Radiobiological principles in intravascular irradiation

Abstract

Background. There is wide interest in the use of intravascular irradiation to control restenosis following balloon angioplasty. Part of the mechanism of restenosis appears to be the proliferation of smooth muscle cells (SMCs), triggered to divide by the damage caused by the angioplasty, and this proliferation can be inhibited by irradiation with γ-rays or β-rays. Methods. In vitro data for the survival of smooth muscle cells exposed to radiation was used to model the likely control of restenosis by radiation. Physical and biological data were used to estimate differences in biological effectiveness of γ-rays and β-rays, as well as the effect on cell killing of extending the exposure time. Results. Based on the radiosensitivity of SMCs, measured in vitro, and the limited proliferative potential of these normal somatic cells, it is possible to understand and to model quantitatively how a single acute γ-ray dose in the range of 15–20 Gy can inhibit restenosis. The few successful trials carried out to date where radiation has been shown to inhibit restenosis have all involved the γ-emitter Iridium-192. The use of this radionuclide involves radiation safety problems and an inconveniently long treatment time. Consequently, there is much interest in developing a β-emitting source that would solve both problems, and a number of different possibilities are being pursued. This development introduces two new problems discussed in this paper. First, β-rays in the megavoltage range are less effective biologically than γ-rays in the kilovoltage range, but the magnitude of the difference is not well known. Second, in the case of a single large dose, such as that proposed to inhibit restenosis, the biological effect will vary substantially as the exposure time varies from 1 to 20 min. If the clinical data are to be compared between centers using a variety of β and γ-emitting radionuclides, these factors will need to be taken into account. Conclusions. Doses of >15 Gy are unlikely to result in elimination of the restenosis problem but should delay onset of restenosis for a significant period; the larger the dose, the longer the delay. Successful trials of endovascular radiation completed to date involve γ-rays, while many systems being developed are based on β-emitting radionuclides. Experimental data are urgently needed so that allowances can be made for the difference in dose-rate and radiation quality between γ and β-emitting radionuclides.