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The radioactive aerosol generated by the Nuclear Power Plant (NPP) decommissioning process can be inhaled by workers and deposited inside the human body, resulting in internal exposure. Because internal exposure, unlike external exposure, is difficult to measure directly, it is all the more necessary to assess the dose workers receive as a result of internal exposure. Precise assessment of the internal exposure necessitates actual measurements in the work environment such as the workers’ respiration rate, kind of nuclide and amount of captured nuclide. However, in the event of difficulties in securing these measurements, the internal exposure dose can be estimated based upon the recommended values by the ICRP (International Commission on Radiological Protection) such as the intake fraction and particle size. In this study, 5 μm was selected as the particle size as recommended by the ICRP, and both heavy and light respiratory rates were used in the calculation. With respect to the nuclides contained in the radioactive aerosol and their concentrations, the data captured for the aerosol in the melting facility on the Kozloduy NPP premises in Bulgaria were applied to estimate workers’ internal exposure. As a result, each worker was found not to have received more than 20 mSv/yr, which is the maximum annual permissible dose for workers.

Purpose The purpose of this study was to study the field size effect on the estimated Relative Biological Effectiveness (RBE) for carbon scanning beam irradiation. Methods A silicon-on-insulator (SOI) microdosimeter system developed by the Centre for Medical Radiation Physics, University of Wollongong, Australia, was used for lineal-energy measurements (microdosimetric quantity). The RBE values were derived based on the modified microdosimetric kinetic model (MKM) at different depths in a water phantom in the scanning carbon beam for various scanned areas. Results Our study shows that the difference in RBE values derived from the SOI microdosimeter measurements with the MKM model and from the Treatment Planning System (TPS). The difference of the RBE values is within 6.5 % at the peak point of the spread-out Bragg Peak (SOBP) region. Compared to the spot-beam, RBE values obtained in the scanned-beam with a larger scanned area of 1.0 × 1.0 cm2 have better agreement with which estimated by the TPS. Conclusions This study shows the possibility of using the SOI microdosimeter system as a quality assurance (QA) tool for RBE evaluation in carbon-pencil beam scanning radiotherapy.

In proton therapy, for both therapeutic effectiveness and patient safety, it is very important to accurately measure the proton dose distribution, especially the range of the proton beam. For this purpose, recently we proposed a new imaging method named gamma electron vertex imaging (GEVI), in which the prompt gammas emitting from the nuclear reactions of the proton beam in the patient are converted to electrons, and then the converted electrons are tracked to determine the vertices of the prompt gammas, thereby producing a 2D image of the vertices. In the present study, we developed a prototype GEVI system, including dedicated signal processing and data acquisition systems, which consists of a beryllium plate (= electron converter) to convert the prompt gammas to electrons, two double-sided silicon strip detectors (= hodoscopes) to determine the trajectories of those converted electrons, and a plastic scintillation detector (= calorimeter) to measure their kinetic energies. The system uses triple coincidence logic and multiple energy windows to select only the events from prompt gammas. The detectors of the prototype GEVI system were evaluated for electronic noise level, energy resolution, and time resolution. Finally, the imaging capability of the GEVI system was tested by imaging a 90 Sr beta source, a 60 Co gamma source, and a 45-MeV proton beam in a PMMA phantom. The overall results of the present study generally show that the prototype GEVI system can image the vertices of the prompt gammas produced by the proton nuclear interactions.

