Techniques of Cell Labeling: An Overview

  • M. L. Thakur
  • S. McKenney
Part of the NATO ASI Series book series (NSSA, volume 88)


Over the past few decades the use of blood cells labeled with radioactive substances has become increasingly popular. The aims of investigations have changed from the study of cell origin to the study of cell kinetics in health and disease and to the use of radiolabeled cells as a non-invasive diagnostic modality. Changed with the times are also the techniques of labeling blood cells with radioactive substances. The importance of techniques lies not only in the efficacy by which the blood cells are labeled but also in the ease by which the procedure is performed. The efficacy, the ease of procedure, and the use of nontoxic substances greatly add to the prevention of cell injury and to the preservation of cell pathophysiologic function.


Cell Label Human Platelet Soluble Agent Platelet Suspension Phagocytic Ability 
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  1. 1.
    J. R. Rubini, E. West-Cott, S. Keller, In vitro DNA-labeling of bone marrow and leukemic blood leukocytes with tritiated Thymidine-II, 3H Thymidine biochemistry in vitro, J Lab Clin Med, 68:566 (1966).Google Scholar
  2. 2.
    T. T. Odell, F. N. Gamble, J. Furth, Life span of naturally labeled platelets of rats, Fed Proc 12: 398 (1953).Google Scholar
  3. 3.
    J. A. Cohen and W. G. P. J. Warringa, the fate of P-32-labeled di-isopropylfluorophosphate in the human body and its use as a labeling agent in the study of the turnover of blood plasma and red cells, J Clin Invest 33: 459 (1954).Google Scholar
  4. 4.
    D. Grob, J. L. Lilienthal, A. M. Harvey, The administration of di-isopropylfluorophosphate (DFPO) to man, Bull Johns Hopkins Hosp 80: 217 (1947).Google Scholar
  5. 5.
    M. L. Thakur and A. Gottschalk, Role of radiopharmaceuticals in nuclear hematology, Radiopharmaceuticals-II The Society of Nuclear Medicine, New York, 341 (1979).Google Scholar
  6. 6.
    M. L. Thakur, Radioisotopic-labeling of platelets: a historical perspective, Semin Thromb Hemostas 9: 79 (1983).Google Scholar
  7. 7.
    M. C. Morgan, R. P. Keating, E. H. Reisner, Labeling rabbit platelets with Iodine-131, Proc Soc Exp Biol Med 85: 420 (1954).Google Scholar
  8. 8.
    B. Stoic, Iodine metabolism in leukocytes: effects of graded iodide concentrations, Biochem Med 10: 293 (1974).Google Scholar
  9. 9.
    J. S. Robertson, W. L. Milne, S. H. Cohn, Labeling and tracing of rat blood platelets with Cr-51, Proc of the 2nd Int Radioisotopic Congress (July 1954) Butterworth Sci. Pub. London, 205 (1954).Google Scholar
  10. 10.
    J. G. McAfee and M. L. Thakur, Survey of radioactive agents for in vitro labeling of phagocytic leukocytes. I. Soluble agents, J Nucl Med 17: 480 (1976).Google Scholar
  11. 11.
    J. G. McAfee and M. L. Thakur, Survey of radioactive agents for in vitro labeling of phagocytic leukocytic. II. Soluble agents, J Nucl Med 17: 488 (1976).Google Scholar
  12. 12.
    A. W. Segal and A. J. Levi, Factors influencing the entry of dye into neutrophils leukocytes in the nitroblue tetrazolium test, Clin Sci Mol Med 48: 201 (1974).Google Scholar
  13. 13.
    A. D. Nunn, The kinetics of incorporation of In-111 into m-tetraphenylporhine, J Radiopharm Chemistry 1–2: 291 (1979).Google Scholar
  14. 14.
    Z. D. Grossman, B. W. Wistow, J. G. McAfee, et al, Platelets labeled with oxine complexes of Tc-99m and In-111. Part 2: Localization of experimetnally induced vascular lesions, J Nucl Med 19: 488 (1978).PubMedGoogle Scholar
  15. 15.
