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Capability of NIPAM polymer gel in recording dose from the interaction of 10B and thermal neutron in BNCT
Author’s Accepted Manuscript Potential application of NIPAM polymer gel for dosimetric purposes in boron neutron capture therapy Azim Khajeali, Ali Reza Farajollahi, Yaser Kasesaz, Roghayeh Khodadadi, Assef Khalili, Alireza Naseri www.elsevier.com/locate/apradiso
PII: DOI: Reference:
S0969-8043(15)30169-X http://dx.doi.org/10.1016/j.apradiso.2015.08.028 ARI7117
To appear in: Applied Radiation and Isotopes Received date: 6 March 2015 Revised date: 10 August 2015 Accepted date: 19 August 2015 Cite this article as: Azim Khajeali, Ali Reza Farajollahi, Yaser Kasesaz, Roghayeh Khodadadi, Assef Khalili and Alireza Naseri, Potential application of NIPAM polymer gel for dosimetric purposes in boron neutron capture therapy, Applied Radiation and Isotopes, http://dx.doi.org/10.1016/j.apradiso.2015.08.028 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Potential application of NIPAM polymer gel for dosimetric purposes in boron neutron capture therapy Azim Khajealib • Ali Reza Farajollahia,c,b,1 • Yaser Kasesazd • Roghayeh Khodadadie,b • Assef Khalilif • Alireza Naseric a
Medical Education Research Center, Tabriz, Iran Faculty of Medicine, Department of Medical Physics, Tabriz University of Medical Sciences, Tabriz, Iran c Imam Reza Educational Hospital, Radiotherapy Department, Tabriz University of Medical Sciences, Tabriz, Iran d Nuclear Science and Technology Research Institute (NSTRI), Tehran, Iran e Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran f Faculty of Paramedicine, Tabriz University of Medical Sciences, Tabriz, Iran b
Abstract The capability of N-Isopropylacrylamide (NIPAM) polymer gel was evaluated in recording the dose resulting from boron neutron capture reaction in BNCT. In this regard, three compositions of the gel with different concentrations of
10
B were prepared and exposed to
gamma radiation and thermal neutrons. Unlike irradiation with gamma rays, the boron-loaded gels irradiated by neutron exhibited sensitivity enhancement compared to the gel without 10B. It was also found that the neutron sensitivity of the gel increased by raising the concentration of the 10
B. It can be concluded that NIPAM gel might be a suitable candidate for measuring the
absorbed dose enhancement due to 10B and thermal neutron reaction in BNCT. Keywords: Gel dosimetry, NIPAM polymer gel, BNCT dosimetry, Automatic irradiation system. 1
Corresponding author. Tel: +98 413 337 69 83 Fax: +98 413 336 46 60 E-mail address: [email protected] (A.R.Farajollahi). 1|Page
1.
Introduction
Boron neutron capture therapy (BNCT) is based on selective accumulation of the stable isotope of boron-10 as a neutron capture agent within the tumor cells with subsequent irradiation of tumor using thermal neutron beams. Fundamental reaction of BNCT occurring between boron and thermal neutrons is:
As could be seen in the equation, 10B promptly disintegrates, upon capturing thermal neutron, into an energetic alpha particle back to back with a recoiling 7Li ion. Both these products have high linear energy transfer (LET) and release their energy over a few microns within tissues, which is proportional to cellular dimensions (Barth et al., 2005; Coderre et al., 2003; Hartman and Carlsson, 1994). Unlike conventional radiotherapy which considers physical targeting of the beam, BNCT takes advantage of physiological targeting of the tumor by administration of boron-containing drugs that are capable of accumulating the
10
B within tumor cells with a minimum achievable
concentration on adjacent normal tissues. In other words, the best possible therapeutic outcome of BNCT relies on the selective accumulation of boron in target cells. This ensures the deposition of a higher radiation dose to the tumor relative to the surrounding healthy tissue by high LET radiation with a short range of penetration. Therefore, this complies well with the aim of radiotherapy to destroy cancer cells with minimal damage to adjacent normal tissues. In general, the total dose from BNCT can be attributed to four components (International Atomic Energy Agency, 2001): 1.
The dose from the emitted energetic alpha particle and the recoil 7Li ion arising from 10B
and thermal neutron reaction (
2|Page
.
2.
The proton dose from the thermal neutron captured by nitrogen (
3.
The gamma radiation dose resulting from the reaction between 1H and thermal neutron
(
.
and also gamma rays accompanying the neutron beam. 4.
Epithermal and fast neutron dose contribution from elastic scattering mainly due to the
interaction with hydrogen atoms ( Since the dose components have different relative biological effectiveness (RBE), it is very important to determine the dose distribution in different normal and tumor tissues to quantify the total dose delivered to the patient and to predict the therapeutic efficacy of BNCT. Thus the dose components must be measured by specific dosimetry procedures. According to ICRU Report 45 the principal method recommended for determining fast and epithermal neutron and photon dose is the dual ionization chamber technique (International Commission on Radiation Units Measurements, 1989). The dose contribution from thermal neutron captured in nitrogen-14 and boron-10 is calculated from the measured thermal neutron flux by Kerma approach described by ICRU Report 57 (International Commission on Radiation Units Measurements, 1998). To measure thermal neutron flux cadmium-covered and cadmium-free gold foils are applied (International Atomic Energy Agency, 2001; Kortesniemi, 2002; Kosunen et al., 1999; Raaijmakers et al., 1995; Rogus et al., 1994). Although these methods are commonly used in clinical dosimetry of BNCT, they have some disadvantages (International Atomic Energy Agency, 2001; Khajeali et al., 2015; Podgoršak, 2005). 1.
The dosimetric process is very time-consuming.
2.
The 14N and 10B doses are not measured directly.
3.
Two different dosimetric methods are required to detect various radiation types and for
the total dose calculation. 4.
Ionization chambers need several correction factors.
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To overcome these limitations, a more efficient and reliable dosimeter is needed. The introduction of gel dosimeters and their unique advantages in measuring radiation dose distribution in different radiotherapy techniques make it a potentially suitable option for dosimetric purposes in BNCT. Generally, radiation-sensitive gels can be classified into Fricke and polymer gels which were first employed in BNCT by Gambarini et al. and Farajollahi et al., respectively (Farajollahi et al., 2000; Gambarini et al., 1994). Although Fricke gels have been more frequently used in BNCT dosimetry, they have a major problem associated with the diffusion of ferrous and ferric ions following irradiation. Thus, the researches’ attention was drawn to the polymer gels to deal with the problem. These gels had high stability in recording 3dimensional (3D) dose information, but their main limitation was their toxic formulation. In 2006, Senden et al. conducted a study in an attempt to remove this limitation, which led to the introduction of a less toxic gel by replacing acrylamide with N-Isopropylacrylamide(NIPAM) in polymer gel
formulation referred to as NIPAM (Senden et al., 2006). Studies carried out to investigate the basic dosimetric characteristics of NIPAM gel have shown that the gel's response is reproducible, with energy and dose rates being independent. It was also shown that NIPAM gel is tissue-equivalent in terms of electron and mass density (Farajollahi et al., 2014). In this study, the potential of NIPAM gel, as a less toxic polymer gel dosimeter, was evaluated for applying radiation dosimetry in BNCT. In this regard, NIPAM gels with different concentrations of
10
B were prepared and irradiated by thermal neutron beam and gamma
radiation. Subsequently, the gels were imaged by an MR scanner and the transverse relaxation rate (R2) maps were obtained by analyzing the images. Finally, the dose‒response curves from each of the gel sets were drawn and suitability of NIPAM gel was evaluated for being employed in BNCT dosimetry to record the dose component due to 10B and thermal neutron interaction.
2.
