Radioembolic beads and methods for treating tumor cells

Abstract

Disclosed herein are methods, devices, and systems including embolic particles for treating tumor cells. An embolic particle may include an inner core and an outer layer. The inner core may have a volume in which a radioisotope may be received, the inner core may include a surface on which a layer may be disposed. An outer layer may have a thickness that may accommodate a therapeutic agent therein, the outer layer may be disposed on a surface of the inner core. The inner core and outer layer may have a combined density sufficient to cause the embolic particles to move along a path with fluid flow, while the embolic particles include dimensions sufficiently large to engage the path to limit fluid flow to tumor cells.

Description

[0001] Cross-references to related applications

[0002] This application claims priority and interest in U.S. Provisional Application No. 63 / 525,400, filed July 7, 2023, the entire contents of which are incorporated herein by reference. Technical Field

[0003] This disclosure relates to injectable particles for endovascular embolization of tumor cells, with or without local delivery of radiation or therapeutic agents. Background Technology

[0004] Malignant tumors of the liver include primary tumors such as hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma, with HCC being the most common primary liver tumor. Additionally, metastatic tumors originating from sites such as the intestines, breast, lungs, and esophagus can also affect the liver. For some patients, surgical resection of the liver tumor can provide a curative treatment. However, many patients with primary or metastatic liver cancer often have underlying medical complications or impaired liver function, which hinder radical liver surgery. Furthermore, the anatomical location or extent of the liver tumor may make it technically inoperable.

[0005] Alternative treatments for patients with inoperable liver tumors include selective intra-arterial embolization of the tumor using microspheres. Liver tumors have an alternative blood supply from normal liver parenchyma. Most primary and metastatic liver tumors receive most of their blood supply from the systemic arterial circulation via branches of the celiac trunk. However, normal hepatocytes receive their blood supply via the portal venous circulation. By utilizing this difference in blood supply, intra-arterial embolization selectively targets the tumor's vascular system while preserving most of the blood supply to normal hepatocytes. Furthermore, similar to the liver, the lungs are supplied with blood by two distinct sources: the pulmonary artery and the bronchial artery. Most lung tumors receive their blood supply from the bronchial artery, while most lung parenchyma receives its blood supply from the pulmonary artery. Therefore, substantially similar to the liver, branches of the bronchial artery can be embolized with a low risk of damage to the surrounding normal lung parenchyma. Additionally, this disclosure also includes applicability in the treatment of gliomas in the brain or spinal cord, as well as prostate tumors, etc.

[0006] Microspheres for use in hepatic tumor embolization can contain drug eluting substances for delivery of chemotherapeutic agents. Alternatively, the microspheres can contain radioactivity for use in procedures commonly referred to as radioembolization. The most commonly used radioisotope is yttrium-90 (Y-90), which is a pure beta-emitting isotope. Y-90 has a half-life of 64.1 hours and the energy of the emitted beta particles is 2.28 MeV. Y-90 is produced by the decay of strontium-90 (a fission product of uranium in a nuclear reactor), and Y-90 decays to zirconium-90. There are currently only two Y-90 microspheres available. The currently available glass spheres are microspheres composed of glass measuring 20 to 30 microns. The currently available resin spheres are resin spheres measuring 20 to 60 microns.

[0007] Radiation in the form of low linear energy transfer kills cancer cells through a known indirect effect. This indirect effect results in strand breaks in the phosphoribose backbone of DNA in chromosomes. Single strand breaks are easily repaired, but double stranded DNA breaks will usually result in cell death at mitosis. This indirect effect is mediated by the formation of hydroxyl and superoxide radicals produced when ionizing radiation passes through the body. The formation of these radicals requires the presence of oxygen, and thus the indirect effect is enhanced in well-oxygenated tissues. This can be mathematically represented as the oxygen enhancement ratio (OER), and tissues with a robust blood supply with well-oxygenated blood have a higher OER. By embolizing the small arteries feeding a tumor, the cancer cells are placed in a more hypoxic environment, resulting in a lower OER, and thus a lower level of tumor cell killing.

[0008] Radiosensitizers are chemicals that enhance radiation-induced cell killing. Hypoxia-sensitive cell radiosensitizers selectively enhance the killing of hypoxic cells while having little effect on cells with normal oxygenation. Nitroimidazoles, a class of antibiotics (metronidazole being the most widely used as an antimicrobial agent), also provide radiosensitization to hypoxia-sensitive cells. Misoidazole, a second-generation 2-nitroimidazole, showed improved outcomes when combined with radiotherapy in a randomized Dutch study (DAHANCA 2) for the treatment of head and neck cancer. More recently, DAHANCA 5-85 showed improvements in both local control and overall survival when nimorazole was added to radiotherapy for the treatment of head and neck cancer. Unfortunately, the systemic use of drugs such as misoidazole and nimorazole is limited by their side effects and the logistic management of precise timing of drug dosage in the context of radiotherapy, including central nervous system toxicity.

[0009] Local delivery of hypoxic cell radiosensitizers can further improve the therapeutic ratio of radiation embolization by enhancing tumor cell killing while mitigating the systemic side effects of radiosensitizing drugs. In 1992, Wang et al. published the results of an animal study involving intrahepatic artery infusion of misotronidazole in rabbits with VX2 hepatocellular carcinoma cells. Following the hepatic artery infusion of misotronidazole, 15 Gy of external beam radiation therapy was administered. Those rabbits undergoing hepatic artery infusion exhibited the greatest tumor response, displaying extensive fibrosis and necrosis, compared to rabbits that did not receive misotronidazole.

