Antibody-Hapten Complexes for Imaging

  • David A. Goodwin
Conference paper
Part of the NATO ASI Series book series (NSSA, volume 152)

Abstract

The tumor uptake of covalently-radiolabeled monoclonal antibodies and their fragments is directly related to the integral of blood concentration over time, the highest tumor concentrations being obtained with whole antibody which has the longest biological half-life in the plasma (1,2,3). Higher tumor to background ratios can be obtained with F(ab′)2 or Fab fragments that disappear more rapidly than whole antibody from the blood but only at the cost of a lower absolute tumor concentration (1,2). Tumor concentration of whole antibody reaches a maximum in approximately one or two days but the major fraction continues to circulate for many days after due to the slow excretion of covalently labeled proteins. This prolonged retention of activity adds a large amount of useless radiation exposure to normal tissue, especially liver, spleen, and bone marrow.

Keywords

Permeability Lymphoma EDTA Recombination Radionuclide 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    A. B. Wilbanks, J. A. Peterson, S. Miller, L. Kauffman, D. Ortendahl, and I. L. Ceriani, Localization of mammary tumors in vivo with 131-labeled Fab fragments of antibodies against mouse mammary epithelial (MME) antigens, Cancer 48:1768–1775 (1981).PubMedCrossRefGoogle Scholar
  2. 2.
    R. L. Wahl, C. W. Parker, and G. W. Philpott, Improved radioimaging and tumor localization with monoclonal F(ab)2, J. Nuc1. Med. 24:316–325 (1983).Google Scholar
  3. 3.
    W. B. Nelp, J. F. Eary, P. Beaumier, K. A. Krohn, I. Hellstrom, and K. E. Hellstrom, Antibody deposition in tumor in relation to blood clearance using a nephrectomized mouse model, J. Nucl. Med. 26:67 (1985). Abstract.Google Scholar
  4. 4.
    D. T. Reardan, C. F. Meares, D. A. Goodwin, M. McTigue, G. S. David, M. R. Stone, J. P. Leung, R. M. Bartholomew, and J. M. Frincke, Antibodies against metal chelates, Nature 316:265–268 (1985).PubMedCrossRefGoogle Scholar
  5. 5.
    D. A. Goodwin, C. F. Meares, W. Chaovapong, M. McTigue, and M. J. McCall, Bifunctional chelates with a haptenic function bind reversibly to monoclonal antibody WC3A11 for radiopharmaceutical delivery, J. Nucl. Med. 27:938 (1986). Abstract.Google Scholar
  6. 6.
    D. A. Goodwin, C. F. Meares, M. McTigue, and G. S. David, Monoclonal antibody hapten radiopharmaceutical delivery, Nucl. Med. Comm. (In press).Google Scholar
  7. 7.
    D. A. Goodwin, S. I. Smith, C. F. Meares, G. S. David, M. McTigue, and R. A. Finston, Chelate chase of radiopharmaceuticals reversibly bound to monoclonal antibodies improves dosimetry, Fourth International Radiopharmaceutical Dosimetry Symposium, Oak Ridge TN, November 5–8, 1985, Proc. Conf-851113-ORAV, 1986, pp.477–492.Google Scholar
  8. 8.
    S. W. Burcheil and B. A. Rhodes, eds., “Radioimmunoimaging and Radioimmunotherapy,” Elsevier, New York (1983).Google Scholar
  9. 9.
    F. H. DeLand, E. E. Kim, G. Simmons, and D. M. Goldenberg, Imaging approach in radioimmunodetection, Cancer Res. 40:3046–3049 (1980).PubMedGoogle Scholar
  10. 10.
    D. A. Goodwin, C. F. Meares, C. I. Diamanti et al., Use of specific antibody for rapid clearance of circulating blood background from radiolabeled tumor imaging proteins, Eur. J. Nucl. Med. 9:209–215 (1984).PubMedCrossRefGoogle Scholar
  11. 11.
    R. H. J. Begent, A. J. Green, K. D. Bagshawe, B. E. Jones, P. A. Keep, F. Searle, R. F. Jewkes, G. M. Barratt, and B. E. Ryman, Liposomally entrapped second antibody improves tumour imaging with radiolabeled (first) antitumour antibody, Lancet 2:739–742 (1982).PubMedCrossRefGoogle Scholar
