|Year : 2015 | Volume
| Issue : 3 | Page : 592-596
Dosimetric properties of N-isopropylacrylamide polymer gel using nonelectrophoresis grade BIS in preparation
Roghayeh Khodadadi1, Azim Khajeali2, Ali Reza Farajollahi3, Jamal Eivazi Ziaei4, Parisa Hajalioghli5
1 Hematology and Oncology Research Center; Department of Medical Physics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
2 Department of Medical Physics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
3 Medical Education Research Center; Department of Medical Physics, Faculty of Medicine; Imam Reza Hospital, Radiotherapy Department, Tabriz University of Medical Sciences, Tabriz, Iran
4 Hematology and Oncology Research Center, Iran
5 Department of Radiology, Faculty of Paramedicine, Tabriz University of Medical Sciences, Tabriz, Iran
|Date of Web Publication||9-Oct-2015|
Ali Reza Farajollahi
Faculty of Medicine, Department of Medical Physics, Tabriz University of Medical Sciences, Tabriz
Source of Support: None, Conflict of Interest: None
Introduction: Unlike availability of the different grades of N, N'-methylenebisacrylamide (BIS), electrophoresis is recommended in literature as a crosslinking agent in gel preparation. As the cost of non-electrophoresis grade BIS is much less than that of electrophoresis, the dosimetric characteristics of the of the polymer gel using non-electrophoresis BIS is evaluated in terms of photon energy and dose rate.
Materials and Methods: To compare the response of this gel with the one that contains electrophoresis grade BIS, two sets of N-isopropylacrylamide (NIPAM) gel were prepared using electrophoresis and non-electrophoresis BIS and irradiated to different gamma doses.
Results: It was shown that the dose-response of NIPAM gel made from non-electrophoresis grade BIS is coincident to that of electrophoresis grade BIS. The study of dose response of NIPAM with non-electrophoresis grade BIS as a function of beam energy revealed no dependence on radiation energies of 1.25 MV from 60 Co and 6 MV and 18MV from linear accelerator. It was found that dose rate has no influence on dose response of NIPAM gel with non-electrophoresis BIS.
Conclusion: Substitution non-electrophoresis grade BIS not only reduces the cost of gel preparation without any adverse effect on its dose response, but also its lower background increases the dynamic range of dose linearity.
Keywords: Cross linker agent, N, N′- methylenebisacrylamide, N-isopropylacrylamide gel, polymer gel dosimetry
|How to cite this article:|
Khodadadi R, Khajeali A, Farajollahi AR, Ziaei JE, Hajalioghli P. Dosimetric properties of N-isopropylacrylamide polymer gel using nonelectrophoresis grade BIS in preparation. J Can Res Ther 2015;11:592-6
|How to cite this URL:|
Khodadadi R, Khajeali A, Farajollahi AR, Ziaei JE, Hajalioghli P. Dosimetric properties of N-isopropylacrylamide polymer gel using nonelectrophoresis grade BIS in preparation. J Can Res Ther [serial online] 2015 [cited 2019 Oct 16];11:592-6. Available from: http://www.cancerjournal.net/text.asp?2015/11/3/592/163732
| > Introduction|| |
In the therapeutic use of ionizing radiation it is very important to validate and verify the delivered dose to the normal healthy tissues and tumors to achieve the best treatment outcome. Until date, several dosimeters with their own advantages and disadvantages have been used for this purpose. Radiographic and radiochromic films have the high special resolution, but their energy dependence, and difficulty in using for teletherapy units calibration are the main problems of using these dosimeters. Thermoluminescent dosimeters are small dosimeters but their readout process in mapping three-dimensional (3D) dose distribution is time-consuming. Ionizing chambers are very accurate and are recommended for reference dosimetry. However, they require complicated correction factors for high-energy beam dosimetry. Diodes are small, accurate sensitive dosimeters but they are not tissue equivalent, and ambient temperature affects on their calibration.  In spite of the important role of common dosimeters in radiation therapy, advanced radiotherapy techniques such as intensity modulated radiation therapy, and stereotactic radiosurgery require 3D absorbed dose measurements that were not met by typical dosimeters. Gel dosimeters are having the characteristic of recording dose distribution in 3D with high spatial resolution, are tissue equivalent phantoms so they can play a key role in the dosimetric process of modern radiation therapy techniques.
Polymer gels are a class of radiation sensitive gels that first introduced by Alexander, et al.  for possible application in modern radiotherapy absorbed dose distribution. The toxic nature of these new dosimeters together with the poisonous effect of oxygen in prohibiting polymerization process and their fairly high cost were important problems associated with these gels. To solve the oxygen problem, MAGIC polymer gel was introduced by Fong, et al.  Furthermore, MAGIC gel made it possible to manufacture the gel in normal atmospheric condition, the toxicity of the monomers and their cost still remained the main concerns of the researchers, until 2006 when Senden, et al. introduced a new formulation of less toxic polymer gel known as N-isopropylacrylamide (NIPAM). In NIPAM polymer gel NIPAM was used instead of acrylamide which is claimed that is much less toxic than the acrylamide.