[0010] Besides radiosensitizing hypoxic cells, many other chemicals and drugs have been shown to possess radiosensitizing properties. Chemotherapy drugs are often delivered simultaneously with external beam radiotherapy, utilizing the synergistic cell-killing effect resulting from radiosensitization. Alkylating agents and antimetabolite chemotherapeutic agents inhibit DNA repair pathways used by cells to repair sublethal damage from ionizing radiation. The accumulation of sublethal damage that is not properly repaired leads to increased cell death. Taxane chemotherapeutic agents and other microtubule inhibitors arrest the cell cycle at the G2-M phase junction, when cells are most sensitive to radiotherapy. Furthermore, there is a well-documented synergistic effect between ionizing radiation and immunotherapy, which upregulates the immune targeting of cancer cells through radiation-induced upregulation of antigen-presenting cells (dendritic cells, etc.) and other pro-inflammatory agents. These drugs include anti-CTLA4 drugs, anti-PD-1 and PDL-1 drugs / checkpoint inhibitors, chimeric antigen receptor T-cell (CAR-T) therapy, and other immunomodulatory agents.

[0011] This document discloses a novel embolic bead that combines a radiation-emitting embolic bead with a component capable of containing and delivering a drug, including a radiosensitizer. The disclosure herein leverages the enhanced radiation-induced cytotoxicity of the radiosensitizer while minimizing the systemic effects of the drug. By combining both onto a single embolic bead, they can be delivered together in a single injection, ensuring co-localization and maximizing the combined efficacy. Summary of the Invention

[0012] This disclosure relates to embolic particles for treating tumor cells. The embolic particles comprise: a core having a volume for containing a radioactive isotope, the core including a surface on which layers can be disposed; an outer layer having a thickness for containing a therapeutic agent, the outer layer being disposed on the surface of the core; and the core and outer layer having a density sufficient to allow the embolic particles to move along a path with fluid flow, while the embolic particles are large enough to engage the path and thus restrict fluid flow to the tumor cells.

[0013] In some implementations, the embolic particles are large enough to substantially block fluid flow through the pathway to tumor cells. The embolic particles can treat at least one of the following: tumors of the liver, lung, prostate, or gliomas of the brain or spinal cord.

[0014] In some implementations, the therapeutic agent may be injected into the outer layer. The outer layer can release the therapeutic agent to the tumor cells while the embolic particles restrict fluid flow to the tumor cells. The embolic particles can treat at least one of the following primary or metastatic tumors: liver, lung, brain or spinal cord, prostate, breast, esophagus, upper respiratory tract including nasopharynx, nasal cavity, oral cavity, oropharynx, hypopharynx, larynx, neck, thyroid gland, lungs, mediastinum, stomach, small intestine, large intestine, pancreas, spine, kidney, ureter, bladder, urethra, vagina, uterus, cervix, ovary, lymph nodes, muscles, and bones.

[0015] In some implementations, the core may be embedded with a radioactive isotope. The core may emit radiation, while the embolic particles restrict fluid flow to irradiate tumor cells. The embolic particles can treat at least one of the following primary or metastatic tumors: liver, lung, brain or spinal cord, prostate, breast, esophagus, upper respiratory tract including nasopharynx, nasal cavity, oral cavity, oropharynx, hypopharynx, larynx, neck, thyroid gland, lungs, mediastinum, stomach, small intestine, large intestine, pancreas, spine, kidney, ureter, bladder, urethra, vagina, uterus, cervix, ovary, lymph nodes, muscles, and bones.

[0016] In some implementations, a radioactive isotope may be embedded in the core, and a therapeutic agent may be impregnated in the outer layer. The embolic particles restrict fluid flow to tumor cells, the core emits radiation to kill tumor cells, and the outer layer releases a therapeutic agent to treat any remaining tumor cells. The radioactive isotope may be yttrium-90 (Y-90). The embolic particles can treat at least one of the following primary or metastatic tumors: liver, lung, brain or spinal cord, prostate, breast, esophagus, upper respiratory tract including nasopharynx, nasal cavity, oral cavity, oropharynx, hypopharynx, larynx, neck, thyroid gland, lungs, mediastinum, stomach, small intestine, large intestine, pancreas, spine, kidney, ureter, bladder, urethra, vagina, uterus, cervix, ovary, lymph nodes, muscles, and bones.

[0017] In some embodiments, the core may be formed of at least one of a polymer, ceramic, glass, or glass-ceramic composite. The core may be sintered and have a porosity of about 10% to about 75%. The outer layer may be formed into a uniform shape around the core. The outer layer may be formed of a polymer. The outer layer may embed a radiopaque material. The embolic particle may have a substantially spherical shape. The size of the embolic particle may be about 15 micrometers to about 1000 micrometers. The embolic particle may include at least one additional layer, which may be different from the core and the outer layer.

[0018] In one embodiment, a kit for treating tumor cells is provided herein. The kit comprises: a plurality of embolic particles; a liquid; and a vial to contain the liquid; each embolic particle comprises: a core having a volume for containing a radioactive isotope, the core including a surface on which layers can be disposed; an outer layer having a thickness for containing a therapeutic agent, the outer layer being disposed on the surface of the core; and the core and outer layer having a density sufficient to allow the embolic particle to move along a path with the fluid flow, while the embolic particle comprising a size large enough to engage the path thereby limiting the fluid flow to the tumor cells; the liquid containing the therapeutic agent, and the plurality of embolic particles being immersed therein to allow the therapeutic agent to be injected into the outer layer.

[0019] In some embodiments, the liquid may be contained in a vial. When multiple embolic particles are placed in the liquid, a therapeutic agent may be injected into the outer layer of the multiple embolic particles. The liquid may include saline. When multiple embolic particles are placed in the liquid, the size of the multiple embolic particles may increase. When multiple embolic particles are placed in the liquid, the multiple embolic particles may maintain the same size.

