JP6212695B2 - Polymer gel dosimeter, radiation measurement method using the dosimeter, information management means and method, system - Google Patents

Description

  The present invention relates to a polymer gel dosimeter. In particular, the present invention relates to a polymer gel dosimeter capable of easily and accurately measuring a radiation irradiation region and a radiation dose.

  There are various types of dosimeters, and polymer gel dosimeters have attracted attention as a tool for measuring dose distribution when performing radiotherapy for tumors.

  A polymer gel dosimeter is one in which a monomer is dispersed in a gel, and when irradiated with radiation, the monomer is polymerized to produce a polymer, thereby utilizing the white turbidity of the gel. In this dosimeter, a polymer is formed in a region irradiated with radiation, and the gel is clouded, so that the actually irradiated region can be visualized. Moreover, since the polymer formed in proportion to the radiation dose increases, the turbidity of the gel is proportional to the radiation dose, and the radiation dose can be measured by measuring the turbidity.

  Conventionally, a polymer gel dosimeter is intended to measure a spatial three-dimensional dose distribution (Patent Documents 1 to 3 and Non-Patent Documents 1 and 2), for example, 10 cm × 10 cm × 10 cm. In general, the length and thickness are approximately the same size.

  As a monomer of the polymer gel dosimeter, acrylamide, acrylic acid or the like has been used in order to enable measurement even at a low dose (Non-patent Documents 3 and 4). However, these monomers are highly toxic and are not desirable for dosimeters that come into contact with living organisms. On the other hand, for the purpose of reducing toxicity, it has been proposed to prepare a dosimeter using monomers such as N-vinylpyrrolidone and N-isopropylacrylamide (Non-Patent Document 5). In addition, the present inventors have proposed a dosimeter having a monomer composition in which 2-hydroxyethyl methacrylate (HEMA) and nonaethylene glycol dimethacrylate (9G) are combined (Non-patent Documents 6 and 7). A dosimeter using a polymerizable polymer has also been proposed for the purpose of accurately measuring the dose distribution in the irradiated space (Patent Document 2).

  As the gel matrix of the polymer gel dosimeter, natural polymer compounds such as agarose, carrageenan, gellan gum, xanthan gum and gelatin are used (Patent Documents 1 and 2), and gelatin is widely used (Non-Patent Documents). 3 and 4). On the other hand, the present inventors have proposed a gel matrix in which a crosslinked structure is introduced into hydroxypropylcellulose by electron beam irradiation (Non-patent Document 8).

JP 2012-002669 A JP 2002-214354 A US Pat. No. 5,321,357

Gel dosimeter for 3D dose distribution measurement in radiation therapy 2007/11/14 Yuichi Sato Main page of Radiation Utilization Technology Database [http://www.rada.or.jp/database/home4/normal/ht-docs/member /synopsis/040334.html] P. Sandilos et al., Journal of Applied Clinical Medical Physics, 7, 13-21 (2006). M.J.Maryanski, et al., Phys. Med. Biol., 39, 1437-1455 (1994). Medical Gel Dosimetry Systems, Inc. [http://www.mgsresearch.com/] R. J. Senden et al., Physics in Medicine and Biology, 51, 3301-3314 (2006). Turbidity associated with irradiation of gel dosimeters based on cellulose, Shinichi Yamashita et al., 54th Annual Meeting of Japanese Society of Radiation Effects, November 2011 Summary of 21st Academic Symposium of MRS-Japan 2011, Shinichi Yamashita et al., Advanced Materials Researches Breakthrough to Ecoinnovations, December 2011 Development of gel dosimeter based on hydropropylcellulose-Effect of detection agent composition on turbidity caused by γ-ray irradiation Shinichi Yamashita et al., 54th Annual Meeting of Radiation Chemistry, September 16, 2011

The inventors of the present invention do not use a polymer gel dosimeter to measure a spatial three-dimensional dose distribution as in the prior art, but can easily measure the radiation dose on the patient surface and can be easily handled thereafter. A dosimeter in the form of a sheet was designed to provide
However, when a dosimeter in which the gel composition was put in a package made of polyethylene, which is a general-purpose polymer, was prepared and irradiated with radiation, it was discovered that the irradiated area did not become cloudy. In addition, a dosimeter in which the gel composition was put in a package made of an ethylene vinyl alcohol copolymer (EVOH) film having an oxygen barrier property was prepared, and the dosimeter was irradiated with radiation and left as it was. We also discovered the phenomenon that the clouded area was enlarged over time and the degree of cloudiness became stronger.

  The inventors of the present invention have found that, as a result of forming the sheet into the first problem, the polymerization of the monomer by radiation irradiation is easily inhibited by oxygen in the air. Further, regarding the latter problem, it has been found that even after irradiation, the polymerization of the monomer gradually proceeds due to residual radicals, and the cloudiness region is enlarged or the cloudiness is increased. Therefore, for the former phenomenon, a configuration in which the polymer gel is shielded from oxygen has been conceived, and for the latter phenomenon, a configuration in which the polymer gel is exposed to oxygen after irradiation is conceived. It came to do.

That is, the present invention provides, in one embodiment, a radiation-sensitive gel composition containing a monomer that can be polymerized by radiation irradiation and a gel matrix that disperses the monomer, and a transparent package that encloses the gel composition. There is provided a dosimeter comprising a dosimeter, wherein the package has an oxygen barrier property at least when irradiated with radiation. In addition, as a solution to the second problem, the present invention provides a dosimeter having a configuration in which the gel composition is shielded from oxygen during irradiation and the gel composition can come into contact with oxygen after irradiation. To do. A typical example of such a dosimeter is a dosimeter whose package is composed of a laminated film having an oxygen permeable layer and a peelable oxygen barrier layer covering the layer, or independently of each other. A dosimeter comprising an oxygen permeable film and an oxygen barrier film present, wherein the oxygen barrier film encloses the oxygen permeable film.
The present invention also provides, in another embodiment, a dosimeter having a monomer composition in which specific monomers are combined, preferably in a specific ratio, according to the range of dose to be measured.

In the dosimeter according to one embodiment of the present invention, as described above, since the gel composition is shielded from oxygen at least during irradiation, the polymerization of the monomer is not hindered in the region irradiated with radiation, and the irradiation region Becomes cloudy. In addition, in the case of a dosimeter having a structure in which the gel composition can come into contact with oxygen in the air after irradiation, further polymerization after irradiation is hindered by oxygen, and the cloudiness area and turbidity due to irradiation are subsequently reduced. Is also saved.
In addition, since the dosimeter of the present invention is sheet-like and easy to handle and is transparent, the irradiation area and dose can be visualized and stored as it is in a medical chart or the like. In addition, from the same characteristics, it is possible to analyze using a device capable of measuring a general absorbance or optical density such as a spectrophotometer or an image data conversion device, and a device that can easily and inexpensively confirm an irradiation region and dose or Can provide a system. Accordingly, the present invention, in yet another embodiment, comprises a sheet-like dosimeter comprising a radiation-sensitive gel composition and a transparent package enclosing the gel composition, and the absorbance or optical properties of the whole or a certain area of the dosimeter. Provided is a simple radiation measurement system or a radiation therapy control system including a device capable of measuring a density or a device capable of generating image data.
Of course, the present invention can also be used for radiation measurement in fields other than medical applications.

Here, definitions of some terms used in the present specification will be described below.
As used herein, “radiation” means high-speed particle beam or electromagnetic wave, carbon beam, α beam, deuteron beam, proton beam, other heavy charged particle beam, β beam, electron beam, It includes neutrons, X-rays, γ-rays and characteristic X-rays generated with orbital electron capture.

  As used herein, “radiation irradiation” is used in a sense that does not include irradiation with natural radiation alone. Therefore, the irradiation of radiation generated by an artificial cause is typically applicable.

