Gel dosimeter containing a sensitizer for measuring radiation doses

Abstract

[Problem] To provide a highly sensitive and safe gel dosimeter. [Solution] A radiation dosimetry gel dosimeter including a monomer that can be polymerized through exposure to radiation, a gelling agent, and a sensitizer comprising inorganic fine particles.

Description

[Technical Field]

[0001] The present invention relates to a gel dosimeter for radiation dosimetry and a gel for measuring radiation dosimetry. More specifically, the present invention relates to a gel dosimeter for measuring radiation dosimetry and a gel for measuring radiation dosimetry for verifying three-dimensional dose distribution in a treatment plan for radiation therapy for cancer, etc. [Background technology]

[0002] High-precision cancer radiation therapy, such as stereotactic radiation therapy (SRT), which delivers pinpoint radiation therapy, and intensity-modulated particle therapy (IMPT), which allows for the three-dimensional contouring of the tumor by varying the dose intensity within the same radiation field, has been introduced. These therapies precisely adjust the cumulative microscopic energy delivery (i.e., dose distribution) to each three-dimensional target location. Particle therapy also utilizes highly focused charged particle beams, such as protons and heavy ions (carbon and neon). Compared to conventional X-ray therapy, particle therapy offers the advantage of more precise control of the radiation location and dose for tumor treatment. The key to particle therapy is to deliver the energy from the particle beam appropriately to the target location, such as a lesion in biological tissue, while minimizing the impact on normal tissue surrounding the target. For these purposes, the radial spread of the particle beam and the position of the Bragg peak of the particle beam are aligned with the target position in the irradiation object.

[0003] In actual radiation therapy planning, the distribution of the dose at each location in the body tissue is optimized in three dimensions. A typical treatment plan involves modifying the dose distribution in the target tissue (the amount of radiation delivered to each location) to suit the treatment objective, while simultaneously minimizing the impact on surrounding normal tissue and organs at risk. To achieve such complex dose distributions, the beam is precisely controlled and may be delivered from multiple directions. This control involves the use of filters and collimators (e.g., range shifters, multi-leaf collimators, and boluses) that are tailored to the target tissue. To achieve highly controlled radiation therapy, advanced quality assurance and quality control (QA / QC) are required for the entire system, including the radiation delivery device, auxiliary equipment, filters, collimators, etc., as well as the irradiation process performed by these devices.

[0004] For the QA / QC of these treatment plans and various devices, a technology capable of accurately integrating and measuring the energy deposition of multiple ionizing radiation beams incident from various directions and with various acceleration energies is required. Accurately measuring the dose at each position by integrating the energy deposition enables the measurement of the three-dimensional energy deposition distribution (dose distribution), which supports the QA / QC. Conventionally, one-dimensional, two-dimensional, or pseudo-three-dimensional (detector placement on an orthogonal plane or cylinder) dosimeters, such as ionization chambers, film, and semiconductor detectors, have been used for this purpose. These dosimeters measure the dose distribution relative to one- or two-dimensional coordinates within the region where the particle beam is aligned with the target position. In addition to these dosimeters, gel dosimeters, which can measure dose distributions using the measurement principles of chemical dosimeters, have recently attracted attention. Another advantage of using gel dosimeters is that they can accurately measure the amount of energy imparted by radiation at each position in water, a material that can be considered equivalent to a living body, and thus can measure the effects of radiation on living body-equivalent and water-equivalent materials.Gel dosimeters can obtain three-dimensional dose distributions while being used as solid phantoms.

[0005] Gel dosimeters capable of measuring three-dimensional dose distributions have been reported, including the Fricke gel dosimeter (Patent Document 1), polymer gel dosimeter (Patent Documents 2 and 3), and dye gel dosimeter. The Fricke gel dosimeter is a gel containing a Fricke dosimeter solution (an aqueous solution containing ferrous sulfate), known as a liquid chemical dosimeter. It utilizes the fact that the oxidation reaction (coloring) of iron from divalent to trivalent upon irradiation increases in proportion to the absorbed dose. On the other hand, the polymer gel dosimeter is a gel in which a monomer is dispersed. Upon irradiation, a polymer is generated in proportion to the dose, and the relaxation time of water in the irradiated area changes. Therefore, dose can be estimated by reading the data using magnetic resonance imaging (MRI). Furthermore, the cloudy areas caused by radiation exposure can also be read using an optical CT scanner. The polymer generated by radiation exposure does not easily diffuse within the gel, and the cloudiness remains stable over time. Furthermore, the cloudy areas appear to float within the transparent gel, providing excellent visual appeal. In recent years, it has been reported that adding magnesium salts or the like to polymer gel dosimeters can provide a sensitizing effect (Non-Patent Document 1). [Prior art documents] [Patent documents]

[0006] [Patent Document 1] Japanese Patent Application Laid-Open No. 2014-209093 [Patent Document 2] Japanese Patent Application Laid-Open No. 2012-2669 [Patent Document 3] Japanese Patent Application Laid-Open No. 2014-185969 [Non-patent literature]

[0007] [Non-Patent Document 1] Radiological Physics and Technology, 2018, Vol.11, p.375-381 Summary of the Invention [Problem to be solved by the invention]

[0008] In order to realize highly controlled radiation therapy, it is desirable to develop more sensitive gel dosimeters and gels for measuring radiation dose. Therefore, an object of the present invention is to provide a gel dosimeter and gel for measuring radiation dose that have superior irradiation sensitivity to conventional gel dosimeters and gels for measuring radiation dose. [Means for solving the problem]

