Search

The nanoparticle-induced dose enhancement effect has been shown to improve the therapeutic efficacy of ionizing radiation in external beam radiotherapy. Whereas previous studies have focused on gold nanoparticles (AuNPs), no quantitative studies have been conducted to investigate the potential superiority of other high atomic number (Z) nanomaterials such as bismuth-based nanoparticles. The aims of this study were to experimentally validate and quantify the dose enhancement properties of commercially available bismuth-based nanoparticles (bismuth oxide (Bi2O3-NPs) and bismuth sulfide (Bi2S3-NPs)), and investigate their potential superiority over AuNPs in terms of radiation dose enhancement. Phantom cuvettes doped with and without nanoparticles where employed for measuring radiation dose enhancement produced from the interaction of radiation with metal nanoparticles. Novel 3D phantoms were employed to investigate the 3D spatial distribution of ionising radiation dose deposition. The phantoms were irradiated with kilovoltage and megavoltage X-ray beams and optical absorption changes were measured using a spectrophotometer and optical CT scanner. The radiation dose enhancement factors (DEFs) obtained for 50 nm diameter Bi2O3-NPs and AuNPs were 1.90 and 1.77, respectively, for 100 kV energy and a nanoparticle concentration of 0.5 mM. In addition, the DEFs of 5 nm diameter Bi2S3-NPs and AuNPs were determined to be 1.38 and 1.51, respectively, for 150 kV energy and a nanoparticle concentration of 0.25 mM. The results demonstrate that both bismuth-based nanoparticles can enhance the effects of radiation. For 6 MV energy the DEFs for all the investigated nanoparticles were lower (

In this paper we introduce three novel PRESAGE ® dosimeters referred to as metal optimized dosimeters (MODs) 1, 2 and 3, and determine their sensitivity, as well as their water equivalency. All three formulations contained very small concentrations (0.01 wt%) of metal compounds. The radiological properties were key factors that were considered when designing and formulating the new dosimeters. The dosimeters were prepared in spectrophotometric cuvettes, irradiated with a 6 MV X-ray beam, and the change in optical density of each dosimeter was measured using a spectrophotometer. Results show that all three MOD formulations exhibit radiological properties closer to water than the recently introduced PRESAGE ® dosimeter formulation referred to as formulation A, with mass densities of the novel formulations varying by only 3.9% from that of water, as compared to 5.3% for the commercial formulation. Whereas the novel formulations have almost identical Z eff values to that of water (Z eff = 7.42), the Z eff for the commercial formulation was 3.7% higher than that of water. Comparison of mass energy coefficients for all MOD formulations showed a maximum variation of approximately 0.6 times closer to water especially MOD 3 whereas commercial formulation was 1.23 times larger than water at approximately 40 keV. The same effect was observed fo r mass attenuation coefficients comparison . MOD 3 was also more sensitive to radiation than MOD 1 and 2 as a result of the inclusion of bromine-based halocarbons in the formulation. All novel MOD formulations were comparable to commercial formulation in terms of probability of Compton scatter and pair production compared to water. However, the probability of photoelectric absorption in the three novel MOD formulations varied significantly less (1.3 times greater) from that of water as compared to the commercial formulation (1.8 times greater). Given that all three novel MOD formulations displayed improved radiological properties over any of the currently available PRESAGE ® dosimeter formulations makes them ideal candidates for tissue mimics in dosimetry of clinical megavoltage and kilovoltage x-ray beams.

The aim of this study is to investigate the radiation-modifying effects of incorporating commercially available bismuth-, tin- and zinc-based compounds in the composition of the PRESAGE dosimeter, and the feasibility of employing such compounds for radiation dose enhancement. Furthermore, we demonstrate that metal compounds can be included in the formulation to yield water-equivalent PRESAGE dosimeters with enhanced dose response. Various concentrations of the metal compounds were added to a newly developed PRESAGE formulation and the resulting dosimeters were irradiated with 100 kV and 6 MV photon beams. A comparison between sensitivity and radiological properties of the PRESAGE dosimeters with and without the addition of metal compounds was carried out. Optical density changes of the dosimeters before and after irradiation were measured using a spectro- photometer. In general, when metal compounds were incorporated in the composition of the PRESAGE dosimeter, the sensitivity of the dosimeters to radiation dose increased depending on the type and concentration of the metal compound, with the bismuth compound showing the highest dose enhancement factor. In addition, these metal compounds were also shown to improve the retention of the post-response absorption value of the PRESAGE dosimeter over a period of 2 weeks. Thus, incorporating 1-3 mM (ca. 0.2 wt%) of any of the three investigated metal compounds in the composition of the PRESAGE dosimeter is found to be an efficient way to enhance the sensitivity of the dosimeter to radiation dose and stabilize its post-response for longer times. Furthermore, the addition of small amounts of the metal compounds also accelerates the polymerization of the PRESAGE dosimeter precursors, significantly reducing the fabrication time. Finally, a novel water-equivalent PRESAGE dosimeter formula optimized with metal compounds is proposed for clinical use in both kilovoltage and megavoltage radiotherapy dosimetry. Refereed/Peer-reviewed

