WO2017101130A1

WO2017101130A1 - New type of three-dimensional gel dosimetry material, and method for preparation thereof

Info

Publication number: WO2017101130A1
Application number: PCT/CN2015/098082
Authority: WO
Inventors: 文万信; 杨韬; 刘汉洲; 闫思齐
Original assignee: 苏州大学张家港工业技术研究院
Priority date: 2015-12-15
Filing date: 2015-12-21
Publication date: 2017-06-22
Also published as: CN105440188B; CN105440188A

Abstract

Disclosed are a new type of three-dimensional gel dosimetry material, and a method for preparation thereof; the three-dimensional gel dosimetry material is used to calculate dosage information according to the intensity of light emitted by quantum dots uniformly distributed in the hydrogel, preventing the problem of Fricke gel dosimetry ion-concentration diffusion; the raw materials required for synthesis of the new type of three-dimensional gel dosimetry material are simple, it is unnecessary to isolate oxygen from the environment, high temperature is not required, synthesis is easy, and high-volume production is convenient; during the process of synthesis, harmful gases are not generated, and harm to the environment is small; the physical and chemical stability of the obtained material is good, and the material is not prone to oxidation, is easy to store, and is convenient to use multiple times. The method for preparing the new type of three-dimensional gel dosimetry material uses radiation crosslinking, implementation is simple and easy, the period of preparation is short, and the new type of three-dimensional dosimetry material prepared using the method is pure and does not contain impurities.

Description

Novel three-dimensional gel dosimeter material and preparation method thereof

The present application claims priority from Chinese Patent Application No. 201510932342.1, filed on Dec. 16, 2015, entitled "A New Type of Three-Dimensional Gel Dosimeter Material and Its Preparation Method", the entire contents of which are incorporated by reference. Combined in this application.

Technical field

The invention relates to the technical field of medical polymer materials, in particular to a novel three-dimensional gel dosimeter material and a preparation method thereof.

Background technique

As one of the main methods of cancer treatment, radiotherapy technology has been developing in the direction of precise radiotherapy in recent years. The International Radiation Unit and Measurement Committee (ICRU) Report No. 24 and Report No. 42 describe the accuracy of radiotherapy dose. Degree, must be within 5%, in order to achieve effective treatment, while reducing the occurrence of complications, to maximize the benefits of irradiation. To achieve these goals, the radiotherapy plan needs to pass quality assurance (QA) measures. There is no uniform standard process for performing dose verification. There have been ionization chamber methods, semiconductor methods, electronic field imaging devices (EPID) and gel dosimeters.

The gel dosimeter is a new type of three-dimensional dosimeter. The gel acts as a support for the spatial structure, and the radiation-sensitive substance is evenly distributed in the gel. The density of the entire system is similar to that of the human body, eliminating the need for density correction. Therefore, the gel dosimeter can be used for the measurement of the three-dimensional dose distribution of the human body, and the spatial resolution is high, the dose is accurate, and the tissue equivalence is good.

Gel dosimeters were first proposed by Gore et al in 1984 and have developed a series of gel dosimeters. The gel dosimeter has good tissue equivalence, and can achieve the spatial resolution of detection ≤1mm ³ , complete the whole detection time ≤1 hour, the precision is 1-2%, and the dose accuracy is 2-4%. According to the physical mechanism of light attenuation, it can be divided into two types: light absorption type and light scattering type.

The light absorption type is typically a Fricke gel, based on the principle that Fe ²⁺ is quantitatively oxidized to Fe ³⁺ after being irradiated, and a color change occurs to cause a shift in the dose absorption line of the dosing agent. Method steps: agarose, gelatin, etc. are added to 75% deionized water, magnetically stirred and heated to fully dissolve; ammonium ferrous sulfate, sulfuric acid is added to 25% deionized water, magnetically stirred, heated, and previously configured The gel solution is mixed to maintain a short high temperature, and magnetic stirring ensures that the two solutions are uniformly mixed; stopping the heating causes the gel to solidify.

The light scattering type mainly relies on radiation polymerization. After the dosimeter is irradiated, the monomer undergoes polymerization reaction. After the macromolecule is formed, the scattering index changes, and the dose distribution information is derived. Method steps: deionized water 89%, gelatin 5%, acrylamide 3%, crosslinker 3%, oxygen scavenger 10 mmol / L. Add gelatin to deionized water, heat it with a magnetic stirrer (43 degrees Celsius) and stir to completely dissolve it; keep the temperature, add cross-linking agent, stir magnetically for 15 minutes; keep the temperature, add acrylamide to stir until transparent; keep the temperature, add The oxygen scavenger was magnetically stirred for 25 minutes; the prepared sample was placed in a mold and sealed for use.

