Skip to main content
Log in

Pharmacokinetic analysis of antibody localization in human colon cancer: Comparison with immunoscintigraphy

  • Original Article
  • Published:
Annals of Nuclear Medicine Aims and scope Submit manuscript

Abstract

The biodistribution and imaging characteristics of the111In-labeled anti CEA monoclonal antibody ZCE-025 were studied in five patients with suspicion of colorectal carcinoma. Evaluation included antibody pharmacokinetics and assessment of antibody distribution in surgical specimen, making a comparison with whole-body imaging with a gamma camera. ZCE-025 localization in tumors was demonstrated by gamma-camera imaging in 4 of the 5 patients, corresponding to surgical findings. Persistent accumulation of111In in the lymph nodes was observed in one patient, whereas surgical exploration of these lymph nodes showed no gross or microscopic evidence of metastases of colon carcinoma. Analysis of individual plasma by size exclusion HPLC showed two radioactivity peaks, labeled antibody and free DTPA. No transchelation of111In to circulating transferrin was observed. The blood clearance was fitted to a two-compartment equation and its half-lives were found to be 10.8±8.7 h and 69.5±21.8 h for t1/2α and t1/2β, respectively. Total urinary excretion averaged 0.3% of the injected dose/h with a small patient to patient variation. At 24 hrs postadministration the predominant radiolabeled species in urine was free DTPA. Thereafter, radioactivity in urine was partly present as a low molecular weight catabolic product. No apparent correlation between CEA content and uptake of111In-ZCE-025 in tumors resected by surgery could be found. How111In-labeled antibody is accumulated into tumors as well as into some non-tumor tissues needs further study.

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. Buchegger F, Haskell CM, Schreyer M, et al: Radiolabeled fragments of monoclonal antibodies against carcinoembryonic antigen for localization of human colon carcinoma grafted into nude mice.J Exp Med 158: 413–427, 1983

    Article  PubMed  CAS  Google Scholar 

  2. Abdel-Nabi HH, Schwartz AN, Higano CS, et al: Colorectal Carcinoma: Detection with indium-111 Anticarcinoembryonic-Antigen Monoclonal Antibody ZCE-025.Radiology 164: 617–621, 1987

    PubMed  CAS  Google Scholar 

  3. Patt YZ, Lamki LM, Haynie TP, et al: Improved Tumor Localization with Increasing Dose of Indium-111-Labeled Anti-Carcinoembryonic Antigen Monoclonal Antibody ZCE-025 in Metastatic Colorectal Cancer.J Clin Oncol 6: 1220–1230, 1988

    PubMed  CAS  Google Scholar 

  4. Duda RB, Zimmer AM, Rosen ST, et al: Radioimmune Localization of Occult Carcinoma.Arch Surg 125: 866–870, 1990

    PubMed  CAS  Google Scholar 

  5. Halpern SE, Haindl W, Beauregard J, et al: Scintigraphy with In-111-labeled Monoclonal Antitumor Antibodies: Kinetics, Biodistribution, and Tumor Detection.Radiology 168: 529–536, 1988

    PubMed  CAS  Google Scholar 

  6. Kxejcarek GE, Tucker KL: Covalent attachment of chelating groups to macromolecules.Biochem Biophys Res Commun 77: 581–585, 1977

    Article  Google Scholar 

  7. Schreyer M, Haskell CM, Girardet C, et al: Localization of tumor-associated antigens on section of human colon carcinoma grafted into nude mice with mouse monoclonal antibodies using the avidin-bioth-immunoperoxidase reaction. InProceedings of the Fourth International Workshop on Immune-deficient Animals in Experimental Research, Basel, S. Karger A.G., pp 287–290, 1984

    Google Scholar 

  8. Nakamura K, Kubo A, Hashimoto S, et al: Radioimmunodetection of human pancreatic tumor xenografts using DU-PAN II monoclonal antibody.Ann Nucl Med 2: 1–6, 1988

    Article  PubMed  CAS  Google Scholar 

  9. Gold P: Specific carcino embryonic antigens of the human digestive system.J Exp Med 122: 467–469, 1965

    Article  PubMed  CAS  Google Scholar 

  10. Lowry OH, Rosebrough NJ, Farr AL, et al: Protein measurement with the Folin Phenol reagent.J Biol Chem 193: 265–275, 1951

    PubMed  CAS  Google Scholar 

  11. Tsutsumi Y, Onoda N, Misawa M, et al: Immunohistochemical demonstration of nonspecific cross-reacting antigen in normal and neoplastic tumor tissue using a monoclonal antibody comparison with carcinoembryonic antigen localization.Acta Pathol Jpn 40: 85–97, 1990

    PubMed  CAS  Google Scholar 

  12. Katayama M, Nakamura K, Kubo A, et al: Immunoscintigraphy of colorectal cancer with In-111-labeled anti CEA monoclonal antibody (ZCE-025).Jpn J Nucl Med 28: 701–109, 1991

    Google Scholar 

  13. Kubo A, Nakamura K, Kodaira S: False positive in Immunoscintigraphy.J Nucl Med 32: 2194–2195, 1991

    PubMed  CAS  Google Scholar 

  14. Mach JP, Buchegger F, Forrni M, et al: Use of radiolabeled monoclonal anti CEA antibodies for the detection of human carcinomas by external photo-scanning and tomoscintigraphy.Immunol Today 2: 239–249, 1981

    Article  Google Scholar 

  15. Hnatowich DJ, Rusckowski M, Brill AB, et al: Pharmacokinetics in Patients of an Anti-Carcinoembryonic Antigen Antibody Radiolabeled with Indium-111 Using a Novel Diethyleneamine Pentaacetic Acid Chelator.Cancer Res 50: 7272–7278, 1990

    PubMed  CAS  Google Scholar 

  16. Sfakianakis GN, Garty II, Serafini AN: Radioantibodies for the Diagnosis and Treatment of Cancer; Radioimmunoimaging (RAI) and Radioimmunotherapy (RAT).Cancer Investigation 8: 381–405, 1990

    Article  PubMed  CAS  Google Scholar 

  17. Lamki LM: Radioimmunoscintigraphy of Cancer. Problems, Pitfalls, and Prospects. InNuclear Medicine Annual 1990, Freeman LM, (ed.), New York, Raven Press, pp 113–150, 1990

    Google Scholar 

  18. Duda RB, Beatty JD, Sheibani K, et al: Imaging of Human Colorectal Adenocarcinoma with Indium-Labeled Anticarcinoembryonic Antigen Monoclonal Antibody.Arch Surg 121: 1315–1319, 1986

    Article  PubMed  CAS  Google Scholar 

  19. Patt YY, Lamki LM, Shanken J, et al: Imaging with indium-111-Labeled Anticarcinoembryonic Antigen Monoclonal Antibody ZCE-025 of Recurrent Colorectal or Carcinoembryonic Antigen-producing Cancer in Patients with Rising Serum Carcinoembryonic Antigen Levels and Occult Metastases.J Clin Ocnol 8: 1246–1254, 1990

    CAS  Google Scholar 

  20. Abdel-Nabi HH, Chan HW, Doerr RJ: Indium-Labeled Anti-Colorectal Carcinoma Monoclonal Antibody Accumulation in Non-Tumored Tissue in Pstients with Colorectal Carcinoma.J Nucl Med 31: 1975–1979, 1990

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kubo, A., Nakamura, K., Katayama, M. et al. Pharmacokinetic analysis of antibody localization in human colon cancer: Comparison with immunoscintigraphy. Ann Nucl Med 6, 21–27 (1992). https://doi.org/10.1007/BF03164638

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03164638

Key words

Navigation