Antibodies

  • Azuwuike Owunwanne
  • Mohan Patel
  • Samy Sadek

Abstract

Antibodies (Abs) are immunoglobulin (Ig) molecules that are formed in response to the presence of foreign substances (antigen, Ag) in the blood. The antibodies have binding sites that recognize the Ag(s) and bind specifically with them. There are five classes of immunoglobulins: gamma, IgG; mu, IgM; alpha, IgA; delta, IgD; and epsilon, IgE [11. The antibodies have Variable’ and ‘constant’ regions of light and heavy chains. The variable region (Fab) contains amino-terminal portions responsible for the antibody’s specificity (the specific binding sites for the antigens). The constant region (Fc) controls the binding of complement, the transport of the antibody molecule across membranes and the binding of antibody to membranes (non-specific binding). The Fab and Fc fragments of an IgG molecule are obtained by enzymatic cleavage using papain, while the Fab’ fragment is obtained using pepsin, as shown in Figure 11.1.

Keywords

Oncol Lysine Fibrinogen Benzyl Maltose 

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References

  1. 1.
    Leder, P. (1982) The genetics of antibody diversity. Sci. Am., 246, 3–115.CrossRefGoogle Scholar
  2. 2.
    Pressman, D. and Korngold, L. (1953) The in vivo localization of anti-Wagner-osteogenic-sarcoma antibodies. Cancer, 6, 7619–23.CrossRefGoogle Scholar
  3. 3.
    Goldenberg, D.M. (1978) Immunodiagnosis and immunodetection of colorectal cancer. Cancer Bull, 30, 213–18.Google Scholar
  4. 4.
    Goldenberg, D.M., Kim, E.E. and DeLand F.H. et al. (1980) Radioimmunodetection of cancer with radioactive antibodies to carcinoembry-onic antigen. Cancer Res., 40, 2984–92.Google Scholar
  5. 5.
    Goldenberg, D.M., Kim, E.E., DeLand F.H. et al. (1980) Clinical studies of the radioimmunodetection of tumors containing alpha-fetoprotein. Cancer, 45, 497–501.CrossRefGoogle Scholar
  6. 6.
    Chetanneau, A., Baum, R.P., Lehur, P.A. et al. (1990) Multi-centre immunoscintigraphic study using indium-111-labeled CEA-specific and/or 19.9 monoclonal antibody F (ab’)2 fragments. Eur. J. Nud. Med., 17, 223–29.CrossRefGoogle Scholar
  7. 7.
    Larson, S.M. (1991) Radioimmunology imaging and therapy. Cancer, 67, 1253–60.CrossRefGoogle Scholar
  8. 8.
    Goldenberg, D.M. and Larson, S. (1992) Radioimmunodetection in cancer identification. J. Nucl. Med., 33, 803–14.Google Scholar
  9. 9.
    Hinkle, G.H., Loesch, J.A., Hill, T.L. et al. (1990) Indium-111-monoclonal antibodies in radio-mmunoscintigraphy. J. Nucl. Med. Tech., 18, 16–25.Google Scholar
  10. 10.
    Benz, P., Oberhausen, E. and Berberich, R. (1991) Monoclonal antibody BW431/26 labelled with technetium-99m and indium-111: an investigation of the biodistribution and the dosimetry in patients. Eur. J. Nucl. Med., 18, 813–16.CrossRefGoogle Scholar
  11. 11.
    Khaw, B.A., Yasuda, T., Gold, H.K. et al. (1989) Acute myocardial infarct imaging with indium-111-labeled monoclonal antimyosin Fab. J. Nucl. Med., 28, 1671–78.Google Scholar
  12. 12.
    Yokoyama, K., Reynolds, J.C., Paik, C.H. et al. (1980) Immunoreactivity affects the biodistrib-ution and tumour targeting of radiolabeled anti-P97 Fab fragment. J. Nucl. Med., 31, 220–22.Google Scholar
  13. 13.
    Goldenberg, D.M. (1988) Targeting of cancer with radiolabeled antibodies: prospects for imaging and therapy. Arch. Pathol. Lab. Med., 112, 580–87.Google Scholar
  14. 14.