Materials and Methods
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As mentioned above, it has been shown that NIPAM gel is tissue-equivalent in terms of electron and mass density in photon irradiation (Farajollahi et al., 2014). Since the elemental composition of the dosimeter is an important factor in tissue equivalency, especially in neutron irradiation, NIPAM gel was evaluated with regard to elemental composition and then compared to the brain tissue. Table 1 shows the elemental composition of the brain tissue, NIPAM gel and the polyethylene terephthalate (PET) vials used for gel irradiation. According to dose components in BNCT, in addition to boron neutron capture reaction, interactions of thermal neutrons with nitrogen and hydrogen in the tissue have a contribution in patient dose due to production of energetic proton, the recoiling
14
C nucleus and gamma
radiation (International Atomic Energy Agency, 2001). Therefore, accuracy of dose measurement in BNCT will be increased if the amount of these elements in the gel be similar to the tissue. As it is indicated in Table 1, the amounts of nitrogen and hydrogen in the gel and brain tissue are nearly close together.
2.1. NIPAM gel preparation NIPAM gel was prepared in line with the formulation originally proposed by Senden et al., according to which 89% of the gel volume consists of deionized water (Senden et al., 2006). To prepare the required amount of the gel, gelatin (300 Bloom Type A) was added to 80% of water and heated up to 50°C. Once the gelatin was completely melted, the solution was cooled down to 37°C and N, N′-Methylenebisacrylamide (BIS) was added to it as a cross-linking agent. After the Bis was dissolved within 15 minutes, N-Isopropylacrylamide (NIPAM) was added to the gel solution at the same temperature. Once the monomers were completely dissolved, a solution of the antioxidant (hydroxymethyl) phosphonium chloride (THPC) and the remaining water were prepared and added to the gel solution at 35°C. Finally, the resultant gel was poured into vials of
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polyethylene terephthalate (PET) and placed in a refrigerator. Table 2 presents the weight percentages of the materials used, all of which are products of Sigma-Aldrich. In the current study, in order to investigate the NIPAM gel capability in recording different dose components in BNCT treatment method, three different combinations of the gel were prepared as follows: 1. 2. 3.
NIPAM NIPAM with 30 ppm of boron-10 NIPAM with 60 ppm of boron-10
Then they were irradiated by gamma rays and neutrons. In this study, boric acid (H3BO3) was used as 10B source. 2.2.
Neutron irradiation
The vials containing the gel were irradiated in front of the thermal neutron column of the Tehran Research Reactor (TRR), which had just been optimized to be employed in BNCT treatment method (Kasesaz et al., 2014). In Kasesaz et al study, which was conducted to design and construct the thermal neutron beam, it was shown that along with the beam there is gamma radiation contamination resulting from the activated materials in the reactor structure. In order to minimize the amount of the gamma radiation dose, they used a 30×30×12-cm lead block in the beam line. The measured gamma radiation dose rate was 0.57 Gyh-1 in this situation (Kasesaz et al., 2014). Prior to the irradiation process, in order to shield this gamma radiation dose and increase the thermal neutron contribution in gel irradiation a 10-cm lead was placed in front of the neutron beam in this study and the dosimetric experiments were carried out using TLD 700 to measure the gamma radiation dose. The results thus obtained indicated that the gamma radiation dose under such circumstances was negligible. Subsequently, the neutron flux in the samples’ positions was measured, through the activation technique as described in ASTM standard procedure (ASTM E262-13). According to the standard method, indium foils are
6|Page
recommended for determining neutron flux in a range of 103‒1012 (ncm-1). Therefore, indium foils measuring 10 mm in diameter and 0.2 mm in thickness were used to measure the neutron flux. In order to separate the activities due to thermal and epithermal neutrons, the bare and cadmium-covered foils were irradiated by the neutron beam. Subsequently, the time required for giving a particular dose to gel vials was determined using MCNP4C Mont Carlo code (Briesmeister, 2000). The results obtained from the neutron activation technique indicated that thermal neutron accounted for about 99% of the beam. Therefore, a thermal neutron beam was considered as a neutron source in the MCNP simulation. The elemental compositions of the vial and NIPAM gel without
10
B were taken from Table 1. Finally the dose rate in the center of the
gel vials was calculated using F4, DE4/DF4 MCNP cards and flux-to-dose conversion factors (International Commission on Radiation Units Measurements, 1992). Using these MCNP cards we can calculate the following quantity:
Where
is the neutron flux in n/cm2 sec and
is the flux to dose conversion function
and E1 and E2 are the lower and upper limits of neutron energy, respectively. Consequently, the vials containing the gel were irradiated by an automatic system capable of providing for dose uniformity (Figure 1).
2.3.
The automatic irradiation system Dosimetric measurements and foil activation showed that the thermal neutron column of the
TRR would be an appropriate choice to be used in this study; however, there were practical complications, including the difficulties associated with opening and closing of the thermal column plug, with a time interval between turning on the reactor and the neutron flux stabilization and the inaccurate sample radiation time. These problems looked particularly acute
7|Page
because of the conditions of our research; there were large numbers of samples in our experiment, and they needed to be irradiated with different doses. Thus, to overcome such complications and facilitate the radiation process, an automatic system was designed and manufactured, which made it possible to radiate the samples in the same position with a high radiation time accuracy and high speed in transferring the samples. The system has three major parts: the sender part, the irradiation part and the control panel (Figure 1). Figure 2 shows a schematic configuration of the irradiation system in front of the thermal column of TRR. The advantage of irradiation system could be summarized as follows: 1.
Irradiation of all the samples in the same position.
2.
Irradiation of the samples after the reactor power is stabilized.
3.
The precision of 0.01 s in setting the radiation time.
4.
The rotation of the samples during radiation, hence the uniformity of the doses.
5.
The system's automatic running, and providing the radiation protection for the radiation
practitioners. 6.
The system’s portable nature.
2.4. Gamma irradiation In order to investigate the possibility of boric acid affecting the NIPAM gel response to gamma rays, the vials containing different amounts of boric acid, together with standard NIPAM gel, were irradiated, using the Co-60 machine in a water bath made of PMMA (Figure 3). To prevent dose gradient in the samples, the vials, having received 50% of the target dose, were rotated 180° on their vertical axes to receive the second 50% of the radiation.
2.5. MRI
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Imaging of the vials was performed by a 1.5 T Siemens MR scanner 24 hours after irradiation. Since temperature fluctuations affect the dosimeter responses, the gels were isothermal at room temperature and were finally imaged inside an expanded polystyrene (EPS) holder. Table 3 shows the protocol used in MR imaging. To obtain the R2 map, the MR images were analyzed by the code written in MATLAB software (2014), finally yielding the dose response map.
3. Results and Discussion Considering the basic characteristics of the gel dosimeter, it was shown that the NIPAM polymer gel might have a potential role in recording the enhanced radiation dose due to the interaction of 10B and thermal neutron as a tissue-equivalent phantom. Therefore, three groups of NIPAM gel with different concentrations of
10
B were prepared and irradiated by gamma rays
and thermal neutrons. The R2 values were then extracted from the samples which were irradiated to specific doses.
3.1. Neutron irradiation The dose‒response curve in neutron irradiation is demonstrated in Figure 4 for the following gels: 1.
NIPAM
2.
NIPAM with 30 ppm of 10B
3.
