Radiopaque glass radioembolic microparticles and related methods

Abstract

A method of performing a radioembolism treatment includes injecting 402 a plurality of radioembolism particles into a blood flow of a patient to treat a target tissue. Each radioembolic particle of the plurality of radioembolic particles includes a radioactive nucleus and a radiopaque layer. The method further includes obtaining 404 an image of the target tissue and the radioembolic particles to determine 406 a radiation dose delivered to the target tissue by the plurality of radioembolic particles, where the image is one of a computed tomography (CT) image and an X-ray image.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to and the benefit of U.S. Provisional Patent Application No. 63 / 342,446, filed on May 16, 2022, which is incorporated herein by reference for all purposes as if fully set forth herein. Technical Field

[0003] The present disclosure relates to radiopaque glass radioembolic particles and related methods. Background Art

[0004] This section provides background information related to the present disclosure which is not necessarily prior art.

[0005] Radioembolization can be used to treat a variety of conditions, such as cancer or other abnormal tissue growth. Radioembolization can be performed to treat abnormal tissue growth located in a patient's liver. Radioembolization can incorporate both embolization and radiation therapy. The treatment can limit the growth of the target tissue, reduce the size of the target tissue, and / or destroy the cells of the target tissue.

[0006] Radioembolism generally involves introducing particles into the patient's bloodstream, the particles being located at or near a target tissue (e.g., a tumor). The particles can block blood vessels at the target tissue, thereby reducing or preventing blood flow to the target tissue. In addition, the particles can include radioactive isotopes that deliver a dose of radiation to the target tissue. Reducing and / or preventing blood flow to the target tissue and the radiation dose to the target tissue can damage the target tissue, reduce the size of the target tissue, and / or reduce the growth of the target tissue.

[0007] Existing radioembolic particles and methods of use suffer from various disadvantages. Existing radioembolic particles are difficult to position in a desired location. In addition, it may be difficult to determine the dose of radiation delivered to the target tissue using existing radioembolic particles. Therefore, existing radioembolic particles may be positioned in suboptimal and / or unknown positions during the treatment process and may deliver unknown radiation doses. Such disadvantages may result in ineffective treatment, suboptimal treatment and / or delivery of radiation doses to healthy tissue. Therefore, there is a need for improved radioembolic particles that can be accurately and repeatedly positioned in a desired location to deliver an effective radiation dose to the target tissue while minimizing harmful effects on healthy tissue. Summary of the invention

[0008] This section provides a general summary of the disclosure, and is not a comprehensive disclosure of its full scope or all of its features.

[0009] In some embodiments of the present disclosure, radioembolic particles are provided that can be used during radioembolic treatment to improve the ability of medical professionals to accurately understand the location of the radioembolic particles during the treatment process. Using this information, the medical professional can take corrective and / or remedial actions to increase or improve the effectiveness of the treatment. The radioembolic particles of the present disclosure can include additives and / or coatings to make the radioembolic particles radiopaque to imaging equipment used in a clinical setting, where the particles are injected into the target tissue.

[0010] The radioembolic particles and related methods of use disclosed herein are improvements over existing particles and methods. The particles and methods of use disclosed herein can be viewed using imaging equipment that can be used in a clinical setting of treatment. Since the radioembolic particles disclosed herein are radiopaque, medical professionals and / or systems used in a clinical setting can determine the exact location of the radioembolic particles and / or determine an accurate understanding of the radiation dose to be delivered by the particles. This information can be used to improve the effectiveness of treatment in destroying target tissue and / or shrinking target tissue or reducing the growth of target tissue. This information can also allow radioembolic particles to be accurately positioned so as to limit undesirable effects on healthy tissue.

[0011] In some embodiments of the present disclosure, a radioembolic particle is provided, which may include: a radioactive core including yttrium and silicon, and a radiopaque additive including at least one of holmium, samarium, iodine, iridium, rhenium, and indium.

[0012] In some embodiments of the present disclosure, a radioembolic particle may include: a radioactive core including yttrium and silicon, and a radiopaque layer applied to the radioactive core, wherein the radiopaque layer includes a tantalum and bismuth coating.

