Microbeam evolution: from single cell irradiation to pre-clinical studies

Ghita, Mihaela; Fernández-Palomo, Cristian; Fukunaga, Hisanori; Fredericia, Pil; Schettino, Giuseppe; Bräuer-Krisch, Elke; Butterworth, Karl T.; McMahon, S. J.; Prise, Kevin M.

doi:10.1080/09553002.2018.1425807

Cited by 29 publications

(17 citation statements)

References 103 publications

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“…The treatment of radio-resistant cancers using Microbeam Radiation Therapy (MRT) is based on the possibility of improved therapeutic ratios resulting from reduced normal tissue complications while maintaining high tumour control probability when exposed to high, spatially fractionated doses. Whilst MRT is currently in the pre-clinical stage, there are many studies demonstrating the efficiency of the MRT treatment modality 10–18 . The underlying physical, chemical, and biological mechanisms that govern the positive selectivity observed between the normal and cancerous tissue response in MRT are yet to be completely understood.…”

Section: Introductionmentioning

confidence: 99%

Validation of a Monte Carlo simulation for Microbeam Radiation Therapy on the Imaging and Medical Beamline at the Australian Synchrotron

Dipuglia

Cameron

Davis

et al. 2019

Sci Rep

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Microbeam Radiation Therapy (MRT) is an emerging cancer treatment modality characterised by the use of high-intensity synchrotron-generated x-rays, spatially fractionated by a multi-slit collimator (MSC), to ablate target tumours. The implementation of an accurate treatment planning system, coupled with simulation tools that allow for independent verification of calculated dose distributions are required to ensure optimal treatment outcomes via reliable dose delivery. In this article we present data from the first Geant4 Monte Carlo radiation transport model of the Imaging and Medical Beamline at the Australian Synchrotron. We have developed the model for use as an independent verification tool for experiments in one of three MRT delivery rooms and therefore compare simulation results with equivalent experimental data. The normalised x-ray spectra produced by the Geant4 model and a previously validated analytical model, SPEC, showed very good agreement using wiggler magnetic field strengths of 2 and 3 T. However, the validity of absolute photon flux at the plane of the Phase Space File (PSF) for a fixed number of simulated electrons was unable to be established. This work shows a possible limitation of the G4SynchrotronRadiation process to model synchrotron radiation when using a variable magnetic field. To account for this limitation, experimentally derived normalisation factors for each wiggler field strength determined under reference conditions were implemented. Experimentally measured broadbeam and microbeam dose distributions within a Gammex RMI457 Solid Water® phantom were compared to simulated distributions generated by the Geant4 model. Simulated and measured broadbeam dose distributions agreed within 3% for all investigated configurations and measured depths. Agreement between the simulated and measured microbeam dose distributions agreed within 5% for all investigated configurations and measured depths.

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Section: Introductionmentioning

confidence: 99%

Validation of a Monte Carlo simulation for Microbeam Radiation Therapy on the Imaging and Medical Beamline at the Australian Synchrotron

Dipuglia

Cameron

Davis

et al. 2019

Sci Rep

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“…Laser micro-irradiation is a widely used approach having led to meaningful findings in cell biology, aging and cancer research 7,8,18,19 . With all its advantages over current existing manual evaluation tools, the Stripenator provides value and utility in objective, fast analyses and enables superior quality, high-throughput studies of migration and accumulation of DNA damage response factors, histone modifications, and DNA repair-related proteins.…”

Section: Resultsmentioning

confidence: 99%

High-throughput Evaluation of Protein Migration and Localization after Laser Micro-Irradiation

Oeck

Malewicz

Krysztofiak

et al. 2019

Sci Rep

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DNA- and histone-related research frequently comprises the quantitative analysis of protein modifications, such as histone phosphorylation. Analysis of accumulation and disappearance of protein foci are used to monitor DNA damage and repair kinetics. If the protein of interest doesn’t accumulate in foci, laser micro-irradiation of single nuclei provides an alternative method to monitor DNA repair proteins and histone dynamics at the DNA damage site. We have developed an automated evaluation tool for standardized, high-throughput analysis of micro-irradiated cells featuring single cell background subtraction and detection across multiple fluorescence channels, allowing for robust statistics.

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“…The first microbeam device was used by Zirkle and Bloom, and consisted of a 2 MV Van de Graaff accelerator that delivered protons (15). Today, new-generation microbeam devices allow reducing the radiation beam to sub-cellular dimensions using collimation assemblies and electromagnetic focusing (16). External alpha particle microbeam irradiation has been and is a very attractive tool for exploring the radiobiology of alpha particles at the subcellular scale (17), although different from TAT in terms of the used dose and dose rate, and the absence of vector (18,19).…”

Section: Revisiting Paradigms: Subcellular Targetsmentioning

confidence: 99%

Revisiting the Radiobiology of Targeted Alpha Therapy

Pouget

Constanzo

2021

Front. Med.

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Targeted alpha therapy (TAT) using alpha particle-emitting radionuclides is in the spotlight after the approval of 223RaCl2 for patients with metastatic castration-resistant prostate cancer and the development of several alpha emitter-based radiopharmaceuticals. It is acknowledged that alpha particles are highly cytotoxic because they produce complex DNA lesions. Hence, the nucleus is considered their critical target, and many studies did not report any effect in other subcellular compartments. Moreover, their physical features, including their range in tissues (<100 μm) and their linear energy transfer (50–230 keV/μm), are well-characterized. Theoretically, TAT is indicated for very small-volume, disseminated tumors (e.g., micrometastases, circulating tumor cells). Moreover, due to their high cytotoxicity, alpha particles should be preferred to beta particles and X-rays to overcome radiation resistance. However, clinical studies showed that TAT might be efficient also in quite large tumors, and biological effects have been observed also away from irradiated cells. These distant effects are called bystander effects when occurring at short distance (<1 mm), and systemic effects when occurring at much longer distance. Systemic effects implicate the immune system. These findings showed that cells can die without receiving any radiation dose, and that a more complex and integrated view of radiobiology is required. This includes the notion that the direct, bystander and systemic responses cannot be dissociated because DNA damage is intimately linked to bystander effects and immune response. Here, we provide a brief overview of the paradigms that need to be revisited.

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Microbeam evolution: from single cell irradiation to pre-clinical studies

Cited by 29 publications

References 103 publications

Validation of a Monte Carlo simulation for Microbeam Radiation Therapy on the Imaging and Medical Beamline at the Australian Synchrotron

Validation of a Monte Carlo simulation for Microbeam Radiation Therapy on the Imaging and Medical Beamline at the Australian Synchrotron

High-throughput Evaluation of Protein Migration and Localization after Laser Micro-Irradiation

Revisiting the Radiobiology of Targeted Alpha Therapy

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