Skip to main content
SpringerLink
Log in

Radiolabelled Monoclonal Antibody Imaging in Cancer

Potential and Limitations

  • Review Article
  • Diagnosis and Prevention
  • Published:
Clinical Immunotherapeutics Aims and scope Submit manuscript

Summary

Anticancer antibodies offer promise of high sensitivity and specificity for the detection of disease, as they bind to tumour-associated antigens usually found only on a given type of tumour. Most studies have shown that radioimmunodetection is superior to other imaging modalides in the detection of disease outside the liver. Indium-111 (111In)-labelled satumomab pendetide is the first radiolabelled monoclonal antibody to be marketed for detection of disease. It is approved for single-time use for the detection of extrahepatic abdominal disease in colon and ovarian cancer.

Optimal radionuclide-antibody conjugation is still not a reality. Antibody labelling with technetium-99m (99mTc), although still under development, appears promising. 111In has suitable half-life and imaging characteristics, but is expensive and has a complex radiation decay scheme, increasing radiation burden; 111In-labelled antibodies result in high hepatic and sometimes bone marrow uptake, precluding their use in the evaluation of hepatic disease. Radioiodine labelling, although easy, is limited to well-equipped nuclear medicine centres. Furthermore, mouse antibodies invariably evoke an immune response in humans, precluding repeated administration.

The nontoxicity, specificity and affinity of antibody binding makes it inevitable that antibodies will be used increasingly in the detection of cancer. Several advances still need to be realised: (a) development of nonimmunogenic molecules such as all-human or humanised antibodies or antibody fragments; (b) development of better linkers, allowing stable conjugation of nuclide to antibody; and (c) characterisation of more restricted and better expressed tumour antigens that will permit rapid targeting of antibody to tumour.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Köhler G, Milstein C. Continuous culture of fused cells secreting antibodies of predefined specificity. Nature 1975; 256: 495–7

    Article  PubMed  Google Scholar 

  2. Kramer EL, Larson SM. Tumor targeting with radiolabeled antibody for diagnosis and therapy. Immunol Allergy Clin North Am 1991; 11: 301–39

    Google Scholar 

  3. Collier DB, Abdel-Nabi H, Doerr RJ, et al. Immunoscintigraphy performed with In-111-labeled CYT-103 in the management of colorectal cancer: comparison with CT. Radiology 1992; 185: 179–86

    PubMed  CAS  Google Scholar 

  4. Goldenberg DM, DeLand F, Kim F, et al. Radiolabeled antibodies to carcinoembryonic antigen for the detection and localization of diverse cancers by external photoscanning. N Engl J Med 1978; 298: 1384–8

    Article  PubMed  CAS  Google Scholar 

  5. Eary JF, Krohn KA, Kishore R, et al. Radiochemistry of halogenated antibodies. In: Zalutsky MR, editor. Antibodies in radiodiagnosis and therapy. Boca Raton: CRC, 1988: 83–100

    Google Scholar 

  6. Gansow OA, Brechbiel MW, Mirzadeh S, et al. Chelates and antibodies: current methods and new directions. Cancer Treat Res 1990; 51: 153–71

    Article  PubMed  CAS  Google Scholar 

  7. Rodriguez-Bigas MA, Bakshi S, Stomper P, et al. 99mTc-IMMU-4 monoclonal antibody scan in colorectal cancer: a prospective study. Arch Surg 1992; 127: 1321–4

    Article  PubMed  CAS  Google Scholar 

  8. Salk D. Technetium-labeled monoclonal antibodies for imaging metastatic melanoma: results of a multicenter clinical study. Semin Oncol 1988; 15: 608–18

    PubMed  CAS  Google Scholar 

  9. Corbisiero RM, Yamauchi DM, Williams LE, et al. Comparison of immunoscintigraphy and computerized tomography in identifying colorectal cancer: individual lesion analysis. Cancer Res 1991; 51: 5704–11

    PubMed  CAS  Google Scholar 

  10. Divgi CR, McDermott K, Griffin TW, et al. Lesion-by-lesion comparison of computerized tomography and indium-111-labeled monoclonal antibody C110 radioimmunoscintigraphy in colorectal carcinoma: a multicenter trial. J Nucl Med 1993; 34: 1656–61

    PubMed  CAS  Google Scholar 

  11. Welt S, Divgi CR, Real FX, et al. Quantitative analysis of antibody localization in human metastatic colon cancer: a phase I study of monoclonal antibody A33. J Clin Oncol 1990; 8: 1894–906

    PubMed  CAS  Google Scholar 

  12. Blottiere HM, Douillard JY, Koprowski H, et al. Immunoglobulin class and immunoglobulin G subclass analysis of human anti-mouse antibody response during monoclonal antibody treatment of cancer patients. Cancer Res 1990; 50: 1051s–4s

    PubMed  CAS  Google Scholar 

  13. Lubeck MD, Steplewski Z, Baglia F, et al. The interaction of murine IgG subclass proteins with human monocyte Fc receptors. J Immunol 1985; 135: 1299–304

    PubMed  CAS  Google Scholar 

  14. Cohen AM, Martin Jr EW, Lavery I, et al. Radioimmunoguided surgery using iodine 125 B72.3 in patients with colorectal cancer. Arch Surg 1991; 126: 349–52

    Article  PubMed  CAS  Google Scholar 

  15. Hertel A, Baum RP, Lorenz M, et al. Immunoscintigraphy using a technetium-99m labelled monoclonal anti-CEA antibody in the follow-up of colorectal cancer and other tumours producing CEA. Br J Cancer 1990; 10 Suppl.: 34–6

