Applied Sciences

Editorial

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2 pages, 161 KiB

Open AccessEditorial

Special Issue on Synchrotron Radiation for Medical Applications

by Orion Itzhak

Appl. Sci. 2023, 13(11), 6609; https://doi.org/10.3390/app13116609 - 29 May 2023

Viewed by 1148

Abstract

X-ray radiation is a widely used tool in the fields of medical physics and diagnostic imaging [...] Full article

(This article belongs to the Special Issue Synchrotron Radiation for Medical Applications)

Research

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14 pages, 2624 KiB

Open AccessArticle

Radiation Damage on Thaumatin: A Case Study of Crystals That Are Larger Than the Microfocusing X-ray Beam

by Ki Hyun Nam

Appl. Sci. 2023, 13(3), 1876; https://doi.org/10.3390/app13031876 - 31 Jan 2023

Cited by 8 | Viewed by 1700

Abstract

Microfocusing X-rays direct high-density photons on crystal samples and can enhance the diffraction limit and quality of collected data. However, these intense X-rays can cause radiation damage to the sample, which often results in undesirable structural information. Accordingly, a data collection strategy that [...] Read more.

Microfocusing X-rays direct high-density photons on crystal samples and can enhance the diffraction limit and quality of collected data. However, these intense X-rays can cause radiation damage to the sample, which often results in undesirable structural information. Accordingly, a data collection strategy that minimizes radiation damage is critical to obtaining accurate structural information. In this study, radiation damage in single-point data collection was investigated at two different X-ray exposure times (1 s and 100 ms) using microfocusing X-rays and a thaumatin crystal larger than the beam. The data collection statistics showed that the diffraction intensity of the Bragg peak did not gradually decrease until the crystal rotation reached 180°, and it significantly decreased after exceeding this value. Thaumatin structures exposed to X-rays for 1 s (Thaumatin^1s) and 100 ms (Thaumatin^100ms) were determined at 1.13 Å resolution. The temperature factors for Asp60, Arg119, Lys163, and Lys187 of thaumatin were increased by radiation damage. Specific radiation damage was observed at the disulfide bond in Thaumatin^1s but was negligible in Thaumatin^100ms. Splitting and reprocessing Thaumatin^100ms showed that electron density maps with minimal radiation damage can be obtained when using minimal data that satisfy the completeness, I/sigma, and CC1/2 parameters. These results expand our understanding of radiation damage phenomena in macromolecules and can be used for data collection applications. Full article

(This article belongs to the Special Issue Synchrotron Radiation for Medical Applications)

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12 pages, 2410 KiB

Open AccessArticle

X-ray-Induced Heating in the Vicinity of the X-ray Interaction Point

by Jangwoo Kim and Ki Hyun Nam

Appl. Sci. 2023, 13(2), 717; https://doi.org/10.3390/app13020717 - 4 Jan 2023

Cited by 4 | Viewed by 2799

Abstract

When X-rays pass through a material, radiation damage occurs, and heat is generated at the X-ray interaction point, which can then be transferred around the X-ray irradiation site. This X-ray-induced heat transfer can affect the temperature of the sample and consequently the experimental [...] Read more.

When X-rays pass through a material, radiation damage occurs, and heat is generated at the X-ray interaction point, which can then be transferred around the X-ray irradiation site. This X-ray-induced heat transfer can affect the temperature of the sample and consequently the experimental environment in serial crystallography (SX) experiments. Here, we investigated radiation damage and measured the level of heating in the vicinity of the X-ray interaction point. In our experimental setup, when water, crystallization solution, and crystal suspension in a glass tube were exposed to X-rays, a temperature increase of approximately 1.0 °C occurred in the vicinity of the X-ray interaction point, with the heat generated by both the sample and the capillary. When Cu and Al/Zn plates were exposed to X-rays, the temperature around the X-ray exposure point increased by approximately 0.3 and 0.4 °C, respectively. The range of temperature rise decreased as the distance from the X-ray exposure point on the Al plate increased. The heat generated by the X-rays and the rise of the heat could be reduced by discontinuously transmitting the X-rays using the shutter. Our results provide useful information for obtaining more accurate experimental parameters. Full article

(This article belongs to the Special Issue Synchrotron Radiation for Medical Applications)

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18 pages, 3814 KiB

Open AccessArticle

Synchrotron Radiation Circular Dichroism, a New Tool to Probe Interactions between Nucleic Acids Involved in the Control of ColE1-Type Plasmid Replication

by Frank Wien, Krzysztof Kubiak, Florian Turbant, Kevin Mosca, Grzegorz Węgrzyn and Véronique Arluison

Appl. Sci. 2022, 12(5), 2639; https://doi.org/10.3390/app12052639 - 3 Mar 2022

Cited by 4 | Viewed by 2301

Abstract

Hfq is a bacterial master regulator which promotes the pairing of nucleic acids. Due to the high molecular weight of the complexes formed between nucleic acids and the amyloid form of the protein, it is difficult to analyze solely by a gel shift [...] Read more.

