Fast dose fractionation using ultra-short laser accelerated proton pulses can increase cancer cell mortality, which relies on functional PARP1 protein

Abstract

Radiotherapy is a cornerstone of cancer management. The improvement of spatial dose distribution in the tumor volume by minimizing the dose deposited in the healthy tissues have been a major concern during the last decades. Temporal aspects of dose deposition are yet to be investigated. Laser-plasma-based particle accelerators are able to emit pulsed-proton beams at extremely high peak dose rates (~109Gy/s) during several nanoseconds. The impact of such dose rates on resistant glioblastoma cell lines, SF763 and U87-MG, was compared to conventionally accelerated protons and X-rays. No difference was observed in DNA double-strand breaks generation and cells killing. The variation of the repetition rate of the proton bunches produced an oscillation of the radio-induced cell susceptibility in HCT116 cells, which appeared to be related to the presence of the PARP1 protein and an efficient parylation process. Interestingly, when laser-driven proton bunches were applied at 0.5 Hz, survival of the radioresistant HCT116 p53−/−cells equaled that of its radiosensitive counterpart, HCT116 WT, which was also similar to cells treated with the PARP1 inhibitor Olaparib. Altogether, these results suggest that the application modality of ultrashort bunches of particles could provide a great therapeutic potential in radiotherapy.

Thermal Neutron Relative Biological Effectiveness Factors for Boron Neutron Capture Therapy from In Vitro Irradiations

“…The U87 cell line was not photon irradiated and the results from Bayart et al [ 27 ], obtained with a Varian NDI 226 X-ray tube of 200 kVp (kilovolt peak) at a dose rate of 1.2 Gy/min, were used. Additionally, the SQ20 cell line was not irradiated at the medical LINAC; data from Cal33, also squamous cell carcinoma, were used for reference.…”

“… Clonogenic survival of six cell lines as a function of the absorbed dose (Gy) following irradiation with photons at the medical linear accelerator, S γ , with neutrons at the ILL beam, S ILL , and, derived, ILL neutrons alone, S n . S γ for U87 from [ 27 ] and S γ for SQ20 from the one obtained for Cal33. The data were obtained from between two and seven individual experiments after photon irradiation and neutron irradiation.…”

Thermal neutron Relative Biological Effectiveness factors for Boron Neutron Capture Therapy from In Vitro Irradiations

“…The U87 cell line was not photon irradiated and results from Bayart et al [20], obtained with a Varian NDI 226 X-ray tube of 200 kVp (kilovolt peak) at a dose rate of 1.2 Gy/min, were used. Also the SQ20 cell line was not irradiated at the medical LINAC; data from Cal33, also squamous cell carcinoma, were used for reference.…”

“…Clonogenic survival of six cell lines as a function of the absorbed dose (Gy) following irradiation with photons at the medical linear accelerator, S, with neutrons at the ILL beam, SILL, and, derived, ILL neutrons alone, Sn. S for U87 from [20] and S for SQ20 from the one obtained for Cal33. Data were obtained from between two and seven individual experiments after photon irradiation and neutron irradiation.…”

Influence of Pre-Plasma on Accelerated Protons in Ultraintense Laser Interaction with Not-So-Thin Foils

“…Since the original investigations, effort has been dedicated 2,3 to enhance the cut-off energy and the flux of the accelerated ions via a number of advances of laser and target specifications using plasma mirror for ultra-high laser contrast with ultra-thin targets 4 , cryogenic 5 or nano-structured targets 6 . To date, however, practical exploitation of laser-driven ion acceleration relies heavily on the original TNSA configuration based on thin foil targets and optimized contrast without plasma mirror, possibly operating at the repetition rate required for applications like radiobiology 7,8 , where high dose irradiation is needed for meaningful studies. In this context, great attention is being dedicated to the control of accelerated ions, including energy cut-off, beam divergence, charge and emittance.…”