Advertisement

Radiometallating Antibodies and Autoantigenic Peptides

  • Janet A. Mercer-Smith
  • Jeanette C. Roberts
  • Dawn Lewis
  • Dean A. Cole
  • Sherri L. Newmyer
  • Louis D. Schulte
  • Patricia L. Mixon
  • Sandra A. Schreyer
  • Steve D. Figard
  • Timothy P. Burns
  • Daniel J. Mccormick
  • Vanda A. Lennon
  • Masatoshi Hayashi
  • David K. Lavallee

Abstract

We have developed methods to radiolabel large molecules, using porphyrins as bifunctional chelating agents for radiometals. The porphyrins are substituted with an N-benzyl group to activate them for radiometallation under mild reaction conditions. Porphyrins that have one functional group for covalent attachment to other molecules cannot cause crosslinking. We have examined the labeling chemistry for antibodies and have developed methods to label smaller biologically active molecules, such as autoantigenic peptides (fragments of the acetylcholine receptor), which are pertinent to myasthenia gravis research. The methods of covalent attachment of these bifunctional chelating agents to large molecules, the radiometallation chemistry, and biological characterization of the radiolabeled compounds will be discussed.

Keywords

Acetylcholine Receptor Covalent Attachment Purify Protein Derivative Free Base Porphyrin Simulated Physiological Condition 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Anderegg, G., 1965, Complexone XXXIX. Die Bildung-Enthalpie und -Entropie der Metallkomplexe der Diathylentriaminpentaacetat-Ions, Heiv. Chim. Acta, 48: 1722.CrossRefGoogle Scholar
  2. Anderson, G. W., Zimmerman, J. E., and Callahan, F. M., 1964, The use of esters of Nhydroxysucciminide in peptide synthesis, J. Am. Chem. Soc., 86: 1839.CrossRefGoogle Scholar
  3. Armitage, N. C., Perkins, A. C., Pimm, M.V., Wastie, M. L., Baldwin, R. W., and Hardcastel, J. D., 1985, Imaging of primary and metastatic colorectal cancer using an 111In-labelled antitumor monoclonal antibody (791T/36), Nucl. Med. Commun., 6: 623.PubMedCrossRefGoogle Scholar
  4. Avrameas, S., 1969, Coupling of enzymes to proteins with glutaraldehyde: use of the conjugates for the detection of antigens and antibodies, Immunochem., 6: 43.CrossRefGoogle Scholar
  5. Browne, E., Kairiki, J. M., amd Doebler, R. E. 1978, in “Table of Isotopes, 7th Edition,” C. M. Ledere and V. S. Shirley, eds., John Wiley, New York, pp. 196–198, 211–212.Google Scholar
  6. Bradford, M. M., 1976, A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding, Anal. Biochem., 72: 248.PubMedCrossRefGoogle Scholar
  7. Buchler, J. W., 1975, Static coordination chemistry of metalloporphyrins, in: “Porphyrins and Metalloporphyrins,” K. M. Smith, ed., Elsevier Scientific, New York, pp. 157–231.Google Scholar
  8. Childs, R. C. and Hnatowich, D. J., 1985, Optimum conditions for labelling of DTPAcoupled antibodies with technetium-99m, J. Nucl. Med., 26: 293.PubMedGoogle Scholar
  9. Clelland, C. O., Giles, D. D., Farley, T. D., Gee, Q., and Wright, J. R., 1986, The intravenous distribution of a radiolabeled potentially useful cluster ion of copper and penicillamine, Physiol. Chem. Phys. Med., 18: 37.Google Scholar
  10. Cole, D. A., Mercer-Smith, J. A., Schreyer, S. A., Norman, J. K., and Lavallee, D. K., 1990a, The biological characteristics of a water soluble porphyrin in rat lymph nodes, Nucl. Med. Biol., 17: 457.Google Scholar
  11. Cole, D. A., Mercer-Smith, J. A., Norman, J. K., Schreyer, S. A., Bullington, K. P., Roberts, J. C., and Lavallee, D. K., 1990b, Copper-67 labeled porphyrin localization in inflamed tissue, in: “Copper Bioavailability and Metabolism,”, C. Kies, ed., Plenum, New York, pp. 259–272.Google Scholar
