Abstract
To understand the inconsistent immunodetection of tumors in vivo, a labelled monoclonal antibody (MAb) against a human follicular cancer cell line (UCLA RO 82 W-1) was used as a model for in vitro and in vivo studies. The 131I labelled MAb × RO 82 W-1 bound to its target cells (10% to 70%) mainly because of the generation of immunoglobulin aggregates. Aggregates generated by the freezing process were shown by Polyacrylamide gel electrophoresis (PAGE) and their removal by filtration. When the aggregated 131I MAb × RO 82 W-1 was injected into BALB/c mice bearing UCLA RO 82 W-1 tumors, a high tumor/blood ratio was found in the large tumors. The tracer concentrated in the macroscopically visible necrotic part of the tumor was largely responsible for the scintigraphic detection. Irrelevant 131I-IgG also concentrated in necrotic regions of tumors. Scintigraphic detection of thyroid tumors in this model was related to the degree to which labeled aggregates of IgG, regardless of their specificity, localized in necrotic regions of the tumors.
Similar content being viewed by others
References
Pressman D., Day E.D., Blau M. The use of paired labelling in the determination of tumor-localizing antibodies. Cancer Res. 17: 845, 1957.
Goldenberg D.M., DeLand F., Euishin K., Bennett S., Primus F.J., Van Nagell Jr J.R., Estes N., DeSimone P., Rayburn P. Use of radiolabelled antibodies to carcinoembryonic antigen for the detection and localization of diverse cancers by external photoscanning. N. Engl. J. Med. 298: 1384, 1978.
Mach J.P., Carrel S., Forni M., Ritschard J., Donath A., Alberto P. Tumor localization of radiolabelled antibodies against carcinoembryonic antigen in patients with carcinoma. N. Engl. J. Med. 303: 5, 1980.
Goldenberg D.M., Preston D.F., Primus F.J., Hansen H.J. Photoscan localization of GH-39 tumors in hamsters using radiolabelled anticarcinoembryonic antigen immunoglobulin G. Cancer Res. 34: 1, 1974.
Stuhlmiller G.M., Sullivan D.C., Vervaert C, Croker B.P., Harris C.C., Seigler H.J. In vivo tumor localization using tumor-specific monkey xenoantibody and murine monoclonal xenoantibody. Ann. Surg. 194: 592, 1981.
Mann B.D., Cohen M.B., Saxton R.E., Morton D.L., Benedict W.F., Korn E.L., Spolter L., Graham L., Chang C.C., Burk M.W. Imaging of human tumor xenografts in nude mice with radiolabelled monoclonal antibodies. Limitations of specificity due to nonspecific uptake of antibody. Cancer 54: 1318, 1984.
Estour B., Van Herle A.J., Juillard G.J.F., Totanes T.L., Sparkes R.S., Giuliano A.E, Klandorf H. Characterization of a human follicular thyroid carcinoma cell line (UCLA RO 82 W-1). Virchows Archiv, B. Cell Pathology 57: 167, 1989.
Gluckman E., Parr M.D., Michelson E., Schroeder M.L. Mixed leukocyte cultures in dogs. A microtechnique using gradient purified cells. Transplantation 15: 642, 1973.
Oi V.T., Herzenberg L.A. Immunoglobulin producing hybrid cell lines. In: Mishell B.B., Shigii S.M. (Eds.), Selected methods in cellular immunology. W.H. Freeman, San Francisco, 1980, p. 351.
Brown J.P., Tamerius J.D., Hellstrom I. Indirect 125I labelled protein. An assay for monoclonal antibodies to cell-surface antigens. J. Immunol. Methods 31: 201, 1979.
Greenwood F.C., Hunter W.M., Glover J.S. The preparation of 131I-labelled human growth hormone of high specific radioactivity. Biochem. J. 89: 114, 1963.
Gautvik K.M., Svindahl K., Skretting A., Stenberg B., Aas M., Myhre L., Ekeland A., Johannesen J.V. Uptake and localization of 1311 labelled anti-calcitonin immunoglobulins in rat medullary thyroid carcinoma tissue. Cancer 50: 1107, 1982.
Anderson C.L., Grey H.M. Receptors for aggregated IgG on mouse lymphocytes. Their presence on thymocytes, thymus-derived, and bone marrow-derived lymphocytes. J. Exp. Med. 139: 1175, 1974.
Laemmli V.K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature (Lond.) 227: 680, 1970.
Krishnan E.C., Krishnan L., Jewell W.R. Characterization of Fc receptors associated with human malignant tumors. J. Surg. Oncol. 16: 179, 1981.
Moshakis v., McIlhinney R.A.J., Raghavan D., Neville A.M. Monoclonal antibodies to detect human tumors: an experimental approach. J. Clin. Pathol. 34: 314, 1981.
Epenetos A.A., Nimmon C.C., Arklie J., Elliott A.T., Hawkins L.A., Knowles R.W., Britton K.E., Bodmer W.F. Detection of human cancer in an animal model using radio-labelled tumour-associated monoclonal antibodies. Br. J. Cancer 46: 18, 1982.
Moshakis V., McIlhinney R.A.J., Raghava D., Neville A.M. Localization of human tumor xenografts after i.v. administration of radio-labelled monoclonal antibodies. Br. J. Cancer 44: 91, 1981.
Yasuda T., Balacios I.E., Khaw B.A., Dec W., Gold H.K., Leinbach R.C., Fallon J.T., Barlai-Kovach M., Strauss H.W., Haber E. Monoclonal indium-III antimyosin antibody imaging versus right ventricular biopsy in diagnosing acute myocarditis. Circulation 72:(Suppl. III), 11A, 1985 (Abstract).
Scully R.E., Mark E.J., McNeely B.U. Case Records of the Massachusetts General Hospital. N. Engl. J. Med. 314: 1240, 1986.
Rubin R.H., Fischman A.J., Callahan R.J., Khaw B.A., Keech F., Ahmad M., Wilkinson R., Strauss H.W. 111In-labeled nonspecific immunoglobulin scanning in the detection of focal infection. N. Engl. J. Med. 321: 935, 1989.
Epstein A.L., Chen F.-M., Taylor CR. A novel method for the detection of necrotic lesions in human cancers. Cancer Res. 48: 5842, 1988.
Lundy J., Mornex F., Keenan A.M., Greiner J.W., Colcher D. Radioimmunodetection of human colon carcinoma xenografts in visceral organs of congenitally athymic mice. Cancer 57: 503, 1986.
Bullard D.E., Adams C.J., Coleman R.E., Bigner D.D. In vivo imaging of intracranial human glioma xenografts comparing specific with nonspecific radiolabeled monoclonal antibodies. J. Neurosurg. 64: 257, 1986.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Van Herle, A.J., Estour, B., Juillard, G. et al. Immunodetection of thyroid tumors: role of immuno aggregates. J Endocrinol Invest 14, 635–646 (1991). https://doi.org/10.1007/BF03347885
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF03347885