Targeted Radionuclides

  • Steven A. Leibel
Part of the Medical Radiology book series (MEDRAD)


Radiolabeled antibodies with specificity against tumor-associated antigens offer an exciting opportunity in oncology. Targeted radionuclides may have application in the diagnosis, staging, and treatment of malignancy as well as in the follow-up of previously treated patients. This review will focus on the use of radiolabeled antibodies to deliver radiation therapy. The historical observations leading to the current interest in targeted radionuclides will be summarized. Tumor antigens which serve as the target for radiolabeled antibodies and pertinent aspects of antibody preparation will be reviewed. The rationale for radioimmunotherapy is based on the ability of radioimmunoglobulin to selectively target to tumor both in patients and in experimental animals. From this research clinical trials have emerged, and the results of these preliminary studies will be presented.


Radiation Therapy Oncology Group Primary Liver Cancer Single Photon Emission Computerize Tomogra Bryonic Antigen Liver Ratio 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Alexander P (1972) Foetal antigens in cancer. Nature 235: 137–181PubMedCrossRefGoogle Scholar
  2. Bagshawe KD, Searle F, Lewis J, Brown P, Keep P (1980) Preliminary therapeutic and localization studies with human chorionic gonadotropin. Cancer Res 40: 3016–3017PubMedGoogle Scholar
  3. Bale WF, Spar IL, Goodland RL, Wolfe DE (1955) In vivo and in vitro studies of labeled antibodies against rat kidney and walker carcinoma. Proc Soc Exp Biol Med 89: 564–568PubMedGoogle Scholar
  4. Beck G, Bollack C (1974) Synthesis of ferritin in cultured hepatoma cells. Fedn Exp Biol Soc 47: 314–317CrossRefGoogle Scholar
  5. Belitsky P, Ghose T, Aqino J (1978) Radionuclide imaging of metastase from renal cell carcinoma by 1311-labeled antitumor antibody. Radiology 126: 515–517PubMedGoogle Scholar
  6. Berche C, Mach J-P, Lumbroso JD, Langlais C, Aubry F, Buchegger F, Carrel S, Rougier P, Parmentier C, Tubiana M (1982) Tomoscintigraphy for detecting gastrointestinal and medullary thyroid cancers: First clinical results using radiolabeled monoclonal antibodies against carcinoembryonic antigen. Br Med J 285: 1447–1451Google Scholar
  7. Burchiel SW (1983) Expression and detection of human tumor-associated antigens: Implications for radioimmunoimaging and radioimmunotherapy. In: Radioimmunoimaging and Radioimmunotherapy, Burchiel SW and Rhodes BA (eds), Elsevier Science Publishing Co., pp 13–23Google Scholar
  8. Carrasquillo JA, Krohn KA, Beaumier P, McGuffin RW, Brown JP, Hellstrom KE, Hellstrom I, Larson SM (1984) Diagnosis of and therapy for solid tumors with radiolabeled antibodies and immune fragments. Cancer Treat Rep 68: 317–328PubMedGoogle Scholar
  9. Clausen J, Edeling C-J, Fogh J (1974) 67Ga binding to human serum proteins and tumor components. Cancer Res 34: 1931–1937Google Scholar
  10. DeLand FH, Goldenberg DM (1983) In vivo cancer diagnosis by radioimmunodetection. In: Radioimmunoimaging and Radioimmunotherapy, Burchiel SW, Rhodes BA (eds), Elsevier Science Publishing Co., pp 329–343Google Scholar
  11. DeNardo GL, DeNardo SJ (1983) Perspectives on the future of radioimmunodiagnosis and radioimmunotherapy and cancer. In: Radioimmunoimaging and Radioimmunotherapy, Burchiel SW, Rhodes BA (eds), Elsevier Science Publishing Co., pp 41–62Google Scholar
  12. DeNardo SJ, DeNardo GL, Peng J-S, Colcher D (1983) Monoclonal antibody radiopharmaceuticals for cancer radioimmunotherapy, Burchiel SW, Rhodes BA (eds), Elsevier Science Publishing Co., pp 409–417Google Scholar
  13. DeNardo GL, Raventos A, Hines HH, Scheibe PO, Macey DJ, Hays MT, DeNardo SJ (1985) Requirements for a treatment planning system for radioimmunotherapy. Int J Radiat Oncol Biol Phys 11: 335–348PubMedCrossRefGoogle Scholar