    M. L. Thakur, Gallium-67 and In-111 radiopharmaceuticals, Int J Appl Radiat Isot 28: 183 (1977).CrossRefGoogle Scholar
  16. 16.
    M. L. Thakur, R. E. Coleman, M. J. Welch, In-111-Labeled leukocytes for the localization of abscesses: preparation, analysis, tissue distribution, and comparison with Gallium-67 citrate in dogs, J Lab Clin Med 89: 217 (1977).Google Scholar
  17. 17.
    Amersham Corporation, In-111-Oxine solution: radiochemical for cell labeling, Code IN 15PA.Google Scholar
  18. 18.
    J. G. McAfee, G. M. Gagne, G. Subramanian, et al, Distribution of leukocytes labeled with In-111-Oxine in dogs with acute inflammatory lesions, J Nucl Med 21: 1059 (1980).Google Scholar
  19. 19.
    M. L. Thakur, A. W. Segal, L. Louis, et al, In-111-labeled cellular blood components: mechanism of labeling and intracellular location in human neutrophils, J Nucl Med 18: 1020 (1977).Google Scholar
  20. 20.
    K. J. Hwang, Mode of interaction of (In3+) 8-hydroxyquinoline with membrane, J Nucl Med 19: 1162 (1978).Google Scholar
  21. 21.
    A. R. Wilkinson, R. J. Hawker, L. M. Hawker, In-111-labeled canine platelets, Thromb Res 13: 175 (1978).Google Scholar
  22. 22.
    U. Scheffel, M. F. Tsan, P. A. McIntyre, Labeling of human platelets with In-111 8-hydroxyquinoline, J Nucl Med 20: 524 (1979).Google Scholar
  23. 23.
    M. L. Thakur, M. J. Welch, J. H., et al, In-111-labeled platelets: studies on preparation and evaluation of in vitro and in vivo functions, Thromb Res 9: 345 (1976).PubMedCrossRefGoogle Scholar
  24. 24.
    G. H. Rannie, M. L. Thakur, W. L. Ford, In-111-labelled lymphocytes: preparation, evaluation and comparison with Cr-51 lymphocytes in rats, Clin Exp Immunol 29: 509 (1977).Google Scholar
  25. 25.
    J. P. Lavender, J. M. Goldman, M. L. Thakur, et al, Kinetics of In-111-Labelled lymphocytes in normal subjects and patients with Hodgkins disease, Br Med J 2: 797 (1978).Google Scholar
  26. 26.
    J. Ferluga, A. C. Allison, M. L. Thakur, Use of In-111 for studies of cytoxicity mediated by lymphocytes or by antibodies and compliments, J Clin Lab Immunol 1: 339 (1979).Google Scholar
  27. 27.
    M. L. Thakur, C. L. Seifert, M. Madsen, et al, Neutrophil labeling: problems and pitfalls, Semin Nucl Med April (1984).Google Scholar
  28. 28.
    D. A. Goodwin, J. T. Bushberg, P. W. Doherty, et al, In-111labeled autologous platelets for location of vascular thrombi in humans, J Nucl Med 19: 626 (1978).Google Scholar
  29. 29.
    M. L. Thakur, L. Walsh, H. L. Malech, et al, In-111-labeled human platelets: improved method efficacy and evaluation, J Nucl Med 22: 381 (1981).Google Scholar
  30. 30.
    M. B. Zucker, Effect of heparin on platelet function, Thrombosis et Diathesis 33: 64 (1974).Google Scholar
  31. 31.
    J. McCullough, B. J. Weiblen, M. E. Clay, et al, Effect of leukocyte antibodies on the in vivo fate of In-111-labeled granulocytes, Blood 58: 164 (1981).Google Scholar
  32. 32.
