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.

Papers:

  • M. Cesaire et al., “Sensitization of chondrosarcoma cells with PARP inhibitor and high-LET radiation”, Journal of Bone Oncology, 17, 100246 (2019)

  • G.A.Malfa et al., “Betula etnensis Raf. (Betulaceae) Extract Induced HO-1 Expression and Ferroptosis Cell Death in Human Colon Cancer Cells”, INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 20-11, 2723 (2019)

  • M. Lasalvia et al., “Raman spectroscopy for the evaluation of the radiobiological sensitivity of normal human breast cells at different time points after irradiation by a clinical proton beam”, ANALYST, 144-6, (2019)

  • F.P. Cammarata et al., “Proton Therapy and Src Family Kinase Inhibitor Combined Treatments on U87 Human Glioblastoma Multiforme Cell Line”,INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 20-19, 4745 (2019)

  • L. Minafra et al. “Proton-irradiated breast cells: molecular points of view”, Journal of Radiation Research, rrz032, https://doi.org/10.1093/jrr/rrz032 (2019)


Abstracts/Conferences

  • PPRIG Proton Physics Workshop 5, NPL, UK, February 2019 “Proton-Boron Capture Therapy (PBCT): enhancing clinical proton biological effectiveness by a nuclear fusion reaction” Speaker: Lorenzo Manti,

  • 16th International Congress of Radiation Research, Manchester UK, August 2019 “ Enhancement of clinical proton effectiveness by nuclear fusion reactions”, Speaker: Lorenzo Manti

  • 6th GI-CoRE Summer School 2019, Hokkaido Summer Institute-Medical Physics School, August 2019 “Enhancing protontherapy effectiveness by means of a boron-mediated nuclear reaction: insights from chromosome aberration studies”. Poster presented by Chiara Feoli