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Breast Cancer Research and Treatment

, Volume 12, Issue 2, pp 177–189 | Cite as

Localization of human breast tumors grafted in nude mice with a monoclonal antibody directed against a defined cell surface antigen of human mammary epithelial cells

  • Roberto L. Ceriani
  • Masao Sasaki
  • Douglas Orthendahl
  • Leon Kaufman
Report

Summary

A mouse monoclonal antibody (BLMRL-HMFG-Mc5) prepared against a defined cell surface antigen of human mammary epithelial cells, non-penetrating glycoprotein (NPGP), was used in imaging and distribution studies in athymic nude mice grafted with human breast tumors. Forin vivo tissue distribution studies,125I-labeled monoclonal antibody was injected into nude mice carrying simulated metastases of human tumors (breast and colon carcinomas). After 22–24 hr the amount of radioactivity per gram of tissue was 3–4 times higher in the breast tumor than in liver, brain, lung, muscle, or spleen. In contrast, colon carcinoma tissue, grafted and treated likewise, did not show higher accumulation of radioactivity relative to other tissues. At 4 days, the incorporation in breast tumors remained almost as high, while the circulating radioactive tracer and the incorporation in tissues other than breast had fallen significantly.

In tumor imaging studies, breast tumor masses as small as 4 mm in diameter were clearly localized on a whole body scan using131I-labeled BLMRL-HMFG-Mc5 antibodies with a High-Purity germanium gamma camera. Normalization of131I-distribution to that of99mTc-pertechnetate increased the specificity of this imaging methodology. The quantitative density of131I-label was 2–3 fold higher over the breast tumor than over comparable areas of the mouse. No positive localization images were obtained for similar implants of colon and lung carcinomas or melanomas after injections of131I-labeled BLMRL-HMFG-Mc5. Localization of human breast tumors in this model can be achieved with131I-labeled anti-breast epithelial monoclonal antibodies.

Key words

breast cancer human tumor explants imaging mammary epithelial antigen monoclonal antibody nude mice 

