International Journal of Radiation Research
Volume:12 Issue: 2, Apr 2014

In this review, we discuss the use of a variety of 3-D models (particularly 3-D skin, lung, breast and endothelial) in radiobiological research and highlight the differences in responses compared to 2-D culturing conditions (monolayers). We review the characteristics of existing 3-D models and aim to point out the substantial advantages 3-D cultures provide for modern radiobiology. In particular, they may facilitate the shift from the classical DNA damage and repair studies mainly carried out in monolayer cultures to the investigation of more generalized responses through pathway analysis and a system biology approach. 3-D models are expected to be very informative for investigations on radiotherapy responses in addressing the low dose risk. However, the 3-D model systems are not as easy to propagate and standardize as monolayer cultures. Therefore, we discuss the problems and limitations of 3-D models and propose ways to overcome some of the problems.

Ionizing radiation induces the production of reactive oxygen species (ROS), which play an important causative role in cell death. The aim of this study was to investigate the protective effects of sulfated derivatives of neutral polysaccharides extracted from Auricularia auricular (SNAAP). Whole blood samples from healthy donors treated with SNAAP at different concentrations (20, 60, 100 μg/mL) were exposed to various doses of X-rays. Wistar rat spleen lymphocytes, in cultures, were treated with SNAAP at different concentrations (20, 60, 100 μg/mL) in the presence p.o 12 hours prior to 8 Gy gamma radiation exposure. Animals were administered with SNAAP at doses of 50, 100 or 200 mg/kg body weight d p.o 7 days prior to sub-lethal doses (6 Gy) of whole body gamma radiation exposure. SNAAP is an effective radio protector against X-ray radiation induced in vitro cellular damage in human peripheral blood. Furthermore, to support this finding the effect of SNAAP on a rat’s spleen lymphocytes, when cultured and examined 24 hours after exposure to 8 Gy γ of radiation, demonstrated the effect of polysaccharides on a rat’s spleen lymphocytes, pretreated by the SNAAP, can increase the cell viability compared with irradiated group at a concentration of 20, 60 and 100 μg/mL. Likewise, this radiation-induced therapy decreased each mouse’s body weight and effectively stimulated the immune system of all radiated mice. Moreover, when induced by Co60, the SNAAP decreased the level of malondialdehyde (MDA) and increased the myeloperoxidase (MPO) and the glutathione peroxidase (GSH-Px) activity in the whole blood supply of the irradiated mice. These encouraging results support further research into the clinical pharmacology of SNAAP as a novel agent for human radiation protection.

Ionizing radiation causes deleterious effects on living system mainly due to oxidative damages of macromolecules and protein is the major target due to its abundance. The aim of this study was to investigate the effects of ionizing radiation induced changes in the molecular properties of bovine serum albumin (BSA); its secondary and tertiary structures, degradation, cross linking and radioprotective role of ferulic acid, a natural antioxidant on these radiation induced changes. This study was carried out to investigate the gamma radiation induced oxidative, structural damage of BSA and radioprotective efficacy of ferulic acid through SDS-PAGE, DTNB assay, DNPH assay, FOX assay methods. Hydroxyl radical scavenging capacity of ferulic acid was estimated using 2-deoxy ribose assay. Further, radiation induced changes in the anisotropy and excitation state lifetimes of BSA were examined. SDS –PAGE data suggested that the loss of protein was linearly dependent on the radiation dose. Gamma-irradiation of BSA caused the formation of protein carbonyls, hydroperoxides and loss of thiols. Ferulic acid protected the radiation induced loss of protein as well as reduced various oxidative damages. Ferulic acid protected the protein from radiation induced damages in a concentration dependent manner. The results provide insight into radiation induced molecular changes in the protein. Ferulic acid protected the BSA from oxidative modification caused by radiation suggesting that ferulic acid possesses strong antiradical properties. Ferulic acid is known to protect DNA, the prime target of radiation and further its ability to protect protein suggesting its ability to protect different biomolecules and therefore can be a good candidate for development radioprotector.