    J. P. Dutcher, C. A. Schiffer, G. S. Johnston, et al, Alloimmunization prevents the migration of transfused In-111-labeled granulocytes to sites of infection, Blood 62: 354 (1983).Google Scholar
  33. 33.
    B. J. Weiblen, J. McCullough, L. Forstrom, et al, Kinetics of In-111-labeled granulocytes, in: “In-111-Labeled Neutrophils, Platelets, and Lymphocytes, M. L. Thakur and A. Gottschalk, eds., Triverium, New York (1979).Google Scholar
  34. 34.
    E. Throsby, Cell-specific and common antigens on human granulocytes and lymphocytes demonstrated with cytotoxic hetero-antibodies, Vox Sang 13: 194 (1967).Google Scholar
  35. 35.
    M. L. Thakur, J. P. Lavender, R. N. Arnot, et al, In-111-labeled autologous leukocytes in man, J Nucl Med 18: 1014 (1977).Google Scholar
  36. 36.
    G. V. R. Born, F. Michal, 5-Hydroxytryptamine Receptors of Platelets in Biochemistry and Pharmacology of Platelets, Elsevier, p. 302 (1975).Google Scholar
  37. 37.
    U. Scheffel, M. F. Tsan, P. A. McIntyre, Labeling of human platelets with In-111 8-hydroxyquinoline, J Nucl Med 20: 524 (1979).Google Scholar
  38. 38.
    J. F. Mustard, D. W. Perry, M. G. Ardlie, et al, Preparation of suspension of washed platelets from humans, Br J Haematol 22: 193 (1972).Google Scholar
  39. 39.
    H. Sinn and D. J. Silvester, Simplified cell labeling with In-111-acetylacetone, Br J Radiol 52: 758 (1979).Google Scholar
  40. 40.
    C. J. Mathias, W. A. Heaton, M. J. Welch, et al, Comparison of In-111-oxine and In-111-acetylacetone for labeling of cells: in vivo and in vitro biological testing, Int J Appl Radiat Isot 32: 651 (1981).Google Scholar
  41. 41.
    W. T. Goedemans, Simplified cell labeling with In-111acetylacetone and In-111-oxine, Br J Radiol 54: 636 (1981).Google Scholar
  42. 42.
    L. A. Spitzangle, C. A. Marino, S. Kasina, Lipophilic chelates of Tc-99m: tropolone, J Nucl Med 22: 981 (1981).Google Scholar
  43. 43.
    M. K. Dewanjee, S. A. Rao, P. Didisheim, In-111-tropolone, a new high affinity platelet label: preparation and evaluation of labeling parameters, J Nucl Med 22: 981 (1981).Google Scholar
  44. 44.
    H. J. Danpure, S. Osman, F. Brady, The labeling of blood cells in plasma with In-111-tropolonate, Br J Radiol 55: 247 (1982).Google Scholar
  45. 45.
    M. Peters, S. H. Saverymuttu, H. J. Reavy, et al, Imaging of inflammation with in-111-tropolonate-labeled leukocytes, J Nucl Med 24: 39 (1983).PubMedGoogle Scholar
  46. 46.
    J. S. Robertson, M. K. Dewanjee, W. L. Dunn, et al, Biodistribution and survival of human platelets labeled in buffered media and plasma, J Nucl Med 24: P73 (1983).Google Scholar
  47. 47.
    R. J. Hawker, C. E. Hall, and E. K. Gunson, In-111-tropolone versus oxine, J Nucl Med 24: 367 (1983).Google Scholar
  48. 48.
    M. R. Hardeman, Tropolone, the favorite ligand for cell labeling?, Eur J Nucl Med 7: 528 (1982).Google Scholar
  49. 49.
    S. Vallabhajosula, M. L. Greenberg, S. J. Goldsmith, The effect of pH on labeling of leukocyte preparation: oxine vs. tropolone, J Nucl Med 24: P301 (1983).Google Scholar
  50. 50.
    K. P. Gutner, J. N. Luken, J. A. Clanton, et al, Neutrophil labeling with In-111: tropolone vs. oxine, Radiology 149: 563 (1983).Google Scholar
  51. 51.
