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 an tibodies (MAb) for the immunodetection of solid tumors. In pancreatic cancer, the results of conventional immunoscintigraphy using intact MA b remain disappointing. Clear immunoscintigraphy with radiolabeled MAb requires a high tumor tissue/blood ratio of radioactivity and a low n ormal tissue/blood ratio of radioactivity. In this study, I-125-labele d Fab fragments produced by papain digestion of MAb A7 were injected i ntravenously into nude mice bearing a human pancreatic cancer (HPC-YS) xenograft previously shown to react specifically with MAb A7. The rad ioactivity of tumors and normal organs was subsequently measured. The tumor tissue/blood ratio of I-125-labeled Fab fragments of MAb A7 was 1.00 +/- 0.24 and 9.68 +/- 2.54 at 2 and 24 h after injection, respect ively. 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 I-125-labeled Fab fragments of MAb A7 was greater than that of intact MAb A7, although the I-125-labeled Fa b accumulation level was much less than that of I-125-labeled intact M Ab A7 in the tumor. When mice bearing tumors which did not react with MAb A7 were studied, I-125-labeled Fab fragments did not specifically localize to the tumors. These results suggest that Fab fragments of MA b A7 may be suitable carriers of radionuclides for the immunodetection of human pancreatic cancer.