As used herein, the terms “oxygen barrier layer”, “oxygen barrier material”, and “oxygen barrier film” refer to gel compositions and oxygen, respectively, at levels that do not interfere with the polymerization of the monomer upon irradiation. Means layers, materials and films that can prevent contact with Usually, the oxygen permeability measured based on JIS K 7126 B method (isobaric method) is less than 20 (cm ³ / m ² · 24h · atm), preferably 5 (cm ³ / m ² · 24h · atm) or less Applicable to layers, materials or films. On the other hand, as used herein, the terms “oxygen permeable layer”, “oxygen permeable material” and “oxygen permeable film”, unless stated otherwise, prevent polymerization of the monomer after irradiation, It means a layer, material or film capable of transmitting oxygen at a level where the cloudy region formed by irradiation does not change for at least 60 days. Usually, the oxygen permeability measured based on JIS K 7126 B method (isobaric method) is 20 (cm ³ / m ² · 24h · atm) or more, preferably 45 (cm ³ / m ² · 24h · atm) or more. Applicable to layers or materials.

  As used herein, “lower alkyl” means linear or branched alkyl having 1 to 10 carbon atoms, preferably 1 to 4 carbon atoms, and “lower alkoxy” means 1 to 1 carbon atoms. Means a linear or branched alkoxy having 10, preferably 1 to 4, and “lower alkoxyalkyl” means a linear or branched alkoxyalkyl having 2 to 10 carbon atoms, preferably 2 to 5 carbon atoms. means.

FIG. 1 is a schematic diagram showing one embodiment of the present invention. 1 indicates a dosimeter, 2 indicates an adhesive layer, 3 indicates a scale, and 4 indicates a portion in which the gel composition is enclosed. FIG. 2A is a schematic view showing an example in which a dosimeter according to one embodiment of the present invention is integrated with a medical chart, and FIG. 2B is a package and an adhesive layer according to one embodiment of the present invention. It is sectional drawing which shows the relationship. 1 indicates a dosimeter, 5 indicates an information management tool, 6 indicates a package, and 7 indicates an adhesive layer. FIG. 3 collectively shows a part of photographs showing a state after irradiating 10 Gy of γ rays using ⁶⁰ Co as a radiation source to the dosimeters obtained in Examples 1 to 18. FIG. 4 shows the dosimeters obtained in Examples 1 to 5 and 7 by irradiating γ rays in the range of 0 to 20 Gy using γ rays with ⁶⁰ Co as a radiation source. It is a graph which shows the relationship between (gamma) dose and a light absorbency at the time of measuring the light absorbency of 660 nm. FIG. 5 is a graph showing the relationship between the content of 9G and the radiation sensitivity (ABS./Gy) for the dosimeters obtained in Examples 1 to 4 and Examples 5 and 6. 6A is a photograph showing the state after irradiating the dosimeter obtained in Example 20 with carbon beams of 0, 5, and 15 Gy, respectively, and FIG. 6B shows the dosimeter obtained in Example 20 It is a photograph which shows the state after irradiating the iron wire of 0, 1, 2, and 5 Gy, respectively. FIGS. 7A to 7C are photographs showing the states after irradiating 2 Gy of γ rays from cobalt 60 to the dosimeters obtained in Examples 19 and 20 and Comparative Example 1, respectively. 8A and B show that the dosimeters of Examples 19 and 20, respectively, were irradiated with 2 Gy of gamma rays from cobalt 60, after which the dosimeter of Example 19 peeled off the oxygen barrier layer, and the dosimeter of Example 20 These are photographs showing the state after opening the oxygen barrier film package and leaving it in the atmosphere for 60 days. FIGS. 9A and 9B show the dosimeters of Example 20 after 5 hours of X-ray irradiation, and after that, when the oxygen barrier film package was left unopened, the dosimeters after 1 hour and 24 hours were measured. It is a photograph showing the state. FIG. 10 is a schematic diagram showing a place where a dosimeter according to the present invention is installed when performing radiation therapy on a bilateral breast in a patient after bilateral breast cancer-preserving surgery. This schematic diagram is created by the treatment planning apparatus. Reference numeral 1 denotes a dosimeter, 2 denotes a gap between radiation bundles scheduled in the treatment plan, 3 denotes a breast, and 4 denotes a radiation bundle. Although not shown in the figure, the source is assumed to be on the left and right underside. FIG. 11 is a photograph showing a state when the dosimeter of Example 1 is attached to the front chest of the patient model. A rectangular sheet in the center of the photograph is a dosimeter, and a broken line is added to show the outline of the dosimeter. FIG. 12 is a photograph of when the dosimeter of Example 1 was attached and irradiated with radiation as shown in FIG. 11 and applied to a scanner (trade name: ES-10000G, manufactured by EPSON). A dotted line indicates the extension of the irradiation region, and a double-headed arrow is added to indicate a gap between the radiation bundles. FIGS. 13A and 13B show the dosimeter at 1 hour and 260 hours after the dosimeter of Example 20 was attached and irradiated with radiation in the same manner as the dosimeter of Example 1 shown in FIG. (Product name: ES-10000G, manufactured by EPSON)) FIG. 14 is a photograph showing a state when the guff chromic is attached to the front chest of the patient model. There is a gap between the gaff chromic and the model surface in the recess of the patient model. FIG. 15 is a test for confirming a gap between radiation bundles when performing whole brain radiation treatment and / or whole spinal cord radiation treatment using a patient model, and it is assumed that a dosimeter according to the present invention is installed. FIG. 1 shows a dosimeter attached to a site where a gap is to be created between the whole brain irradiation beam bundle and the spinal beam bundle in a treatment plan in which whole brain irradiation and whole spinal cord irradiation are performed simultaneously. The dosimeter affixed on the site | part which is going to produce a clearance gap between two irradiation bundle | flux for spinal cords in the treatment plan of irradiation is shown. FIG. 16 is a photograph showing a state when the dosimeter of Example 1 is attached from the temporal region to the lateral neck of the patient model. FIG. 17 is a photograph of the dosimeter 1 ′ that has been attached and irradiated with radiation as shown in FIG. 15 applied to a scanner (trade name: ES-10000G, manufactured by EPSON). Double arrows indicate gaps in the radiation bundle. FIG. 18 is a photograph showing a state when the gaffchromic is attached from the temporal region to the lateral neck of the patient model. It can be confirmed that there is a gap between the model surface and the gaff chromic in the side neck.

  The present invention relates to a sheet dosimeter comprising a gel composition that becomes clouded by irradiation and a transparent package that encloses the gel composition. Hereinafter, embodiments of the present invention will be specifically described.

1. Radiation sensitive gel composition The gel composition which comprises the dosimeter by this invention should just be cloudy by irradiation. Specifically, a composition in which a monomer polymerizable by irradiation with radiation is dispersed in a gel matrix can be given as a typical example.

  The monomer for obtaining the dosimeter of the present invention only needs to have a carbon-carbon unsaturated bond that can be polymerized by the action of radiation, and one or more kinds of various monomers can be selected depending on the use of the dosimeter. It can be included. However, (meth) acrylic monomers and (meth) acrylamide monomers are preferred in terms of high sensitivity. From the viewpoint of preventing the generated polymer from diffusing and moving in the gel matrix to prevent the white turbid region from changing, and increasing the radiation sensitivity of the dosimeter, a polymer having a crosslinked structure can be formed. Therefore, it is preferable to include a radiation polymerizable monomer (hereinafter referred to as a polyfunctional monomer) having two or more unsaturated bonds in one molecule.

(Meth) acrylic monomers include methyl (meth) acrylate, ethyl (meth) acrylate, 2-methoxymethyl (meth) acrylate, 2-ethoxyethyl (meth) acrylate, 2-hydroxyethyl (meth) acrylate, methyl ( (Meth) acrylate, ethyl (meth) acrylate, butyl (meth) acrylate, 2-methoxyethyl (meth) acrylate, 2-hydroxypropyl (meth) acrylate, methoxyethyl (meth) acrylate, ethoxyethyl (meth) acrylate, triethylene Monofunctional (meth) acrylic monomers such as glycol monomethyl ether mono (meth) acrylate, triethylene glycol monoethyl ether mono (meth) acrylate, and ethylene glycol di (meth) acrylate Relate: Diethylene glycol di (meth) acrylate, triethylene glycol di (meth) acrylate, tetraethylene glycol di (meth) acrylate, nonaethylene glycol di (meth) acrylate, tetradecaethylene glycol di (meth) acrylate, tricosaethylene glycol Polyethylene glycol di (meth) acrylate such as di (meth) acrylate; propylene glycol di (meth) acrylate; dipropylene glycol di (meth) acrylate, tripropylene glycol di (meth) acrylate, nonapropylene glycol di (meth) acrylate, etc. Polypropylene glycol di (meth) acrylate; 1,3-butanediol di (meth) acrylate, 1,4-butanediol di (meth) acrylate DOO, include polyfunctional (meth) acrylic monomers such as other di (meth) acrylates such as neopentyl glycol di (meth) acrylate and 1,6-hexanediol di (meth) acrylate.

