Radioimmunotherapy of Renal Cancer

  • Chaitanya Divgi
Part of the Medical Radiology book series (MEDRAD)


Renal cancer is an aggressive, radio-resistant cancer, with, until recently, ineffective systemic therapy. Early success with immunotherapy, particularly therapy with high doses of interleukin-2, spurred the investigation of antibodies that target cell surface antigens overexpressed in renal cancer. The incidence of renal cancer has changed with the increasing use of imaging in medical management. Renal masses are now usually detected serendipitously during abdominal imaging for other conditions. Consequently, a greater fraction of these masses are benign and small. This decrease in median size permits curative surgery and decreases the need for subsequent systemic therapy. The recent increase in effective molecular therapies with very acceptable toxicity profiles has led to a further decrease in the need for and study of toxic systemic therapies, including chemotherapy and radioimmunotherapy. It is clear now that the renal cancer with the greatest propensity to metastasis, and hence the only renal cancer for which aggressive systemic therapies may be warranted, is the clear cell phenotype. Carbonic anhydrase-IX is a cell surface antigen overexpressed in the vast majority of clear cell renal cancers, and G250 is an antibody that has been radiolabeled and extensively studied as a therapeutic (and diagnostic) agent in clear cell renal cell cancer (ccRCC). This chapter will review studies with murine and chimeric G250 (girentuximab), with reference to characteristics of systemic macromolecular radiotherapy when relevant. Potential for combination with other systemic therapies will be summarized.