    T. Uchida, K. Tasunaga, S. Kariyone, et al, Survival and sequestration of Cr-51- and Tc-99m-labeled platelets, J Nucl Med 15: 801 (1974).Google Scholar
  52. 52.
    N. Linhart, B. Bok, M. Meigan, et al, Technetium-99m-labeled human leukocytes: in vitro and animal studies, in: “In-111Labeled Neutrophils, Platelets, and Lymphocytes,” M. L. Thakur, and A. Gottschalk, eds., Trivirum, New York (1979).Google Scholar
  53. 53.
    N. A. Farid, S. M. White, L. L. Heck, et al, Tc-99m-labeled leukocytes: preparation and use in identification of abscesses and tissue rejection, Radiolog 148: 827 (1983).Google Scholar
  54. 54.
    D. English and B. R. Anderson, Labeling of phagocytes from human blood with Tc-99m-sulfur colloid, J Nucl Med 16: 5 (1975).Google Scholar
  55. 55.
    H. J. Scroth, E. Oberhausen, R. Berberich, Cell labeling with colliodal substances in whole blood, Eur J Nucl Med 6: 469 (1981).Google Scholar
  56. 56.
    F. Lomas, Private Communications Google Scholar
  57. 57.
    M. A. Zimmer and S. M. Spies, Leukocyte labeling with colloidal In-111 in whole blood, Int J Appl Radiat Isot 34: 1544 (1983).Google Scholar
  58. 58.
    H. Showell, R. J. Freer, S. H. Zigmond, et al, The structure activity relationship of synthetic peptides as chemotactic factors and inducers of lysosomal enzyme secretion for neutrophils, J Exp Med 143: 1154 (1976).Google Scholar
  59. 59.
    R. J. Freer, A. R. Day, N. Muthukumarswami, D. Pinon, A. Wu, H. J. Showell, E. L. Becker, Formyl peptide chemoattractants: a model of the receptor on rabbit neutrophils, Biochemistry 21: 257 (1982).Google Scholar
  60. 60.
    W. A. Marasco, H. J. Showell, R. J. Freer, E. L. Becker, Anti-f-Met-Leu-Phe: similarities in fine specificity with the formyl peptide chemotaxis receptor of the neutrophil, J Immunol 128: 956 (1982).PubMedGoogle Scholar
  61. 61.
    S. S. Zogbhi, M. L. Thakur, A. Gottschalk, A potential radioactive agent for the selective labeling of human neutrophils in vitro, Int J Appl Radiat Isot (in press).Google Scholar
  62. 62.
    R. C. Verma, L. R. Bennett, T. Kawada, et al, Receptor mediated selective radiolabeling of neutrophils, J Nucl Med 24: P7 (1983).Google Scholar
  63. 63.
    H. Zola, P. McNamara, Thomas et al, The preparation and properties of monoclonal antibodies against human granulocyte membrane antigens, Br J Haematol 48: 481 (1981).Google Scholar
  64. 64.
    K. M. Skubitz, Y. Zhen, J. T. August, A human granulocyte-specific antigen characterized by use of monoclonal antibodies, Blood 61: 19 (1983).Google Scholar
  65. 65.
    H. L. Malech, Private Communication.Google Scholar
  66. 66.
    D. J. Hnatowich, W. W. Layne, R. L. Childs, The preparation and labeling of DTPA-coupled albumin, Int J Appl Radiat Isot 33: 327 (1982).Google Scholar
  67. 67.
    C. H. Paik, M. A. Ebbert, P. R. Murphy, et al, Factors influencing DTPA conjugation with antibodies by cyclic DTPA anhydride, J Nucl Med 24: 1158 (1983).Google Scholar
  68. 68.
