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Indium-111 myosin-specific antibodies and technetium-99m pyrophosphate in the detection of acute cardiac rejection of transplanted hearts: studies in a heterotopic rat heart model

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Abstract

111In-labelled myosin-specific antibodies were evaluated as an indicator of early changes in acute rejection in a rat heart heterotopic transplant model. Uptake of antibodies was measured in allograft and isograft hearts of animals undergoing different regimens of cyclosporine treatment and compared with the uptake of technetium-99m pyrophosphate. The data were correlated with histological estimation of the severity of myocyte necrosis and signs of early rejection (venous cuffing and endocardial inflammation, indicators of perivascular infiltrate and intermyocyte extension, respectively). Myocyte necrosis in transplanted hearts was reflected by increases in technetium-99m pyrophosphate accumulation (r=0.88) but was poorly correlated with labelled antibody uptake (r=0.58). There was no positive correlation between the degree of early cardiac rejection and uptake of either of the radiopharmaceuticals: accumulation of the labelled antibodies paradoxically declined with increased histological severity scores, whereas that of technetium-99m pyrophosphate remained unchanged. Cyclosporine treatment augmented the uptake of labelled antibodies in transplanted hearts. This may be due to alterations in plasma membrane permeability brought about by the drug, resulting in a rise in antibody binding to intracellular myosin.

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References

  • Addonizio LJ, Michler RE, Marboe C, Esser PE, Johnson LL, Seldin DW, Gersony WM, Alderson PO, Rose EA, Cannon PJ (1987) Imaging of cardiac allograft rejection in dogs using 111indium monoclonal antimyosin Fab. J Am Coll Cardiol 9:555–564

    Google Scholar 

  • Aherne T, Tscholakoff D, Finkbeiner W, Sechtem U, Derugin N, Yee E, Higgins CB (1986) Magnetic resonance imaging of cardiac transplants: the evaluation of rejection of cardiac allografts with and without immunosuppression. Circulation 74:145–156

    Google Scholar 

  • Billingham ME (1980) Diagnosis of cardiac rejection by endomyocardial biopsy. Heart Transplant 1:25–30

    Google Scholar 

  • Buja LM, Parkey RW, Dees JH, Stokely EM, Harris RA, Bonte FJ, Willerson JT (1975) Morphologic correlates of 99mTc-stannous pyrophosphate imaging of acute myocardial infarctions in dogs. Circulation 52:596–607

    Google Scholar 

  • Carrio I, Berna L, Ballester M, Estorch M, Obrador D, Cladellas M, Abadal L, Ginjaume M (1988) Indium-111 antimyosin scintigraphy to assess myocardial damage in patients with suspected myocarditis and cardiac rejection. J Nucl Med 29:1893–1900

    Google Scholar 

  • Dawkins KD, Oldershaw PJ, Billingham ME et al. (1984) Changes in diastolic function as a noninvasive marker of cardiac allograft rejection. Heart Transplant 3:286–294

    Google Scholar 

  • Frist W, Yasuda T, Segall G, Khaw BA, Strauss HW, Gold H, Stinson E, Oyer P, Baldwin J, Billingham M, McDougall IR, Haber E (1987) Noninvasive detection of human cardiac transplant rejection with indium-111 antimyosin (Fab) imaging. Circulation 76:81–85

    Google Scholar 

  • Herskowitz A, Soule LM, Mellits D, Traill TA, Achuff SC, Reitz BA, Borkon AM, Baumgartner WA, Baughman KL (1987) Histologic predictors of acute cardiac rejection in human endomyocardial biopsies: a multivariate analysis. J Am Coll Cardiol 9:802–810

    Google Scholar 

  • Holman L, Chisholm RJ, Braunwald E (1978) The prognostic implication of acute myocardial infarct scintigraphy with 99mTc-pyrophosphate. Circulation 57:320–326

    Google Scholar 

  • Johnson LL, Seldin DW, Becker LC, LaFrance ND, Liberman HA, James C, Mattis JA, Dean RT, Brown J, Reiter A, Arneson V, Cannon PJ, Berger HJ (1989) Antimyosin imaging in acute transmural myocardial infarctions: results of a multicenter clinical trial. J Am Coll Cardiol 13:27–35

    Google Scholar 

  • Khaw BA, Beller GA, Haber E, Smith TW (1976) Localization of cardiac myosin-specific antibody in myocardial infarction. J Clin Invest 58:439–446

