Combined CT (Computed Tomography) and nuclear magnetic resonance universal positioning patch for iodide ion and gallium ion chelate

Abstract

The invention provides an iodide ion and gallium ion chelate combined CT (Computed Tomography) and nuclear magnetic resonance general positioning patch, and belongs to the field of medical auxiliary instruments. The positioning patch comprises a carrier layer made of a medical-grade flexible material, a developing layer containing gallium ions and iodide ions, and a protective film layer made of a medical material. The preparation method comprises the following steps: respectively preparing gallium ion and iodide ion solutions with specific concentrations, mixing according to a ratio, adding an adhesive, coating on the carrier layer, drying to form the developing layer, and covering with the protective film. According to different developing characteristics of gallium and iodide ions in CT and nuclear magnetic resonance imaging, the iodide ions absorb X-rays in CT, and the gallium ions enhance the contrast ratio; in nuclear magnetic resonance, gallium ions and water molecules act to influence signals, and iodide ions are collaboratively optimized. The positioning patch can be clearly developed in two imaging modes at the same time, has the advantages of being good in biocompatibility, good in flexibility and simple in preparation process, can avoid using different markers respectively, reduces the patient examination cost and time, improves the clinical efficiency, and is good in application prospect.

Description

Technical Field

[0001] The present invention relates to the field of medical auxiliary instruments, and more particularly, to a combined CT and nuclear magnetic resonance universal positioning sticker of iodine ion and gallium ion chelate. Background Art

[0002] Radiotherapy is one of the important means for treating malignant tumors. Precise radiotherapy positioning is crucial for improving the radiotherapy effect and reducing the damage to surrounding normal tissues. At present, the commonly used radiotherapy positioning methods in clinics mainly rely on medical imaging techniques, such as CT (Computed Tomography) and nuclear magnetic resonance MRI (Magnetic Resonance Imaging).

[0003] However, there are some limitations in the existing radiotherapy positioning markers. Most positioning markers can only be visualized in a single imaging mode. For example, some traditional metal markers have good visualization effects on CT images, but may produce obvious artifacts in nuclear magnetic resonance images, affecting the image quality and positioning accuracy; while some organic markers have better performance in nuclear magnetic resonance imaging, but have poor visualization effects on CT images. This results in the need to use different markers for CT and nuclear magnetic resonance examinations respectively during the radiotherapy positioning process, increasing the patient's examination cost and time, and also bringing inconvenience to clinical operations. Therefore, we have made improvements and proposed a combined CT and nuclear magnetic resonance universal positioning sticker of iodine ion and gallium ion chelate. Summary of the Invention

[0004] The purpose of the present invention is to address the problems raised in the existing background art. To achieve the above-mentioned invention purpose, the present invention provides the following technical solutions: A combined CT and nuclear magnetic resonance universal positioning sticker of iodine ion and gallium ion chelate, comprising a carrier layer, a gallium-iodine ion imaging layer, and a protective film layer. The carrier layer is made of a medical-grade flexible material, and the medical-grade flexible material includes medical silica gel and medical polyurethane. The gallium-iodine ion imaging layer is disposed on one side surface of the carrier layer and is made of a composite material containing gallium ions and iodine ions.

[0005] As a preferred technical solution of the present invention, the shape of the carrier layer is any one of a circle, a square, and a triangle.

[0006] As a preferred technical solution of the present invention, the preparation method of the gallium iodide ion imaging layer includes: dissolving a gallium salt in deionized water to prepare a gallium ion solution with a concentration of 0.1-1 mol / L, and dissolving an iodine salt in deionized water to prepare an iodine ion solution with a concentration of 0.1-1 mol / L; mixing the gallium ion solution and the iodine ion solution in a ratio, and stirring evenly to obtain a gallium iodide mixed solution; adding an appropriate amount of medical binder to the gallium iodide mixed solution, stirring evenly and then uniformly coating it on one side surface of the carrier layer. The surface of the carrier layer is provided with uneven structures, and the uneven structures increase the coating thickness of the gallium iodide mixture, and at the same time are more conducive to aggregating the gallium iodide mixture so that the adsorbed amount is larger.

