Immunodetection of Thyroid Tumors: Role of Immuno Aggregates

Overview

Journal J Endocrinol Invest

Publisher Springer

Specialty Endocrinology

Date 1991 Sep 1

PMID 1774449

Authors

A J Van Herle

B Estour

G Juillard

A Giuliano

R A Hawkins

K van Herle

Affiliations

Soon will be listed here.

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 x 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 x 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.

References

Anderson C, Grey H . Receptors for aggregated IgG on mouse lymphocytes: their presence on thymocytes, thymus-derived, and bone marrow-derived lymphocytes. J Exp Med. 1974; 139(5):1175-88. PMC: 2139647. DOI: 10.1084/jem.139.5.1175. View

Laemmli U . Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970; 227(5259):680-5. DOI: 10.1038/227680a0. View

Bullard D, Adams C, Coleman R, Bigner D . In vivo imaging of intracranial human glioma xenografts comparing specific with nonspecific radiolabeled monoclonal antibodies. J Neurosurg. 1986; 64(2):257-62. DOI: 10.3171/jns.1986.64.2.0257. View

Gautvik K, Svindahl K, Skretting A, Stenberg B, Myhre L, Ekeland A . Uptake and localization of 131I-labeled anti-calcitonin immunoglobulins in rat medullary thyroid carcinoma tissue. Cancer. 1982; 50(6):1107-14. DOI: 10.1002/1097-0142(19820915)50:6<1107::aid-cncr2820500614>3.0.co;2-j. View

Lundy J, Mornex F, Keenan A, GREINER J, Colcher D . Radioimmunodetection of human colon carcinoma xenografts in visceral organs of congenitally athymic mice. Cancer. 1986; 57(3):503-9. DOI: 10.1002/1097-0142(19860201)57:3<503::aid-cncr2820570317>3.0.co;2-j. View

Goldenberg D, Deland F, Kim E, Bennett S, Primus F, van Nagell Jr J . Use of radiolabeled antibodies to carcinoembryonic antigen for the detection and localization of diverse cancers by external photoscanning. N Engl J Med. 1978; 298(25):1384-6. DOI: 10.1056/NEJM197806222982503. View

Brown J, Tamerius J, Hellstrom I . Indirect 125I-labeled protein A assay for monoclonal antibodies to cell surface antigens. J Immunol Methods. 1979; 31(3-4):201-9. DOI: 10.1016/0022-1759(79)90132-7. View

Moshakis V, McIlhinney R, Raghavan D, Neville A . Localization of human tumour xenografts after i.v. administration of radiolabeled monoclonal antibodies. Br J Cancer. 1981; 44(1):91-9. PMC: 2010661. DOI: 10.1038/bjc.1981.153. View

Rubin R, Fischman A, CALLAHAN R, Khaw B, Keech F, Ahmad M . 111In-labeled nonspecific immunoglobulin scanning in the detection of focal infection. N Engl J Med. 1989; 321(14):935-40. DOI: 10.1056/NEJM198910053211404. View

10.

Mann B, Cohen M, Saxton R, Morton D, Benedict W, Korn E . Imaging of human tumor xenografts in nude mice with radiolabeled monoclonal antibodies. Limitations of specificity due to nonspecific uptake of antibody. Cancer. 1984; 54(7):1318-27. DOI: 10.1002/1097-0142(19841001)54:7<1318::aid-cncr2820540715>3.0.co;2-j. View

11.

Estour B, Van Herle A, Juillard G, Totanes T, Sparkes R, Giuliano A . Characterization of a human follicular thyroid carcinoma cell line (UCLA RO 82 W-1). Virchows Arch B Cell Pathol Incl Mol Pathol. 1989; 57(3):167-74. DOI: 10.1007/BF02899078. View

12.

Gluckman E, Parr M, Mickelson E, Schroeder M, Storb R . Mixed leukocyte cultures in dogs. A microtechnique using gradient-purified cells. Transplantation. 1973; 15(6):642-5. DOI: 10.1097/00007890-197306000-00024. View

13.

Mach J, Carrel S, Forni M, Ritschard J, Donath A, Alberto P . Tumor localization of radio-labeled antibodies against carcinoembryonic antigen in patients with carcinoma: a critical evaluation. N Engl J Med. 1980; 303(1):5-10. DOI: 10.1056/NEJM198007033030102. View

14.

Stuhlmiller G, Sullivan D, Vervaert C, Croker B, Harris C, Seigler H . In vivo tumor localization using tumor-specific monkey xenoantibody, alloantibody, and murine monoclonal xenoantibody. Ann Surg. 1981; 194(5):592-601. PMC: 1345264. DOI: 10.1097/00000658-198111000-00007. View

15.

Pressman D, DAY E, Blau M . The use of paired labeling in the determination of tumor-localizing antibodies. Cancer Res. 1957; 17(9):845-50. View

16.

GREENWOOD F, Hunter W, GLOVER J . THE PREPARATION OF I-131-LABELLED HUMAN GROWTH HORMONE OF HIGH SPECIFIC RADIOACTIVITY. Biochem J. 1963; 89:114-23. PMC: 1202279. DOI: 10.1042/bj0890114. View

17.

Epstein A, Chen F, Taylor C . A novel method for the detection of necrotic lesions in human cancers. Cancer Res. 1988; 48(20):5842-8. View

18.

Goldenberg D, PRESTON D, Primus F, Hansen H . Photoscan localization of GW-39 tumors in hamsters using radiolabeled anticarcinoembryonic antigen immunoglobulin G. Cancer Res. 1974; 34(1):1-9. View

19.

. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 18-1986. A 44-year-old woman with substernal pain and pulmonary edema after severe emotional stress. N Engl J Med. 1986; 314(19):1240-7. DOI: 10.1056/NEJM198605083141908. View

20.

Krishnan E, Krishnan L, JEWELL W . Characterization of Fc receptors associated with human malignant tumors. J Surg Oncol. 1981; 16(2):179-88. DOI: 10.1002/jso.2930160210. View