    Google Scholar 

  • Khaw BA, Fallon JT, Beller GA, Haber E (1979) Specificity of localization of myosin-specific antibody fragments in experimental myocardial infarction. Histologic, histochemical, autoradiographic and scintigraphic studies. Circulation 60:1527–1531

    Google Scholar 

  • Khaw BA, Fallon JT, Strauss HW, Haber E (1980) Myocardial infarct imaging of antibodies to canine cardiac myosin with indium-111-diethylenetriamine pentaacetic acid. Science 209:295–297

    Google Scholar 

  • Khaw BA, Mattis JA, Melincoff G, Strauss HW, Gold HK, Haber E (1984) Monoclonal antibody to cardiac myosin: imaging of experimental myocardial infarction. Hybridoma 3:11–23

    Google Scholar 

  • Khaw BA, Gold HK, Yasuda T, Leinbach RC, Kanke M, Fallon JT, Barlai-Kovach M, Strauss HW, Sheehan F, Haber E (1986) Scintigraphic quantification of myocardial necrosis in patients after intravenous injection of myosin-specific antibody. Circulation 74:501–508

    Google Scholar 

  • Khaw BA, Yasuda T, Gold HK, Leinbach RC, Johns JA, Kanke M, Barlai-Kovach M, Strauss HW, Haber E (1987) Acute myocardial infarct imaging with 111In-labeled monoclonal antimyosin Fab. J Nucl Med 28:1671–1678

    Google Scholar 

  • LaFrance ND, Hall T, Dolher W, Koller D, Cole P, Barkon A, Traill T, Jacobus W, Norris S, Hutchins G, Braun J, Baumgartner W, Reitz B, Wagner HN (1986) In-111 antimyosin monoclonal antibody in detecting rejection of heart transplants. J Nucl Med 27:910–911

    Google Scholar 

  • McGregor CGA, Hatz R, Aziz S, Billingham MB, McDougall IR (1984) Technetium-99m pyrophosphate in diagnosis of acute cardiac rejection in the rat with effect of cyclosporin. J Nucl Med 25:870–873

    Google Scholar 

  • Nicchitta CV, Kamoun M, Williamson JR (1985) Cyclosporin augments receptor-mediated cellular Ca2+ fluxes in isolated hepatocytes. J Biol Chem 260:13613–13618

    Google Scholar 

  • Nishimura T, Sada M, Sasaki H, Yutani C, Hayashi M, Amemiya H, Fujita T, Akutsu T, Manabe H (1987) Identification of cardiac rejection in heterotopic heart transplantation using 111In-antimyosin. Eur J Nucl Med 13:343–347

    Google Scholar 

  • Ono K, Lindsey ES (1969) Improved technique of heart transplantation in rats. J Thorac Cardiovasc Surg 57:225–229

    Google Scholar 

  • Owunwanne A, Shihab-Eldeen A, Sadek S, Junaid T, Yacoub T, Abdel-Dayem HM (1990) Radiopharmaceutical investigation of cyclosporin A cardiotoxicity and correlation with histopathological finding. J Nucl Med (abstract) 31:834

    Google Scholar 

  • Tamaki N, Yamada T, Matsumori A, Yoshida A, Fujita T, Ohtani H, Watanabe Y, Yonekura Y, Endo K, Konishi J, Kawai C (1990) Indium-111-antimyosin antibody imaging for detecting different stages of myocardial infarction: comparison with technetium-99m-pyrophosphate imaging. J Nucl Med 31:136–142

    Google Scholar 

  • Ueda K, Baumgartner WA, Beschorner WE, Borkon MA, Soule LM, Reitz BR, Herskowitz A (1985) Histologic pattern of early heart allograft rejection under cyclosporin treatment. Heart Transplant 4:296–301

    Google Scholar 

  • Volpini M, Giubbini R, Gei P, Cuccia C, Franzoni P, Riva S, Terzi A, Metra M, Bestagno M, Visioli O (1989) Diagnosis of acute myocardial infarction by 111In antimyosin antibodies and correlation with the traditional techniques for the evaluation of extent and localization. Am J Cardiol 63:7–13

    Google Scholar 

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Takeda, K., Ueda, K., Scheffel, U. et al. Indium-111 myosin-specific antibodies and technetium-99m pyrophosphate in the detection of acute cardiac rejection of transplanted hearts: studies in a heterotopic rat heart model. Eur J Nucl Med 18, 461–466 (1991). https://doi.org/10.1007/BF00181284

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  • DOI: https://doi.org/10.1007/BF00181284

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