NIPAM with 60 ppm of 10B
The parameters of the least squares fit and R-squared values for this figure are reported in Table 4. As can be seen in the table, there is approximately 24% sensitivity enhancement (increased slope of the dose-response curve) in the gel with 30 ppm of 10B in comparison with the gel without 10B. The effect of increased boron concentration on the neutron sensitivity of the
9|Page
gel was also evaluated by adding 60 ppm of
10
B to the gel. It was shown that the sensitivity is
increased by 41% and 14% in comparison with the gel without and with 30 ppm of respectively. As it is clear, the sensitivity of the gel increased with an increase in
10
B,
10
B
concentration from 30 ppm to 60 ppm. The increased sensitivity is due to the enhance dose resulting from thermal neutron reaction with
10
B and its corresponding dose components. The
regression analysis of the data indicated that the increase in slope of the curves is significant with P<0.001. Table 5 presents R2 values for three different NIPAM gels irradiated with different neutron doses. As can be seen, the background R2 value of un-irradiated gels having boric acid (as a source of 10B) increases with increasing concentration of 10B. The gels containing 30 and 60 ppm of
10
B, in comparison to the gels without
10
B, exhibited 9.8% and 14.5% increase in the
background R2, respectively. This is likely due to the boric acid acting as an additional relaxation agent. These results are in accordance with the results of a study carried out using BANG polymer gel by Farajollahi et al (Farajollahi et al., 2000). The comparison of R2 values for the gels irradiated with different neutron doses indicated that these values for gels containing 30 and 60 ppm of
10
B increased by, on average, as much as
13.6% and 19.4%, respectively, compared with the gel lacking interaction of the thermal neutron with
10
10
B. This is resulted from the
B, indicating the capability of the NIPAM gel in
recording the dose resulting from this reaction. The potential of polymer gel dosimeters in recording the enhanced dose resulting from the reaction of the thermal neutron with
10
B was
previously demonstrated in 2000 at Birmingham through irradiating BANG gel containing different amounts of
10
B in neutron beam from Dynamitron and the comparison of R2 profiles
(Farajollahi et al., 2000).
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Drawing the dose‒response curve for NIPAM gel with and without 10B irradiated by thermal neutron beam in the present study provided the percentage of increased dose for gels with 10B as compared with the ones without 10B.
3.2. Gamma irradiation In order to investigate whether or not the dose‒response curve is influenced by the 10B in the gel irradiated by gamma radiation, three different gels (standard, with 30 ppm and 60 ppm 10B) and their dose‒response curves were obtained (Figure 5). As the figure shows the background increased for the gels containing 10B; however, in contrast to the neutron radiation, there was no increase in the dose or a change in the sensitivity (Table 6). This was investigated by Farajollahi et al on BANG gel polymers in 2000. Radiating the BANG polymer gel with and without 10B by Co-60 source, they observed that the calibration curves from the gel with and without 30 ppm 10
B corresponded with each other, but in the case of the gels containing 60 ppm
10
B, the
background was found to have increased without there being a change in the slope, which was interpreted as the boron's having no effect on BANG gel's response to gamma radiation (Farajollahi et al., 2000).
3.3. The comparison of NIPAM gel response to neutron and gamma radiation Figure 6 shows the dose‒response curve associated with NIPAM gel irradiated by neutron and gamma radiation doses up to 10 Gy. As the figure indicates the sensitivity of NIPAM gel to neutron is less than that to gamma radiation, and the correlation of the data points (R-square) in gamma irradiation is better than neutron irradiation. Such differences could be attributed to the differences of gamma and neutron radiations in the way they transfer their energy, i.e. gamma ray inflicts damages mostly indirectly through producing free radicals, while neutron, in contrast, produces alpha particles, recoil protons and heavier nuclear fragments, inflicting
11 | P a g e
damages directly (Hall and Giaccia, 2012). In this study, the observed low gel sensitivity in thermal neutron irradiation is in accordance with the results of studies were conducted to employ polymer gels for measuring dose resulting from high LET particles such as proton and heavy ions (Gustavsson et al., 2004; Heufelder et al., 2003; Jirasek and Duzenli, 2002; Ramm et al., 2000). In these studies, it was found that the gel sensitivity for high LET particles is significantly smaller than high-energy photons, and the gel sensitivity decreases as radiation LET increases.
3.4. Investigation of dose uniformity As it was mentioned above, in order to overcome the complexities associated with neutron irradiation, an automatic radiation system was designed and manufactured, one feature of which was its capability to yield dose uniformity in the samples containing gels. In order to establish how much uniformity had been achieved in the vials irradiated with the automatic system, a number of vials containing gels was irradiated by a neutron beam with the system in rotation-off mode, and their dose profiles were compared with the ones produced using the system in rotation-on mode. Figure 7 shows the dose profiles obtained from the vials irradiated with the absorbed doses of 7 and 10 Gy with and without rotating mode. As it can be observed from the figure, the rotation of vials during radiation causes the dose gradient not to be formed in the gel, which provides for a higher precision and accuracy of the dose measurement.
4.
Conclusion
The results indicated that NIPAM gel, as a 3D dosimeter with high spatial resolution, could be a suitable candidate for measuring the absorbed dose enhancement due to
10
B and thermal
neutron interaction in BNCT treatment method. Further studies are required to investigate the possibility of NIPAM gel application in treatment planning evaluation of BNCT.
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References ASTM E262-13, Standard Test Method for Determining Thermal Neutron Reaction Rates and Thermal Neutron Fluence Rates by Radioactivation Techniques, ASTM International, West Conshohocken, PA, 2013, www.astm.org. Barth, R.F., Coderre, J.A., Vicente, M.G., Blue, T.E., 2005. Boron neutron capture therapy of cancer: current status and future prospects. Clinical cancer research : an official journal of the American Association for Cancer Research 11, 3987-4002. Briesmeister, J.F.E., 2000. "MCNP—A General Monte Carlo N-Particle Transport Code. Version 4C." LA-13709M. Coderre, J.A., Turcotte, J.C., Riley, K.J., Binns, P.J., Harling, O.K., Kiger, W.S., 3rd, 2003. Boron neutron capture therapy: cellular targeting of high linear energy transfer radiation. Technology in cancer research & treatment 2, 355-375. Farajollahi, A.R., Bonnett, D.E., Tattam, D., Green, S., 2000. The potential use of polymer gel dosimetry in boron neutron capture therapy. Physics in medicine and biology 45, N9. Farajollahi, A.R., Pak, F., Horsfield, M., Myabi, Z., 2014. The basic radiation properties of the Nisopropylacrylamide based polymer gel dosimeter. International Journal of Radiation Research 12, 347354. Gambarini, G., Arrigoni, S., Bonardi, M., Cantone, M.C., deBartolo, D., Desiati, S., Facchielli, L., Sichirollo, A.E., 1994. A system for 3-D absorbed dose measurements with tissue-equivalence for thermal neutrons. Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment 353, 406-410. Gustavsson, H., Bäck, S.Å.J., Medin, J., Grusell, E., Olsson, L.E., 2004. Linear energy transfer dependence of a normoxic polymer gel dosimeter investigated using proton beam absorbed dose measurements. Physics in medicine and biology 49, 3847. Hall, E.J., Giaccia, A.J., 2012. Radiobiology for the Radiologist. Wolters Kluwer Health. Hartman, T., Carlsson, J., 1994. Radiation dose heterogeneity in receptor and antigen mediated boron neutron capture therapy. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 31, 61-75. Heufelder, J., Stiefel, S., Pfaender, M., Ludemann, L., Grebe, G., Heese, J., 2003. Use of BANG polymer gel for dose measurements in a 68 MeV proton beam. Med Phys 30, 1235-1240. International Atomic Energy Agency, 2001. Current Status of Neutron Capture Therapy. International Commission on Radiation Units Measurements, 1989. Clinical Neutron Dosimetry, Part 1: Determination of Absorbed Dose in a Patient Treated by External Beams of Fast Neutrons. ICRU Report 45. International Commission on Radiation Units Measurements, 1992. Photon, Electron, Proton and Neutron Interaction Data for Body Tissues. ICRU Report 46. International Commission on Radiation Units Measurements, 1998. Conversion Coefficients for Use in Radiological Protection Against External Radiation. ICRU Report 57. Jirasek, A., Duzenli, C., 2002. Relative effectiveness of polyacrylamide gel dosimeters applied to proton beams: Fourier transform Raman observations and track structure calculations. Med Phys 29, 569-577. Kasesaz, Y., Khalafi, H., Rahmani, F., Ezzati, A., Keyvani, M., Hossnirokh, A., Shamami, M.A., Amini, S., 2014. Design and construction of a thermal neutron beam for BNCT at Tehran Research Reactor. Applied Radiation and Isotopes 94, 149-151. Khajeali, A., Farajollahi, A.R., Khodadadi, R., Kasesaz, Y., Khalili, A., 2015. Role of gel dosimeters in boron neutron capture therapy. Applied Radiation and Isotopes. Kortesniemi, M., 2002. Solutions for Clinical Implementation of Boron Neutron Capture Therapy in Finland. University of Helsinki. Kosunen, A., Kortesniemi, M., Ylä-Mella, H., Seppälä, T., Lampinen, J., Serén, T., Auterinen, I., Järvinen, H., Savolainen, S., 1999. Twin Ionisation Chambers for Dose Determiniations in Phantom in an Epithermal Neutron Beam. Radiation Protection Dosimetry 81, 187-194. Podgoršak, E.B., 2005. Radiation oncology physics: a handbook for teachers and students. International Atomic Energy Agency.
