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Species and immunoglobulin preparation related effects on the biodistribution of technetium-99m-labelled immunoglobulin G in a baboon model

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Abstract

Technetium-99m-labelled immunoglobulin G (99mTc-IgG) is a convenient and useful radio-pharmaceutical for the scintigraphic detection of inflammatory foci. However, unfavourable physiological biodistribution patterns such as high activities in the liver and especially in the kidneys impede the efficacy of this agent. This report describes biodistribution studies in the baboon model of various thiol reduction-mediated 99mTc-labelled immunoglobulins, including human IgG preparations (Sandoglobulin and Sigma: γ-globulins prepared from Cohn fractions II and III) as well as baboon IgG preparations (Sigma: γ-globulins prepared from Cohn fractions II and III and IgG isolated from the serum obtained from specific animals). The biodistribution studies demonstrated differences in kidney concentration, i.e. human IgG (Sandoglobulin) > baboon IgG (cross-over animal experiments with IgG isolated from the serum of the different animals) > human IgG (Sigma)≈ baboon IgG (Sigma)≈baboon IgG (own IgG isolated from the serum of a specific animal, labelled with 99mTc and reinjected). Differences in liver concentration were also observed: human IgG (Sandoglobulin)<human IgG(Sigma)≈baboon IgG (Sigma)≈baboon IgG (own IgG)≈IgG (cross-over). Characteristic were the relatively high activities in the liver and kidneys compared to those in other organs with high blood supply, and a relatively high retention in the blood pool. The results indicate that the effect of the heterologous antibody system is insignificant. These studies also demonstrate the suitability of the baboon model for evaluation of 99mTc-IgG preparations for scintigraphic purposes and suggest that damage to the Fc portion of the IgG molecule during Sandoglobulin preparation may be the cause of the high kidney accumulation of 99mTc-Sandoglobulin.

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References

  1. Buscombe JR, Lui D, Ensing G, De Jong R, Ell PJ. 99mTc-human immunoglobulin (HIG) — first results of a new agent for the localization of infection and inflammation. Eur J Nucl Med 1990; 16:649–655.

    Google Scholar 

  2. Van der Lubbe PAHM, Arndt JW, Calame W, Ferreira TC, Pauwels EKJ, Breedveld FC. Measurement of synovial inflammation in rheumatoid arthritis with technetium 99m-labelled human polyclonal immunoglobulin G. Eur J Nucl Med 1991; 18:119–123.

    Google Scholar 

  3. Dormehl IC, Louw WKA, Hugo N, Redelinghuys IF, Fourie PJ. Thiol reduction-mediated 99mTc-IgG for scintigraphy of inflammatory lesions in the baboon model. Am J Physiol Imag 1991; 6:176–182.

    Google Scholar 

  4. Oyen WJG, Claessens RAMJ, Van der Meer JWM, Corstens FHM. Biodistribution and kinetics of radiolabeled proteins in rats with focal infection. J Nucl Med 1992; 33:388–394.

    Google Scholar 

  5. Fishman AJ, Rubin RH, White JA, Locke E, Wilkinson RA, Nedelman M, Callahan RJ, Khaw BA, Strauss HW. Localization of Fc and Fab fragments of nonspecific polyclonal IgG at focal sites of inflammation. J Nucl Med 1990: 31:1199–1205.

    Google Scholar 

  6. Saptogino A, Becker W, Wolf F. 99mTc-labelled polyclonal human immunoglobulin for localization of inflammatory sites —early in vitro results. Nucl Med 1990; 29:54–58.

    Google Scholar 

  7. Calame W, Feitsma HIJ, Ensing GJ, Arndt J-W, Von Furth R, Pauwels EKJ. Binding of 99mTc-labelled polyclonal human immunoglobulin to bacteria as a mechanism for scintigraphic detection of infection. Eur J Nucl Med 1991; 18:396–400.

    Google Scholar 

  8. Hopkins SJ. Sandoglobulin. Drugs of Today 1985; 21:279–282.

    Google Scholar 

  9. Lanteigne D, Hnatowich DJ. The labeling of DTPA-coupled proteins with 99mTc. Int J Appl Radiat Isot 1984; 35:617–621.

    Google Scholar 

  10. Mather SJ, Ellison D. Reduction-mediated technetium-99m labeling of monoclonal antibodies. J Nucl Med 1990; 31:692–697.

    Google Scholar 

  11. Goedemans WT, Panek KJ, Ensing GJ, De Jong MTM. A new, simple method for labelling of proteins with 99mTc by derivatization with 1-imino-4-mercaptobutyl groups. In: Nicolini M, Bandoli G, Mazzi U, eds. Technetium and rhenium in chemistry and nuclear medicine 3. New York: Raven; 1990:595–603.

