Enhancement in cell killing by proton beams in the presence of boron (natural mixture natB: 80% 11B, 20% 10B) was reported, selectively in the Bragg peak region, putatively due to the proton-11B capture reaction. However, as some groups observed no such enhancement or assigned it to secondary neutron-10B capture, proton-boron capture therapy (PBCT) remains controversial. We previously validated this concept for U-87 MG glioblastoma cells. To test its generality and potential applicability for these tumours, we assessed PBCT using three further cell lines widely used in glioblastoma research. In U251 cells, natB enhanced cell killing by protons in Bragg peak but also in plateau regions, effects of 10B were even higher, and were found also for 18MV but not 6 MV photon beams (above and below photo-neutron production thresholds, respectively), suggesting a key role of secondary neutrons. For A172 and T98G cells, no enhancement was found at all. This variability among cell lines may stem from differences in boron uptake and/or in intercellular signalling likely needed to amplify the initial events in a few hit cells to population-level effects. Together with recent negative studies, the results suggest that potential clinical applications of PBCT are less promising than originally thought.

• Keywords
• Cell survival, Glioblastoma cell lines, Proton beams, Proton-boron capture therapy, Secondary neutrons,
• MeSH
• Boron * pharmacology   MeSH
• Glioblastoma * radiotherapy   pathology   MeSH
• Humans MeSH
• Cell Line, Tumor MeSH
• Brain Neoplasms * radiotherapy   pathology   MeSH
• Proton Therapy * methods   MeSH
• Protons MeSH
• Boron Neutron Capture Therapy * methods   MeSH
• Cell Survival radiation effects   drug effects   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Boron * MeSH
• Protons MeSH

Boron has been suggested to enhance the biological effectiveness of proton beams in the Bragg peak region via the p + 11B → 3α nuclear capture reaction. However, a number of groups have observed no such enhancement in vitro or questioned its proposed mechanism recently. To help elucidate this phenomenon, we irradiated DU145 prostate cancer or U-87 MG glioblastoma cells by clinical 190 MeV proton beams in plateau or Bragg peak regions with or without 10B or 11B isotopes added as sodium mercaptododecaborate (BSH). The results demonstrate that 11B but not 10B or other components of the BSH molecule enhance cell killing by proton beams. The enhancement occurs selectively in the Bragg peak region, is present for boron concentrations as low as 40 ppm, and is not due to secondary neutrons. The enhancement is likely initiated by proton-boron capture reactions producing three alpha particles, which are rare events occurring in a few cells only, and their effects are amplified by intercellular communication to a population-level response. The observed up to 2-3-fold reductions in survival levels upon the presence of boron for the studied prostate cancer or glioblastoma cells suggest promising clinical applications for these tumour types.

• Keywords
• Biological effectiveness, Cell survival, Proton radiotherapy, Proton-boron capture therapy, Sodium mercaptododecaborate (BSH),
• MeSH
• Boron chemistry   MeSH
• Glioblastoma radiotherapy   drug therapy   MeSH
• Humans MeSH
• Cell Line, Tumor MeSH
• Prostatic Neoplasms radiotherapy   drug therapy   MeSH
• Proton Therapy * methods   MeSH
• Protons MeSH
• Boron Neutron Capture Therapy * methods   MeSH
• Cell Survival drug effects   radiation effects   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Boron MeSH
• Protons MeSH