[0020] This document discloses a method for preparing embolic particles. The method includes: providing a core having a volume in which a radioactive isotope can be contained, the core comprising a surface on which a layer can be disposed; providing a composition in which a therapeutic agent can be injected; and disposing the composition on the surface of the core to produce an outer layer.

[0021] In some embodiments, the core may include a hollow inner chamber for containing a radioactive isotope or therapeutic agent. The method may additionally include injecting a radioactive isotope into the core. The method may also include activating the radioactive isotope, causing the embolic particles to emit radiation. The method may further include injecting a therapeutic agent into the outer layer. The therapeutic agent may be premixed with the outer layer prior to the deployment step.

[0022] This article discloses a method for treating tumor cells using embolic particles. The method includes providing a plurality of embolic particles, each embolic particle having a core and an outer layer, the core having a volume for containing a radioactive isotope, and the outer layer having a thickness for containing a therapeutic agent; identifying a target site containing tumor cells to be treated; and delivering the embolic particles into a lumen and causing the plurality of embolic particles to move along a path with fluid flow to the target site, such that the embolic particles engage with the path, thereby restricting fluid flow to the tumor cells.

[0023] In some embodiments, the method may further include activating a radioactive isotope within the core. The method may also include irradiating tumor cells at the target site. In some embodiments, the method may further include impregnating a therapeutic agent into the respective outer layers of a plurality of embolic particles. This impregnation step may further include placing the plurality of embolic particles in a fluid containing the therapeutic agent to inject the therapeutic agent into at least the outer layers. The size of each embolic particle may restrict the movement of each embolic particle through a lumen at the target site to prevent the plurality of embolic particles from migrating out of the target site. The delivery step may include delivering the plurality of embolic particles through arterial branches supplying the tumor cells. The method may also include treating at least one of the following: tumors of the liver, lung, prostate, or gliomas of the brain or spinal cord with the plurality of embolic particles.

[0024] This article discloses an embolic particle. The particle comprises a body of ceramic material; a density sufficient to provide buoyancy for the particle to flow in a fluid of a certain volume; and a diameter allowing the particle to reside in a lumen at a predetermined location.

[0025] In some implementations, the embolic particles can treat at least one of the following primary or metastatic tumors: liver, lung, brain or spinal cord, prostate, breast, esophagus, upper respiratory tract including nasopharynx, nasal cavity, oral cavity, oropharynx, hypopharynx, larynx, neck, thyroid gland, lungs, mediastinum, stomach, small intestine, large intestine, pancreas, spine, kidney, ureter, bladder, urethra, vagina, uterus, cervix, ovary, lymph nodes, muscles, and bones. The body may be coated with at least one layer.

[0026] In some embodiments, the body may comprise a plurality of interstitial pores. At least a portion of the plurality of interstitial pores may be interconnected. The density of the particle may be a function of the density of the plurality of interstitial pores. The body may be sintered to a porosity of about 10% to 75%. Embolized particles can treat at least one of the following primary or metastatic tumors: liver, lung, brain or spinal cord, prostate, breast, esophagus, upper respiratory tract including nasopharynx, nasal cavity, oral cavity, oropharynx, hypopharynx, larynx, neck, thyroid gland, lung, mediastinum, stomach, small intestine, large intestine, pancreas, spine, kidney, ureter, bladder, urethra, vagina, uterus, cervix, ovary, lymph nodes, muscle, and bone.

[0027] In some embodiments, the body may include a hollow cavity for containing a drug or radiosensitizing compound. The particle may also contain a liquid disposed within the hollow cavity. The embolic particles can treat at least one of the following primary or metastatic tumors: liver, lung, brain or spinal cord, prostate, breast, esophagus, upper respiratory tract including nasopharynx, nasal cavity, oral cavity, oropharynx, hypopharynx, larynx, neck, thyroid gland, lung, mediastinum, stomach, small intestine, large intestine, pancreas, spine, kidney, ureter, bladder, urethra, vagina, uterus, cervix, ovary, lymph nodes, muscle, and bone. The body may include a plurality of interstitial spaces radially arranged outside the hollow cavity. At least a portion of the plurality of interstitial spaces may be interconnected with each other. In some embodiments, at least a portion of the plurality of interstitial spaces may be interconnected from the hollow cavity to the outer surface of the body, such that any drug or radiosensitizing compound can enter or exit the particle from the hollow cavity. The particle density may be a function of the size of the hollow cavity and the density of the plurality of interstitial spaces. The body can be sintered to a porosity of approximately 10% to 75%. Attached Figure Description

[0028] Figure 1A This is a partial cross-sectional perspective view of an embolic bead according to one embodiment of the present disclosure.

[0029] Figure 1B It is a partially cutaway perspective view of an embolic bead having a core containing radioactive isotope particles, the core being surrounded by an outer layer containing a radiosensitizing drug.

[0030] Figure 1C This is a cross-sectional view of an embolic bead according to one embodiment of the present disclosure.

[0031] Figure 2A This is a partially cutaway perspective view of an embolic bead composed of a single uniform sphere, according to one embodiment of the present disclosure.

[0032] Figure 2B It is a partially cutaway perspective view of an embolic bead containing a single, uniform sphere containing both a radioactive isotope and a radiosensitizing drug.

[0033] Figures 3A to 3C This is a cross-sectional view of an embolic bead according to some embodiments of this disclosure.

[0034] Figure 4A and 4B This is an example of an injection method based on some implementation schemes of this disclosure.

[0035] Figure 5 This is a cross-sectional view of an embolic bead according to one embodiment of the present disclosure.