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Raaijmakers, C.P., Konijnenberg, M.W., Verhagen, H.W., Mijnheer, B.J., 1995. Determination of dose components in phantoms irradiated with an epithermal neutron beam for boron neutron capture therapy. Med Phys 22, 321-329. Ramm, U., Weber, U., Bock, M., Kramer, M., Bankamp, A., Damrau, M., Thilmann, C., Bottcher, H.D., Schad, L.R., Kraft, G., 2000. Three-dimensional BANG gel dosimetry in conformal carbon ion radiotherapy. Physics in medicine and biology 45, N95-102. Rogus, R.D., Harling, O.K., Yanch, J.C., 1994. Mixed field dosimetry of epithermal neutron beams for boron neutron capture therapy at the MITR-II research reactor. Med Phys 21, 1611-1625. Senden, R.J., Jean, P.D., McAuley, K.B., Schreiner, L.J., 2006. Polymer gel dosimeters with reduced toxicity: a preliminary investigation of the NMR and optical dose–response using different monomers. Physics in medicine and biology 51, 3301.
Figure captions: Figure 1. a) The sender part. b) The irradiation part. c) The control panel. d) The irradiation part installed in front of the neutron beam. f) The irradiated vials.
Figure 2. Schematic drawing of the automatic transfer system setup in neutron irradiation. 1) Vial position before irradiation. 2) Sender part. 3) Data cable. 4) Steering tube. 5, 6) Thermal column plug. 7) Lead. 8) Thermal neutron beam. 9) Irradiation part. 10) Vial position during irradiation. 11) Collimator. 12) Lead chamber. 13) Control panel. 14 | P a g e
Figure 3. The vials containing NIPAM, NIPAM with 30 and 60 ppm of
10
B in a rectangular
water phantom to be irradiated by Co-60 radiotherapy machine.
Figure 4. Dose‒response curve of NIPAM, NIPAM with 30 and 60 ppm of 10B irradiated with a neutron beam. 15 | P a g e
Figure 5. Dose‒response curve for NIPAM, NIPAM with 30 and 60 ppm of Co-60.
Figure 6. Dose‒response curve for NIPAM in gamma and neutron irradiations.
16 | P a g e
10
B irradiated by
Figure 7. Dose profiles for rotated and fixed vials containing NIPAM gel irradiated by a neutron beam.
Table captions: Table 1. The elemental composition of the brain tissue, NIPAM gel and the polyethylene terephthalate (PET) vials. ICRU 44 brain tissue
NIPAM gel
PET vial
(wt%)
(wt%)
(wt%)
Element
17 | P a g e
18 | P a g e
H
10.7
10.81
4.2
C
14.5
6.51
62.5
N
2.2
1.65
----
O
71.2
80.42
33.3
Na
0.2
----
----
P
0.4
0.29
----
S
0.2
----
----
Cl
0.3
0.33
----
K
0.3
----
----
Density(g/cm3)
1.04
1.03
1.38
Table 2. Different components and their weight percent in gel preparation.
19 | P a g e
Component
Weight percent
Water
89 wt%
Gelatin 300 Bloom Type A
5 wt%
N-Isopropylacrylamide (NIPAM)
3 wt%
N, N′-Methylenebisacrylamide (BIS)
3 wt%
Tetrakis (hydroxymethyl) phosphonium chloride (THPC)
10 mM
Table 3. MRI protocol uesed for scaning gel dosimeters. Sequence T2 weighted-multiple spin echoes Matrix Size 512×512 Slice Thickness (mm) 5 Repetition Time(TR)(ms) 4000 Echo Time(TE)(ms) 20 Inter Echo Time Spacing(ms) 20 Number of Slices 1 Number of Echoes 32 Number of accusation 2
Table 4. Parameters of the least squares fit for NIPAM, NIPAM with 30 and 60ppm
10
B in
neutron irradiation. Gel type
Slope
Intercept Value
R2
Sensitivity enhancement compared to NIPAM without 10B
Sensitivity enhancement compared to NIPAM with 30ppm 10B
Value
Standard error
NIPAM without 10B
0.025
±0.0005
1.498
±0.005
0.9942
---
---
NIPAM with 30ppm 10B
0.031
±0.0009
1.676
±0.009
0.992
23.62%
---
NIPAM with 60ppm 10B
0.036
±0.0010
1.741
±0.01
0.990
40.55%
13.69%
20 | P a g e
Standard error
Table 5. Comparison of R2 values for NIPAM, NIPAM with 30ppm and NIPAM with 60ppm 10B in neutron irradiation. NIPAM
Dose (Gy)
0 1 2 3 4 5 7 9 12 15 17 20
21 | P a g e
R2 value (1/s)
1.49 1.50 1.55 1.59 1.61 1.62 1.68 1.74 1.80 1.87 1.93 2.00
NIPAM with 30ppm 10B
NIPAM with 60ppm 10B
R2
R2
Enhancement% Value (1/s)
1.63 1.73 1.76 1.78 1.80 1.84 1.90 1.95 2.04 2.13 2.22 2.31
Compared to NIPAM 9.4 15.3 13.5 11.9 11.8 13.6 13.1 12.1 13.3 13.9 15.0 15.5
Value (1/s)
1.7 1.81 1.86 1.88 1.89 1.93 2 2.08 2.2 2.29 2.36 2.48
Enhancement% Compared to Compared NIPAM to NIPAM with 30ppm 10 B 14.1 4.3 20.7 4.6 20.0 5.7 18.2 5.6 17.4 5.0 19.1 4.9 18.8 5.3 19.6 6.7 22.2 7.8 22.5 7.5 22.3 6.3 24.3 7.4
Table 6. Comparison of R2 values for NIPAM, NIPAM with 30 and 60ppm irradiated by Co-60. NIPAM Dose (Gy)
0 1 2 3 5 7 10
R2 value (1/s) 1.50 1.61 1.69 1.78 1.94 2.13 2.38
NIPAM with 30ppm 10B
NIPAM with 60ppm 10B
R2
R2
Enhancement% Value (1/s) 1.65 1.76 1.86 1.94 2.12 2.33 2.51
Compared to NIPAM 10.0 9.3 10.1 9.0 9.3 9.4 5.5
Enhancement% Value (1/s) 1.72 1.84 1.94 2.03 2.22 2.38 2.55
Compared to NIPAM 14.7 14.3 14.8 14.0 14.4 11.7 7.1
Compared to NIPAM with 30ppm 10B 4.2 4.5 4.3 4.6 4.7 2.1 1.6
Highlights
Three compositions of NIPAM gel with different concentration of 10B have been exposed by gamma and thermal neutron. The vials containing NIPAM gel have been irradiated by an automatic system capable of providing for dose uniformity. Suitability of NIPAM polymer gel in measuring radiation doses in BNCT has been investigated.