Purpose To develop a user-friendly program for biological modeling to analyze radiation-induced responses at the scales of the cell population and organ. Methods The program offers five established cell population surviving fraction (SF) models to estimate the SF and the relative biological effectiveness (RBE) from clonogenic assay data, and two established models to calculate the normal tissue complication probability (NTCP) and tumor control probability (TCP) from radiation treatment plans. Users can also verify the results with multiple types of quantitative analyses and graphical representation tools. Results Users can verify the estimated SF, model parameters, RBE, and the respective uncertainties in the calculations of the SF and RBE modes. The qualities of the treatment plans can also be compared with at most three rival plans in terms of the NTCP, TCP, uncomplicated TCP (UCP), and user-dependent weight-based UCP (UUCP), in the calculation of the NTCP and TCP modes. Based on the validation study on accuracy and speed, the averaged mean relative errors (MREs) of the estimated parameters for all tested cell lines were not higher than 0.3% in each of the studied SF models, and the averaged MREs of the calculated NTCP and TCP for all tested treatment plans were not higher than 0.1%. The computation times for SF, RBE, NTCP, and TCP were less than 1.5 s. Conclusions The dose response analysis program can provide a trustworthy and convenient environment for researchers to analyze radiation-induced biological effects.

The aim of the present study was to find the optimum dynamic conformal arc (DCA)-based radiosurgery conditions for treatment of patients with intracranial tumors. DCA plans were generated on a commercial treatment-planning system (BrainSCAN v.5.31) for various beam-number and gantry-angle combinations by using computed tomography (CT) scans to delineate the planning target volume (PTV) and the organs at risk (OARs). To evaluate planning quality related to the various planning conditions, we analyzed the dose quality factors (DQFs) for 22 patients as a function of the number and the total angle of arcs related to the target volume, which were determined on the basis of patient-specific features. When the total angle of arcs was less than 250°, the DQF values were under 0.98 (worst group). When the total angle of arcs was more than 350 degrees, the DQF values were maximized, and the highest DQF values (best group, DQF > 0.995) occurred in the range between 50 and 120°/cm3 for the total angle/target volume condition. In this optimal range of angle/volume, the asymmetric distribution of the arcs resulted in decreased DQF values. For a relatively large target volume (more than 10 cm3), the DQF values were lower than these for a relatively small target volume (less than 10 cm3). Re-planning results showed that the planning quality could be improved using optimized planning conditions. We expect that this study will provide a basis for the evaluation of various DCA conditions prior to actual planning and treatment.

// Eun Ho Kim 1 , Mi-Sook Kim 2 , Yoshiya Furusawa 3 , Akiko Uzawa 3 , Soorim Han 1 , Won-Gyun Jung 1 , Sei Sai 3 1 Division of Heavy Ion Clinical Research, Korea Institute of Radiological and Medical Sciences, Gongneung-dong, Nowon-Gu, Seoul, South Korea 2 Department of Radiation Oncology, Korea Institute of Radiological and Medical Sciences, Seoul, South Korea 3 Department of Basic Medical Sciences for Radiation Damages, National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan Correspondence to: Mi-Sook Kim, email: mskim@kirams.re.kr Sei Sai, email: sai.sei@qst.go.jp Keywords: metformin, carbon ion beam, radiosensitivity, hepatocellular carcinoma cell, DNA damage Received: August 04, 2016 Accepted: October 19, 2016 Published: October 27, 2016 ABSTRACT The purpose of this study was to investigate the effect of metformin on the responses of hepatocellular carcinoma (HCC) cells to γ–rays (low-linear energy transfer (LET) radiation) and carbon-ion beams (high-LET radiation). HCC cells were pretreated with metformin and exposed to a single dose of γ–rays or carbon ion beams. Metformin treatment increased radiation-induced clonogenic cell death, DNA damage, and apoptosis. Carbon ion beams combined with metformin were more effective than carbon ion beams or γ-rays alone at inducing subG1 and decreasing G2/M arrest, reducing the expression of vimentin, enhancing phospho-AMPK expression, and suppressing phospho-mTOR and phospho-Akt. Thus, metformin effectively enhanced the therapeutic effect of radiation with a wide range of LET, in particular carbon ion beams and it may be useful for increasing the clinical efficacy of carbon ion beams.