  12. Cole, W. C., DeNardo, S. J., Meares, C. F., McCall, M. J., DeNardo, G. L., Epstein, A. L., O’Brien, H. A., and Moi, M. K., 1987, Comparative serum stability of radiochelates for antibody radiopharmaceuticals, J. Nucl. Med., 28: 83.PubMedGoogle Scholar
  13. Davis, M.-T. B and Preston, J. F., 1981, A simple modified carbodiimide method for conjugation of small molecular weight compounds to immunoglobulin G with minimal protein crosslinking, Anal. Biochem., 116: 402.PubMedCrossRefGoogle Scholar
  14. Eckelman, W. C. and Paik, C. H., 1989, Labeling antibodies with metals using bifunctional chelates, in: “Antibodies in Radiodiagnosis and Therapy,” M. R. Zalutsky, ed., CRC Press, Boca Raton, Florida, pp. 103–128.Google Scholar
  15. Keenan, A. M., Harbert, J. C., and Larson, S. M., 1985, Monoclonal antibodies in nuclear medicine, J. Nucl. Med., 26: 531.PubMedGoogle Scholar
  16. Kohler, G. and Milstein, C., 1975, Continuous cultures of fused cells secreting antibody of pre-defined specificity, Nature, 256: 495.PubMedCrossRefGoogle Scholar
  17. Laemmli, U. K., 1970, Cleavage of structural proteins during the assembly of the head of bacteriophage T4., Nature, 227: 680.PubMedCrossRefGoogle Scholar
  18. Lavallee, D. K., White, A., Diaz, A., Battioni, J. P., and Mansuy, D., 1986, Efficient metalloporphyrin synthesis under mild conditions using N-benzyl porphyrins, Tetrahedron Lett., 217, 3521.CrossRefGoogle Scholar
  19. Lennon, V. A., 1979, Immunological mechanisms in myasthenia gravis–a model of a receptor disease, in: “Clinical Immunology Update: Reviews for Physicians,” E. Franklin, ed., Elsevier, North Holland, New York, pp. 259–289.Google Scholar
  20. Lennon, V. A., McCormick, D. J., Lambert, E. H., Griesmann, G. E., and Atassi, M.Z., 1985, Region of peptide 125–147 of acetylcholine receptor a subunit is exposed at the neuromuscular junction and induces experimental autoimmune myasthenia gravis, T-cell immunity, and modulating autoantibodies, Proc. Natl. Acad. Sci., 82: 8805.PubMedCrossRefGoogle Scholar
  21. Margerum, D. W., Cayby, G. R., Weatherburn, D. C., and Pagenkopf, G. K., 1978, Kinetics and mechanisms of complex formation and ligand exchange, in: “Coordination Chemistry,” Vol. 2, ACS Monograph 174, American Chemical Society, Washington, D. C., p. 1.Google Scholar
  22. Maziere, B., Stulzaft, O., Verret, M. M., Comar, D., and Syrota, A., 1983, [55Co]- and [64Cu]-DTPA: New radiopharmaceuticals for quantitative tomocisternography, Inn. J. Appl. Radiat. Isot„ 34: 595.Google Scholar
  23. McCormick, D. J., Griesmann, G. E., Huang, Z.-X., Lambert, E. H., Lennon, V. A., 1987, Myasthenogenicity of human acetylcholine receptor a—subunit peptide 125–147 does not does not require intramolecular disulfide cyclization, J. Immunology, 139: 2615.Google Scholar
  24. Mercer-Smith, J. A., Moody, D. C., O’Brien, H. A., and Taylor, W. A., 1984, Synthesis of copper-67 meso-tetra(4-carboxyphenyl) porphine, Abstract NUCL-52, in: “Proceedings of the 188th American Chemical Society National Meeting,” Philadelphia, PA, August 26–31.Google Scholar
  25. Mercer-Smith, J. A., Roberts, J. C., Figard, S. D., and Lavallee, D. K. 1988, The development of copper-67-labeled porphyrin-antibody conjugates, in: “Antibody-Mediated Delivery Systems,” J. D. Rodwell, ed., Marcel Dekker, New York, pp. 317–352.Google Scholar
  26. Mercer-Smith, J. A., Cole, D. A., Roberts, J. C., Lewis, D., Behr, M. J., and Lavallee, D. K., 1990, The biodistribution of radiocopper-labeled compounds, in: “Copper Bioavailability and Metabolism,” C. Kies, ed., Plenum, New York, 1990, pp. 103–121.Google Scholar
  27. Paik, C. H., Ebbert, M. A., Murphy, P. R., Lassman, C. R., Reba, R. C., Eckelman, W. C., Pak, K. Y., Powe, J., Steplewski, Z., and Koprowski, H., 1983, Factors influencing DTPA conjugation with antibodies by cyclic DTPA anhydride, J. Nucl., Med., 24: 1158.PubMedGoogle Scholar
