Monoclonal Antibody Labeling with Indium-111 and Gadolinium via DTPA Chelation on Selective and Nonselective Sites of the Antibody

  • J. C. Saccavini
  • C. Curtet
  • J. Bohy
  • C. Tellier
Conference paper
Part of the NATO ASI Series book series (NSSA, volume 152)


The recent development of hybridoma technology has allowed the production of large quantities of monoclonal antibodies with predefined specificity (1); this has resulted in a renewed interest in their use as immunodiagnostic reagents. Radiolabeled monoclonal antibodies are today widely used for specific localization of tumors and metastases (2–4). The success of immunoscintigraphy has generated interest in the application of monoclonal antibodies as specific carriers of paramagnetic agents for magnetic resonance imaging (MRI). MRI has certain advantages over immunoscintigraphy — no ionizing radiation is involved, and the spatial resolution is higher and equals that of computed tomography. Early investigators felt that differences in relaxation times between malignant tumor and normal tissue made contrast agents unnecessary. However, despite the intrinsic tissue contrast, the injection of contrast agents, e.g., gadolinium-diethylenetriaminepentaacet ic acid (Gd-DTPA) increases the sensitivity and specificity of MR imaging as demonstrated by several investigators (5–7). Of the available paramagnetic ions, gadolinium has the greatest effect on proton relaxation time. Its association with DTPA produces a compound that gives a marked reduction in the proton relaxation time in vitro and in vivo and produces minimal acute toxicity with imaging doses (8,9).