    Goldenberg, D.M., DeLand F., Kim, E.E. et al. (1978) Use of radiolabeled antibodies to carci-noembryonic antigen for detection and localisation of diverse cancers by external photoscanning. N. Engl. J. Med., 298, 1384–88.CrossRefGoogle Scholar
  15. 15.
    Sharkey, R.M., Goldenberg, D.M., Goldenberg, H. et al. (1990) Murine monoclonal antibodies against carcinoembryonic antigen. Immunological, pharmacokinetic, and targeting properties in humans. Cancer Res., 50, 2823–31.Google Scholar
  16. 16.
    Weinstein, J.N., Eger, R.R., Covell, D.G. et al. (1989) The pharmacology of monoclonal antibodies. Ann. NY Acad. Sci., 507, 199–210.CrossRefGoogle Scholar
  17. 17.
    Frist, W., Yasuda, T., Segall, G. et al. Noninvasive detection of human cardiac transplant rejection with In-111-labeled monoclonal anti-myosin (Fab) imaging. Circulation, 76, 81–5.Google Scholar
  18. 18.
    Oster, Z.H., Srivastava, S.C., Som, P. et al. (1983) Thrombus radioimmunoscintigraphy: an approach using monoclonal antiplatelet antibody. Proc. Natl. Acad. Sci. USA, 82, 3465–88.CrossRefGoogle Scholar
  19. 19.
    Rosebrough, S.F., Grossman, Z.D., McAfee, J.G. et al. (1988) Thrombus localization with indium-111 and iodine-131-labeled fibrin-specific monoclonal antibody and its (Fab’)2 and Fab fragments. J. Nucl. Med., 29, 1212–22.Google Scholar
  20. 20.
    Locher, J.T., Seybold, K., Andres, R.Y. et al. (1986) Imaging of inflammatory and infectious lesions after injection of radiolabeled monoclonal antigranulocyte antibodies. Nucl. Med. Commun., 7, 659–60.Google Scholar
  21. 21.
    Joseph, K., Koffen, H., Bosslet, K. et al. (1978) In vivo labeling of granulocytes with Tc-99m anti-NCA monoclonal antibodies for imaging inflammation. Eur. J. Nucl. Med., 14, 367–73.Google Scholar
  22. 22.
    Fischman, A.J., Rubin, R.H., Khaw, B.A. et al. (1988) Detection of acute inflammation with In-111-labeled non-specific polyclonal IgG. Semin. Nucl. Med., 18, 335–44.CrossRefGoogle Scholar
  23. 23.
    Fischman, A.J., Khaw, B.A., Strauss, H.W. et al. (1989) Quo vadis radioimmune imaging. J. Nucl. Med., 30, 1911–15.Google Scholar
  24. 24.
    Goldenberg, D.M., Sharkey, R. and Ford, E. (1987) Anti-antibody enhancement of iodine-131 anti CEA radioimmunodetection in experimental and clinical studies. J. Nucl. Med., 28, 1604–10.Google Scholar
  25. 25.
    Wahl, R.L., Parker, C.W. and Philpott, G.W. (1983) Improved radioimaging with tumour localization with monoclonal F (ab’) J. Nucl. Med., 24, 316–25.Google Scholar
  26. 26.
    Bucheggar, F., Haskell, C.M., Schreyer, M. et al. (1983) Radiolabeled fragments of monoclonal antibodies against carcinoembroyonic antigens for localization of human colon carcinoma grafted to nude mice. J. Exp. Med., 158, 413–27.CrossRefGoogle Scholar
  27. 27.
    Bucheggar, F., Pfister, C., Fournier, K. et al. (1989) Ablation of human colon carcinoma in nude mice by I-131-labeled monoclonal anti-carcino-embryonic antigen antibody F (ab’)2 fragments. J. Clin. Invest., 83, 1449–56.CrossRefGoogle Scholar
  28. 28.
    Delaloye, B., Bischof-delaloye, A., Bacheggar, F. et al. (1988) Detection of colorectal carcinoma by emission computerized tomography after injection of I-123-labeled Fab or F(ab’)2 fragments from monoclonal anti-carcino-embryonic antigen antibodies. J. Clin. Invest., 77, 301–11.CrossRefGoogle Scholar
  29. 29.
    Larson, S.M., Carrasquillo, J.A., Krohn, K.A. et al. (1983) Localization of I-131-labeled P97 specific Fab fragments in human melanoma as a basis for radiotherapy. J. Clin. Invest., 72, 2101–14.CrossRefGoogle Scholar
