An ionization radiation gel dosimeter and its preparation method

Abstract

The present invention relates to an ionizing radiation gel dosimeter and a preparation method thereof, belonging to the technical field of radiation dosimetry. The preparation method of the present invention includes the following steps: dissolving a fluorescent substance sensitive to ionizing radiation and a gel substrate in water, and reacting under the action of persulfate to obtain the ionizing radiation gel dosimeter. The fluorescent signal of the ionizing radiation gel dosimeter of the present invention has a good linear response in the ionizing radiation dose range of 0-15 Gy (R<supgt;2< / supgt; = 0.99). After irradiation with the same dose, the fluorescence intensity change of the dosimeter added with persulfate is greater than that of the dosimeter not added with persulfate. When m(CCA):m(APS) = 1:1, the slope of the fitting line is the largest and the sensitivity of the dosimeter is higher. The obtained fluorescent signal can be maintained for two weeks and also has good stability in the range of 25-65 °C, meeting the requirements of clinical radiotherapy dose measurement.

Description

Technical Field

[0001] The present invention belongs to the technical field of radiation dose, and particularly relates to an ionization radiation gel dosimeter and a preparation method thereof. Background Art

[0002] In recent years, the incidence and mortality of malignant tumors globally have been increasing year by year, seriously threatening the lives and health of the global public. Radiotherapy is one of the main methods for clinical treatment of malignant tumors. However, inaccurate dose delivery will bring serious side effects to patients. Therefore, precise radiotherapy is playing an increasingly important role in improving the curative effect, delaying the progression of the disease, improving the prognosis, and enhancing the quality of life of patients. This requires that the radiation dosimeter can accurately measure the three-dimensional dose distribution and provide high spatial resolution.

[0003] Traditional dosimeters are usually one-dimensional or two-dimensional, such as ionization chambers, diodes, metal-oxide-semiconductor field-effect transistors (MOSFETs), thermoluminescent dosimeters (TLDs), radiographic films, etc. Currently, ionization chambers are used as references for calibrating radiotherapy. However, ionization chambers are difficult to miniaturize and cannot be implanted into patients. Diodes are widely used for routine in-vivo dosimetry, especially for whole-body irradiation monitoring. However, diodes show a dependence of the dose response on environmental changes and need to be frequently recalibrated. The main advantages of MOSFETs are that they can perform instantaneous measurements and are small in size, suitable for implantable dosimeters. However, the sensitivity is easily changed and the service life is limited. TLDs have good sensitivity and a wide measurement dynamic range. However, due to the attenuation phenomenon, it is impossible for TLDs to directly and continuously monitor the dose. Radiographic films have excellent two-dimensional spatial resolution, but the useful dose range is limited and the energy dependence is obvious.

[0004] Gel dosimeters are the only three-dimensional dosimeters suitable for absolute dose measurement. Polymer gels are applicable in the fields of brachytherapy, conformal and intensity-modulated radiotherapy, stereotactic radiotherapy, etc. Currently, they are mainly used to simulate and check treatment plans before clinical application. However, in the representative Fricke dosimeter, Fe 3+ ions are prone to diffusion and the position resolution is poor. Gel-based gel dosimeters are greatly affected by oxygen and temperature during measurement, and this method is insensitive to low doses.