[0009] The present inventors have conducted extensive research into highly sensitive gel dosimeters and gels for measuring radiation doses, and as a result have discovered a sensitizing effect of gel dosimeters and gels for measuring radiation doses using a sensitizer made of inorganic fine particles, thereby completing the present invention. That is, in a first aspect, the present invention relates to a gel dosimeter for measuring radiation dose, which includes a monomer polymerizable by irradiation with radiation, a gelling agent, and a sensitizer made of inorganic fine particles. As a second aspect, the present invention relates to the gel dosimeter for measuring radiation dose according to the first aspect, characterized in that the gelling agent is one or more gelling agents selected from the group consisting of gelatin, agarose, xanthan gum, carrageenan, gellan gum, chitosan, and alginic acid, or sodium, potassium, magnesium, and calcium salts thereof, including partially neutralized salts thereof. As a third aspect, the present invention relates to the gel dosimeter for measuring radiation dose according to the first aspect, characterized in that the gelling agent is a gelling agent made of polyvinyl alcohol and glutaraldehyde or borax. As a fourth aspect, the present invention relates to the gel dosimeter for measuring radiation dose according to the first aspect, characterized in that the gelling agent is a gelling agent comprising a water-soluble organic polymer (A) having an organic acid structure, an organic acid salt structure, or an organic acid anion structure, a silicate (B), and a dispersant (C) for the silicate. As a fifth aspect, the present invention relates to a gel dosimeter for measuring radiation dose according to the fourth aspect, in which the water-soluble organic polymer (A) is a fully neutralized or partially neutralized polyacrylate having a weight-average molecular weight of 1,000,000 to 10,000,000. As a sixth aspect, the present invention relates to the gel dosimeter for measuring radiation dose according to the fourth or fifth aspect, in which the silicate (B) is one or more water-swellable silicates selected from the group consisting of smectite, bentonite, vermiculite, and mica. As a seventh aspect, the present invention relates to the gel dosimeter for measuring radiation dose according to any one of the fourth to sixth aspects, in which the dispersant (C) is one or more selected from the group consisting of sodium orthophosphate, sodium pyrophosphate, sodium tripolyphosphate, sodium tetraphosphate, sodium hexametaphosphate, sodium polyphosphate, sodium etidronate, sodium poly(meth)acrylate, ammonium poly(meth)acrylate, sodium acrylate / sodium maleate copolymer, ammonium acrylate / ammonium maleate copolymer, sodium hydroxide, hydroxylamine, sodium carbonate, sodium silicate, polyethylene glycol, polypropylene glycol, sodium humate, and sodium lignosulfonate, as well as potassium salts corresponding to these salts. As an eighth aspect, the present invention relates to the gel dosimeter for measuring radiation dose according to any one of the first to seventh aspects, characterized in that the monomer polymerizable by irradiation with radiation is a water-soluble polymerizable monomer. As a ninth aspect, the present invention relates to the gel dosimeter for measuring radiation dose according to any one of the first to eighth aspects, further comprising a crosslinking agent. According to a tenth aspect, the present invention relates to a gel dosimeter for measuring radiation dose according to the ninth aspect, characterized in that the crosslinking agent is a water-soluble polyfunctional acrylamide monomer. According to an eleventh aspect, the sensitizer made of inorganic fine particles is selected from the group consisting of silica sol, alumina sol, and zirconium sol. Near The present invention relates to a gel dosimeter for measuring radiation dose according to any one of the first to tenth aspects, which contains one or more sols selected from the group consisting of sols. As a twelfth aspect, the present invention relates to the gel dosimeter for measuring radiation dose according to any one of the first to eleventh aspects, further comprising an oxygen scavenger. As a thirteenth aspect, the present invention relates to any one of the first to twelfth aspects, further comprising a stabilizer. This invention relates to a gel dosimeter for measuring radiation dose. As a fourteenth aspect, the present invention relates to the gel dosimeter for measuring radiation dose according to any one of the first to thirteenth aspects, further comprising a buffer solution. As a fifteenth aspect, the present invention relates to the gel dosimeter for measuring radiation dose according to the fourteenth aspect, wherein the buffer solution is one or more selected from the group consisting of phosphoric acid, citric acid, acetic acid, boric acid, tartaric acid and salts thereof, Tris, and HEPES. As a sixteenth aspect, the present invention relates to a gel for measuring radiation dosimetry, which includes a monomer polymerizable by irradiation with radiation, a gelling agent, and a sensitizer made of inorganic fine particles. As a seventeenth aspect, the present invention relates to a method for producing a gel for measuring radiation dosimetry, which includes a step of mixing a monomer polymerizable by irradiation with radiation, a gelling agent, and a sensitizer consisting of inorganic fine particles. The eighteenth aspect relates to a method for measuring radiation dose using a gel containing a sensitizer consisting of a monomer polymerizable by irradiation with radiation, a gelling agent, and inorganic fine particles. [Effects of the Invention]

[0010] The gel dosimeter and gel for measuring radiation dose of the present invention contain a sensitizer made of inorganic fine particles, and therefore have superior radiation sensitivity compared to conventional gel dosimeters and gels.

[0011] Furthermore, in the gel dosimeter and gel for measuring radiation dose of the present invention, in addition to the widely used gelatin and agarose, various gelling agents can be used, such as a hydrogel made of a water-soluble organic polymer, a silicate and a dispersant for the silicate, and a hydrogel made of polyvinyl alcohol and glutaraldehyde or borax. [Brief explanation of the drawings]

[0012] [Figure 1] FIG. 1 is a diagram showing the results of an X-ray irradiation experiment of a gel dosimeter in Experimental Example 1. DETAILED DESCRIPTION OF THE INVENTION

[0013] The components of the gel dosimeter and gel of the present invention include a monomer polymerizable by irradiation with radiation, a gelling agent, and a sensitizer. In addition to the above components, a crosslinking agent, an oxygen scavenger, a stabilizer, a buffer, and other components may be optionally blended as needed within a range that does not impair the intended effects of the present invention.