From the literature the electrophoresis N, N'-methylenebisacrylamide (BIS) [Figure 1] was used as a cross-linking agent in preparation of the polymer gel which has significantly higher price in comparison with nonelectrophoresis one. ,,,,
The electrophoresis grade N, N'- methylenebisacrylamide (BIS) which had been used in literature since the introduction of polymer gels as a cross-linking agent, has significantly higher price than nonelectrophoresis one. Any possibility of replacing electrophoresis with nonelectrophoresis grade BIS could reduce the cost of the gel. As any changes in this regard could possibly effect on gel performance therefore the aim of this study is to explore the possibility of substituting electrophoresis one with non-electrophoresis BIS and also verification of its dosimetric properties.
| > Materials and methods|| |
To investigate the feasibility of using nonelectrophoresis grade BIS in gel manufacturing, NIPAM gel was prepared based on a recipe that was introduce by Senden, et al.  with modification of replacing nonelectrophoresis BIS with electrophoresis one. To prepare required amount of the gel the gelatin was added to 80% of total required deionized water. Then, the solution was heated up to 50°C. Once the gelatin was completely melted, the solution temperature was reduced to 37°C while stirring, nonelectrophoresis N, N'-methylenebisacrylamide (BIS) was added up to it as the cross-linker agent. As soon as the BIS was approximately dissolved, NIPAM was added to the solution at the same temperature and stirred up until the monomers were completely disappeared. A solution of the 10 Mm antioxidant tetrakis (hydroxymethyl) phosphonium chloride (THPC) then was prepared using the remaining 20% of the deionized water and added to the solution at 35°C. Finally, the gel solutions were transferred into vials and placed in the refrigerator for 10 min to solidify.
The vials containing polymer gel were irradiated using cobalt-60 therapy machine located in Tabriz Imam Khomeini Teaching Hospital 2 h after manufacturing in a 26 cm × 11 cm radiation field [Figure 2]. The test vials were placed in water filled cubic polymethyl methacrylate phantom for irradiation. To avoid dose gradient over the diameter of the samples they were turned 180° on their vertical axis halfway through the irradiation. [Figure 3] shows the vials containing NIPAM gel after irradiating by cobalt-60 machine.
|Figure 2: The vials containing NIPAM gel in a rectangular water phantom for irradiating by cobalt-60 radiotherapy machine|
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|Figure 3: The vials containing NIPAM gel after irradiating by cobalt-60 machine|
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Magnetic resonance imaging
The samples were imaged 24 h after irradiation using Siemens 1.5T magnetic resonance imaging (MRI) scanner in Tabesh medical imaging center (Tabriz, Iran). Since gel temperature in MRI affects on dosimeter's response, the gel vials were brought to a fixed temperature using a water bath in all measurements. Vials were finally placed in the expanded polystyrene holder before imaging [Figure 4]. The characteristics of the MRI protocol are listed in [Table 1].
|Figure 4: Gel samples in expanded poly styrene holder to be imaged by magnetic resonance imaging|
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To investigate the reproducibility of gel response; all of the polymer gel dosimetric steps including manufacturing, irradiation and imaging were repeated 3 times while keeping the irradiation condition, scanning parameters and temperature in time of imaging unchanged.
On exploring the possibility of using nonelectrophoresis BIS in NIPAM gel recipe the next step was comparing the dose response of NIPAM gel consisting electrophoresis and nonelectrophoresis grade BIS. To achieve this goal the gel was prepared as mentioned above with the same fractions and weight percentages of the monomers and gelatin but after dissolving the gelatin the solution was divided into two parts and manufacturing processes were continued using non and electrophoresis grade BIS to produce different gels. [Table 2] shows the weight percentages of material used in the construction of NIPAM gel with electrophoresis and nonelectrophoresis grade BIS.
The same irradiation and MRI facilities and procedures were used for these gels.
| > Results|| |
MR images were analyzed using image processing software JIM to extract R2 values for each gel and ultimately dose response curves were plotted.