Nude Mouse Tumor Uptake Carbohydrate Moiety Colorectal Tumor Cell Polymeric Chelate 
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  1. 1.
    G. Kohler and C. Milstein, Continuous cultures of fused cells secreting antibody of predefined specificity, Nature 256:495 (1975).PubMedCrossRefGoogle Scholar
  2. 2.
    J. F. Chatal, J. C. Saccavini, P. Fumoleau, J. Y. Douillard, C. Curtet, M. Kremer, B. Le Mevel and H. Koprowski, Immunoscintigraphy of colon carcinoma, J. Nucl. Med. 25:307 (1984).PubMedGoogle Scholar
  3. 3.
    J. P. Mach, J. F. Chatal, J. D. Lumbroso, F. Buchegger, M. Forni, J. Ritschard, C. Berche, J. Y. Douillard, S. Carrel, M. Herlyn, Z. Steplewski and H. Koprowski, Tumor localization in patients by radiolabeled monoclonal antibodies against colon carcinoma, Cancer Res. 43:5593 (1983).PubMedGoogle Scholar
  4. 4.
    D. M. Goldenberg, F. Deland, Kim, S. Bennet, F. J. Primus, J. R. Yan Nager, N. Estes, P. DeSimoni and P. Rayburn, Use of radiolabeled antibodies to carcinoembryonic antigen for detection and localization of diverse cancers by external photoscanning, N. Engl. J. Med. 298:1384 (1978).PubMedCrossRefGoogle Scholar
  5. 5.
    G. Strich, P. L. Hagan, K. H. Gerber and R. A. Slutsky, Tissue distribution and magnetic resonance spin lattice relaxation effects of Gd-DTPA, Radiol. 154:723 (1985).Google Scholar
  6. 6.
    V. M. Runge, J. A. Clanton, C. A. Price, C. J. Wehr and A. E. James, The use of Gd-DTPA as a perfusion agent and marker of blood brain barrier disruption, Magn. Res. Imag. 3:43 (1985).CrossRefGoogle Scholar
  7. 7.
    G. E. Wesley, C. B. Higgins, M. T. McNamara, B. L. Engelstad, M. J. Lipton, R. Sievers, R. L. Ehman, J. Lovin and R. C. Brasch, Effect of Gd-DTPA on the magnetic relaxation times of normal and infarcted myocardium, Radiol. 153:165 (1984).Google Scholar
  8. 8.
    G. Wolf, Tissue specific nuclear magnetic resonance contrast agents, Invest. Radiol. 19 (Suppl). S 148 (1984).Google Scholar
  9. 9.
    R. A. Slutsky, T. Peterson, J. J. Brown and G. Strich, Hemodynamic effects of rapid and slow infusions of MnCl2 and Gd-DTPA in dogs, Radiol. 154:733 (1985).Google Scholar
  10. 10.
    J. Y. Douillard, J. F. Chatal, J. C. Saccavini, C. Curtet, M. Kremer, P. Peuvrel and H. Koprowski, Pharmacokinetic study of radiolabeled anti-colorectal carcinoma monoclonal antibodies in tumor bearing nude mice, Eur. J. Nucl. Med. 11:107 (1985).PubMedCrossRefGoogle Scholar
  11. 11.
    H. Koprowski, Z. Steplewski, K. Mitchell, D. Herlyn and P. Fuhrer, Colorectal carcinoma antigens detected by hybridoma antibodies, Somatic Cell Genet. 5:957 (1979).PubMedCrossRefGoogle Scholar
  12. 12.
    J. L. Magnani, M. Brockhauss, D. F. Smith, D. Herlyn, M. Blaszczyk, K. F. Mitchell, Z. Steplewski and H. Koprowski, A monosialoganlioside is a monoclonal antibody defined antigen of colon carcinoma, Science 212:55 (1981).PubMedCrossRefGoogle Scholar
  13. 13.
    D. J. Hnatowich, W. W. Layne and R. L. Childs, The preparation and labeling of DTPA coupled albumin, Int. J. Appl. Radiat. Isot. 33:327 (1982).PubMedCrossRefGoogle Scholar
  14. 14.
    U. Bachrach and B. Reches, Enzymic assay for spermine and spermidine, Anal. Biochem. 17:38 (1966).PubMedCrossRefGoogle Scholar
  15. 15.
    E. Ishikawa, M. Imagawa, S. Hashida, S. Yoshitake, Y. Hamaguchi and N. Tetsuo, Enzyme labeling of antibodies and their fragments for enzyme immunoassay and immunohistochemical staining, J. Immunoassay 4 (3), 209 (1983).PubMedCrossRefGoogle Scholar
  16. 16.
    W. A. Tompkins, A. M. Watrach and J. D. Schmale, J. Natl. Can. Inst. 52:1101 (1974).Google Scholar
  17. 17.
    P. P. Pitmer and J. S. Whidby, Simulation of nuclear magnetic resonance spin lattice relaxation time measurements for examination of systematic and random error effects, Anal. Chem. 51:2203 (1979).CrossRefGoogle Scholar
  18. 18.
    C. H. Paik, M. A. Ebbert, P. R. Murphy, C. R. Lassman, R. C. Reba, W. C. Eckelman, K. Y. Pak, J. Powe, Z. Steplewski and H. Koprowski, Factors influencing DTPA conjugation to antibodies via cyclic DTPA anhydride, J. Nucl. Med. 24:1158 (1983).PubMedGoogle Scholar
  19. 19.
    G. Strich, P. L. Hagan, K. H. Gerber and R. A. Slutsky, Tissue distribution and resonance spin lattice relaxation effects of Gd-DTPA, Radiol. 154:723 (1985).Google Scholar
  20. 20.
    I. Solomon and N. Bloemberger, Nuclear magnetic interactions in the HF Molecule, J. Chem. Phys. 25:261 (1956).CrossRefGoogle Scholar
  21. 21.
    S. Halpern and P. Hagan, Effect of protein mass on the pharmaco-kinetics of murine monoclonal antibodies, J. Nucl. Med. 26:818 (1985).PubMedGoogle Scholar
  22. 22.
    H. J. Weimann, R. C. Brasch, W. R. Press and G. E. Vesley, Characteristics of Gd-DTPA complex: a potential NMR contrast agent, Am. J. Rad. 142:625 (1984).Google Scholar
  23. 23.
    W. T. Anderson-Bery, M. Strand, T. E. Lempert, A. E. Rosenbaum and P. M. Joseph, Nuclear magnetic resonance and gamma camera tumor imaging using gadolinium labeled monoclonal antibodies, J. Nucl. Med. 27:829 (1986).Google Scholar
  24. 24.
    P. Shreve and A. M. Aisen, Monoclonal antibodies labeled with polymeric paramagnetic ion chelates, Magn. Reson. Med. 3:336 (1986).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1988

Authors and Affiliations

  • J. C. Saccavini
    • 1
  • C. Curtet
    • 1
    • 2
  • J. Bohy
    • 1
  • C. Tellier
    • 1
    • 3
  1. 1.ORIS IndustrieGif sur YvetteFrance
  2. 2.UER MedicineU-211 INSERMNantesFrance
  3. 3.RMN et Radioactivite Chimique U A 472NantesFrance

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