[0005] Polyacrylamide-coumarin-3-carboxylic acid (CCA) itself has basically no fluorescence. Ionizing radiation causes water to generate hydroxyl radicals, which can react with CCA to form a strongly fluorescent substance, 7-hydroxycoumarin-3-carboxylic acid (7OH-CCA). Therefore, it is often used as an ionizing radiation dosimeter. In 1994, Collins et al. studied a coumarin chemical dosimeter for radiotherapy based on coumarin. The fluorescence intensity was linearly related to the irradiation dose from 0 to 50 Gy. When the dose was greater than 50 Gy, the fluorescence intensity showed saturation. Sandwall et al. injected CCA into gelatin to synthesize a new radiofluorescent gel dosimeter, and used the pH value to improve the sensitivity of the CCA gel dosimeter. This is consistent with the earlier findings of Manevich et al. that the fluorescence quantum yield of 7OH-CCA increases under alkaline conditions. In 2018, Maeyama et al. developed a radiation-induced fluorescent gel (RFG) containing nanoclay using CCA. The reaction of CCA with OH· was inhibited in gelatin, while the nanoclay gel had better optical transmittance than gelatin. In addition, the high pH of the clay also significantly improved the sensitivity. Li Wenxiang et al. also reported the construction of a nanohydrogel dosimeter by modifying polyacrylamide microgels with CCA. The fluorescence response of the coumarin dosimeter has a good linear relationship with the irradiated dose, and the fluorescence yield increases linearly with the concentration of 7OH-CCA. The polyacrylamide CCA gel dosimeter has the advantages of high fluorescence quantum yield, high photostability, tunable fluorescence emission, and good biocompatibility, and can be used as a label-free fluorescent probe in the fields of chemical sensing and biomedical detection. However, in the preparation methods disclosed in the above literature, increasing the pH value of the system and adding trichloroacetic acid are the only methods to solve the low sensitivity. The preparation process is complex and costly. Only gelatin can be used as the gel matrix material, and the obtained dosimeter has low sensitivity. Summary of the Invention

[0006] To this end, the technical problem to be solved by the present invention is to overcome the problems such as low sensitivity of the polyacrylamide CCA gel dosimeter in the prior art.

[0007] To solve the above technical problems, the present invention provides an ionizing radiation gel dosimeter and a preparation method thereof.

[0008] The first object of the present invention is to provide a preparation method of an ionizing radiation gel dosimeter, which includes the following steps: dissolving a fluorescence substance sensitive to ionizing radiation and a gel substrate in water, and reacting under the action of persulfate to obtain the ionizing radiation gel dosimeter.

[0009] In an embodiment of the present invention, the fluorescence substance sensitive to ionizing radiation is a fluorescence substance with a carboxyl group, an amino group or a hydroxyl group.

[0010] In one embodiment of the present invention, the fluorescent substance sensitive to ionizing radiation is coumarin-3-carboxylic acid, aminophenyl fluorescein or hydroxyphenyl fluorescein. The fluorescent substance sensitive to ionizing radiation reacts with the hydroxyl radicals generated by irradiation of water to form a fluorescent substance.

[0011] In one embodiment of the present invention, the gel substrate is one or more of polyacrylamide, polyacrylic acid, sodium alginate and chitosan.

[0012] In one embodiment of the present invention, the molecular weight of the polyacrylamide is 2 million - 14 million.

[0013] In one embodiment of the present invention, the persulfate is one or more of ammonium persulfate, potassium persulfate and sodium persulfate. The addition of persulfate plays a sensitizing role and generates more fluorescent substances.

[0014] In one embodiment of the present invention, the concentration of the persulfate is 0.01 - 1 mg / mL.

[0015] In one embodiment of the present invention, the mass ratio of the fluorescent substance sensitive to ionizing radiation to the gel substrate is 0.005:1 - 1.2.

[0016] The second object of the present invention is to provide an ionizing radiation gel dosimeter prepared by the method described above.

[0017] The third object of the present invention is to provide an application of the ionizing radiation gel dosimeter described above in ionizing radiation dose measurement.

[0018] The technical solution of the present invention has the following advantages compared with the prior art:

[0019] (1) By introducing persulfate in the preparation of the ionizing radiation gel dosimeter of the present invention, the disadvantage of low sensitivity of the polyacrylamide CCA gel dosimeter is effectively solved. Under ionizing radiation, sulfate radicals can react with the fluorescent substance sensitive to ionizing radiation through the electron transfer mechanism of the benzene ring to form radical cations. Subsequently, the radical cations form OH· adducts through hydration. Such peroxy radicals either form many products through cleavage or form hydroxycoumarin through elimination. The OH· adduct can also evolve into the corresponding hydroxycoumarin through disproportionation.