  30. 30.
    Bucheggar, F., Pelegrin, A., Delaloye, B. et al. (1990) Iodine-131-labeled MAb F (ab’)2 fragments are more efficient and less toxic than intact anti-CEA antibodies in radioimmunother-apy of large human colon carcinoma grafted in nude mice. J. Nucl. Med., 31, 1035–44.Google Scholar
  31. 31.
    Warren, L., Back, C.A. and Tuszynski, G.P. (1978) Glycopeptide changes and malignant transformation. A possible role for carbohydrate in malignant behaviour. Biochim. Biophys. Acta, 516, 97–127.Google Scholar
  32. 32.
    Goldenberg, D.M., Goldenberg, H., Sharkey, R.M. et al. (1990) Clinical studies of cancer ra-dioimmuno detection with carcinoembryonic antigen monoclonal antibody fragments labelled with I-123 or Tc-99m. Cancer Res., 50, 909–21.Google Scholar
  33. 33.
    Pinsky, C.M., Goldenberg, D.M., Wlodkowski, T.J. et al. (1991) Detection of occult metastasis of colorectal cancer by the use of anti-CE A Fab’ fragments labelled with Tc-99m (Abstract). J. Nucl. Med., 32, 1053.Google Scholar
  34. 34.
    Baum, R.P., Hertel, A., Lorenz, M. et al. (1989) Tc-99m-labelled anti-CEA monoclonal antibody for tumour immunoscintigraphy: first clinical results. Nucl. Med. Commun., 10, 345–52.CrossRefGoogle Scholar
  35. 35.
    Carney, P.L., Rogers, P.E. and Johnson, D.K. (1989) Dual isotope study of Iodine-125 and Indium-111-labelled antibody in athymic mice. J. Nucl. Med., 30, 374–84.Google Scholar
  36. 36.
    Hnatowich, D.J. and McGraw, J. (1988) DTPA-coupled proteins procedures and precautions. Nucl Med. Biol., 14, 563–68.Google Scholar
  37. 37.
    Fritzberg, H.R. and Beamier, P.L. (1992) Targeted proteins for diagnostic imaging: does chemistry make a difference? (editorial). J. Nucl Med., 33, 394–97.Google Scholar
  38. 38.
    Hunter, W.M. and Greenwood, F.C. (1962) Preparation of iodine-131-labelled growth hormone of high specific radioactivity. Nature, 194, 495–96.CrossRefGoogle Scholar
  39. 39.
    Matzku, S., Kirchgessner, H., Digold, W.G. et al. (1985) Immunoreactivity of monoclonal anti-melanoma antibodies in relation to the amount of radioactive iodine substituted to the antibody molecule. Eur. J. Med., 11, 260–64.CrossRefGoogle Scholar
  40. 40.
    Markwell, A.A.K. (1982) A new solid-state reagent to iodinate proteins. Ann. Biochem., 125, 427–32.CrossRefGoogle Scholar
  41. 41.
    Lee, D.S.C. and Griffiths, J. (1984) Comparative studies of iodobeads and chloramine-T methods for the radioiodination of human alphafetoprotein. J. Immunol Methods, 74, 181–89.CrossRefGoogle Scholar
  42. 42.
    Haisma, H.J., Hilgers, J. and Zurawski, V.R. (1986) Iodination of monoclonal antibodies for diagnosis and radiotherapy using convenient one-vial method. J. Nucl. Med., 27, 1890–95.Google Scholar
  43. 43.
    Thorell, J.I. and Johanson, B.G. (1972) Enzymatic iodination of polypeptides with I-123 to high specific activity. Biochem. Biophys. Res. Commun., 48, 464–71.CrossRefGoogle Scholar
  44. 44.
    Newman, P.J., Kahn, R.A. and Hines, A.J. (1981) Detection and characterization of monoclonal antibodies to platelet membrane proteins. J. Cell. Biol., 90, 249–53.CrossRefGoogle Scholar
  45. 45.
    Bhargawa, K.K. and Acharya, S.A. (1989) Labelling of monoclonal antibodies with radionuclides. Semin. Nucl. Med., 19, 187–201.CrossRefGoogle Scholar
  46. 46.
    Hodalgo, J.U. and Nadler, S.B. (1962) Stability studies on I-131 labelled albumin. J. Nucl. Med., 3, 268–72.Google Scholar