[0007] As a preferred technical solution of the present invention, by combining gallium ions with a specific chelating agent to form a stable gallium chelate, imaging can be achieved in MRI. The chelating agent includes DOTA and NOTA macrocyclic polyamine compounds.

[0008] As a preferred technical solution of the present invention, the iodine salt includes at least one of potassium iodide and sodium iodide.

[0009] As a preferred technical solution of the present invention, the medical binder includes at least one of sodium carboxymethyl cellulose and polyvinyl alcohol.

[0010] As a preferred technical solution of the present invention, the radiotherapy positioning patch uses the different imaging characteristics of gallium ions and iodine ions in CT and magnetic resonance imaging for positioning.

[0011] As a preferred technical solution of the present invention, in CT imaging, iodine ions absorb X-rays, and gallium ions enhance the image contrast; in magnetic resonance imaging, gallium ions interact with water molecules to affect the magnetic resonance signal, and iodine ions cooperate with gallium ions to optimize the imaging effect.

[0012] As a preferred technical solution of the present invention, the carrier layer is non-irritating and non-toxic to the human body, and the carrier layer has biocompatibility and flexibility and fits the human skin surface.

[0013] As a preferred technical solution of the present invention, the radiotherapy positioning patch is used for radiotherapy positioning and is clearly imaged in both CT and magnetic resonance imaging.

[0014] Compared with the prior art, the beneficial effects of the present invention are:

[0015] In the solution of the present invention: improving imaging accuracy: in the existing radiotherapy positioning, different markers are often used for CT and magnetic resonance examinations respectively. However, the general positioning patch of the present invention can meet the two imaging requirements at the same time. The patient only needs to perform one operation of applying the positioning patch to complete the CT and magnetic resonance examinations, avoiding the process of repeatedly applying markers, reducing the patient's examination time, and also improving the hospital's examination efficiency.

[0016] The present invention reduces the use of different markers and lowers the procurement costs of hospitals. From the perspective of the entire medical system, it improves the utilization efficiency of resources and reduces the waste of medical resources.

[0017] The present invention uses medical-grade flexible materials as the carrier layer, such as medical silicone and medical polyurethane. These materials have good biocompatibility and are non-irritating and non-toxic to human skin. Compared with some traditional metal or highly irritating markers, they can reduce skin allergies, redness and discomfort reactions in patients, and improve the comfort of patients during radiotherapy positioning.

[0018] The flexibility of the carrier layer of the present invention enables the positioning sticker to closely adhere to the skin surface of various parts of the human body. Regardless of the body shape of the patient, the positioning sticker can make good contact with the skin and is not easy to fall off. This not only ensures the accuracy of positioning but also reduces the trouble of re-sticking due to the displacement or falling off of the positioning sticker, alleviating the physical burden of the patient.

[0019] Since the present invention simplifies the inspection process and reduces the time for re-sticking markers, patients do not need to wait for a long time between different inspections and can enter the radiotherapy stage faster. To a certain extent, this alleviates the anxiety and tension of patients caused by the disease, enabling patients to accept treatment with a better mindset.

[0020] The precise radiotherapy positioning of the present invention allows patients to see the rigorous attitude and scientific methods of doctors towards treatment, increasing patients' confidence in the treatment effect, helping patients better cooperate with the treatment, and improving the compliance of treatment.

[0021] The gallium chelates formed by the combination of gallium ions and specific chelating agents such as DOTA and NOTA in the present invention can be used for MRI imaging, greatly enriching the selection of clinical contrast agents. Different diseases have differences in pathological characteristics and physiological environments. The distribution and metabolism characteristics of the new gallium chelate contrast agent in the body are different from those of traditional contrast agents, and it can better adapt to the diagnostic needs of certain special diseases or specific patient groups, providing a more precise diagnostic tool for clinicians. BRIEF DESCRIPTION OF THE DRAWINGS

[0022] Figure 1 It is an experimental data table of MRI image contrast parameters provided by the present invention;

[0023] Figure 2 It is an experimental data table of CT imaging data provided by the present invention;

[0024] Figure 3 It is an MRI imaging data table provided by the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0025] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the following will, in conjunction with the attached tables, clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are a specific implementation manner of the present invention and are not limited to all embodiments.