    Google Scholar 

  12. Canfield SM, Morrison SL. The binding affinity of human IgG for its high affinity Fc receptor is determined by multiple amino acids in the CH2 domain and is modulated by the hinge region. J Exp Med 1991; 173:1483–1491.

    Google Scholar 

  13. Kassis AI. Optimizing antibodies for use in nuclear medicine [editorial]. J Nucl Med 1991; 32:1751–1753.

    Google Scholar 

  14. Fridman EP, Popova VN. Species of the genus Papio (Cercopithecidae) as subjects of biomedical research: I. Biological basis of experiments on baboons. J Med Primatol 1988; 17:291–307.

    Google Scholar 

  15. Fridman EP, Popova VN. Species of the genus Papio (Cercopithecidae, primates) as subjects of biomedical research: II. Quantitative characteristics of contemporary use of baboon species in medical and biological investigations. J Med Primatol 1988; 17:309–318.

    Google Scholar 

  16. Kistler P, Friedli H. Ethanol precipitation. In: Curling JM, ed. Methods of plasma protein fractionation. London: Academic; 1980:3–15.

    Google Scholar 

  17. Le Moli S, Nisini R, Fattorossi A, Matricardi PM, D'Amelio R. Intravenous immunoglobulin preparations: comparative in vitro study of Fc mediated functions. J Clin Lab Immunol 1989; 29:79–84.

    Google Scholar 

  18. Burchiel SW, Khaw BA, Rhodes BA, Smith TW, Haber E. Immunopharmacokinetics of radiolabeled antibodies and their fragments. In: Burchiel SW, Rhodes BA, eds. Tumor imaging. The radiochemical detection of cancer. Paris: Masson; 1982:125–139.

    Google Scholar 

  19. Aarli A, Matre R, Thunold S. IgG Fc receptors on epithelial cells of distal tubuli and on epithelial cells in human kidney. Int Arch Allergy Appl Immunol 1991; 95:64–69.

    Google Scholar 

  20. Sands H, Jones PL. Methods for the study of the metabolism of radiolabeled monoclonal antibodies by liver and tumor. J Nucl Med 1987; 28:390–398.

    Google Scholar 

  21. Devey ME. The biological and pathological significance of antibody affinity. In: French MAH, ed. Immunoglobulins in health and disease. Lancaster: MTP; 1986:55–73.

    Google Scholar 

  22. Herrera AM, Saunders NB, Baker JR. Immunoglobulin composition of three commercially available intravenous immunoglobulin preparations. J Allergy Clin Immunol 1989; 84:556–561.

    Google Scholar 

  23. Van Furth R, Braat AGP, Leijh PCJ, Gardi A. Opsonic and physicochemical characteristics of intravenous immunoglobulin preparations. Vox Sang 1987; 53:70–75.

    Google Scholar 

  24. Khaw B-A, Klibanov A, O'Donnell SM, Saito T, Nossif N, Slinkin MA, Newell JB, Strauss HW, Torchilin VP. Gamma imaging with negatively charge-modified monoclonal antibody: modification with synthetic polymers. J Nucl Med 1991; 32:1742–1751.

    Google Scholar 

  25. Triguero D, Buciak JL, Pardridge WM. Cationization of immunoglobulin G results in enhanced organ uptake of the protein after intravenous administration in rats and primate. J Pharmacol Exp Ther 1991; 258:186–192.

    Google Scholar 

  26. Serafini AN, Garty I, Vargas-Cuba R, Friedman A, Rauh DA, Neptune M, Landress L, Sfakianakis GN. Clinical evaluation of a scintigraphic method for diagnosing inflammations/infections using indium-111-labeled nonspecific human IgG. J Nucl Med 1991; 32:2227–2232.

    Google Scholar 

  27. Fritzberg AR, Beaumier PL. Editorial—Targeted proteins for diagnostic imaging: Does chemistry make a difference? J Nucl Med 1992; 33:394–397.

    Google Scholar 

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Authors and Affiliations

  1. Atomic Energy Corporation of South Africa Limited, Pretoria, South Africa

    W. K. A. Louw

  2. AEC Institute for Life Sciences, University of Pretoria, Pretoria, South Africa

    I. C. Dormehl, N. Hugo & I. F. Redelinghuys

Authors
  1. W. K. A. Louw
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  2. I. C. Dormehl
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  3. N. Hugo
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  4. I. F. Redelinghuys
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Louw, W.K.A., Dormehl, I.C., Hugo, N. et al. Species and immunoglobulin preparation related effects on the biodistribution of technetium-99m-labelled immunoglobulin G in a baboon model. Eur J Nucl Med 20, 96–100 (1993). https://doi.org/10.1007/BF00168867

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  • DOI: https://doi.org/10.1007/BF00168867

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