[0036] Figure 6 An injection method according to one embodiment of this disclosure is shown.

[0037] Figure 7A and 7B This is an example of an injection method based on some implementation schemes of this disclosure. Detailed Implementation

[0038] In one embodiment, this disclosure overcomes the disadvantages of the aforementioned prior art devices by providing embolic beads or particles that allow for the co-administration of radioembolization and a therapeutic agent (e.g., a radiosensitizer). The embolic beads of the present invention initially result in increased tumor cell death due to tumor irradiation. In some embodiments, the embolic beads of the present invention combine a radiation source with a drug-eluting component containing a therapeutic agent (e.g., a radiosensitizer), such that the administration of radiotherapy is performed simultaneously with the administration of the radiosensitizer, or the administration of radiotherapy is followed by the administration of the radiosensitizer. In some embodiments, the embolic beads allow for the simultaneous administration of two therapeutic agents at the same location in the tumor microvascular system. Drug delivery from the outer layer may depend on the formulation of the outer layer to allow for immediate drug release upon delivery (by dissolving the outer layer) or delayed / timed drug release (slower dissolution of the outer layer). Advantageously, the embolic beads of the present invention allow for combined forms of treatment in interventional oncology while minimizing the radiation resistance of tumor cells due to hypoxia or other cellular and molecular processes, providing optimized activity and good flow properties. Such a device allows for curative treatment of a variety of tumors, such as liver tumors, in an outpatient setting.

[0039] In other words, in several embodiments, the embolic beads of the present invention can advantageously provide at least dual treatment for certain tumor cells. By providing a single particle type having a radiation source for radiotherapy (e.g., radiotherapy for liver cancer) and a drug-eluting component containing a therapeutic agent, the embolic beads of the present invention provide a more effective treatment than a single treatment. The embolic beads of the present invention provide significant benefits not found in prior art treatments. That is, while prior art treatments use only one of radiation or a radiosensitizer, this disclosure provides a more comprehensive treatment than previously provided.

[0040] Generally, liver cancer can be treated with embolization. Embolization can be used for tumors that cannot be removed by conventional surgery. For example, embolization can be used in cases where the tumor is too large to be treated with ablation (e.g., tumor diameter greater than 5 cm) and there is still sufficient liver function. Embolization reduces blood supply to normal liver tissue, so it may not be a good option for some patients whose liver is damaged by diseases such as hepatitis or cirrhosis. However, because the liver has two blood supplies, the hepatic artery, which normally supplies blood to cancer in the liver, can be blocked or otherwise restricted, while allowing the portal vein to supply blood to healthy liver cells. Similarly, the lungs are supplied with blood by two different supplies from the pulmonary artery and the bronchial arteries. Just as liver tumors attach to the hepatic artery, almost all lung tumors attach to the bronchial arteries. Therefore, much like with the liver, branches of the bronchial arteries can be embolized without damaging the remaining healthy tissue in the lungs. Other organs and anatomical sites in the body allow for the direct implantation of radiation sources into interstitial tissues or body cavities; this process is called interstitial or intracavitary brachytherapy. The embolic beads of the present invention can also be used for interstitial or intracavitary brachytherapy, providing a method for anatomically and locally delivering therapeutic radiation and therapeutic agents (e.g., radiosensitizers) simultaneously via a route other than arterial embolization. Therefore, this disclosure includes applicability in the treatment of primary or metastatic tumors in the following areas: brain or spinal cord, prostate, breast, esophagus, upper respiratory and digestive tract including nasopharynx, nasal cavity, oral cavity, oropharynx, hypopharynx, larynx, neck, thyroid gland, lungs, mediastinum, stomach, small intestine, large intestine, spine, kidneys, ureters, bladder, urethra, vagina, uterus, cervix, ovary, lymph nodes, muscles, and bones, etc.

[0041] According to one embodiment of this disclosure, the embolic bead comprises a radioembolization or radiotherapy portion and a drug elution portion or a radiosensitizer elution portion. In one embodiment, the radioembolization portion may be an internal part of an embolization and may be made of a substantially rigid material, such as a polymer, glass, ceramic, or glass-ceramic composite. In one embodiment, to provide a radiotherapy-capable internal part, the internal part may be injected or embedded with Y-90 or a resin containing Y-90. Alternatively, any similar radioisotope may be used as a radiotherapy source. Thus, substantially rigid particulate materials similar to glass or resin may also be used as a substrate for the radioisotope. In some embodiments, the radiation-emitting portion may be a homogeneous mixture of glass, polymer or hydrogel, ceramic, glass-ceramic composite, or any other material having a radiation-emitting radioisotope. Alternatively, the radiation-emitting portion may be a non-homogeneous mixture of glass, polymer or hydrogel, ceramic or glass-ceramic composite, or any other material having a radiation-emitting radioisotope.

[0042] In some embodiments, radioembolic beads may be coated, encapsulated, or otherwise combined with a drug-eluting compound or drug capable of carrying a therapeutic agent for slow release after or during the irradiation period. For example, in one embodiment, the therapeutic agent may be released after the irradiation period to ensure the elimination of any tumor cells not killed by irradiation. Drug-eluting embolic agents may comprise a poly-vinyl-alcohol (PVA) polymer doped with sulfonyl groups, which allows electrostatic charges to bind to polarized molecules. Some examples include DC / LC beads and QuadraSphere beads. Other embolic beads for chemoembolization may comprise iodized oil, gelatin sponge, polymethyl methacrylate (Oncozene), and biodegradable starch (Spherex). However, it should be understood that these embolic beads do not share the same drug-eluting properties as PVA polymers.

