Radiochemistry of Monoclonal Antibody Labeling

  • Lee C. Washburn

Abstract

Monoclonal antibodies (MoAbs) to tumor-associated antigens are useful for targeting radionuclides to tumors for both diagnostic and therapeutic applications. MoAbs have been radiolabeled with numerous gamma-, beta-, alpha-, positron-, and Auger electron-emitting radionuclides. Key radionuclide examples for each type of emission are shown in Table 1. Some radionuclides, e.g., iodine-131 (131I), exhibit both beta and gamma emissions and, therefore, may be used for both radioimmunodiagnosis (RID) and radioimmunotherapy (RIT). The chemical properties of the radionuclides listed in Table 1 are very different, and consequently different radiolabeling methods must be used. The purposes of this paper are to review the radiochemistry involved in labeling MoAbs with several of the radionuclides commonly used in nuclear medicine and to examine some special techniques aimed at increasing the tumor-to-nontumor concentration ratios obtained with radiolabeled MoAbs.

Keywords

Active Ester Sodium Cyanoborohydride Bifunctional Chelate Oligosaccharide Moiety Bifunctional Chelate Agent 
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.

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References

  1. 1.
    Pressman D., Day, E.D., and Blau, M. The use of paired labeling in the determination of tumor-localizing antibodies. Cancer Res. 17: 845–850 (1957).PubMedGoogle Scholar
  2. 2.
    Fraker, P.J. and Speck, J.C. Protein and cell membrane iodinations with a sparingly soluble chloroamide, 1,3,4,6-tetrachloro-3a,6adiphenylglycoluril. Biochem. Biophys. Res. Commun. 80: 849–857 (1978).PubMedCrossRefGoogle Scholar
  3. 3.
    Markwell, M.A.K. A new solid-state reagent to iodinate proteins. I. Conditions for the efficient labeling of antiserum. Anal. Biochem. 125: 427–432 (1982).Google Scholar
  4. 4.
    Marchalonis, J.J. An enzymic method for the trace iodination of immunoglobulins and other proteins. Biochem. J. 113: 299–305 (1969).PubMedGoogle Scholar
  5. 5.
    Order, S.E. Monoclonal antibodies: Potential role in radiation therapy and oncology. Int. J. Radiat. Oncol. Biol. Phys. 8: 1193–1201 (1982).Google Scholar
  6. 6.
    Zalutsky, M.R. and Narula, A.S. A method for the radiohalogenation of proteins resulting in decreased thyroid uptake of radioiodine. Appl. Radiat. Isot. 38: 1051–1055 (1987).CrossRefGoogle Scholar
  7. 7.
    Wilbur, D.S., Hyalarides, M.D., Hadley, S., Schroeder, J., and Fritzberg, A.R. A general approach to radiohalogenation of proteins. Radiohalogenation of organometallic intermediates containing protein reactive substituents. J. Label. Compds. Radiopharm. 26: 316–318 (1989).CrossRefGoogle Scholar
  8. 8.
    Srivastava, P.C., Buchsbaum, D.J., Allred, J.F., Brubaker, P.G., Hanna, D.E., and Spicker, J.K. A new conjugating agent for radioiodination of proteins: Low in vivo deiodination of radiolabeled antibody in a tumor model. BioTechnioues 8: 536–545 (1990).Google Scholar
  9. 9.
    Sundberg, M.W., Meares, C.F., Goodwin, D.A., and Diamanti, C.I. Selective binding of metal ions to macromolecules using bifunctional analogues of EDTA. J. Med. Chem. 17: 1304–1307 (1974).PubMedCrossRefGoogle Scholar
  10. 10.
    Krejcarek, G.E. and Tucker, K.L. Covalent attachment of chelating groups to macromolecules. Biochem. Biophys. Res. Comm. 77: 581–585 (1977).PubMedCrossRefGoogle Scholar
  11. 11.
    Hnatowich, D.J., Layne, W.W., and Childs, R.L. The preparation and labeling of DTPA-coupled albumin. Int. J. Appl. Radiat. Isot. 33: 327–332 (1982).PubMedCrossRefGoogle Scholar
  12. 12.
    Hnatowich, D.J., Layne, W.W., Childs, R.L., Lanteigne, D., and Davis, M.A. Radioactive labeling of antibody: A simple and efficient method. Science 220: 613–615 (1983).PubMedCrossRefGoogle Scholar
  13. 13.