[0014] [Gelling agent] The gelling agent can be one that can gel at room temperature a composition containing a radiation-polymerizable monomer, a gelling agent, a sensitizer consisting of inorganic fine particles, and other desired components, and that does not inhibit the radical polymerization of the radical-polymerizable monomer by radiation at a level that allows it to be used as a gel dosimeter. For example, a gelling agent that is used in conventional polymer gel dosimeters can be used. Examples of gelling agents include gelatin, agarose, xanthan gum, carrageenan, gellan gum, chitosan, and alginic acid, which are natural polymers derived from animals and plants, or their salts or partially neutralized salts, as well as gelling agents made from artificial or synthetic components such as water-soluble organic polymers (A) having an organic acid structure, organic acid salt structure, or organic acid anion structure, silicates (B), and dispersants for the silicates (C), and gelling agents made from polyvinyl alcohol and glutaraldehyde or borax.

[0015] The content of the natural polymer is 0.01% by mass to 30% by mass, preferably 0.05% by mass to 20% by mass, based on 100% by mass of the gel dosimeter.

[0016] Examples of the water-soluble organic polymer (A) having the organic acid structure, organic acid salt structure, or organic acid anion structure include water-soluble organic polymers that have, as side chains of the organic polymer, a plurality of organic acid groups such as carboxyl groups, sulfonyl groups, and phosphonyl groups, or salt structures thereof, or anion structures thereof, and that are soluble in water. Examples of the water-soluble organic polymer (A) include those having a carboxyl group such as poly(meth)acrylic acid, carboxyvinyl polymer, carboxymethyl cellulose, or a salt thereof; those having a sulfonyl group such as polystyrene sulfonic acid or a salt thereof; and those having a phosphonyl group such as polyvinyl phosphonic acid or a salt thereof. Preferred are salts of polyacrylic acid. In the present specification, (meth)acrylic acid refers to both acrylic acid and methacrylic acid.

[0017] The water-soluble organic polymer (A) preferably has a straight-chain structure free from branched or chemically crosslinked structures, and either a fully neutralized or partially neutralized product of a polymer having an organic acid group can be used.

[0018] Examples of the organic acid group having a salt structure include sodium salts, ammonium salts, potassium salts, and lithium salts of the organic acid group. Examples of compounds having an anionic structure include compounds having a structure in which a cation dissociates from an organic acid group or a salt of an organic acid. The water-soluble organic polymer (A) may be, for example, a completely or partially neutralized organic polymer having organic acid groups, or a mixture thereof.

[0019] The weight average molecular weight of the water-soluble organic polymer (A) is, for example, 1 million to 10 million, for example, 2.5 million to 5 million, in terms of polyethylene glycol, as determined by gel permeation chromatography (GPC).

[0020] The water-soluble organic polymer (A) is preferably a fully neutralized or partially neutralized polyacrylate, more preferably a fully neutralized or partially neutralized polyacrylate having a weight-average molecular weight of 1,000,000 to 10,000,000. Furthermore, the water-soluble organic polymer (A) is preferably a fully neutralized or partially neutralized polyacrylate having a weight-average molecular weight of 1,000,000 to 10,000,000, more preferably a fully neutralized or partially neutralized linear polyacrylate having a weight-average molecular weight of 2,500,000 to 5,000,000. The degree of neutralization of the partially neutralized product is 10% to 90%, preferably 30% to 80%.

[0021] The content of the water-soluble organic polymer (A) is 0.01 to 20% by mass, preferably 0.05 to 10% by mass, based on 100% by mass of the gel dosimeter or gel.

[0022] Examples of the silicate (B) include water-swellable silicates such as smectite, bentonite, vermiculite, and mica, and those that form colloids using water or a water-containing liquid as a dispersion medium are preferred. The shape of the primary particles of silicate may be discoid, plate-like, spherical, granular, cubic, needle-like, rod-like, amorphous, etc., and discoid or plate-like particles with a diameter of 5 nm to 1000 nm are preferred.

[0023] Specific examples of silicates include layered silicates. Commercially available examples include Laponite XLG (synthetic hectorite), XLS (synthetic hectorite containing sodium pyrophosphate as a dispersant), XL21 (sodium magnesium fluorosilicate), RD (synthetic hectorite), RDS (synthetic hectorite containing inorganic polyphosphate as a dispersant), and S482 (synthetic hectorite containing sodium etidronate as a dispersant), all manufactured by BYK Additives; Kunipia (montmorillonite), Sumecton SA (synthetic saponite), Sumecton ST (synthetic saponite), Sumecton SWN (synthetic smectite), and Sumecton SWF (synthetic smectite), all manufactured by Kunimine Industries Co., Ltd.; and Bengel (refined natural bentonite) manufactured by Hojun Co., Ltd.

[0024] The content of the silicate (B) is 0.01 to 20% by mass, preferably 0.05 to 10% by mass, based on 100% by mass of the gel dosimeter or gel.

[0025] The silicate dispersant (C) may be a dispersant or deflocculating agent used to improve the dispersibility of the silicate or to delaminate the layered silicate. For example, a phosphate-based dispersant, a carboxylate-based dispersant, an alkali-acting dispersant, or an organic deflocculating agent may be used.