  Examples of the (meth) acrylamide monomer include N-vinylpyrrolidone, (meth) acrylamide, N-isopropyl (meth) acrylamide, (meth) acryloyl-L-alanine methyl ester, (meth) acryloyl-L-proline. Monofunctional such as methyl ester, N-vinylpyrrolidone, (meth) acryloylmorpholine, N-hydroxymethyl (meth) acrylamide, N-hydroxyethyl (meth) acrylamide, N-methoxymethyl (meth) acrylamide, methylenebis (meth) acrylamide And polyfunctional (meth) acrylamide monomers such as N, N′-methylenebis (meth) acrylamide and N, N′-ethylenebis (meth) acrylamide.

Each of the above monomers can be used alone or in combination of two or more in the gel composition. However, because of its low toxicity and transparency, the marking on the patient's body surface should be confirmed during radiotherapy. In that it has the merit of being able to
2-hydroxyethyl (meth) acrylate, 2-hydroxypropyl (meth) acrylate, methoxyethyl (meth) acrylate, ethoxyethyl (meth) acrylate, triethylene glycol monomethyl ether mono (meth) acrylate, and triethylene glycol monoethyl ether A monofunctional (meth) acrylic monomer selected from the group consisting of mono (meth) acrylates;
A polyfunctional (meth) acrylic monomer selected from the group consisting of the above-mentioned polyethylene glycol di (meth) acrylates;
From N-vinylpyrrolidone (NVP), (meth) acryloylmorpholine, N-hydroxymethyl (meth) acrylamide, N-hydroxyethyl (meth) acrylamide, and N-methoxymethyl (meth) acrylamide, N-isopropylacrylamide (NIPAM) Monofunctional (meth) acrylamide monomers selected from the group consisting of: or the above-mentioned polyfunctional (meth) acrylamide monomers are preferred, and these monofunctional (meth) acrylamide monomers can be increased in white turbidity and sensitivity to radiation. A combination of at least one functional monomer and at least one multifunctional monomer is more preferable, and at least one of these monofunctional (meth) acrylic monomers and these multifunctional (meth) acrylic monomers Combination with at least one kind, or these monofunctionality A combination of at least one of the (meth) acrylamide monomers and at least one of these polyfunctional (meth) acrylamide monomers is more preferable.

As a combination of a monofunctional (meth) acrylic monomer and a polyfunctional (meth) acrylic monomer, 2-hydroxypropyl (meth) acrylate, methoxyethyl is more advantageous in terms of greater turbidity due to the polymer formed. A combination of any one selected from the group consisting of (meth) acrylate and ethoxyethyl (meth) acrylate and the above-described polyethylene glycol di (meth) acrylate is preferable, and 2-hydroxyethyl methacrylate and nonaethylene glycol di A combination with (meth) acrylate is particularly preferred.
In addition, as a combination of a monofunctional (meth) acrylamide monomer and a polyfunctional (meth) acrylamide monomer, N-methoxymethylmethacrylamide or N-isopropylacrylamide and N, N′- A combination with methylenebisacrylamide is preferred, and a combination of N-isopropylacrylamide and N, N′-methylenebisacrylamide is particularly preferred.

  In addition to or in place of the polyfunctional (meth) acrylic monomer, other divinyl compounds such as divinylbenzene may be contained, and in addition to or in place of the polyfunctional (meth) acrylamide monomer. An isocyanurate compound such as tri (3-butenoyloxyethyl) isocyanurate may be contained.

In the dosimeter of this invention, it is preferable to select 2 or more types from the monomer mentioned above according to the range of the radiation dose to measure, and to adjust the composition ratio. For example, in the case of measuring the radiation irradiation region and the radiation dose in the range of the radiation dose of about 0.1 to 40 Gy, preferably 0.1 to 20 Gy,
Selected from the group consisting of 2-hydroxyethyl methacrylate, 2-hydroxypropyl methacrylate, methoxyethyl methacrylate, ethoxyethyl methacrylate, triethylene glycol monomethyl ether monomethacrylate and triethylene glycol monoethyl ether monomethacrylate, preferably 2-hydroxyethyl methacrylate A monofunctional (meth) acrylic monomer selected from the group consisting of 2-hydroxypropyl methacrylate, methoxyethyl methacrylate and ethoxyethyl methacrylate, and polyethylene glycol di (meth) acrylate, preferably nonaethylene glycol dimethacrylate combination;
A monofunctional (meth) acrylamide monomer selected from the group consisting of N-vinylpyrrolidone, (meth) acryloylmorpholine, N-hydroxymethylacrylamide, N-hydroxyethylacrylamide and N-methoxymethylmethacrylamide, preferably A combination of N-isopropylacrylamide and N, N′-methylenebisacrylamide;
Selected from the group consisting of 2-hydroxyethyl methacrylate, 2-hydroxypropyl methacrylate, methoxyethyl methacrylate, ethoxyethyl methacrylate, triethylene glycol monomethyl ether monomethacrylate and triethylene glycol monoethyl ether monomethacrylate, preferably 2-hydroxyethyl methacrylate A combination of a monofunctional (meth) acrylic monomer selected from the group consisting of 2-hydroxypropyl methacrylate, methoxyethyl methacrylate and ethoxyethyl methacrylate with N, N′-methylenebisacrylamide; or
A monofunctional (meth) acrylamide monomer selected from the group consisting of N-vinylpyrrolidone, (meth) acryloylmorpholine, N-hydroxymethylacrylamide, N-hydroxyethylacrylamide and N-methoxymethylmethacrylamide, preferably It is preferred to select a combination of N-isopropylacrylamide and polyethylene glycol di (meth) acrylate, preferably nonaethylene glycol dimethacrylate.

In addition, by adjusting the composition ratio of the above-mentioned monofunctional monomer and polyfunctional monomer according to the range of radiation dose to be measured, a more sensitive dosimeter can be obtained or a wider range of radiation dose can be measured. A dosimeter.
For example, in a monomer composition combining 2-hydroxyethyl methacrylate (HEMA) and nonaethylene glycol dimethacrylate (9G), when measuring a low level (0.1-5 Gy) radiation dose, The weight ratio (9G / HEMA) is preferably 1 to 6, more preferably 1.5 to 5, still more preferably 2 or more, and still more preferably 3 or more. The above is particularly preferable. In order to maintain a relatively high sensitivity while maintaining the proportional relationship between the radiation dose and the white turbidity to some extent within a radiation dose range of 2 to 15 Gy, the weight ratio of the latter to the former (9G / HEMA) is 0. 0.1 to 3, preferably 1 to 2, more preferably 1.2 to 1.7, and particularly preferably 1.3 to 1.6. In order to maintain the proportional relationship between the radiation dose and the white turbidity within a radiation dose level exceeding 15 Gy, specifically in the range of 3 to 40 Gy, the weight ratio of the latter to the former (9 G / HEMA) Is preferably 0.01 to 1.7, more preferably 0.02 to 1.5, still more preferably 0.05 to 1.4, and more preferably 0.1 to 1.3. It is particularly preferred that

  Similarly, in the case of a monomer composition combining 2-hydroxypropyl methacrylate (HPMA) and nonaethylene glycol dimethacrylate (9G), when measuring radiation dose at a low level (0.1 to 3 Gy), the latter with respect to the former The weight ratio (9G / HPMA) is preferably 1 to 6, more preferably 1.1 to 5, still more preferably 1.2 or more, and 1.3 or more. Even more preferably, it is particularly preferably 1.5 or more. In addition, the weight ratio of the latter to the former (9 G / HPMA) is 0 from the point of maintaining the proportional relationship between the radiation dose and the white turbidity while maintaining a relatively high sensitivity in the radiation dose range of 2 to 15 Gy. .1 to 2, preferably 0.15 to 1.5, more preferably 0.18 to 1.0, and particularly preferably 0.2 to 0.8. preferable. In addition, the weight ratio of the latter to the former (9 G / HPMA) is 0.01 to 1 from the viewpoint of maintaining the proportional relationship between the radiation dose and the turbidity within a radiation dose range of 15 Gy or more, usually about 5 to 30 Gy. Preferably 0.02 to 0.8, more preferably 0.03 to 0.5, and particularly preferably 0.05 to 0.3.

