Experimental Validation of Proton Boron Capture Therapy for Glioma Cells

Overview

Journal Sci Rep

Specialty Science

Date 2023 Jan 24

PMID 36693879

Authors

Tatiana Shtam

Vladimir Burdakov

Alina Garina

Luiza Garaeva

Nhan Hau Tran

Andrey Volnitskiy

Eva Kuus

Dmitry Amerkanov

Fedor Pack

Georgy Andreev

Andrey Lubinskiy

Konstantin Shabalin

Nicolay Verlov

Evgeniy Ivanov

Victor Ezhov

Dmitry Lebedev

Andrey L Konevega

Affiliations

Soon will be listed here.

Abstract

Proton boron capture therapy (PBCT) has emerged from particle acceleration research for enhancing the biological effectiveness of proton therapy. The mechanism responsible for the dose increase was supposed to be related to proton-boron fusion reactions (B + p → 3α + 8.7 MeV). There has been some experimental evidence that the biological efficiency of protons is significantly higher for boron-11-containing prostate or breast cancer cells. The aim of this study was to evaluate the sensitizing potential of sodium borocaptate (BSH) under proton irradiation at the Bragg peak of cultured glioma cells. To address this problem, cells of two glioma lines were preincubated with 80 or 160 ppm boron-11, irradiated both at the middle of 200 MeV beam Spread-Out Bragg Peak (SOBP) and at the distal end of the 89.7 MeV beam SOBP and assessed for the viability, as well as their ability to form colonies. Our results clearly show that BSH provides for only a slight, if any, enhancement of the effect of proton radiation on the glioma cells in vitro. In addition, we repeated the experiments using the Du145 prostate cancer cell line, for which an increase in the biological efficiency of proton irradiation in the presence of sodium borocaptate was demonstrated previously. The data presented add new argument against the efficiency of proton boron capture therapy when based solely on direct dose-enhancement effect by the proton capture nuclear reaction, underlining the need to investigate the indirect effects of the secondary alpha irradiation depending on the state and treatment conditions of the irradiated tissue.

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References

Kageji T, Nagahiro S, Mizobuchi Y, Matsuzaki K, Nakagawa Y, Kumada H . Boron neutron capture therapy (BNCT) for newly-diagnosed glioblastoma: comparison of clinical results obtained with BNCT and conventional treatment. J Med Invest. 2014; 61(3-4):254-63. DOI: 10.2152/jmi.61.254. View

Weber D, Lim P, Tran S, Walser M, Bolsi A, Kliebsch U . Proton therapy for brain tumours in the area of evidence-based medicine. Br J Radiol. 2019; 93(1107):20190237. PMC: 7066950. DOI: 10.1259/bjr.20190237. View

Cirrone G, Manti L, Margarone D, Petringa G, Giuffrida L, Minopoli A . First experimental proof of Proton Boron Capture Therapy (PBCT) to enhance protontherapy effectiveness. Sci Rep. 2018; 8(1):1141. PMC: 5773549. DOI: 10.1038/s41598-018-19258-5. View

Dirven L, Aaronson N, Heimans J, Taphoorn M . Health-related quality of life in high-grade glioma patients. Chin J Cancer. 2014; 33(1):40-5. PMC: 3905089. DOI: 10.5732/cjc.013.10214. View

Ricard D, Idbaih A, Ducray F, Lahutte M, Hoang-Xuan K, Delattre J . Primary brain tumours in adults. Lancet. 2012; 379(9830):1984-96. DOI: 10.1016/S0140-6736(11)61346-9. View

Miyatake S, Kawabata S, Hiramatsu R, Kuroiwa T, Suzuki M, Ono K . Boron Neutron Capture Therapy of Malignant Gliomas. Prog Neurol Surg. 2018; 32:48-56. DOI: 10.1159/000469679. View

Jhaveri J, Cheng E, Tian S, Buchwald Z, Chowdhary M, Liu Y . Proton vs. Photon Radiation Therapy for Primary Gliomas: An Analysis of the National Cancer Data Base. Front Oncol. 2018; 8:440. PMC: 6279888. DOI: 10.3389/fonc.2018.00440. View

Chiniforoush T, Hadadi A, Kasesaz Y, Sardjono Y . Evaluation of effectiveness of equivalent dose during proton boron fusion therapy (PBFT) for brain cancer: A Monte Carlo study. Appl Radiat Isot. 2021; 170:109596. DOI: 10.1016/j.apradiso.2021.109596. View

Zhang D, Zhou T, He F, Rong Y, Lee S, Wu S . Reactive oxygen species formation and bystander effects in gradient irradiation on human breast cancer cells. Oncotarget. 2016; 7(27):41622-41636. PMC: 5173083. DOI: 10.18632/oncotarget.9517. View

10.