Abbreviations

NPGP

non-penetrating glycoprotein

CEA

carcinoembryonic antigen

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References

  1. 1.
    Baldwin RW, Byers VS: Monoclonal antibodies for cancer detection and therapy. Academic Press, New York, 1985Google Scholar
  2. 2.
    Goldenberg DM, DeLand F, Kim E, Bennett S, Primus FJ, Nagell J, Estes N, DeSimone P, Rayburn P: Use of radiolabeled antibodies to carcinoembryonic antigen for the detection and localization of diverse cancers by external photoscanning. N Engl J Med 25: 1384–1388, 1978Google Scholar
  3. 3.
    Franchimont P, Zangerle PF, Hendrick JC, Reuter A, Collin C: Simultaneous assays of cancer-associated antigens in benign and malignant breast diseases. Cancer 39: 2806–2812, 1977PubMedGoogle Scholar
  4. 4.
    Kleinberg DL: Human lactalbumin: Measurement in serum and in breast cancer organ cultures by radioimmunoassay. Science 190: 276–278, 1975PubMedGoogle Scholar
  5. 5.
    Dao TL, Ip C, Patel J: Serum sialyltransferase and 5′-nucleotidase as reliable biomarkers in women with breast cancer. J Natl Cancer Inst 65: 529–534, 1980PubMedGoogle Scholar
  6. 6.
    Kloppel TM, Keenan TW, Freeman MJ, Morre DJ: Glycolipid-bound sialic acid in serum: Increased levels in mice and humans bearing mammary carcinomas. Proc Natl Acad Sci USA 74: 3011–3013, 1977PubMedGoogle Scholar
  7. 7.
    Ceriani RL, Thompson K, Peterson JA, Abraham S: Surface differentiation antigens on human mammary epithelial cells carried on the human milk fat globule. Proc Natl Acad Sci USA 74: 582–586, 1977PubMedGoogle Scholar
  8. 8.
    Peterson JA, Buehring GC, Taylor-Papadimitriou J, Ceriani RL: Expression of human mammary epithelial (HME) antigens in primary cultures of normal and abnormal breast tissue. Int J Cancer 22: 655–661, 1978PubMedGoogle Scholar
  9. 9.
    Sasaki M, Peterson JA, Ceriani RL: Quantitation of human mammary epithelial (HME) antigens in cells cultured from normal and cancerous breast tissue. In Vitro 17: 150–158, 1981PubMedGoogle Scholar
  10. 10.
    Keenan TW, Franke WW, Mather IH, Morre DJ: Endomembrane composition and function in milk formation.In Larson BL, (ed): Lactation: A Comprehensive Treatise, Vol 4. Academic Press, New York, 1977, pp 405–436Google Scholar
  11. 11.
    Ceriani RL, Miller S, Orthendahl D, Wara WM, Sasaki M, Peterson JA, Kaufman L: Use of human mammary epithelial antigens (HME-Ags) in breast cancer diagnosis. Cancer Detection and Prevention 4: 603–609, 1981PubMedGoogle Scholar
  12. 12.
    Kaufman L, Hosir K, Lorenz V, Shosa D, Hoenninger J, Cheng A, Okerlund M, Hattner RS, Price DC, Williams S, Ewins JH, Armantrout GA, Camp DC, Lee K: Imaging characteristics of a small germanium camera. Invest Radiol 13: 223–232, 1978PubMedGoogle Scholar
  13. 13.
    Wilbanks T, Peterson JA, Miller S, Kaufman L, Orthendahl D, Ceriani RL: Localization of mammary tumorsin vivo with131I-labeled Fab fragments of antibodies against mouse mammary epithelial antigens. Cancer 48: 1768–1775, 1981PubMedGoogle Scholar
  14. 14.
    Wilbanks T, Peterson JA, Miller S, Kaufman L, Orthendahl D, Ceriani RL: Imaging of mammary tumors with cell-type specific antibodies by a High Purity germanium camera. In: Burchiel S, Rhodes B (eds): Tumor Imaging: The Radioimmunochemical Detection of Cancer. Masson, New York, 1982, pp 215–226Google Scholar
  15. 15.
    Ceriani RL, Peterson JA, Lee JY, Moncada R, Blank EW: Characterization of cell surface antigens of normal human mammary epithelial cells with monoclonal antibodies. Somatic Cell Genetics 9: 415–427, 1983PubMedGoogle Scholar
  16. 16.
    Brodsky FM, Parham P, Barnstable CJ, Crumpton MJ, Bodmer WF: Monoclonal antibodies for analysis of the HLA system. Immunol Rev 47: 1–61. 1979Google Scholar
  17. 17.
    Greenwood FC, Hunter WM: The preparation of131I-la-beled human growth hormone of high specific radioactivity. Biochem J 89: 114–123, 1963PubMedGoogle Scholar
  18. 18.
    Watts J, Hosick K, Williams S, Kaufman L: Computer controlled gamma camera. IEEE Transactions on Nuclear Sciences, NS27: 533–536, 1980Google Scholar
  19. 19.
    Haynie TP, Glenn HJ: Current status of tumor imaging.In: Burchiel SW, Rhodes BA (eds): Tumor Imaging: The Radioimmunochemical Detection of Cancer. Masson, New York, 1982, pp 17–25Google Scholar
  20. 20.
    Taylor-Papadimitriou J, Peterson J, Arklie J, Burchell J, Ceriani RL, Bodmer WF: Monoclonal antibodies to epithelial-specific components of the human milk fat globule membrane: Production and reaction with cells in culture. Int J Cancer 28: 17–21, 1981PubMedGoogle Scholar
  21. 21.
    Ritz J, Schlossman SF: Utilization of monoclonal antibodies in the treatment of leukemia and lymphoma. Blood 59: 1–11, 1982PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1988

Authors and Affiliations

  • Roberto L. Ceriani
    • 1
  • Masao Sasaki
    • 1
  • Douglas Orthendahl
    • 2
  • Leon Kaufman
    • 2
  1. 1.John Muir Cancer and Aging Research InstituteWalnut CreekUSA
  2. 2.Radiologic Imaging LaboratoryUniversity of CaliforniaSouth San FanciscoUSA

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