Evaluation of BPA uptake in clear cell sarcoma (CCS) in vitro and development of an in vivo model of CCS for BNCT studies

Fujimoto, Takuya; Andoh, Tooru; Sudo, Tamotsu; Fujita, Ikuo; Imabori, Masaya; Moritake, Hiroshi; Sugimoto, Tohru; Sakuma, Yoshiko; Takeuchi, Tamotsu; Shinmoto, Hiroshi; Epstein, Alan L.; Akisue, Toshihiro; Kirihata, Mitsunori; Kurosaka, Masahiro; Fukumori, Yoshinobu; Ichikawa, Hideki

doi:10.1016/j.apradiso.2011.02.006

Cited by 13 publications

(2 citation statements)

References 14 publications

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“…Indeed, the contribution of RIBEs as a concomitant mechanism assisting the enhancement of proton biological efficacy by PBCT is being currently investigated by us, together with the use of other 11 B carriers, namely boronophenylalanine (BPA), in line with work from Hideghety et al (67), whose overall positive assessment on the potential of PBCT was accompanied by suggestions on the use of more clinically viable boron delivery agents based on a thorough assessment of the experience accumulated in BNCT. With regard to this, it is important to highlight that the choice of the agent (BSH) and concentration (80 ppm) used in this study as well as in the previous experimental work on PBCT (14) was indeed based on the BNCT experience with similar 10 B-enriched compounds (81)(82)(83)(84)(85), the BSH molecule having a high boron content in its natural isotopic abundance (80% 11 B, 20% 10 B). In fact, being well aware of the poor penetrability of BSH into the cell, compared for example to the above-mentioned BPA, irradiations were always performed on cells that had been pretreated with BSH and that were in BSH-containing medium at the moment of the irradiation.…”

Section: The Proton-boron Capture Therapy (Pbct) Approach and Its Perspectives In Protontherapymentioning

confidence: 99%

The Proton-Boron Reaction Increases the Radiobiological Effectiveness of Clinical Low- and High-Energy Proton Beams: Novel Experimental Evidence and Perspectives

et al. 2021

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Protontherapy is a rapidly expanding radiotherapy modality where accelerated proton beams are used to precisely deliver the dose to the tumor target but is generally considered ineffective against radioresistant tumors. Proton-Boron Capture Therapy (PBCT) is a novel approach aimed at enhancing proton biological effectiveness. PBCT exploits a nuclear fusion reaction between low-energy protons and 11B atoms, i.e. p+11B→ 3α (p-B), which is supposed to produce highly-DNA damaging α-particles exclusively across the tumor-conformed Spread-Out Bragg Peak (SOBP), without harming healthy tissues in the beam entrance channel. To confirm previous work on PBCT, here we report new in-vitro data obtained at the 62-MeV ocular melanoma-dedicated proton beamline of the INFN-Laboratori Nazionali del Sud (LNS), Catania, Italy. For the first time, we also tested PBCT at the 250-MeV proton beamline used for deep-seated cancers at the Centro Nazionale di Adroterapia Oncologica (CNAO), Pavia, Italy. We used Sodium Mercaptododecaborate (BSH) as 11B carrier, DU145 prostate cancer cells to assess cell killing and non-cancer epithelial breast MCF-10A cells for quantifying chromosome aberrations (CAs) by FISH painting and DNA repair pathway protein expression by western blotting. Cells were exposed at various depths along the two clinical SOBPs. Compared to exposure in the absence of boron, proton irradiation in the presence of BSH significantly reduced DU145 clonogenic survival and increased both frequency and complexity of CAs in MCF-10A cells at the mid- and distal SOBP positions, but not at the beam entrance. BSH-mediated enhancement of DNA damage response was also found at mid-SOBP. These results corroborate PBCT as a strategy to render protontherapy amenable towards radiotherapy-resilient tumor. If coupled with emerging proton FLASH radiotherapy modalities, PBCT could thus widen the protontherapy therapeutic index.

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Section: The Proton-boron Capture Therapy (Pbct) Approach and Its Perspectives In Protontherapymentioning

confidence: 99%

The Proton-Boron Reaction Increases the Radiobiological Effectiveness of Clinical Low- and High-Energy Proton Beams: Novel Experimental Evidence and Perspectives

et al. 2021

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“…2.6 × 10 10 10 B atoms per cell, an amount superior to the target amount needed to yield lethal cellular damage following BNCT, which is ca. 1.2–2.1 × 10 9 10 B atoms per cell [ 26 ].…”

Section: Resultsmentioning

confidence: 99%

Exploring the Physical and Biological Aspects of BNCT with a Carboranylmethylbenzo[b]acridone Compound in U87 Glioblastoma Cells

Belchior¹,

Fernandes²,

Lamotte³

et al. 2022

IJMS

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Boron neutron capture therapy (BNCT) is a re-emerging technique for selectively killing tumor cells. Briefly, the mechanism can be described as follows: after the uptake of boron into cells, the thermal neutrons trigger the fission of the boron atoms, releasing the α-particles and recoiling lithium particles and high-energy photons that damage the cells. We performed a detailed study of the reactor dosimetry, cellular dose assessment, and radiobiological effects induced by BNCT in glioblastoma (GBM) cells. At maximum reactor power, neutron fluence rates were ϕ0 = 6.6 × 107 cm−2 s−1 (thermal) and θ = 2.4 × 104 cm−2 s−1 with a photon dose rate of 150 mGy·h−1. These values agreed with simulations to within 85% (thermal neutrons), 78% (epithermal neutrons), and 95% (photons), thereby validating the MCNPX model. The GEANT4 simulations, based on a realistic cell model and measured boron concentrations, showed that >95% of the dose in cells was due to the BNC reaction. Carboranylmethylbenzo[b]acridone (CMBA) is among the different proposed boron delivery agents that has shown promising properties due to its lower toxicity and important cellular uptake in U87 glioblastoma cells. In particular, the results obtained for CBMA reinforce radiobiological effects demonstrating that damage is mostly induced by the incorporated boron with negligible contribution from the culture medium and adjacent cells, evidencing extranuclear cell radiosensitivity.

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Clear Cell Sarcoma

et al. 2020

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Evaluation of BPA uptake in clear cell sarcoma (CCS) in vitro and development of an in vivo model of CCS for BNCT studies

Cited by 13 publications

References 14 publications

The Proton-Boron Reaction Increases the Radiobiological Effectiveness of Clinical Low- and High-Energy Proton Beams: Novel Experimental Evidence and Perspectives

The Proton-Boron Reaction Increases the Radiobiological Effectiveness of Clinical Low- and High-Energy Proton Beams: Novel Experimental Evidence and Perspectives

Exploring the Physical and Biological Aspects of BNCT with a Carboranylmethylbenzo[b]acridone Compound in U87 Glioblastoma Cells

Clear Cell Sarcoma

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