Skip to main content

Advertisement

Log in

Immunoscintigraphic localization of renal tumours in an extracorporeal perfusion model with a monoclonal antibody against γ-glutamyltransferase

  • Original articles
  • Published:
Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Summary

Monoclonal antibody 138H11 against human γ-glutamyltransferase has been shown to react immunohistochemically with 98% of all tested clear-cell type and chromophilic renal cell carcinomas, but not with renal chromophobic carcinomas, Duct-Bellini carcinomas or oncocytomas. In normal kidney the target epitopes of mAb 138H11 are located in the luminal brush-border membrane of proximal tubule cells, whereas in renal carcinomas the epitopes are found surrounding the whole tumour cells. These results form the basis of the present immunoscintigraphic study designed to evaluate mAb 138H11 in an extracorporeal perfusion model. Immediately after nephrectomy, human tumour-bearing kidneys were perfused with99mTc-labelled mAb 138H11 in Euro-Collins solution. High specific uptake in 4/4 renal clear cell carcinomas could be demonstrated by planar immunoscintigraphy and single-photon-emission computed tomography, “regions of interest” investigation and immunohistochemistry. In contrast, a perfused oncocytoma showed up as an unlabelled lesion. The results indicate a possible use for mAb 138H11 in immunoscintigraphy or even therapy, provided high tumour uptake can be confirmed in patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Ahmad S, Okine L, Wood R, Aljian J, Vistica DT (1987) Gammaglutamyl transpeptidase and maintenance of thiol pools in tumour cells resistant to alkylating agents. J Cell Physiol 131: 240

    PubMed  Google Scholar 

  2. Baum RP, Hertel A, Lorenz M, Schwarz A, Encke A, Hör G (1989)99Tcm-labelled anti-CEA monoclonal antibody for tumour immunoscintigraphy: first clinical results. Nucl Med Commun 10: 345

    PubMed  Google Scholar 

  3. Bazeed MA, Schärfe T, Becht E, Jurincic C, Alken P, Thüroff JW (1986) Conservative surgery of renal cell carcinoma. Eur Urol 12: 238

    PubMed  Google Scholar 

  4. Brubaker LH, Vogel CL, Einhorn LH, Birch R (1986) Treatment of advanced adenocarcinoma of the kidney with ICRF-187: a southeastern cancer study group trial. Cancer Treat Rep 70: 915

    PubMed  Google Scholar 

  5. DeKernion JB (1983) Treatment of advanced renal cell carcinoma — traditional methods and innovative approaches. J Urol 130: 2

    PubMed  Google Scholar 

  6. DeKernion JB (1986) Renal cell carcinoma. J Urol 136: 882

    PubMed  Google Scholar 

  7. Epenetos AA, Oberhausen E, Reisfeld RA (eds) (1988) Immunotherapy and scintigraphy of tumours with monoclonal antibodies. Zuckschwerdt, München

    Google Scholar 

  8. Finstad CL, Cordon-Cardo C, Bander NH, Whitmore WF, Melamed MR, Old LJ (1985) Specificity analysis of mouse monoclonal antibodies defining cell surface antigens of human renal cancer. Proc Natl Acad Sci USA 82: 2955

    PubMed  Google Scholar 

  9. Fischer P, Scherberich JE, Wolf GB, Schoeppe W (1988) Novel monoclonal antibody 70H9 may demonstrate incomplete processing of a membrane glycoprotein from human kidney proximal tubule in renal cancer cells. Immunobiology 178: 34

    Google Scholar 

  10. Fischer P, Scherberich JE, Schoeppe W (1990) Comparative biochemical and immunological studies on gamma-glutamyltransferases from human kidney and renal cell carcinoma applying monoclonal antibodies. Clin Chim Acta 191: 185

    PubMed  Google Scholar 

  11. Fischer P, Störkel S, Haase W, Scherberich JE (1991) Differential diagnosis of histogenetically distinct human epithelial renal tumours with a monoclonal antibody against γ-glutamyltransferase. Cancer Immunol Immunother 33: 382

    PubMed  Google Scholar 

  12. Gams RA, Nelson O, Birch R (1986) Phase II evaluation of mitoxantrone in advanced renal cell carcinoma: a southeastern cancer study group trial. Cancer Treat Rep 70: 921

    PubMed  Google Scholar 

  13. Golimbu M, Al-Askari S, Tessler A, Morales P (1986) Aggressive treatment of metastatic renal cancer. J Urol 136: 805

    PubMed  Google Scholar 

  14. Hada T, Higashino K, Yamamoto H, Yamamura Y, Matsuda M, Osafune M, Kotake T, Sonoda T (1978) A novel gamma-glutamyl transpeptidase in renal carcinoma in comparison with normal kidney enzyme. Clin Chim Acta 85: 267

    PubMed  Google Scholar 

  15. Hanke P, Wolf G, Scherberich JE, Karich H, Fischer P, Schoeppe W, Jonas D (1988) Charakterisierung humaner Nierenadenokarzinome mit Hilfe von Leitenzymen, Lektinrezeptoren und monoklonalen Antikörpern. Verh Dtsch Ges Urol 39: 341