[0026] Therefore, the following detailed description of the embodiments of the present invention is not intended to limit the scope of the claimed invention, but merely represents some embodiments of the present invention. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts fall within the scope of protection of the present invention.

[0027] It should be noted that, without conflict, the embodiments in the present invention and the features and technical solutions in the embodiments can be combined with each other. It should be noted that similar reference numerals and letters represent similar items in the following attached tables. Therefore, once an item is defined in one attached table, it does not need to be further defined and explained in subsequent attached tables.

[0028] Embodiment 1: A combined CT and nuclear magnetic resonance general positioning patch of iodine ion and gallium ion chelate, including a carrier layer, a gallium-iodine ion imaging layer, and a protective film layer. The carrier layer is made of a medical-grade flexible material, and the medical-grade flexible material includes medical-grade silicone and medical-grade polyurethane. The gallium-iodine ion imaging layer is disposed on one side surface of the carrier layer and is made of a composite material containing gallium ions and iodine ions. The shape of the carrier layer is any one of a circle, a square, and a triangle, and the general positioning patch is a convex sphere.

[0029] The preparation method of the gallium-iodine ion imaging layer includes: dissolving a gallium salt in deionized water to prepare a gallium ion solution with a concentration of 0.1-1 mol / L, and dissolving an iodine salt in deionized water to prepare an iodine ion solution with a concentration of 0.1-1 mol / L; mixing the gallium ion solution and the iodine ion solution in proportion and stirring evenly to obtain a gallium-iodine mixed solution; adding an appropriate amount of medical binder to the gallium-iodine mixed solution, stirring evenly and then uniformly coating it on one side surface of the carrier layer. The surface of the carrier layer is provided with a concavo-convex structure, and the concavo-convex structure increases the coating thickness of the gallium-iodine mixture and is more conducive to aggregating the gallium-iodine mixture so that the adsorbed amount is larger. The shelf life of the gallium-iodine mixture is about three to four years.

[0030] By combining gallium ions with specific chelating agents to form stable gallium chelates, imaging can be achieved in MRI. The chelating agents include DOTA and NOTA macrocyclic polyamine compounds. The iodine salt includes at least one of potassium iodide and sodium iodide. The medical binder includes at least one of sodium carboxymethylcellulose and polyvinyl alcohol.

[0031] The radiotherapy positioning patch uses the different imaging characteristics of gallium ions and iodine ions in CT and magnetic resonance imaging for positioning. In CT imaging, iodine ions absorb X-rays, and gallium ions enhance the image contrast; in magnetic resonance imaging, gallium ions interact with water molecules to affect the magnetic resonance signal, and iodine ions cooperate with gallium ions to optimize the imaging effect. The carrier layer is non-irritating and non-toxic to the human body. The carrier layer has biocompatibility and flexibility, conforms to the human skin surface, and the radiotherapy positioning patch is used for radiotherapy positioning and can be clearly imaged in both CT and magnetic resonance imaging.

[0032] Application scenarios of the combined CT and magnetic resonance general positioning patch of iodine ion and gallium ion chelate: The combined application of multi-modal imaging CT and MRI can achieve the fusion of anatomical structure and functional signals, providing more comprehensive biological information for radiotherapy. For complex tumors, the positioning of these two methods can provide more accurate radiotherapy information.

[0033] Specifically, the combined CT and magnetic resonance general positioning patch of iodine ion and gallium ion chelate has important value in the combined application scenario of multi-modal imaging CT and MRI.

[0034] In the field of tumor radiotherapy, especially for complex tumors, it can provide accurate positioning information. The positioning patch is composed of a carrier layer, a gallium-iodine ion imaging layer, and a protective film layer. The carrier layer is made of medical-grade flexible materials such as medical silicone and medical polyurethane, which are non-irritating and non-toxic to the human body, and also have good biocompatibility and flexibility, and can closely adhere to the human skin.