Hfq is a bacterial master regulator which promotes the pairing of nucleic acids. Due to the high molecular weight of the complexes formed between nucleic acids and the amyloid form of the protein, it is difficult to analyze solely by a gel shift assay the complexes formed, as they all migrate at the same position in the gel. In addition, precise kinetics measurements are not possible using a gel shift assay. Here, we used a synchrotron-based biophysical approach, synchrotron radiation circular dichroism (SRCD), to probe the interaction of the Escherichia coli Hfq C-terminal amyloid region with nucleic acids involved in the control of ColE1-like plasmid replication. We observed that this C-terminal region of Hfq has an unexpected and significant effect on the annealing of nucleic acids involved in this process and, more importantly, on their alignment. Functional consequences of this newly discovered property of the Hfq amyloid region are discussed in terms of the biological significance of Hfq in the ColE1-type plasmid replication process and antibiotic resistance. Full article

(This article belongs to the Special Issue Synchrotron Radiation for Medical Applications)

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16 pages, 4193 KiB

Open AccessArticle

Incorporating Clinical Imaging into the Delivery of Microbeam Radiation Therapy

by Jason Paino, Micah Barnes, Elette Engels, Jeremy Davis, Susanna Guatelli, Michael de Veer, Chris Hall, Daniel Häusermann, Moeava Tehei, Stéphanie Corde, Anatoly Rosenfeld and Michael Lerch

Appl. Sci. 2021, 11(19), 9101; https://doi.org/10.3390/app11199101 - 30 Sep 2021

Cited by 5 | Viewed by 2740

Abstract

Synchrotron microbeam radiation therapy is a promising pre-clinical radiation treatment modality; however, it comes with many technical challenges. This study describes the image guidance protocol used for Australia’s first long-term pre-clinical MRT treatment of rats bearing 9L gliosarcoma tumours. The protocol utilises existing [...] Read more.

Synchrotron microbeam radiation therapy is a promising pre-clinical radiation treatment modality; however, it comes with many technical challenges. This study describes the image guidance protocol used for Australia’s first long-term pre-clinical MRT treatment of rats bearing 9L gliosarcoma tumours. The protocol utilises existing infrastructure available at the Australian Synchrotron and the adjoining Monash Biomedical Imaging facility. The protocol is designed and optimised to treat small animals utilising high-resolution clinical CT for patient specific tumour identification, coupled with conventional radiography, using the recently developed SyncMRT program for image guidance. Dosimetry performed in small animal phantoms shows patient dose is comparable to standard clinical doses, with a CT associated dose of less than

1.39

c

Gy and a planar radiograh dose of less than

0.03

c

Gy. Experimental validation of alignment accuracy with radiographic film demonstrates end to end accuracy of less than

\pm 0.34

m

m

in anatomical phantoms. Histological analysis of tumour-bearing rats treated with microbeam radiation therapy verifies that tumours are targeted well within applied treatment margins. To date, this technique has been used to treat 35 tumour-bearing rats. Full article

(This article belongs to the Special Issue Synchrotron Radiation for Medical Applications)

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10 pages, 3793 KiB

Open AccessArticle

Synchrotron X-ray Irradiation of a Rat’s Head Model: Monte Carlo Study of Chromatic Gel Dosimetry

by Yarden Peleg Walg, Yanai Krutman, Amir Berman and Itzhak Orion

Appl. Sci. 2021, 11(16), 7389; https://doi.org/10.3390/app11167389 - 11 Aug 2021

Cited by 3 | Viewed by 2012

Abstract

Accurate treatment planning in radiotherapy essentially decreases damage to healthy tissue surrounding the tumor. Due to plans to use a direct, highly collimated, narrow beam with high intensity to treat small area tumors, researchers have studied microbeam radiation therapy extensively. Using a synchrotron [...] Read more.

