OST6 to KT005 cells was higher than that of radiolabeled OST7 in vitro, 125I-labeled OST6 showed a faster clearance from the circulation and a lower accumulation in the transplanted tumor than 125I-labeled OST7. In contrast to the radioiodinated antibodies, the in vivo tumor accumulation of 111In-labeled OST6 was higher, although not significantly, than that of 111In-labeled OST7. OST15 showed the lowest binding in vitro, and its in vivo tumor localization was also lower than the others. The discrepancy in tumor uptake between OST6 and OST7 labeled with either 125I or 111In may have been a result of differing blood clearance. These results suggest that binding studies can be used to exclude from in vivo use those antibodies which show very poor binding in vitro, while in vivo serum clearance may be a better test for choosing antibodies with similar binding.
Sakahara
H
H
Department of Nuclear Medicine, Faculty of Medicine, Kyoto University, Japan.
Endo
K
K
Koizumi
M
M
Nakashima
T
T
Kunimatsu
M
M
Watanabe
Y
Y
Kawamura
Y
Y
Nakamura
T
T
Tanaka
H
H
Kotoura
Y
Y
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D006801:Humans; D007205:Indium Radioisotopes; D007457:Iodine Radioisotopes; D051379:Mice; D009368:Neoplasm Transplantation; D012516:Osteosarcoma / Q000276:immunology / Q000378:metabolism*; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D007205:Indium Radioisotopes; D007457:Iodine Radioisotopes