First experimental proof of Proton Boron Capture Therapy (PBCT) to enhance protontherapy effectiveness

Cirrone, G.A.P.; Manti, Lorenzo; Margarone, D.; Petringa, Giada; Giuffrida, L.; Minopoli, Antonio; Picciotto, A.; Russo, G.; Cammarata, Francesco Paolo; Pisciotta, Pietro; Perozziello, F. M.; Romano, F.; Marchese, Valentina; Milluzzo, G.; Scuderi, V.; Cuttone, G.; Korn, G.

doi:10.1038/s41598-018-19258-5

Cited by 98 publications

(182 citation statements)

References 63 publications

(79 reference statements)

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“…The ratio between the dose from the proton boron capture and the one due to the primary proton, as a function of the depth inside the tissue, is shown in the right panel of Figure 4. It can be noted that, apart from being very low in absolute, the depth profile of this ratio is opposite to what would be desirable for enhancing the therapeutic effectiveness of proton therapy, and it is in clear contradiction with the experimental results of Cirrone et al 4 .…”

Section: Estimate Of the P+ 11 B→3α Dose Contributionmentioning

confidence: 62%

“…According to Ref. 4 , the maximum effect of PBCT is obtained at the end of the proton range, due to a resonance-like structure peaking around 700 keV. At its maximum, a cross section of ∼1 barn has been reported by Segel et al 7,8 .…”

Section: Estimate Of the P+ 11 B→3α Dose Contributionmentioning

confidence: 84%

“…Another important aspect that can be investigated with the simulations is the presence of additional reactions that could contribute to explain the decrease in cell survival probability observed in Ref. 4 . In particular, since natural boron was used in the measurement, one may wander whether secondary neutrons produced by proton interaction with oxygen would give rise to the 10 B(n, α) 7 Li reaction, i.e.…”

Section: Geant4 Simulationsmentioning

confidence: 99%

“…Simulations were performed with a proton energy distribution that reproduces the dose distribution, the so-called Spread Out Bragg Peak, of the proton therapy facility of INFN-Laboratori Nazionali del Sud, shown in Ref. 4 , and used in the measurement described therein. As a software replica of the cell irradiation experiment described in Ref.…”

Section: Geant4 Simulationsmentioning

confidence: 99%

“…4 "Proton Boron Capture Therapy" (PBCT), is a two-component treatment modality in which a therapeutic dose is produced by proton-induced reactions on boron, selectively delivered to the tumor by means of a suitable carrier. The effect of PBCT is demonstrated by Cirrone et al 4 by irradiating samples of prostatic tumor cells with and without boron. It is shown that the presence of boron in a concentration of several tens ppm leads to an important decrease in the cell survival probability.…”

Section: Introductionmentioning

confidence: 99%

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On the (un)effectiveness of proton boron capture in proton therapy

et al. 2019

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We present calculations and simulations on the role of the p+ 11 B→3α reaction in proton therapy. This reaction has been recently suggested to be responsible for a decrease in the survival probability of tumor cells, when they are irradiated with low-energy protons. However, at the concentration levels typical of the proposed boron carrier (sodium borocaptate, Na 2 B 12 H 11 SH, in short BSH), i.e. less than 100 ppm, both calculations and Monte Carlo simulations suggest that the dose related to this reaction is orders of magnitude lower than the dose delivered by the primary proton beam inside the tissues. These calculations cast some doubts on the claim of an important role played by Proton Boron Capture in enhancing the therapeutic effectiveness of proton therapy, and suggest that other mechanisms should be investigated in order to explain the observed decrease in the survival probability.