[0013] In some embodiments of the present disclosure, a radioembolic treatment is provided. The radioembolic treatment may include injecting a plurality of radioembolic particles into a patient's bloodstream to treat a target tissue. Each of the plurality of radioembolic particles may include a radioactive core and a radiopaque additive or a radiopaque layer. The method may also include obtaining an image of the target tissue and the radioembolic particles to determine a radioactive dose delivered to the target tissue by the plurality of radioembolic particles, wherein the image includes one of a computed tomography (CT) image and an X-ray image.

[0014] In some embodiments, a radioembolic particle is provided. The radioembolic particle may include: a radioactive material including yttrium and silicon, and a radiopaque material.

[0015] In one aspect, the radiopaque material can be an additive including at least one of holmium, samarium, iodine, iridium, rhenium, and indium.

[0016] In another aspect, radioactive material and radiopaque material may be mixed in the radioembolic particles.

[0017] In another aspect, the radiopaque material may be a radiopaque layer and the radioactive material may be a radionucleus.The radiopaque layer may be applied to the radionucleus and the radiopaque layer may be a tantalum and bismuth coating.

[0018] In another aspect, the radiopaque material may be a radiopaque layer and the radioactive material may be a radionucleus.The radiopaque layer may be applied to the radionucleus and the radiopaque layer may be a tantalum oxide coating.

[0019] In some embodiments, a method for performing radioembolic treatment is provided. The method may include delivering a plurality of radioembolic particles into a patient's bloodstream to treat a target tissue, each of the plurality of radioembolic particles including a radioactive core and a radiopaque layer. The method may also include obtaining an image of the target tissue and the radioembolic particles to determine a radioactive dose delivered to the target tissue by the plurality of radioembolic particles, wherein the image includes one of a computed tomography (CT) image and an X-ray image.

[0020] In some embodiments, a method of making a radioembolic particle is provided. The method may include combining a radioactive material with a radiopaque material, the radioactive material including yttrium and silicon.

[0021] In one aspect, the radiopaque material can be an additive including at least one of holmium, samarium, iodine, iridium, rhenium, and indium.

[0022] In another aspect, additives may be mixed with the glass particle composition to form radiopaque glass particles.

[0023] In another aspect, the radiopaque material can be a radiopaque layer applied to the radioactive nucleus, and the radiopaque layer includes a tantalum and bismuth coating or a tantalum oxide coating.

[0024] In another aspect, the radioactive material can be yttrium and silica-based glass particles.

[0025] In another aspect, the glass particles can be coated with the radiopaque layer by chemical vapor deposition or spray coating.

[0026] In another aspect, the method may include depositing a plurality of glass particles including yttrium and silicon into a reactor to obtain radioactive material in the form of a plurality of radioactive glass particles. The step of combining the radioactive material with the radiopaque material may include applying a radiopaque layer to the plurality of radioactive glass particles.

[0027] In another aspect, the radiopaque layer can be a tantalum and bismuth coating.

[0028] In another aspect, the radiopaque layer can be a tantalum oxide coating.

[0029] Further areas of applicability will become apparent from the description provided herein.The description and specific examples in this summary are intended for purposes of illustration only and are not intended to limit the scope of the present disclosure. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] The drawings described herein are for illustrative purposes only of selected embodiments and not all possible implementations, and are not intended to limit the scope of the present disclosure.

[0031] Figure 1 is a diagram illustrating an example radioembolization system according to some embodiments of the present disclosure.

[0032] Figure 2 is a flow chart illustrating an example method of producing radiopaque glass microspheres of the present disclosure.

[0033] Figure 3 is a flow chart illustrating an example method of producing radiopaque glass microspheres of the present disclosure.

[0034] Figure 4 is a flow chart illustrating an example treatment method according to some embodiments of the present disclosure.

[0035] Corresponding reference numerals indicate corresponding parts throughout the several views of the drawings. DETAILED DESCRIPTION

[0036] Example embodiments will now be described more fully with reference to the accompanying drawings.

[0037] Example embodiments are provided so that the present disclosure will be thorough and will fully convey the scope to those skilled in the art. Many specific details, such as examples of specific components, devices, and methods, are set forth to provide a thorough understanding of the embodiments of the present disclosure. It will be apparent to those skilled in the art that specific details need not be employed, that the example embodiments may be embodied in many different forms, and that they should not be construed as limiting the scope of the present disclosure. In some example embodiments, well-known processes, well-known device structures, and well-known techniques are not described in detail.