[0043] In one embodiment, the radioembolic beads may comprise a Y-90-containing glass, ceramic, or resin radioembolic core coated with a drug-eluting shell (e.g., a PVA polymer or other polymer). Other known or unknown drug-eluting coatings, or other methods of incorporating drugs within or on the surface of the particles, are included within the scope and spirit of this disclosure. For example, the PVA polymer may carry a hypoxia-based cell radiosensitizer for slow elution into the irradiated area.

[0044] In some embodiments, the embolic beads 1 of this disclosure may have a diameter greater than about 15 micrometers to prevent embolism through arteriovenous shunts and non-target organ embolism, biliary ischemia, hepatobiliary infarction, or other adverse effects. In one embodiment, the embolic beads may include an upper size threshold of 1,000 micrometers, as larger sizes can cause blockage of commonly used microcatheters. Additionally, large particles can cause proximal arterial blockage and promote hypoxia, and may sub-select for more resistant cancer cell populations. However, in practice, the embolic particles can be of any size to meet clinical requirements for achieving the desired anatomical distribution.

[0045] The present disclosure will now be described in detail below with reference to the accompanying drawings. This disclosure is not intended to be limited to the described embodiments; rather, this detailed description is provided to enable any person skilled in the art to prepare and practice the present disclosure.

[0046] Go to Figure 1A and 1BIn one embodiment, the embolic bead 1 may consist of a core 2 and an outer layer 3. The overall size of the embolic bead 1 may be any value from about 5 micrometers to about 1000 micrometers. The term size or dimension as used herein may refer to external dimensions, including width, length, diameter, etc. The embolic bead 1 may be any regular or irregular 3D shape, including but not limited to spheres, hemispheres, cubes, cones, cylinders, octahedrons, etc. The figures presented in this disclosure are shown as spherical or circular. These are purely illustrative and do not reflect the only embodiments in which the particles may be. In some embodiments, at least a portion of the embolic bead 1 may have a radiopaque material embedded therein. The radiopaque material may advantageously allow visualization of the delivery of one or more embolic beads 1 to a target site (e.g., to the location of a tumor) in a patient.

[0047] According to one embodiment, the core 2 may be made of polymer, glass, ceramic, glass-ceramic composite, resin, or a combination thereof. A core made of any other biocompatible material capable of containing a radioactive isotope is also within the scope of this disclosure. In one embodiment, the core 2 of the embolized bead 1 may provide a volume therein for the placement of a radioactive isotope 7, which, when the embolized bead 1 is deployed to a tumor site, delivers local radiotherapy to the surrounding tumor. Exemplary radioactive isotopes used in such procedures may be yttrium-90 (Y-90) or holmium-166, but the use of any known or unknown radioactive isotope emitting β or γ is also within the scope of this disclosure. In some embodiments, such as Figure 1A and 1B As shown, kernel 2 can be solid, such as a solid sphere. Or, as... Figure 1C As shown, the core 2 may be porous, having a plurality of irregularly or regularly positioned pores 11; and includes a hollow internal cross-section 10 for containing additional drugs or radiosensitizing compounds, including those described above. In some cases, the core 2 may be a solid or hollow core sintered to a porosity of about 10% to 75%. Deposition of the fluid in the hollow internal cross-section 10 can be achieved by immersing the embolic beads 1 in a specific fluid bath and allowing the fluid to deposit inside the particles (e.g., through the pores 11). The particles can then be filtered out to separate them from the fluid bath. Filtering the embolic beads 1 from the fluid bath may be performed before or during the injection of the embolic beads 1. In some embodiments, the core 2 may be coated with at least one outer layer, such as an outer layer 3.

[0048] In one embodiment, the outer layer 3 may comprise a drug-eluting or releasing glass, ceramic, ceramic / glass, resin, polymer, metal, or other biocompatible material capable of deposition, adhesion, coating, or otherwise attaching to the core 2 and enabling drug delivery and elution upon in vivo deployment. In one embodiment, the outer layer 3 may be deposited or coated onto the core 2 such that the resulting embolic bead 1 does not have any rough or jagged edges to prevent the embolic bead 1 from damaging any healthy tissue it comes into contact with during administration. In some embodiments, the outer layer 3 of the embolic bead 1 may have a thickness capable of accommodating therapeutic agents (e.g., radiosensitizing compounds, hypoxic cytotoxic agents, immunotherapy, CAR-T therapy, etc.) and thus have a resulting volume, said therapeutic agent being dispersed or emitted from the embolic bead into the surrounding tumor and body tissue at the same time or at different times when a radioisotope compound is used to treat the tumor. In one embodiment, the compound may be a hypoxic cytotoxic agent, such as nitroimidazole. However, the use of any known or unknown therapeutic compound is within the scope of this disclosure. In some implementations, the outer core 3 may remain intact after delivery to the target site in the patient's body, or alternatively, the outer core 3 may be absorbed into the body after delivery. Furthermore, although the figure shows a core 2 containing a radioactive isotope and an outer layer 3 containing a drug-eluting portion, the positions of these two layers can be reversed, with the core containing the drug-eluting portion and the outer layer containing the radioactive isotope. In this configuration, the materials constituting the core and outer layer may also need to be reversed. Alternatively, as... Figure 2A and 2B As shown, in some embodiments, the embolic bead 4 can be a homogeneous material 5 forming the entire bead, such as resin, glass, polymer, or ceramic-glass composite. A radioactive isotope 9 and a radiosensitizer 8 can be mixed within the embolic bead 4.