[0020] (2) After the ionizing radiation gel dosimeter of the present invention is irradiated by ionizing radiation, the fluorescent substance sensitive to ionizing radiation generates more fluorescein molecules that produce significant fluorescence under the action of persulfate, and increase with the increase of the radiation dose within a certain range.

[0021] (3) The fluorescence signal of the ionization radiation gel dosimeter described in the present invention has a good linear response in the ionization radiation dose range of 0-15 Gy (R 2 = 0.99). After irradiation with the same dose, the change in fluorescence intensity of the dosimeter with persulfate added is greater than that of the dosimeter without persulfate added. When m(CCA):m(APS) = 1:1, the slope of the fitting line is the largest and the sensitivity of the dosimeter is higher. The obtained fluorescence signal can be maintained for two weeks and also has good stability in the range of 25-65 °C, meeting the requirements of clinical radiotherapy dose measurement. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] In order to make the content of the present invention more clearly understood, the following further details the present invention according to specific embodiments of the present invention in conjunction with the drawings, wherein:

[0023] Figure 1 It is a dose response test chart of the polyacrylamide coumarin gel dosimeter of Comparative Example 1 under different APS contents of the present invention.

[0024] Figure 2 It is a dose response test chart of the dosimeter of Comparative Example 1 of the present invention.

[0025] Figure 3 It is a dose response test chart of the dosimeter of Comparative Example 2 under different APS contents of the present invention.

[0026] Figure 4 It is a dose response test chart of the polyacrylamide coumarin gel dosimeter under different conditions of the present invention; wherein, a is unirradiated; b-e are irradiated with 5 Gy X-rays.

[0027] Figure 5 It is a temperature stability test chart of the polyacrylamide coumarin gel dosimeter of the present invention. SPECIFIC EMBODIMENTS

[0028] The following further illustrates the present invention in conjunction with the drawings and specific embodiments, so that those skilled in the art can better understand the present invention and be able to implement it, but the embodiments cited do not limit the present invention.

[0029] Experimental raw materials

[0030] Polyacrylamide was purchased from Aladdin, model P108471-500g; product number C1603072.

[0031] Example 1

[0032] An ionization radiation gel dosimeter and its preparation method specifically include the following steps:

[0033] First, add 0.002 g of coumarin-3-carboxylic acid to 20 mL of PBS(×0.1) solution, heat and stir at 100 °C for 1 h to completely dissolve the coumarin-3-carboxylic acid. Then, add 0.4 g of polyacrylamide to the above solution, heat and stir at 50 °C for 0.5 h until the polyacrylamide is completely dissolved to obtain a mixed solution. After cooling to 50 °C, add 5 mL of ammonium persulfate solution (0.4 mg / mL, dissolved in PBS), and mix evenly at room temperature. Let it stand overnight to obtain an ionizing radiation gel dosimeter. Before irradiation, place the product in a 4 °C refrigerator and store it in the dark.

[0034] Example 2

[0035] An ionizing radiation gel dosimeter and its preparation method specifically include the following steps:

[0036] First, add 0.002 g of coumarin-3-carboxylic acid to 20 mL of PBS(×0.1) solution, heat and stir at 100 °C for 1 h to completely dissolve the coumarin-3-carboxylic acid. Then, add 0.4 g of polyacrylamide to the above solution, heat and stir at 50 °C for 0.5 h until the polyacrylamide is completely dissolved to obtain a mixed solution. After cooling to 50 °C, add 5 mL of potassium persulfate solution (0.4 mg / mL, dissolved in PBS), and mix evenly at room temperature. Let it stand overnight to obtain an ionizing radiation gel dosimeter. Before irradiation, place the product in a 4 °C refrigerator and store it in the dark.