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PII: DOI: Reference:
S0969-8043(15)30169-X http://dx.doi.org/10.1016/j.apradiso.2015.08.028 ARI7117
To appear in: Applied Radiation and Isotopes Received date: 6 March 2015 Revised date: 10 August 2015 Accepted date: 19 August 2015 Cite this article as: Azim Khajeali, Ali Reza Farajollahi, Yaser Kasesaz, Roghayeh Khodadadi, Assef Khalili and Alireza Naseri, Potential application of NIPAM polymer gel for dosimetric purposes in boron neutron capture therapy, Applied Radiation and Isotopes, http://dx.doi.org/10.1016/j.apradiso.2015.08.028 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Potential application of NIPAM polymer gel for dosimetric purposes in boron neutron capture therapy Azim Khajealib • Ali Reza Farajollahia,c,b,1 • Yaser Kasesazd • Roghayeh Khodadadie,b • Assef Khalilif • Alireza Naseric a
Medical Education Research Center, Tabriz, Iran Faculty of Medicine, Department of Medical Physics, Tabriz University of Medical Sciences, Tabriz, Iran c Imam Reza Educational Hospital, Radiotherapy Department, Tabriz University of Medical Sciences, Tabriz, Iran d Nuclear Science and Technology Research Institute (NSTRI), Tehran, Iran e Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran f Faculty of Paramedicine, Tabriz University of Medical Sciences, Tabriz, Iran b
Abstract The capability of N-Isopropylacrylamide (NIPAM) polymer gel was evaluated in recording the dose resulting from boron neutron capture reaction in BNCT. In this regard, three compositions of the gel with different concentrations of
10
B were prepared and exposed to
gamma radiation and thermal neutrons. Unlike irradiation with gamma rays, the boron-loaded gels irradiated by neutron exhibited sensitivity enhancement compared to the gel without 10B. It was also found that the neutron sensitivity of the gel increased by raising the concentration of the 10
B. It can be concluded that NIPAM gel might be a suitable candidate for measuring the
absorbed dose enhancement due to 10B and thermal neutron reaction in BNCT. Keywords: Gel dosimetry, NIPAM polymer gel, BNCT dosimetry, Automatic irradiation system. 1
Corresponding author. Tel: +98 413 337 69 83 Fax: +98 413 336 46 60 E-mail address: [email protected] (A.R.Farajollahi). 1|Page
1.
Introduction
Boron neutron capture therapy (BNCT) is based on selective accumulation of the stable isotope of boron-10 as a neutron capture agent within the tumor cells with subsequent irradiation of tumor using thermal neutron beams. Fundamental reaction of BNCT occurring between boron and thermal neutrons is:
As could be seen in the equation, 10B promptly disintegrates, upon capturing thermal neutron, into an energetic alpha particle back to back with a recoiling 7Li ion. Both these products have high linear energy transfer (LET) and release their energy over a few microns within tissues, which is proportional to cellular dimensions (Barth et al., 2005; Coderre et al., 2003; Hartman and Carlsson, 1994). Unlike conventional radiotherapy which considers physical targeting of the beam, BNCT takes advantage of physiological targeting of the tumor by administration of boron-containing drugs that are capable of accumulating the
10
B within tumor cells with a minimum achievable
concentration on adjacent normal tissues. In other words, the best possible therapeutic outcome of BNCT relies on the selective accumulation of boron in target cells. This ensures the deposition of a higher radiation dose to the tumor relative to the surrounding healthy tissue by high LET radiation with a short range of penetration. Therefore, this complies well with the aim of radiotherapy to destroy cancer cells with minimal damage to adjacent normal tissues. In general, the total dose from BNCT can be attributed to four components (International Atomic Energy Agency, 2001): 1.
The dose from the emitted energetic alpha particle and the recoil 7Li ion arising from 10B
and thermal neutron reaction (
2|Page
.
2.
The proton dose from the thermal neutron captured by nitrogen (
3.
The gamma radiation dose resulting from the reaction between 1H and thermal neutron
(
.
and also gamma rays accompanying the neutron beam. 4.
Epithermal and fast neutron dose contribution from elastic scattering mainly due to the
interaction with hydrogen atoms ( Since the dose components have different relative biological effectiveness (RBE), it is very important to determine the dose distribution in different normal and tumor tissues to quantify the total dose delivered to the patient and to predict the therapeutic efficacy of BNCT. Thus the dose components must be measured by specific dosimetry procedures. According to ICRU Report 45 the principal method recommended for determining fast and epithermal neutron and photon dose is the dual ionization chamber technique (International Commission on Radiation Units Measurements, 1989). The dose contribution from thermal neutron captured in nitrogen-14 and boron-10 is calculated from the measured thermal neutron flux by Kerma approach described by ICRU Report 57 (International Commission on Radiation Units Measurements, 1998). To measure thermal neutron flux cadmium-covered and cadmium-free gold foils are applied (International Atomic Energy Agency, 2001; Kortesniemi, 2002; Kosunen et al., 1999; Raaijmakers et al., 1995; Rogus et al., 1994). Although these methods are commonly used in clinical dosimetry of BNCT, they have some disadvantages (International Atomic Energy Agency, 2001; Khajeali et al., 2015; Podgoršak, 2005). 1.
The dosimetric process is very time-consuming.
2.
The 14N and 10B doses are not measured directly.
3.
Two different dosimetric methods are required to detect various radiation types and for
the total dose calculation. 4.
Ionization chambers need several correction factors.
3|Page
To overcome these limitations, a more efficient and reliable dosimeter is needed. The introduction of gel dosimeters and their unique advantages in measuring radiation dose distribution in different radiotherapy techniques make it a potentially suitable option for dosimetric purposes in BNCT. Generally, radiation-sensitive gels can be classified into Fricke and polymer gels which were first employed in BNCT by Gambarini et al. and Farajollahi et al., respectively (Farajollahi et al., 2000; Gambarini et al., 1994). Although Fricke gels have been more frequently used in BNCT dosimetry, they have a major problem associated with the diffusion of ferrous and ferric ions following irradiation. Thus, the researches’ attention was drawn to the polymer gels to deal with the problem. These gels had high stability in recording 3dimensional (3D) dose information, but their main limitation was their toxic formulation. In 2006, Senden et al. conducted a study in an attempt to remove this limitation, which led to the introduction of a less toxic gel by replacing acrylamide with N-Isopropylacrylamide(NIPAM) in polymer gel
formulation referred to as NIPAM (Senden et al., 2006). Studies carried out to investigate the basic dosimetric characteristics of NIPAM gel have shown that the gel's response is reproducible, with energy and dose rates being independent. It was also shown that NIPAM gel is tissue-equivalent in terms of electron and mass density (Farajollahi et al., 2014). In this study, the potential of NIPAM gel, as a less toxic polymer gel dosimeter, was evaluated for applying radiation dosimetry in BNCT. In this regard, NIPAM gels with different concentrations of
10
B were prepared and irradiated by thermal neutron beam and gamma
radiation. Subsequently, the gels were imaged by an MR scanner and the transverse relaxation rate (R2) maps were obtained by analyzing the images. Finally, the dose‒response curves from each of the gel sets were drawn and suitability of NIPAM gel was evaluated for being employed in BNCT dosimetry to record the dose component due to 10B and thermal neutron interaction.
2.
