Radiobiology as Applied to Radionuclide Therapy with an Emphasis on Low Dose Rate Radiation Effects

Abstract

The last 20 years has seen an explosive growth in our understanding of the molecular underpinnings of the response of human cells and tissues to ionizing radiation (IR) and the application of this information to the treatment of cancer. For reasons such as ease of data interpretation and relevance to conventional external-beam radiotherapy (XRT) for cancer, much of this understanding has been derived from studies of single or fractionated doses of X-rays or γ-rays in the 1–10 Gy dose range, typically delivered at a relatively high dose rate (HDR) on the order of 1 Gy/min. How realistically do such studies inform us of the biological basis of systemic radionuclide therapy (SRT) when the dose is delivered via the decay of a radiopharmaceutical at a low dose rate (LDR) over a protracted period of time? The sense that there may be some issues in extrapolating these earlier radiobiological principles to SRT derives in part from a number of recent observations that are not easily explained by conventional thinking. First are the unexpectedly good tumor responses to SRT that have sometimes been reported in the clinical literature. Second are a number of new questions that are raised by laboratory studies using LDR exposures, including whether phenomena such as bystander effects and inverse dose-rate effects contribute to the efficacy of SRT.