  47. 47.
    DeNardo, G.L., Young, W.C, DeNardo, S.J. et al. (1986) Urinary metabolities after injection of mono clonal antibodies (MAB) or fibrinogen (F) radioiodinated with a small and large number of iodine atoms (abstract). J. Nucl. Med., 27, 958.Google Scholar
  48. 48.
    Engler, D. and Burger, A.G. (1984) The deiodin-ation of the iodothryonines and of their derivatives in man. Endocrine Rev., 5, 151–84.CrossRefGoogle Scholar
  49. 49.
    Bolton, A.E. and Hunter, W.M. (1973) The labeling of proteins to high specific radioactivities by conjugation to I-125 containing acylating agent. Biochem. J. 33, 529–37.Google Scholar
  50. 50.
    Bhargava, K.K. and Chervu, L.R. (1987) N-hydroxysuccinimide hippuran ester: application for radiolabelling of macromolecules. Biochem. Biophys. Res. Commun., 144, 323–28.CrossRefGoogle Scholar
  51. 51.
    Wilbur, D.S., Hadley, S.W. and Hylarides, M.D. (1989) Development of a stable radioiodi-nating reagents to label monoclonal antibodies for radiotherapy of cancer. J. Nucl. Med., 30, 216–26.Google Scholar
  52. 52.
    Krejcanek, G.E., Tucker, K.L. (1977) Covalent attachment of chelating groups to macromolecules. Biochem. Biophys. Res. Commun., 77, 581–85.CrossRefGoogle Scholar
  53. 53.
    Hnatowich, D.J., Layne, W.W., Childs, R.L. (1982) The preparation and labelling of DTPA-coupled albumin. Int. J. Appl. Radiat. Isot., 33, 327–32.CrossRefGoogle Scholar
  54. 54.
    Paik, C.H., Ebbert, M.A., Murphy, P.R. et al. (1983) Factors influencing DTPA conjugation with antibodies by cyclic DTPA anhydride. J. Nucl. Med., 24, 1158–63.Google Scholar
  55. 55.
    Scheinberg, D.A., Strand, M. and Gansow, O.A. (1982) Tumour imaging with radioactive metal chelates conjugated to monoclonal antibodies. Science, 215, 1511–13.CrossRefGoogle Scholar
  56. 56.
    Khaw, B.A., Gansow, O.A., Brechbiel, M.W. et al. (1990) Use of isothiocyanato benzyl-DTPA derivatized monoclonal antimyosin Fab for enhanced in-vivo target localization. J. Nucl. Med., 31, 211–17.Google Scholar
  57. 57.
    Mirzadeh, S.M., Brechbiel, M.W., Atcher, R.A. et al. (1990) Radiometal labelling of immunoproteins: covalent linkage of 2-(4-isothiocyanatobenzyl) DTPA ligands to immunoproteins. Bioconjug. Chem., 1, 59–65.CrossRefGoogle Scholar
  58. 58.
    Gansow, O.A. (1991) Newer approaches to the radiolabelling of monoclonal antibodies by use of metal chelates. Nucl. Med. Biol., 18, 369–81.Google Scholar
  59. 59.
    Eckelman, W.C., Karesh, S.M. and Reba, R.C. (1975) New compounds: fatty acid and long chain hydrocarbon derivatives containing a strong chelating agent. J. Pharmacol. Sci., 64, 704–6.CrossRefGoogle Scholar
  60. 60.
    Khaw, B.A., Strauss, H.W., Moore, R. et al. (1987) Myocardial damage delineated by indium-111 antimyosin Fab and technetium-99m, pyrophosphate. J. Nucl. Med., 28, 76–82.Google Scholar
  61. 61.
    Product Information (1986) Myoscint. Centocor Europe, Leiden, The Netherlands.Google Scholar
  62. 62.
    Khaw, B.A., Beller, G.A., Haber, E. et al. (1976) Localisation of cardiac myosin specific antibody in myocardial infarction. J. Clin, Invest., 58, 439–46.CrossRefGoogle Scholar
  63. 63.
    Owunwanne, A., Malki, A., Sadek, S. et al. (1989) Investigative study of radiopharmaceuticals useful for imaging skeletal muscle injury in experimental animals. Am. J. Physiol. Imaging., 4,62-5Google Scholar
  64. 64.