  14. Epenetos AA, Britton KE, Mather S, Shepherd J, Granowska M, Taylor-Papadimitriou J, Nimmon CC, Durbin H, Hawkins LR, Malpas JS, Bodmer WF (1982) Targeting of iodine-123-labelled tumour-associated monoclonal antibodies to ovarian, breast, and gastrointestinal tumours. Lancet 2: 999–1006PubMedCrossRefGoogle Scholar
  15. Epenetos AA, Courtenay-Luck N, Hainan KE, Hooker G, Hughes JMB, Krausz T, Lambert J, Lavender JP, MacGregor WG, McKenzie CJ, Munro A, Myers MJ, Orr JS, Pearse EE, Snook D, Webb B, Burchell J, Durbin H, Kemshead J, Taylor-Papadimitriou J (1984) Antibody-guided irradiation of malignant lesions: Three cases illustrating a new method of treatment. A report from the Hammersmith Oncology Group and the Imperial Cancer Research Fund. Lancet 1: 1441–1443Google Scholar
  16. Epenetos AA, Shepherd J, Britton KE, Mather S, TaylorPapadimitriou J, Granowska M, Durbin H, Nimmon CC, Hawkins LR, Malpas JS, Bodmer WF (1985) 1231 radio-iodinated antibody imaging of occult ovarian cancer. Cancer 55: 984–987Google Scholar
  17. Eshhar Z, Order SE, Katz DH (1974) Ferritin, a Hodgkin’s disease associated antigen. Proc Nat Acad Sci USA 71: 3956–3960PubMedCrossRefGoogle Scholar
  18. Ettinger DS, Dragon LH, Klein J, Sgagias M, Order SE (1979) Isotopic immunoglobulin in an integrated multimodal treatment program for a primary liver cancer: A case report. Cancer Treat Rep 63: 131–134Google Scholar
  19. Ettinger DS, Order SE, Wharam MD, Parker MK, Klein JL, Leichner PK (1982) Phase I—II study of isotopic immunoglobulin therapy for primary liver cancer. Cancer Treat Rep 66: 289–297PubMedGoogle Scholar
  20. Farrands PA, Perkins AC, Pimm MV, Hardy JD, Embleton MJ, Baldwin RW, Hardcastle JD (1982) Radioimmunodetection of human colorectal cancers by an anti-tumour monoclonal antibody. Lancet 2: 397–400PubMedCrossRefGoogle Scholar
  21. Friedman MA (1983) Primary hepatocellular cancer-present results and future prospects. Int J Radiat Oncol Biol Phys 9: 1841–1850PubMedGoogle Scholar
  22. Gold P, Freedman SE (1965) Specific carcinoembryonic antigens of the human digestive system. J Exp Med 122: 467–481PubMedCrossRefGoogle Scholar
  23. Goldenberg DM (1976) Oncofetal and other tumor-associated antigens of the human digestive system. Curr Topics Pathol 63: 289–342CrossRefGoogle Scholar
  24. Goldenberg DM, DeLand FH (1982) Review. History and status of tumor imaging with radiolabeled antibodies. J Biol Resp Mod 1: 121–136Google Scholar
  25. Goldenberg DM, DeLand F, Kim E, Bennett S, Primus FJ, van Nagell JB Jr, Estes N, DeSimone P, Rayburn P (1978) Use of radiolabeled antibodies to carcinoembryonic antigen for the detection and localization of diverse cancers by external photoscanning. N Engl J Med June 22: 1384–1388CrossRefGoogle Scholar
  26. Goldenberg DM, Kim EE, DeLand F, Spremulli E, Nelson MO, Gockerman JP, Primus FJ, Corgan RL, Alpert E (1980a) Clinical studies on the radioimmunodetection of tumors containing alpha-fetoprotein. Cancer 45: 2500–2505PubMedCrossRefGoogle Scholar
  27. Goldenberg DM, Kim EE, DeLand FH, van Nagell JR Jr, Javadpour N (1980b) Radioimmunodetection of cancer using radioactive antibodies to human chorionic gonadotropin. Science 208: 1284–1286PubMedCrossRefGoogle Scholar
  28. Gropp C, Havemann K, Lehmann F-G (1978) Carcinoembryonic antigen and ferritin in patients with lung cancer before and during therapy. Cancer 42: 2802–2808PubMedCrossRefGoogle Scholar
  29. Kohler G, Milstein C (1975) Continuous cultures of fused cells secreting antibody of predefined specificity. Nature 256: 495–497PubMedCrossRefGoogle Scholar
  30. Larson SM, Brown JP, Wright PW, Carrasquillo JA, Hellstrom I, Hellstrom KE (1983 a) Imaging of melanoma with 131I-labeled monoclonal antibodies. J Nucl Med 24: 123–129Google Scholar