Gold nanoparticles (AuNps), because of their high atomic number (Z), have been demonstrated to absorb low-energy X-rays preferentially, compared with tissue, and may be used to achieve localized radiation dose enhancement in tumors. The purpose of this study is to introduce the first example of a novel multicompartment radiochromic radiation dosimeter and to demonstrate its applicability for 3-dimensional (3D) dosimetry of nanoparticle-enhanced radiation therapy.A novel multicompartment phantom radiochromic dosimeter was developed. It was designed and formulated to mimic a tumor loaded with AuNps (50 nm in diameter) at a concentration of 0.5 mM, surrounded by normal tissues. The novel dosimeter is referred to as the Sensitivity Modulated Advanced Radiation Therapy (SMART) dosimeter. The dosimeters were irradiated with 100-kV and 6-MV X-ray energies. Dose enhancement produced from the interaction of X-rays with AuNps was calculated using spectrophotometric and cone-beam optical computed tomography scanning by quantitatively comparing the change in optical density and 3D datasets of the dosimetric measurements between the tissue-equivalent (TE) and TE/AuNps compartments. The interbatch and intrabatch variability and the postresponse stability of the dosimeters with AuNps were also assessed.Radiation dose enhancement factors of 1.77 and 1.11 were obtained using 100-kV and 6-MV X-ray energies, respectively. The results of this study are in good agreement with previous observations; however, for the first time we provide direct experimental confirmation and 3D visualization of the radiosensitization effect of AuNps. The dosimeters with AuNps showed small (3.5%) interbatch variability and negligible (0.5%) intrabatch variability.The SMART dosimeter yields experimental insights concerning the spatial distributions and elevated dose in nanoparticle-enhanced radiation therapy, which cannot be performed using any of the current methods. The authors concluded that it can be used as a novel independent method for nanoparticle-enhanced radiation therapy dosimetry.

It is generally accepted that the PRESAGE(®) radiochromic dosimeter is not sensitive to oxygen, however, this claim has not been supported or verified experimentally. Therefore, the aim of this study was to experimentally determine the potential influence of oxygen on dose sensitivity of the PRESAGE(®) dosimeter and its reporting system. Batches of PRESAGE(®) and its radical initiator-leuco dye reporting system were prepared in aerobic and anaerobic conditions. The anaerobic batches were deoxygenated by bubbling nitrogen through the dosimeter precursors or reporting system for 10 min. The dosimeters and reporting systems were prepared in spectrophotometric cuvettes and glass vials, respectively, and were irradiated with 6 MV photons to various radiation doses. Changes in optical density of the dosimeters and reporting system before and after irradiation were measured using a spectrophotometer. The overall results show that oxygen has some influence on the dosimetric characteristics of PRESAGE(®), although the radical initiator does appear to oxidize the leucomalachite green even in the presence of oxygen. Deoxygenation of the reporting system leads to an increase in sensitivity to radiation dose by ~30% when compared to the non-deoxygenated system. A minor increase in sensitivity (~5%) was also achieved by deoxygenating the PRESAGE(®) precursor prior to casting. In addition, dissolved oxygen measurements revealed low levels of dissolved oxygen (0.40 ± 0.04 mg l(-1)) in the polyurethane precursor used to fabricate the PRESAGE(®) dosimeters, as compared to water (8.60 ± 0.03 mg l(-1)) and the reporting system alone (1.30 ± 0.10 mg l(-1)). The results suggest that the presence of oxygen does not inhibit the radiochromic properties of the PRESAGE(®) system. However, deoxygenation of the dosimeter precursors prior to casting improves the dosimeters dose sensitivity by ~5%, which might be particularly useful for measuring low radiation doses. Nevertheless, we believe this is not sufficient enough to recommend the deoxygenation of commercial PRESAGE(®) precursor prior to casting. In addition, there were no observed changes in the dose linearity, absorption spectrum and post-response photofading characteristics of the PRESAGE(®) under the conditions investigated.