// Eun Ho Kim 1 , Mi-Sook Kim 2, * , Kyung-Hee Lee 3 , Jae-Soo Koh 4 , Won-Gyun Jung 1 , Chang-Bae Kong 3, * 1 Division of Heavy Ion Clinical Research, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, South Korea 2 Department of Radiation Oncology, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, South Korea 3 Department of Orthopaedic Surgery, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, South Korea 4 Department of Pathology, Korea Institute of Radiological and Medical Sciences, Seoul 139-706, South Korea * These authors have contributed equally to this work Correspondence to: Mi-Sook Kim, email: mskim@kirams.re.kr Chang-Bae Kong, email: cbkongmd@gmail.com Keywords: zoledronic acid, radiosensitivity, osteosarcoma cells, apoptosis, DNA damage Received: December 30, 2015 Accepted: September 12, 2016 Published: September 27, 2016 ABSTRACT To overcome radioresistance in the treatment of osteosarcoma, a primary malignant tumor of the bone, radiotherapy is generally combined with radiosensitizers. The purpose of this study was to investigate a third-generation bisphosphonate, zoledronic acid (ZOL), as a radiosensitizer for osteosarcoma. We found that exposure of KHOS/NP osteosarcoma cells to 20 μM ZOL decreased the γ-radiation dose needed to kill 90% of cells. This radiosensitizing effect of ZOL was mediated through decreased mitochondrial membrane potential, increased levels of reactive oxygen species, increased DNA damage (as assessed by counting γ-H2AX foci), decreased abundance of proteins involved in DNA repair pathways (ATR, Rad52, and DNA-PKcs), and decreased phosphorylation of PI3K-Akt and MAPK pathway proteins (Raf1, MEK1/2, ERK1/2, and Akt), as compared to γ-irradiation alone. Cells treated with ZOL plus γ-irradiation showed impaired cell migration and invasion and reduced expression of epithelial-mesenchymal transition markers (vimentin, MMP9, and Slug). In Balb/c nude mice, the mean size of orthotopic osteosarcoma tumors 2 weeks post-inoculation was 195 mm 3 following γ-irradiation (8 Gy), while it was 150 mm 3 after γ-irradiation plus ZOL treatment (0.1 mg/kg twice weekly for 2 weeks). These results provide a rationale for combining ZOL with radiotherapy to treat osteosarcoma.

Colorectal cancer is one of the most common cancers worldwide. Previous studies suggest that chemoradiotherapy is more effective for the treatment of colorectal cancer than is radiotherapy or chemotherapy alone. To enhance the radiosensitivity of tumor cells, several investigators have used targeted therapeutic agents that act as radiosensitizers. In the present study, we provide a scientific rationale for the clinical application of SU5416, an inhibitor of vascular endothelial growth factor receptor-2, as a radiosensitizer for colorectal cancer. Two human colorectal adenocarcinoma cell lines, HCT116 and HT-29, were treated with SU5416 and radiation alone or radiation followed by SU5416. In vitro tests were performed using colony forming assays, flow cytometric analysis, immunohistochemistry, senescence-associated β-galactosidase, tumor cell motility and invasion assays. The combination of radiation and SU5416 synergistically inhibited cell survival and induced apoptosis through reactive oxygen species, enhanced IR-induced premature senescence, and inhibited DNA repair activity, cell migration and invasion. Collectively, our results favor the use of SU5416 and radiotherapy as a combination therapy for the treatment of colon cancer and it can be combined successfully with a radiation regimen to potentiate its antitumor and antimetastatic activities for future clinical trials.

Characteristic x rays generated by a collision between a tungsten target and relativistic electron beams generated from a compact electrostatic accelerator based on a Marx generator and a Blumlein pulse-forming line can induce transient ionizing radiation in electronics. While the decelerated electron beam is close to a collector out of range of an external magnetic field, Bremsstrahlung x rays occur at the same time. Compton scattering also occurs through secondary reaction interactions with quasi-stationary particles such as ejected inner shell electrons or photons. During a simulation, a semiconductor process is used to analyze the effects and processes of photocurrents derived from the flow of the drain current when transient pulses generated from the compact electrostatic accelerator are incident in the pMOSFET-AD420-based detector. The photocurrent induced from the detector is also measured by experimental results in comparison with a computer simulation, and a photocurrent detection experiment was then conducted with a high-pulse-current compact electrostatic accelerator. In addition, data pertaining to the irradiation dose rate and photon emission rate were obtained. In order to confirm the radiation pattern in the situation of Compton scattering, the ionizing radiation effect in the photosensitive phosphor was identified using a fluorescent lamp. During the experiment, a relativistic electron beam operating at high energy and current levels at a maximum of 1MeV-10 kA was utilized.

