Variations among glioblastoma cell lines in boron-mediated enhancement of cell killing by proton beams

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.