Mapping the Relative Biological Effectiveness of Proton, Helium and Carbon Ions with High-Throughput Techniques

SIMPLE SUMMARY: Although particle therapy using protons and heavier ions has many inherent advantages when compared to x-rays for cancer treatment, numerous unknowns still exist in the radiobiology of particle therapy. Informative high-accuracy biological effects data are lacking and difficult to obtain. This study aimed to provide a novel high-throughput experimental method to more efficiently obtain large amounts of biophysical data of particle therapy and to correlate the biological responses with the physical characteristics of particle beams. ABSTRACT: Large amounts of high quality biophysical data are needed to improve current biological effects models but such data are lacking and difficult to obtain. The present study aimed to more efficiently measure the spatial distribution of relative biological effectiveness (RBE) of charged particle beams using a novel high-accuracy and high-throughput experimental platform. Clonogenic survival was selected as the biological endpoint for two lung cancer cell lines, H460 and H1437, irradiated with protons, carbon, and helium ions. Ion-specific multi-step microplate holders were fabricated such that each column of a 96-well microplate is spatially situated at a different location along a particle beam path. Dose, dose-averaged linear energy transfer (LET(d)), and dose-mean lineal energy (y(d)) were calculated using an experimentally validated Geant4-based Monte Carlo system. Cells were irradiated at the Heidelberg Ion Beam Therapy Center (HIT). The experimental results showed that the clonogenic survival curves of all tested ions were y(d)-dependent. Both helium and carbon ions achieved maximum RBEs within specific y(d) ranges before biological efficacy declined, indicating an overkill effect. For protons, no overkill was observed, but RBE increased distal to the Bragg peak. Measured RBE profiles strongly depend on the physical characteristics such as y(d) and are ion specific.