[0026] Examples of suitable dispersants include phosphate dispersants such as sodium orthophosphate, sodium pyrophosphate, sodium tripolyphosphate, sodium tetraphosphate, sodium hexametaphosphate, sodium polyphosphate, sodium etidronate, and the corresponding potassium salts; carboxylate dispersants such as sodium poly(meth)acrylate, ammonium poly(meth)acrylate, sodium acrylate / sodium maleate copolymer, ammonium acrylate / ammonium maleate copolymer, and the corresponding potassium salts; alkali dispersants such as sodium hydroxide, hydroxylamine, and the corresponding potassium salts; compounds that react with polyvalent cations to form insoluble salts or complexes such as sodium carbonate, sodium silicate, and the corresponding potassium salts; and organic deflocculants such as polyethylene glycol, polypropylene glycol, sodium humate, lignin, sodium sulfonate, and the corresponding potassium salts. The preferred phosphate dispersant is sodium pyrophosphate; the preferred carboxylate dispersant is low-molecular-weight sodium polyacrylate with a weight-average molecular weight of 1,000 to 20,000; and the preferred organic deflocculant is polyethylene glycol (e.g., PEG 900).

[0027] It is known that low-polymerized sodium polyacrylate interacts with silicate particles to generate negative charges derived from carboxy anions on the particle surface, dispersing the silicate through charge repulsion, thereby acting as a dispersant.

[0028] The content of the dispersant (C) is 0.01 to 20% by mass, preferably 0.05 to 10% by mass, more preferably 0.5 to 5% by mass, based on 100% by mass of the gel dosimeter or gel. When a silicate containing a dispersant is used, a dispersant may or may not be further added.

[0029] When a gelling agent containing components (A) to (C) is used in the present invention, a preferred combination of the water-soluble organic polymer (A), silicate (B), and dispersant for the silicate (C) is, in 100% by mass of the gel dosimeter or gel, 0.05% to 10% by mass of fully neutralized or partially neutralized linear sodium polyacrylate having a weight-average molecular weight of 2.5 million to 5 million as (A), 0.05% to 10% by mass of water-swellable smectite or saponite as (B), and 0.5% to 5% by mass of sodium pyrophosphate or sodium etidronate, or 0.5% to 5% by mass of sodium polyacrylate having a weight-average molecular weight of 1,000 to 20,000 as (C).

[0030] The polyvinyl alcohol has a degree of polymerization of 10 to 8000, preferably 100 to 5000, more preferably 500 to 3000, and a degree of saponification of 80% to 99%, preferably 88% to 99%.

[0031] In the present invention, when a gelling agent composed of polyvinyl alcohol and glutaraldehyde or borax is used, a preferred combination thereof is 1 to 10% by mass of polyvinyl alcohol and 0.01 to 1% by mass of glutaraldehyde, or 1 to 10% by mass of polyvinyl alcohol and 0.1 to 1% by mass of borax, relative to 100% by mass of the gel dosimeter or gel.

[0032] [Radiation-polymerizable monomers] The gel dosimeter and gel of the present invention contain a monomer that can be polymerized by irradiation, for example, a monomer that initiates polymerization by radicals generated by irradiating a monomer or a solvent such as water. The gel dosimeter and gel of the present invention are useful as polymer gel dosimeters that measure radiation dose based on the amount of polymer produced (white turbidity, relaxation rate, etc.) in the irradiated area, since polymer is produced in response to the radiation dose. The monomer polymerizable by irradiation with radiation is not particularly limited as long as it dissolves or disperses uniformly in the solvent used in the gel dosimeter and the gel and has a carbon-carbon unsaturated bond that can be polymerized by the action of radiation. Examples include radical polymerizable monomers having an acrylic structure or a vinyl structure, and preferably water-soluble polymerizable monomers. Examples of the water-soluble polymerizable monomer include (meth)acrylic acid, methyl (meth)acrylate, ethyl (meth)acrylate, butyl (meth)acrylate, 2-methoxymethyl (meth)acrylate, 2-ethoxyethyl (meth)acrylate, triethylene glycol monoethyl ether mono(meth)acrylate, (meth)acrylamide, hydroxyethyl (meth)acrylate, N-isopropyl (meth)acrylamide, N,N-dimethyl (meth)acrylamide, N,N-diethyl (meth)acrylamide, 4-(meth)acryloylmorpholine, N-vinylpyrrolidone, N-vinylacetamide, (meth)acryloyl-L-alanine methyl ester, and (meth)acryloyl-L-proline methyl ester. The water-soluble polymerizable monomer may be used as a single component or as a mixture of two or more components. The content of the monomer polymerizable by irradiation is 0.01 to 30% by mass, preferably 0.1 to 20% by mass, and more preferably 0.5 to 15% by mass, based on 100% by mass of the gel dosimeter.

[0033] [Sensitizer] The sensitizer may be inorganic fine particles, and water-dispersible inorganic fine particles are particularly preferred. For example, silica sol, alumina sol, zirconium sol, etc. Near Examples of silica sols that are readily available as commercial products include Snowtex (registered trademark) (manufactured by Nissan Chemical Industries, Ltd.), Silicadol (registered trademark) (manufactured by Nippon Chemical Industry Co., Ltd.), and Quattron (manufactured by Fuso Chemical Industry Co., Ltd.). The inorganic fine particles are preferably water-dispersed colloidal silica, more preferably colloidal silica having a particle size of 4 to 60 nm. Examples include SNOWTEX (registered trademark) XS, S, 30, 50-T, 30L, and YL, which are Na+-stable alkaline sols; SNOWTEX (registered trademark) OXS, OS, O, O-40, OL, and OYL, which are acidic (e.g., pH: 2 to 4); SNOWTEX (registered trademark) NXS, NS, N, and N-40, which are alkaline (e.g., pH: 9 to 10); SNOWTEX (registered trademark) CXS, C, and CM, which have improved stability in the neutral range; and SNOWTEX (registered trademark) AK, AK-L, and AK-YL, which are surface-cationic acidic sols. Among these, Snowtex (registered trademark) XS, S, 30, 50-T, OXS, OS, O, O-40, NXS, NS, N, N-40, CXS, C, CM, and AK, which have a particle size of 4 to 25 nm, are preferred, and Snowtex (registered trademark) XS, S, OXS, NXS, and CXS, which have a particle size of 4 to 10 nm, are particularly preferred, with Snowtex (registered trademark) OXS being most preferred. The content of the water-dispersible inorganic fine particles is 0.01 to 50% by mass, preferably 0.05 to 10% by mass, and more preferably 0.1 to 5% by mass, calculated as the solid content in colloidal silica, based on 100% by mass of the gel dosimeter.