[0038] The terms used herein are only used to describe the purpose of specific example embodiments and are not intended to be restrictive. As used herein, the singular forms "one", "an" and "the" may also be intended to include plural forms unless the context clearly indicates otherwise. The terms "include", "comprise", "contain", and "have" are inclusive, and therefore specify the existence of stated features, integral bodies, steps, operations, elements and / or parts, but do not exclude the existence or addition of one or more other features, integral bodies, steps, operations, elements, parts and / or their groups. The method steps, processes and operations described herein should not be interpreted as necessarily requiring them to be performed in the specific order discussed or shown, unless specifically identified as the order of execution. It should also be understood that additional or alternative steps may be adopted.

[0039] When an element or layer is referred to as being "on," "engaged to," "connected to," or "coupled to" another element or layer, it may be directly on, directly engaged to, directly connected to, or directly coupled to another element or layer, or there may be intermediate elements or layers. In contrast, when an element is referred to as being "directly" "on," "directly engaged to," "directly connected to," or "directly coupled to" another element or layer, there may be no intermediate elements or layers. Other words used to describe the relationship between elements should be interpreted in a similar manner (e.g., "between" versus "directly between," "adjacent" versus "directly adjacent," etc.). As used herein, the term "and / or" includes any and all combinations of one or more of the associated listed items.

[0040] Although the terms first, second, third, etc. can be used herein to describe various elements, components, regions, layers and / or sections, these elements, components, regions, layers and / or sections should not be limited by these terms. These terms can only be used to distinguish an element, component, region, layer or section from another region, layer or section. Terms such as "first", "second" and other numerical terms do not imply order or sequence when used in this article unless clearly indicated by context. Therefore, the first element, component, region, layer or section discussed below can be referred to as the second element, component, region, layer or section without departing from the teaching of the exemplary embodiment.

[0041] Spatially relative terms such as "inside", "outside", "below", "below", "lower", "above", "upper", etc. may be used herein to describe the relationship between an element or feature as shown in the figure and another (one or more) element or feature for ease of description. Spatially relative terms may be intended to cover different orientations of the device in use or operation other than the orientation depicted in the figure. For example, if the device in the figure is turned over, the elements described as "below" or "below" other elements or features will be oriented to be "above" other elements or features. Therefore, the example term "below" can cover both the orientation above and below. The device can be oriented in other ways (rotated 90 degrees or in other orientations), and the spatially relative descriptors used herein are interpreted accordingly.

[0042] In various embodiments of the present disclosure, radiopaque glass radioembolic particles are provided. Radiopaque glass radioembolic particles can be used for radioembolic treatment to treat abnormal tissue in a patient. In an example radioembolic treatment, the radioembolic particles of the present disclosure can be injected into the patient's bloodstream and guided to a target tissue (e.g., a tumor). The radioembolic particles can stop and / or reduce the blood supply to the target tissue and also deliver a dose of radiation to the target tissue. The radioembolic treatment can destroy the target tissue, reduce the size of the target tissue, and / or limit the growth of the target tissue.

[0043] The radioembolic particles of the present disclosure are an improvement over existing radioembolic particles because the radioembolic particles of the present disclosure are radiopaque. The term "radiopaque" is used in the present disclosure to describe the property of the particles that makes the particles opaque to various forms of radiation, such as X-rays. Utilizing this property, the radioembolic particles of the present disclosure are visible in 2D and 3D X-ray images and in beam computed tomography (CT) images.

[0044] Existing radioembolic particles are not radiopaque. Existing radioembolic particles are not visible in X-ray based images. However, X-ray imaging equipment is often used in clinical settings (e.g., operating rooms) where radioembolic treatments are performed. Images of target tissue obtained during treatment may show the location of tracer particles, but such tracer particles are not particles that deliver radiation to the target tissue. Existing treatment methods and existing radioembolic particles do not provide accurate representative information for the location of the radioembolic particles.

