Keywords: laser driven electron source, high dose rate, breast cancer, flash effect Internship Duration: 30/11/-1 - 30/11/-1
Head of the hosting team: S. Dobosz Dufrénoy
Website: Click here
Address of the host laboratory: CEA-Paris Saclay Team Physics at High Intensity CEA Paris Saclay / DRF-IRAMIS-LIDYL bât 701 p 50 91191 Gif sur Yvette France
Supervisor 1: Dobosz Dufrénoy SandrineE-mail: sandrine.dobosz@cea.fr Phone: +33 1 69086340
Supervisor 2: Bourneuf Emmanuelle
Radiotherapy is one of the most widely used therapeutic modalities in the treatment of cancer. Despite major advances in terms of targeting and efficiency, improvements remain necessary in order to control tumor volume while sparing surrounding healthy tissues. In this context, increasing the dose rate has shown very promising results. Indeed, the use of ultra-high dose rate (UHDR) beams not only induces tumor control similar to a conventional dose rate, but also increases the preservation of healthy tissues, thanks to the FLASH effect. The mechanisms underlying this effect are only partially known, however the first preclinical trials on animal models are very encouraging. Some particle sources can deliver extreme dose rates (of the order of 10^9 to 10^12 Gy/s), but are not yet ready for biomedical applications. We propose to use one very promising UHDR source (laser-driven electron source) to evaluate the biological effects of such a dose rate on in vitro models of breast cancer. The proposed project is a very transversal project, and will be carried out in collaboration with 3 teams. Most of the internship will take place in team 1 which has the high dose rate irradiation source (laser-plasma accelerator) and experiments, biology-oriented, will be carried out between the 3 laboratories during the internship, supervised by physicists and biologists from the 3 teams. The internship will firstly consist of contributing to extreme dose rate irradiation of several breast cancer cell lines. This part of the internship will take place in the CEA LIDYL laboratory, which has a source of electrons accelerated by an intense laser capable of delivering the extreme doses of around 10^12Gy/s necessary for carrying out these preliminary studies. The trainee will participate in the implementation of a dedicated, adapted device for the irradiation of biological material (modification of an incubator at the end of the line in order to optimize the cell culture conditions, adaptation of the electron beam according to the supports and doses, dosimetry, etc.). The electron bunches are very short duration but the dose per pulse is very low (of the order of a few tens of mGy/pulse). It is therefore necessary to accumulate numerous shots in order to obtain a total dose equivalent to 2 or 4Gy. This incubator will be modified and adapted to these unique irradiation conditions, and the irradiation conditions will be modified in order to study the effects on cancer cells. The irradiated cells will then be analysed in the two biology teams (IJClab and IRCM), where they will be subject to cell biology, molecular biology and modeling tests, in order to evaluate the effects of the extreme dose rate. The objective of the internship is to establish an innovative irradiation bench meeting the constraints of the experimental environment to test the extreme dose rate effect in radiobiology and to evaluate the effects of such a dose rate on models of breast cancer.
electron diagnostics, ultra high intense laser, cell biology, molecular biology, microscopy, biological analysis
Dickson LT et al. Physical Review Accelerators and Beams., Oct, 2022. Vol. 25, pp. 101301. American Physical Society. (2022) Bontemps I et al., Oncol Rep. 2023 Jan;49(1):4 hybrid E/M state in breast cancer cells. Hullo M et al., Int J Mol Sci. 2021 Apr 23;22(9):4436. Maitrallain et al., NIMA Vol. 908, pp. 159-166, (2018).
