Advertisement

Amyloidosis pp 163-174 | Cite as

In Vivo Radioimmunodetection of Amyloid Deposits in Experimental Amyloidosis

  • John Marshall
  • William McNally
  • Dan Muller
  • George Meincken
  • Irwin Fand
  • S. C. Srivastava
  • Harold Atkins
  • David D. Wood
  • Peter D. Gorevic

Abstract

Two rat IgG monoclonal antibodies (MAbs) to mouse AA protein have been used as reagents for an ELISA assay for SAA, for the demonstration of tissue deposits by the immunoperoxidase method, and for the definition of AA polymorphs in solubilized amyloidotic tissue specimens run onto two-dimensional (2D) gels and probed as Western Blots. Both MAbs localize to tissue deposits in vivo when labelled (MAb*) with I125 or I123 and injected into colchicine-pretreated amyloidotic mice, assessed by (a) whole-body autoradiography (WBAR) (b) external photoscanning (c) tissue autoradiography of perfused organs. Serum t 1/2 of MAb* in amyloidotic animals was greatly accelerated compared to controls, and sustained concentration of label was found in spleen, liver, and kidney quantitated by organ counts up to 96 h post injection. MAb* label copurified with amyloid fibrils up to 10-fold over saline-soluble proteins and residue following homogenization in distilled water and acid extraction; purified fibrils contained AA protein and MAb* heavy and light chain visualized on 2D gels and by autoradiography. Animals were also injected with a mixture of the two MAbs, one labeled with Indium111-DTPA (126 μCi), the other with I125 (6 μCi) and serially scanned over a 48 h period. Fractionation of serum taken after injection showed both isotopes to be present as uncomplexed IgG in blood. WBAR was performed at 48 h and at a time at which I125/In111 radioactivity was calculated to be 127/1; autoradiograms were similar and confirmed localization of both isotopes to tissue deposits in amyloidotic animals. These studies provide evidence that MAbs to amyloid subunit proteins may be useful re-agents for the in vivo radioimmunodetection of some of the amyloid diseases.