    Buckley, R.G. and Searle, F. An efficient method for labelling antibodies with 111In. FEBS Lett. 166: 202–204 (1984).PubMedCrossRefGoogle Scholar
  14. 14.
    Paxton, R.J., Jakowatz, J.G., Beatty, J.D., Beatty, B.G., Vlahos, W.G., Williams, L.E., Clark, B.R., and Shively, J.E. Highspecific-activity 11.1 In-labeled anticarcinoembryonic antigen monoclonal antibody: Improved method for the synthesis of diethylenetriaminepentaacetic acid conjugates. Cancer Res. 45: 5694–5699 (1985).PubMedGoogle Scholar
  15. 15.
    Washburn, L.C., Lee, Y-C.C., Sun, T.T.H., Byrd, B., Crook, J.E., Stabin, M.G., and Steplewski, Z. Preclinical assessment of 9°Y-labeled monoclonal antibody C017–1A, a potential agent for radioimmunotherapy of colorectal carcinoma. Nucl. Med. Biol. 15: 707–711 (1988).Google Scholar
  16. 16.
    Roselli, M., Schlom, J., Gansow, 0.A., Raubitschek, A., Mirzadeh, S., Brechbiel, M.W., and Colcher, D. Comparative biodistributions of yttrium-and indium-labeled monoclonal antibody B72.3 in athymic mice bearing human colon carcinoma xenografts. J. Nucl. Med. 30: 672–682 (1989).PubMedGoogle Scholar
  17. 17.
    Washburn, L.C., Sun, T.T.H., Lee, Y-C.C., Byrd, B.L., Holloway, E.G., Crook, J.E., Stubbs, J.B., Stabin, M.G., Brechbiel, M.W., Gansow, 0.A., and Steplewski, Z. Comparison of five bifunctional chelate techniques for °Y-labeled monoclonal antibody C017–1A. Nucl. Med. Biol. (in press).Google Scholar
  18. 18.
    Meares, C.F., McCall, M.J., Reardan, D.T., Goodwin, D.A., Diamanti, C.I., and McTigue, M. Conjugation of antibodies with bifunctional chelating agents: Isothiocyanate and bromoacetamide reagents, methods of analysis, and subsequent addition of metal ions. Anal. Biochem. 142: 68–78 (1984).PubMedCrossRefGoogle Scholar
  19. 19.
    Brechbiel, M.W., Gansow, O.A., Atcher, R.W., Schlom, J., Estaban, J. Simpson, D., and Colcher, D. Synthesis of 1-(p-isothiocyanato- benzyl) derivatives of DTPA and EDTA. Antibody labeling and tumor imaging studies. Inorg. Chem. 25: 2772–2781 (1986).Google Scholar
  20. 20.
    Rodwell, J.D., Alvarez, V.L., Lee, C., Lopes, A.D., Goers, J.W.F., King, H.D., Powsner, H.J., and McKearn, T.J. Site-specific covalent modification of monoclonal antibodies: In vitro and in vivo evaluations. Proc. Natl. Acad. Sci. USA 83: 2632–2636 (1986).PubMedCrossRefGoogle Scholar
  21. 21.
    Deshpande, S.V., DeNardo, S.J., Kukis, D.L., Moi, M.K., McCall, M.J., DeNardo, G.L., and Meares, C.F. Yttrium-90-labeled monoclonal antibody for therapy: Labeling by a new macrocyclic bifunctional chelating agent. J. Nucl. Med. 31: 473–479 (1990).PubMedGoogle Scholar
  22. 22.
    Gansow, 0.A., Kumar, K., Brechbiel, M.W., Mirzadeh, S., Anderson-Berg, W.T., Ruegg, C.L., and Strand, M. Bismuth complexes of the bifunctional DTPA’s and of the polyazacycloalkane-N-acetic acid DOTA. J. Nucl. Med. 31:824 (1990) abstract.Google Scholar
  23. 23.
    Washburn, L.C., Lee, Y-C.C., Sun, T.T.H., Byrd, B.L., Holloway, E.C., Crook, J.E., Brechbiel, M.W., Gansow, O.A., and Steplewski, Z. pNH2-Bz-DOTA-3A, a new bifunctional chelate reagent for labeling monoclonal antibodies with Y-90. J. Nucl. Med. 31:824 (1990) abstract.Google Scholar
  24. 24.
    Deshpande, S.V., DeNardo, S.J., Meares, C.F., McCall, M.J., Adams, G.P., Moi, M.K., and DeNardo, G.L. Copper-67-labeled monoclonal antibody Lym-1, a potential radiopharmaceutical for cancer therapy: Labeling and biodistribution in RAJI tumored mice. J. Nucl. Med. 29: 217–225 (1988).PubMedGoogle Scholar
  25. 25.
    Ehrhardt, G.J., Ketring, A.R., Turpin, T.A., Razavi, M.S., Vanderheyden, J.L., and Fritzberg, A.R. An improved tungsten188/rhenium-188 generator for therapeutic applications. J. Nucl. Med. 28:656–657 (1987) abstract.Google Scholar
  26. 26.
    Callahan, A.P., Rice, D.E. and Knapp, F.F., Jr. Rhenium-188 for therapeutic applications from an alumina-based tungsten188/rhenium-188 radionuclide generator. NucCompact-Eur./Amer. Comm. Nucl. Med. 20: 3–6 (1989).Google Scholar