    Google Scholar 

  16. Inoue M, Shinozuka S, Morino Y (1986) Mechanism of renal peritubular extraction of plasma glutathione. The catalytic activity of contralumenal gamma-glutamyltransferase is prerequisite to the apparent peritubular extraction of plasma glutathione. Eur J Biochem 157: 605

    PubMed  Google Scholar 

  17. Jäger W, Feistel H, Paterok EM, Ronay G, Tulusan AH, Wolf F, Lang N (1990) Resection guided by antibodies (REGAJ): a diagnostic procedure during second-look operation in ovarian cancer patients. Br J Cancer 62 [Suppl X]: 18

    Google Scholar 

  18. Luner SJ, Ghose T, Chatterjee S, Chruz HN, Belitsky P (1986) Monoclonal antibodies to kidney and tumour-associated antigens of human renal cell carcinoma. Cancer Res 46: 5816

    PubMed  Google Scholar 

  19. McKinstry CC, McIlrath EM (1987) Staging of the abdominal extent of renal carcinoma by computed tomography. Eur J Radiol 7: 165

    PubMed  Google Scholar 

  20. Nieroda CA, Mojzisik C, Sardi A, Farrar WB, Hinkle G, Siddiqi MA, Ferrara PJ, James A, Schlom J, Thurston MO, Martin EW Jr (1989) Staging of carcinoma of the breast using a hand-held gamma detecting probe and monoclonal antibody B72.3. Surg Gynecol Obstet 169: 35

    PubMed  Google Scholar 

  21. Nieroda CA, Mojzisik C, Sardi A, Ferrara P, Hinkle G, Thurston MO, Martin EW Jr (1989) The impact of radioimmunoguided surgery (RIGS) on surgical decision-making in colorectal cancer. Dis Colon Rectum 32: 927

    PubMed  Google Scholar 

  22. Oosterwijk E, Ruiter DJ, Wakka JD, Huiskens VD, Meij JW, Jonas U, Fleuren G-J, Zwartendijk J, Hoedemaeker P, Warnaar SO (1986) Immunohistochemical analysis of monoclonal antibodies to renal antigens: application in the diagnosis of renal cell carcinoma. Am J Pathol 123: 301

    PubMed  Google Scholar 

  23. Schärfe T, Becht E, Kaltwasser R, Thüroff JW, Jacobi GH, Hohenfellner R (1985) Tumour-specific monoclonal antibodies for renal cell carcinoma. Eur Urol 11: 117

    PubMed  Google Scholar 

  24. Scherberich JE, Stefanescu T, Gauhl C, Sayre R, Kleemann B, Mondorf W (1979) Lectin receptors of plasma-membranes from human kidney and renal adenocarcinoma. Protides Biol Fluids 27: 499

    Google Scholar 

  25. Scherberich JE, Mauck J, Hess H, Mondorf W, Falkenberg FW (1984) Monoclonal antibodies against renal adenocarcinoma: evaluation of epitopes in common with placental and fetal tissue. Protides Biol Fluids 31: 845

    Google Scholar 

  26. Schwarz A, Steinsträßer A (1987) A novel approach to Tc-99m-labelled monoclonal antibodies. J Nucl Med 28: 721

    Google Scholar 

  27. Smith SJ, Bosniak MA, Megibow AJ, Hulnik DH, Horii SC, Raghavendra BN (1989) Renal cell carcinoma: earlier discovery and increased detection. Radiology 170: 699

    PubMed  Google Scholar 

  28. Tate SS, Meister A (1985) Gamma-glutamyl transpeptidase from kidney. Methods Enzymol: 400

  29. Vanderlaan M, Phares W (1981) Gamma-glutamyl transpeptidase: a tumour cell marker with a pharmacological function. Histochem J 13: 865

    PubMed  Google Scholar 

  30. Van Dijk J, Oosterwijk E, Van Kroonenburgh MJPG, Jonas U, Fleuren GJ, Paulwels EKJ, Warnaar SO (1988) Perfusion of tumourbearing kidneys as a model for scintigraphic of monoclonal antibodies. J Nucl Med 29: 1078

    PubMed  Google Scholar 

  31. Vessella RL (1991) Radioimmunoconjugates in renal cell carcinoma. In: Immunotherapy of renal cell carcinoma. Springer, Berlin Heidelberg New York, p 38

    Google Scholar 

  32. Vessella RL, Moon TD, Chiou R-K, Nowak JA, Arfman EW, Palme DF, Peterson GA, Lange PH (1985) Monoclonal antibodies to human renal cell carcinoma: recognition of shared and restricted tissue antigens. Cancer Res 45: 6131

    PubMed  Google Scholar 

  33. Waldmann TA (1991) Monoclonal antibodies in diagnosis and therapy. Science 52: 1657

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fischer, P., Baum, R.P., Tauber, M. et al. Immunoscintigraphic localization of renal tumours in an extracorporeal perfusion model with a monoclonal antibody against γ-glutamyltransferase. Cancer Immunol Immunother 35, 283–288 (1992). https://doi.org/10.1007/BF01789336

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01789336

Key words

Navigation