Renal Cancer Clear Cell Renal Cancer Renal Cortical Tumor Clear Cell Renal Cell Cancer Hematopoietic Toxicity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. American Cancer Society (2011) Cancer facts & figures 2011. American Cancer Society, Atlanta Google Scholar
  2. Berland LL, Silverman SG, Gore RM et al (2010 Oct) Managing incidental findings on abdominal CT: white paper of the ACR incidental findings committee. J Am Coll Radiol 7(10):754–773PubMedCrossRefGoogle Scholar
  3. Brouwers AH, Buijs WC, Oosterwijk E, Boerman OC, Mala C, De Mulder PH, Corstens FH, Mulders PF, Oyen WJ (2003) Targeting of metastatic renal cell carcinoma with the chimeric monoclonal antibody G250 labeled with (131)I or (111)In: an intrapatient comparison. Clin Cancer Res 9(10 Pt 2):3953S–3960SPubMedGoogle Scholar
  4. Brouwers AH, van Eerd JE, Frielink C, Oosterwijk E, Oyen WJ, Corstens FH, Boerman OC (2004) Optimization of radioimmunotherapy of renal cell carcinoma: labeling of monoclonal antibody cG250 with 131I, 90Y, 177Lu, or 186Re. J Nucl Med 45:327–337PubMedGoogle Scholar
  5. Brouwers AH, Buijs WC, Mulders PF, de Mulder PH, van den Broek WJ, Mala C, Oosterwijk E, Boerman OC, Corstens FH, Oyen WJ (2005a) Radioimmunotherapy with [131I]cG250 in patients with metastasized renal cell cancer: dosimetric analysis and immunologic response. Clin Cancer Res 11(19 Pt 2):7178s–7186sPubMedCrossRefGoogle Scholar
  6. Brouwers AH, Mulders PF, de Mulder PH, van den Broek WJ, Buijs WC, Mala C, Joosten FB, Oosterwijk E, Boerman OC, Corstens FH, Oyen WJ (2005b) Lack of efficacy of two consecutive treatments of radioimmunotherapy with 131I-cG250 in patients with metastasized clear cell renal cell carcinoma. J Clin Oncol 23:6540–6548PubMedCrossRefGoogle Scholar
  7. Carrasquillo JA, Bunn PA Jr, Keenan AM, Reynolds JC, Schroff RW, Foon KA, Su MH, Gazdar AF, Mulshine JL, Oldham RK et al (1986) Radioimmunodetection of cutaneous T-cell lymphoma with 111In-labeled T101 monoclonal antibody. N Engl J Med 315:673–680PubMedCrossRefGoogle Scholar
  8. Cheville JC, Lohse CM, Zincke H et al (2003) Comparisons of outcome and prognostic features among histologic subtypes of renal cell carcinoma. Am J Surg Pathol 27:612–624PubMedCrossRefGoogle Scholar
  9. Cho DC, Atkins MB (2011 Aug) Future directions in renal cell carcinoma: 2011 and beyond. Hematol Oncol Clin N Am 25(4):917–935CrossRefGoogle Scholar
  10. Clarke K, Lee FT, Brechbiel MW, Smyth FE, Old LJ, Scott AM (2000) In vivo biodistribution of a humanized anti-Lewis Y monoclonal antibody (hu3S193) in MCF-7 xenografted BALB/c nude mice. Cancer Res 60:4804–4811PubMedGoogle Scholar
  11. Divgi CR, Bander NH, Scott AM, O’Donoghue JA, Sgouros G, Welt S, Finn RD, Morrissey F, Capitelli P, Williams JM, Deland D, Nakhre A, Oosterwijk E, Gulec S, Graham MC, Larson SM, Old LJ (1998) Phase I/II radioimmunotherapy trial with iodine-131-labeled monoclonal antibody G250 in metastatic renal cell carcinoma. Clin Cancer Res 4:2729–2739PubMedGoogle Scholar
  12. Divgi CR, O’Donoghue JA, Welt S, O’Neel J, Finn R, Motzer RJ, Jungbluth A, Hoffman E, Ritter G, Larson SM, Old LJ (2004) Phase I clinical trial with fractionated radioimmunotherapy using 131I-labeled chimeric G250 in metastatic renal cancer. J Nucl Med 45:1412–1421PubMedGoogle Scholar
  13. Kattan MW, Reuter V, Motzer RJ et al (2001) A postoperative prognostic nomogram for renal cell. J Urol 166:63–67PubMedCrossRefGoogle Scholar
  14. Linehan WM, Walther MM, Zbar B (2003) The genetic basis of cancer of the kidney. J Urol 170:2163–2172PubMedCrossRefGoogle Scholar
  15. Loh A, Sgouros G, O’Donoghue JA, Deland D, Puri D, Capitelli P, Humm JL, Larson SM, Old LJ, Divgi CR (1998) Pharmacokinetic model of iodine-131-G250 antibody in renal cell carcinoma patients. J Nucl Med 39(3):484–489PubMedGoogle Scholar
  16. Motzer RJ, Bukowski RM (2006) Targeted therapy for metastatic renal cell carcinoma. J Clin Oncol 24:5601–5608PubMedCrossRefGoogle Scholar
  17. Motzer RJ, Bacik J, Mariani T et al (2002) Treatment outcome and survival associated with metastatic renal cell carcinoma of non-clear cell histology. J Clin Oncol 20:2376–2381PubMedCrossRefGoogle Scholar
  18. National comprehensive cancer network clinical practice guidelines in oncology—kidney cancer. Version 2.2011;NCCN.orgGoogle Scholar
  19. Oosterwijk E, Ruiter DJ, Hoedemaeker PJ, Pauwels EK, Jonas U, Zwartendijk J, Warnaar SO (1986) Monoclonal antibody G 250 recognizes a determinant present in renal-cell carcinoma and absent from normal kidney. Int J Cancer 38:489–494PubMedCrossRefGoogle Scholar
  20. Oosterwijk E, Bander NH, Divgi CR, Welt S, Wakka JC, Finn RD, Carswell EA, Larson SM, Warnaar SO, Fleuren GJ et al (1993) Antibody localization in human renal cell carcinoma: a phase I study of monoclonal antibody G250. J Clin Oncol 11:738–750PubMedGoogle Scholar
  21. Oosterwijk E, Divgi CR, Brouwers A, Boerman OC, Larson SM, Mulders P, Old LJ (2003 Aug) Monoclonal antibody-based therapy for renal cell carcinoma. Urol Clin N Am 30(3):623–631CrossRefGoogle Scholar
  22. Oosterwijk-Wakka JC, Kats-Ugurlu G, Leenders WP, Kiemeney LA, Old LJ, Mulders PF, Oosterwijk E (2011) Effect of tyrosine kinase inhibitor treatment of renal cell carcinoma on the accumulation of carbonic anhydrase IX-specific chimeric monoclonal antibody cG250. BJU Int 107:118–125PubMedCrossRefGoogle Scholar
  23. Sorbellini M, Kattan MW, Snyder ME et al (2005) A postoperative prognostic nomogram predicting recurrence for patients with conventional clear cell renal cell carcinoma. J Urol 173:48–51PubMedCrossRefGoogle Scholar
  24. Steffens MG, Boerman OC, Oosterwijk-Wakka JC, Oosterhof GO, Witjes JA, Koenders EB, Oyen WJ, Buijs WC, Debruyne FM, Corstens FH, Oosterwijk E (1997) Targeting of renal cell carcinoma with iodine-131-labeled chimeric monoclonal antibody G250. J Clin Oncol 15:1529–1537PubMedGoogle Scholar
  25. Steffens MG, Boerman OC, de Mulder PH, Oyen WJ, Buijs WC, Witjes JA, van den Broek WJ, Oosterwijk-Wakka JC, Debruyne FM, Corstens FH, Oosterwijk E (1999) Phase I radioimmunotherapy of metastatic renal cell carcinoma with 131I-labeled chimeric monoclonal antibody G250. Clin Cancer Res 5(10 Suppl):3268s–3274sPubMedGoogle Scholar
  26. Stillebroer AB, Mulders PF, Boerman OC, Oyen WJ, Oosterwijk E (2010) Carbonic anhydrase IX in renal cell carcinoma: implications for prognosis, diagnosis, and therapy. Eur Urol 58:75–83PubMedCrossRefGoogle Scholar
  27. Stillebroer AB, Zegers CM, Boerman OC, Oosterwijk E, Mulders PF, O’Donoghue JA, Visser EP, Oyen WJ (2012) Dosimetric analysis of 177Lu-cG250 radioimmunotherapy in renal cell carcinoma patients: correlation with myelotoxicity and pretherapeutic absorbed dose predictions based on 111In-cG250 imaging. J Nucl Med 53:82–89PubMedCrossRefGoogle Scholar
  28. Welt S, Divgi CR, Real FX, Yeh SD, Garin-Chesa P, Finstad CL, Sakamoto J, Cohen A, Sigurdson ER, Kemeny N et al (1990) Quantitative analysis of antibody localization in human metastatic colon cancer: a phase I study of monoclonal antibody A33. J Clin Oncol 8:1894–1906PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  1. 1.RadiologyColumbia UniversityNew YorkUSA

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