  The monomer composition for producing the dosimeter of the present invention increases the radiation sensitivity, while avoiding unintentional polymerization due to the residual monomer after irradiation, in terms of the weight of the entire gel composition (in terms of solid content) On the other hand, it is preferable to set it as 0.1-30 weight% content (solid content conversion value), and it is more preferable to set it as 0.5-10 weight% content (solid content conversion value).

In the present invention, the gel matrix is not particularly limited as long as it is a gel capable of dispersing a monomer. It is highly biocompatible, transparent, and can be marked through the dosimeter with markings on the target surface when the dosimeter is installed.
Natural polymers such as gum, agar, agarose, gellan gum, xanthan gum, gelatin, karaya gum, carrageenan, cellulose and starch;
Lower alkyl group-substituted cellulose derivatives such as methylcellulose and ethylcellulose, lower alkoxyalkyl group-substituted cellulose derivatives such as carboxymethylcellulose, hydroxy lower alkyl group-substituted cellulose derivatives such as hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, and lower such as carboxymethylchitosan Polysaccharides such as alkoxyalkyl group-substituted chitosan derivatives, lower alkoxyalkyl group-substituted chitin derivatives such as carboxymethyl chitin, lower alkoxyalkyl group-substituted starch derivatives such as carboxymethyl starch, and lower alkoxyalkyl group-substituted carrageenan derivatives such as carboxymethyl carrageenan Derivatives;
Synthetic polymers such as polyethylene oxide, polyvinyl pyrrolidone, and polyvinyl alcohol; or compounds having a cross-linked structure formed by a covalent bond are preferable.
In addition, these molecular weights are 1,000-5,000,000 normally, Preferably they are 100,000-1,000,000.

  In this invention, it is preferable to select suitably the component and composition for forming a gel matrix according to the use and application site | part of a dosimeter. For example, when measuring the irradiation dose on the surface of an object with an uneven shape, such as when checking the radiation dose during irradiation of both breasts or whole spinal cord spinal cord, the dosimeter is the shape of the object to be measured. It is required to be deformed to conform to Thus, in such applications, the gel matrix with a gelling compound that can form a gel that makes the dosimeter easily deformable, such as polyvinyl alcohol, polyvinylpyrrolidone, methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, etc. It is preferable to constitute.

  Moreover, in the dosimeter of this invention, in order to raise the radiation sensitivity of a dosimeter and to make it deformable according to the shape of a measuring object, the gel matrix which can contain a monomer solution more than fixed is preferable. For this reason, the gel matrix for the dosimeter of the present invention usually has a degree of swelling of 1 to 200, preferably 5 to 100, more preferably 10 to 50, still more preferably 20 to 35.

Further, in the dosimeter of the present invention, it is possible to prevent a region clouded by irradiation from changing after irradiation, and in particular, a dosimeter used by installing on a body surface of a living body such as a person exceeds 35 degrees. It is important that the gel does not dissolve even at temperature to cause destruction or fluctuation of the cloudy part. From such a viewpoint, it is preferable that the gel matrix is composed of a compound in which a crosslinked structure by a covalent bond is introduced into the natural polymer, polysaccharide derivative and synthetic polymer described above.
Such chemical crosslinking may be introduced using a polymerization initiator such as azobisisobutyronitrile (AIBN), benzoyl peroxide (BPO), persulfate, etc., but no additional compound is required, A chemical cross-linked structure induced by radiation is preferable in that a gel having a uniform structure can be formed.

  A conventional general method may be used as the method of radiation crosslinking. Examples of radiation that induces a crosslinking reaction include α rays, β rays, γ rays, electron rays, X rays, and the like. From the viewpoint of industrial production, γ rays from a cobalt 60 ray source, electron rays from an accelerator. Is preferred.

  In the dosimeter of the present invention, a gel matrix having an appropriate degree of cross-linking is preferable in order to prevent the cloudy region formed by radiation irradiation from being destroyed or fluctuated by an external influence (for example, load or impact). For example, the gel fraction is preferably 30 to 99, more preferably 60 to 95. Similarly, the degree of swelling is preferably 1 to 200, more preferably 2 to 100, still more preferably 5 to 80, still more preferably 8 to 60, and 10 to 50. It is particularly preferred. The degree of cross-linking of the gel matrix can be changed by adjusting the radiation dose when, for example, inducing a cross-linking reaction by radiation, and it varies depending on the conditions such as the monomer composition, but usually at a dose of 1 to 200 kGy. The crosslinking reaction can be induced, and it is preferable to induce the crosslinking reaction at a dose of 5 to 100 kGy. If the irradiation dose is too small, formation of a crosslinked structure becomes insufficient, and the gel shape cannot be maintained in a swollen state. On the contrary, if the irradiation dose is too large, the cross-linking points become too dense and further the decomposition reaction proceeds, so that the gel becomes brittle.

In the gel composition of the present invention, an oxygen scavenger such as ascorbic acid or tetrakishydroxymethylphosphonium chloride (THPC) may be included in the solution (1) in order to prevent inhibition of the radiation polymerization reaction due to mixed oxygen. Moreover, in order to suppress the polymerization by the residual monomer after irradiation, a free radical scavenger such as hydroquinone or an ultraviolet absorber such as guaiazulene may be included.
Further, a coloring agent or the like may be included depending on the purpose of use.

Examples of the solvent contained in the gel matrix include water, an organic solvent such as ethanol, an aqueous inorganic salt solution, and the like, and water is preferable in terms of a bio-equivalent composition. In addition, the content of the solvent in the gel matrix varies depending on the type of gel. For example, when the gel is composed of a superabsorbent polymer such as hydroxypropylcellulose, the shape of the object on which the dosimeter is installed is set. A gel matrix containing 50 to 99.5% by weight of water is preferred in order to be deformable accordingly.
For example, Germatic uses a gelling compound in a solvent to form a paste, the paste is molded into a sheet, and a crosslinking reaction is induced by radiation or the like as necessary, and non-crosslinked substances are excluded as necessary. It can be prepared by post-drying.

2. Package In the dosimeter of the present invention, the package in which the gel composition is enclosed is preferably oxygen-barrier at least during radiation irradiation, usually after preparation of the dosimeter until radiation irradiation is completed. Thereby, it can avoid that the polymerization of the monomer by irradiation is prevented by the presence of oxygen.
Such oxygen barrier properties can be achieved in various configurations. For example, the package is composed of a single or multilayer film including at least an oxygen barrier layer, or the package is composed of a plurality of films independent of each other. The gel composition can be prevented from coming into contact with oxygen by constituting and providing at least one film with an oxygen barrier property.
Typical examples of the multilayer film include a film in which an oxygen permeable layer and an oxygen barrier layer are laminated, and a film in which an oxygen barrier material is deposited on an oxygen permeable layer. In such a laminated film, the oxygen permeable layer is usually located inside, and the oxygen barrier layer is provided so as to cover it.
Similarly, in a film composed of a plurality of mutually independent films, an oxygen permeable film is usually located inside and an oxygen barrier film is provided so as to cover it.

  In the dosimeter of the present invention, the gel composition only needs to be shielded from oxygen at the time of irradiation, usually from the preparation of the dosimeter to the end of irradiation, and it is not necessary to maintain the oxygen barrier state after irradiation. Rather, it is preferable that the gel composition be in contact with oxygen after irradiation. In the dosimeter having such a configuration, it is possible to avoid the polymerization of the monomer due to residual radicals after irradiation and fluctuation of the cloudiness area or increase in cloudiness, and the cloudiness area and cloudiness reflecting the radiation irradiation area. Can be stored for a long time.