Dose response of NIPAM with nonelectrophoresis grade BIS
As can be seen from [Figure 5] using nonelectrophoresis BIS in gel recipe given a promising response to gamma radiation from 60 Co and confirms the suitability of nonelectrophoresis grade BIS in NIPAM gel manufacturing. The reproducibility of the response using nonelectrophoresis BIS in three different batches of gel is illustrated in [Figure 6]. From the graph, the response of the gel was found highly reproducible within ±2%.
|Figure 5: Dose response curve of NIPAM gel with non-electrophoresis grade BIS. The error of 3.5% is indicated for each data points|
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|Figure 6: Reproducibility in dose response of three batches of NIPAM polymer gel with non-electrophoresis grade BIS|
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Since the independence of dose response to beam energy is a concern in radiation dosimetry,  the gel response was evaluated in irradiating by different photon energies. In this regards, three vials containing the gel were exposed to 5 Gy, by a 6 MV and 18 MV linear accelerator and a 60 Co radiotherapy machine. Subsequently, the gels imaging were done as described before. The results of R2 measurement for different beam energies are shown in [Figure 7]. As it can be seen from figure, the dose response of NIPAM gel prepared with nonelectrophoresis is independent of beam energy within less than ± 2% error. The dependence of the gel response to dose rate was also investigated by irradiation the gel vials to the absorbed dose of 5 Gy, in varying source surface distance (SSD) including 100, 110, 120, and 130 cm. The obtained results showed that R2 values for different dose rate are correspondence within less than ± 2% error [Figure 8].
|Figure 7: Dose response of NIPAM gel with non-electrophoresis grade BIS to different beam energies|
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|Figure 8: Dose response of NIPAM gel with non-electrophoresis grade BIS in irradiation with different SSD|
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Comparison of dose response of NIPAM gels with electrophoresis and nonelectrophoresis grade BIS
As shown in [Figure 9] and [Table 3], the sensitivity of the gel as defined by the slope of the dose response curves are close together in both gels. If the backgrounds are subtracted from all dose values [Figure 10] no differences can be seen in the dose response of the gels within P > 0.05. The compared values are summarized in [Table 3] and [Table 4].
|Figure 9: Dose response curves of NIPAM gels with electrophoresis and non-electrophoresis grade BIS|
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|Figure 10: Dose response curves of NIPAM gels with electrophoresis and non-electrophoresis grade BIS with subtracted backgrounds|
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| > Discussion|| |
Radiation dosimetry by polymer gels takes advantage of polymerization and cross-linking of the polymer monomers upon irradiation. Since using N, N'-methylenebisacrylamide (BIS) as a cross-linker agent in polymer gel recipes is associated with some problems such as primary cyclization reactions, low water solubility and presence of free-radical inhibitors, recently different materials have been proposed as a substitution to BIS in polymer gel recipe.  All of the tested candidates for replacing BIS provided low dose response factors in comparison with the standard polymer gel recipe containing BIS, except N, N'-ethylene-bisacrylamide with similar dosimetric characteristics to BIS but it is not recommended as it significantly expensive than BIS. Therefore N, N'-methylenebisacrylamide still remained as an integral component of polymer gels. In addition, different grades of BIS are available, such as the ones used in molecular biology and for electrophoresis; suitable for electrophoresis and nonelectrophoresis. However, there appears to be a sort of emphasis in the literature on using electrophoresis BIS in polymer gel recipe, which seems to have led to a kind of assumption among researchers that the other grades of BIS might not work as well in polymer gel recipes. Yet, this study revealed that not only can nonelectrophoresis grade BIS be employed in NIPAM polymer gel formulation, but its cost is also considerably lower than that for electrophoresis. Moreover as illustrated in [Figure 9] NIPAM gel with nonelectrophoresis grade was found to have significantly less background in comparison with the standard recipe which could possibly lead to increased saturation point.
The study of dose response of NIPAM with nonelectrophoresis grade BIS as a function of beam energy revealed no dependence on radiation energies of 1.25 MV from 60 Co and 6 MV and 18 MV from a linear accelerator. One of the desirable features for a dosimeter in determining radiation dose distribution in 3D is its independence from dose rate. In this study, it was found dose rate has no influence on the NIPAM with nonelectrophoresis grade BIS gel's dose response. It can be concluded that the results of this study can be comparable to that of Farajollahi, et al. which Effect of beam energy and dose rate dependence of NIPAM with electrophoresis grade BIS was investigated. 
Both gels have exhibited the same sensitivity due to the identical slopes thus neither one has distinct advantages over the other a side from the fact that nonelectrophoresis grade BIS is much cheaper than the electrophoresis one.
| > Conclusion|| |
It can be concluded that NIPAM gel with non-electrophoresis grade BIS have suitable potential for applying in radiation dosimetry process as a tissue equivalent phantom-dosimeter capable of measuring dose distribution in 3D with high spatial resolution. Moreover, since the non-electrophoresis BIS has lower price than electrophoresis grad, the new gel formulation evaluated in this study, could be recommended for employing in the gel preparation to reduction of the cost of studies.
The authors would like to thank Hematology and Oncology Research Center for supporting this project (grant No. 17/92, which was a port of MSc thesis No. 92/2-2/2).
Financial support and sponsorship
Tabriz University of Medical Sciences.
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7], [Figure 8], [Figure 9], [Figure 10]
[Table 1], [Table 2], [Table 3], [Table 4]