Keywords

Amyloid Deposit Post Injection Amyloid Fibril Tissue Deposit Amyloid Disease 
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. 1.
    S. Fujihara, J. E. Balow, J. C. Costa, and G. G. Glenner, Lab. Invest., 43:358 (1980); T. Shirahama, M. Skinner, and A. S. Cohen, Histochemistry, 72: 161 (1981).PubMedCrossRefGoogle Scholar
  2. 2.
    J. D. Sipe, T. F. Ignaczak, P. S. Pollock, and G. G. Glenner, J. Immunol., 116:1151 (1976); G. Marhaug, Scand. J. Immunol., 18:329 (1983); M. J. M. Saraiva, P. P. Costa, and D. S. Goodman, J. Lab. Clin. Med., 102: 590 (1983).PubMedGoogle Scholar
  3. 3.
    K. P. W. J. McAdam, et al., Ann. N.Y. Acad. Sci., 389:126 (1982); G. Marhaug, et al., Clin. Exp. Immunol., 50:390 (1982); R. Linke, J. Histochem. Cytochem., 32:322 (1984); C. J. Rosenthal, A. Huq, and M. E. Martin, Routh Intl. Symposium of amyloidosis, November 9–12, 1984.Google Scholar
  4. 4.
    D. Pressman, Cancer Res., 40:2960 (1980); R. W. Baldwin, M. J. Embleton, and M. R. Price, Molec. Aspects Med., 4:329 (1980); Tumor Imaging (S. E. Burchiel, R. A. Rhodes, and B. E. Friedman, eds.), Masson, New York (1982); R. Levy and R. A. Miller, Fed. Proc., 42: 2650 (1983).PubMedGoogle Scholar
  5. 5.
    B. A. Khaw et al., J. Clin. Invest., 58:439 (1976); J. Nucl. Med., 23: 1011 (1982); N. C. Engleberg and B. I. Eisenstein, New Engl. J. Med., 311: 892 (1984).PubMedCrossRefGoogle Scholar
  6. 6.
    R. T. Schultz, Amer. J. Pathol., 86: 321 (1977).Google Scholar
  7. 7.
    D. D. Wood, M. Gammon, and M. J. Staruch, J. Immunol. Meth., 55: 19 (1982).CrossRefGoogle Scholar
  8. 8.
    J.-L. Guesdon, T. Ternynck, and S. Avrameas, J. Histochem. Cytochem., 27: 1131 (1979).PubMedCrossRefGoogle Scholar
  9. 9.
    M. D. Benson, et al., J. Clin. Invest., 59:412 (1977); M. D. Benson and E. Kleiner, J. Immunol., 124:495 (1980); M. J. Selinger, et al., Nature, 285: 498 (1980).PubMedCrossRefGoogle Scholar
  10. 10.
    W. C. Eckelmari, S. M. Karesh, and R. C. Reba, J. Pharm. Sci., 64:704 (1975); G. E. Krejcarek and K. Tucker, Biochim. Biophys. Res. Comm., 77:581 (1977); D. A. Scheinberg, M. Strand, and 0. A. Ganslow, Science, 215:1511 (1982); J. Powe, et al., Cancer Drug Delivery, 1: 125 (1984).PubMedCrossRefGoogle Scholar
  11. 11.
    P. D. Gorevic, A. B. Cleveland, and D. D. Wood, Arth. Rheum., 25: S141 (1982).Google Scholar
  12. 12.
    I. Fand and W. P. McNally, in: Current Trends in Morphological Techniques (J. E. Johnson, Jr., ed.), CRC Press, Inc., Boca Raton, Florida, Vol. 2, p. 1 (1981).Google Scholar
  13. 13.
    A. Henrickson, in: Current Trends in Morphological Techniques (J. E. Johnson, Jr., ed.), CRC Press, Inc., Boca Raton, Florida, Vol. 2, p. 29 (1981).Google Scholar
  14. 14.
    M. Pras, et al., J. Clin. Invest., 47:924 (1968); M. Pras and T. Reshef, Biochim. Biophys. Acta, 271: 193 (1972).PubMedGoogle Scholar
  15. 15.
    N. G. Anderson and N. L. Anderson, Anal. Biochem., 85:331 (1978); 85: 312 (1978); P. D. Gorevic, et al., Amer. J. Ophth., 98: 216 (1984).Google Scholar
  16. 16.
    H. L. Spiegelberg and W. D. Weigle, J. Exp. Med., 121:323 (1965); T. W. Smith, B. L. Lloyd, N. Spicer, and E. Haber, Clin. Exp. Immunol., 36:384 (1979); S. J. Nelson and D. D. Manning, J. Immunol., 175:2339 (1980); S. W. Burchiel, et al., in: Tumor Imaging (S. W. Burchiel and B. A. Rhodes, eds.), Masson Publishing, New York, p. 128 (1982).Google Scholar
  17. 17.
    G. Telium, Acta. Pathol. Microbiol. Scand., 61: 21 (1964).Google Scholar
  18. 18.
    W. F. Bale, M. A. Contreras, and E. D. Grady, Cancer Res., 40:2965 (1980); W. C. EekeIman, C. H. Paik, and R. C. Reiba, Cancer Res., 40: 3036 (1980).Google Scholar
  19. 19.
    E. Calkins and A. S. Cohen, Bull. Rheum. Dis., 10:215 (1960); H. Benhold and H. Steilner, in: Protides of the Biological Fluids ( H. Peeters, ed.), Pergamon Press, Oxford (1973), p. 113.Google Scholar
  20. 20.
    D. M. Goldenberg, et al., New Engl. J. Med., 298:1384 (1978); J. P. Mach, et al., Immunol. Today, 2: 239 (1981).CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • John Marshall
    • 1
  • William McNally
    • 2
  • Dan Muller
    • 1
  • George Meincken
    • 3
  • Irwin Fand
    • 2
  • S. C. Srivastava
    • 3
  • Harold Atkins
    • 3
  • David D. Wood
    • 4
  • Peter D. Gorevic
    • 1
  1. 1.Department of MedicineUSA
  2. 2.Long Island Research InstituteSUNY at Stony BrookUSA
  3. 3.Brookhaven National LaboratoriesUptonUSA
  4. 4.Ayerst LaboratoriesPrincetonUSA

Personalised recommendations