  As such a dosimeter, for example, the package is composed of a film having an oxygen permeable layer and an oxygen barrier layer, and the oxygen barrier layer is detachably laminated, or the packages are independent of each other. A typical example is a dosimeter including an existing oxygen permeable film and an oxygen barrier film, wherein the oxygen permeable film is sealed with an oxygen barrier film. In the latter dosimeter, if an oxygen barrier film is opened with scissors or a knife, the film can be ventilated. However, it is convenient to provide an opening structure such as a cutting tape. Examples of the peelable oxygen barrier layer in the former dosimeter include, for example, an oxygen barrier layer that is detachably attached via an adhesive layer, and the adhesive layer is generally known. Things can be used.

  As another example of the embodiment in which the gel composition can be brought into contact with the outside air after irradiation, a package enclosing the gel composition is formed of an oxygen barrier film, and the gel composition is separated from the outside air after irradiation. A dosimeter provided with an opening structure that can be contacted can be mentioned. For example, a part of the package can be made of a breakable material or structure, a part of the package can be provided with an opening, and a structure that can be sealed with a removable lid, or a chuck, a zipper, etc. can be opened and closed at the end of the package By providing the structure, the gel composition can be brought into contact with the outside air after the radiation irradiation. Further, when an opening / closing structure such as a chuck or a zipper is provided, it is effective that an opening structure such as a cutting tape is further provided in that the package can be easily sealed.

  Examples of oxygen barrier materials include polyvinylidene chloride (PVDC) film, PVDC film such as laminate film obtained by laminating PVDC film on biaxially oriented polypropylene (OPP) film; polyvinyl alcohol (PVA) film, PVA film on OPP film PVA-based films such as laminate films laminated with; films made of other polymers such as ethylene vinyl alcohol copolymer (EVOH) films, EVOH films and nylon films, polyethylene films such as polyethylene and polypropylene, and polyethylene terephthalate (PET) films EVOH-based films such as laminates laminated with a film made of polyolefin such as nylon, polyethylene or polypropylene, silica, alumina, Laminated film coated with metal and inorganic materials such as crystalline carbon; or polyolefin film such as nylon film, polyethylene, polypropylene, etc .; polymer film such as polyethylene terephthalate (PET) film; reduced iron / sodium chloride, sodium sulfite, ascorbic acid And a film mixed with a substance having an action of absorbing oxygen by reacting with oxygen such as cobalt salt.

  In the dosimeter of the present invention, the marking on the patient's body surface can be confirmed with the dosimeter installed, and it is practically useful to be able to visually confirm the irradiation area with the dosimeter installed after radiation irradiation. In this respect, the oxygen barrier material is preferably an EVOH / PE laminated film, an EVOH / PE / nylon laminated film, a PET / silica vapor deposited film, a nylon / silica vapor deposited film, or the like. Moreover, also when setting it as the dosimeter which can be deform | transformed according to the shape of the installed place, it is preferable to comprise by EVOH / PE laminated film, EVOH / PE / nylon laminated film, etc.

  Examples of the oxygen permeable material include a transparent point, polyolefin (PO) such as low density or high density polyethylene (PE) and polypropylene (PP), nylon such as nylon 6 and nylon 66, polyethylene terephthalate (PET), Polycarbonate, ethylene-vinyl acetate copolymer and the like are preferable, and they are excellent in plasticity and can be made into a deformable dosimeter according to the concavo-convex shape. Therefore, low density or high density polyethylene (PE), polypropylene (PP Polyolefin (PO) such as), nylon such as nylon 6 and nylon 66, and the like are more preferable.

In the dosimeter of the present invention, the material constituting the package may contain an ultraviolet absorber or an ultraviolet absorbing film.
In the dosimeter of the present invention, the package enclosing the gel composition is preferably free from oxygen, and is preferably evacuated or filled with an inert gas such as nitrogen gas. When the package includes an oxygen permeable film and an oxygen barrier film that wraps the oxygen permeable film, the atmosphere between them is also evacuated or filled with an inert gas such as nitrogen gas so as not to contain oxygen. It is preferable.

3. Use of Dosimeter The dosimeter according to the present invention can be used to measure various types of radiation that can cause polymerization of monomers, such as carbon rays, alpha rays, deuteron rays, proton rays, and other heavy charged particles. It can be used for measurement of characteristic X-rays that are generated along with X-rays, β-rays, electron beams, neutron beams, X-rays, γ-rays and orbital electron capture.

  In addition, as described above, the dosimeter of the present invention can be adapted to the range of radiation dose to be measured by appropriately changing the monomer composition. As a typical application, an example in which a dose and an irradiation range are measured at the time of radiotherapy in which radiation such as gamma rays of about 1 to 20 Gy is irradiated at one time can be given.

  The dosimeter of the present invention is a dosimeter that can be easily deformed when the measurement site of the measurement target has an uneven shape, and is deformed according to the surface shape of the measurement site and is brought into close contact with the body surface of the target. At this time, the dosimeter may be more securely fixed to the measurement site by providing an adhesive layer on a part of the surface of the package.

The cloudy area after irradiation may be detected with the naked eye, but when measuring the dose more accurately, the cloudiness is measured by absorbance or optical density using an ultraviolet-visible spectrophotometer, etc. The dose may be determined from Moreover, the radiation irradiation area | region can also be specified by measuring the light absorbency or optical density of the whole gel of a dosimeter, or a fixed area | region. When measuring the absorbance or optical density of a dosimeter, it can be measured at a wavelength of 200 to 900 nm, but is preferably 380 to 780 nm in terms of a simple visible light range, and the absorbance or optical at a wavelength of 600 to 700 nm. It is more preferable to measure the concentration. In addition, using an image data conversion device such as a commercially available scanner (for example, EPSON ES-10000G), the dosimeter after irradiation is converted into image data. The turbidity can be converted into a numerical value, or can be graphically or graphed by various display methods. Also, obtain a function of white turbidity and dose based on the absorbance or optical density obtained when each dosimeter is irradiated with a known dose, and quantify the dose when actually irradiated based on this calibration curve. You can also.
In addition, when confirming that the planned irradiation area matches the actual irradiation area during radiotherapy, mark the planned irradiation area on the target body surface, and irradiate the dosimeter with radiation. You may make it closely_contact | adhere to the body surface of the area | region containing a plan site | part, and collate the marked site | part and a cloudiness area | region after irradiation.

  It is convenient that a scale is written on at least a part of the surface of the package in that the shape and size of the cloudy region and the positional relationship with the surrounding body part can be confirmed. Such a scale is preferably provided so as to surround the periphery of the region where the gel composition exists, as shown in FIG. The scale may be a scale or a grid.

After measuring the clouded area after irradiation, it is convenient to manage the dosimeter 1 of the present invention integrally with an information management tool 5 such as a medical chart as shown in FIG. 2A.
At this time, in order to integrate with the information management tool 5, for example, a means for fixing the dosimeter to the package or the information management tool may be provided. As such a fixing means, as shown in FIG. 2B, an adhesive layer 7 provided on at least a part of the surface of the package 6 or a part of the surface of the information management tool can be exemplified.
For example, the dosimeter package consists of a peelable oxygen barrier layer and a laminated film having an oxygen permeable layer, and an adhesive layer is provided on at least part of the surface of the oxygen permeable layer opposite to the oxygen barrier layer. An example of removing the oxygen barrier layer after irradiation and attaching a dosimeter to the diagnostic chart with the adhesive layer on the opposite side can be given. In such a dosimeter, the clouded area is stored for a long time, so if you look at the information management tool during the subsequent treatment, etc., you can visually confirm the radiation dose and area during the radiation treatment together with other information be able to.

  Absorbance or optical density data or image data obtained by measuring the dosimeter of the present invention is associated with body part information of a subject to be irradiated with radiation, and the irradiation position of the radiation irradiation apparatus is specified based on the information. Can be used. Moreover, it can collate with the irradiation plan site | part information of the object irradiated with radiation, and it can utilize in order to verify the shift | offset | difference with respect to the irradiation plan site | part of a radiation irradiation region.