[0045] Existing treatment methods may include post-treatment imaging, where the location of the radioembolic particles may be determined using a single photon emission computed tomography (SPECT) imaging device and / or a positron emission tomography (PET) imaging device or other post-treatment device. Such post-treatment devices require the patient to be moved from a clinical setting (e.g., an operating room) to another location to perform such image capture. This requirement does not allow a medical professional to determine the location of the radioembolic particles during treatment so that corrective or remedial action can be taken in real time.

[0046] Therefore, the radiopaque radioembolic particles of the present disclosure are an improvement over existing particles and treatment methods by allowing imaging to be performed in a clinical setting without the need to move the patient from the operating room. X-ray equipment and / or beam CT scanning equipment can be used in a clinical setting to provide information to medical professionals about the location of the radioembolic particles. Accurate and reliable dose maps can be created and determined in real time so that treatment can be adjusted while the patient is in the clinical setting. These improvements can result in increased effectiveness of treatment and reduced likelihood that healthy tissue will be unnecessarily harmed during treatment.

[0047] Reference now Figure 1 , an example radioembolization system is shown. The radioembolization system may include a source 102 of radioembolic particles, an imaging device 106, and a radioembolization calculation device 108. The source 102 of radioembolic particles 104 may be any suitable receptacle, such as a bag, a syringe, or other container that may hold the radioembolic particles 104 for delivery to a patient 110. The radioembolic particles 104 may be delivered to the bloodstream of the patient 110 using a catheter or other suitable device. The source 102 may be a syringe that may be injected with saline or other delivery fluid.

[0048] The radioembolic particles 104 can be delivered to a predetermined vascular network of the target tissue. For example, if the radioembolic treatment is used to treat a tumor in the liver, the liver can be imaged prior to the radioembolic treatment to determine the vasculature that delivers blood to the tumor. During the radioembolic treatment, the catheter can be positioned to deliver the radioembolic particles to the predetermined vasculature.

[0049] As will be further described below, the radioembolic particles 104 of the present disclosure are both radiopaque and radioactive when delivered to the target tissue of the patient 110. The imaging device 106 can be used to obtain images of the radioembolic particles 104 in the patient 110. The location and distribution of the radioembolic particles 104 can be seen in the captured images. The imaging device 106 is a portable X-ray-based device that can be used in an operating room or in other clinical environments where radioembolic treatment is being performed. The imaging device 106 can be, for example, a portable X-ray device or a beam CT imaging device. Traditionally, such a device can be used to view the position of a catheter, needle or other medical device relative to the target tissue. The radiopaque radioembolic particles of the present disclosure are also visible in the images captured by the imaging device 106.

[0050] The images obtained by the imaging device 106 may be provided to the radioembolization calculation device 108. The images may be displayed or analyzed by a suitable dose mapping engine or other software to determine a dose map describing the radiation dose delivered to the target based on the location and distribution of visible radiopaque radioembolic particles.

[0051] If the medical professional and / or the radioembolization calculation device 108 determines that the radiation dose is insufficient, and / or if the location and distribution of the radioembolic particles are not satisfactory for the desired treatment, the distribution and / or location of the radioembolization may be changed and / or supplemented. For example, an additional number of radioembolic particles may be delivered to the target tissue. Such changes may be made to deliver a satisfactory radiation dose to the target tissue and / or to prevent undesirable damage to healthy tissue.

[0052] In some embodiments of the present disclosure, the radioembolic particles are glass radioembolic particles. Such particles can be made into various sizes. In some embodiments, the shape of the glass radioembolic particles can be generally spherical, and the glass radioembolic particles can have a diameter of about 20 microns to about 30 microns in diameter. Other suitable sizes can also be used.

[0053] Glass radioembolic particles can be made of various suitable materials. In some examples, glass radioembolic particles are made of yttrium and silicon compositions. Glass radioembolic particles are biocompatible to be delivered to a target tissue of a patient.

[0054] Reference now Figure 2, a first example radiopaque radioembolic glass particle process is shown. Initial yttrium and silica-based glass particles 202 can be combined with a radiopaque additive 204. The radiopaque additive 204 can be a suitable material that blocks X-ray radiation so that the radioembolic particles are visible in an X-ray-based image. In various examples, the radiopaque additive 204 can include at least one of holmium, samarium, iodine, iridium, rhenium, or indium. The addition of the radiopaque additive results in a radiopaque yttrium glass radioembolic particle 206.