  31. Larson SM, Carrasquillo JA, Krohn KA, Brown JP, McGuffin RW, Ferens JM, Grahan MM, Hill LD, Beaumier PL, Hellstrom KE, Hellstrom I (1983 b) Localization of 131I-labeled p97-specific fab fragments in human melanoma as a basis for radiotherapy. J Clin Invest 72: 2101–2114Google Scholar
  32. Leibel SA (1983) Radioimmunotherapy (chapter 27). Modern Radiation Oncology, Gilbert HA (eds), JB Lippincott Co., pp 581–606Google Scholar
  33. Leibel SA, Klein JL, Sgagias M, Leichner P, Order SE (1981) The integration of tumor associated antigens in cancer management. Sem Oncol 8: 92–102Google Scholar
  34. Leichner PK, Klein JL, Fishman EK, Siegelman SS, Ettinger DS, Order SE (1984) Comparative tumor dose from 131I-labeled polyclonal antiferritin, anti-AFP, and anti-CEA in primary liver cancer. Cancer Drug Delivery 1: 321–328PubMedCrossRefGoogle Scholar
  35. Leichner PK, Klein JL, Siegelman SS, Ettinger DS, Order SE (1983) Dosimetry of 131I-labeled antiferritin in hepatom: Specific activities in the tumor and liver. Cancer Treat Rep 67: 647–658Google Scholar
  36. Lenhard RE Jr, Order SE, Spunberg JJ, Asbell SO, Leibel SA (1985) Isotopic immunoglobulin: A new systemic therapy for advanced hodgkins disease. J Clin Oncol 3: 1296–1300Google Scholar
  37. Mach J-P, Buchegger F, Forni M, Ritschard J, Berche C, Lumbroso JD, Schreyer M, Girardet C, Accolla RS, Carrel S (1981) Use of radiolabelled monoclonal anti-CEA antibodies for the detection of human carcinomas by external photoscanning and tomoscintigraphy. Immunol Today 2: 239–249CrossRefGoogle Scholar
  38. Mach J-P, Buchegger F, Forni M, Ritschard J, Carrel S, Haskell CM (1983) Radiolabeled polyclonal and monoclonal antiCEA antibodies for the in vivo detection of human colorectal carcinoma. In: Radioimmunoimaging and radioimmunotherapy, Burchiel SW, Rhodes BA (eds), Elsevier Science Publishing Co., pp 345–356Google Scholar
  39. Marchese MJ, Hall EJ, Hilaris BS (1984) Encapsulated iodine-125 in radiation oncology. I. Study of the relative biological effectiveness ( RBE) using low dose rate irradiation of mammalian cell cultures. Am J Clin Oncol 7: 607–611Google Scholar
  40. Matsumoto Y, Suziki T, Asad I, Ozawa K, Tobe T, Honjol I (1982) Clinical classification of hepatoma in Japan according to serial changes in serum alpha-feto protein levels. Cancer 49: 354–360PubMedCrossRefGoogle Scholar
  41. Moylan DJ, Order SE, Zinreich E, Leibel SA, Spunberg J, Asbell SO, Klein JL, Leichner P, Ettinger D, Powers G (1985) Phase I trial of radiolabeled antibody as an adjuvant to radiation therapy for unresectable non-small cell bronchogenic carcinoma: A radiation therapy oncology group study. Cancer Treat RepGoogle Scholar
  42. Munro HN, Linder MC (1978) Ferritin: Structure, biosynthesis and role in iron metabolism. Physiol Rev 58: 317–396Google Scholar
  43. Old LJ, Stockert E, Boyse EA, Kin JH (1968) Antigenic modulation and loss of TL antigen from cells exposed to TL antibody: Study of the phenomenon in vitro. J Exp Med 127: 523–539PubMedCrossRefGoogle Scholar
  44. Olsson L, Kaplan HS (1980) Human hybridomas producing monoclonal antibodies of predefined antigenic specificity. Proc Natl Acad Sci USA 77: 5429–5431PubMedCrossRefGoogle Scholar
  45. Order SE (1982) Monoclonal antibodies: Potential role in radiation therapy and oncology. Int J Radiat Oncol Biol Phys 8: 1193–1201PubMedGoogle Scholar
  46. Order SE (1984) Radioimmunoglobulin therapy of cancer. Comp Ther 10: 9–18Google Scholar
  47. Order SE, Bloomer WD, Jones AG, Kaplan WD, Davis MA, Adelstein J, Hellman S (1975) Radionuclide immunoglobulin lymphangiography: A case report. Cancer 35: 1487–1492Google Scholar
  48. Order SE, Kirkman R, Knapp R (1974) Serologic immunotherapy: Results and probable mechanism of action. Cancer 34: 175–183Google Scholar