Materials and Methods
4|Page
As mentioned above, it has been shown that NIPAM gel is tissue-equivalent in terms of electron and mass density in photon irradiation (Farajollahi et al., 2014). Since the elemental composition of the dosimeter is an important factor in tissue equivalency, especially in neutron irradiation, NIPAM gel was evaluated with regard to elemental composition and then compared to the brain tissue. Table 1 shows the elemental composition of the brain tissue, NIPAM gel and the polyethylene terephthalate (PET) vials used for gel irradiation. According to dose components in BNCT, in addition to boron neutron capture reaction, interactions of thermal neutrons with nitrogen and hydrogen in the tissue have a contribution in patient dose due to production of energetic proton, the recoiling
14
C nucleus and gamma
radiation (International Atomic Energy Agency, 2001). Therefore, accuracy of dose measurement in BNCT will be increased if the amount of these elements in the gel be similar to the tissue. As it is indicated in Table 1, the amounts of nitrogen and hydrogen in the gel and brain tissue are nearly close together.
2.1. NIPAM gel preparation NIPAM gel was prepared in line with the formulation originally proposed by Senden et al., according to which 89% of the gel volume consists of deionized water (Senden et al., 2006). To prepare the required amount of the gel, gelatin (300 Bloom Type A) was added to 80% of water and heated up to 50°C. Once the gelatin was completely melted, the solution was cooled down to 37°C and N, N′-Methylenebisacrylamide (BIS) was added to it as a cross-linking agent. After the Bis was dissolved within 15 minutes, N-Isopropylacrylamide (NIPAM) was added to the gel solution at the same temperature. Once the monomers were completely dissolved, a solution of the antioxidant (hydroxymethyl) phosphonium chloride (THPC) and the remaining water were prepared and added to the gel solution at 35°C. Finally, the resultant gel was poured into vials of
5|Page
polyethylene terephthalate (PET) and placed in a refrigerator. Table 2 presents the weight percentages of the materials used, all of which are products of Sigma-Aldrich. In the current study, in order to investigate the NIPAM gel capability in recording different dose components in BNCT treatment method, three different combinations of the gel were prepared as follows: 1. 2. 3.
NIPAM NIPAM with 30 ppm of boron-10 NIPAM with 60 ppm of boron-10
Then they were irradiated by gamma rays and neutrons. In this study, boric acid (H3BO3) was used as 10B source. 2.2.
Neutron irradiation
The vials containing the gel were irradiated in front of the thermal neutron column of the Tehran Research Reactor (TRR), which had just been optimized to be employed in BNCT treatment method (Kasesaz et al., 2014). In Kasesaz et al study, which was conducted to design and construct the thermal neutron beam, it was shown that along with the beam there is gamma radiation contamination resulting from the activated materials in the reactor structure. In order to minimize the amount of the gamma radiation dose, they used a 30×30×12-cm lead block in the beam line. The measured gamma radiation dose rate was 0.57 Gyh-1 in this situation (Kasesaz et al., 2014). Prior to the irradiation process, in order to shield this gamma radiation dose and increase the thermal neutron contribution in gel irradiation a 10-cm lead was placed in front of the neutron beam in this study and the dosimetric experiments were carried out using TLD 700 to measure the gamma radiation dose. The results thus obtained indicated that the gamma radiation dose under such circumstances was negligible. Subsequently, the neutron flux in the samples’ positions was measured, through the activation technique as described in ASTM standard procedure (ASTM E262-13). According to the standard method, indium foils are
6|Page
recommended for determining neutron flux in a range of 103‒1012 (ncm-1). Therefore, indium foils measuring 10 mm in diameter and 0.2 mm in thickness were used to measure the neutron flux. In order to separate the activities due to thermal and epithermal neutrons, the bare and cadmium-covered foils were irradiated by the neutron beam. Subsequently, the time required for giving a particular dose to gel vials was determined using MCNP4C Mont Carlo code (Briesmeister, 2000). The results obtained from the neutron activation technique indicated that thermal neutron accounted for about 99% of the beam. Therefore, a thermal neutron beam was considered as a neutron source in the MCNP simulation. The elemental compositions of the vial and NIPAM gel without
10
B were taken from Table 1. Finally the dose rate in the center of the
gel vials was calculated using F4, DE4/DF4 MCNP cards and flux-to-dose conversion factors (International Commission on Radiation Units Measurements, 1992). Using these MCNP cards we can calculate the following quantity:
Where
is the neutron flux in n/cm2 sec and
is the flux to dose conversion function
and E1 and E2 are the lower and upper limits of neutron energy, respectively. Consequently, the vials containing the gel were irradiated by an automatic system capable of providing for dose uniformity (Figure 1).
2.3.
The automatic irradiation system Dosimetric measurements and foil activation showed that the thermal neutron column of the
TRR would be an appropriate choice to be used in this study; however, there were practical complications, including the difficulties associated with opening and closing of the thermal column plug, with a time interval between turning on the reactor and the neutron flux stabilization and the inaccurate sample radiation time. These problems looked particularly acute
7|Page
because of the conditions of our research; there were large numbers of samples in our experiment, and they needed to be irradiated with different doses. Thus, to overcome such complications and facilitate the radiation process, an automatic system was designed and manufactured, which made it possible to radiate the samples in the same position with a high radiation time accuracy and high speed in transferring the samples. The system has three major parts: the sender part, the irradiation part and the control panel (Figure 1). Figure 2 shows a schematic configuration of the irradiation system in front of the thermal column of TRR. The advantage of irradiation system could be summarized as follows: 1.
Irradiation of all the samples in the same position.
2.
Irradiation of the samples after the reactor power is stabilized.
3.
The precision of 0.01 s in setting the radiation time.
4.
The rotation of the samples during radiation, hence the uniformity of the doses.
5.
The system's automatic running, and providing the radiation protection for the radiation
practitioners. 6.
The system’s portable nature.
2.4. Gamma irradiation In order to investigate the possibility of boric acid affecting the NIPAM gel response to gamma rays, the vials containing different amounts of boric acid, together with standard NIPAM gel, were irradiated, using the Co-60 machine in a water bath made of PMMA (Figure 3). To prevent dose gradient in the samples, the vials, having received 50% of the target dose, were rotated 180° on their vertical axes to receive the second 50% of the radiation.
2.5. MRI
8|Page
Imaging of the vials was performed by a 1.5 T Siemens MR scanner 24 hours after irradiation. Since temperature fluctuations affect the dosimeter responses, the gels were isothermal at room temperature and were finally imaged inside an expanded polystyrene (EPS) holder. Table 3 shows the protocol used in MR imaging. To obtain the R2 map, the MR images were analyzed by the code written in MATLAB software (2014), finally yielding the dose response map.
3. Results and Discussion Considering the basic characteristics of the gel dosimeter, it was shown that the NIPAM polymer gel might have a potential role in recording the enhanced radiation dose due to the interaction of 10B and thermal neutron as a tissue-equivalent phantom. Therefore, three groups of NIPAM gel with different concentrations of
10
B were prepared and irradiated by gamma rays
and thermal neutrons. The R2 values were then extracted from the samples which were irradiated to specific doses.
3.1. Neutron irradiation The dose‒response curve in neutron irradiation is demonstrated in Figure 4 for the following gels: 1.
NIPAM
2.
NIPAM with 30 ppm of 10B
3.