[0055] Various processes for adding radiopaque additives 204 to glass particles 202 may be employed. In some embodiments, radiopaque additives 204 are mixed with glass particle components and form radiopaque glass particles 206. For example, holmium, samarium, iodine, iridium, rhenium, indium, or their oxides may be mixed and melted with glass components in a suitable furnace. The mixture may then be crushed into small pieces. The composition may then be passed through a spheroidizing device to form the composition into particles or microspheres. In such examples, the radiopaque component is inherently contained within the glass particles to obtain radiopaque glass radioembolic particles 206.

[0056] Reference now Figure 3 , another example process 300 for producing radiopaque glass particles is shown. Process 300 describes a process for coating radioembolic particles with radioactivity. Process 300 may begin with yttrium and silica-based glass particles 302 as previously described. Glass particles 302 may then undergo neutron activation, in which the glass particles 302 may be deposited in a reactor and irradiated to produce Y-90 from Y-89 contained in the glass particles 302. Thus, after neutron activation 304, particles 302 have been converted to radioactive yttrium and silica-based glass particles 306.

[0057] The radioactive yttrium and silica-based glass particles 306 may then be coated with a radiopaque coating 308. The radiopaque coating 308 may be any suitable coating that is biocompatible and has radiopaque properties that may be added to the radioactive glass particles 306. For example, the radiopaque coating 308 may be a tantalum oxide layer. In another example, the radiopaque coating 308 may be a layer of tantalum and bismuth.

[0058] The radiopaque coating 308 can be applied to the outer surface of the radioactive glass particle 306. In one example, the radiopaque coating 308 can be applied to the radioactive glass particle 306 using a chemical vapor deposition process. In another example, the radiopaque coating 308 can be applied by a spray coating process. In such a process, the coating material (e.g., in powder form) can be melted and then sprayed onto the outer surface of the radioactive glass particle 306 using a suitable nozzle. In other examples, the radiopaque coating 308 can be applied to the radioactive glass particle 306 using other processes.

[0059] Process 300 results in radiopaque yttrium glass radioembolic microparticles 310. Microparticles 310 can then be delivered to a clinical site for use in a radioembolic treatment. Radiopaque radioactive microparticles 310 can not only deliver the desired clinical effects of blocking blood flow and delivering radiation to target tissue, but can also be visualized in real time during treatment using imaging equipment commonly available in a clinical setting.

[0060] Reference now Figure 4 , a method 400 for performing a radioembolic treatment is shown. The method 400 may utilize the radiopaque radioembolic particles previously described. The method 400 may begin at step 402, where the radiopaque radioembolic particles are delivered to a target tissue. The particles may be delivered using the radioembolic system 100 previously described. The particles may be delivered into the bloodstream using a catheter or other suitable delivery device.

[0061] At step 404, an image of the radiopaque radioembolic particles in the target tissue is obtained. The imaging device 106 of the radioembolization system 100 can be used to obtain the image. Since the particles are radiopaque, the image can show the radioactive particles in real time during delivery of the particles and / or during one or more intervals during the treatment process. The image can be used to determine the location, distribution, and concentration of the particles in the target tissue.

[0062] At step 406, the radiation dose may be determined based on the images obtained at step 404. The radiation dose may be accurately determined in real time or at a suitable time point after delivery of the particles to the target tissue. In some examples, the radiation dose may be determined using the radioembolization calculation device 108.

[0063] At step 408, it may be determined whether the radiopaque radioembolic particle is located in the desired location. Prior to treatment, a diagnostic or other procedure that can analyze the vasculature of the target tissue may be used to determine the desired location in the target tissue. The desired location may correspond to the location of the blood supply to the target tissue. The desired location may also correspond to multiple locations of the blood supply so that radiation is delivered to the target tissue. In some examples, step 408 may be performed by the radioembolic computing device 108 using appropriate mapping and other tools. If the radiopaque radioembolic particle is located in the desired location, the method 400 may end.

[0064] If the radiopaque radioembolic particles are not located in the desired location, the method 400 may proceed to step 410. At step 410, the medical professional may take action to increase the likelihood of effective treatment. For example, the medical professional may change the distribution of the radiopaque radioembolic particles. The change may include the delivery of additional radioembolic particles. It may be necessary to insert an additional catheter for such delivery, or it may be necessary to deliver an additional number of radioembolic particles at the same location.