Ramsar (Mazandran province) is known for its extremely high levels of natural background radiation. Although no excess cancer rate is reported in these areas by epidemiological studies, the study of tumor markers in the inhabitants of these areas may shed some light on the impact of high levels of background radiation on cancer induction. The level of background gamma radiation as well as indoor radon was determined using RDS-110 and CR-39 dosimeters. Thirty five individuals from a high background radiation area (HBRA) and 53 individuals from a normal background radiation area (NBRA) were randomly selected to participate in the study. Commercial ELISA kits (sandwich type ELISA tests) were used to measure the serum levels of PSA, CA15.3, CA125, Cyfra21-1, CEA, CA19.9, AFP and Tag72 tumor markers. Among the eight biomarkers investigated, the means of PSA, CA15.3, CA125, CA19.9 and AFP concentrations between the HBRAs and NBRAs were not significantly different. However, Cyfra21, CEA and Tag72 in HBRA group revealed statistically significant increases compared to those of NBRA group (P<0.05). Furthermore, a statistically significant correlation between the external gamma dose as well as indoor radon level and the concentration of CEA (P<0.001), Cyfra-21(P<0.001) and TAG 72 (P<0.001 and 0.01 respectively) biomarkers were observed. Chronic exposure to high background radiation induces significant alterations in Cyfra21, CEA and Tag72 levels. We believe that studies with other relevant tumor markers might overcome the limitations of epidemiological studies on cancer incidence in high background radiation areas.

In this study, Quantitative 32P bremsstrahlung planar and SPECT imaging and consequent dose assessment were carried out as a comprehensive phantom study to define an appropriate method for accurate Dosimetry in clinical practice. CT, planar and SPECT bremsstrahlung images of Jaszczak phantom containing a known activity of 32P were acquired. In addition, Phantom contour was determined for attenuation correction and image registration. Reconstructed SPECT slices were corrected for attenuation effect using two different conventional Chang`s method and an expectation maximization algorithm followed by CT and SPECT image registration. Cumulated activity was calculated by a predefined calibration factor. Both attenuation correction algorithms were quantitatively assessed by the Monte Carlo SIMIND program. Acquired planar Bremsstrahlung images were quantified by the Conjugate View Method, as well. Calculated activities were statistically different among various quantification methods (P= 0.0001). When iterative expectation maximization algorithm and applied methods were used, mean calculated activity had the least difference with real activity of ±3%. Quantitative 32P Bremsstrahlung SPECT imaging could accurately determine administered activity and assess radiation dose if precise attenuation correction and appropriate registration with CT were done even without sophisticated scatter correction or when SPECT/CT machines are not available. Therefore, it has the potential of specific tumor/organ dosimetry in clinical practice. The best method for calculating activity is quantitative SPECT using iterative expectation maximization algorithm. Additionally, applied method for determining phantom contour was practical for attenuation correction and image registration.

The aim of this work was to establish how well gel dosimeters performed, as substitutes for brain tissue compared with standard phantom materials such as water, polymethyl-methacrylate (or PMMA), A150 plastic and TE- liquid phantom material for dosimetry of neutron beams in boron neutron capture therapy. Thermal neutron fluence, photon dose and epithermal neutron dose distributions were computed for the epithermal neutron beam of the optimized linac based BNCT. Amongst all investigated phantom materials, TE-liquid was shown to be a better substitute for brain tissue than other phantom materials. The differences between TE- liquid and brain at the depth of 6.1 cm for thermal neutron fluence, gamma dose and epithermal neutron dose distributions was calculated 2.80%, 2.40% and -13.87%, respectively. In comparison with the other gel dosimeters, LMD2 provided a better simulation of radiation transport in the brain. It's results differed from the real brain, at the depth of 6.1 cm, for thermal neutron fluence, gamma dose and epithermal neutron dose distributions, by -1.27%, 4.20% and 21.05% respectively. Even though, in gamma dose distribution the LMD2 has large deviation from brain tissue distribution, the deviation is approximately independent of depth, so the results can be multiplied by a constant coefficient to be more consistent with reality. Even though, TE- liquid showed satisfactory results for brain tissue substitution in BNCT, but some properties of gel dosimeters such as three dimensionality, make LMD2 a potentially good dosimeter for dosimetric verification in BNCT.

To reduce the dose to normal tissues surrounding the treated breast, a uniform magnetic field was used within a humanoid phantom in breast radiotherapy. Monte Carlo simulations were performed with GEANT4, irradiating humanoid phantoms in a magnetic field. To reconstruct phantoms, computed tomography (CT) data slices of four patients were used for the Monte Carlo simulations. All of them had left breast cancer either or not mastectomy. In the simulations, the planning and methods of chest wall irradiation were similar to the actual clinical planning. Utilizing magnetic field will help to produce uniform dose distribution to the breast with a sharp dose-volume histogram (DVH) curve for the planning target volume (PTV), however, for the ipsilateral lung and chest wall skin the mean dose was reduced by a mean of 16% and 12% at 1.5 T, and 9% and 7% at 3 T, respectively. The magnetic field was shown to restrict the lateral spread of secondary electrons to the contralateral organs, resulting in significient dose reductions to the contralateral breast (CB) and contralateral chest wall skin (CCWS) by a mean (range) of 28% (21-37%) and 58% (44-75%) at 1.5 T, and 48% (32-81) and 66% (54-73%) at 3 T, respectively. The simulations established that the magnetic field can reduce the dose to the internal and contralateral tissues and increase it to the PTV with sharper edge DVH curve.

