Preparation method of customizable nuclide hydrogel applicator

Abstract

The invention discloses a preparation method of a customizable nuclide hydrogel applicator. The preparation method comprises the following steps: acquiring an image of a focus part; performing three-dimensional modeling on the focus according to the image; the three-dimensional model of the focus is sliced, and a mold matched with the focus in shape is printed through a 3D printer; and adding the nuclide solution and the hydrogel precursor solution into a mold, carrying out illumination curing, taking out the hydrogel applicator, and packaging the hydrogel applicator between two layers of transparent adhesive tapes. According to the application, the nuclide hydrogel applicator matched with the focus part can be customized according to different shapes of focuses, and the treatment effect can be improved. And compared with the tedious process of preparing the applicator by mainly depicting the shape of a focus by medical staff in clinical application at present, the preparation method disclosed by the invention is safer, more efficient and higher in shape adaptability.

Description

Technical Field

[0001] The present application relates to the technical field of biomedical devices, and in particular to a method for preparing a customizable radionuclide hydrogel applicator. Background Art

[0002] Isotope radiotherapy is an effective means of treating capillary hemangioma clinically. It uses the beta rays released by isotopes to treat. This method can provide targeted treatment to local areas and has a low recurrence rate. Phosphorus 32 is a radioactive isotope of the element phosphorus, with the symbol 32 P is the radiation source for applicators commonly used in hospitals. 32 P has a short half-life, so 32 The P applicator can be customized on-site according to the lesion site.

[0003] The Chinese patent application with publication number CN116196541A discloses a phosphorus isotope patch, which includes a first base layer, a second base layer and a phosphorus isotope layer, wherein the phosphorus isotope layer is disposed between the first base layer and the second base layer. However, the preparation steps of the phosphorus isotope patch of this structure include: drawing a shape, cutting a pattern, calculating an area, dripping a nuclide once, drying once, dripping a nuclide twice, and drying twice, so there are problems such as time-consuming preparation, waste of nuclide, and release of radioactive aerosols into the environment during the preparation process. Summary of the invention

[0004] The purpose of the present application is to provide a method for preparing a customizable radionuclide hydrogel applicator. The preparation method of the present application utilizes 3D printing technology to customize an applicator that matches the shape of the lesion site for the patient's lesion. The preparation process is simpler, more efficient, and safer, and the prepared applicator has a better therapeutic effect.

[0005] The present application provides a method for preparing a customizable radionuclide hydrogel applicator, comprising:

[0006] Collect images of the lesion site;

[0007] Perform three-dimensional modeling of the lesion based on the images;

[0008] Slice the three-dimensional model of the lesion and use a 3D printer to print a mold that matches the shape of the lesion.

[0009] The nuclide solution and the hydrogel precursor solution are added into the mold, cured by light, and the hydrogel applicator is taken out and packaged between two layers of transparent tape.

[0010] In some embodiments, the mold material is ABS.

[0011] In some embodiments, the hydrogel precursor solution is prepared by the following method:

[0012] Mix acrylamide and water in a mass ratio of 5-20:20, and perform ultrasonic treatment for 5-10 minutes to dissolve the acrylamide;

[0013] Add N,N'-methylenebisacrylamide and perform ultrasonication for 5-10 minutes to dissolve N,N'-methylenebisacrylamide. The mass ratio of N,N'-methylenebisacrylamide to acrylamide is 1:500-700.

[0014] Add α-ketoglutaric acid and sonicate again for 5 min-10 min, the mass ratio of α-ketoglutaric acid to acrylamide is 1:100-200.

[0015] In some embodiments, the radioactivity of the nuclide is 0.5 mCi / mL-2 mCi / mL.

[0016] In the present application, the amount of the radionuclide solution added is determined according to the volume of the hydrogel precursor solution, so that the radioactivity of the radionuclide is 0.5 mCi / mL-2 mCi / mL.

[0017] In some embodiments, the three-dimensional model of the lesion is sliced ​​using the slicing software PrusaSlicer.