Existing gel dosimeters such as Fricke gel dosimeters, Fe ²⁺ is easily oxidized by oxygen to Fe ³⁺ , the preparation and storage conditions are harsh, not suitable for long-term preservation, the dose information carrier Fe ^{3+ is} easily diffused, gradient information Will be lost in a short time, time and temperature stability is poor, not suitable for long-term preservation, the cost of use is too high, only for one-time use; polymer gel dosimeter relies on the scattering effect to detect, while the scattering signal will also be on the detector Adjacent elements of the array cause interference, which reduces the accuracy and accuracy of dose detection; some gels, such as PAGAT gels, are prone to deformation at higher temperatures and also lose spatial distribution information of the dose.

In view of the above, the designer actively researches and innovates, in order to create a new three-dimensional gel dosimeter material and its preparation method, so that it has more industrial value.

Summary of the invention

In order to solve the above technical problems, the object of the present invention is to provide a novel three-dimensional gel dosimeter material which is easy to store, is not easily oxidized, can save cost, can be reused, has good stability, and can obtain accurate dose space distribution information. And its preparation method.

The invention provides a novel three-dimensional gel dosimeter material, comprising: a hydrogel, wherein the hydrogel is doped with quantum dots, and the monomer of the hydrogel is acrylic acid, acrylamide, acrylate One or more of the three, the quantum dots being cadmium compound semiconductor nanoparticles.

The invention provides a novel method for preparing a three-dimensional gel dosimeter material, which comprises the following steps:

Step (1) adding a certain volume ratio of deionized water and isopropanol to the irradiation tube, and uniformly mixing to obtain a "1#" solution;

Step (2) adding a certain amount of hydrogel monomer to the "1#" solution, and uniformly stirring to obtain a "2#" solution;

Step (3) adding a certain amount of cadmium chloride and sodium thiosulfate in the "2#" solution, and uniformly stirring to obtain a "3#" solution;

Step (4) introducing a nitrogen gas in the "3#" solution, sealing the irradiation tube, and then irradiating through a cobalt source or an electron beam to obtain a novel three-dimensional dose gel material sample;

Step (5) to clean the new three-dimensional dose gel material sample, and finally obtain a pure new three-dimensional dose gel material.

Further, the volume ratio of isopropyl alcohol to deionized water in the "1#" solution described in the step (1) ranges from 1:10 to 1:100.

Further, the hydrogel monomer in the step (2) is one or more of acrylic acid, acrylamide and acrylate.

Further, the concentration of cadmium chloride in the "3#" solution described in the step (3) is 0.0001 mol/L to 0.01 mol/L.

Further, the concentration ratio of cadmium chloride to sodium thiosulfate in the "3#" solution described in the step (3) ranges from 1:1 to 1:2.5.

Further, the dose of the irradiation in the step (4) is 20 kGy-100 kGy.

Further, the time for discharging oxygen through the nitrogen gas in the step (5) is 20 minutes.

By the above scheme, the present invention has at least the following advantages: a novel three-dimensional gel dosimeter material proposed by the present invention calculates dose information based on the luminous intensity of quantum dots uniformly dispersed in a hydrogel, avoiding Fricke gel. The ion concentration diffusion problem of the dosimeter; the new three-dimensional gel dosimeter material synthesis material is simple, and does not need to isolate oxygen in the environment, does not need high temperature, is easy to synthesize, and is convenient for mass production; no harmful gas is generated during the synthesis process, The environmental hazard is small; the obtained material has good physical and chemical stability, is not easily oxidized, is easy to store, and is convenient for multiple use.

The invention adopts the preparation method of radiation crosslinking, has simple operation and short preparation period, and the novel three-dimensional dosimeter material prepared by the method is pure and free of impurities.

A novel three-dimensional gel dosimeter material is synthesized by the method of the present invention. The addition of quantum dots, also known as semiconductor nanoparticles, in polymer hydrogels has quantum size effects, surface effects, dielectric confinement effects, and good light stability. The fluorescence generated by excitation is strongly dependent on the size of quantum dots and can be widely used in cell labeling, in vivo imaging, and clinical diagnosis. Broken. It has been found that the quantum dots of Group II-VI elements are water-soluble, and the yield is high. The quantum dots containing cadmium (element symbol: Cd) have strong luminescence intensity. CdX, X is S, Se, Te, etc., and quantum dots will exhibit different colors due to different sizes. The quantum dots in the novel three-dimensional gel dosimeter material synthesized by the invention are excited by different intensity radiation to generate fluorescence with different intensities, and the fluorescence signals generated by the CCD camera are detected to reconstruct the three-dimensional distribution information of the dose.