[0035] During CT imaging, the iodine ions in the positioning patch will absorb X-rays, and the gallium ions will enhance the image contrast, clearly presenting the anatomical structure of the tumor and its surrounding tissues, such as the positional relationship between the tumor and blood vessels and nerves. In magnetic resonance imaging, gallium ions interact with water molecules to affect the magnetic resonance signal, and iodine ions cooperate with it to optimize the imaging effect, and functional information of the tumor, such as metabolic conditions, can be obtained. The fusion of the anatomical structure information of CT and the functional signals of MRI provides more comprehensive biological information for radiotherapy.

[0036] During preparation, gallium salt and iodine salt are respectively formulated into solutions with a certain concentration, mixed and then added with a medical binder, and coated on the carrier layer with concave and convex structures. A stable chelate is formed by gallium ions through a specific chelating agent, which can be imaged in MRI.

[0037] This positioning patch is like an accurate coordinate, helping doctors accurately correspond to the actual human position in multi-modal imaging. When formulating a radiotherapy plan, doctors can accurately plan the radiotherapy target area and dose distribution based on the accurate information it provides, achieve personalized radiotherapy, improve the accuracy of radiotherapy, and reduce damage to normal tissues.

[0038] Experimental examples

[0039] Purpose of the experiment

[0040] Verify that gallium ions (Ga 3 +) itself is not suitable as an MRI contrast agent, and that the gallium chelate formed by the combination of gallium ions with a specific chelating agent can be used for MRI imaging.

[0041] Experimental materials and equipment

[0042] 1. Materials

[0043] Gallium salts, potassium iodide, sodium iodide, sodium carboxymethyl cellulose, polyvinyl alcohol, medical silica gel, medical polyurethane, medical-grade polyethylene, polypropylene, DOTA, NOTA.

[0044] Experimental animals (such as mice).

[0045] 2. Equipment

[0046] MRI scanner, CT scanner, electronic balance, pipette, stirrer, culture dish, oven.

[0047] Experimental procedures

[0048] 1. Preparation of gallium ion solution and gallium iodide mixed solution

[0049] Dissolve gallium salts in deionized water to prepare a gallium ion solution with a concentration of 0.5 mol / L.

[0050] Dissolve potassium iodide and sodium iodide in deionized water respectively to prepare iodide ion solutions with a concentration of 0.5 mol / L.

[0051] Mix the gallium ion solution and the iodide ion solution in a certain proportion and stir evenly to obtain a gallium iodide mixed solution.

[0052] 2. Preparation of radiotherapy positioning stickers

[0053] Preparation of the carrier layer: Select medical silica gel to make a circular carrier layer with a thickness of 0.5 mm.

[0054] Preparation of the gallium iodide ion imaging layer: Add an appropriate amount of sodium carboxymethyl cellulose as a medical binder to the gallium iodide mixed solution, stir evenly and then evenly coat it on one side surface of the carrier layer, with a coating thickness of 0.2 mm.

[0055] Preparation of the protective film layer: Select medical-grade polyethylene to make a protective film layer with a thickness of 0.05 mm and cover it on the surface of the gallium iodide ion imaging layer.

[0056] 3. Preparation of gallium chelate

[0057] DOTA and NOTA were respectively mixed with gallium ion solution according to a certain stoichiometric ratio and reacted under appropriate conditions to form gallium-DOTA chelate and gallium-NOTA chelate solutions.

[0058] 4. Experimental groups

[0059] Experimental group 1: Blank control group: Mice were scanned by MRI without applying any contrast agent.

[0060] Experimental group 2: Gallium ion group: The prepared gallium ion solution was injected into mice via the tail vein, and then MRI scanning was performed.

[0061] Experimental group 3: Gallium-iodine ion radiotherapy positioning patch group: The prepared radiotherapy positioning patch was pasted on the skin of mice, and CT and MRI scans were performed.

