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Radiohalogenation of Monoclonal Antibodies: Experiences with Radioiodination of Monoclonal Antibodies for Radioimmunotherapy

  • James C. Reynolds
  • Patrick Maloney
  • Mark Rotman
  • Richard Fejka
  • Raymond A. Farkas
  • Kunihiko Yokoyama
  • Steven M. Larson
Part of the NATO ASI Series book series (NSSA, volume 152)

Abstract

At the National Institutes of Health, an apparatus was developed to radiolabel monoclonal antibodies for use in both imaging and radioimmuno-therapy. Up to 600 mCi of I-131 can be safely handled in this labeling hood which is shown schematically in Figure 1. The hood was designed so that two iodinations could be performed at the same time. Often these include specific and nonspecific (isotype matched) antibodies. To construct the apparatus, a standard fume hood was reinforced with steel and a steel frame was assembled inside the hood to support standard two inch lead bricks. The frame itself has two doors of steel encased lead. The entire apparatus is covered by a plexiglass safety box which has on its upper surface four fan and charcoal filter units to trap volatilized radioiodine. The internal components of the apparatus include a reaction vessel, a Sephadex gel filtration chromatography column, a gamma detector, product and waste vials, tubing and three-way stopcocks connecting these items, and a peristaltic pump. Small bore arterial pressure tubing (internal volume of 0.55 ml per 12 inch segment) with luer lock fittings connect the reaction vial to the column and the column to the product and waste vials. The reaction vial sits in a lead pig on top of a flat vortex mixer whose speed is controlled by a variable voltage supply. The peristaltic pump in the system is capable of driving fluid through the relatively rigid arterial pressure tubing at a rate of 1 ml per minute.

Keywords

Human Serum Albumin Benzyl Alcohol Gamma Detector Reaction Vial Size Exclusion HPLC 
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.
    “Points to Consider in the Manufacture of Injectable Monoclonal Antibody Products Intended for Human Use In Vivo.” Office of Biologics Research and Review, Center for Drugs and Biologics, U.S. FDA. Revised Draft of June 11, 1984.Google Scholar
  2. 2.
    J. M. Ferens, K. A. Krohn, P. L. Beaumier, J. P. Brown, I. Hellstrom, K. E. Hellstrom, J. A. Carrasquillo, and S. M. Larson, High-Level Iodination monoclonal antibody fragments for radiotherapy, J. Nucl. Med. 25: 367–370 (1984).PubMedGoogle Scholar
  3. 3.
    D. Colcher, M. Zalutsky, W. Kaplan, W. Kufe, F. Austin, and J. Schlom, Radiolocalization of human mammary tumors in athymic mice by a monoclonal antibody, Cancer Res. 42:736–742 (1983).Google Scholar
  4. 4.
    R. J. McConahey, and F. J. Dixon, A Method of Trace Iodination of Proteins For Immunological Studies, Int. Arch Allergy 29:185–189 (1966).PubMedCrossRefGoogle Scholar
  5. 5.
    S. M. Larson, J. P. Brown, P. W. Wright, J. A. Carrasquillo, I. Hellstrom, and K.E. Hellstrom, Imaging of Melanoma with I-131-Labeled Monoclonal Antibodies, J. Nucl. Med. 24: 123–129 (1983).PubMedGoogle Scholar
  6. 6.
    T. Lindmo, E. Boven, F. Cuttitta, J. Fedorko, and P. A. Bunn, Determination of the Immunoreactive Fraction of Radio labeled Monoclonal Antibodies by Linear Extrapolation to Binding at Infinite Antigen Excess, J. Immunol. Meth. 72:77–89 (1984).CrossRefGoogle Scholar
  7. 7.
    S. Matsku, H. Kirchgessner, W. G. Dippold, and J. Bruggen, Immunoreactivity of monoclonal anti-melanoma antibodies in relation to the amount of radioactive iodine substituted to the antibody molecule, Eur. J. Nucl. Med. 11: 260–264 (1985).CrossRefGoogle Scholar
  8. 8.
    J. Reynolds, R. Fejka, M. Rotman, R. Farkas, and S. Larson, Loss of Immunoreactivity of I-131 labeled Monoclonal Antibody with Storage is Related to Radiation Damage, J. Nucl. Med. 26:113 (1985).Google Scholar
  9. 9.
    A. Fernau, and W. Pauli, Uber die Einwirkung der durchdringenden Radiumstrahlung auf anorganische und Biokolloide, I. Biochem Z 70:420–441 (1915).Google Scholar
  10. 10.
    O. Yamamoto, Ionized Radiation-induced Cross linking in Proteins, in: “Protein Cross Linking: Biochemical and Molecular Aspects,” M. Friedman, ed., Advances in Experimental Medicine and Biology, Vol. 86A, Plenum Press (1976), pp. 509–547.Google Scholar
  11. 11.
    H. J. Kim, L. K. Mee, S. J. Adelstein, and I. A. Taub, Binding Site Specificity of the Radiolytically induced Cross Linking of Phenylalanine to Glucagon, Rad. Res. 98:26–36 (1984).CrossRefGoogle Scholar
  12. 12.
    G. R. Kepner, and R. I. Macey, Membrane Enzyme Systems Molecular Size Determinations by Radiation Inactivation, Biochimica et Biophysica Acta 163:188–203 (1968).PubMedCrossRefGoogle Scholar
  13. 13.
    R. Kishore, J. Eary, K. A. Krohn, et al, Autoradiolysis of Iodinated Monoclonal Antibody Preparations, Nuc. Med. Biol. 13:457–459 (1986).Google Scholar
  14. 14.
    S. M. Larson, A Tentative Biological Model for the Localization of Radiolabelled Antibody in Tumor: The Importance of Immunoreactivity, Nucl. Med. Biol. 13:393–399 (1986).Google Scholar

Copyright information

© Springer Science+Business Media New York 1988

Authors and Affiliations

  • James C. Reynolds
    • 1
  • Patrick Maloney
    • 1
  • Mark Rotman
    • 1
  • Richard Fejka
    • 1
  • Raymond A. Farkas
    • 1
  • Kunihiko Yokoyama
    • 1
  • Steven M. Larson
    • 1
  1. 1.National Institutes of HealthBethesdaUSA

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