[0034] In the gel dosimeter and gel of the present invention, other sensitizers can be used in combination with the sensitizer made of inorganic fine particles. For example, it is known that the radiation sensitivity of gel dosimeters can be increased by the use of magnesium salts, such as magnesium chloride and magnesium sulfate. When the above-mentioned magnesium salt is used in combination, the content thereof is 0.1% by mass to 50% by mass, preferably 0.5% by mass to 25% by mass, and more preferably 1% by mass to 10% by mass, based on 100% by mass of the gel dosimeter or gel.

[0035] [Other additives] The gel dosimeter and gel of the present invention may contain a crosslinking agent, an oxygen scavenger, a stabilizer, a buffer, etc., within a range that does not impair the effects of the present invention, in order to promote a polymerization reaction due to radiation irradiation and increase radiation sensitivity.

[0036] [Crosslinking agent] A crosslinking agent can be added to the gel dosimeter of the present invention to convert the polymer produced by irradiation into a polymer with a crosslinked structure. A polymer with a crosslinked structure has reduced water solubility and is more likely to precipitate (make the gel opaque). In addition, a polymer with a crosslinked structure is less likely to diffuse or move within the gel. The crosslinking agent may be a polyfunctional monomer having two or more unsaturated bonds in one molecule, and examples thereof include FAM-301, FAM-401, FOM-03006, FOM-03007, FOM-03008, and FOM-03009 (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.), N,N'-methylenebisacrylamide, N,N'-diallylacrylamide, N,N'-diacryloylimide, triallyl formal, 1,3,5-triacryloylhexahydro-1,3,5-triazine, diallylnaphthalene, ethylene glycol diacrylate, ethylene glycol dimethacrylate, and various polyethylene glycol di(meth)acrylates. acrylate, propylene glycol diacrylate, propylene glycol dimethacrylate, various polypropylene glycol di(meth)acrylates, 1,3-butylene glycol diacrylate, 1,3-butylene glycol dimethacrylate, 1,4-butylene glycol dimethacrylate, various polybutylene glycol di(meth)acrylates, glycerol dimethacrylate, neopentyl glycol dimethacrylate, trimethylolpropane triacrylate, trimethylolpropane trimethacrylate, tetramethylolmethane tetramethacrylate, and divinyl compounds such as divinylbenzene. Among these, water-soluble polyfunctional acrylamide monomers are preferred, including N,N'-methylenebisacrylamide, FAM-301, FAM-401, and FOM-03006 (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) The content of the crosslinking agent is 0.01% to 20% by mass, preferably 0.1% to 10% by mass, and more preferably 0.5% to 5% by mass, based on 100% by mass of the gel dosimeter or gel.

[0037] [Oxygen absorber] An oxygen scavenger can be added to the gel dosimeter and gel of the present invention in order to remove oxygen that inhibits the polymerization reaction of monomers that can be polymerized by irradiation with radiation. Examples of oxygen scavenger include tetrakis(hydroxymethyl)phosphonium chloride (THPC), ascorbic acid, sodium ascorbate, copper sulfate, etc. The content of the oxygen scavenger is 0.01% to 50% by mass, preferably 0.05% to 10% by mass, and more preferably 0.1% to 5% by mass, based on 100% by mass of the gel dosimeter. Another example of an oxygen scavenger is a combination of glucose and glucose oxidase. The glucose content is 0.01% to 10% by mass, preferably 0.1% to 5% by mass, and more preferably 0.5% to 3% by mass, based on 100% by mass of the gel dosimeter. The activity of glucose oxidase is 10 units / g to 1,000,000 units / g, preferably 100 units / g to 500,000 units / g, and more preferably 1,000 units / g to 300,000 units / g, where 1 unit is the amount of glucose oxidase that oxidizes 1.0 μmol of β-D-glucose to D-gluconolactone and hydrogen peroxide per minute at 25°C and pH 7.0. The glucose oxidase content is 0.1 ppm to 10,000 ppm, preferably 0.5 ppm to 5,000 ppm, and more preferably 1 ppm to 1,000 ppm, based on 100% by mass of the gel dosimeter. Catalase may also be added to decompose hydrogen peroxide generated during glucose oxidation.

[0038] [Stabilizer] A stabilizer can be added to the gel dosimeter and gel of the present invention to prevent deterioration or inactivation before irradiation. Examples of the stabilizer include polymerization inhibitors, radical scavengers, and antioxidants, such as hydroquinone, 4-methoxyphenol, and N,N'-diisobutyl-p-phenylenediamine. The content of the stabilizer is 0.1 ppm to 10,000 ppm, preferably 1 ppm to 5,000 ppm, and more preferably 10 ppm to 3,000 ppm, based on 100% by mass of the gel dosimeter.

[0039] [Buffer] The gel dosimeter of the present invention may contain a buffer. If the pH of the gel dosimeter needs to be adjusted, a buffer can be added to adjust the gel dosimeter and gel to a desired pH. Examples of buffers include, but are not limited to, phosphoric acid, citric acid, acetic acid, boric acid, tartaric acid and salts thereof, Tris, and HEPES. These buffers may be used alone or in combination of two or more.