Endothelial cells (ECs), that comprise the tumor vasculature, are critical targets for anticancer radiotherapy. The aim of this work was to study the mechanism by which SU5416, a known anti-angiogenesis inhibitor, modifies the radiation responses of human vascular ECs. Two human endothelial cell lines (HUVEC and 2H11) were treated with SU5416 alone, radiation alone, or a combination of both. In vitro tests were performed using colony forming assays, FACS analysis, western blotting, immunohistochemistry, migration assay, invasion assays and endothelial tube formation assays. The combination of radiation and SU5416 significantly inhibited cell survival, the repair of radiation-induced DNA damage, and induced apoptosis. It also caused cell cycle arrest, inhibited cell migration and invasion, and suppressed angiogenesis. In this study, our results first provide a scientific rationale to combine SU5416 with radiotherapy to target ECs and suggest its clinical application in combination cancer treatment with radiotherapy.

We investigated the parameter optimization of the ridge filter’s thickness for carbon-ion therapy by using a Monte Carlo simulation. For this study, a ridge filter was designed for the spreadout Bragg peak (SOBP) by considering the relative biological effectiveness (RBE). The thickness, height, and width of the ridge filter were designed by using the FLUKA and the GEANT4 codes, and we analyzed and compared the results of the physical dose distributions for the FLUKA and the GEANT4 codes. The results showed that the minimum width of the groove for the ridge filter should be at least 0.5 cm for an appropriate biological dose. The SOBP sections were 8 cm, 9 cm, and 10 cm, respectively, when the heights were 3.5 cm, 4.0 cm, and 4.5 cm. The height of the ridge filter was designed to be associated with the SOBP width. Also, the results for the FLUKA and the GEANT4 codes showed that the average value of the difference was 3% and that the maximum error was 5%; however, the trends were similar. Therefore, the height and the width of the groove for the ridge filter are important parameters for deciding the length and the plateau of the SOBP.

The Korea Heavy Ion Medical Accelerator project focuses on the development of medical accelerator facilities for delivering carbon-ion beams to cancer patients. The purpose of the present study was to estimate the clinical need for carbon-ion therapy in Korea. Seven tumor sites, namely head and neck, liver, lung, colon and rectum, prostate, bone and soft tissue, and pancreas were selected as eligible sites for receiving carbon-ion radiotherapy (RT) by radiation oncologists of the Korea Institute of Radiological and Medical Sciences. Cancer incidence data for the selected tumor sites were obtained from the Korea National Cancer Incidence Database in order to estimate the potential medical need for carbon-ion RT. The carbon-ion RT adaption rate was assessed based on the clinical experience of other carbon-ion therapy facilities. An estimation model was constructed for estimating the medical need for carbon-ion RT, and from this, 25 606 patients were deemed to be potential candidates for carbon-ion RT. This estimated potential need corresponded to 10% of newly diagnosed cancer patients in Korea. The realistic estimation was calculated as ranging between 4000 and 6300 patients, depending on the carbon-ion RT adaptation rate. This estimated medical need corresponded to 2-3% of newly diagnosed cancer patients in Korea. Taken together, our findings suggest that there is a clear medical need for carbon-ion RT in Korea, with at least 4000 potential patients per year.

