Biodistribution of murine and chimeric Fab fragments of the monoclonal antibody A7 in human pancreatic cancer.
Much recent research has focused on the use of monoclonal antibodies (MAbs) in the immunodetection of solid tumors. Fab fragments of MAbs are more suitable for immunoscintigraphy than intact MAbs. Recently, human-mouse chimeric antibodies have been developed in an effort to reduce human antimouse antibody (HAMA) production by murine MAbs in humans. In this study, 125I-labeled murine and chimeric Fab fragments of the MAb A7 were injected i.v. into nude mice bearing a human pancreatic cancer (HPC-YS) xenograft. The radioactivity in tumors and in normal tissues was subsequently measured. The tumor tissue/blood ratio (T/B) of 125I-labeled murine and chimeric Fab fragments of MAb A7 increased with time in a similar manner and reached 9.68 +/- 2.54 and 10.49 +/- 1.50, respectively, 24 h after injection. Moreover, the T/Bs of 125I-labeled murine and chimeric Fab fragments of MAb A7 were greater than the T/B of intact MAb A7. When mice bearing tumors that did not react with MAb A7 were studied, 125I-labeled murine and chimeric Fab fragments did not localize specifically to the tumors. These results suggests that chimeric Fab fragments of MAb A7 are useful carriers of radionuclides for the immunodetection of human pancreatic cancer, with equivalent activity to murine Fab fragments and less theoretical potential to induce a HAMA response.
Otsuji
E
E
First Department of Surgery, Kyoto Prefectural University of Medicine, Japan.
Yamaguchi
T
T
Yamaoka
N
N
Kotani
T
T
Kato
M
M
Taniguchi
K
K
Kiyamura
K
K
Takahashi
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging / Q000276:immunology* / Q000378:metabolism; D016719:Radioimmunodetection; D011993:Recombinant Fusion Proteins / Q000276:immunology* / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments; D011993:Recombinant Fusion Proteins