The advantages of proton beam in radiation therapy- like small lateral scattering as well as absence of exit dose tail in the organs which are after the tumor- make it capable of delivering more treatment doses to the target and much lesser to the critical tissues near it. In this study, the Monte Carlo MCNPX code has been used to simulate a slab head phantom irradiated by proton pencil beams. The simplified slab has tissue compositions of the ICRU 46, and the necessary data have been taken from adult male phantom of MIRD-ORNL family series. Suitable energy range of incident proton beams has been estimated in order to have the Bragg peaks inside the brain tissue. Energy straggling or, rather, range straggling, and multiple scattering which affect the lateral broadening of incident beams, have been investigated. The results show that the FWHM (Full Wide in Half Maximum) increases more than six times from 1.73 mm to 10.78 mm for the energy range of 50 - 135 MeV. The FWHM values of lateral dose profiles change from 1 mm in 50 MeV to 7.5 mm in 135 MeV, and it has been shown that when a pencil beam is used to irradiate a tissue, the absorbed dose in depth along the central axis does not show a Bragg peak pattern.

The purpose of this study is to fabricate inexpensive in-house low cost homogeneous and heterogeneous human equivalent thorax phantom and assess the dose accuracy of the Treatment Planning Systems (TPS) calculated values for different lung treatment dosimetery. It is compared with Thermoluminescent Dosimeter (TLD) measurement. Homogeneous and heterogeneous thorax human equivalent phantoms were fabricated using bee’s wax (density=0.99 g/cm3) as a tissue simulating material, with inserts of cork (density=0.2 g/cm3) and Teflon (density=2 g/cm3) as lung and spine simulating material respectively. Lithium fluoride (LiF) TLD capsules were irradiated for different thoracic tumor treatment techniques using the locally fabricated homogeneous and heterogeneous phantoms. The 3D TPS calculated values of homogeneous and heterogeneous phantoms were compared with TLD measured values. Experiments were carried out for different thoracic tumour treatment techniques for small and larger field sizes and also with and without wedge for Cobalt – 60 photon beams. Plato TPS were used to calculate the inhomogeneity for the homogeneous and heterogeneous phantoms. TLD and 3D TPS calculated values were found to have deviation of ± 5%. Both the homogeneous and heterogeneous phantoms has proved to be a valuable tools in the development and implementation of external beam radiotherapy (EBRT) in the clinical thorax region and in the verification of absolute dose and dose distributions in the regions of clinical and dosimetric interest.

Radioactive yttrium glass microspheres are used for liver cancer treatment. These yttrium aluminum silicate microspheres are synthesized from yttrium, aluminum and silicone oxides by melting. There are two known processes used to transform irregular shaped glass particles into microspheres, these ‘spheroidization by flame’ and ‘spheroidization by gravitational fall in a tubular furnace’. Yttrium aluminum silicate microspheres with the approximate size of 20-50 µm were obtained when an aqueous solution of YCl3 and AlCl3 was added to tetraethyl orthosilicate (TEOS) and pumped in to silicone oil and stirred constantly the temperature of 80˚C. The resulting spherical shapes were then investigated for crystallization, chemical bonds, composition and distribution of elements by scanning electron microscopy (SEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), carbon/sulfur analysis, X-ray photoelectron spectroscopy (XPS) and SEM/EDS analysis. The particles produced by the above-mentioned method were regular and nearly spherical in shape. The results of topographical analysis of a cross-section showed that form of the microspheres had formed a ‘boiled egg’ structure. This method has an advantage over other methods in that the process does not require high temperatures. This paper reports on a novel method to produce yttrium glass microspheres. The resulting microspheres were formed with a silicon crust so the proposed method is expected to be suitable for application in the production of radioactive seed sources for implantation in tumors and cancer tissue.

Primary rhabdomyosarcoma (RMS) of the kidney is a rare malignant mesenchymal tumor with an aggressive clinical course. Adult renal RMS is typically a pleomorphic histologic subtype and only a few cases have ever been reported. We herein present a new case of renal RMS of the embryonal histologic subtype in a 26-year-old woman.