Presenter(s)
A. Vasan1, P. Biswal1, S. K. Samala2, K. Koushki1, N. Gundapaneni2, P. M. Q. Mai1, G. Raja1, L. W. Cheung3, Y. Mackeyev4, N. Sahoo5, and S. Krishnan1; 1The University of Texas Health Science Center at Houston, Houston, TX, 2University of Texas Health Science Center Houston, Houston, TX, 3University of Texas Health Science Center at Houston, Houston, TX, 4Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 5The University of Texas MD Anderson Cancer Center, Houston, TX
Purpose/Objective(s): Proton boron fusion therapy (PBFT) offers a potential advantage over conventional photon therapy by limiting damage to surrounding normal tissue. Unlike photons, which deposit energy primarily at the entry of the tissue and along their entire path, protons deposit most of their energy at the end of their path known as the Bragg peak. PBFT seeks to further enhance this effect by exploiting the fusion reaction between protons and Boron-11, generating three alpha particles per interaction that may increase biological effectiveness. Despite its theoretical promise, PBFT remains controversial due to inconsistent experimental results. Another unresolved issue is whether the biological enhancement is driven by proton-boron fusion or by secondary neutrons generated during beam interaction that induce a secondary boron neutron capture therapy (BNCT) effect. This study aimed to investigate the effectiveness of Boron-11 and Boron-10 in combination with proton radiation in glioblastoma cell lines. Natural boron (N-BSH; 80% Boron-11 and 20% Boron-10) was used as the proposed fusion target, while Boron-10 (B10-BSH) served as a control for any secondary BNCT-related effect.
Materials/Methods: Glioblastoma cells were treated with purified N-BSH or B10-BSH (773 mM) or media for 24 hours. The samples were radiated with 0, 1, 2, 3 or 4 Gy proton at the distal portion of the spread-out Bragg Peak. Cells were then re-seeded in fresh media and incubated for 10-12 days. The surviving fraction was determined using clonogenic assay, and dose-response curves were generated to evaluate biological effects. To assess DNA damage, gH2AX assay was performed 1 hour after 2 Gy irradiation. Immunofluorescence images were acquired and fluorescence intensity was quantified. Statistical analysis was performed by two-way ANOVA.
Results: Clonogenic survival analysis of GBM cells demonstrated substantial overlap of survival curves across all experimental conditions at the distal region of the Bragg peak. No statistically significant reduction in survival was observed in the N-BSH or B10-BSH-treated groups compared with no-boron controls across the tested proton doses. The GL261 cell line showed a 20-30% decrease in survival (P<0.05) upon treatment with N-BSH or B10-BSH alone in the absence of radiation, suggesting intrinsic chemical-associated toxicity. Importantly, the addition of boron did not further enhance proton-induced cytotoxicity. Aligning with the cell survival data, there was no significant difference in ?H2AX foci formation between irradiated boron-treated groups and the proton-only group.
Conclusion: Collectively, these findings show no evidence of increased biological effectiveness associated with boron supplementation under the experimental conditions tested.