WE‐EF‐BRA‐05: Experimental Design for High‐Throughput In‐Vitro RBE Measurements Using Protons, Helium and Carbon Ions
Purpose: To design and validate experimental setups for investigation of dose and LET effects in cell kill for protons, helium and carbon ions, in high throughput and high accuracy cell experiments. Methods: Using the Geant4 Monte Carlo toolkit, we designed 3 custom range compensators to simultaneously expose cancer cells to different doses and LETs from selected portions of pristine ion beams from the entrance to points just beyond the Bragg peak. To minimize the spread of LET, we utilized mono-energetic uniformly scanned beams at the HIT facility with support from the DKFZ. Using different entrance doses and LETs, a matrix of cell survival data was acquired leading to a specific RBE matrix. We utilized the standard clonogenic assay for H460 and H1437 lung-cancer cell lines grown in 96-well plates. Using these plates, the data could be acquired in a small number of exposures. The ion specific compensators were located in a horizontal beam, designed to hold two 96-wells plates (12 columns by 8 rows) at an angle of 30o with respect to the beam direction. Results: Using about 20 hours of beam time, a total of about 11,000 wells containing cancer cells could be irradiated. The H460 and H1437 cell lines exhibited a significant dependence on LET when they were exposed to comparable doses. The results were similar for each of the investigated ion species, and indicate the need to incorporate RBE into the ion therapy planning process. Conclusion: The experimental design developed is a viable approach to rapidly acquire large amounts of accurate in-vitro RBE data. We plan to further improve the design to achieve higher accuracy and throughput, thereby facilitating the irradiation of multiple cell types. The results are indicative of the possibility to develop a new degree of freedom (variable RBE) for future clinical ion therapy optimization. Work supported by the Sister Institute Network Fund (SINF), University of Texas MD Anderson Cancer Center.