Skip to main content
Log in

Specific targeting of infectious foci with radioiodinated human recombinant interleukin-1 in an experimental model

  • Original Article
  • Published:
European Journal of Nuclear Medicine Aims and scope Submit manuscript

Abstract

In the present study, radioiodinated human recombinant interleukin-1 (IL-1) was investigated for its potential to image infectious foci in vivo in an animal model of infection. Twenty-four hours after induction of aStaphylococcus aureus abscess in the left calf muscle, mice were i.v. injected with both iodine-125 labelled IL-1 and iodine-131 labelled myoglobin, a size-matched control agent. The animals were killed for tissue biodistribution studies at 2, 6, 12, 24 and 48 h p.i. Gamma camera images were obtained at 6, 24 and 48 h after injecting mice with123I-IL-1. Radioiodinated IL-1 rapidly cleared from the body; after 12 h the abscess was the organ with the highest activity. The absolute abscess uptake of125I-IL-1 remained high compared to131I-myo-globin, resulting in significantly higher abscess-to-muscle ratios of125I-IL-1 compared to 1311-myoglobin. The ratios of125I-IL-1 reached the ultimate value of 44.4±10.8 at 48 h p.i., whereas the ratios of131I-myoglobin did not exceed 5.9±0.7. Gamma camera imaging revealed clearly visible abscesses. In conclusion, our results demonstrate specific retention of radioiodinated IL-1 in the abscess, presumably by interaction of IL-1 with its receptor on the inflammatory cells. The high target to-background ratios that were obtained over the course of time indicate that the IL-1 receptor may be a valuable target for the imaging of infectious foci.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Corstens FHM, Oyen WIG, Becker WS. Radioimmunoconjugates in the detection of infection and inflammation.Semin Nucl Med 1993; 23: 148–164.

    Google Scholar 

  2. Corstens FHM, van der Meer JWM. Chemotactic peptides: new locomotion for imaging of infection?J Nucl Med 1991; 32: 491–494.

    Google Scholar 

  3. Signore A, Chianelli M, Toscano A, et al. A radiopharmaceutical for imaging areas of lymphocytic infiltration:123I-inter-leukin-2. Labelling procedure and animal studies.Nucl Med Commun 1992; 13: 713–722.

    Google Scholar 

  4. Hay RV, Skinner RS, Newman OC, et al. Nuclear imaging of acute inflammatory lesions with recombinant human interleukin-8 [abstract].J Nucl Med 1993; 34: 104P.

    Google Scholar 

  5. Dinarello CA. Interleukin-l and interleukin-1 antagonism.Blood 1991; 77: 1627–1652.

    Google Scholar 

  6. Ward PA. Chemotaxis. In: Parker CW, ed.Clinical immunology, 1st edn. Philadelphia: W.B. Saunders; 1980: 272–297.

    Google Scholar 

  7. Newton RC, Uhl J, Covington M, Back O. The biodistribution and clearance of radiolabelled human interleukin-1 beta in mice.Lymphokine Res 1988; 7: 207–210.

    Google Scholar 

  8. Fraker PJ, Speck JC. Protein and cell membrane iodination with a sparingly soluble chloramide 1,3,4,6-tetrachloro3α-6α-diphenyl-glucouril.Biochem Biophys Res Commun 1978; 80:849–857.

    Google Scholar 

  9. Zubler RH, Erard F, Lees RK, et al. Mutant EL-4 thymoma cells polyclonally activate murine and human B cells via direct cell interaction.J Immunol 1985; 134: 3662.

    Google Scholar 

  10. Lowenthal JW, MacDonald HR. Binding and internalization of interleukin-1 by T -cells.J Exp Med 1986; 164: 1060–1074.

    Google Scholar 

  11. Lindmo T, Boven E, Cuttitta F, Fedorko J, Bunn PA. Determination of the immunoreactive fraction of radiolabelled monoclonal antibodies by linear extrapolation to binding at infinite antigen excess.J Immunol Methods 1984; 72: 77–89.

    Google Scholar 

  12. Scatchard G. The attractions of proteins for small molecules and ions.Ann NYAcad Sci 1949; 51: 660–672.

    Google Scholar 

  13. Oyen WJG, Claessens RAMJ, van der Meer JWM, Corstens FHM. Biodistribution and kinetics of radiolabelled proteins in rats with focal infection.J Nucl Med 1992; 33: 388–393.

    Google Scholar 

  14. Oyen WJG, Claessens RAMJ, Raemakers JMM, de Pauw BE, van der Meer JWM, Corstens FHM. Diagnosing infection in febrile granulocytopenic patients with indium-111 labelled human IgG.J Clin Oncol 1992; 10: 61–68.

    Google Scholar 

  15. Peters AM, Roddie ME, Danpure HJ, et al. Technetium-99mHMPAO-labelled leucocytes: comparison with111In-tropolonate-labelled granulocytes.Nucl Med Commun 1988; 9: 449–463.

    Google Scholar 

  16. Babich JW, Graham W, Barrow SA, et al. Technetium-99m-labelled chemotactic peptides: comparison with indium-111-labelled white blood cells for localizing acute bacterial infection in the rabbit.J Nucl Med 1993; 34: 2176–2181.

    Google Scholar 

  17. Goins B, Klipper R, Rudolph AS, Cliff RO, Blumhardt R, Phillips WT. Biodistribution and imaging studies of technetium-99m-labelled liposomes in rats with focal infection.J Nucl Med 1993; 34: 2160–2168.

    Google Scholar 

  18. Van Furth R, Cohn ZA, Hirsch JG, et al. The mononuclear phagocytic system: a new classification of macrophages, monocytes, and their precursor cells.Bull World Health Organ 1972; 46: 845–852.

    Google Scholar 

  19. Smith J, Urba W, Steis R, et al. Interleukin-1 alpha: results of a phase I toxicity and immunomodulatory trial.Am Soc Clin Oncol 1990; 9: 717.

    Google Scholar 

  20. Gehrke L, Jobling SA, Paik LSK, McDonald B, Rosenwasser LJ, Auron PE. A point mutation uncouples human interleukin1β biological activity and receptor binding. J Biol Chem 1990; 265: 5922–5925.

    Google Scholar 

  21. Camacho NP, Smith DR, Goldman A. Structure of an interleukin-1β mutant with reduced bioactivity shows multiple subtle changes in conformation that affect protein-protein recognition.Biochemistry 1993; 32: 8749–8757.

    Google Scholar 

  22. Arend WP. Interleukin 1 receptor antagonist. A new member of the imerleukin 1 family.J Clin Invest 1991; 88: 1445–1451.

    Google Scholar 

  23. Granowitz EV, Porat R, Mier JW, et al. Pharmacokinetics, safety and immunomodulatory effects of human recombinant Interleukin-1 receptor antagonist in healthy humans.Cytokine 1992; 4: 353–360.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

van der Laken, C.J., Boerman, O.C., Oyen, W.J.G. et al. Specific targeting of infectious foci with radioiodinated human recombinant interleukin-1 in an experimental model. Eur J Nucl Med 22, 1249–1255 (1995). https://doi.org/10.1007/BF00801608

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00801608

Key words

Navigation