Magnetic resonance-guided radiation therapy (MRgRT) benefits from performing treatment response assessments at the beginning and end of treatment and also during the treatment itself allowing for more normal tissue sparing and better tumor conformality. Gel dosimeters have been shown to demonstrate 3D dose distributions from conventional treatment units. This qualitative study assessed the value of gel dosimetry to measure volumetric dose distributions delivered by an MR-linac (MRL) while using the MR component for readout. Polymer gels in custom-designed glass cylinders of 5 cm diameter and 4 cm height were obtained from MGS Research Inc. (Madison, CT). In addition, Fricke-type dosimeters were prepared in-house with 0.05 mM xylenol orange. For this preliminary study, the dosimeters were irradiated in air, with a part of each dosimeter outside the treatment field to act as a reference. MR imaging was performed with the MRL to observe the change in paramagnetic properties pre and post irradiation using a T2 sequence for polymer gels and a T1-weighted sequence for Fricke gels. MRI during irradiation was done in the MRL using a fast sequence of TR = 5 ms and TE = 1.7 ms. Spin-spin relaxation rate (R2) maps were generated from the polymer gel images and line profiles across the penumbra were analyzed. R2 has previously been shown to be proportional to absorbed dose. When Fricke dosimeters are exposed to ionizing radiation, ferrous ions are oxidized to ferric ions. The paramagnetic spin changes, which are dependent on the concentrations of ferrous and ferric ion species, were observable on T1-weighted images due to changes in the spin-lattice relaxation rate (R1 = 1/T1). We observed a mean increase in pixel value of 53% from un-irradiated to irradiated regions of about 20 Gy. The increase in pixel value and corresponding dose was visible during irradiation using a fast MR sequence. The polymer gels also responded quickly. At 5 minutes after irradiation, the line profiles on the R2 map through the penumbra region showed the fall-off of the radiation field in both dosimeters. 20 hours after irradiation the polymerization of the gel was presumably completed. The overall signal was both higher on the R2 gray scale maps and more pronounced on the R2 color maps. The line profiles across the penumbra regions exhibited a similar trend for both field edges compared to the profiles at 5 minutes post-irradiation. Over the time frame tested, the dosimeter appears stable. These qualitative results indicate that gel dosimetry offers a promising means of measuring relative volumetric dose distributions delivered by an MR-Linac. Refereed/Peer-reviewed

In this study we carry out a comparison between the commercially available leucomalachite green (LMG) dye and three newly synthesised derivatives (with either methoxy, chloro or bromo substituents) incorporated into the PRESAGE dosimeter to determine their effect on the sensitivity and post- response photostability of the dosimeter. In addition, the influence of the new LMG derivatives on the basic radiological properties of the PRESAGEs dosimeter was also investigated. The dosimeters were prepared in spectrophotometric cuvettes, irradiated with a 6 MV X-ray beam, and the change in optical density of each dosimeter was measured using a spectrophotometer. For all of the new LMG derivatives investigated, the sensitivity of the resulting dosimeters to radiation dose increased significantly relative to the unmodified LMG dosimeter, and was dependent on the type of LMG derivative used, with the bromo substituted derivative showing the highest increase in sensitivity (450%), followed by chloro and methoxy substituted derivatives (340 and 200%, respectively). Overall, the new LMG derivatives had only a minimal influence on the radiological properties of the PRESAGE dosimeter, with the exception of the bromo substituted LMG, which increased the effective atomic number (Zeff) of the dosimeter by 9%. All of the LMG dyes investigated showed similar post-response photostability characteristics, with the methoxy substituted LMG showing a slight improvement in post-response photoretention. Refereed/Peer-reviewed

The aim of this study is to investigate the effect of trihalomethane radical initiators on the radiological properties, radiation dose sensitivity and post response photo-stability of the PRESAGE dosimeter. Different PRESAGE dosimeters containing 50 and 100 mM of iodoform (CHI3), bromoform (CHBr3) or chloroform (CHCl3) radical initiators where fabricated and irradiated with 6 MV photons for a range of radiation doses from 0 to 30 Gy. A comparison between sensitivity and radiological properties of the PRESAGE dosimeters with the different radical initiators was carried out. Optical density changes of the dosimeters before and after irradiation were measured using a spectrophotometer. The incorporation of different radical initiators in the composition of the PRESAGE dosimeter resulted in variation of the radiation dose sensitivity and radiological properties of the dosimeters depending on the type and concentration of the radical initiator used, with iodoform showing the highest dose-response slope followed by bromoform and chloroform. However, at 100 mM iodoform, the effective atomic number was significantly higher than water (Zeff ¼ 16). This enhancement in dose-response was found to be directly related to the carbon-halogen bond dissociation energy and to the radiological properties of each individual radical initiator used in this study. Furthermore, the post-response stability of the PRESAGE dosimeters over two weeks remained stable regardless of the trihalomethane radical initiator employed, with negligible change in the post-response stability and linearity of the PRESAGE dosimeters. Refereed/Peer-reviewed