[0040] The gel dosimeter and gel of the present invention may also contain a pH adjuster such as glucono-δ-lactone, perchloric acid, sulfuric acid, or sodium chloride. Furthermore, the gel dosimeter and gel of the present invention may contain a free radical scavenger such as hydroquinone or phenylenediamine, or an ultraviolet absorber such as guaiazulene, in order to suppress polymerization of residual monomers after irradiation. Furthermore, the gel dosimeter and gel of the present invention may contain a colorant or the like, if necessary.

[0041] [Gel dosimeter and method of manufacturing the gel] The method for producing the gel dosimeter and gel of the present invention is not particularly limited. For example, a monomer polymerizable by radiation and a gelling agent can be mixed in a predetermined ratio, and a sensitizer and, if desired, other components such as a crosslinking agent, an oxygen scavenger, a stabilizer, and a buffering agent can be further added and mixed to form a uniform solution or a transparent dispersion. Each component can be dissolved or dispersed in a solvent as needed. The solvent is not particularly limited as long as it can dissolve or uniformly disperse each component of the gel dosimeter, but water is preferred. Water can be mixed with an aqueous solvent such as methanol, ethanol, isopropanol, or glycerol.

[0042] When a gel-forming composition containing components (A) to (C) is used as a gelling agent, one example of a method is to mix two of these components, for example, components (A) to (C), to prepare a uniform solution, then add the remaining components and monomers, and further add and mix other components such as a sensitizer and, if desired, a crosslinking agent, an oxygen scavenger, and a stabilizer to prepare a uniform solution. For example, an aqueous dispersion of component (B), component (C), and water is added to an aqueous solution of component (A), a monomer polymerizable by irradiation with radiation, a sensitizer, and optionally other components and water, and the mixture is heated and mixed as necessary to form a homogeneous solution.

[0043] When a natural polymer derived from an animal or plant is used as the gelling agent, a method can be used in which a monomer polymerizable by irradiation, a natural polymer, a sensitizer, and other components, if desired, are added to water, and the mixture is heated, if necessary, to mix and prepare a homogeneous solution.

[0044] Methods for mixing the components include mechanical or manual stirring, ultrasonic stirring, and continuous mixing by line mixing, with mechanical stirring and continuous mixing being particularly preferred. For mechanical stirring, magnetic stirrers, propeller stirrers, planetary mixers, dispersers, homogenizers, shakers, vortex mixers, ball mills, kneaders, ultrasonic oscillators, and the like can be used. Of these, planetary mixers are preferred. For continuous mixing, line mixers (manufactured by Satake Chemical Machinery Co., Ltd.), in-line mixers (manufactured by Silverson Nippon Co., Ltd.), Vibro mixers (manufactured by Reika Kogyo Co., Ltd.), static mixers (manufactured by Noritake Company Ltd., Japan Flow Control Co., Ltd., Sanyo Seiki Co., Ltd., etc.), spiral mixers (manufactured by Japan Flow Control Co., Ltd.), Flowmix (manufactured by Mountec Co., Ltd.), and Sukeya mixers (manufactured by Sakura Seisakusho Co., Ltd.) can be used. Of these, static mixers are preferred.

[0045] The temperature during mixing is, for example, the freezing point to the boiling point of the aqueous solution or aqueous dispersion, preferably -5°C to 100°C, more preferably 0°C to 50°C.

[0046] Immediately after mixing, the mixture is weak and in a sol state, but it gels when left to stand. The standing time is preferably 2 to 100 hours. The standing temperature is -5 to 100°C, preferably 0 to 30°C.

[0047] <Radiation dosimeter> Because the gel dosimeter and gel for measuring radiation dose of the present invention are suitable as materials for measuring radiation dose, the gel dosimeter or gel for measuring radiation dose can be filled into a container to form a radiation dosimeter, for example, a phantom. The container is not particularly limited as long as it is non-sensitive to MRI, transparent to radiation, solvent-resistant, airtight, etc., and its material is preferably glass, PET, polyethylene, polypropylene, acrylic resin, polyester, ethylene-vinyl alcohol copolymer, etc. If the container is transparent, three-dimensional dose distribution can be measured not only by MRI but also by optical CT, which is capable of three-dimensional measurement of opacity. Furthermore, after filling the container, the air may be purged with nitrogen gas, etc.

[0048] <Radiation dose measurement method> In the present invention, the radiation dose-measuring gel dosimeter and the absorbed dose of the gel can be measured by a method used for conventional polymer gel dosimeters. For example, the radiation dose-measuring gel dosimeter and the absorbed dose of the gel of the present invention can be measured by a medical imaging diagnostic device. The medical imaging diagnostic device is a device that can read out a three-dimensional image in order to determine the spatial absorbed dose distribution, and examples thereof include three-dimensional imaging devices such as an MRI device (Magnetic Resonance Imaging), an X-ray CT device (X-ray Computed Tomography), and an optical CT device, with an MRI device being preferred. In the present invention, the method for measuring the absorbed dose of a gel dosimeter for measuring radiation dose preferably involves measuring the relaxation time of each part of the gel dosimeter for measuring radiation dose using an MRI device. Specifically, examples of such a method include a method in which the absorbed dose is calculated from an R2 image obtained by imaging with an MRI device using the transverse relaxation rate R2-absorbed dose characteristics, and the absorbed dose distribution of the gel dosimeter for measuring radiation dose after irradiation is quantified. [Example]

[0049] The present invention will now be described in detail with reference to examples, but the present invention is not limited to these examples.

[0050] [Production Example 1: Production of silicate aqueous dispersion] 14.4 parts of Sumecton SWF (Kunimine Industries Co., Ltd.), 1.5 parts of etidronate disodium hydrate (Tokyo Chemical Industry Co., Ltd.), and 84.1 parts of water were mixed and stirred at 25°C until a uniform aqueous dispersion was obtained, yielding a silicate aqueous dispersion.

