Development of an in vitro irradiation station for broad beam radiobiological experiment: study of A549 non-small cell lung cancer cell response after irradiation with charged particles of different LET

Abstract

Lung cancer is the leading cause of cancer related death. Currently, the average 5-year survival rate is only about 15 % and new modalities are under investigation to increase the patient survival as well as to improve the patient quality of life. Among the new modalities developed for the treatment of lung cancer, we find hadron-therapy and radio-immunotherapy both using charged particles. However, the studies performed about the potential benefit of such treatments emphasize that more data and fundamental works are needed to better understand the cellular response. In this work, the results obtained after the irradiation of A549 lung cancer cells with different types of charged particles (beta particles, protons, alpha particles and carbon ions) were compared to the standard X-ray irradiation. On one hand, the beta particles irradiations were performed with a liquid source at a low-dose-rate as found in actual radio-immunotherapy. On the other hand, a broad beam in vitro irradiation station was developed to perform heavy charged particles radiobiological experiment. For that purpose, the incident beam must be mono-energetic, uniform and stable. Although this can be obtained with the 2 MV Tandem accelerator of the LARN laboratory, one needs a system to check these requirements before performing the irradiation. The setup developed in this work allows visualising the beam to adjust the accelerator parameters in order to obtain a uniform beam. This system enables us to check the dose-rate and uniformity of the irradiated area before to proceed to the irradiation. Moreover, an online monitoring system has been developed to assess the dose-rate during the irradiation. The entire irradiation system has been validated by establishing the surviving fraction curves of A549 lung cancer cells after irradiation with protons, alpha particles and carbons ions. The results obtained have shown an increased efficiency of heavy charged particles in comparison to X-rays. The experiments carried out on A549 lung cancer cells with 10 keV/µm proton broad beam and with low-dose-rate beta particles have highlighted a hypersensitive response at low doses. This result is very interesting for the new modalities under development. Indeed, unlike cancer cells, normal cells have efficient repair mechanism and take the required time to repair. Hence, work with a lower dose-rate and/or dose, may lead to lower complication and a better patient’s quality of life with a same local control of the tumour.

Date of Award	24 Aug 2012
Original language	French
Awarding Institution	University of Namur
Supervisor	Stephane Lucas (Supervisor), Carine Michiels (Co-Supervisor), Muriel Lepere (President), Frank DECONNINCK (Jury), Thierry Vander Borght (Jury) & Philippe MARTINIVE (Jury)