Accurate treatment planning in radiotherapy essentially decreases damage to healthy tissue surrounding the tumor. Due to plans to use a direct, highly collimated, narrow beam with high intensity to treat small area tumors, researchers have studied microbeam radiation therapy extensively. Using a synchrotron beam as the radiation source may help to limit damage, but treatment planning using computerized simulations and dosimetry is still necessary to achieve optimal results. For this purpose, PDA-gel dosimeters were developed and their sensitivity around a 150 keV induced synchrotron X-ray radiation beam was examined via Monte Carlo simulations using the EGS5 code system. The microbeam development is now at the animal study stage. In this study, we simulate the irradiation of a rat’s brain. The simulation results obtained spectra for two types of PDA-gel dosimeters that were compared with the spectrum obtained in a modelized brain tumor of a rat. Additionally, percentage depth dose curves were calculated for the brain tissue and the two gels. Correction equations for the dosimeters were obtained from the dose-difference plots. For further references, these equations can be used to calculate the actual dose in a brain tumor in a rat. The Monte Carlo simulations demonstrate that PDA-gel dosimeters can be used for treatment planning using synchrotron irradiations. Full article

(This article belongs to the Special Issue Synchrotron Radiation for Medical Applications)

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Review

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26 pages, 3026 KiB

Open AccessReview

Light-Activating PROTACs in Cancer: Chemical Design, Challenges, and Applications

by Arvind Negi, Kavindra Kumar Kesari and Anne Sophie Voisin-Chiret

Appl. Sci. 2022, 12(19), 9674; https://doi.org/10.3390/app12199674 - 26 Sep 2022

Cited by 10 | Viewed by 2650

Abstract

Nonselective cell damage remains a significant limitation of radiation therapies in cancer. Decades of successful integration of radiation therapies with other medicinal chemistry strategies significantly improved therapeutic benefits in cancer. Advancing in such technologies also led to the development of specific photopharmcology-based approaches [...] Read more.

Nonselective cell damage remains a significant limitation of radiation therapies in cancer. Decades of successful integration of radiation therapies with other medicinal chemistry strategies significantly improved therapeutic benefits in cancer. Advancing in such technologies also led to the development of specific photopharmcology-based approaches that improved the cancer cell selectivity and provided researchers with spatiotemporal control over the degradation of highly expressed proteins in cancer (proteolysis targeting chimeras, PROTACs) using a monochrome wavelength light source. Two specific strategies that have achieved notable successes are photocage and photoswitchable PROTACs. Photocaged PROTACs require a photolabile protecting group (PPG) that, when radiated with a specific wavelength of light, irreversibly release PPG and induce protein degradation. Thus far, diethylamino coumarin for estrogen-related receptor α (ERRα), nitropiperonyloxymethyl (BRD4 bromodomain protein), and 4,5-dimethoxy-2-nitrobenzyl for (BRD4 bromodomain protein, as well as BTK kinase protein) were successfully incorporated in photocaged PROTACs. On the other hand, photoswitches of photoswitchable PROTACs act as an actual ON/OFF switch to target specific protein degradation in cancer. The ON/OFF function of photoswitches in PROTACs (as photoswitchable PROTACs) provide spatiotemporal control over protein degradation, and to an extent are correlated with their photoisomeric state (cis/trans-configuration), showcasing an application of the photochemistry concept in precision medicine. This study compiles the photoswitchable PROTACs targeted to bromodomain proteins: BRD 2, 3, and 4; kinases (BCR-ABL fusion protein, ABL); and the immunophilin FKBP12. Photocaging of PROTACs found successes in selective light-controlled degradation of kinase proteins, bromodomain-containing proteins, and estrogen receptors in cancer cells. Full article

(This article belongs to the Special Issue Synchrotron Radiation for Medical Applications)

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19 pages, 7442 KiB

Open AccessReview

Synchrotron X-ray Radiation (SXR) in Medical Imaging: Current Status and Future Prospects

by Mahbubunnabi Tamal, Murad Althobaiti, Abdul-Hakeem Alomari, Sumaiya Tabassum Dipty, Khadiza Tun Suha and Maryam Al-Hashim

Appl. Sci. 2022, 12(8), 3790; https://doi.org/10.3390/app12083790 - 8 Apr 2022

Cited by 4 | Viewed by 8960

Abstract

Synchrotron X-ray radiation (SXR) has been widely studied to explore the structure of matter. Recently, there has been an intense focus on the medical application of SXR in imaging. This review is intended to explore the latest applications of SXR in medical imaging [...] Read more.