  Therefore, in another embodiment of the present invention, an apparatus capable of measuring absorbance or optical density or converting it to image data for the entire dosimeter of the present invention or a certain area, and calculating an irradiation scheduled area and a planned dose of a radiation irradiation target. Calculate the radiation irradiation area and dose based on the treatment planning device, the absorbance or optical density or image data for the entire dosimeter or a certain area, and the position information of the dosimeter calculated by the position measuring device. It is possible to provide a radiotherapy control system including an irradiation scheduled area calculated by the treatment planning apparatus and a verification device for verifying the planned dose.

  In such a system, the collation device can feed back information on the difference between the radiation irradiation region and the dose to the irradiation planned region and the planned dose based on the collation result to the treatment planning device. Based on the fed back information, the irradiation planned area and the planned dose can be reconstructed. Therefore, the radiotherapy control system according to the present invention is combined with a radiotherapy apparatus, and the radiotherapy is performed by the radiotherapy apparatus on the basis of an instruction regarding an irradiation scheduled area and an expected dose from a confirmed or reconstructed therapy planning apparatus. A system can also be provided.

The radiotherapy control system according to the present invention may further include an output device and / or an image display device so that a collation result from the collation device can be output and / or displayed.
In the treatment planning device, the irradiation planned area and the planned dose are calculated based on the appearance shape and size of the radiation irradiation target, the data on the irradiation target including the treatment site and the information on the radiation scheduled to be used. It can be calculated based on CT data or MRI data of the irradiation target. In addition, the positional information for identifying the location where the dosimeter is installed is, for example, a marker that can be recognized by CT images or the like is installed in advance on the site where the dosimeter to be irradiated is to be installed, and a CT scan or the like is performed. It is obtained by converting it into data together with data related to the irradiation target. At this time, place a visible mark on the part with an oily magic etc., and when installing a dosimeter at the time of treatment, install the dosimeter while looking through this mark, and information on the installation position and the actual The installation position can be matched. Examples of the image data conversion device include an optical scanner and a digital camera.

  As described above, the dosimeter according to the present invention can be typically used when measuring the irradiation area and dose of the irradiation target when performing radiotherapy, but is not limited thereto. It can be used for various applications such as an indicator for confirming whether radiation sterilization has been performed.

  Hereinafter, the present invention will be described in more detail with reference to examples. However, the present invention is not limited to the following examples.

1. Preparation of Gel Matrix Material Pure water was added to hydroxypropylcellulose (hereinafter abbreviated as HPC, grade 1000-5000 cP, manufactured by Wako Pure Chemical Industries, Ltd.) to prepare a 20 wt% HPC paste. The paste was sandwiched between PET films and pressed to form a sheet having a thickness of 1 mm, and then placed in a polyethylene-nylon bag, deaerated and sealed. An HPC gel was prepared by irradiating the enclosed HPC with an electron beam with a dose of 10 kGy to induce a crosslinking reaction. The electron beam irradiation was performed using a Cockcroft-Walton type 2 MeV electron beam accelerator installed at the Takasaki Quantum Applied Research Laboratory, Japan Atomic Energy Agency. The obtained HPC gel was immersed in an excessive amount of distilled water to remove non-crosslinked HPC, and then vacuum dried to prepare a gel matrix material.

2. Preparation of gel composition <Preparation Example 1>
A monomer comprising 1% by weight of 2-hydroxyethyl methacrylate (HEMA), 4% by weight of nonaethylene glycol dimethacrylate (9G), and 0.16% by weight of tetrakishydroxymethylphosphonium chloride (THPC). A gel composition was prepared by immersing in an aqueous solution and impregnating the monomer into each gel (hereinafter referred to as gel composition 1).

<Preparation Example 2-18>
A gel composition was prepared in the same manner as in Preparation Example 1 except that the monomer aqueous solution having the composition shown in the following table was used (hereinafter referred to as gel composition 2-18).

* Numerical values in the table indicate parts by weight.
Abbreviations in the table are as follows.
HEMA: 2-hydroxyethyl methacrylate
HPMA: 2-hydroxypropyl methacrylate
MEMA: Methoxyethyl methacrylate
EEMA: Ethoxyethyl methacrylate
TGMEMA: Triethylene glycol monomethyl ether monomethacrylate
NVP: N-vinylpyrrolidone
MMMAAm: N-methoxymethyl methacrylamide
HMAAm: N-hydroxymethylacrylamide
NIPAAm: N-isopropylacrylamide
AAm: Acrylamide
9G: Nonaethylene glycol dimethacrylate
MBAAm: N, N'-methylenebisacrylamide
THPC: Tetrakishydroxymethylphosphonium chloride
HPC: Hydroxypropylcellulose
MC: Methylcellulose
PVA: Polyvinyl alcohol

3. Preparation of dosimeters <Examples 1 to 18>
Gel compositions 1 to 18 are made of an ethylene-vinyl alcohol copolymer (EVOH) film (trade name: Bijin, manufactured by Krillon Kasei Co., Ltd., oxygen barrier film / oxygen permeability: 4.8 cm ³ / m ² · 24h · atm), degassed and sealed to create a dosimeter.

<Comparative Example 1>
Gel composition 1 is put into a package made of polyethylene (PE) (oxygen permeable film / oxygen permeability: 2900 cm ³ / m ² · 24h · atm) film, degassed and sealed to create a dosimeter did.

<Comparative example 2>
Gel composition 1 is put in a package made of PE / nylon film (trade name: Hiryu, oxygen permeable film / oxygen permeability: 45 cm ³ / m ² · 24h · atm), deaerated and sealed. A dosimeter was created.

<Example 19>
The gel composition 1 is put into a package made of a PE / nylon film (oxygen permeable film) described in Comparative Example 2, deaerated, sealed, and further an EVOH film (oxygen) having a peelable adhesive layer. A dosimeter was prepared by adhering a barrier film to the entire package.

<Example 20>
The gel composition 1 is put into a package made of PE / nylon film (oxygen permeable film) described in Comparative Example 2, deaerated and sealed, and further a second package made of EVOH film (oxygen barrier film). The dosimeter was made by degassing and sealing.

4). Evaluation of gel matrix material, gel composition, and dosimeter <gel fraction and swelling degree>
The gel fraction of the gel matrix material and the degree of swelling of the gel compositions 1-16 were measured.

  The gel fraction was determined from the ratio between the weight of the HPC charged in preparing the gel matrix material and the weight of the gel matrix material after removing the non-crosslinked HPC and vacuum drying.

The degree of swelling is the weight of the aqueous monomer solution that can be held by 1 g of the gel matrix material, and was determined by the following equation.
Swelling degree = (Ws−Wd) / Wd
(Ws represents the weight of the gel composition after being immersed in the monomer aqueous solution, and Wd represents the weight of the gel matrix material after vacuum drying).

The gel fraction of the gel matrix material (crosslinked with 10 kGy irradiation) was 76%.
The degree of swelling of each gel composition is shown in Table 2 below.

As described above, there was no change depending on the type of monomer, and it was 26 ± 1.

<Opacity of each dosimeter>
The dosimeters obtained in Examples 1 to 18 were irradiated with 10 Gy of γ rays using ⁶⁰ Co as a radiation source, and the state of the dosimeter after irradiation was confirmed with the naked eye. The dosimeter was placed in an aluminum bag immediately after preparation and stored refrigerated, taken out 30 minutes before radiation irradiation, returned to room temperature, and used for the test (the same applies to the following tests). The results are shown in FIG. Although there was a difference in the degree of cloudiness, it was possible to confirm the cloudiness sufficiently discriminable by visual observation with any dosimeter.

<Effect of monomer composition on radiation dose measurement range>
About the dosimeters obtained in Examples 1 to 5 and 7, using gamma rays with ⁶⁰ Co as a radiation source, gamma rays are irradiated in the range of 0.5 to 20 Gy, and the influence of the monomer composition on the radiation measurement range investigated. The measurement results are shown in FIG.