  28. Paul, R. and Anderson, G. W., 1960, N,N’-Carbonyldiimidazole, a new peptide forming reagent, J. Am. Chem. Soc., 82: 4596.CrossRefGoogle Scholar
  29. Popot, J.-L. and Changeux, J.-P., 1984, Nicotinic receptor of acetylcholine: Structure of an oligomeric integral membrane protein, Physiol. Rev., 64: 1162.PubMedGoogle Scholar
  30. Raman, S., and Pinajian, J. J., 1969, Decay of 67Cu, Nucl. Phys., A131: 393.CrossRefGoogle Scholar
  31. Roberts, J. C., Figard, S. D. Mercer-Smith, J. A., Svitra, Z. V., Anderson, W. L., and Lavallee, D. K., 1987, Preparation and characterization of copper-67 porphyrinantibody conjugates, J. Immunol. Methods, 105: 153.PubMedCrossRefGoogle Scholar
  32. Roberts, J. C., Newmyer, S. L., Mercer-Smith, J. A., Schreyer, S. A., and Lavallee, D. K., 1989, Labeling antibodies with copper radionuclides using N-4-nitrobenzyl-5(4-carboxyphenyl)-10,15,20-tris(4-sulfophenyl) porphine, Int. J. Appl. Radiat. Isot., 40: 775.CrossRefGoogle Scholar
  33. Roberts, J. C., Adams, Y. A., Tomalia, D. A., Mercer-Smith, J. A., and Lavallee, D. K., 1990, Using starburst dendrimers as linker molecules to radiolabel antibodies, Bioconjugate Chem., 2: 305.CrossRefGoogle Scholar
  34. Ruben, S., Kamen, M. D., Allen, M. B., and Nahinsky, P., 1942, Some exchange experiments with radioactive tracers, J. Am. Chem. Soc., 64: 2297.CrossRefGoogle Scholar
  35. Sands, H. and Gallagher, B. M., 1989, Physiological, pharmacological, and immunological aspects of antibody targeting, in “Antibodies in Radiodiagnosis and Therapy,” M. R. Zalutsky, ed., CRC Press, Boca Raton, Florida, pp. 129–151.Google Scholar
  36. Taylor Jr., A., Milton, W., Eyre, H., Christian, P., Wu, F., Hagan, P., Alazraki, N., Datz, F. L., and Unger, M., 1988, Radioimmunodetection of human melanoma with indium-111-labeled monoclonal antibody, J. Nucl. Med., 29: 329.PubMedGoogle Scholar
  37. Tsugikazu, T., Suzuki, T., and Tokunaga, E., 1981, Cleavage of human serum immunoglobulin G. by an immobilized pepsin preparation, Biochim. Biophys. Acta, 660: 186–192.CrossRefGoogle Scholar
  38. Vandlen, R. L., Wu, WC.-S., Eisenach, J.C., and Raftery, M.A., 1979, Studies of the composition of purified Torpedo californica acetylcholine receptor and its subunits, Biochemistry, 18: 1845.PubMedCrossRefGoogle Scholar
  39. Wessels, B. W. and Rogus, R. D., 1984, Radionuclide selection and model absorbed dose calculations for radiolabeled tumor associated antibodies, Med. Phys., 11: 638.PubMedCrossRefGoogle Scholar
  40. Yokoyama, K., Carrasquillo, J. A., Chang, A. E., Colcher, D., Roselli, M., Sugarbaker, P., Sindelar, W., Reynolds, J. C., Perentesis, P., Gansow, O. A., Francis, B., Adams, R., Finn, R., Schlom, F., and Larson, S. M., 1989, Differences in biodistribution of indium-111 and iodine-131-labeled B72.3 monoclonal antibodies in patients with colorectal cancer, J. Nucl. Med., 30: 320.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • Janet A. Mercer-Smith
    • 1
  • Jeanette C. Roberts
    • 1
  • Dawn Lewis
    • 1
  • Dean A. Cole
    • 1
  • Sherri L. Newmyer
    • 1
  • Louis D. Schulte
    • 1
  • Patricia L. Mixon
    • 1
  • Sandra A. Schreyer
    • 1
  • Steve D. Figard
    • 1
  • Timothy P. Burns
    • 1
  • Daniel J. Mccormick
    • 2
  • Vanda A. Lennon
    • 2
  • Masatoshi Hayashi
    • 2
  • David K. Lavallee
    • 3
  1. 1.Nuclear and Radiochemistry Group (INC-11)Los Alamos National LaboratoryLos AlamosUSA
  2. 2.Neuroimmunology Laboratory, Departments of Immunology and NeurologyMayo ClinicRochesterUSA
  3. 3.Provost’s Office, Hunter CollegeCity University of New YorkNew YorkUSA

Personalised recommendations