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Experimental Design and Preliminary Results for High-Resolution and High-Throughput In-Vitro Measurements of Proton RBE


F Guan

F Guan*, R Mohan, J Dinh, M Kerr, L Perles, D Mirkovic, U Titt, X Zhu, M Gillin, R Meyn, S Lin, D Grosshans, UT MD Anderson Cancer Center, Houston, TX

TH-F-105-3 Thursday 2:00PM - 2:50PM Room: 105

Purpose: To design, develop and test a novel system for rapidly acquiring large amounts of in-vitro RBE data for protons as a function of LET, dose per fraction, dose rate, end point, and oxygenation for a wide range of cell lines.
Methods: Using the Geant4 Monte Carlo toolkit, we designed a specialized range compensator to simultaneously expose cells plated in 96 wells (12 columns by 8 rows) to different doses and variable LETs from selected portions of pristine proton beams from the entrance to points just beyond the Bragg peak. The use of 96-well plates can facilitate future high-throughput and high-resolution measurements. To minimize the spread of LET, we utilized monoenergetic uniformly scanned proton beams. Using a sequence of entrance doses and variable LETs, an RBE matrix related to different pairs of doses and LETs can be acquired in a relatively small number of exposures. In this study, we utilized the standard clonogenic assay for lung-cancer cell lines grown in 96-well plates. The compensator is mounted in the scanning beam snout with the beam directed toward the ceiling. In each exposure, one 96-well plate was positioned downstream for irradiation.
Results: Experimental data for lung cancer cells exposed to 79.7 MeV protons showed a significant increase in cell kill as a function of LET at locations close to the distal edge of the Bragg peak. For LET values of 8.34, 11.6, 13.5 and 14.6 keV/μm, the surviving fractions were found to be 0.24, 0.18, 0.088 and 0.031 at 4 Gy and 0.11, 0.074, 0.024 and 0.0035 at 6 Gy.
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.


Funding Support, Disclosures, and Conflict of Interest: NCI grant P01CA021239

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