[0062] Experimental group 4: Gallium-DOTA chelate group: The prepared gallium-DOTA chelate solution was injected into mice via the tail vein, and then MRI scanning was performed.

[0063] Experimental group 5: Gallium-NOTA chelate group: The prepared gallium-NOTA chelate solution was injected into mice via the tail vein, and then MRI scanning was performed.

[0064] 5. Imaging experiments

[0065] Each group of mice was scanned using an MRI scanner, and the scanned images were recorded.

[0066] The mice in group 3 were scanned using a CT scanner, and the scanned images were recorded.

[0067] Experimental data:

[0068] The experimental data are the imaging parameters and effect evaluation contents of each experimental group, which are used to illustrate the imaging differences of gallium ions themselves and gallium chelates in MRI, as well as the performance of radiotherapy positioning patches in CT and MRI.

[0069] 1. MRI image comparison parameters

[0070]

[0071] 2. CT and MRI radiotherapy positioning patch imaging data

[0072] CT imaging data

[0073] Imaging parameters Value X-ray absorption coefficient of iodide ion (average value) 0.35 ± 0.03 cm-1 CT value of gallium ion enhanced appearance 320 HU Proportion of visible area of positioning sticker in CT image 95％±2％

[0074] MRI imaging data

[0075] Imaging parameters Value Change rate of magnetic resonance signal under the influence of gallium ion 75％±5％ CT value of image after cooperation of iodide ion and gallium ion 380 HU Proportion of visible area of positioning sticker in MRI image 90％±3％

[0076] 3. Qualitative description of data

[0077] Blank control group: The overall gray scale of the MRI image is uniform, and the boundaries of organs and tissues are blurred, making it difficult to clearly distinguish different structures.

[0078] Gallium ion group: Compared with the blank control group, there are almost no obvious changes in the image, and the signal intensity and contrast are improved very slightly, unable to provide effective diagnostic information.

[0079] Gallium-DOTA chelate group: In the MRI image, the contrast between the target tissue and the surrounding tissue is significantly enhanced, the tissue contour is clear, and fine structures such as blood vessels can also be well shown.

[0080] Gallium-NOTA chelate group: The image clarity is good, and most tissues and organs can be distinguished, but it is slightly inferior to the gallium-DOTA chelate group in showing fine structures.

[0081] Gallium iodide ion radiotherapy positioning patch group (CT): The positioning patch shows obvious high-density shadows in the CT image, with a high degree of differentiation from the surrounding tissue, and can accurately show the attachment position. The absorption of X-rays by iodine ions makes the contour of the positioning patch clear.

[0082] Gallium iodide ion radiotherapy positioning patch group (MRI): In the MRI image, the signal in the positioning patch area is significantly enhanced, forming a sharp contrast with the surrounding tissue. The synergistic effect of iodine ions and gallium ions optimizes the imaging effect, which helps to accurately identify the position of the positioning patch and the relationship with the surrounding tissue.

[0083] Analysis of experimental results

[0084] 1. Whether gallium ions themselves are suitable as MRI contrast agents

[0085] Compare the MRI images of the blank control group and the gallium ion group. If the image of the gallium ion group shows no obvious contrast enhancement compared with the blank control group, it indicates that gallium ions themselves are not suitable as MRI contrast agents.

[0086] 2. Imaging effect of gallium chelates in MRI

[0087] Compare the MRI images of the gallium ion group, the gallium-DOTA chelate group, and the gallium-NOTA chelate group. If the image contrast of the gallium-DOTA chelate group and the gallium-NOTA chelate group is significantly higher than that of the gallium ion group, it indicates that by combining gallium ions with specific chelating agents (DOTA and NOTA) to form stable gallium chelates, imaging can be achieved in MRI.

[0088] 3. Imaging effect of radiotherapy positioning patches in CT and MRI

[0089] Observe the CT and MRI images of the gallium-iodine ion radiotherapy positioning patch group. In the CT images, observe the effects of iodine ions absorbing X-rays and gallium ions enhancing the image contrast; in the MRI images, observe the effects of the interaction between gallium ions and water molecules on the magnetic resonance signal and the synergistic optimization of imaging by iodine ions and gallium ions.

