Experimental Radioimmunotherapy: Biological Effectiveness and Comparison with External Beam Radiation

  • D. J. Buchsbaum
  • P. L. Roberson
Part of the Recent Results in Cancer Research book series (RECENTCANCER, volume 141)


Wessels (1990; Wessels et al. 1989) proposed that in order to assist in the prediction of the clinical efficacy of radioimmunotherapy (RIT) a radiobiological characterization of a tumor in animals be performed by correlating animal model data of external beam radiation therapy (XRT) and data of RIT in the same model and then measuring the absorbed dose in each. The fundamental question is whether or not the overall effect of 1 cGY of RIT is equivalent to that of 1 cGy of XRT. The dose rate at which the two are delivered is different, XRT being delivered at a high dose rate while RIT irradiation is delivered at a low dose rate, usually at rates lower than with implant therapy. In addition, the dose rate is decreasing with time due to the physical decay and biological clearance of the radionuclide from tumor and normal tissues. Furthermore, there are many geometric and biological factors that affect the homogeneity of dose deposition from RIT. A similar comparison approach would be used to convert animal RIT data to clinical RIT trials as has been used to compare animal and clinical XRT data (Wessels 1990; Knox et al. 1992; Fowler 1990; Orton and Cohen 1988; Dale 1985). By deriving a ratio of radiobiological response for the same tumor cell line between RIT and XRT in animals, a predictive response ratio would be obtained when examining the potential efficacy of different radiolabeled monoclonal antibodies (MAbs) for clinical trials.