[0018] In some embodiments, three-dimensional modeling of the lesion is performed according to the image, including:

[0019] Correct the image for planar distortion;

[0020] Perform histogram statistics to determine the pixel segmentation threshold;

[0021] According to the pixel segmentation threshold, the enhancement function is used to perform feature processing to obtain a ternary image;

[0022] The ternary image is morphologically filtered using the eight-connectivity method to detect edge color values, thereby determining the lesion outline and coordinates, and calculating the lesion area.

[0023] The determined lesion outline is taken as the XY plane, scaled toward the XY plane, and extruded toward the Z axis to obtain a superimposed 3D lesion model and an enlarged model, and further a three-dimensional model matching the lesion shape is obtained through Boolean operations; wherein the Z axis refers to the direction perpendicular to the XY plane.

[0024] In some embodiments, it also includes: establishing a neural network training set with real lesion images for training and data annotation, optimizing the plane distortion calibration using a regression model, and optimizing the contour edge color value evaluation standard using a Bayesian classifier to further improve the accuracy of wound contour recognition.

[0025] Compared with the prior art, this application has the following advantages and beneficial effects:

[0026] 1. This application uses image technology to model the patient's lesion site, and then uses 3D printing technology to print out a mold that matches the shape of the lesion site. Based on the mold, a radionuclide hydrogel applicator that matches the patient's lesion can be prepared. This application can customize radionuclide hydrogel applicators that match the lesion site for lesions of different shapes, which helps to improve the treatment effect. Moreover, compared with the current cumbersome clinical process of mainly relying on medical staff to trace the shape of the lesion to prepare the applicator, the preparation method of this application is safer, more efficient, and has a higher degree of shape adaptability.

[0027] 2. The hydrogel matrix used in this application has the advantages of easy preservation, fast gelation, and excellent mechanical strength, which meets the needs of clinical application of the applicator. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 A schematic diagram of the preparation method of this application;

[0029] Figure 2 Schematic diagram of the preparation process of Example 1 of the present application, wherein Figure (a) is an image of the patient's lesion site, Figure (b) is a mask generated for the image of the patient's lesion site, Figure (c) is a three-dimensional model file in obj format, Figure (d) is a gcode slice file, Figure (e) is a 3D printed ABS mold, and Figure (f) is the resulting nuclide hydrogel applicator;

[0030] Figure 3 This is an electron microscope photo of the hydrogel sample obtained in Example 2;

[0031] Figure 4 is the tensile strength data of the hydrogel sample in Example 3;

[0032] Figure 5 The nuclide hydrogel applicator in Example 4 32 P element retention data. DETAILED DESCRIPTION

[0033] In order to make the purpose, technical solutions and beneficial effects of the present application more clear, the present application will be further described in detail below in conjunction with embodiments.

[0034] Example 1

[0035] The following will refer to Figure 1 The specific steps of the method for preparing the customizable radionuclide hydrogel applicator in this embodiment are provided:

[0036] 1. Take a white circular sticker with a diameter of 5 mm and stick it next to the patient's lesion without covering the lesion. The white circular sticker plays a role in plane distortion correction and area calibration;

[0037] 2. Use a mobile phone to take pictures of the lesion, keeping the phone as parallel to the lesion as possible;

[0038] 3. Import the image of the lesion into the computer and process it into a three-dimensional model file in obj format;

[0039] 4. Import the 3D model file into the slicing software PrusaSlicer for slicing to obtain the gcode slice file;

[0040] 5. Import the gcode slice file into the 3D printer, use ABS as the printing consumables, and print out an ABS mold that matches the shape of the lesion;

[0041] 6. Add the prepared nuclide solution and hydrogel precursor solution into the mold, cure them with ultraviolet light of 365nm for 5 minutes, and remove the hydrogel applicator after they are completely cured;

[0042] 7. Encapsulate the hydrogel applicator between two layers of transparent tape to obtain a nuclide hydrogel applicator.

[0043] In this embodiment, the hydrogel precursor solution is prepared by the following method:

[0044] Acrylamide (CAS No.: 79-06-1) and water were mixed in a mass ratio of 5:20, and ultrasonicated for 5 minutes to dissolve the acrylamide; N,N'-methylenebisacrylamide (CAS No.: 79-06-1) was added, and ultrasonicated for 5 minutes to dissolve N,N'-methylenebisacrylamide, and the mass ratio of N,N'-methylenebisacrylamide to acrylamide was 1:500; α-ketoglutaric acid (CAS No.: 328-50-7) was added and ultrasonicated again for 5 minutes, and the mass ratio of α-ketoglutaric acid to acrylamide was 1:100; the prepared hydrogel precursor solution was stored in the dark.