    K. H. Konig, B. Steinberch, G. Schneewieg, et al, Zur chromamtographi von metallchelaten fresenius, Z Anal Chem 297: 144 (1979).Google Scholar
  69. M. L. Thakur, M. J. Barry, Preparation and evaluation of a new In-111 agent for efficient labeling of human platelets in plasma, J Lab Com. Radíopharm 19:1410 (1982).Google Scholar
  70. 70.
    S. L. Propst-Proctor, M. F. Dillingham, I. R. McDougall, et al, The white blood cell scan in orthopedics, Clin Orthop 168: 157 (1982).Google Scholar
  71. 71.
    J. P. Dutcher, C. A. Schiffer, G. S. Johnston, Rapid migration of In-111-labeled granulocytes to sites of infection, N Engl J Med 304: 586 (1981).Google Scholar
  72. 72.
    M. H. Rovekamp, M. R. Hardeman, J. B. van der Shoot, et al, In-111-labeled leukocyte scintigraphy in the diagnosis of inflammatory disease-first results, Br J Surg 68: 150 (1981).Google Scholar
  73. 73.
    G. N. Sfakianakis, W. Al-Sheikh, A. Heal, et al, Comparisons of scintigraphy with In-111 leukocytes and Ga-67 in the diagnosis of occult sepsis, J Nucl Med 23: 618 (1982).Google Scholar
  74. 74.
    M. R. Hardeman, E. G. J. Eitjes-van Overbeek, A. J. M. van Velzen, Labeling techniques of granulocytes and platelets with In-111-oxine, Nucl Geneeskunding Bull 4: 8 (suppl.) (1982).Google Scholar
  75. 75.
    H. Sinzinger, C. Leithner, R. Hofer, Continuous monitoring of human kidney transplants byautologous-labeled platelets, Nucl Geneeskunding Bull 4: 44 (suppl.) (1982).Google Scholar
  76. 76.
    K. H. Laws, J. A. Clanton, V. A. Starnes, et al, Kinetics and imaging of In-111-labeled autologous platelets in experimental myocardial infarction, Circulation 67: 110 (1983).Google Scholar
  77. 77.
    A. Heynes, Dup., P. N. Badenhorst, H. Pieters, et al, Preparation of a viable population of In-111-labeled human platelets, Thromb Haemost 42: 1473 (1980).Google Scholar
  78. 78.
    J. L. Ritchie, J. R. Stratton, B. Thiele, et al, In-111 platelet imaging for detection of platelet deposition in abdominal aneurysms and prosthetic arterial grafts, Am J Cardiol 47: 882 (1981).Google Scholar
  79. 79.
    A. W. Heaton, H. H. Davis, M. J. Welch, et al, In-111: a new radionuclide label for studying human platelet kinetics, Br J Haeamatology 42: 613 (1979).Google Scholar
  80. 80.
    M. G. Lotter, P. N. Badenhorst, A. Heyns, Dup. et al, Kinetics, distribution, and sites of destruction of canine blood platelets with In-111-oxine, J Nucl Med 21: 36 (1980).Google Scholar
  81. 81.
    Hill-Zoble, U. Scheffel, P. A. McIntyre, et al, In-111-oxinelabeled rabbit platelets: in vivo distribution and site of destruction, Blood 61: 149 (1983).Google Scholar
  82. 82.
    A. R. Wilkinson, R. J. Hawker, L. M. Hawker, In-111-labeled canine platelets, Thromb Res 13: 175 (1978).Google Scholar
  83. 83.
    I. Klonizakis, A. M. Peters, M. L. Fitzpatrick, et al, Radionuclide distribution following injection of In-111-labeled platelets, Br J Haematol 46: 595 (1980).Google Scholar
  84. 84.
    A. Heynes, Dup., M. G. Lotter, P. N. Badenhorst, et al, Kinetics, distribution, and sites of destruction of In-111-labeled human platelets, Br J Haematol 44: 269 (1980).Google Scholar

Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • M. L. Thakur
    • 1
  • S. McKenney
    • 1
  1. 1.Thomas Jefferson UniversityPhiladelphiaUSA

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