[0051] [Production Example 2: Production of highly polymerized sodium polyacrylate aqueous solution] Four parts of highly polymerized sodium polyacrylate (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.: degree of polymerization 22,000 to 70,000), 1.6 parts of magnesium chloride hexahydrate, and 94.4 parts of water were mixed and stirred at 25°C until a uniform aqueous solution was obtained, thereby obtaining an aqueous solution of highly polymerized sodium polyacrylate.

[0052] [Example 1: Production of a gel dosimeter using a water-soluble organic polymer, a silicate, and a silicate dispersant as a gelling agent] 1.5 parts of N,N'-methylenebisacrylamide (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.), 1.5 parts of N,N-dimethylacrylamide (manufactured by Tokyo Chemical Industry Co., Ltd.), 6 parts of 4-acryloid morpholine (manufactured by Tokyo Chemical Industry Co., Ltd.), 1 part of glucose (manufactured by Junsei Chemical Co., Ltd.), 10 ppm of glucose oxidase (manufactured by Tokyo Chemical Industry Co., Ltd.), and 10 parts (corresponding to 1 part solids) of Snowtex ST-OXS (manufactured by Nissan Chemical Industries, Ltd.: colloidal silica with a solids concentration of 10%) were added to 58 parts of water and stirred at 20 to 25°C until homogeneous. 11 parts of the aqueous solution of highly polymerized sodium polyacrylate produced in Production Example 2 were added, and the mixture was stirred at 20 to 25°C until homogeneous. 11 parts of the aqueous silicate dispersion produced in Production Example 1 were added, and the mixture was stirred at 20 to 25°C for 3 minutes. The resulting mixture was filled into a 15 mL PET container and left to stand at 20°C to 25°C for 24 hours to obtain a sample for X-ray irradiation experiments.

[0053] [Example 2: Production of a gel dosimeter using a water-soluble organic polymer, a silicate, and a silicate dispersant as a gelling agent] 1.5 parts of N,N'-methylenebisacrylamide (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.), 1.5 parts of N,N-dimethylacrylamide (manufactured by Tokyo Chemical Industry Co., Ltd.), 6 parts of 4-acryloid morpholine (manufactured by Tokyo Chemical Industry Co., Ltd.), 1 part of glucose (manufactured by Junsei Chemical Co., Ltd.), 10 ppm of glucose oxidase (manufactured by Tokyo Chemical Industry Co., Ltd.), and 20 parts (equivalent to 2 parts solids) of Snowtex ST-OXS (manufactured by Nissan Chemical Industries, Ltd.: colloidal silica with a solids concentration of 10%) were added to 48 parts of water and stirred at 20 to 25°C until homogeneous. 11 parts of the aqueous solution of highly polymerized sodium polyacrylate produced in Production Example 2 were added, and the mixture was stirred at 20 to 25°C until homogeneous. 11 parts of the aqueous silicate dispersion produced in Production Example 1 were added, and the mixture was stirred at 20 to 25°C for 3 minutes. The resulting mixture was filled into a 15 mL PET container and left to stand at 20°C to 25°C for 24 hours to obtain a sample for X-ray irradiation experiments.

[0054] [Example 3: Production of a gel dosimeter using a water-soluble organic polymer, a silicate, and a silicate dispersant as a gelling agent] 1.5 parts of N,N'-methylenebisacrylamide (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.), 1.5 parts of N,N-dimethylacrylamide (manufactured by Tokyo Chemical Industry Co., Ltd.), 6 parts of 4-acryloid morpholine (manufactured by Tokyo Chemical Industry Co., Ltd.), 1 part of glucose (manufactured by Junsei Chemical Co., Ltd.), 10 ppm of glucose oxidase (manufactured by Tokyo Chemical Industry Co., Ltd.), and 30 parts (equivalent to 3 parts solids) of Snowtex ST-OXS (manufactured by Nissan Chemical Industries, Ltd.: colloidal silica with a solids concentration of 10%) were added to 38 parts of water and stirred at 20 to 25°C until homogeneous. 11 parts of the aqueous solution of highly polymerized sodium polyacrylate produced in Production Example 2 were added, and the mixture was stirred at 20 to 25°C until homogeneous. 11 parts of the aqueous silicate dispersion produced in Production Example 1 were added, and the mixture was stirred at 20 to 25°C for 3 minutes. The resulting mixture was filled into a 15 mL PET container and left to stand at 20°C to 25°C for 24 hours to obtain a sample for X-ray irradiation experiments.

[0055] Comparative Example 1: Production of a gel dosimeter using a water-soluble organic polymer, a silicate, and a silicate dispersant as a gelling agent 1.5 parts of N,N'-methylenebisacrylamide (Fujifilm Wako Pure Chemical Industries, Ltd.), 1.5 parts of N,N-dimethylacrylamide (Tokyo Chemical Industry Co., Ltd.), 6 parts of 4-acryloid morpholine (Tokyo Chemical Industry Co., Ltd.), 1 part of glucose (Junsei Chemical Co., Ltd.), and 10 ppm of glucose oxidase (Tokyo Chemical Industry Co., Ltd.) were added to 68 parts of water and stirred at 20 to 25°C until homogeneous. 11 parts of the aqueous solution of highly polymerized sodium polyacrylate produced in Production Example 2 were added, and the mixture was stirred at 20 to 25°C until homogeneous. 11 parts of the aqueous silicate dispersion produced in Production Example 1 were added, and the mixture was stirred at 20 to 25°C for 3 minutes. The resulting mixture was filled into a 15 mL PET container and allowed to stand at 20 to 25°C for 24 hours to obtain a sample for X-ray irradiation experiments.