  27. 27.
    Rhodes, B.A., Torvestad, D.A., Burchiel, S.W., and Austin, R.K. A kit for direct labeling of antibody and antibody fragments with Tc-99m. J. Nucl. Med. 21:P54 (1980) abstract.Google Scholar
  28. 28.
    Rhodes, B.A. and Burchiel, S.W. Radiolabeling of antibodies with technetium-99m. In: “Radioimmunoimaging and Radioimmunotherapy,” Burchiel, S.W. and Rhodes, B.A., eds., Elsevier, New York, pp. 207–222 (1983).Google Scholar
  29. 29.
    Sundrehage, E. Formation of 99mTc-immunoglobulin G complexes free from radiocolloids, quality controlled by radioimmunoelectrophoresis. Eur. J. Nucl. Med. 7: 549–552 (1982).CrossRefGoogle Scholar
  30. 30.
    Griffiths, G.L., Chang, C.-H., Newman, E.S., Ostella, F., Hansen, H.J., and Goldenberg, D.M. The generation of rhenium-labeled antibodies by direct labeling methods. J. Nucl. Med. 31:905 (1990) abstract.Google Scholar
  31. 31.
    Childs, R.L. and Hnatowich, D.J. Optimal conditions for labeling of DTPA-coupled antibodies with technetium-99m. J. Nucl. Med. 26: 293–295 (1985).PubMedGoogle Scholar
  32. 32.
    Fritzberg, A.R., Abrams, P.G., Beaumier, P.L., Kasina, S., Morgan, A.C., Rao, T.N., Reno, J.M., Sanderson, J.A., Srinivasan, A., Wilbur, D.S., and Vanderheyden, J.-L. Specific and stable labeling of antibodies with technetium-99m with a diamide dithiolate chelating agent. Proc. Natl. Acad. Sol.. USA 85: 4025–4029 (1988).CrossRefGoogle Scholar
  33. 33.
    Vanderheyden, J.-L., Gofinch, S., Srinivasan, A., Su, F.M., Venkatesan, P., Woodhouse, C., Sanderson, J., Woods, M., Wilkening, D., Beaumier, P., Reno, J., and Fritzberg, A. Preparation and characterization of Re-186 labeled NR-00–02 F(ab’)2: A new anti-CEA antibody fragment for radioimmunotherapy. J. Nucl. Med. 30:793 (1989) abstract.Google Scholar
  34. 34.
    Haseman, M.K., Goodwin, D.A., Meares, C.F., Kaminski, M.S., Wensel, T.G., McCall, M.J., and Levy, R. Metabolizable 111In chelate- conjugated anti-idiotype monoclonal antibody for radioimmunodetection of lymphoma in mice. Eur. J. Nucl. Med. 12: 455–460 (1986).PubMedCrossRefGoogle Scholar
  35. 35.
    Paik, C.H., Wu, R.S., Quadri, S.M., Goldenberg, D.M., and Reba, R.C. Introduction of diester linkage between antibody and DTPA for investigation of its effect on biodistribution. J. Label. Compds. Radiopharm. 26: 314–315 (1989).CrossRefGoogle Scholar
  36. 36.
    Quadri, S.M., Zhang, Y., Klein, J.L., Leichner, P.K., and Williams, J.R. Linker-modulated biodistribution of In-111 and Y-90 labeled MoAb antiferritin immunoconjugates in nude mice. J. Nucl. Med. 31:823 (1990) abstract.Google Scholar
  37. 37.
    Hnatowich, D.J., Virzi, F., and Rusckowski, M. Investigations of avidin and biotin for imaging applications. J. Nucl. Med. 28: 1294–1302 (1987).PubMedGoogle Scholar
  38. 38.
    Goodwin, D.A., Meares, C.F., McCall, M.J., and McTigue, M. Pretargeted immunoscintigraphy with chimeric antibodies. J. Nucl. Med. 28:561 (1987) abstract.Google Scholar
  39. 39.
    Stickney, D.R., Frincke, J.M., Slater, J.B., Ahlem, C.N., Merchant, B., and Slater, J.M. Bifunctional antibody technology: Clinical applications for CEA expressing tumors. In: Abstracts, Third International Conference on Monoclonal Antibody Immunoconjugates for Cancer, San Diego, California, p. 24 (1988).Google Scholar
  40. 40.
    Lamki, L.M., Patt, Y.Z. Rosenblum, M.G., Shanken, L.J., Thompson, L.B., Schweighardt, S.A., Frincke, J.M., and Murray, J.L. Metastatic colon cancer: Radioimmunoscintigraphy with a stabilized In-111-labeled F(ab’)2 fragment of an anti-CEA monoclonal antibody. Radiology 174: 147–151 (1990).PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • Lee C. Washburn
    • 1
  1. 1.Medical Sciences DivisionOak Ridge Associated UniversitiesOak RidgeUSA

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