Synchrotron activation radiotherapy: Effects of dose-rate and energy spectra to tantalum oxide nanoparticles selective tumour cell radiosentization enhancement

Engels, Elette; Lerch, Michael L. F; Tehei, Moeava; Konstantinov, Konstantin; Guatelli, Susanna; Rosenfeld, Anatoly B.; Corde, Stéphanie

doi:10.1088/1742-6596/777/1/012011

Cited by 10 publications

(16 citation statements)

References 3 publications

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“…Synchrotron radiation was superior to conventional X-rays in the treatment of 9LGS if delivered at a dose rate of 205 Gy/s. This expands on previous findings 48 , showing that the 9LGS can be radiosensitized using synchrotron high dose rate fields, similar to FLASH therapies 39 .…”

Section: Discussionsupporting

confidence: 86%

Toward personalized synchrotron microbeam radiation therapy

Engels

Davis

et al. 2020

Sci Rep

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Synchrotron facilities produce ultra-high dose rate X-rays that can be used for selective cancer treatment when combined with micron-sized beams. Synchrotron microbeam radiation therapy (MRT) has been shown to inhibit cancer growth in small animals, whilst preserving healthy tissue function. However, the underlying mechanisms that produce successful MRT outcomes are not well understood, either in vitro or in vivo. this study provides new insights into the relationships between dosimetry, radiation transport simulations, in vitro cell response, and pre-clinical brain cancer survival using intracerebral gliosarcoma (9LGS) bearing rats. As part of this groundbreaking research, a new image-guided MRT technique was implemented for accurate tumor targeting combined with a pioneering assessment of tumor dose-coverage; an essential parameter for clinical radiotherapy. Based on the results of our study, we can now (for the first time) present clear and reproducible relationships between the in vitro cell response, tumor dose-volume coverage and survival post MRT irradiation of an aggressive and radioresistant brain cancer in a rodent model. our innovative and interdisciplinary approach is illustrated by the results of the first long-term MRT pre-clinical trial in Australia. Implementing personalized synchrotron MRT for brain cancer treatment will advance this international research effort towards clinical trials.

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Section: Discussionsupporting

confidence: 86%

Toward personalized synchrotron microbeam radiation therapy

Engels

Davis

et al. 2020

Sci Rep

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“…Ta 2 O 5 NPs are manufactured according to Brown et al [28] and added to the cell culture flask to incubate for 24 hours. The toxicity to the cells with concentrations of 50-500 µg/mL, after 24 hrs incubation, was found to be very low, with cell clonogenic survival of 80-100% [28,30]. Therefore, there is no lethality towards cells besides that induced due to ionising radiation.…”

Section: Motivation Of the Geant4 Simulation Study: Experimental Measmentioning

confidence: 95%

“…The details of the radiobiological experiments will be object of a separate article. Ta 2 O 5 NPs are nano-structured ceramic particles that have shown to enhance conventional kV and MV radiotherapy [29,30]. Ta 2 O 5 NPs are manufactured according to Brown et al [28] and added to the cell culture flask to incubate for 24 hours.…”

Section: Motivation Of the Geant4 Simulation Study: Experimental Measmentioning

confidence: 99%

“…High-Z nanoparticles (NPs) have been shown to improve the effectiveness of dose conformity to tumour tissue in the case of conventional unsegmented kilovoltage X-rays [19][20][21][22][23][24][25][26][27][28][29][30]. The advantages of NPs, besides the primary benefit of enhancing tumour radiosensitivity, often include biocompatibility, permeability to cell membranes due to their nano-scale dimensions, ability to specifically target certain tumours when coated and actively accumulate at tumour sites with leaky vasculature [21,22].…”

Section: Introductionmentioning

confidence: 99%

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Optimizing dose enhancement with Ta 2 O 5 nanoparticles for synchrotron microbeam activated radiation therapy

et al. 2016

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Microbeam Radiation Therapy (MRT) exploits tumour selectivity and normal tissue sparing with spatially fractionated kilovoltage X-ray microbeams through the dose volume effect. Experimental measurements with Ta 2 O 5 nanoparticles (NPs) in 9L gliosarcoma treated with MRT at the Australian Synchrotron, increased the treatment efficiency. Ta 2 O 5 NPs were observed to form shells around cell nuclei which may be the reason for their efficiency in MRT. In this article, our experimental observation of NP shell formation is the basis of a Geant4 radiation transport study to characterise dose enhancement by Ta 2 O 5 NPs in MRT. Our study showed that NP shells enhance the physical dose depending microbeam energy and their location relative to a single microbeam. For monochromatic microbeam energies below ∼70 keV, NP shells show highly localised dose enhancement due to the short range of associated secondary electrons. Low microbeam energies indicate better targeted treatment by allowing higher microbeam doses to be administered to tumours and better exploit the spatial fractionation related selectivity observed with MRT. For microbeam energies above ∼100 keV, NP shells extend the physical dose enhancement due to longer-range secondary electrons. Again, with NPs selectively internalised, the local effectiveness of MRT is expected to increase in the tumour. Dose enhancement produced by the shell aggregate varied more significantly in the cell population, depending on its location, when compared to a homogeneous NP distribution. These combined simulation and experimental data provide first evidence for optimising MRT through the incorporation of newly observed Ta 2 O 5 NP distributions within 9L cancer cells. Disciplines Engineering | Science and Technology Studies Publication DetailsEngels, E., Corde, S., McKinnon, S., Incerti, S., Konstantinov, K., Rozenfeld, A., Tehei, M., . Optimizing dose enhancement with Ta2O5 nanoparticles for synchrotron microbeam activated radiation therapy. Physica Medica: an international journal devoted to the applications of physics to medicine and biology, 32 (12)

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“…Tantalum metal is a high-Z metal with an atomic number of 73. Tantalum pentoxide (Ta 2 O 5 ) NPs were reported to be biocompatible and capable of drug loading [116]. In 2013, Brown et al first reported the utility of Ta 2 O 5 nanoceramics as a radiosensitizer (Fig.…”

Section: Other Nanoparticlesmentioning

confidence: 99%

Radiosensitizing high-Z metal nanoparticles for enhanced radiotherapy of glioblastoma multiforme

et al. 2020

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Radiotherapy is an essential step during the treatment of glioblastoma multiforme (GBM), one of the most lethal malignancies. The survival in patients with GBM was improved by the current standard of care for GBM established in 2005 but has stagnated since then. Since GBM is a radioresistant malignancy and the most of GBM recurrences occur in the radiotherapy field, increasing the effectiveness of radiotherapy using high-Z metal nanoparticles (NPs) has recently attracted attention. This review summarizes the progress in radiotherapy approaches for the current treatment of GBM, the physical and biological mechanisms of radiosensitization through high-Z metal NPs, and the results of studies on radiosensitization in the in vitro and in vivo GBM models using high-Z metal NPs to date.

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Synchrotron activation radiotherapy: Effects of dose-rate and energy spectra to tantalum oxide nanoparticles selective tumour cell radiosentization enhancement

Cited by 10 publications

References 3 publications

Toward personalized synchrotron microbeam radiation therapy

Toward personalized synchrotron microbeam radiation therapy

Optimizing dose enhancement with Ta 2 O 5 nanoparticles for synchrotron microbeam activated radiation therapy

Radiosensitizing high-Z metal nanoparticles for enhanced radiotherapy of glioblastoma multiforme

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