The above description is only an overview of the technical solutions of the present invention, and the technical means of the present invention can be more clearly understood and implemented in accordance with the contents of the specification. Hereinafter, the preferred embodiments of the present invention will be described in detail below.

detailed description

The specific embodiments of the present invention are further described in detail below with reference to the embodiments. The following examples are intended to illustrate the invention but are not intended to limit the scope of the invention.

Embodiment 1:

Step (1), adding 5 mL of isopropanol and 65 mL of deionized water (volume ratio 1:13) to the irradiation tube, and uniformly mixing to obtain a "1#" solution;

Step (2), adding 30 mL of acrylic acid to the "1#" solution, and uniformly stirring to obtain a "2#" solution;

Step (3), adding 0.0001 mol of cadmium chloride and 0.0002 mol of sodium thiosulfate in the "2#" solution, and uniformly stirring to obtain a "3#" solution;

Step (4), removing oxygen in the system by introducing nitrogen gas into the "3#" solution for 20 minutes, sealing the irradiation tube, and then irradiating 20 kGy through the cobalt source to obtain a novel three-dimensional dose gel material sample;

Step (5), cleaning the new three-dimensional dose gel material sample, and finally obtaining a pure new three-dimensional dose gel material.

Embodiment 2:

Step (2), adding 30 mL of acrylic acid to the "1#" solution, stirring uniformly to obtain "2#" solution liquid;

Step (4), removing oxygen in the system by introducing nitrogen gas into the "3#" solution for 20 minutes, sealing the irradiation tube, and then irradiating 30 kGy through the cobalt source to obtain a novel three-dimensional dose gel material sample;

Embodiment 3:

Step (4), removing oxygen in the system by introducing nitrogen gas into the "3#" solution for 20 minutes, sealing the irradiation tube, and then irradiating 100 kGy through the cobalt source to obtain a novel three-dimensional dose gel material sample;

In the first, second and third examples, acrylic acid was used as the gel monomer, cadmium chloride and sodium thiosulfate were used as the raw materials for quantum dot synthesis, and isopropanol was added as the reducing agent. The new dosage was 20kGy, 30kGy and 100kGy. Three-dimensional dose gel material.

Embodiment 4:

Step (1), adding 7 mL of isopropanol and 70 mL of deionized water (volume ratio 1:10) to the irradiation tube, and uniformly mixing to obtain a "1#" solution;

Step (2), add 30 mL of acrylic acid, 5 g of acrylamide to the "1#" solution, and mix well. Obtaining a "2#" solution;

Embodiment 5:

Step (1), adding 0.7 mL of isopropanol and 70 mL of deionized water (volume ratio of 1:100) to the irradiation tube, and uniformly mixing to obtain a "1#" solution;

Step (2), adding 30 mL of acrylic acid and 5 g of acrylamide to the "1#" solution, and uniformly stirring to obtain a "2#" solution;

In the first to third embodiments, the volume of isopropanol and deionized water in the "1#" solution is 1:13; in the fourth to fifth embodiments, the volume ratio of isopropanol to deionized water in the "1#" solution is: 1 : 10 and 1:100.

Example 6:

Step (3), adding 0.00001 mol of cadmium chloride and 0.00002 mol of sodium thiosulfate in the "2#" solution, and uniformly stirring to obtain a "3#" solution;

Example 7:

Step (3), adding 0.001 mol of cadmium chloride and 0.002 mol of sodium thiosulfate in the "2#" solution, and uniformly stirring to obtain a "3#" solution;

In Examples 1 to 5, 0.0001 mol of cadmium chloride and 0.0002 mol of sodium thiosulfate were added to the solution of "2#"; in Example 6, 0.00001 mol of cadmium chloride and 0.00002 mol of sodium thiosulfate were added to the solution of "2#". In Example 7, 0.001 mol of cadmium chloride and 0.002 mol of sodium thiosulfate were added to the "2#" solution.