[0049] In some embodiments, the therapeutic agent may be a radiosensitizer, which may be a nitroimidazole hypoxic cell radiosensitizer. Alternatively, the drug elution fraction may contain any other therapeutic compound, including but not limited to non-nitroimidazole hypoxic cell radiosensitizers, radiosensitizing chemotherapeutic agents such as taxanes (e.g., paclitaxel) or platinum-containing compounds (e.g., cisplatin), or other radiosensitizing compounds yet to be identified.

[0050] In some embodiments, the embolization bead 1 of the present invention may comprise a core 2 and an outer layer 3, wherein the core 2 does not contain radioactive material and the outer layer does not contain a therapeutic agent. In such cases, the embolization bead 1 can perform TAE or bland embolization on the tumor to deprive the tumor of its energy source. Alternatively, in some cases, the embolization bead 1 of the present invention can be used for trans-arterial chemoembolization (TACE). TACE is typically used as the initial embolization type for large hepatocellular carcinomas that cannot be treated with surgery or ablation, and is combined with chemotherapy (chemo). For example, the drug-eluting portion may contain doxorubicin, cisplatin, epirubicin, miriplatin, carboplatin, mitomycin C, gemcitabine, or 5-FU. In the treatment of metastatic tumors originating from hepatocellular carcinoma (HCC), the drug-eluting fraction may contain certain systemic agents, including atezolizumab, bevacizumab, tremelimumab-actl, darvalumab, soreafenib, lenvatinib, pembrolizumab, nivolumab, ipilimumab, regorafenib, cabozantinib, ramucirumab, dostarlimab, or selpercatinib.In some implementations, in the treatment of metastatic tumors originating from colorectal cancer, the drug-eluting fraction may contain 5 FU, Oxaliplatin, Leukovorin, Capecitabine, Irinotecan, Bevacizumab, Panitumumab, Nivolumab, Ipilimumab, Pembrolizumab, Trastuzumab, Pertuzumab, Lapatinib, Tucatinib, Ramoximumab, Ziv-aflibercept, Cetuximab, Panitumumab, Encorafenib, Dotalilimumab-gxly, Lapatinib, Fam-traztuzumabderuxtecan, Regorafenib, Trifluridine, or Tipiracil.

[0051] In some implementations, when treating metastatic tumors originating from cholanigiocarcinoma, the drug-eluting fraction may contain those drugs that are typically used in conjunction with TACE, including doxorubicin, cisplatin, epirubicin, miplatin, carboplatin, mitomycin C, gemcitabine, or 5-FU. Alternatively, the drug-eluting fraction may contain any of the following: 5-FU, capecitabine, oxaliplatin, leucovorin, gemcitabine, cisplatin, durvalumab, paclitaxel & NAB-paclitaxel, regorafenib, irinotecan, lenvatinib, pembrolizumab, entrectinib, larotrectinib, nivolumab, ipilimumab, pralsetinib, selpercatinib, dotalimab-gxly, dabrafenib, trametinib, futibatinib, pemigatinib, ivosidenib, trastuzumab, or pertuzumab.

[0052] In some implementations, when treating metastatic tumors originating from breast cancer, the drug-eluting fraction may contain adriamycin, cyclophosphamide, paclitaxel, docetaxel, olaparib, pebrolizumab, carboplatin, epirubicin, methotrexate, 5-FU, capecitabine, trastuzumab, pertuzumab, neratinib, TDM-1, tamoxifen, anastrozole, letrozole, ribociclib, abemaciclib, palbociclib, fulvestrant, exemestane, or everolimus. In some implementations, when treating metastatic tumors originating from non-small cell lung cancer, the drug-eluting fraction may contain carboplatin, paclitaxel, cisplatin, pemetrexed, gemcitabine, docetaxel, vinorelbine, etoposide, nivolumab, osimertinib, atezolizumab, pembrolizumab, or darvalumab. In some implementations, when treating metastatic tumors originating from prostate cancer, the drug-eluting fraction may contain nilutamide, flutamide, bicalutamide, abiraterone, enzalutamide, apalutamide, darolutamide, docetaxel, ketoconazole, cabazitaxel, carboplatin, mitoxantrone, or pembrolizumab. In some implementations, when treating metastatic tumors originating from pancreatic cancer, the drug-eluting fraction may contain 5FU, oxaliplatin, irinotecan, leucovorin, gemcitabine, paclitaxel, Nab-paclitaxel, cisplatin, erlotinib, dabrasfenib, trametinib, pembrolizumab, larotrectinib, entrectinib, dabrasfenib, olaparib, or rucaparib.

[0053] By combining a radioisotope and a drug-eluting layer infused with a therapeutic agent onto the same embolizing bead or microparticle, tumor cell killing can be enhanced while maintaining a simplified procedure requiring only a single hepatic artery cannulation and a single injection of the therapeutic substance. Furthermore, the range of β-particles emitted by Y-90 in tissue is only on the order of approximately 1 mm. Therefore, ensuring co-localization of the radiation source and the radiosensitizer elution is crucial. This can be achieved by co-application onto the same embolizing bead, as combining a radioembolizing bead with separate drug-eluting particles does not guarantee that the two therapeutic agents will be delivered to the same anatomical location. In some embodiments, in addition to bio-radioembolization involving simultaneous delivery of therapeutic agents, the embolizing beads of the present invention can be used for TAE (or mild embolization), TACE (or chemoembolization), and TARE (or radioembolization). In the case of TARE, the embolizing beads of the present invention can have the ability to deliver the drug if the physician chooses to do so. In some embodiments, in the case of TARE, the embolizing bead 1 of the present invention can activate the radioactive material embedded in the core 2 without embedding the therapeutic agent within the outer layer 3. In one such embodiment, the embolic bead 1 can be injected into a patient so that the embolic bead 1 treats the tumor at the target site by emitting radiation only. In some embodiments, the therapeutic substance can be injected into the outer layer 3 after delivery to a hospital or healthcare facility but before injection into the patient. In some embodiments, the embolic beads of the present invention can provide a specific combination of a specific drug with radiation-emitting beads. In some cases, the embolic beads of the present invention may not have an activated radioisotope, which would produce particles with a core and a polymer coated on the outside, and would also be used in the TAE and TACE markets. Thus, the embolic beads of the present invention allow for embolic beads that can have radiation emission, drug delivery, and embolization capabilities, while some embolic beads may only have drug delivery and embolization (radiation-free).