NIPAM with 60 ppm of 10B
The parameters of the least squares fit and R-squared values for this figure are reported in Table 4. As can be seen in the table, there is approximately 24% sensitivity enhancement (increased slope of the dose-response curve) in the gel with 30 ppm of 10B in comparison with the gel without 10B. The effect of increased boron concentration on the neutron sensitivity of the
9|Page
gel was also evaluated by adding 60 ppm of
10
B to the gel. It was shown that the sensitivity is
increased by 41% and 14% in comparison with the gel without and with 30 ppm of respectively. As it is clear, the sensitivity of the gel increased with an increase in
10
B,
10
B
concentration from 30 ppm to 60 ppm. The increased sensitivity is due to the enhance dose resulting from thermal neutron reaction with
10
B and its corresponding dose components. The
regression analysis of the data indicated that the increase in slope of the curves is significant with P<0.001. Table 5 presents R2 values for three different NIPAM gels irradiated with different neutron doses. As can be seen, the background R2 value of un-irradiated gels having boric acid (as a source of 10B) increases with increasing concentration of 10B. The gels containing 30 and 60 ppm of
10
B, in comparison to the gels without
10
B, exhibited 9.8% and 14.5% increase in the
background R2, respectively. This is likely due to the boric acid acting as an additional relaxation agent. These results are in accordance with the results of a study carried out using BANG polymer gel by Farajollahi et al (Farajollahi et al., 2000). The comparison of R2 values for the gels irradiated with different neutron doses indicated that these values for gels containing 30 and 60 ppm of
10
B increased by, on average, as much as
13.6% and 19.4%, respectively, compared with the gel lacking interaction of the thermal neutron with
10
10
B. This is resulted from the
B, indicating the capability of the NIPAM gel in
recording the dose resulting from this reaction. The potential of polymer gel dosimeters in recording the enhanced dose resulting from the reaction of the thermal neutron with
10
B was
previously demonstrated in 2000 at Birmingham through irradiating BANG gel containing different amounts of
10
B in neutron beam from Dynamitron and the comparison of R2 profiles
(Farajollahi et al., 2000).
10 | P a g e
Drawing the dose‒response curve for NIPAM gel with and without 10B irradiated by thermal neutron beam in the present study provided the percentage of increased dose for gels with 10B as compared with the ones without 10B.
3.2. Gamma irradiation In order to investigate whether or not the dose‒response curve is influenced by the 10B in the gel irradiated by gamma radiation, three different gels (standard, with 30 ppm and 60 ppm 10B) and their dose‒response curves were obtained (Figure 5). As the figure shows the background increased for the gels containing 10B; however, in contrast to the neutron radiation, there was no increase in the dose or a change in the sensitivity (Table 6). This was investigated by Farajollahi et al on BANG gel polymers in 2000. Radiating the BANG polymer gel with and without 10B by Co-60 source, they observed that the calibration curves from the gel with and without 30 ppm 10
B corresponded with each other, but in the case of the gels containing 60 ppm
10
B, the
background was found to have increased without there being a change in the slope, which was interpreted as the boron's having no effect on BANG gel's response to gamma radiation (Farajollahi et al., 2000).
3.3. The comparison of NIPAM gel response to neutron and gamma radiation Figure 6 shows the dose‒response curve associated with NIPAM gel irradiated by neutron and gamma radiation doses up to 10 Gy. As the figure indicates the sensitivity of NIPAM gel to neutron is less than that to gamma radiation, and the correlation of the data points (R-square) in gamma irradiation is better than neutron irradiation. Such differences could be attributed to the differences of gamma and neutron radiations in the way they transfer their energy, i.e. gamma ray inflicts damages mostly indirectly through producing free radicals, while neutron, in contrast, produces alpha particles, recoil protons and heavier nuclear fragments, inflicting
11 | P a g e
damages directly (Hall and Giaccia, 2012). In this study, the observed low gel sensitivity in thermal neutron irradiation is in accordance with the results of studies were conducted to employ polymer gels for measuring dose resulting from high LET particles such as proton and heavy ions (Gustavsson et al., 2004; Heufelder et al., 2003; Jirasek and Duzenli, 2002; Ramm et al., 2000). In these studies, it was found that the gel sensitivity for high LET particles is significantly smaller than high-energy photons, and the gel sensitivity decreases as radiation LET increases.
3.4. Investigation of dose uniformity As it was mentioned above, in order to overcome the complexities associated with neutron irradiation, an automatic radiation system was designed and manufactured, one feature of which was its capability to yield dose uniformity in the samples containing gels. In order to establish how much uniformity had been achieved in the vials irradiated with the automatic system, a number of vials containing gels was irradiated by a neutron beam with the system in rotation-off mode, and their dose profiles were compared with the ones produced using the system in rotation-on mode. Figure 7 shows the dose profiles obtained from the vials irradiated with the absorbed doses of 7 and 10 Gy with and without rotating mode. As it can be observed from the figure, the rotation of vials during radiation causes the dose gradient not to be formed in the gel, which provides for a higher precision and accuracy of the dose measurement.
4.
Conclusion
The results indicated that NIPAM gel, as a 3D dosimeter with high spatial resolution, could be a suitable candidate for measuring the absorbed dose enhancement due to
10
B and thermal
neutron interaction in BNCT treatment method. Further studies are required to investigate the possibility of NIPAM gel application in treatment planning evaluation of BNCT.
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References ASTM E262-13, Standard Test Method for Determining Thermal Neutron Reaction Rates and Thermal Neutron Fluence Rates by Radioactivation Techniques, ASTM International, West Conshohocken, PA, 2013, www.astm.org. Barth, R.F., Coderre, J.A., Vicente, M.G., Blue, T.E., 2005. Boron neutron capture therapy of cancer: current status and future prospects. Clinical cancer research : an official journal of the American Association for Cancer Research 11, 3987-4002. Briesmeister, J.F.E., 2000. "MCNP—A General Monte Carlo N-Particle Transport Code. Version 4C." LA-13709M. Coderre, J.A., Turcotte, J.C., Riley, K.J., Binns, P.J., Harling, O.K., Kiger, W.S., 3rd, 2003. Boron neutron capture therapy: cellular targeting of high linear energy transfer radiation. Technology in cancer research & treatment 2, 355-375. Farajollahi, A.R., Bonnett, D.E., Tattam, D., Green, S., 2000. The potential use of polymer gel dosimetry in boron neutron capture therapy. Physics in medicine and biology 45, N9. Farajollahi, A.R., Pak, F., Horsfield, M., Myabi, Z., 2014. The basic radiation properties of the Nisopropylacrylamide based polymer gel dosimeter. International Journal of Radiation Research 12, 347354. Gambarini, G., Arrigoni, S., Bonardi, M., Cantone, M.C., deBartolo, D., Desiati, S., Facchielli, L., Sichirollo, A.E., 1994. A system for 3-D absorbed dose measurements with tissue-equivalence for thermal neutrons. Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment 353, 406-410. Gustavsson, H., Bäck, S.Å.J., Medin, J., Grusell, E., Olsson, L.E., 2004. Linear energy transfer dependence of a normoxic polymer gel dosimeter investigated using proton beam absorbed dose measurements. Physics in medicine and biology 49, 3847. Hall, E.J., Giaccia, A.J., 2012. Radiobiology for the Radiologist. Wolters Kluwer Health. Hartman, T., Carlsson, J., 1994. Radiation dose heterogeneity in receptor and antigen mediated boron neutron capture therapy. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 31, 61-75. Heufelder, J., Stiefel, S., Pfaender, M., Ludemann, L., Grebe, G., Heese, J., 2003. Use of BANG polymer gel for dose measurements in a 68 MeV proton beam. Med Phys 30, 1235-1240. International Atomic Energy Agency, 2001. Current Status of Neutron Capture Therapy. International Commission on Radiation Units Measurements, 1989. Clinical Neutron Dosimetry, Part 1: Determination of Absorbed Dose in a Patient Treated by External Beams of Fast Neutrons. ICRU Report 45. International Commission on Radiation Units Measurements, 1992. Photon, Electron, Proton and Neutron Interaction Data for Body Tissues. ICRU Report 46. International Commission on Radiation Units Measurements, 1998. Conversion Coefficients for Use in Radiological Protection Against External Radiation. ICRU Report 57. Jirasek, A., Duzenli, C., 2002. Relative effectiveness of polyacrylamide gel dosimeters applied to proton beams: Fourier transform Raman observations and track structure calculations. Med Phys 29, 569-577. Kasesaz, Y., Khalafi, H., Rahmani, F., Ezzati, A., Keyvani, M., Hossnirokh, A., Shamami, M.A., Amini, S., 2014. Design and construction of a thermal neutron beam for BNCT at Tehran Research Reactor. Applied Radiation and Isotopes 94, 149-151. Khajeali, A., Farajollahi, A.R., Khodadadi, R., Kasesaz, Y., Khalili, A., 2015. Role of gel dosimeters in boron neutron capture therapy. Applied Radiation and Isotopes. Kortesniemi, M., 2002. Solutions for Clinical Implementation of Boron Neutron Capture Therapy in Finland. University of Helsinki. Kosunen, A., Kortesniemi, M., Ylä-Mella, H., Seppälä, T., Lampinen, J., Serén, T., Auterinen, I., Järvinen, H., Savolainen, S., 1999. Twin Ionisation Chambers for Dose Determiniations in Phantom in an Epithermal Neutron Beam. Radiation Protection Dosimetry 81, 187-194. Podgoršak, E.B., 2005. Radiation oncology physics: a handbook for teachers and students. International Atomic Energy Agency.