  12. 12.
    J. N. Weinstein, R. J. Parker, A. M. Keenan et al., Monoclonal antibodies in the lymphatics: Toward the diagnosis and therapy of tumor metastases, Science 218:1334–1337 (1982).PubMedCrossRefGoogle Scholar
  13. 13.
    D. A. Goodwin, C. F. Meares, M. J. McCall, M. K. Haseman, M. McTigue, C. I. Diamanti, and W. Chaovapong, Chelate conjugates of monoclonal antibodies for imaging lymphoid structures in the mouse. J. Nucl. Med. 26:493–502 (1985).PubMedGoogle Scholar
  14. 14.
    M. K. Haseman, D. A. Goodwin, C. F. Meares, M. S. Kaminski, T. G. Wensel, M. J. McCall, and R. Levy, Metabolizable In-111 chelate conjugated anti-idiotype monoclonal antibody for radioimmunodetection of lymphoma in mice, Eur. J. Nucl. Med., Submitted.Google Scholar
  15. 15.
    D. A. Goodwin, C. F. Meares, M. McTigue, and M. R. Stone, Hapten monoclonal antibody complexes as drug carrier systems, Amer. Chem. Soc. Annual National Meeting, Miami Beach, Florida, 48 (1985). Abstract.Google Scholar
  16. 16.
    D. A. Goodwin, C. F. Meares, G. S. David, M. McTigue, M. J. McCall, J. M. Frincke, M. R. Stone, R. M. Bartholomew, and J. P. Leung, Monoclonal antibodies as reversible equilibrium carriers of radiopharmaceuticals, Int. J. Nucl. Med. Biol. 13:383–391 (1986).Google Scholar
  17. 17.
    W. P. Arend and F. J. Silverblatt, Serum disappearance and catabolism of homologous immunoglobulin fragments in rats, Clin. Exp. Immunol. 22:502–513 (1975).PubMedGoogle Scholar
  18. 18.
    A. A. Epenetos, Antibody guided lymphangiography in the staging of cervical cancer, Br. J. Cancer 51:805–808 (1985).PubMedCrossRefGoogle Scholar
  19. 19.
    D. H. Schmidt, B. M. Kaufman, and V. P. Butler, Jr., Persistence of hapten-antibody complexes in the circulation of immunized animals after a single intravenous injection of hapten, J. Exp. Med. 139: 278–294 (1974).PubMedCrossRefGoogle Scholar
  20. 20.
    S. A. Berson, R. S. Yalow, A. Bauman, M. A. Rothschild, and K. Newerly, Insulin-I131 metabolism in human subjects: Demonstration of insulin binding globulin in the circulation of insulin treated subjects, J. Clin. Invest. 35:170 (1956).PubMedCrossRefGoogle Scholar
  21. 21.
    D. A. Goodwin, C. F. Meares, C. I. Diamanti et al., Biological properties of molecules labelled with metal ions using bifunctional chelates, in: “Medical Radionuclide Imaging,” IAEA, Vienna, 2:61–69 (1976).Google Scholar
  22. 22.
    C. F. Meares, D. T. Reardan, M. T. McCall et al., Conjugation of antibodies with bifunctional chelating agents bearing isothiocyanate or bromoacetamide groups and subsequent addition of metal ions. Anal. Biochem. 142:68–78 (1984).PubMedCrossRefGoogle Scholar
  23. 23.
    M. K. Moi, C. F. Meares, M. J. McCall, W. C. Cole, and S. J. DeNardo, Copper chelates as probes of biological systems: Stable copper complexes with a macrocyclic bifunctional chelating agent, Anal. Biochem. 148:249–253 (1985).PubMedCrossRefGoogle Scholar
  24. 24.
    C. Milstein and A. C. Cuello, Hybrid hybridomas and their use in immunohistochemistry, Nature (London) 305:537–540 (1983).CrossRefGoogle Scholar
  25. 25.
    M. Brennan, P. F. Davison, and H. Paulus, Preparation of bispecific antibodies by chemical recombination of monoclonal immunoglobulin G1 fragments, Science 229:81 (1985).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1988

Authors and Affiliations

  • David A. Goodwin
    • 1
    • 2
  1. 1.Veterans Administration Medical CenterPalo AltoUSA
  2. 2.Stanford University School of MedicinePalo AltoUSA

Personalised recommendations