Skip to main content
Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1993 Aug;84(8):914–920. doi: 10.1111/j.1349-7006.1993.tb02066.x

Enhanced Tumor Localization of Radiolabeled Fab Fragments of Monoclonal Antibody A7 in Nude Mice Bearing Human Pancreatic Carcinoma Xenografts

Eigo Otsuji 1,, Toshiharu Yamaguchi 1, Nobuki Yamaoka 1, Makoto Kato 1, Tatsuya Kotani 1, Kazuya Kitamura 1, Nozomi Yamaguchi 2, Toshio Takahashi 1
PMCID: PMC5919260  PMID: 8407556

Abstract

Much recent research has been directed toward the use of monoclonal antibodies (MAb) for the inimunodetection of solid tumors. In pancreatic cancer, the results of conventional immunoscintigraphy using intact MAb remain disappointing. Clear immunoseintigrapliy 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.

Keywords: Pancreatic cancer, Tumor imaging, Monoclonal antibody A7, Fab fragment

Full Text

The Full Text of this article is available as a PDF (621.8 KB).

References

  • 1.Keenan M. A. , Colcher D. , Larson S. M. and Schlom J , Radioimmunoscintigraphy of human colon cancer xeno‐grafts in nude mice with radiolabeled monoclonal anti‐ body B72.3 . J. Nucl. Med. , 25 , 1197 – 1203 ( 1984. ). [PubMed] [Google Scholar]
  • 2.Wahl , R. L. , Parker , C. W. and Philpott , G. W.Improved radioimaging and tumor localization with monoclonal F(ab')2 . J. Nucl. Med. , 24 , 316 – 325 ( 1983. ). [PubMed] [Google Scholar]
  • 3.Khaw , B. , Cooney , J. , Edgington , T. and Strauss , H. W.Differences in experimental tumor localization of dual‐labeled monoclonal antibody . J. Nucl. Med. , 27 , 1293 – 1299 ( 1986. ). [PubMed] [Google Scholar]
  • 4.Pimm , M. V. , Perkins , A. C. , Armitage , N. C. and Baldwin , R. W.The characteristics of blood‐borne radio‐labels and the effect of anti‐mouse IgG antibodies on localization of radiolabeled monoclonal antibody in cancer patients . J. Nucl. Med. , 26 , 1011 – 1023 ( 1985. ). [PubMed] [Google Scholar]
  • 5.Khaw , B. A. , Mattis , J. A. , Melincoff , G. , Strauss , H. W. , Gold H. K. and Haber , E.Monoclonal antibody to cardiac myosin: imaging of experimental myocardial infarction . Hybridoma , 3 , 11 – 23 ( 1984. ). [DOI] [PubMed] [Google Scholar]
  • 6.Ballou , B. , Levine , G. , Hakala , T. R. and Solter , D.Tumor location detected with radioactively labeled monoclonal antibody and external scintigraphy . Science , 206 , 844 – 847 ( 1979. ). [DOI] [PubMed] [Google Scholar]
  • 7.Andrew , S. M. , Pimm , M. V. , Perkins , A. C. and Baldwin , R. W.Comparative imaging and biodistribution studies with an anti‐CEA monoclonal antibody and its F(ab')zand Fab fragments in mice with colon carcinoma xenografts . Eur, J. Nucl. Med. , 12 , 167 – 175 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 8.Brown , B. A. , Comeau , R. D. , Jones , P. L. , Liberatore , F. A. , Neacy , W. P. , Sands , H. and Gallagher , B. M.Pharmacokinetics of the monoclonal antibody B72.3 and its fragments labeled with either 125I or 111In . Cancer Res. , 47 , 1149 – 1154 ( 1987. ). [PubMed] [Google Scholar]
  • 9.Roe , R. , Robins , R. A. , Laxton R. R. and Baldwin , R. W.Kinetics of divalent monoclonal antibody binding to tumor cell surface antigens using flow cytometry: standardization and mathematical analysis . Mol. Immunol. , 22 , 11 – 21 ( 1985. ). [DOI] [PubMed] [Google Scholar]