    Elgazzar, A.M., Malki, A.A., Abdel-Dayem, H.M. et al. (1989) Indium-111 monoclonal antimyosin antibody in assessing skeletal muscle damage in trauma. Nucl Med. Commun., 10, 477–85.CrossRefGoogle Scholar
  65. 65.
    Allen, M.D., Tsubi, H., Togo, T. et al. (1989) Detection of cardiac allograft rejection and myocyte necrosis by monoclonal antibody to cardiac myosin. Transplantation, 48, 923–28.CrossRefGoogle Scholar
  66. 66.
    Yasuda, T., Palacios, I.F, Dec, G.W. et al (1987) Indium-111 monoclonal antimyosin antibody imaging in the diagnosis of acute myocarditis. Circulation, 76, 306–11.CrossRefGoogle Scholar
  67. 67.
    Khaw, B.A., Strauss, H.W., Pohost, G.M. et al. (1983) Relation of immediate and delayed thallium-201 distribution to localisation of iodine-125 antimyosin antibody in acute experimental myocardial infarction. Am. J. Cardiol, 51, 1428–32.CrossRefGoogle Scholar
  68. 68.
    Khaw, B.A. and Narula, J. (1991) Of antimyosin imaging and histopathology of myocardial infarction: when, where and why? J. Nucl Med., 32, 867–70.Google Scholar
  69. 69.
    Shively, J.E. and Beatty, J.D. (1985) CEA-related antigens: molecular biology and clinical significance: Crit. Rev. Oncol. Hematol., 2, 355–99.CrossRefGoogle Scholar
  70. 70.
    Hnatowich, D.J., Layne, W.W., Childs, R.L. et al. (1983) Radioactive labelling of antibody: a simple and efficient method. Science, 220, 613–15.CrossRefGoogle Scholar
  71. 71.
    Hnatowich, DJ., Childs, R.L., Lanteigne, D. et al. (1983) The preparation of DTPA-coupled antibodies radiolabeled with metallic radionuclides: an improved method. J. Immunol Methods, 65, 145–47.CrossRefGoogle Scholar
  72. 72.
    Kuhlmann, L. and Steinstrasser, A. (1988) Effect of DTPA to antibody ratio on chemical, immunological and biological properties of In-111-labelled F(ab’)2 fragment of the antibody 431.31. Nucl. Med. Biol., 15, 617–27.Google Scholar
  73. 73.
    Bosslet, K., Steinstrasser, A., Schwarz, A. et al. (1985) Immunohistochemical localisation and molecular characteristics of three monoclonal antibody-defined epitopes detectable on carci-noembryonic antigen (CEA). Int. J. Cancer., 36, 75–84.CrossRefGoogle Scholar
  74. 74.
    Esteban, J.M., Schlom, J., Gansow, O.A. et al. (1987) New method for the chelation of indium-111 to monoclonal antibodies: biodis-tribution and imaging of athymic mice bearing human colon carcinoma xenografts. J. Nucl. Med., 28, 861–70.Google Scholar
  75. 75.
    Bo-Anders, J., Strand, S.E., Anderson, L. (1992) Radiation dosimetry for indium-111-labelled anti-CEA-F(ab’)2 fragments evaluated from tissue distribution in rats. J. Nucl Med., 33, 1654–60.Google Scholar
  76. 76.
    Ingvar, C., Wingardh, K., Ljungberg et al. (1991) Quantitative biokinetic study of In-111-F(ab’)2 in patients with colorectal cancer. Antibody Immunoconj. Radiopharmacol, 4, 587–93.Google Scholar
  77. 77.
    Hnatowich, D.J., Griffin, T.W., Kosciuczyk, C. et al. (1985) Pharmacokinetics of an indium-111-labelled monoclonal antibody in cancer patients. J. Nucl. Med., 26, 849–58.Google Scholar
  78. 78.
    Nabi, H.A. and Doerr, R.J. (1992) Radiolabeled monoclonal antibody imaging (immunoscinti-graphy) of colorectal cancers: current status and future perspectives. Am. J. Surg., 163, 448–56.CrossRefGoogle Scholar
  79. 79.
    Goldenberg, D.M., Goldenberg, H., Sharkey, R.M. et al. (1989) Imaging of colorectal carcinoma with radiolabelled antibodies. Semin, Nucl. Med., 19, 262–81.CrossRefGoogle Scholar
  80. 80.
    Product Information (1992) Oncoscint CR/OV, Cytogen, New Jersey.Google Scholar