Regarding the dosimeter of the monomer composition combining HEMA and 9G, as shown in FIG. 4, in the dosimeter of Example 1 where HEMA: 9G = 1: 4, the rise at the low dose is the earliest and the dose is from 0 to 5 Gy. The turbidity increased in proportion, but then reached a peak. In the dosimeter of Example 2 in which HEMA: 9G = 2: 3, the turbidity increased almost in proportion to the dose from 0 to 10 Gy with the next fastest rise at a low dose. The dosimeters of Examples 3 and 4 with HEMA: 9G = 3: 2 and HEMA: 9G = 4: 1, respectively, have a slow rise at a low dose, but the turbidity increases in proportion to the dose from 0 to 15 Gy. did.
Therefore, in a dosimeter having a monomer composition combining HEMA and 9G, in order to detect low-dose radiation with high sensitivity, a high-sensitivity dosimeter can be produced by increasing the content of 9G. In particular, HEMA: 9G = 1: 4, a highly sensitive dosimeter was obtained, and it was found that the measurement range could be widened by increasing the HEMA content ratio to a ratio of HEMA: 9G = 2: 3 or higher. FIG. 5 shows the relationship between the content of 9G and the radiation sensitivity in a dosimeter with a monomer composition combining HEMA and 9G.

Regarding the dosimeter of the monomer composition combining HPMA and 9G, as shown in FIG. 4, in the dosimeter of Example 5 in which the monomer composition is HPMA: 9G = 1: 4, the rise at a low dose is quickly 0 to 5 Gy. The turbidity increased almost in proportion to the dose, but then reached a peak. In addition, it was found that the absorbance at the same dose is higher and the sensitivity is higher than the dosimeter of Example 1 in which HEMA and 9G are combined at the same ratio. In addition, as shown in FIG. 5, the dosimeter having a monomer composition combining HPMA and 9G has a sensitivity higher than that of the dosimeter of Example 2 where HEMA: 9G = 2: 3 even when HPMA: 9G = 4: 1. Even if the ratio between HPMA and 9G was changed, a highly sensitive dosimeter could be obtained. Therefore, a dosimeter having a monomer composition combining HPMA and 9G is particularly preferable for measuring low-dose radiation. Specifically, it is preferable for measuring radiation in a measurement range of 0.1 to 5 Gy. It has been found that it is more preferable to measure radiation in a measurement range of 1 to 3 Gy.
A similar tendency was observed in a dosimeter having a monomer composition combining MEMA and 9G.

<Influence of radiation species>
About the dosimeter obtained in Example 20, the carbon beam and iron wire which are heavy charged particle beams were irradiated, and white turbidity was investigated. The carbon and iron wires were irradiated using a heavy ion beam cancer treatment apparatus (HIMAC) of the National Institute of Radiological Sciences. As a result, with any heavy particle beam irradiation, an increase in the degree of white turbidity was observed with increasing dose. The dosimeter after irradiation is shown in FIG.

<Influence on white turbidity due to differences in packaging film>
The dosimeters obtained in Examples 19 and 20 and Comparative Example 1 were irradiated with 2 Gy of γ rays from cobalt 60, and the turbidity was observed. The test results are shown in FIG.

  As shown in FIG. 7C, the dosimeter of Comparative Example 1 in which the gel composition was enclosed in an oxygen permeable package did not become clouded by irradiation. On the other hand, as shown in FIGS. 7A and 7B, the dosimeter of Example 19 in which the gel composition was sealed in a package in which the oxygen barrier film was attached to the entire oxygen permeable film, and the polymer gel in the package made of the oxygen permeable film. In the dosimeter of Example 20, which was sealed and sealed with a package made of an oxygen barrier film, it became cloudy. In addition, in the dosimeters of the examples and comparative examples produced this time, both contained an oxygen scavenger in the gel composition, but in the dosimeter of the comparative example in which the polymer gel was sealed in the package of the oxygen permeable film, It turned out that it did not become cloudy at all, and it was difficult to use it as a dosimeter by simply adding an oxygen scavenger.

<Effect of turbidity on storage stability due to differences in packaging film>
The dosimeters obtained in Examples 19 and 20 were irradiated with 2 Gy of gamma rays from cobalt 60, and after the irradiation, the dosimeter of Example 19 peeled off the oxygen barrier layer, and the dosimeter of Example 20 The package was opened and the package enclosing the polymer gel was taken out and left in the atmosphere at room temperature for 60 days, and the change in the cloudy region was observed. The results are shown in FIGS. 8A and B.

  As shown in FIGS. 8A and B, the dosimeters obtained in Examples 19 and 20 are both preserved even after 60 days have passed since the white turbidity immediately after irradiation shown in FIGS. 7A and B. It was.

<Effect 2 on storability of turbidity due to difference in packaging film>
The dosimeter obtained in Example 20 was irradiated with X-rays at 5 Gy, and after irradiation, the second package was left as it was without being opened, and the change over time in the cloudy region was observed. The results are shown in FIGS. 9A and B.

  As shown in FIG. 9A, it was slightly cloudy at the time when 1 hour passed from the irradiation, but as shown in FIG. 9B, the degree of cloudiness increased after 24 hours.

5. Example of use of dosimeter of the present invention 5-1. Use in patients undergoing radiation therapy to both breasts after bilateral breast-conserving surgery After breast-conserving surgery for breast cancer, radiation therapy to the breast is the standard treatment to prevent recurrence. For example, after performing bilateral breast preservation in a patient with bilateral breast cancer, radiation is often applied to the bilateral breasts based on a treatment plan as shown in FIG. At this time, if the radiation bundles targeting the left and right breasts overlap on the patient's front chest, a local high dose may be generated at the same site, which may cause skin ulcers and necrosis. In actual treatment, breasts and sagging skin may not always follow the irradiation plan, and it is important to confirm that there is no actual overlap of radiation bundles.

  Therefore, first, as shown in FIG. 11, the dosimeter obtained in Example 1 was affixed to the front chest of the patient model to confirm the installation state. Next, in the same state, X-rays from the accelerator were irradiated to the dose line according to the irradiation plan shown in FIG. Further, after irradiation, the second package was opened, and the change over time in the cloudiness region of the dosimeter was observed. As a comparison object, a similar test was performed using a gaphromic film (registered trademark, manufactured by ISP), which is a sheet-like dosimeter currently on the market.

As shown in FIG. 11, in the dosimeter of Example 1, it can be arranged to fit the shape of the body surface of a patient model having an uneven portion, and there is no overlap of irradiation as shown in FIG. 12. I was able to confirm. Moreover, as shown in FIG. 13, the change was not recognized by the cloudiness area | region by the dosimeter 1 hour after irradiation, and the dosimeter after 260-hour progress.
On the other hand, as shown in FIG. 14, it is difficult to accurately place the irradiation overlap in the concave portion in the gaphromomic film, because it cannot be placed in the shape of the patient's body surface.

5-2. Use in patients undergoing whole-brain whole spinal irradiation Patients with brain tumors such as medulloblastoma receive whole-brain irradiation and / or whole spinal cord irradiation as radiation therapy. If radiation overlaps at the spinal cord at this time, the radiation below the tolerable dose to the spinal cord may cause complete paralysis of nerves below that site. In actual treatment, in order to irradiate uniformly on the spinal surface, an irradiation plan is made so that a slight gap is formed on the body surface in consideration of the property that the radiation spreads conically. However, in the actual treatment, there is a case where the gap is not necessarily formed according to the irradiation plan, and it is important to confirm whether the gap is actually formed on the body surface according to the treatment plan.

Therefore, first, the dosimeter obtained in Example 1 was attached from the temporal region to the lateral neck of the patient model, and the installation status was confirmed. As a comparison object, a similar test was performed using a gaphromic film (registered trademark, manufactured by ISP), which is a sheet-like dosimeter currently on the market.
As shown in FIG. 16, in the dosimeter obtained in Example 1, it was possible to arrange the dosimeter with a perfect fit to the shape of the patient's body surface having an uneven portion. On the other hand, as shown in FIG. 18, in the gaphromomic film, it was not possible to arrange it with a perfect fit to the shape of the patient's body surface, and a gap was formed between the patient model surface and the film.

  Next, as shown in FIG. 15, the dosimeter 1 ′ obtained in Example 1 is attached to a site where a gap is to be created between two irradiation bundles for spinal cord in a treatment plan for whole spinal cord irradiation, and then from the accelerator. X-rays were irradiated, and it was confirmed that there was actually no overlapping of radiation bundles on the body surface. As shown in FIG. 17, it was confirmed that there was no overlap of irradiation.