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Raaijmakers, C.P., Konijnenberg, M.W., Verhagen, H.W., Mijnheer, B.J., 1995. Determination of dose components in phantoms irradiated with an epithermal neutron beam for boron neutron capture therapy. Med Phys 22, 321-329. Ramm, U., Weber, U., Bock, M., Kramer, M., Bankamp, A., Damrau, M., Thilmann, C., Bottcher, H.D., Schad, L.R., Kraft, G., 2000. Three-dimensional BANG gel dosimetry in conformal carbon ion radiotherapy. Physics in medicine and biology 45, N95-102. Rogus, R.D., Harling, O.K., Yanch, J.C., 1994. Mixed field dosimetry of epithermal neutron beams for boron neutron capture therapy at the MITR-II research reactor. Med Phys 21, 1611-1625. Senden, R.J., Jean, P.D., McAuley, K.B., Schreiner, L.J., 2006. Polymer gel dosimeters with reduced toxicity: a preliminary investigation of the NMR and optical dose–response using different monomers. Physics in medicine and biology 51, 3301.
Figure captions: Figure 1. a) The sender part. b) The irradiation part. c) The control panel. d) The irradiation part installed in front of the neutron beam. f) The irradiated vials.
Figure 2. Schematic drawing of the automatic transfer system setup in neutron irradiation. 1) Vial position before irradiation. 2) Sender part. 3) Data cable. 4) Steering tube. 5, 6) Thermal column plug. 7) Lead. 8) Thermal neutron beam. 9) Irradiation part. 10) Vial position during irradiation. 11) Collimator. 12) Lead chamber. 13) Control panel. 14 | P a g e
Figure 3. The vials containing NIPAM, NIPAM with 30 and 60 ppm of
10
B in a rectangular
water phantom to be irradiated by Co-60 radiotherapy machine.
Figure 4. Dose‒response curve of NIPAM, NIPAM with 30 and 60 ppm of 10B irradiated with a neutron beam. 15 | P a g e
Figure 5. Dose‒response curve for NIPAM, NIPAM with 30 and 60 ppm of Co-60.
Figure 6. Dose‒response curve for NIPAM in gamma and neutron irradiations.
16 | P a g e
10
B irradiated by
Figure 7. Dose profiles for rotated and fixed vials containing NIPAM gel irradiated by a neutron beam.
Table captions: Table 1. The elemental composition of the brain tissue, NIPAM gel and the polyethylene terephthalate (PET) vials. ICRU 44 brain tissue
NIPAM gel
PET vial
(wt%)
(wt%)
(wt%)
Element
17 | P a g e
18 | P a g e
H
10.7
10.81
4.2
C
14.5
6.51
62.5
N
2.2
1.65
----
O
71.2
80.42
33.3
Na
0.2
----
----
P
0.4
0.29
----
S
0.2
----
----
Cl
0.3
0.33
----
K
0.3
----
----
Density(g/cm3)
1.04
1.03
1.38
Table 2. Different components and their weight percent in gel preparation.
19 | P a g e
Component
Weight percent
Water
89 wt%
Gelatin 300 Bloom Type A
5 wt%
N-Isopropylacrylamide (NIPAM)
3 wt%
N, N′-Methylenebisacrylamide (BIS)
3 wt%
Tetrakis (hydroxymethyl) phosphonium chloride (THPC)
10 mM
Table 3. MRI protocol uesed for scaning gel dosimeters. Sequence T2 weighted-multiple spin echoes Matrix Size 512×512 Slice Thickness (mm) 5 Repetition Time(TR)(ms) 4000 Echo Time(TE)(ms) 20 Inter Echo Time Spacing(ms) 20 Number of Slices 1 Number of Echoes 32 Number of accusation 2
Table 4. Parameters of the least squares fit for NIPAM, NIPAM with 30 and 60ppm
10
B in
neutron irradiation. Gel type
Slope
Intercept Value
R2
Sensitivity enhancement compared to NIPAM without 10B
Sensitivity enhancement compared to NIPAM with 30ppm 10B
Value
Standard error
NIPAM without 10B
0.025
±0.0005
1.498
±0.005
0.9942
---
---
NIPAM with 30ppm 10B
0.031
±0.0009
1.676
±0.009
0.992
23.62%
---
NIPAM with 60ppm 10B
0.036
±0.0010
1.741
±0.01
0.990
40.55%
13.69%
20 | P a g e
Standard error
Table 5. Comparison of R2 values for NIPAM, NIPAM with 30ppm and NIPAM with 60ppm 10B in neutron irradiation. NIPAM
Dose (Gy)
0 1 2 3 4 5 7 9 12 15 17 20
21 | P a g e
R2 value (1/s)
1.49 1.50 1.55 1.59 1.61 1.62 1.68 1.74 1.80 1.87 1.93 2.00
NIPAM with 30ppm 10B
NIPAM with 60ppm 10B
R2
R2
Enhancement% Value (1/s)
1.63 1.73 1.76 1.78 1.80 1.84 1.90 1.95 2.04 2.13 2.22 2.31
Compared to NIPAM 9.4 15.3 13.5 11.9 11.8 13.6 13.1 12.1 13.3 13.9 15.0 15.5
Value (1/s)
1.7 1.81 1.86 1.88 1.89 1.93 2 2.08 2.2 2.29 2.36 2.48
Enhancement% Compared to Compared NIPAM to NIPAM with 30ppm 10 B 14.1 4.3 20.7 4.6 20.0 5.7 18.2 5.6 17.4 5.0 19.1 4.9 18.8 5.3 19.6 6.7 22.2 7.8 22.5 7.5 22.3 6.3 24.3 7.4
Table 6. Comparison of R2 values for NIPAM, NIPAM with 30 and 60ppm irradiated by Co-60. NIPAM Dose (Gy)
0 1 2 3 5 7 10
R2 value (1/s) 1.50 1.61 1.69 1.78 1.94 2.13 2.38
NIPAM with 30ppm 10B
NIPAM with 60ppm 10B
R2
R2
Enhancement% Value (1/s) 1.65 1.76 1.86 1.94 2.12 2.33 2.51
Compared to NIPAM 10.0 9.3 10.1 9.0 9.3 9.4 5.5
Enhancement% Value (1/s) 1.72 1.84 1.94 2.03 2.22 2.38 2.55
Compared to NIPAM 14.7 14.3 14.8 14.0 14.4 11.7 7.1
Compared to NIPAM with 30ppm 10B 4.2 4.5 4.3 4.6 4.7 2.1 1.6
Highlights
Three compositions of NIPAM gel with different concentration of 10B have been exposed by gamma and thermal neutron. The vials containing NIPAM gel have been irradiated by an automatic system capable of providing for dose uniformity. Suitability of NIPAM polymer gel in measuring radiation doses in BNCT has been investigated.
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