[0045] In this embodiment, the nuclide solution is phosphorus [ 32 P] acid sodium salt oral solution, Na2H 32 The radioactivity of PO4 aqueous solution is 0.5mCi / mL.

[0046] Example 2

[0047] The difference between this embodiment and embodiment 1 lies in the hydrogel precursor solution and the nuclide solution.

[0048] In this embodiment, the hydrogel precursor solution is prepared by the following method:

[0049] Acrylamide (CAS No.: 79-06-1) and water were mixed in a mass ratio of 10:20, and ultrasonicated for 5 minutes to dissolve the acrylamide; N,N'-methylenebisacrylamide (CAS No.: 79-06-1) was added, and ultrasonicated for 5 minutes to dissolve N,N'-methylenebisacrylamide, and the mass ratio of N,N'-methylenebisacrylamide to acrylamide was 1:600; α-ketoglutaric acid (CAS No.: 328-50-7) was added and ultrasonicated again for 5 minutes, and the mass ratio of α-ketoglutaric acid to acrylamide was 1:150; the prepared hydrogel precursor solution was stored in the dark.

[0050] In this embodiment, the nuclide solution is phosphorus [ 32 P] acid sodium salt oral solution, Na2H 32 The radioactivity of PO4 aqueous solution is 1mCi / mL.

[0051] The hydrogel precursor solution obtained in this example was freeze-dried to obtain a hydrogel sample. The hydrogel sample was cut into a cross section, dried, and gold-sprayed on the cross section in sequence. The microscopic morphology of the cross section of the hydrogel sample was observed using a desktop scanning electron microscope. The obtained electron microscope photograph is shown in FIG. Figure 3 .from Figure 3 It can be seen that pores of different pore sizes are distributed in the cross-linked network structure of the hydrogel, and the water in the pores can load radionuclides used for radiation therapy.

[0052] Example 3

[0053] In this example, 4 groups of hydrogel samples were prepared, and the tensile strength of the 4 groups of hydrogel samples was tested respectively.

[0054] In this embodiment, the preparation method of the hydrogel sample is as follows:

[0055] Acrylamide (CAS No.: 79-06-1) and water were mixed and ultrasonicated for 10 minutes to dissolve the acrylamide; the mass ratios of acrylamide to water in the four groups of hydrogel samples were 5:20, 10:20, 15:20, and 20:20, respectively;

[0056] Add N,N'-methylenebisacrylamide (CAS No.: 79-06-1) and sonicate for 5 minutes to dissolve N,N'-methylenebisacrylamide. The mass ratio of N,N'-methylenebisacrylamide to acrylamide is 1:600.

[0057] α-Ketoglutaric acid (CAS No.: 328-50-7) was added and ultrasonicated again for 5 minutes to obtain a hydrogel solution, and the mass ratio of α-ketoglutaric acid to acrylamide was 1:100.

[0058] The hydrogel solution was photocured by ultraviolet light with a wavelength of 365 nm to obtain a hydrogel sample. The hydrogel sample was prepared into a specimen with a width of 12 mm and a thickness of 2 mm. The tensile strength of the specimens was tested by a universal testing machine. The tensile interval was 20 mm. The tensile strength data is shown in Figure 4 As shown. Figure 4 It can be seen that after the mass ratio of acrylamide to water reaches 10:20, as the acrylamide content increases, its elongation at break remains basically unchanged, maintaining at about 2500%; while the hydrogel modulus gradually increases, which is reflected in the softness and hardness of the hydrogel on a macro scale. The results show that all four samples can meet the application requirements.

[0059] Example 4

[0060] The difference between this embodiment and embodiment 1 lies in the hydrogel precursor solution and the nuclide solution. In this embodiment, three groups of nuclide hydrogel applicator samples with different nuclide radioactivity are prepared.