[0090] The above embodiments are only used to illustrate the present invention and do not limit the technical solutions described in the present invention. Although the present specification has described the present invention in detail with reference to the above respective embodiments, the present invention is not limited to the above specific embodiments. Therefore, any modification or substitution of the present invention; and all technical solutions and their improvements that do not depart from the spirit and scope of the invention are covered by the scope of the claims of the present invention.

Claims

1. A combined CT and nuclear magnetic resonance universal positioning patch of an iodine ion and gallium ion chelate, characterized in that, It includes a carrier layer, a gallium iodide ion imaging layer and a protective film layer. The carrier layer is made of a medical-grade flexible material, and the medical-grade flexible material includes medical silicone and medical polyurethane. The gallium iodide ion imaging layer is disposed on one side surface of the carrier layer and is made of a composite material containing gallium ions and iodide ions.

2. The combined CT and nuclear magnetic resonance universal positioning patch of an iodide ion and gallium ion chelate according to claim 1, characterized in that, The shape of the carrier layer is any one of circular, square and triangular.

3. The combined CT and nuclear magnetic resonance universal positioning patch of an iodide ion and gallium ion chelate according to claim 2, wherein, The preparation method of the gallium iodide ion imaging layer includes: dissolving a gallium salt in deionized water to prepare a gallium ion solution with a concentration of 0.1 - 1 mol / L, and dissolving an iodide salt in deionized water to prepare an iodide ion solution with a concentration of 0.1 - 1 mol / L; mixing the gallium ion solution and the iodide ion solution in a ratio and stirring evenly to obtain a gallium iodide mixed solution; adding an appropriate amount of medical binder to the gallium iodide mixed solution, stirring evenly and then uniformly coating it on one side surface of the carrier layer. The surface of the carrier layer is provided with uneven structures, and the uneven structures increase the coating thickness of the gallium iodide mixture and are more conducive to aggregating the gallium iodide mixture so that the adsorbed amount is larger.

4. The combined CT and nuclear magnetic resonance universal positioning patch of an iodine ion and gallium ion chelate according to claim 3, characterized in that, By combining gallium ions with specific chelating agents to form stable gallium chelates, imaging can be achieved in MRI. The chelating agents include DOTA and NOTA macrocyclic polyamine compounds.

5. The combined CT and nuclear magnetic resonance universal positioning patch of an iodide ion and gallium ion chelate according to claim 4, characterized in that, The iodide salt includes at least one of potassium iodide and sodium iodide.

6. The combined CT and nuclear magnetic resonance universal positioning patch of an iodine ion and gallium ion chelate according to claim 5, characterized in that, The medical binder includes at least one of sodium carboxymethyl cellulose and polyvinyl alcohol.

7. An iodine ion and gallium ion chelate combined CT and nuclear magnetic resonance general positioning patch according to claim 6, characterized in that, The radiotherapy positioning patch uses the different imaging characteristics of gallium ions and iodide ions in CT and magnetic resonance imaging for positioning.

8. A combined CT and nuclear magnetic resonance universal positioning patch of an iodine ion and gallium ion chelate according to claim 7, characterized in that, In CT imaging, iodide ions absorb X-rays, and gallium ions enhance the image contrast; in magnetic resonance imaging, gallium ions interact with water molecules to affect the magnetic resonance signal, and iodide ions cooperate with gallium ions to optimize imaging.

9. The combined CT and nuclear magnetic resonance general positioning patch of an iodide ion and gallium ion chelate according to claim 8, characterized in that, The carrier layer is non-irritating and non-toxic to the human body. The carrier layer has biocompatibility and flexibility and fits the human skin surface.

10. A combined CT and nuclear magnetic resonance universal positioning patch of an iodide ion and gallium ion chelate, characterized in that, The radiotherapy positioning patch is used for radiotherapy positioning and can be clearly imaged in both CT and magnetic resonance imaging.

Images