Studying effects of gold nanoparticle on dose enhancement in megavoltage radiation

Background: Gold nanoparticles are emerging as promising agents for cancer therapy and are being investigated as drug carriers, photothermal agents, contrast agents and radiosensitisers. Objective: The aim of this study is to understand characteristics of secondary electrons generated from interaction of gold nanoparticles GNPs with x-rays as a function of nanoparticle size and beam energy and thereby further understanding of GNPenhanced radiotherapy. Methods: Effective range, defection angle, dose deposition, energy, and interaction processes of electrons produced from the interaction of x-rays with a GNP were calculated by Monte Carlo simulations. The MCNPX code was used to simulate and track electrons generated from 30 and 50 nm diameter GNP when it is irradiated with a cobalt-60 and 6MV photon and electron beam in water. Results: When a GNP was present, depending on beam types used, secondary electron production increased by 10- to 2000-fold compared to absence of a GNP. Conclusion: GNPs with larger diameters also contributed to more doses. © 2015, Shiraz University of Medical Sciences. All rights reserved

DNA Damage of Glioblastoma Multiform Cells Induced by Beta Radiation of Iodine-131 in The Presence or Absence of Topotecan: A Picogreen and Colonogenic Assay

Objective: Glioblastoma multiforme (GBM), one of the most common and aggressive malignant brain tumors, is highly resistant to radiotherapy. Numerous approaches have been pursued to find new radiosensitizers. We used a picogreen and colonogenic assay to appraise the DNA damage and cell death in a spheroid culture of GBM cells caused by iodine-131 (I-131) beta radiation in the presence of topotecan (TPT). Materials and Methods: U87MG cells were cultured as spheroids with approximate diameters of 300 μm. Cells were treated with beta radiation of I-131 (at a dose of 2 Gy) and/ or TPT (1 μg/ml for 2 hours). The numbers of cells that survived were compared with untreated cells using a colonogenic assay. In addition, we evaluated possible DNA damages by the picogreen method. The relation between DNA damage and cell death was assessed in the experimental study of groups. Results: The findings showed that survival fraction (SF) in the I-131+TPT group (39) was considerably less than the I-131 group (58.92; p<0.05). The number of single strand breaks (SSB) and double strand breaks (DSB), in the DNA of U87MG cells treated with beta radiation of I-131 and TPT (I-131+TPT) significantly increased compared to cells treated with only I-131 or TPT (p<0.05). The amount of SSB repair was more than DSB repair (p<0.05). The relationship between cell death and DNA damage was close (r�0.6) and significant (p<0.05) in the irradiated and treated groups. Also the maximum rate of DNA repair occurred 24 hours after the treatments. A significant difference was not observed on other days of the restoration. Conclusion: The findings in the present study indicated that TPT can sensitize U87MG cells to radiation and increase DNA damages. Potentially, TPT can cause an increase in damage from DSB and SSB by its inhibitory effects on topoisomerase enzyme and the cell cycle. The increased complex damages following the use of a genotoxic agent and beta I-131 radiation, causes a significant increase the cell death because of the difficult repair process. By assessing the relationship between DNA damage and cell death, the picogreen method can be useful in predicting colonogenic assay. Consequently, it is suggested that co-treatment with I-131 beta radiation and TPT can improve GBM treatment

Effect of gold nanoparticles on prostate dose distribution under Ir-192 internal and 18 MV external radiotherapy procedures using gel dosimetry and monte carlo method

Background: Gel polymers are considered as new dosimeters for determining radiotherapy dose distribution in three dimensions. Objective: The ability of a new formulation of MAGIC-f polymer gel was assessed by experimental measurement and Monte Carlo (MC) method for studying the effect of gold nanoparticles (GNPs) in prostate dose distributions under the internal Ir-192 and external 18MV radiotherapy practices. Method: A Plexiglas phantom was made representing human pelvis. The GNP shaving 15 nm in diameter and 0.1 mM concentration were synthesized using chemical reduction method. Then, a new formulation of MAGIC-f gel was synthesized. The fabricated gel was poured in the tubes located at the prostate (with and without the GNPs) and bladder locations of the phantom. The phantom was irradiated to an Ir-192 source and 18 MV beam of a Varian linac separately based on common radiotherapy procedures used for prostate cancer. After 24 hours, the irradiated gels were read using a Siemens 1.5 Tesla MRI scanner. The absolute doses at the reference points and isodose curves resulted from the experimental measurement of the gels and MC simulations following the internal and external radiotherapy practices were compared. Results: The mean absorbed doses measured with the gel in the presence of the GNPs in prostate were 15 and 8 higher than the corresponding values without the GNPs under the internal and external radiation therapies, respectively. MC simulations also indicated a dose increase of 14 and 7 due to presence of the GNPs, for the same experimental internal and external radiotherapy practices, respectively. Conclusion: There was a good agreement between the dose enhancement factors (DEFs) estimated with MC simulations and experiment gel measurements due to the GNPs. The results indicated that the polymer gel dosimetry method as developed and used in this study, can be recommended as a reliable method for investigating the DEF of GNPs in internal and external radiotherapy practices. © 2015 Shiraz University of Medical Sciences. All Rights Reserved

