WP4 - Radiobiology

Leader: L. Manti

The objective of this WP is the radiobiological investigation of the possibility to enhance the biological effectiveness of clinical proton beams by means of nuclear fusion reactions, namely p+¹¹B→3α (p-B) and p+¹⁹F→¹⁶O+ α (p-F). Specifically, the WP4 aims at: a) corroborating previously obtained results [1], showing experimentally for the first time that treating cells with a boron carrier initially employed in Boron-Neutron Capture Therapy (BNCT), i.e. BSH or sodium borocaptate (Na₂B₁₂H₁₁SH), led to a significant increase in proton-induced cancer cell death; b) extending such a binary approach to increase proton biological effectiveness to the p-F reaction; c) unravelling the underlying biophysical mechanism(s).

The working hypothesis is that the high Linear Energy Transfer (LET) possessed by the short-range (in the order of a few cells’ nuclei) particles generated by the p-B and p-F reactions results in a highly localised increase of proton Relative Biological Effectiveness (RBE)being thus the reason why more cancer cells can be killed by the same dose of protons as delivered in the absence of the boron/fluorine carriers. This is because it is known that high-LET radiation causes peculiarly complex DNA damage [2], consisting of clustered lesions (CL) in close spatio-temporal proximity, which is more difficult for the cells to repair compared to that induced by sparsely ionizing radiation such as photons and electrons (used in conventional radiotherapy) as well by the low-LET protons in protontherapy: at the mid-SOBP of a typical proton clinical beam the LET is 3-4 keV/um, while the LET of the products of the above-mentioned reactions exceed 100 keV/um along their tracks, thereby coinciding with the expected maximum RBE.