[0054] In some implementations, the radiosensitizer can be used to treat various metastatic tumors affecting the liver. For example, the radiosensitizer may be a nitroimidazole hypoxic cell radiosensitizer. Alternatively, the drug elution fraction may contain any other radiosensitizing compound, including but not limited to non-nitroimidazole hypoxic cell radiosensitizers, radiosensitizing chemotherapeutic agents such as taxanes (e.g., paclitaxel), or platinum-containing compounds (e.g., cisplatin), or other unidentified radiosensitizing compounds. For example, in some implementations, in the treatment of metastatic tumors in the liver originating from colorectal cancer, the drug-eluting portion or outer layer 3 may be injected with the following: 5-FU, oxaliplatin, leucovorin, capecitabine, irinotecan, bevacizumab, panitumumab, nivolumab, ipilimumab, pembrolizumab, trastuzumab, pertuzumab, lapatinib, tucatinib, ramoximumab, Ziv-aflibercept, cetuximab, panitumumab, cannefenib, dotalimumab-gxly, lapatinib, Fam-detrastuzumab, regorafenib, trifluralin, or tipiridine.

[0055] In some embodiments, the core 2 may have a first material density, and the outer layer 3 may have a second material density. In some embodiments, the first material density may be greater than the second material density. However, advantageously, the embolic bead 1 made of the core 2 and the outer layer 3 may have a lower overall or combined density than the core 2 alone, such that the embolic bead 1 may have buoyancy or neutral buoyancy in a fluid, thus giving it advantageous flow characteristics in a fluid (e.g., human blood). Advantageous flow characteristics can be understood to mean that the embolic bead 1 can flow in a fluid without sinking and remaining within a lumen (e.g., a human artery or vein). The lower density of the embolic bead 1 may be a function of the volume ratio of the core 2 to the outer layer 3. In some embodiments, the lower density may also be a function of the physical properties of the core 2. For example, a core 2 with pores or a hollow cavity may be more buoyant than a solid core of the same size.

[0056] In some embodiments, the embolic bead 1 can be constructed from any combination of layers, such as a core 2 of a radiation-emitting material 7 and an outer layer 3 of a drug-eluting material 6, as... Figure 1A and 1B As shown in the diagram. Alternatively, the embolic bead 1 can be formed from any number of layers, as shown in the diagram. Figure 3A As shown, some of these combinations are: one of the layers is a radiation-emitting layer 2, and one of the layers is a drug-eluting layer 3. In some embodiments, such as Figure 3BAs shown, the embolic bead 1 may be incorporated into a binding layer 20 that bonds the drug elution layer 3 to other layers (e.g., the radiation-emitting layer 2). The binding layer 20 may be incorporated at the interface of any of the multiple layers. The binding layer may be a binder, which may be a polymer in nature or utilize some form of ionic bonding. The embolic bead 1 may be incorporated into a sacrificial encapsulation layer 30, which contains the eluting drug, such as..., relative to the rest of the particle. Figure 3C As shown in the diagram. When the granules are administered to the patient, the sacrificial layer dissolves and disappears, thereby exposing the drug-eluting layer 3 at the desired target location.

[0057] In the method of use, it may be necessary to activate drug elution. For example, to initiate drug delivery at the target site, it may include eliminating the sacrificial layer 30 to expose the drug elution layer 3, such as... Figure 3C As shown, or by activating an already exposed drug layer. Activation can be accomplished in a variety of ways, including: exposing the embolic bead 1 to body fluids; exposing the embolic bead 1 to body temperature; exposing the embolic bead 1 to an external energy source, such as radiation, heat, MRI, or ultrasound; exposing the embolic bead 1 to a fluid, such as saline, outside the patient's body prior to particle administration; exposing the embolic bead 1 to light; exposing the embolic bead 1 to magnetic forces; injecting CO2 that can react with the drug; and / or radiation emission from isotope fragmentation within nucleus 2 to convert the drug. In some embodiments, the method may include percutaneously delivering an energy delivery device (such as ablation / thermia) to the target site after delivery of the embolic bead 1, and delivering energy at the target site using the energy delivery device (such as ablation / thermia). In one embodiment, the method of activating the drug may include using an internal gas source within the implanted particle, which expands and causes the particle to rupture or form a pore upon exposure to body temperature or some other energy source.

[0058] In some embodiments, a method is provided for delivering micron-sized embolic beads 1 that can be mixed into fluid 40 to emit radiation. For example, the embolic beads 1 and fluid 40 can be simultaneously injected into a patient, such as... Figure 4A As shown in the diagram. In some embodiments, fluid 40 may be a chemotherapeutic agent, a hypoxia radiosensitizing agent, or any other agent used to treat tumor cells. The term radiosensitizer as used herein may refer to a hypoxia cell radiosensitizer, a bioreducing agent, a radiosensitizing chemotherapeutic agent, an immunotherapeutic agent, or any other radiosensitizing chemical, protein, drug, or compound known now or in the future. Embolizing beads 1 and fluid 40 may be contained in a single vial 100 and thus delivered to a clinician for use. For example, embolic beads 1 may be transported without any therapeutic agent contained in the drug eluent 3. In such a case, the hospital may mix embolic beads 1 with the therapeutic agent via fluid 40 before administering embolic beads 1 to the patient.