Monte Carlo calculation of neutron doses to organs of a female undergoing a pelvic 18 MV irradiation

Applying of high-energy photon beams beside all advantages obstacled by photoneutrons that may cause extra dose to the patient that has not been considered in routine radiotherapy. The purpose of this study is calculation of neutron and gamma doses to a female undergoing a pelvic 18 MV irradiation. A simplified Linac head model as a sphere with 10 cm radius of tungsten and with the total spectrum of an isotropic neutron distribution was located inside a typical bunker. The female anthropomorphic phantom was irradiated with equal weighted four-field pelvic box (18MV). MCNPX (2.4.0) code was used to calculate of absorbed doses. The greatest effective dose, 1.04 mSv Gy-1, was calculated for the AP field while the lowest effective dose, 0.36 mSv Gy-1, was obtained for the RL field. The Percent risk of fatal second malignancy of neutron contamination following a 70 Gy x-ray treatment dose (with equal weights for each field, 17.5 Gy) is 0.152 , including 0.056 for the AP field, 0.033 for the PA field, 0.031 for the RL field and 0.032 for the LL field. If this dose delivered only with the AP field, the risk would be 0.224 , which is 32 higher than that is in case of 4-field irradiation. Our present analysis shows that this simplified model can be used to estimating of photoneutron doses

The effects of backscattered radiation into beam monitor chamber: Study of 6 and 18 MV conventional and removed flattening filter clinical accelerator

In some linear accelerators (Linac), the collected charges in beam monitor chamber (BMC) is partly caused by the backscattered particles from the accelerator components downstream the BMC that influence the Linac output factors. In the intensity modulated radiation therapy technique, the desired dose distribution can be achieved through an unflattened beam. Although removing the flattening filter provides some advantages, the amount of backscatter radiation into BMC can be changed. In this study, contribution of backscattered particles into the BMC response of a Varian 2300 C/D Linac with and without a flattening filter was determined for 6, 18 MV photon beams. The experimental procedure included telescopic method and calculation procedure consisted of Monte Carlo simulation (MCNPX, version 2.4.0), were used to investigate the contribution of backscattered particles into the BMC performance. Our results showed a 2.3 and 3 increase in backscatter for a 0.5 � 0.5 cm2 field compared to a 40 � 40 cm2 field for 6 MV and 18 M V, respectively. The energy deposition from backscattered radiation is mainly caused by backscattered electrons. Removing the flattening filter did not change the BMC performance for a conventional Linac with a flattening filter. However, this result was not valid for small fields (e.g. 0.5 � 0.5 cm2, 18 MV). The corrected backscatter factors is necessary to taking into account the contribution of backscattered radiation in the monitor chamber response for small fields in the case of the free flattening filter Linacs (18 MV)

Genotoxic damage to glioblastoma cells treated with 6 MV X-radiation in the presence or absence of methoxy estradiol, IUDR or topotecan

Objective: To explore the cumulative genotoxic damage to glioblastoma (GBM) cells, grown as multicellular spheroids, following exposure to 6 MV X-rays (2 Gy, 22 Gy) with or without, 2-methoxy estradiol (2ME2), iododeoxyuridine (IUDR) or topotecan (TPT), using the Picogreen assay. Materials and Methods: The U87MG cells cultured as spheroids were treated with 6 MV X-ray using linear accelerator. Specimens were divided into five groups and irradiated using X-ray giving the dose of 2 Gy after sequentially incubated with one of the following three drug combinations: TPT, 2-ME2/TPT, IUDR/TPT or 2ME2/IUDR/TPT. One specimen was used as the irradiated only sample (R). The last group was also irradiated with total dose of 22 Gy (each time 2 Gy) of 6 MV X-ray in 11 fractions and treated for three times. DNA damage was evaluated using the Picogreen method in the experimental study. Results: R/TPT treated group had more DNA damage double strand break (DSB)/single strand break (SSB) compared with the untreated group (P<0.05). Moreover the R/TPT group treated with 2ME2 followed by IUDR had maximum DNA damage in spheroid GBM indicating an augmented genotoxicity in the cells. The DNA damage was induced after seven fractionated irradiation and two sequential treatments with 2ME2/IUDR/TPT. To ensure accuracy of the slope of dose response curve the fractionated radiation was calculated as 7.36 Gy with respect to α/β ratio based on biologically effective dose (BED) formulae. Conclusion: Cells treated with 2ME2/IUDR showed more sensitivity to radiation and accumulative DNA damage. DNA damage was significantly increased when GBM cells treated with TPT ceased at S phase due to the inhibition of topoisomerase enzyme and phosphorylation of Chk1 enzyme. These results suggest that R/TPT-treated cells increase sensitivity to 2ME2 and IUDR especially when they are used together. Therefore, due to an increase in the level of DNA damage (SSB vs. DSB) and impairment of DNA repair machinery, more cell death will occur. This in turn may improve the treatment of GBM. © 2015, Royan Institute (ACECR). All rights reserved

