Optimization of the sensitivity and stability of the PRESAGE™ dosimeter using trihalomethane radical initiators

Abstract

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 (Z_eff=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.

Introduction

During the last few decades, radiotherapy treatment delivery techniques have developed into an extremely valuable modality for delivering high curative or palliative doses of ionizing radiation to cancer patients in a way that is safer and more accurate than ever before (Doran, 2009). However, one major hurdle with respect to the planning and delivery of radiotherapy is the preservation of normal tissue while still ensuring the effective death of tumor cells. Hence, the radiation dose delivery to the target must be limited by the tolerance of non-tumor cells to minimize toxicity to normal, healthy tissue (Baldock et al., 2010, Mah et al., 2011). To increase the therapeutic benefits of radiotherapy, recently introduced techniques such as intensity modulated radiation therapy (IMRT) and stereotactic radiosurgery (SRS) aim to deliver a high radiation dose by modulating the intensity of the radiation beam to the tumor while sparing the surrounding normal, healthy tissue (McMahon et al., 2011). This allows conforming the radiation dose in such a way that enables dose escalation in the target volume, whilst simultaneously minimizing the dose to organs at risk, thus reducing the radiation-related side effects (Baldock et al., 2010, Doran, 2009). However, protocols for these complex treatment delivery techniques have been developed to involve very steep dose gradients and are therefore, extremely sensitive to errors in treatment delivery. As a result, three dimensional (3D) polymer gel dosimeters were developed as part of the process of monitoring and improving dose delivery. 3D polymer gel and radiochromic dosimeters are fabricated from radiation-sensitive materials that change their properties (e.g., optical absorption/scattering, X-ray absorption, NMR or acoustic) when absorbing a radiation dose. As a result each type of dosimeter interacts differently with radiation, and has a unique method of recording the radiation dose distribution in 3D compared to conventional ion chambers and two-dimensional dosimeters (2D) such as films, which are limited to point or planar measurement (Baldock et al., 2010, Doran, 2009).

Polymer gel dosimeters can be divided into two main types, namely Fricke and polymer gels. Both systems are composed of a hydrogel matrix that preserves the 3D spatial dose distribution in the dosimeter. In Fricke gels, the Fricke solution (an acidic oxygenated aqueous solution of ferrous ion, Fe²⁺) is based upon the oxidation of ferrous (Fe²⁺) ions into ferric (Fe³⁺) ions (Baldock et al., 2010, Schreiner, 2004). When the solution is irradiated, water decomposition occurs leading to the formation of hydroperoxy radicals (HO₂^·). The hydroperoxyl radicals react with ferrous ions, leading to their conversion to ferric ions (Schreiner, 2004). The ferric ions have a different longitudinal (R1) nuclear magnetic relaxation rate than water. Therefore, the dose distribution can be derived from R1 images obtained by magnetic resonance imaging (MRI) (Schreiner, 2004). However, it is worth noting that several groups have reported degradation of the stored 3D dose distribution in Fricke gels, attributed to the diffusion of ferrous and ferric ions (Balcom et al., 1995, Baldock et al., 2001).

The second type of gel dosimeter, polymer gels, consists of monomers dissolved in a viscous matrix. Upon irradiation, a polymerization reaction takes place resulting in cross-linking of the co-monomers to afford a random 3D cross-linked polymer network. For example, the copolymerization of acrylamide and N,N′-methylenebisacrylamide within a water-based gelatin matrix (Maryanski et al., 1997). The degree of radiation-induced polymerization is dose-dependent and the resulting cross-linked polymer network influences the mobility of the surrounding water molecules, thus affecting the transverse (R2) nuclear magnetic relaxation rates. Therefore, dose maps from polymer gels are constructed from MRI (R2) images (Lepage et al., 2001, Maryanski et al., 1993, Maryanski et al., 1996). In addition, the potential application of the optical-CT system as an alternative imaging technique to MRI has also been demonstrated for polymer gel dosimeters (Gore et al., 1996). One of the major advantageous of polymer gels over Fricke gels is their integrity in dose distribution (Maryanski et al., 1993), although it is worth noting that polymer gels are sensitive to atmospheric oxygen (McAuley, 2006). As a result, normoxic polymer gels were developed, which can be fabricated, stored and irradiated under normal atmospheric conditions (Fong et al., 2001). Nevertheless, both Fricke and polymer gels require supporting containers since they are not solid. This major limitation is not desirable when using optical imaging as it increases refraction and reflection at the surface of the container and hence, leads to significant artefacts that require optical modeling to minimize (Doran, 2009).

The PRESAGE™/optical-CT dosimetry system has recently been introduced as a novel 3D radiochromic dosimetric system and proven to be capable of 3D dosimetry of several common clinical applications (Andrew et al., 2011, Brady et al., 2010, Clift et al., 2010, Doran et al., 2006, Radwan and Azzazy, 2009, Thomas et al., 2011). The PRESAGE dosimeter differs significantly from gel dosimeters, consisting of a clear polyurethane resin containing radiation-sensitive reporter components (leuco dye) and halogenated carbon radical initiators. Halogenated carbons (or halocarbons) are a class of organic compounds containing covalently bonded halogens, such as chlorine (Cl), bromine (Br) or iodine (I). Upon irradiation of the dosimeter free radicals are generated from the homolysis of the bond between carbon and the halogen. These radicals oxidize the leuco dye, leading to a change in color (optical density) caused by the radiolytic oxidation of the leuco dye (Guo et al., 2006a, Guo et al., 2006b). The change in optical density is linear with respect to the absorbed radiation dose (Adamovics and Maryanski, 2006). Some of the attractive features and potential advantages of the PRESAGE dosimeter over gel dosimeters include its lack of sensitivity to oxygen and diffusion (Mostaar et al., 2010). Furthermore, in contrast to polymer gel dosimeters that use precursors dissolved in a fluidic matrix, the PRESAGE dosimeter is solid, easily handleable, can be fashioned into any shape and requires no supporting container. The latter is particularly important from an optical imaging prospective as it means that light has to pass through fewer interfaces on its transit through the dosimeter, therefore minimizing optical artefacts and simplifying any optical modeling required (Doran, 2009).

Previous studies have reported that the sensitivity of the PRESAGE dosimeters can be optimized by varying the weight percent (wt%) of the radical initiator in the composition (Adamovics et al., 2006, Adamovics and Maryanski, 2006, Mostaar et al., 2010). However, the effect of the type and concentration of the halogen in the radical initiator on the sensitivity of the dosimeter to radiation dose and stability has thus far not been investigated. Such investigation is valuable when formulating PRESAGE dosimeters for different dosimetric applications. For example, to detect low radiation doses (<100 mGy), such as those delivered by diagnostic imaging scanners, the dosimeter should be very sensitive to radiation dose. In contrast, in special cases where very high radiation doses (>150 Gy) are delivered to targets such as in microbeam radiotherapy (MRT) (Bencokova et al., 2007, Kashino et al., 2009, Laissue et al., 1998) or high linear energy transfer (LET) particle proton therapy (Al-Nowais et al., 2009a, Tominaga et al., 2009), the PRESAGE dosimeter should ideally be less sensitive to radiation dose so it can still give a linear response at very high doses and not become saturated (complete saturation of the dye) at the estimated saturation absorbance of 2.6 at ca. 150 Gy (Al-Nowais et al., 2009b).

The aim of this study is to investigate the influence of I, Br, and Cl based trihalomethane radical initiators on radiation dose sensitivity, post-response stability and radiological properties of the PRESAGE dosimeter. Also, to suggest specific dosimetric cases where a PRESAGE dosimeter with a specific radical initiator might be desirable.