Synchrotron X-ray radiation (SXR) has been widely studied to explore the structure of matter. Recently, there has been an intense focus on the medical application of SXR in imaging. This review is intended to explore the latest applications of SXR in medical imaging and to shed light on the advantages and drawbacks of this modality. The article highlights the latest developments in other fields that can greatly enhance the capability and applicability of SXR. The potentials of using machine and deep learning (DL)-based methods to generate synthetic images to use in regular clinics along with the use of photon counting X-ray detectors for spectral medical imaging with SXR are also discussed. Full article

(This article belongs to the Special Issue Synchrotron Radiation for Medical Applications)

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20 pages, 1614 KiB

Open AccessFeature PaperReview

Non-Targeted Effects of Synchrotron Radiation: Lessons from Experiments at the Australian and European Synchrotrons

by Cristian Fernandez-Palomo, Zacharenia Nikitaki, Valentin Djonov, Alexandros G. Georgakilas and Olga A. Martin

Appl. Sci. 2022, 12(4), 2079; https://doi.org/10.3390/app12042079 - 17 Feb 2022

Cited by 3 | Viewed by 3035

Abstract

Studies have been conducted at synchrotron facilities in Europe and Australia to explore a variety of applications of synchrotron X-rays in medicine and biology. We discuss the major technical aspects of the synchrotron irradiation setups, paying specific attention to the Australian Synchrotron (AS) [...] Read more.

Studies have been conducted at synchrotron facilities in Europe and Australia to explore a variety of applications of synchrotron X-rays in medicine and biology. We discuss the major technical aspects of the synchrotron irradiation setups, paying specific attention to the Australian Synchrotron (AS) and the European Synchrotron Radiation Facility (ESRF) as those best configured for a wide range of biomedical research involving animals and future cancer patients. Due to ultra-high dose rates, treatment doses can be delivered within milliseconds, abiding by FLASH radiotherapy principles. In addition, a homogeneous radiation field can be spatially fractionated into a geometric pattern called microbeam radiotherapy (MRT); a coplanar array of thin beams of microscopic dimensions. Both are clinically promising radiotherapy modalities because they trigger a cascade of biological effects that improve tumor control, while increasing normal tissue tolerance compared to conventional radiation. Synchrotrons can deliver high doses to a very small volume with low beam divergence, thus facilitating the study of non-targeted effects of these novel radiation modalities in both in-vitro and in-vivo models. Non-targeted radiation effects studied at the AS and ESRF include monitoring cell–cell communication after partial irradiation of a cell population (radiation-induced bystander effect, RIBE), the response of tissues outside the irradiated field (radiation-induced abscopal effect, RIAE), and the influence of irradiated animals on non-irradiated ones in close proximity (inter-animal RIBE). Here we provide a summary of these experiments and perspectives on their implications for non-targeted effects in biomedical fields. Full article

(This article belongs to the Special Issue Synchrotron Radiation for Medical Applications)

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14 pages, 1295 KiB

Open AccessReview

Synchrotron FTIR Microspectroscopy Investigations on Biochemical Changes Occurring in Human Cells Exposed to Proton Beams

by Ines Delfino, Valerio Ricciardi and Maria Lepore

Appl. Sci. 2022, 12(1), 336; https://doi.org/10.3390/app12010336 - 30 Dec 2021

Cited by 8 | Viewed by 2572

Abstract

Fourier transform infrared microspectroscopy using a synchrotron radiation source (SR-μFTIR) has great potential in the study of the ionizing radiation effects of human cells by analyzing the biochemical changes occurring in cell components. SR-μFTIR spectroscopy has been usefully employed in recent years in [...] Read more.

Fourier transform infrared microspectroscopy using a synchrotron radiation source (SR-μFTIR) has great potential in the study of the ionizing radiation effects of human cells by analyzing the biochemical changes occurring in cell components. SR-μFTIR spectroscopy has been usefully employed in recent years in some seminal work devoted to shedding light on processes occurring in cells treated by hadron therapy, that is, radiotherapy with charged heavy particles (mainly protons and carbon ions), which is gaining popularity as a cancer treatment modality. These studies are particularly useful for increasing the effectiveness of radiotherapy cancer treatments with charged particles that can offer significant progress in the treatment of deep-seated and/or radioresistant tumors. In this paper, we present a concise revision of these studies together with the basic principles of μFTIR spectroscopy and a brief presentation of the main characteristics of infrared SR sources. From the analysis of the literature regarding the SR-μFTIR spectroscopy investigation on human cells exposed to proton beams, it is clearly shown that changes in DNA, protein, and lipid cell components are evident. In addition, this review points out that the potential offered by SR-μFTIR in investigating the effects induced by charged particle irradiation have not been completely explored. This is a crucial point for the continued improvement of hadron therapy strategies. Full article

(This article belongs to the Special Issue Synchrotron Radiation for Medical Applications)

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