High-dose-rate 192Ir brachytherapy dose verification: A phantom study

Background: The high-dose-rate (HDR) brachytherapy might be an effective tool for palliation of dysphagia. Because of some concerns about adverse effects due to absorbed radiation dose, it is important to estimate absorbed dose in risky organs during this treatment. Objectives: This study aimed to measure the absorbed dose in the parotid, thyroid, and submandibular gland, eye, trachea, spinal cord, and manubrium of sternum in brachytherapy in an anthropomorphic phantom. Materials and Methods: To measure radiation dose, eye, parotid, thyroid, and submandibular gland, spine, and sternum, an anthropomorphic phantom was considered with applicators to set thermoluminescence dosimeters (TLDs). A specific target volume of about 23 cm3 in the upper thoracic esophagus was considered as target, and phantom planned computed tomography (CT) for HDR brachytherapy, then with a micro-Selectron HDR (192Ir) remote after-loading unit. Results: Absorbed doses were measured with calibrated TLDs and were expressed in centi-Gray (cGy). In regions far from target (� 16 cm) such as submandibular, parotid and thyroid glands, mean measured dose ranged from 1.65 to 5.5 cGy. In closer regions (� 16 cm), the absorbed dose might be as high as 113 cGy. Conclusions: Our study showed similar depth and surface doses; in closer regions, the surface and depth doses differed significantly due to the role of primary radiation that had imposed a high-dose gradient and difference between the plan and measurement, which was more severe because of simplifications in tissue inhomogeneity, considered in TPS relative to phantom. © 2015, Iranian Journal of Cancer Prevention

Comparing the dosimetric characteristics of the electron beam from dedicated intraoperative and conventional radiotherapy accelerators

The specific design of the mobile dedicated intraoperative radiotherapy (IORT) accelerators and different electron beam collimation system can change the dosimetric characteristics of electron beam with respect to the conventional accelerators. The aim of this study is to measure and compare the dosimetric characteristics of electron beam produced by intraoperative and conventional radiotherapy accelerators. To this end, percentage depth dose along clinical axis (PDD), transverse dose profile (TDP), and output factor of LIAC IORT and Varian 2100C/D conventional radiotherapy accelerators were measured and compared. TDPs were recorded at depth of maximum dose. The results of this work showed that depths of maximum dose, R90, R50, and RP for LIAC beam are lower than those of Varian beam. Furthermore, for all energies, surface doses related to the LIAC beam are substantially higher than those of Varian beam. The symmetry and flatness of LIAC beam profiles are more desirable compared to the Varian ones. Contrary to Varian accelerator, output factor of LIAC beam substantially increases with a decrease in the size of the applicator. Dosimetric characteristics of beveled IORT applicators along clinical axis were different from those of the flat ones. From these results, it can be concluded that dosimetric characteristics of intraoperative electron beam are substantially different from those of conventional clinical electron beam. The dosimetric characteristics of the LIAC electron beam make it a useful tool for intraoperative radiotherapy purposes

Chronological response of prostacyclin changes to moderately low doses of radiation in rat cervical spinal cord

Background: Study of vascular and its secretory profile changes is an important issue in pathogenesis of radiation myelopathy. This paper reports the prostacyclin concentration changes after low-moderate doses of X-irradiation within a short period of time. Materials and Methods: Cervical cords of Wistar rats were irradiated to doses of 0.5, 1, 2, 4 and 6 Gy X-rays. After 24 hours, 2 and 13 weeks post-irradiation, prostacyclin contents were quantified and cords specimens were also stained routinely for histological studies. Results: Twenty four hours post-irradiation, showed a decrease in the content of prostacyclin after doses of 0.5 and 1 Gy 91.67±1.47 96.80±2.17 of respectively age-matched control group. After 2 weeks the concentration of prostacyclin showed significant decreases after 6 Gy. After 13 weeks irradiation shows marked differences even after a small dose of 2 Gy (p<0.001), and after doses of the low dose group. The differences between concentration values at doses of 4 Gy and 6 Gy were significant in comparison with the control (p<0.001 and p<0.002, respectively). Conclusion: Results suggested that the response of the vascular tissues to low and moderate doses of radiation occurs prior to that of the nervous tissue of the spinal cord. It means that the asymptomatic interval after radiation is characterized by sequential physiological changes which are imperfectly reflected in routine histological study and that even in the histologically unaffected spinal cord; severe impairment is present in substructures and biochemistry of irradiated spinal