A new treatment facility for heavy ion therapy since 2010 was constructed. In the broad beam, a range shifter, ridge filter and multi leaf collimator (MLC) for the generation of the spread-out Bragg peak is used. In this case, secondary neutrons produced by the interactions of the ion field with beam-modifying devices (e.g. double-scattering system, beam shaping collimators and range compensators) are very important for patient safety. Therefore, these components must be carefully examined in the context of secondary neutron yield and associated secondary cancer risk. In this article, Monte Carlo simulation has been carried out with the FLUktuierende KAskade particle transport code, the fluence and distribution of neutron generation and the neutron dose equivalent from the broad beam components are compared using carbon and proton beams. As a result, it is confirmed that the yield of neutron production using a carbon beam from all components of the broad beam was higher than using a proton beam. The ambient dose by neutrons per heavy ion and proton ion from the MLC surface was 0.12-0.18 and 0.0067-0.0087 pSv, respectively, which shows that heavy ions generate more neutrons than protons. However, ambient dose per treatment 2 Gy, which means physical dose during treatment by ion beam, is higher than carbon beam because proton therapy needs more beam flux to make 2-Gy prescription dose. Therefore, the neutron production from the MLC, which is closed to the patient, is a very important parameter for patient safety.

Proton therapy, thanks to the dose characteristics of the Bragg peak, according to which most of the radiation energy is delivered at the end of the beam with a very high dose gradient at the distal edge, can deliver a highly conformal radiation dose to the treatment volume. Currently, however, the benefit of this high dose gradient is not fully utilized in clinical practice due mainly to the dose-distribution uncertainty in the beam direction (i.e., the uncertainty of the beam range in the patient). In this paper, we present an imaging system based on gamma electron vertex imaging (GEVI), which is suitable for high-energy (1–30 MeV) gammas, and test its performance for therapeutic proton beams. GEVI images prompt gamma vertices, which are closely correlated with the dose distribution at the distal edge, by converting prompt gammas to electrons via Compton scattering and then tracking the recoiled electrons. Our experimental results show that the GEVI system can image the 2D vertices of the prompt gammas and, thus, can be utilized for the measurement of proton-beam ranges in patients. We believe, indeed, that GEVI makes possible real-time monitoring of in-vivo proton-beam ranges, whose utility significantly improves treatment effectiveness and enhances patient safety. We also expect that the GEVI system will find applications in other fields (e.g., gamma-ray astronomy, nuclear engineering, and high-energy physics) requiring high-energy-gamma (1–30 MeV) imaging.

When a semiconductor element is irradiated with radiation in the form of a transient pulse emitted from a nuclear explosion, a large amount of charge is generated in a short time in the device. A photocurrent amplified in a certain direction by these types of charges cause the device to break down and malfunction or in extreme cases causes them to burn out. In this study, a pulse-type γ-ray generator based on a relativistic electron beam accelerator (γ=2.2, β=0.89) which functions by means of tungsten impingement was constructed and tested in an effort to investigate the process and effects of the photocurrent formed by electron hole pairs (EHP) generated in a pMOSFET device when a transient radiation pulse is incident in the device. The pulse-type γ-ray irradiating device used here to generate the electron beam current in a short time was devised to allow an increase in the irradiation dose. A precise signal processing circuit was constructed to measure the photocurrent of the small signal generated by the pMOSFET due to the electron beam accelerator pulse signal from the large noise stemming from the electromagnetic field around the relativistic electron beam accelerator. The pulse-type γ-ray generator was installed to meet the requirements of relativistic electron beam accelerators, and beam irradiation was conducted after a beam commissioning step.

The aim of this study is to investigate the dose-deposition enhancement by alpha-particle irradiation in a cellular model using carbon and oxygen chemical compositions.A simulation study was performed to study dose enhancement due to carbon and oxygen for a human cell where Geant4 code used for the alpha-particle irradiation to the cellular phantom. The characteristic of dose enhancement in the nucleus and cytoplasm by the alpha-particle radiation was investigated based on concentrations of the carbon and oxygen compositions and was compared with those by gold and gadolinium.The results show that both the carbon and oxygen-induced dose enhancement was found to be more effective than those of gold and gadolinium. We found that the dose-enhancement effect was more dominant in the nucleus than in the cytoplasm if carbon or oxygen is uniformly distributed in a whole cell. In the condition that the added chemical composition was inserted only into the cytoplasm, the effect of the dose enhancement in nucleus becomes weak.We showed that high-stopping-power materials offer a more effective dose-enhancement efficacy and suggest that the carbon nanotubes and oxygenation are promising candidates for dose utilization as dose enhancement tools in particle therapy., Comment: 19 pages, 6 figures, 4 tables. presented to 7th KOREA-JAPAN Joint Meeting on Medical Physics (2014.09.25) accepted to Journal of the Korean Physical Society (2015.03.10)

