Advertisement

European Journal of Nuclear Medicine

, Volume 23, Issue 4, pp 414–421 | Cite as

Technetium-99m labelled hydrazinonicotinamido human non-specific polyclonal immunoglobulin G for detection of infectious foci: a comparison with two other technetium-labelled immunoglobulin preparations

  • Roland A. M. J. Claessens
  • Otto C. Boerman
  • Emile B. Koenders
  • Wim J. G. Oyen
  • Jos W. M. van der Meer
  • Frans H. M. Corstens
Original Article

Abstract

Recently a new linker — hydrazinonicotinate (HYNIC) — was introduced for labelling of proteins and peptides with technetium-99m. HYNIC and other linkers have been used for labelling of human non-specific polyclonal immunoglobulin G (hIgG) with99mTc for the detection of infections. In this study we compared the tissue distribution of three different99mTc-hIgG preparations in groups of five Wistar rats with a focal intramuscular infection withStaphylococcus aureus. We compared99mTc-HYNIC-hIgG with99mTc-hIgG labelled via the so-called Schwarz method (reduction of disulphide bonds) and with the99mTc-labelled commercially available Technescan-HIG. Unlike the HYNIC linker, in the two other labelling methods free sulph-hydryl groups are involved in the binding of99mTc. High-performance liquid chromatography analysis of the labelled preparations and of plasma samples revealed aggregate or polymer formation in all three agents; this was least pronounced in the product labelled by means of the Schwarz method. The tested preparations did not show signs of degradation in vitro. The difference in linker chemistry was reflected in the tissue distribution. Thus the biodistribution of99mTc-HYNIC-hIgG was significantly different from the distribution of the two other preparations: abscess (1.4%±0.2%ID/g), muscle, liver, spleen, plasma, lung, bone marrow, and small intestine concentrations were higher at 24 h p.i.; kidney uptake (1.19%±0.08%ID/g) was significantly lower. The abscess-to-plasma and the abscess-to-muscle ratios (0.5 and 11, respectively), however, were in the same range for the three preparations tested. Quantitative analysis of the scintigraphs revealed that the total body clearance of99mTc-HYNIC-hIgG was significantly slower than for the other agents. The abscess uptake of99mTc-HYNIC-hIgG as a percentage of the remaining body activity was significantly higher. Based on its high abscess uptake, its low uptake in the kidneys and the high percentage of its abscess uptake in relation to the remaining body activity, we conclude that99mTc-HYNIC-hIgG seems superior to the two other preparations tested for the detection of infections.