    CAS  Google Scholar 

  16. Steis RG, Carrasquillo JA, McCabe R, et al. Toxicity, immunogenicity, and tumor radioimmunodetecting ability of two human monoclonal antibodies in patients with metastatic colorectal carcinoma. J Clin Oncol 1990; 8: 476–90

    PubMed  CAS  Google Scholar 

  17. Surwit EA, Childers JM, Krag DN, et al. Clinical assessment of 111In-CYT-103 immunoscintigraphy in ovarian cancer. Gynecol Oncol 1993; 48: 285–92

    Article  PubMed  CAS  Google Scholar 

  18. Rubin SC. Monoclonal antibodies in the management of ovarian cancer: a clinical perspective. Cancer 1993; 71: 1602–12

    Article  PubMed  CAS  Google Scholar 

  19. Divgi CR, Larson SM. Radiolabeled monoclonal antibodies in the diagnosis and treatment of malignant melanoma. Semin Nucl Med 1989; 19: 252–61

    Article  PubMed  CAS  Google Scholar 

  20. Balaban EP, Walker BS, Cox JV, et al. Detection and staging of small cell lung carcinoma with a technetium-labeled monoclonal antibody: a comparison with standard staging methods. Clin Nucl Med 1992; 17: 439–45

    Article  PubMed  CAS  Google Scholar 

  21. Friedman S, Sullivan K, Salk D, et al. Staging non-small cell carcinoma of the lung using technetium-99m-labeled monoclonal antibodies. Hematol Oncol Clin North Am 1990; 4: 1069–78

    PubMed  CAS  Google Scholar 

  22. Divgi CR, Welt S, Kris MG, et al. Phase I and imaging trial of indium 111-labeled anti-epidermal growth factor receptor monoclonal antibody 225 in patients with squamous cell lung carcinoma. J Natl Cancer Inst 1991; 83: 97–104

    Article  PubMed  CAS  Google Scholar 

  23. Oosterwijk E, Bander NH, Divgi CR, et al. Antibody localization in human renal cell carcinoma: a phase I study of monoclonal antibody G250. J Clin Oncol 1993; 11: 738–50

    PubMed  CAS  Google Scholar 

  24. Kramer EL, DeNardo SJ, Liebes L, et al. Radioimmunolocalization of metastatic breast carcinoma using indium-111-methyl benzyl DTPA BrE-3 monoclonal antibody: phase I study. J Nucl Med 1993; 34: 1067–74

    PubMed  CAS  Google Scholar 

  25. Baum RP, Adams S, Kiefer J, et al. A novel technetium-99m labeled monoclonal antibody (174H.64) for staging head and neck cancer by immuno-SPECT. Acta Oncol 1993; 32: 747–51

    Article  PubMed  CAS  Google Scholar 

  26. Carrasquillo JA, Bunn Jr PA, Keenan AM, et al. Radioimmunodetection of cutaneous T-cell lymphoma with 111in-labeled T101 monoclonal antibody. N Engl J Med 1986; 315: 673–80

    Article  PubMed  CAS  Google Scholar 

  27. Kaminski MS, Zasadny KR, Francis IR, et al. Radioimmunotherapy of B-cell lymphoma with [131I]anti-B1 (anti-CD20) antibody. N Engl J Med 1993; 329: 459–65

    Article  PubMed  CAS  Google Scholar 

  28. Press OW, Eary JF, Appelbaum FR, et al. Radiolabeled-antibody therapy of B-cell lymphoma with autologous bone marrow support. N Engl J Med 1993; 329: 1219–24

    Article  PubMed  CAS  Google Scholar 

  29. Baum RP, Niesen A, Hertel A, et al. Initial clinical results with technetium-99m-labeled LL2 monoclonal antibody fragment in the radioimmunodetection of B-cell lymphomas. Cancer 1994; 73 Suppl.: 896–9

    Article  PubMed  CAS  Google Scholar 

  30. Serafini AN, Vargas-Cuba R, Moffat F, et al. Radioimmunoscintigraphy (RIS) of colorectal cancer with Tc-99m-IgG3 labeled whole human monoclonal antibody (HuMoAb) 88BV59 [abstract]. Eur J Nucl Med 1993; 20: 855

    Google Scholar 

  31. Billetta R, Lobuglio AF. Chimeric antibodies. Int Rev Immunol 1993; 10: 165–76

    Article  PubMed  CAS  Google Scholar 

  32. Caron PC, Co MS, Bull MK, et al. Biological and immunological features of humanized M195 (anti-CD33) monoclonal antibodies. Cancer Res 1992; 52: 6761–7

    PubMed  CAS  Google Scholar 

  33. Milenic DE, Yokota T, Filpula DR, et al. Construction, binding properties, metabolism, and tumor targeting of a single-chain Fv derived from the pancarcinoma monoclonal antibody CC49. Cancer Res 1991; 51: 6363–71

    PubMed  CAS  Google Scholar 

  34. Yokota T, Milenic DE, Whitlow M, et al. Rapid tumor penetration of a single-chain Fv and comparison with other immunoglobulin forms. Cancer Res 1992; 52: 3402–8

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Nuclear Medicine Service, Memorial Sloan-Kettering Cancer Center, Cornell University Medical College, New York, New York, 10021, USA

    Chaitanya R. Divgi

Authors
  1. Chaitanya R. Divgi
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Divgi, C.R. Radiolabelled Monoclonal Antibody Imaging in Cancer. Clin. Immunother. 3, 218–226 (1995). https://doi.org/10.1007/BF03259057

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03259057

Keywords

Search

Navigation