  • 10.Tsuda , T. , Koshiba , H. , Usui , T. , Kubota , M. , Kikuchi , K. and Morita , K.Radioimmunoscintigraphy of human pancreatic carcinoma xenografts in nude mice with 131I labeled monoclonal antibody . Ann. Nucl. Med. , 4 , 71 – 74 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 11.Kotanagi , H. , Takahashi , T. , Masuko , Y. , Hashimoto , Y. and Koyama , K.A monoclonal antibody against human colon cancers . Tohoku J. Exp. Med. , 148 , 353 – 360 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 12.Kitamura , K. , Takahashi , T. , Yamaguchi , T. , Yokota , T. , Noguchi , A. , Amagai , T. and Imanishi , J.Immunochemical characterization of the antigen recognized the murine monoclonal antibody A7 against human colorectal cancer . Tohoku J. Exp. Med. , 157 , 83 – 93 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 13.Otsuji , E. , Yamaguchi , Y. , Yanamaguchi , N. , Koyama , K. , Imanishi , J. , Yamaoka , N. and Takahashi , T.Expression of the cell surface antigen detected by the monoclonal antibody A7 in pancreatic carcinoma cell lines . Surg. Today , 22 , 351 – 356 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 14.Takahashi , T. , Yamaguchi , T. , Kitamura , K. , Suzuyama , H. , Honda , M. and Hashimoto , Y.Clinical application of monoclonal antibody‐drug conjugates for immunotargeting chemotherapy of colorectal carcinoma . Cancer , 61 , 881 – 888 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 15.Otsuji , E. , Yamaguchi , T. , Yamaoka , N. , Yamaguchi , N. , Imanishi , J. and Takahashi , T.Biodistribution of monoclonal antibody A7 and its F(ab')2 fragment in athymic nude mice bearing human pancreatic carcinoma . J. Surg. Oncol. , 50 , 173 – 178 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 16.Yamaguchi , N. , Yamamura , Y. , Koyama , K. , Otsuji , E. , Imanishi , J. and Ashihara , T.Characterization of new human pancreatic cancer cell lines which propagate in a protein‐free chemically defined medium . Cancer Res. , 50 , 7008 – 7012 ( 1990. ). [PubMed] [Google Scholar]
  • 17.Otsuji , E. , Takahashi , T. , Yamaguchi , T. , Yamaguchi , N. and Imanishi , J.Specific cytotoxic effect of neocarzinostatin conjugated to monoclonal antibody A7 on human pancreatic carcinoma . Gastroenterol. Jpn. , 25 , 244 – 248 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 18.Hunter , W. M. and Greenwood , F. C.Preparation of iodine, 131I‐labelled human growth hormone of high specific activity . Nature , 194 , 495 – 496 ( 1962. ). [DOI] [PubMed] [Google Scholar]
  • 19.Laemmli , U. K.Cleavage of structural proteins during the assembly of the head of bacteriophage. T4 . Nature , 227 , 680 – 685 ( 1970. ). [DOI] [PubMed] [Google Scholar]
  • 20.Hansson , Y. , Paulie , S. , Ben‐Aissa , H. , Rudberg , U. , Karlsson , A. and Perlmann , P.Radioimmunolocalization of bladder tumors xenotransplanted in nude mice . Anticancer Res. , 8 , 435 – 442 ( 1988. ). [PubMed] [Google Scholar]
  • 21.Pimm , M. V. , Andrew , S. M. and Baldwin , R. W.Blood and tissue kinetics of radiolabeled anti‐CEA monoclonal antibody and F(ab')2 and Fab fragments in nude mice with human tumour xenografts: implications for tumour imaging and radioimmunotherapy . Nucl. Med. Comrmtn. , 10 , 585 – 593 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 22.Reintgen , D. S. , Simizu , K. , Coleman , E. , Briner , W. , Kitzmliller , J. , Eisenbarth , G. and Seigler , H. F.Immunodiagnosis of tumors in vivo using radiolabeled antibody A285 . J. Surg. Oncol , 23 , 205 – 211 ( 1983. ). [DOI] [PubMed] [Google Scholar]
  • 23.Spiegelberg , H. L. and Weigle , W. O.The catabolism of homologous and heterologous 7s gamma globulin fragments . J. Exp. Med. , 121 , 323 – 338 ( 1965. ). [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Japanese Journal of Cancer Research : Gann are provided here courtesy of Wiley

RESOURCES