[0037] Example 3

[0038] An ionizing radiation gel dosimeter and its preparation method specifically include the following steps:

[0039] First, add 0.002 g of coumarin-3-carboxylic acid to 20 mL of PBS(×0.1) solution, heat and stir at 100 °C for 1 h to completely dissolve the coumarin-3-carboxylic acid. Then, add 0.4 g of polyacrylamide to the above solution, heat and stir at 50 °C for 0.5 h until the polyacrylamide is completely dissolved to obtain a mixed solution. After cooling to 50 °C, add 5 mL of sodium persulfate solution (0.4 mg / mL, dissolved in PBS), and mix evenly at room temperature. Let it stand overnight to obtain an ionizing radiation gel dosimeter. Before irradiation, place the product in a 4 °C refrigerator and store it in the dark.

[0040] Comparative Example 1

[0041] Add 0.002 g of coumarin-3-carboxylic acid and 0.003 g of agarose into 20 mL of PBS (×0.1) solution, heat and stir at 100 °C for 1 h to completely dissolve coumarin-3-carboxylic acid and agarose. Cool to room temperature. After agarose cools and solidifies, add 5 mL of sodium persulfate solution (0.4 mg / mL, dissolved in PBS), and mix evenly at room temperature. Let stand overnight to obtain the dosimeter. Before irradiation, place the product in a refrigerator at 4 °C and store it in the dark.

[0042] Comparative Example 2

[0043] First, add 0.002 g of coumarin-3-carboxylic acid into 20 mL of PBS (×0.1) solution, heat and stir at 100 °C for 1 h to completely dissolve coumarin-3-carboxylic acid. After the solution cools to room temperature, add 0.4 g of clay, stir for 0.5 h, then add 5 mL of sodium persulfate solution (0.4 mg / mL, dissolved in PBS), and mix evenly at room temperature. Let stand overnight to obtain the dosimeter. Before irradiation, place the product in a refrigerator at 4 °C and store it in the dark.

[0044] Test Example 1

[0045] Perform a responsiveness test on the dosimeters prepared in Example 1 and Comparative Examples 1-2. The results are as Figures 1-3 shown.

[0046] Figure 1 For the dose responsiveness of the polyacrylamide coumarin gel dosimeter of Example 1 at different APS contents, from Figure 1 it can be seen that at the same APS content, as the radiation dose increases, the fluorescence intensity of the coumarin-3-carboxylic acid gel dosimeter increases linearly, indicating that coumarin-3-carboxylic acid reacts with the hydroxyl radicals generated by the radiolysis of water to form fluorescent 7-hydroxy-coumarin-3-carboxylic acid. When the APS content is increased, for the same irradiation dose, the gel dosimeter with a higher APS content has a stronger fluorescence signal than the gel dosimeter with a lower APS content, indicating that more 7-hydroxy-coumarin-3-carboxylic acid is generated after irradiation with APS added. It is confirmed by HPLC that more 7-hydroxy-coumarin-3-carboxylic acid is generated in the gel dosimeter with APS solution added than without APS solution added. Adding the APS solution plays a role in sensitization and improves the sensitivity of the gel dosimeter.

[0047] Figure 2 For the dose responsiveness of the dosimeter of Comparative Example 1, from Figure 2 it can be seen that clay itself has no response to radiation, but it has a great influence on the fluorescence signal as a gel substrate. Therefore, the use of clay is not considered in the present invention.

[0048] Figure 3 For the dose responsiveness of the dosimeter of Comparative Example 2 at different APS contents, from Figure 3It can be seen that when the CCA concentration is 0.1 mg / mL and the same concentration and volume of APS solution are added, as the irradiation dose increases, the fluorescence signal intensity increases. When the volume of the APS solution is increased and the irradiation dose is the same, the fluorescence signal intensity of the gel dosimeter with a higher APS content increases, indicating that the APS solution has a sensitizing effect on this gel dosimeter. The disadvantage is that the APS solution is added after the agarose gel has cooled to room temperature. At this time, the agarose has already formed a gel, and the subsequently added APS solution does not fully penetrate into the gel, resulting in stratification between the solution and the gel.

