Protontherapy is an important radiation modality that has been used to treat cancer for
over 60 years. In the last 10 years, clinical proton therapy has been rapidly growing with
more than 80 facilities worldwide [1]. The interest in proton therapy stems from the physical
properties of protons allowing for a much improved dose shaping around the target and
greater healthy tissue sparing. One shortcoming of protontherapy is its inability to treat
radioresistant cancers, being protons radiobiologically almost as effective as photons. Heavier
particles, such as 12C ions, can overcome radioresistance but they present radiobiological and
economic issues that hamper their widespread adoption. Therefore, many strategies have
been designed to increase the biological effectiveness of proton beams. Examples are chemical
radiosensitizing agents or, more recently, metallic nanoparticles. The goal of this project is
to investigate the use of nuclear reactions triggered by protons generating short-range high-
LET alpha particles inside the tumours, thereby allowing a highly localized DNA-damaging
action. Specifically, we intend to consolidate and explain the promising results recently
published in [2], where a significant enhancement of biological effectiveness was achieved
by the p-11B reaction. Clinically relevant binary approaches were first proposed with Boron
Neutron Capture Therapy (BNCT), which exploits thermal neutron capture in 10B, suitably
accumulated into tumour before irradiation. The radiosensitising effects due to the presence
of 10B will be compared to those elicited by p-11B, using the same carrier and relating the
observed effects with intracellular 11B and 10B distribution as well as modelled particle action
and measured dose deposition at the micro/nanometer scale. Moreover, the p-19F reaction,
which also generates secondary particles potentially leading to local enhancement of proton
effectiveness, will be investigated. The in-vivo imaging of 11B and 19F carriers will be studied,
in particular by optimizing 19F-based magnetic resonance