Colorectal cancer is one of the most common malignancies in the world, and is generally treated more effectively by chemoradiotherapy rather than radiotherapy or chemotherapy alone. Targeted radiosensitizers are often used in order to enhance the radiosensitivity of tumor cells. The aim of the present study was to identify the mechanism of radiosensitization by sorafenib in colorectal cancer. Three human colorectal adenocarcinoma cell lines (HCT116, HT29 and SW480) were treated with sorafenib alone or radiation followed by sorafenib. In vitro tests were performed using colony forming assays, FACS analysis, immunohistochemistry, tumor cell motility assays, invasion assays and endothelial tube formation assays. Sorafenib enhanced the anti-proliferative effects of radiation, reducing colony formation, increasing G2/M arrest and enhancing radiation-induced apoptosis by reactive oxygen species. Sorafenib also inhibited the repair of radiation-induced DNA damage by blocking the activation of DNA-dependent protein kinase. Combination treatment significantly inhibited tumor cell migration, tumor cell invasion and vascular endothelial growth factor-mediated angiogenesis in vitro. Taken together, our results provide a scientific rationale for the use of sorafenib with radiotherapy in colon cancer and suggest a clinical utility for this approach.

The purpose of this study was to investigate the efficacy of metformin as a radiosensitizer for use in combination therapy for human hepatocellular carcinoma (HCC). Three human HCC cell lines (Huh7, HepG2, Hep3B) and a normal human hepatocyte cell line were treated with metformin alone or with radiation followed by metformin. In vitro tests were evaluated by clonogenic survival assay, FACS analysis, western blotting, immunofluorescence and comet assay. Metformin significantly enhanced radiation efficacy under high and low Linear Energy Transfer (LET) radiation conditions in vitro. In combination with radiation, metformin abrogated G2/M arrest and increased the cell population in the sub-G1 phase and the ROS level, ultimately increasing HCC cellular apoptosis. Metformin inhibits the repair of DNA damage caused by radiation. The radiosensitizing effects of metformin are much higher in neutron (high LET)-irradiated cell lines than in gamma (low LET)-irradiated cell lines. Metformin only had a moderate effect in normal hepatocytes. Metformin enhances the radiosensitivity of HCC, suggesting it may have clinical utility in combination cancer treatment with high-LET radiation.

Purpose: The significant issue of particle therapy such as proton and carbon ion was a accurate dose delivery from beam line to patient. For designing the complex delivery system, Monte Carlo simulation can be used for the simulation of various physical interaction in scatters and filters. In this report, we present the development of Monte Carlo simulation platform to help design the prototype of particle therapy nozzle and performed the Monte Carlo simulation using Geant4. Also we show the prototype design of particle therapy beam nozzle for Korea Heavy Ion Medical Accelerator (KHIMA) project in Korea Institute of Radiological and Medical Science(KIRAMS) at Republic of Korea. Methods: We developed a simulation platform for particle therapy beam nozzle using Geant4. In this platform, the prototype nozzle design of Scanning system for carbon was simply designed. For comparison with theoretic beam optics, the beam profile on lateral distribution at isocenter is compared with Mont Carlo simulation result. From the result of this analysis, we can expected the beam spot property of KHIMA system and implement the spot size optimization for our spot scanning system. Results: For characteristics study of scanning system, various combination of the spot size from accerlator with ridge filter and beam monitor was tested as simple design for KHIMA dose delivery system. Conclusion: In this report, we presented the part of simulation platform and the characteristics study. This study is now on-going in order to develop the simulation platform including the beam nozzle and the dose verification tool with treatment planning system. This will be presented as soon as it is become available.