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Boron neutron capture therapy (BNCT) is an emerging radiation therapy based on the interaction between a non-radioactive boron-10 labelled compound and low-energy thermal neutrons. This interaction leads to the production of α-particles, known to be more effective in inducing cell death than conventional X-rays. Due to their short range in tissue, the induced cell damage remains confined to cells containing boron atoms. Thus, BNCT has the potential to revolutionize radiation oncology by positioning itself as a selective and targeted radiotherapy. However, the concentration of boron in the tissue cannot be determined at irradiation time, limiting the optimal use of this technology in the clinic. In this project, we propose to modify BPA, a clinically approved boron-compound by grafting MRI contrast agents (157Gd and 19F) onto it. This creates a theragnostic vector that opens the door to personalized medicine in BNCT. We will study the toxicity and internalization of our compounds in in vitro systems. Intracellular microdistribution of these compounds will be implemented in Monte Carlo codes to predict the influence of each compound on the delivered dose. The biodistribution kinetics of the compounds and their accumulation in the target tissues will be studied in murine models already available in the laboratory. The obtained MRI images will be used for the implementation of a personalized treatment plan that will guide irradiation experiments. Irradiation of our biological systems will be performed to evaluate tumor control, additive or synergistic effect of Gd or F moities and the radiobiological responses (DNA damages, ...) using cellular and molecular biology analyses. Finally, the damage to healthy tissues will be assessed by ex-vivo histological analyses. All the information collected will lay the foundation for clinical trials that will start at the end of this project.
• F.R.S.-FNRS et Fonds associés (hors FRIA)