[0065] After making changes or adjustments at step 410, method 400 may return to step 404 to re-execute steps 404 to 408. In this way, the treatment may be adjusted or changed in real time while the patient is still in a clinical setting (e.g., an operating room). Existing treatments require moving the patient to a different environment to obtain SPECT or PET images to quantify the location and / or distribution of radioembolic particles or the radiation dose delivered to the target tissue. If correction is required, the patient must be moved back to the operating room for subsequent treatment, and / or future treatments may need to be performed.

[0066] The radiopaque radioembolic particles and methods of the present disclosure are improvements over existing methods by providing real-time accurate images of the location and distribution of radioembolic particles. This increases the likelihood of effective radioembolic treatment. The radioembolic particles of the present disclosure can also reduce the likelihood of damaging healthy tissue because the location of the radioembolic particles when delivered to the target tissue can be imaged and visible in real time.

[0067] The foregoing description of the embodiments has been provided for the purpose of illustration and description. It is not intended to be exhaustive or to limit the present disclosure. The individual elements or features of a particular embodiment are generally not limited to that particular embodiment, but are interchangeable where applicable and can be used in selected embodiments, even if not specifically shown or described. The individual elements or features of a particular embodiment can also be varied in a variety of ways. Such variations should not be considered as departing from the present disclosure, and all such modifications are intended to be included within the scope of the present disclosure.

Claims

1. A radioactive embolic particle, comprising: Radioactive materials including yttrium and silicon; as well as Radiopaque material.

2. The radioembolic particle of claim 1, wherein the radiopaque material is an additive comprising at least one of holmium, samarium, iodine, iridium, rhenium, and indium.

3. The radioembolic particle of claim 2, wherein the radioactive material and the radiopaque material are mixed in the radioembolic particle.

4. The radioembolic particle of claim 1, wherein the radiopaque material is a radiopaque layer and the radioactive material is a radionuclide, the radiopaque layer being applied to the radionuclide, wherein the radiopaque layer comprises a tantalum and bismuth coating.

5. The radioembolic particle of claim 1, wherein the radiopaque material is a radiopaque layer and the radioactive material is a radionucleus, the radiopaque layer being applied to the radionucleus, wherein the radiopaque layer comprises a tantalum oxide coating.

6. A method of performing a radioembolization treatment, comprising: delivering a plurality of radioembolic particles into a patient's bloodstream to treat a target tissue, each radioembolic particle of the plurality of radioembolic particles comprising a radioactive core and a radiopaque layer; as well as An image of the target tissue and the radioembolic particles is obtained to determine a radiation dose delivered to the target tissue by the plurality of radioembolic particles, wherein the image comprises one of a computed tomography (CT) image and an X-ray image.

7. A method for preparing radioactive embolic particles, comprising: A radioactive material is combined with a radiopaque material, the radioactive material comprising yttrium and silicon.

8. The method of claim 7, wherein the radiopaque material is an additive comprising at least one of holmium, samarium, iodine, iridium, rhenium, and indium.

9. The method of claim 8, wherein the additive is mixed with a glass particle component to form radiopaque glass particles.

10. The method of claim 7, wherein the radiopaque material is a radiopaque layer applied to a radioactive nucleus, wherein the radiopaque layer comprises a tantalum and bismuth coating or a tantalum oxide coating.

11. The method of claim 7, wherein the radioactive material comprises yttrium and silica-based glass particles.

12. The method of claim 11, wherein the glass particles are coated with the radiopaque layer by chemical vapor deposition or spray coating.

13. The method according to claim 7, comprising: depositing a plurality of glass particles comprising yttrium and silicon into a reactor to obtain said radioactive material in the form of a plurality of radioactive glass particles; Wherein the step of combining the radioactive material with the radiopaque material comprises applying a radiopaque layer to the plurality of radioactive glass particles.

14. The method of claim 13, wherein the radiopaque layer comprises a tantalum and bismuth coating.

15. The method of claim 13, wherein the radiopaque layer comprises a tantalum oxide coating.

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