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.