Félicien HESPEELS - Défense de thèse de doctorat en sciences physiques

Theoretical and experimental study of the proton induced secondary electron emission from nanometer gold targets

Membres du jury

Anne-Catherine HEUSKIN (UNamur), présidente; Stéphane LUCAS (UNamur), secrétaire; Anne-Catherine WERA (UNamur); David STRIVAY (ULiège); Emanuele SCIFONI (TIFPA, Italie); Michael Kraemer (GSI, Allemagne).

Résumé

Among the various available cancer treatment modalities (surgery, chemotherapy…), radiation therapy is now established as the principal option for treatment. Radiotherapeutic treatments rely on the deposition of a high enough quantity of energy in tumor cells, by X-ray or charged particle irradiation, to damage the cancer cells and induce tumor death.

The main limitation of modern radiotherapy is the non-negligible dose received by the healthy tissues surrounding the tumor during the treatment, which causes huge side effects. Consequently, one of the current challenges is to maximize the damage in the tumor while sparring the heathy tissues.

Cancer radiation therapy with charged particle beams presents major advantages when compared to conventional X-ray radiotherapy. Since charged particles have specific ballistic properties (High LET, Bragg peak) and a higher RBE, their use promises a better therapeutic outcome than classical X-ray photons.

However, charged particle radiotherapy still suffers from the limitation that healthy tissues located upstream the tumor are damaged during the treatment. Thanks to their capability to enhance the radiation effect, NPs of high Z are considered to improve the therapy efficacy. The cell killing enhancement effect of a combined treatment of proton radiation and NPs has already been extensively investigated. However, the fundamental processes involved are not yet perfectly understood. In this context, numerous studies have investigated the possible physical, chemical and biological mechanisms responsible for cell death enhancement.

In this thesis, we focus on the role played by the secondary electrons emitted from GNPs during proton irradiation. Various studies based on Monte Carlo simulations were carried out to investigate the mechanisms involved in the secondary electron emission from GNPs under proton irradiation.

To reproduce charged particle interactions and energy loss in matter, Monte Carlo codes rely on the use of interaction cross sections and stopping powers. Since charged particles and secondary electrons generated in matter undergo multiple interactions, the secondary electrons energy distribution after target irradiation can be used to assess the accuracy of the cross sections and stopping power used in MC simulation. This work provides secondary electron energy spectra measurements from carbon and gold targets, obtained after proton irradiation. Thanks to these experimental data, we evaluated the ability of the TRAX and Geant4 MC toolkits to reproduce electron emission from solid.

The results obtained in the framework of this study demonstrate that the single interaction approach used in TRAX is adapted to reproduce secondary electron emission in gold targets. On the other hand, the standard electron generation threshold implemented in the condensed-history models used in Geant4 is not adapted to reproduce low energy electron emission in gold targets.

Based on the validated TRAX code, we investigated the dose enhancement around a GNP due to the secondary electron emitted from the GNP after proton irradiation. We showed that no killing enhancement effect is expected unless the GNP is in close proximity to key cellular functional elements (DNA, mitochondria…). Thus, it should be considered that the GNP radioenhancement effect due to secondary electrons is correlated to the GNPs localization in the cell. Finally, regarding the low encounter probability between charged particles and GNPs, we concluded that the secondary electron emitted from a GNP could not explain on its own the killing enhancement effect.

Altogether, the valuable results obtained during this research enable a better understanding of the role of secondary electron in the GNP radiosensitizing effect.

 

La défense de thèse est publique.

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