As described above, the dosimeter of the present invention is effective for easily and accurately measuring the radiation dose and irradiation area during radiotherapy, and according to a preferred embodiment of the present invention, it is particularly useful for measurement at uneven portions. It is. However, the dosimeter according to the present invention can be applied to other than the measurement at the time of radiotherapy, and the design can be appropriately modified according to the monitoring of the radiation in various situations.

Claims (27)

A sheet-shaped dosimeter comprising a radiation-sensitive gel composition containing a monomer polymerizable by radiation irradiation and a gel matrix in which the monomer is dispersed, and a transparent package enclosing the gel composition,
The package is characterized that you have configured to Ri oxygen barrier property der at least irradiation, and the radiation-sensitive gel composition after radiation irradiation becomes possible contact with the outside air, dosimeter.   The dosimeter according to claim 1, wherein the package is made of a multilayer film including a transparent oxygen-permeable layer and a transparent oxygen barrier layer covering the transparent oxygen-permeable layer.   The dosimeter according to claim 2, wherein the oxygen barrier layer is laminated on the oxygen permeable layer in a peelable state.   The dosimeter according to claim 1, wherein the package includes an oxygen-permeable film and an oxygen-barrier film that exist independently of each other, and the oxygen-barrier film surrounds the oxygen-permeable film. It said oxygen burr Africa Irumu has a structure that allows the outside air introduction into the inside of the oxygen barrier film dosimeter according to claim 4.   The dosimeter according to claim 1, wherein the package is made of an oxygen barrier material and has a structure that allows introduction of outside air into the package.   The dosimeter according to any one of claims 1 to 6, wherein the dosimeter can be deformed in conformity with the uneven shape of the installation target. It is a dosimeter for measuring a radiation dose of 0.1 to 20 Gy, and the monomer is 2-hydroxyethyl (meth) acrylate, 2-hydroxypropyl (meth) acrylate, methoxyethyl (meth) acrylate, ethoxyethyl ( A monofunctional (meth) acrylic monomer selected from the group consisting of (meth) acrylate, triethylene glycol monomethyl ether mono (meth) acrylate and triethylene glycol monoethyl ether mono (meth) acrylate, and polyethylene glycol di (meth) ) In combination with acrylates;
N-vinylpyrrolidone, (meth) acrylamide, N-isopropyl (meth) acrylamide, (meth) acryloylmorpholine, N-hydroxymethyl (meth) acrylamide, N-hydroxyethyl (meth) acrylamide and N-methoxymethyl (meth) acrylamide A combination of a monofunctional (meth) acrylamide monomer selected from the group consisting of and N, N′-methylenebis (meth) acrylamide;
2-hydroxyethyl (meth) acrylate, 2-hydroxypropyl (meth) acrylate, methoxyethyl (meth) acrylate, ethoxyethyl (meth) acrylate, triethylene glycol monomethyl ether mono (meth) acrylate and triethylene glycol monoethyl ether mono A combination of a monofunctional methacrylic monomer selected from the group consisting of (meth) acrylates and N, N′-methylenebis (meth) acrylamide; or
The group consisting of N-vinylpyrrolidone, (meth) acrylamide, N-isopropyl (meth) acrylamide, acryloylmorpholine, N-hydroxymethyl (meth) acrylamide, N-hydroxyethyl (meth) acrylamide and N-methoxymethyl (meth) acrylamide The dosimeter of any one of Claim 1 to 7 including the combination of the monofunctional (meth) acrylamide type monomer selected from these, and polyethyleneglycol di (meth) acrylate. The dosimeter for measuring a dose of 0.1 to 5 Gy, wherein the monomer includes a combination of methoxyethyl methacrylate (MEMA) and nonaethylene glycol dimethacrylate (9G). The dosimeter according to item 1. A dosimeter for measuring a dose of 0.1 to 3 Gy, wherein the monomer contains a combination of 2-hydroxypropyl methacrylate (HPMA) and nonaethylene glycol dimethacrylate (9G) The dosimeter according to any one of claims 1 to 8 , wherein a weight ratio (9G / HPMA) of nonaethylene glycol dimethacrylate is 1.1 to 5 . A dosimeter for measuring a dose of 2 to 15 Gy, wherein the monomer includes a combination of 2-hydroxypropyl methacrylate (HPMA) and nonaethylene glycol dimethacrylate (9G), and nonaethylene for 2-hydroxypropyl methacrylate The dosimeter according to any one of claims 1 to 8 , wherein a weight ratio (9G / HPMA) of glycol dimethacrylate is 0.18 to 1.0. The gel matrix is
A natural polymer selected from the group consisting of agar, agarose, gellan gum, xanthan gum, gelatin, karaya gum, carrageenan, cellulose and starch;
Lower alkyl group substituted cellulose derivatives, lower alkoxyalkyl group substituted cellulose derivatives, hydroxy lower alkyl group substituted cellulose derivatives, lower alkoxyalkyl group substituted chitosan derivatives, lower alkoxyalkyl group substituted chitin derivatives, lower alkoxyalkyl group substituted starch derivatives, and lower alkoxyalkyls A polysaccharide derivative selected from the group consisting of group-substituted carrageenan derivatives;
A synthetic polymer selected from the group consisting of polyethylene oxide, polyvinyl pyrrolidone and polyvinyl alcohol; and at least one compound selected from the group consisting of compounds having a cross-linked structure formed by a covalent bond. Item 12. The dosimeter according to any one of Items 1 to 11 . The dosimeter according to any one of claims 1 to 12, wherein the radiation-sensitive gel composition contains an oxygen scavenger .   The dosimeter of any one of Claims 1-13 provided with the adhesion layer in at least one part of the surface of the said package.   The dosimeter according to any one of claims 1 to 12, wherein a scale is marked on at least a part of the package.   A means for managing information including radiation dose, comprising the dosimeter according to any one of claims 1 to 15. The dosimeter according to any one of claims 7 to 16, wherein the dosimeter is deformed according to a surface shape of a measurement object and is closely adhered to the surface of the object,
Next, irradiate an area including at least a part of the area where the dosimeter is installed,
Measuring the area of cloudiness and / or the degree of cloudiness of the irradiated dosimeter,
Radiation measurement method.   Marking the irradiation target site on the surface of the object, bringing the dosimeter into close contact with the target surface in the region including the irradiation target site, and collating the marked site with the cloudy region after the irradiation The method of claim 17, comprising:   The method according to claim 17 or 18, wherein the measurement of the cloudy area and / or the degree of cloudiness is performed with the naked eye, or using an apparatus or an image data conversion apparatus capable of measuring absorbance or optical density.   An information management method in which the dosimeter according to any one of claims 1 to 15 is integrated with means for managing information including radiation dose after irradiation.   A simple radiation measurement system comprising: the dosimeter according to any one of claims 1 to 15; and a device capable of measuring absorbance or optical density or a device capable of converting into image data for the whole or a certain region of the dosimeter. . A device capable of measuring absorbance or optical density for the whole or a partial region of the dosimeter according to any one of claims 1 to 15, or a device capable of converting the region into image data,
A treatment planning device for calculating an irradiation scheduled area and a planned dose of a radiation irradiation target;
Based on the absorbance or optical density or image data of the whole or a part of the dosimeter and the position information of the place where the dosimeter is installed, the radiation irradiation region and the dose are calculated, and these are calculated as the irradiation planned region and the irradiation region. A radiotherapy control system comprising a collation device for collating with a planned dose.   The system according to claim 22, wherein the collation device feeds back information related to the collation result to the treatment planning device.   The system according to claim 22 or 23, further comprising an output device and / or an image display device, wherein the result of the collation can be output and / or displayed.   The said irradiation scheduled area | region and the said scheduled dose are calculated based on the information regarding the irradiation object including the external appearance shape of the said irradiation object, a magnitude | size, and a treatment site | part, and the information regarding the radiation to be used. The system according to item 1.   26. The system according to claim 25, wherein the information regarding the irradiation target or the position information specifying the place where the dosimeter is installed is calculated based on CT data or MRI data of the radiation irradiation target. A radiation therapy system comprising: the system according to any one of claims 22 to 26; and a therapy device that performs radiation irradiation based on an instruction from the therapy planning device.