[0049] Test Example 2

[0050] Based on Example 1, the dose response effect of the polyacrylamide coumarin gel dosimeter was investigated under different conditions. CCA = 0.1 mg / mL, polyacrylamide = 0.01 g / mL. The addition amounts of APS (0.1 mg / mL) were (a) 0, (b) 0, (c) 200, (d) 600, (e) 1000 μL APS, respectively, and different volumes of PBS were added to make the total volume 2 mL. The gel dosimeter was irradiated with 5 Gy photon beam, and irradiated with a 365 nm ultraviolet lamp under darkroom conditions. The results are as Figure 4 shown.

[0051] From Figure 4 it can be seen that the unirradiated gel dosimeter has no color. After irradiation, as the APS content increases, the gel dosimeter shows visible blue fluorescence, and the fluorescence intensity gradually increases. The blue light indicates that after irradiation, coumarin-3-carboxylic acid reacts with the hydroxyl radicals generated by the radiolysis of water to form fluorescent 7-hydroxycoumarin-3-carboxylic acid, and as the APS content increases, the content of 7-hydroxycoumarin-3-carboxylic acid generated increases, indicating that APS does play a sensitizing role.

[0052] Test Example 3

[0053] The temperature stability of the ionizing radiation gel dosimeter prepared in Example 1 was tested. The fluorescence intensity (λ ex / λ em = 400 / 450 nm) of the hydrogel sample irradiated with 5 Gy was measured at different temperatures using a fully functional microplate reader. The temperatures were set to: 25, 35, 45, 55, 65 °C, and the relationship between the ionizing radiation dose and the fluorescence intensity was established. The results are as Figure 5 shown.

[0054] From Figure 5 it can be seen that taking the PAA-APF hydrogel dosimeter irradiated with 5 Gy as an example, its temperature stability was studied. The temperature stability coefficient was defined as: (FL temp / FL 25 ) × 100%, where FL25 and FL temp are the fluorescence values of the coumarin-3-carboxylic acid hydrogel dosimeter at 450 nm at 25 °C and different temperatures, respectively. Compared with FL 25 , even when measured at 65 °C, the fluorescence signal of FL 65 is still 95.08 ± 0.6%, indicating that the dosimeter of the present invention has good temperature stability.

[0055] Obviously, the above embodiments are merely examples for clear illustration and are not limitations on the implementation manners. For those of ordinary skill in the art, other different forms of changes or modifications can be made based on the above description. It is not necessary and impossible to enumerate all the implementation manners here. And the obvious changes or modifications derived therefrom are still within the protection scope of the present invention.

Claims

1. A preparation method of an ionizing radiation gel dosimeter, characterized in that, It includes the following steps: dissolving a fluorescent substance sensitive to ionizing radiation and a gel substrate in water, and reacting under the action of persulfate to obtain the ionizing radiation gel dosimeter; the fluorescent substance sensitive to ionizing radiation is a fluorescent substance with a carboxyl group, an amino group or a hydroxyl group; the persulfate is one or more of ammonium persulfate, potassium persulfate and sodium persulfate; the gel substrate is one or more of polyacrylamide, polyacrylic acid, sodium alginate and chitosan.

2. The preparation method of the ionizing radiation gel dosimeter according to claim 1, characterized in that, The fluorescent substance sensitive to ionizing radiation is coumarin-3-carboxylic acid, aminophenyl fluorescein or hydroxyphenyl fluorescein.

3. The preparation method of the ionizing radiation gel dosimeter according to claim 1, characterized in that, The molecular weight of the polyacrylamide is 2 million - 14 million.

4. The preparation method of the ionizing radiation gel dosimeter according to claim 1, characterized in that, The concentration of the persulfate is 0.01 - 1 mg / mL.

5. The preparation method of the ionizing radiation gel dosimeter according to claim 1, characterized in that, The mass ratio of the fluorescent substance sensitive to ionizing radiation to the gel substrate is 0.005:1 - 1.

2.

6. An ionizing radiation gel dosimeter prepared by the method according to any one of claims 1-5.

7. An application of the ionizing radiation gel dosimeter according to claim 6 in ionizing radiation dose measurement.

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