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Section: Estimate Of the P+ 11 B→3α Dose Contributionmentioning

confidence: 62%

Section: Estimate Of the P+ 11 B→3α Dose Contributionmentioning

confidence: 84%

Section: Geant4 Simulationsmentioning

confidence: 99%

Section: Geant4 Simulationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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On the (un)effectiveness of proton boron capture in proton therapy

et al. 2019

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Technical note: Monte Carlo study of the mechanism of proton–boron fusion therapy

2021

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Proton beam therapy has been found to have enhanced biological effectiveness in targets that contain the boron isotope 11 B, with the alpha particles resulting from the p + 11 B → 3α reaction being hypothesized as the mechanism; in this study, we aimed to elucidate the causes of the enhanced biological effectiveness of proton-boron fusion therapy by performing a detailed Monte Carlo study of the p + 11 B → 3α reaction in a phantom geometry. Methods: We utilized the Geant4 toolkit to create Monte Carlo particle physics simulations. These simulations consisted of a proton beam with a range 30 mm, creating a Spread-Out Bragg Peak with a modulation width of 10 mm, directed into a water phantom containing a region of boron material. Energy deposition, particle energy, and particle fluence were scored along the path of the beam and grouped by particle species. The scoring was performed using a series of cylindrical volumes with a radius of 2.5 mm and depth of 0.1 mm, constructed such that the depth was parallel to the proton beam. Root was then used to perform the data analysis. Results: Our simulations showed that the dose delivered by alpha particles produced by p + 11 B → 3α was several orders of magnitude lower than the dose delivered directly by protons, even when the boron uptake region was comprised entirely of natural boron or pure 11 B. Conclusions: Our findings do not support the theory that an alpha particlebased mechanism is responsible for the enhanced biological effectiveness of proton-boron fusion therapy. We conclude that any enhanced biological effect seen in experimental studies was not caused by fusion reactions between protons and 11 B nuclei. However, it is necessary to reproduce the past experiments that indicated significant dose enhancement.

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Effect of boron compounds on the biological effectiveness of proton therapy

et al. 2022

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We assessed whether adding sodium borocaptate (BSH) or 4borono-L-phenylalanine (BPA) to cells irradiated with proton beams influenced the biological effectiveness of those beams against prostate cancer cells to investigate if the alpha particles generated through proton-boron nuclear reactions would be sufficient to enhance the biological effectiveness of the proton beams. Methods: We measured clonogenic survival in DU145 cells treated with 80.4ppm BSH or 86.9-ppm BPA, or their respective vehicles, after irradiation with 6-MV X-rays, 1.2-keV/μm (low linear energy transfer [LET]) protons, or 9.9-keV/μm (high-LET) protons. We also measured γH2AX and 53BP1 foci in treated cells at 1 and 24 h after irradiation with the same conditions. Results: We found that BSH radiosensitized DU145 cells across all radiation types. However, no difference was found in relative radiosensitization, characterized by the sensitization enhancement ratio or the relative biological effectiveness, for vehicle-versus BSH-treated cells. No differences were found in numbers of γH2AX or 53BP1 foci or γH2AX/53BP1 colocalized foci for vehicle-versus BSH-treated cells across radiation types. BPA did not radiosensitize DU145 cells nor induced any significant differences when comparing vehicle-versus BPA-treated cells for clonogenic cell survival or γH2AX and 53BP1 foci or γH2AX/53BP1 colocalized foci. Conclusions: Treatment with 11 B, at concentrations of 80.4 ppm from BSH or 86.9 ppm from BPA, had no effect on the biological effectiveness of proton beams in DU145 prostate cancer cells. Our results agree with published theoretical calculations indicating that the contribution of alpha particles from such reactions to the total absorbed dose and biological effectiveness is negligible. We also found that BSH radiosensitized DU145 cells to X-rays, low-LET protons, and high-LET protons but that the radiosensitization was not related to DNA damage. K E Y W O R D Salpha particles, proton-boron capture therapy, proton-boron nuclear reaction, relative biological effectiveness, sensitization enhancement ratio 6098

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First experimental proof of Proton Boron Capture Therapy (PBCT) to enhance protontherapy effectiveness

Cited by 98 publications

References 63 publications

On the (un)effectiveness of proton boron capture in proton therapy

On the (un)effectiveness of proton boron capture in proton therapy

Technical note: Monte Carlo study of the mechanism of proton–boron fusion therapy

Effect of boron compounds on the biological effectiveness of proton therapy

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