  81. 81.
    Yokoyama, K., Carrasquillo, J.A., Chang, A.E. et al. (1989) Differences in biodistribution of indium-111-and iodine-131-labelled B72.3 monoclonal antibodies in patients with colorectal cancer. J. Nucl. Med., 30, 320–27.Google Scholar
  82. 82.
    Verbruggen, A.M. (1990) Radiopharmaceuticals: state of the art. Eur. J. Nucl. Med., 17, 346–60.CrossRefGoogle Scholar
  83. 83.
    Rhodes, B.A. and Burchiel, S.W. (1983) Radiolabeling of antibodies with technetium-99m, in Radioimmunoimaging and Radioimmu-notherapy (eds S.W. Burchiel and B.A. Rhodes), Elsevier, New York, pp. 207–22.Google Scholar
  84. 84.
    Rhodes, B.A., Zamora, P.O., Newell, K.D. et al. (1989) Technetium-99m labelling of marine monoclonal antibody fragments. J. Nucl. Med., 27, 685–93.Google Scholar
  85. 85.
    Pak, K.Y., Nedelmen, M.A., Stewarz, R. et al. (1986) A rapid and efficient method for labelling IgG antibodies with Tc-99m and comparison to Tc-99m Fab’ antibody fragments (abstract). J. Nucl. Med., 30, 793.Google Scholar
  86. 86.
    Schwarz, A. and Steinstrasser, A. (1987) A novel approach to Tc-99m-labelled monoclonal antibodies (abstract). J. Nucl. Med., 28, 721.Google Scholar
  87. 87.
    Thakur, M.L., Defulvio, J. and Park, C.H. (1990) Use of ascorbic acid (AA) for direct Tc-99m labeling of monoclonal antibodies (MAbs) (abstract). Eur. J. Nucl. Med., 16, 392.Google Scholar
  88. 88.
    Goedemans, W.T., Panek, K.J., Ensing, G.J. et al. (1990) A new simple method for labelling of proteins with Tc-99m by derivatization with I-imino-4-mercaptobutyl groups, in Technetium and Rhenium in Chemistry and Nuclear Medicine, Vol. 3 (eds M. Nicolini, G. Bandolini and U. Mazzi), Cortina International, Verona and Raven Press, New York, pp. 595–604.Google Scholar
  89. 89.
    Joiris, E., Bastin, B. and Thornback, J.R. (1990) A new method for labelling of monoclonal antibodies, their fragments and other proteins with technetium-99m, in Technetium and Rhenium in Chemistry and Nuclear Medicine, Vol. 3 (eds M. Nicolini, G. Bandolini and U. Mazzi), Cortina International, Verona and Raven Press, New York, pp. 609–14.Google Scholar
  90. 90.
    Fritzberg, A.R., Abrams, P.G., Beaunier, P.C. et al. (1988) Specific and stable labeling of antibodies with technetium-99m with a di-amidedithiolate chelating agent. Proc. Natl Acad. Sci. USA, 85, 4025–29.CrossRefGoogle Scholar
  91. 91.
    Dean, R.T., Weber, R., Pak, K. et al. (1990) New facile methods for stably labelling antibodies with technetium-99m, in Technetium and Rhenium in Chemistry and Nuclear Medicine, Vol. 3 (eds M. Nicolini, G. Bandolini and U. Mazzi), Cortina International, Verona and Raven Press, New York, pp. 605–8.Google Scholar
  92. 92.
    Esienhart, M., Brandan, W., Missfeldt, M. (1989) Synthesis and in-vivo testing of bro-mobutyl amine substituted 1, 2-dithio-5, 9-diazacycloundecane: a verstile precursor for new Tc-99m-bis (aminoethanethiol) complexes. Nucl. Med. Biol., 16, 805–11.Google Scholar

Copyright information

© Azuwuike Owunwanne, Mohan Patel and Samy Sadek 1995

Authors and Affiliations

  • Azuwuike Owunwanne
    • 1
  • Mohan Patel
    • 2
  • Samy Sadek
    • 3
  1. 1.Department of Nuclear Medicine, Faculty of MedicineKuwait UniversityKuwait
  2. 2.Kuwait Central Radiopharmacy Kuwait Cancer Control CenterMinistry of Public HealthKuwait
  3. 3.Department of Nuclear Medicine Faculty of MedicineKuwait UniversityKuwait

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