Dose Rate Athymic Nude Mouse Medical Internal Radiation Dose Dose Inhomogeneity Tumor Volume Doubling Time 
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. Buchsbaum DJ, Lawrence TS (1991) Tumor therapy with radiolabeled monoclonal antibodies. Antibody Immunoconj Radiopharm 4: 245–272Google Scholar
  2. Buchsbaum DJ, Ten Haken RK, Heidorn DB, Lawrence TS, Glatfelter AA, Terry VH, Guilbault DM, Steplewski Z, Lichter AS (1990) A comparison of 131I-labeled monoclonal antibody 17-1A treatment to external beam irradiation on the growth of LS174T human colon carcinoma xenografts. Int J Radiat Oncol Biol Phys 18: 1033–1041PubMedCrossRefGoogle Scholar
  3. Buchsbaum DJ, Langmuir VK, Wessels BW (1993) Experimental radioimmunotherapy. Med Phys 20: 551–567PubMedCrossRefGoogle Scholar
  4. Buras RR, Wong JYC, Kuhn JA, Beatty BG, Williams LE, Wanek PM, Beatty JD (1993) Comparison of radioimmunotherapy and external beam radiotherapy in colon cancer xenografts. Int J Radiat Oncol Biol Phys 28: 473–479Google Scholar
  5. Dale RG (1985) The application of the linear quadratic dose-effect equation to fractionated and protracted radiotherapy. Br J Radiol 58: 515–528PubMedCrossRefGoogle Scholar
  6. Dillehay LE (1990) A model of cell killing by low-dose-rate radiation including repair of sublethal damage, G2 block, and cell division. Radiat Res 124: 201–207PubMedCrossRefGoogle Scholar
  7. Dillehay LE, Chang G, Williams JR (1988) Effects of methylxanthines on cell-cycle redistribution and sensitization to killing by low-dose-rate-radiation. Monogr Natl Cancer Inst 6: 173–176Google Scholar
  8. Fowler JF (1989) Fractionation and therapeutic gain. In: Steel GG, Adams GE, Horwitch A (eds) The biological basis of radiotherapy. Elsevier, Amsterdam, pp 181–207Google Scholar
  9. Fowler JF (1990) Radiobiological aspects of low dose rates in radioimmunotherapy. Int J Radiat Oncol Biol Phys 18: 1261–1269PubMedCrossRefGoogle Scholar
  10. Knox SJ, Levy R, Miller RA, Uhland W, Schiele J, Ruehl W, Finston R, Day-Lollini P, Goris ML (1990) Determinants of the antitumor effect of radiolabeled monoclonal antibodies. Cancer Res 50: 4935–4940PubMedGoogle Scholar
  11. Knox SJ, Goris ML, Wessels BW (1992) Overview of comparative studies comparing radioimmunotherapy with dose equivalent external beam irradiation. Radiother Oncol 23: 111–117PubMedCrossRefGoogle Scholar
  12. Knox SJ, Sutherland W, Goris ML (1993a) Determinants of low dose rate effects associated with radioimmunotherapy. Antibody Immunoconj Radiopharm 6: 197–207Google Scholar
  13. Knox SJ, Sutherland W, Goris ML (1993b) Correlation of tumor sensitivity to low-dose-rate irradiation with G2/M-phase block and other radiobiological parameters. Radiat Res 135: 24–31PubMedCrossRefGoogle Scholar
  14. Langmuir VK, Sutherland RM (1988) Radiobiology of radioimmuntherapy: current status. Antibody Immunoconj Radiopharm 1: 195–211Google Scholar
  15. Langmuir VK, Fowler JF, Knox SJ, Wessels BW, Sutherland RM, Wong JYC (1993) Radiobiology of radiolabeled antibody therapy as applied to tumor dosimetry. Med Phys 20: 601–610PubMedCrossRefGoogle Scholar
  16. Malaise EP, Fertil B, Chavaudra N, Guichard M (1986) Distribution of radiation sensitivities for human tumor cells of specific histological types: comparison of in vitro to in vivo data. Int J Radiat Oncol Biol Phys 12: 617–624PubMedCrossRefGoogle Scholar
  17. Mitchell JB, Bedford JS, Bailey SM (1979) Dose-rate effects in mammalian cells in culture. III. Comparison of cell-killing and cell proliferation during continuous irradiation for six different cell lines. Radiat Res 79: 737–751Google Scholar
  18. Molthoff CFM, Pinedo HM, Schluper HMM, Rutgers DH, Boven E (1992) Comparison of 131I-labelled anti-episialin 139H2 with cisplatin, cyclophosphamide or external-beam radiation for anti-tumor efficacy in human ovarian cancer xenografts. Int J Cancer 51: 108–115PubMedCrossRefGoogle Scholar
  19. Neacy WP, Wessels BW, Bradley EW, Kovandi S, Justice T, Danskin S, Sands H (1986) Comparison of radioimmunotherapy (RIT) and 4MV external beam radiotherapy of human tumor xenografts in athymic mice. J Nucl Med 27: 902–903Google Scholar
  20. Orton CG, Cohen LA (1988) A unified approach to dose-effect relationships in radiotherapy. I. Modified TDF and linear quadratic equations. Int J Radiat Oncol Biol Phys 14: 549–556Google Scholar
  21. Rofstad R (1985) Human tumor xenografts in radiotherapeutic research. Radiother Oncol 3: 35–46PubMedCrossRefGoogle Scholar
  22. Schmidberger H, Buchsbaum DJ, Blazar BR, Everson P, Vallera DA (1991) Radiotherapy in mice with yttrium-90-labeled anti-Ly1 monoclonal antibody: therapy of the T cell lymphoma EL4. Cancer Res 51: 1883–1890PubMedGoogle Scholar
  23. Wessels BW (1990) Current status of animal radioimmunotherapy. Cancer Res Suppl 50: 970s–973sGoogle Scholar
  24. Wessels BW, Vessella RL, Palme DF, Berkopec JM, Smith GK, Bradley EW (1989) Radiobiological comparison of external beam irradiation and radioimmunotherapy in renal cell carcinoma xenografts. Int J Radiat Oncol Biol Phys 17: 1257–1263PubMedCrossRefGoogle Scholar
  25. Williams JA, Edwards JA, Dillehay LE (192a) Quatitative comparison of radiolabeled antibody therapy and external beam radiotherapy in the treatment of human glioma xenografts. Int J Radiat Oncol Biol Phys 24:111–117Google Scholar
  26. Williams JR, Zhang Y-G, Dillehay LE (1992b) Sensitization processes in human tumor cells during protracted irradiation: possible exploitation in the clinic. Int J Radiat Oncol Biol Phys 24: 699–704PubMedCrossRefGoogle Scholar
  27. Wong JYC, Williams LE, Demidecki AJ, Wessels BW, Yan XW (1991) Radiobiologic studies comparing yttrium-90 irradiation and external beam irradiation in vitro. Int J Radiat Oncol Biol Phys 20: 715–722PubMedCrossRefGoogle Scholar
  28. Yorke ED, Wessels BW, Bradley EW (1991) Absorbed dose averages and dose heterogeneities in radioimmunotherapy. Antibody Immunoconj Radiopharm 4: 623–629Google Scholar

Copyright information

© Springer-Verlag Berlin · Heidelberg 1996

Authors and Affiliations

  • D. J. Buchsbaum
    • 1
  • P. L. Roberson
    • 2
  1. 1.Department of Radiation OncologyUniversity of Alabama at BirminghamBirminghamUSA
  2. 2.Department of Radiation OncologyUniversity of MichiganAnn ArborUSA

Personalised recommendations