Fujimura A, Yasui S, Igawa K, Ueda A, Watanabe K, Hanafusa T . In Vitro Studies to Define the Cell-Surface and Intracellular Targets of Polyarginine-Conjugated Sodium Borocaptate as a Potential Delivery Agent for Boron Neutron Capture Therapy. Cells. 2020; 9(10). PMC: 7598271. DOI: 10.3390/cells9102149. View

11.

Lorimore S, Kadhim M, Pocock D, Papworth D, Stevens D, Goodhead D . Chromosomal instability in the descendants of unirradiated surviving cells after alpha-particle irradiation. Proc Natl Acad Sci U S A. 1998; 95(10):5730-3. PMC: 20447. DOI: 10.1073/pnas.95.10.5730. View

12.

Kabalka G, Yao M, Marepally S, Chandra S . Biological evaluation of boronated unnatural amino acids as new boron carriers. Appl Radiat Isot. 2009; 67(7-8 Suppl):S374-9. PMC: 2861333. DOI: 10.1016/j.apradiso.2009.03.104. View

13.

Chandra S, Lorey II D, Smith D . Quantitative subcellular secondary ion mass spectrometry (SIMS) imaging of boron-10 and boron-11 isotopes in the same cell delivered by two combined BNCT drugs: in vitro studies on human glioblastoma T98G cells. Radiat Res. 2002; 157(6):700-10. DOI: 10.1667/0033-7587(2002)157[0700:qssims]2.0.co;2. View

14.

Volnitskiy A, Shtam T, Burdakov V, Kovalev R, Konev A, Filatov M . Abnormal activity of transcription factors gli in high-grade gliomas. PLoS One. 2019; 14(2):e0211980. PMC: 6366868. DOI: 10.1371/journal.pone.0211980. View

15.

Frosina G . Radiotherapy of High-Grade Gliomas: First Half of 2021 Update with Special Reference to Radiosensitization Studies. Int J Mol Sci. 2021; 22(16). PMC: 8396323. DOI: 10.3390/ijms22168942. View

16.

Wilkinson B, Morgan H, Gondi V, Larson G, Hartsell W, Laramore G . Low Levels of Acute Toxicity Associated With Proton Therapy for Low-Grade Glioma: A Proton Collaborative Group Study. Int J Radiat Oncol Biol Phys. 2016; 96(2S):E135. DOI: 10.1016/j.ijrobp.2016.06.930. View

17.

Blaha P, Feoli C, Agosteo S, Calvaruso M, Cammarata F, Catalano R . The Proton-Boron Reaction Increases the Radiobiological Effectiveness of Clinical Low- and High-Energy Proton Beams: Novel Experimental Evidence and Perspectives. Front Oncol. 2021; 11:682647. PMC: 8274279. DOI: 10.3389/fonc.2021.682647. View

18.

Ali M, Oliva C, Noman A, Allen B, Goswami P, Zakharia Y . Radioresistance in Glioblastoma and the Development of Radiosensitizers. Cancers (Basel). 2020; 12(9). PMC: 7564557. DOI: 10.3390/cancers12092511. View

19.

Stupp R, Taillibert S, Kanner A, Kesari S, Steinberg D, Toms S . Maintenance Therapy With Tumor-Treating Fields Plus Temozolomide vs Temozolomide Alone for Glioblastoma: A Randomized Clinical Trial. JAMA. 2015; 314(23):2535-43. DOI: 10.1001/jama.2015.16669. View

20.

Shin H, Yoon D, Jung J, Kim M, Suh T . Prompt gamma ray imaging for verification of proton boron fusion therapy: A Monte Carlo study. Phys Med. 2016; 32(10):1271-1275. DOI: 10.1016/j.ejmp.2016.05.053. View