Key words

Hydrazinonicotinamide Immunoglobulin G Infection Inflammation 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Rubin RH, Young LS, Hansen WP, et al. Specific and nonspecific imaging of localized Fisher immunotype 1Pseudomonas aeruginosa infection with radiolabeled monoclonal antibody.J Nucl Med 1988; 29: 651–656.Google Scholar
  2. 2.
    Rubin RH, Fischman AJ, Callahan RJ, et al.111In-labeled nonspecific immunoglobulin scanning in the detection of focal infection.N Engl J Med 1989; 321: 935–940.Google Scholar
  3. 3.
    LaMuraglia GM, Fischman AJ, Strauss HW, et al. Utility of the indium 111-labeled human immunoglobulin G scan for the detection of focal vascular graft infection.J Vasc Surg 1989; 10: 20–27; discussion 27-28.Google Scholar
  4. 4.
    Oyen WJ, Claessens RA, van Horn JR, et al. Scintigraphic detection of bone and joint infections with indium-111-labeled nonspecific polyclonal human immunoglobulin G,J Nucl Med 1990; 31: 403–412.Google Scholar
  5. 5.
    Oyen WJ, Claessens RA, Raemaekers JM, et al. Diagnosing infection in febrile granulocytopenic patients with indium-111-labeled human immunoglobulin G.J Clin Oncol 1992; 10:61–68.Google Scholar
  6. 6.
    Fischman AJ, Rubin RH, Khaw BA, et al. Detection of acute inflammation with111In-labeled nonspecific polyclonal IgG.Semin Nucl Med 1988; 18: 335–344.Google Scholar
  7. 7.
    Corstens FH, Oyen WJ, Becker WS. Radioimmunoconjugates in the detection of infection and inflammation.Semin Nucl Med 1993; 23: 148–164.Google Scholar
  8. 8.
    Oyen WJ, Claessens RA, van der Meer JW, et al. Biodistribution and kinetics of radiolabeled proteins in rats with focal infection.J Nucl Med 1992; 33: 388–394.Google Scholar
  9. 9.
    Abrams MJ, Juweid M, tenKate CI, et al. Technetium-99m-human polyclonal IgG radiolabeled via the hydrazino nicotinamide derivative for imaging focal sites of infection in rats.J Nucl Med 1990; 31: 2022–2028.Google Scholar
  10. 10.
    Schwartz DA, Abrams MJ, Hauser MM, et al. Preparation of hydrazino-modified proteins and their use for the synthesis of99mTc-protein conjugates.Bioconjug Chem 1991; 2: 333–336.Google Scholar
  11. 11.
    Schwarz A, Steinsträsser A. A novel approach to99mTc-labeled monoclonal antibodies [abstract].J Nucl Med 1987; 28: 721.Google Scholar
  12. 12.
    King TP, Zhao SW, Lam T. Preparation of protein conjugates via intermolecular hydrazone linkage.Biochemistry 1986; 25: 5774–5779.Google Scholar
  13. 13.
    Larsen SK, Caldwell G, Higgins III JD, et al. Technetium complex of tricine: useful precursor for the99mTc-labelling of hydrazino nicotinamide modified proteins [abstract].J Labelled Compd Radiopharm 1994; 35: 1–2.Google Scholar
  14. 14.
    Mather SJ, Ellison D. Reduction-mediated technetium-99m labeling of monoclonal antibodies.J Nucl Med 1990; 31: 692–697.Google Scholar
  15. 15.
    Riddles PW, Blakeley RL, Zerner B. Ellman's reagent: 5,5′-di-thiobis(2-nitrobenzoic acid) — a reexamination.Anal Biochem 1979; 94: 75–81.Google Scholar
  16. 16.
    Verbeke K, Hjelstuen O, Debrock E, et al. Comparative evaluation of99mTc-Hynic-HSA and99mTc-MAG3-HSA as possible blood pool agents.Nucl Med Commun 1995; 16: 942–957.Google Scholar
  17. 17.
    Mardirossian G, Wu C, Rusckowski M, et al. The stability of99mTc directly labelled to an Fab' antibody via stannous ion and mercaptoethanol reduction.Nucl Med Commun 1992; 13: 503–512.Google Scholar
  18. 18.
    Claessens RAMJ, Koenders EB, Oyen WJ, et al. Release of technetium from99mTc-IgG in infectious foci [abstract].J Nucl Med 1994; 35: 45P.Google Scholar
  19. 19.
    Moretti JL, Rapin JR, Saccavini JC, et al. 2,3-Dimercaptosuccinic acid chelates: their structure and biological behavior [abstract].Nucl Med Biol 1982; II: 1651–1654.Google Scholar
  20. 20.
    Kagi JH, Himmelhoch SR, Whanger PD, et al. Equine hepatic and renal metallothioneins. Purification, molecular weight, amino acid composition, and metal content.J Biol Chem 1974; 249: 3537–3542.Google Scholar
  21. 21.
    Chervu LR, Blaufox MD. Renal radiopharmaceuticals — an update.Semin Nucl Med 1982; 12: 224–245.Google Scholar

Copyright information

© Springer-Verlag 1996

Authors and Affiliations

  • Roland A. M. J. Claessens
    • 1
  • Otto C. Boerman
    • 1
  • Emile B. Koenders
    • 1
  • Wim J. G. Oyen
    • 1
  • Jos W. M. van der Meer
    • 1
  • Frans H. M. Corstens
    • 1
  1. 1.Department of Nuclear MedicineUniversity Hospital NijmegenNijmegenThe Netherlands

Personalised recommendations