Enhanced tumor localization of radiolabeled Fab fragments of monoclonal antibody A7 in nude mice bearing human pancreatic carcinoma xenografts.
Much recent research has been directed toward the use of monoclonal antibodies (MAb) for the immunodetection of solid tumors. In pancreatic cancer, the results of conventional immunoscintigraphy using intact MAb remain disappointing. Clear immunoscintigraphy with radiolabeled MAb requires a high tumor tissue/blood ratio of radioactivity and a low normal tissue/blood ratio of radioactivity. In this study, 125I-labeled Fab fragments produced by papain digestion of MAb A7 were injected intravenously into nude mice bearing a human pancreatic cancer (HPC-YS) xenograft previously shown to react specifically with MAb A7. The radioactivity of tumors and normal organs was subsequently measured. The tumor tissue/blood ratio of 125I-labeled Fab fragments of MAb A7 was 1.00 +/- 0.24 and 9.68 +/- 2.54 at 2 and 24 h after injection, respectively. The tumor tissue/blood ratio of radioactivity was significantly higher than those of normal organs at 24 h after injection. Moreover, the tumor tissue/blood ratio of 125I-labeled Fab fragments of MAb A7 was greater than that of intact MAb A7, although the 125I-labeled Fab accumulation level was much less than that of 125I-labeled intact MAb A7 in the tumor. When mice bearing tumors which did not react with MAb A7 were studied, 125I-labeled Fab fragments did not specifically localize to the tumors. These results suggest that Fab fragments of MAb A7 may be suitable carriers of radionuclides for the immunodetection of human pancreatic cancer.
Otsuji
E
E
First Department of Surgery, Kyoto Prefectural University of Medicine.
Yamaguchi
T
T
Yamaoka
N
N
Kato
M
M
Kotani
T
T
Kitamura
K
K
Yamaguchi
N
N
Takahashi
T
T
D000818:Animals; D000911:Antibodies, Monoclonal; D006801:Humans; D007140:Immunoglobulin Fab Fragments; D007457:Iodine Radioisotopes; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging*; D016719:Radioimmunodetection / Q000379:methods
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D007457:Iodine Radioisotopes