[0056] [Experimental Example 1: X-ray irradiation experiment of gel dosimeter] Each gel dosimeter sample obtained in Examples 1 to 3 and Comparative Example 1 was irradiated with 0.5, 1, 3, 5, or 7 Gy of X-rays using an X-ray irradiator (MBR-1520R-4, manufactured by Hitachi Power Solutions Co., Ltd.) under conditions of a tube voltage of 150 kV and a tube current of 20 mA. After irradiation, each sample was analyzed by MRI measurement using a 3T MRI (Prisma, manufactured by Siemens). A mixed turbo spin echo sequence was applied as a pulsed magnetic field for analysis. The T2 relaxation time (transverse relaxation time) of each sample was obtained, and the transverse relaxation rate R2 (i.e., 1 / T2) and ΔR2, with the unirradiated sample set as 0 (reference), were calculated. A correlation graph between ΔR2 and the irradiated X-ray dose for Examples 1 to 3 and Comparative Example 1 is shown in Figure 1.

[0057] From FIG. 1, it can be seen that the samples of Examples 1 to 3 have larger X-ray irradiation sensitivity (ΔR2) values ​​than the sample of Comparative Example 1, which indicates that the sensitivity was improved by adding the sensitizer (Snowtex ST-OXS). [Industrial Applicability]

[0058] The gel dosimeter for radiation dosimeter of the present invention can be easily manufactured using raw materials that are easily available industrially, and has excellent radiation sensitivity and linearity, so it can be applied to various radiation therapies.

Claims

1. The composition includes a monomer polymerizable by irradiation with radiation, a gelling agent, and a sensitizer made of inorganic fine particles, the sensitizer composed of inorganic fine particles includes one or more selected from the group consisting of silica sol, alumina sol, and zirconia sol; Gel dosimeter for measuring radiation dose.

2. 2. The gel dosimeter for measuring radiation dose according to claim 1, wherein the gelling agent is one or more gelling agents selected from the group consisting of gelatin, agarose, xanthan gum, carrageenan, gellan gum, chitosan, and alginic acid or sodium, potassium, magnesium, and calcium salts thereof, including partially neutralized salts thereof.

3. 2. The gel dosimeter for measuring radiation dose according to claim 1, wherein the gelling agent is a gelling agent made of polyvinyl alcohol and glutaraldehyde or borax.

4. 2. The gel dosimeter for measuring radiation dose according to claim 1, wherein the gelling agent comprises a water-soluble organic polymer (A) having an organic acid structure, an organic acid salt structure, or an organic acid anion structure, a silicate (B), and a dispersant (C) for the silicate.

5. 5. The gel dosimeter for measuring radiation dose according to claim 4, wherein the water-soluble organic polymer (A) is a fully or partially neutralized polyacrylate having a weight-average molecular weight of 1,000,000 to 10,000,000.

6. 6. The gel dosimeter for measuring radiation dose according to claim 4 or 5, wherein the silicate (B) is one or more water-swellable silicates selected from the group consisting of smectite, bentonite, vermiculite, and mica.

7. 7. The gel dosimeter for measuring radiation dose according to any one of claims 4 to 6, wherein the dispersant (C) is one or more selected from the group consisting of sodium orthophosphate, sodium pyrophosphate, sodium tripolyphosphate, sodium tetraphosphate, sodium hexametaphosphate, sodium polyphosphate, sodium etidronate, sodium poly(meth)acrylate, ammonium poly(meth)acrylate, sodium acrylate / sodium maleate copolymer, ammonium acrylate / ammonium maleate copolymer, sodium hydroxide, hydroxylamine, sodium carbonate, sodium silicate, polyethylene glycol, polypropylene glycol, sodium humate, and sodium lignosulfonate, as well as potassium salts corresponding to these salts.

8. 8. The gel dosimeter for measuring radiation dose according to claim 1, wherein the monomer polymerizable by irradiation with radiation is a water-soluble polymerizable monomer.

9. The gel dosimeter for measuring radiation dose according to claim 1 , further comprising a crosslinking agent.

10. 10. The gel dosimeter for measuring radiation dose according to claim 9, wherein the crosslinking agent is a water-soluble polyfunctional acrylamide monomer.

11. The gel dosimeter for measuring radiation dose according to any one of claims 1 to 10, further comprising an oxygen scavenger.

12. The gel dosimeter for measuring radiation dose according to any one of claims 1 to 11, further comprising a stabilizer.

13. The gel dosimeter for measuring radiation dose according to any one of claims 1 to 12, further comprising a buffering agent.

14. 14. The gel dosimeter for measuring radiation dose according to claim 13, wherein the buffer is one or more selected from the group consisting of phosphoric acid, citric acid, acetic acid, boric acid, tartaric acid and salts thereof, Tris, and HEPES.

15. The composition includes a monomer polymerizable by irradiation with radiation, a gelling agent, and a sensitizer made of inorganic fine particles, the sensitizer composed of inorganic fine particles includes one or more selected from the group consisting of silica sol, alumina sol, and zirconia sol; Radiation dosimetry gel.

16. The method includes a step of mixing a monomer polymerizable by irradiation with radiation, a gelling agent, and a sensitizer comprising inorganic fine particles, the sensitizer composed of inorganic fine particles includes one or more selected from the group consisting of silica sol, alumina sol, and zirconia sol; A method for manufacturing a gel for measuring radiation dosimetry.

17. A method for measuring a radiation dose using a gel containing a sensitizer made of a monomer polymerizable by irradiation with radiation, a gelling agent, and inorganic fine particles, comprising: The method, wherein the sensitizer composed of inorganic fine particles contains one or more kinds selected from the group consisting of silica sol, alumina sol, and zirconia sol.

Images