[0061] In this embodiment, the hydrogel precursor solution is prepared by the following method:

[0062] Acrylamide (CAS No.: 79-06-1) and water were mixed in a mass ratio of 15:20, and ultrasonicated for 10 minutes to dissolve the acrylamide; N,N'-methylenebisacrylamide (CAS No.: 79-06-1) was added, and ultrasonicated for 5 minutes to dissolve N,N'-methylenebisacrylamide, and the mass ratio of N,N'-methylenebisacrylamide to acrylamide was 1:700; α-ketoglutaric acid (CAS No.: 328-50-7) was added and ultrasonicated again for 5 minutes, and the mass ratio of α-ketoglutaric acid to acrylamide was 1:200; the prepared hydrogel precursor solution was stored in the dark.

[0063] In this embodiment, the nuclide solution is phosphorus [ 32 P] acid sodium salt oral solution, Na2H 32 The radioactivity of PO4 aqueous solution was 0.5mCi / mL, 1mCi / mL, and 2mCi / mL respectively.

[0064] ICP (inductively coupled plasma spectrometer) was used for quantitative analysis to statistically analyze the three groups of radionuclide hydrogel applicator samples. 32 P content statistics, see Figure 5 .from Figure 5 It can be seen that each group of samples after gelation 32 The loss of P was kept within 12%, proving that the nuclide utilization rate was high during the hydrogel preparation process.

[0065] Note that the above are only preferred embodiments of the present application and the technical principles used. Those skilled in the art will understand that the present application is not limited to the specific embodiments described herein, and that various obvious changes, readjustments and substitutions can be made by those skilled in the art without departing from the protection scope of the present application. Therefore, although the present application is described in more detail through the above embodiments, the present application is not limited to the above embodiments, and may also include more other equivalent embodiments without departing from the concept of the present application, all of which belong to the protection scope of the present application.

Claims

1. A method for preparing a customizable radionuclide hydrogel applicator, characterized in that: include: Collect images of the lesion site; Perform three-dimensional modeling of the lesion based on the images; Slice the three-dimensional model of the lesion and use a 3D printer to print a mold that matches the shape of the lesion. The nuclide solution and the hydrogel precursor solution are added into the mold, cured by light, and the hydrogel applicator is taken out and packaged between two layers of transparent tape.

2. The preparation method according to claim 1, characterized in that: The mold material is ABS.

3. The preparation method according to claim 1, characterized in that: The hydrogel precursor solution is prepared by the following method: Mix acrylamide and water in a mass ratio of 5-20:20, and perform ultrasonic treatment for 5-10 minutes to dissolve the acrylamide; Add N,N'-methylenebisacrylamide and perform ultrasonication for 5-10 minutes to dissolve N,N'-methylenebisacrylamide. The mass ratio of N,N'-methylenebisacrylamide to acrylamide is 1:500-700. Add α-ketoglutaric acid and sonicate again for 5 min-10 min, the mass ratio of α-ketoglutaric acid to acrylamide is 1:100-200.

4. The preparation method according to claim 1, characterized in that: The radioactivity of the nuclide is 0.5mCi / mL-2mCi / mL.

5. The preparation method according to claim 1, characterized in that: The slicing software PrusaSlicer is used to slice the three-dimensional model of the lesion.

6. The preparation method according to claim 1, characterized in that: The three-dimensional modeling of the lesion according to the image includes: Correct the image for planar distortion; Perform histogram statistics to determine the pixel segmentation threshold; According to the pixel segmentation threshold, the enhancement function is used to perform feature processing to obtain a ternary image; The ternary image is morphologically filtered using the eight-connectivity method to detect edge color values, thereby determining the lesion outline and coordinates, and calculating the lesion area. The determined lesion outline is taken as the XY plane, scaled toward the XY plane, and extruded toward the Z axis to obtain a superimposed 3D lesion model and an enlarged model, and further a three-dimensional model matching the lesion shape is obtained through Boolean operations; wherein the Z axis refers to the direction perpendicular to the XY plane.

7. The preparation method according to claim 6, characterized in that: Also includes: A neural network training set was established based on real lesion images for training and data annotation. The regression model was used to optimize the plane distortion calibration. The Bayesian classifier was used to optimize the contour edge color value evaluation standard to further improve the accuracy of wound contour recognition.

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