Dose-rate effects in targeted radiotherapy.

The physical dose delivered in radio-immunotherapy (RIT) may not, by itself, be a reliable indicator of the likely effectiveness of the treatment. Radiobiological considerations, in particular those relating to the dose-rate, are also very relevant. Dose-rate effects are important in conventional radiotherapy because of their ability to produce differential sparing effects between normal and malignant tissue. With targeted radiotherapy, in which dose-rates are likely to vary both spatially and temporally, the instantaneous dose-rate is additionally relevant since it determines whether or not any on-going clonogenic tumour re-population can be controlled. Therefore, for RIT in particular, there are two separate facets to the dose-rate effect, one concerned with the relative ability of different tissues to recover from radiation damage, the other concerned with the absolute ability to control concurrent tumour re-growth. In this article these two aspects are examined in terms of the linear-quadratic model and the implications assessed. Other radiobiological issues, such as re-oxygenation and cell cycle re-distribution are not discussed here.

[1]  W. E. Liversage.  A critical look at the ret. , 1971, The British journal of radiology.

[2]  R G Dale,et al.  The application of the linear-quadratic dose-effect equation to fractionated and protracted radiotherapy. , 1985, The British journal of radiology.

[3]  R. Dale,et al.  Cell loss factors and the linear-quadratic model. , 1995, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[4]  T. Wheldon,et al.  The radiobiology of targeted radiotherapy. , 1990, International journal of radiation biology.

[5]  R. Sutherland,et al.  Dosimetry models for radioimmunotherapy. , 1988, Medical physics.

[6]  I. Turesson,et al.  The predictive value of skin telangiectasia for late radiation effects in different normal tissues. , 1986, International journal of radiation oncology, biology, physics.

[7]  J. O’Donoghue.  The Impact of Tumor Cell Proliferation in Radioimmunotherapy , 1994, Cancer.

[8]  G. Barendsen,et al.  Dose fractionation, dose rate and iso-effect relationships for normal tissue responses. , 1982, International journal of radiation oncology, biology, physics.

[9]  K. Trott,et al.  What is known about tumour proliferation rates to choose between accelerated fractionation or hyperfractionation? , 1985, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[10]  D. Goodhead.  Saturable repair models of radiation action in mammalian cells. , 1985 .

[11]  W. M. Gray,et al.  Cumulative Radiation Effect Part III: Continuous radiation therapy — Short-lived sources , 1973 .

[12]  R. Hawkins.  A statistical theory of cell killing by radiation of varying linear energy transfer. , 1994, Radiation research.

[13]  R G Dale,et al.  Time-dependent tumour repopulation factors in linear-quadratic equations--implications for treatment strategies. , 1989, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[14]  K H Chadwick,et al.  A molecular theory of cell survival. , 1973, Physics in medicine and biology.

[15]  S. B. Field,et al.  The response of mouse skin to irradiation with neutrons from the 62 MV cyclotron at Clatterbridge, U.K. , 1988, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[16]  S B Curtis,et al.  Lethal and potentially lethal lesions induced by radiation--a unified repair model. , 1986, Radiation research.

[17]  Albrecht M. Kellerer,et al.  THEORY OF DUAL RADIATION ACTION. , 1972 .

[18]  M. Frankenberg-Schwager.  Review of repair kinetics for DNA damage induced in eukaryotic cells in vitro by ionizing radiation. , 1989, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[19]  J F Fowler,et al.  Rapid repopulation in radiotherapy: a debate on mechanism. The phantom of tumor treatment--continually rapid proliferation unmasked. , 1991, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[20]  A. Barrett,et al.  Strategies for systemic radiotherapy of micrometastases using antibody-targeted 131I. , 1988, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[21]  S. Tucker,et al.  Isoeffect models and fractionated radiation therapy. , 1987, International journal of radiation oncology, biology, physics.

[22]  Rapid repopulation in radiotherapy: Debate on mechanism , 1992 .

[23]  M. Chappell,et al.  Model based calculation for effective cancer radioimmunotherapy. , 1995, The British journal of radiology.

[24]  K. Trott,et al.  Possible dose rate dependence of recovery kinetics as deduced from a preliminary analysis of the effects of fractionated irradiations at varying dose rates. , 1988, The British journal of radiology.

[25]  J. Fowler.  The linear-quadratic formula and progress in fractionated radiotherapy. , 1989, The British journal of radiology.

[26]  W. Millar.  Application of the linear-quadratic model with incomplete repair to radionuclide directed therapy. , 1991, The British journal of radiology.

[27]  G. Steel,et al.  Differences in radiation response among human cervix carcinoma cell lines. , 1988, Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology.

[28]  R. Pedley,et al.  Comparative radioimmunotherapy using intact or F(ab')2 fragments of 131I anti-CEA antibody in a colonic xenograft model. , 1993, British Journal of Cancer.

[29]  J. Fowler.  Radiobiological aspects of low dose rates in radioimmunotherapy. , 1990, International journal of radiation oncology, biology, physics.

[30]  J. Fowler,et al.  Dose-rate effects: some theoretical and practical considerations. , 1960, The British journal of radiology.

[31]  S. Goddu,et al.  Application of the linear-quadratic model to radioimmunotherapy: further support for the advantage of longer-lived radionuclides. , 1994, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[32]  J L Humm,et al.  Dosimetric aspects of radiolabeled antibodies for tumor therapy. , 1986, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[33]  H D Thames,et al.  An 'incomplete-repair' model for survival after fractionated and continuous irradiations. , 1985, International journal of radiation biology and related studies in physics, chemistry, and medicine.

[34]  C. Orton,et al.  A simplification in the use of the NSD concept in practical radiotherapy. , 1973, The British journal of radiology.

[35]  R. Dale,et al.  Effect of tumour shrinkage on the biological effectiveness of permanent brachytherapy implants. , 1994, The British journal of radiology.

[36]  J. Fowler,et al.  Radiobiology of radiolabeled antibody therapy as applied to tumor dosimetry. , 1993, Medical physics.