  49. Order SE, Klein JL, Ettinger D, Alderson P, Siegelman S, Leichner P (1980 a) Phase I—II study of radiolabeled antibody integrated in the treatment of primary hepatic malignancies. Int J Radiat Oncol Biol Phys 6: 703–710Google Scholar
  50. Order SE, Klein JL, Ettinger D, Alderson P, Siegelman S, Leichner P (1980b) Use of isotopic immunoglobulin in therapy. Cancer Res 40: 3001–3007PubMedGoogle Scholar
  51. Order SE, Klein JL, Leichner PK (1981) Antiferritin IgG antibody for isotopic cancer therapy. Oncology 38: 154–160PubMedCrossRefGoogle Scholar
  52. Order SE, Leibel S (1984) Radiolabelled antibodies in the treatment of primary liver cancer. Applied Radiology 15: 67–73Google Scholar
  53. Order SE, Stillwagon GB, Klein JL, Leichner PK, Siegel-man SS, Fishman EK, Ettinger DS, Haulk T, Kopher K, Finney K, Surdyke M, Self S, Leibel S (1985) 131I antiferritin, a new treatment modality in hepatoma. Clin Oncol 3: 1573–1582Google Scholar
  54. Pauwels EKJ, Cleton FJ (1984) Radiolabelled monoclonal antibodies: A new diagnostic tool in nuclear medicine. Radiother Oncol 1: 333–338Google Scholar
  55. Pressman D, Keighley G (1948) The zone of activity of antibodies as determined by the use of radioactive tracers: The zone of activity of nephritoxic anti-kidney serum. J Immunol 59: 141–146Google Scholar
  56. Pressman D, Korngold L (1953) The in vivo localization of anti-wagner-osteogenic-sarcoma antibodies. Cancer 6: 619–623PubMedCrossRefGoogle Scholar
  57. Quinones J, Mizejewski G, Beierwaltes H (1971) Choriocarcinoma scanning using radiolabeled antibody to chorionic gonadotropin. J Nucl Med 12: 69–75PubMedGoogle Scholar
  58. Rhodes BA, Burke DJ, Breslow K, Reed K, Austin R, Burchiel SW (1983) Effects of circulating antigen on antibody localization in vivo. In: Radioimmunoimaging and Radioimmunotherapy, Burchiel SW, Rhodes BA (eds), Elsevier Science Publishing Co., pp 25–39Google Scholar
  59. Rostock RA, Klein JL, Leichner PK, Kopher KA, Order SE (1983) Selective tumor localization in experimental hepatoma by radiolabeled antiferritin antibody. Int J Radiat Oncol Biol Phys 9: 1345–1350PubMedCrossRefGoogle Scholar
  60. Rostock RA, Klein JL, Kopher KA, Order SE (1984 a) Variables affecting the tumor localization of 131I-antiferritin in experimental hepatoma. Am J Clin Oncol 6: 9–18Google Scholar
  61. Rostock RA, Klein JL, Leichner PK, Order SE (1984b) Distribution of and physiologic factors that affect 1311 antiferritin tumor localization in experimental hepatoma. Int J Radiat Oncol Biol Phys 10: 1135–1141PubMedCrossRefGoogle Scholar
  62. Sarcione EJ, Smalley JR, Lema MJ, Stutzman L (1977) Increased ferritin synthesis and release by hodgkin’s disease peripheral blood lymphocytes. Int J Cancer 20: 339–346PubMedCrossRefGoogle Scholar
  63. Scheinberg DA, Strand M, Gansow OA (1982) Tumor imaging with radioactive metal chelates conjugated to monoclonal antibodies. Science 215: 1511–1513PubMedCrossRefGoogle Scholar
  64. Sears HF, Atkinson B, Mattis J, Ernst C, Herlyn D, Steplewski Z, Hayry P, Koprowski H (1982) Phase-I clinical trial of monoclonal antibody in treatment of gastrointestinal tumours. Lancet 1: 762–765PubMedCrossRefGoogle Scholar
  65. Sherman DM, Carabell SC, Belli JA, Hellman S (1982) The effect of dose rate and adriamycin on the tolerance of thoracic radiation in mice. Int J Radiat Oncol Biol Phys 8: 45–51PubMedGoogle Scholar
  66. Spar IL, Bale WF, Marrack D, Dewey WC, McCardle RJ, Harper PV (1967) 131I-labeled antibodies to human fibrinogen. Cancer 20: 865–870Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1988

Authors and Affiliations

  • Steven A. Leibel
    • 1
  1. 1.School of MedicineUniversity of CaliforniaSan FranciscoUSA

Personalised recommendations