Example 8:

Step (3), adding 0.0001 mol of cadmium chloride and 0.0001 mol of sodium thiosulfate in the "2#" solution, and uniformly stirring to obtain a "3#" solution;

Example 9:

Step (3), adding 0.0001 mol of cadmium chloride and 0.00025 mol of sodium thiosulfate in the "2#" solution, and uniformly stirring to obtain a "3#" solution;

In Examples 1-7, the ratio of the concentration of cadmium chloride to sodium thiosulfate in the "3#" solution is 1:2; Example VIII, the ratio of the concentration of cadmium chloride to sodium thiosulfate in the "3#" solution It is 1:1; in Example 9, the ratio of the concentration of cadmium chloride to sodium thiosulfate in the "3#" solution is 1:2.5.

Example 10:

Step (2), adding 30 mL of acrylic acid, 5 g of acrylamide, 2 g of acrylate in the "1#" solution, and uniformly stirring to obtain a "2#" solution;

Examples 1 to 3, using acrylic acid as a single gel monomer; Examples 4-9, using acrylic acid and acrylamide as a gel monomer; Example 10, using acrylic, acrylamide and acrylate as a gel monomer.

The invention adopts the method of radiation crosslinking, the operation is simple and easy, the preparation cycle is short, and the novel three-dimensional dosimeter material prepared by the method is pure and free of impurities.

A novel three-dimensional gel dosimeter material is synthesized by the method of the present invention. The addition of quantum dots, also known as semiconductor nanoparticles, in polymer hydrogels has quantum size effects, surface effects, dielectric confinement effects, and good light stability. The fluorescence generated by the excitation is strongly dependent on the size of the quantum dots and can be widely used in cell labeling, in vivo imaging, and clinical diagnosis. It has been found that the quantum dots of Group II-VI elements are water-soluble, and the yield is high. The quantum dots containing cadmium (element symbol: Cd) have strong luminescence intensity. CdX, X is S, Se, Te, etc., and quantum dots will exhibit different colors due to different sizes. The quantum dots in the novel three-dimensional gel dosimeter material synthesized by the invention are excited by different intensity radiation to generate fluorescence with different intensities, and the fluorescence signals generated by the CCD camera are detected to reconstruct the three-dimensional distribution information of the dose.

The above is only a preferred embodiment of the present invention, and is not intended to limit the present invention. It should be noted that those skilled in the art can make some improvements without departing from the technical principles of the present invention. And modifications and variations are also considered to be within the scope of the invention.

Claims

A novel three-dimensional gel dosimeter material, comprising: a hydrogel, wherein the hydrogel is doped with quantum dots, and the monomers of the hydrogel are acrylic acid, acrylamide, and acrylate. One or more of the quantum dots are cadmium compound semiconductor nanoparticles.
A novel method for preparing a three-dimensional gel dosimeter material, comprising: the following steps:

Step (1) adding a certain volume ratio of deionized water and isopropanol to the irradiation tube, and uniformly mixing to obtain a "1#" solution;

Step (2) adding a certain amount of hydrogel monomer to the "1#" solution, and uniformly stirring to obtain a "2#" solution;

Step (3) adding a certain amount of cadmium chloride and sodium thiosulfate in the "2#" solution, and uniformly stirring to obtain a "3#" solution;

Step (4) introducing a nitrogen gas in the "3#" solution, sealing the irradiation tube, and then irradiating through a cobalt source or an electron beam to obtain a novel three-dimensional dose gel material sample;

Step (5) to clean the new three-dimensional dose gel material sample, and finally obtain a pure new three-dimensional dose gel material.
The method for preparing a novel three-dimensional gel dosimeter material according to claim 2, wherein the volume ratio of isopropyl alcohol to deionized water in the "1#" solution described in the step (1) is 1: 10 to 1:100.
The method for preparing a novel three-dimensional gel dosimeter material according to claim 2, wherein the hydrogel monomer in the step (2) is one of acrylic acid, acrylamide, and acrylate. Several.
The method for preparing a novel three-dimensional gel dosimeter material according to claim 2, wherein the concentration of cadmium chloride in the "3#" solution in the step (3) is 0.0001 mol/L to 0.01 mol/ L.
The method for preparing a novel three-dimensional gel dosimeter material according to claim 2, wherein the concentration ratio of cadmium chloride to sodium thiosulfate in the "3#" solution in the step (3) is 1 :1~1:2.5.
The method for preparing a novel three-dimensional gel dosimeter material according to claim 2, wherein the dose of the irradiation in the step (4) is 20 kGy to 100 kGy.
A method for preparing a novel three-dimensional gel dosimeter material according to claim 2, characterized in that Therefore, the time for discharging oxygen through the nitrogen gas in the step (5) is 20 minutes.