[0059] In some embodiments, the embolic beads 1 may require fluid 40 to “activate” the drug-eluting layer 3, which may be a polymer layer. In the case of a polymer layer or coating, fluid 40 may be about 100% aqueous NaCl 0.9% solution, a nonionic contrast agent medium, or about a 50 / 50 mixture of aqueous NaCl 0.9% solution and a contrast agent. Alternatively, fluid 40 may be any therapeutic agent disclosed herein. When the polymer layer (e.g., drug-eluting layer 3) is exposed to fluid 40, the embolic beads 1 may expand, causing their diameter to increase. Alternatively, exposure of the embolic beads to fluid 40 may activate the drug-eluting layer 3 without causing the embolic beads 1 to expand. In some embodiments, the introduction of the embolic beads 1 into fluid 40 may occur before or after the embolic beads 1 are transported to a hospital. In an alternative embodiment, the radiation-emitting micron-sized embolic beads 1 are delivered in a separate vial 100 from fluid 40, wherein the two are mixed and injected via a delivery mechanism, such as... Figure 4B As shown in the image.

[0060] In some implementations, the embolic beads may be radiation-emitted drug-eluting embolic beads. For example, with... Figure 1A and 1B Compared to the embolic beads 1, the particles 50 can be a single mixture of the base material 52, the radiation-emitting isotope 54, and the drug 56, such as Figure 5 As shown in the figures. When the base material is absorbed in the body, the drug can be released at timed intervals, advantageously allowing the drug 56 and the radiation-emitted isotope 54 to be delivered to the patient in larger quantities without causing harmful side effects. Particle 50 can be formulated with an overall size of about 5 micrometers to about 1000 micrometers. Particle 50 can be made of any bioabsorbable material (e.g., polymers, hydrogels, etc.). Particle 50 can be any regular or irregular 3D shape, including spheres, hemispheres, cubes, cones, cylinders, octahedrons, etc. Although the figures presented in this disclosure show particles 50 as spherical or circular, these figures are purely illustrative and do not reflect the only embodiments in which the particles can be.

[0061] According to one embodiment, in the delivery method of the embolic beads of the present invention, the method may encompass the non-simultaneous delivery of radiation-emitting embolic particles 1 and fluid 40 (e.g., a chemotherapeutic agent, a hypoxia radiosensitizer, or any other agent for treating tumor cells), such as... Figure 6As shown in the diagram. In some embodiments, fluid 40 may first be delivered via microcatheter 400 to an arterial branch 200 supplying tumor 300. Whether immediately or subsequently, the method may include delivering radioembolic beads 1 into the same arterial branch 200. The idea is to deliver fluid 40 or a drug to tumor 300, and the radioembolic beads 1 may block the lumen to trap the drug in place and prevent systemic migration of the drug. Additionally and advantageously, the radioembolic beads 1 may additionally deliver necessary radiation to treat tumor 300. Alternatively, the method may include delivering the drug directly to the tumor using an ultrasound-guided percutaneous approach, followed by delivery of radioembolization using standard techniques with a microcatheter placed in an appropriate blood vessel.

[0062] Some embodiments may include a combination of two separate particles. One particle 70 may be a radiation-emitting micron-sized embolic bead, and the second particle 80 may be micron-sized and drug-eluting. Drug elution may be performed in any of the manner described in the above embodiments. In some embodiments, the drug may be a chemotherapeutic agent, a hypoxia radiosensitizer, or any other agent for treating tumor cells, such as those disclosed herein. Particles 70 and 80 may be any shape or substance as described in the other embodiments above. The two particles 70 and 80 may be the same substance or different substances and may have the same or different densities. In some embodiments, the two particles 70 and 80 may have the same size and shape, or alternatively, they may have two different sizes and shapes. The two particles 70 and 80 may have been mixed together, such as... Figure 7A As shown, or it may be mixed when injected into the patient via a delivery device, such as Figure 7B As shown in the diagram. Alternatively, in some embodiments, the delivery method may involve first injecting the drug-eluting particles 80 individually into the patient, followed by the injection of radiation-emitting particles 70, or vice versa. The ratio of one type of particle to another can be quite wide.

[0063] In some implementations, CAR-T therapy or other cell therapies may be added as an additional element in addition to the drugs added to embolic beads 1. Cell therapies (including CAR-T) typically require the extraction of a patient's natural cells, genetic modification of these cells, and reintroduction of the modified cells into the patient. In the case of CAR-T, the patient's T cells (both CD4 and CD8) can be collected from the patient. The T cells are then genetically modified using gene-editing technologies (e.g., CRISPR / Cas9) to recognize and target tumor-specific antigens. The modified T cells can then be reintroduced into the patient via infusion to stimulate an immune response targeting cancer cells. CAR-T can not only include targeting specific antigens and proteins but can also be tailored to target hypoxic cancer cells. This differs from hypoxic cell radiosensitization because CAR-T may be more like a bioreducing agent with direct toxicity to hypoxic cells. Therefore, CAR-T therapy can be introduced in addition to hypoxic cell radiosensitizers, but not necessarily as a replacement for them. Systemic administration of CAR-T therapy often leads to cytokine release syndrome (CRS), a potentially life-threatening inflammatory response to treatment. Direct local delivery of CAR-T cells to the tumor (e.g., using the embolic beads of this invention) can reduce the severity of CRS.

[0064] Introducing CAR-T into embolic beads 1 can generate radioembolization in the following modes. In one embodiment, embolic beads 1 can provide 1) vascular embolization to prevent blood flow to tumor cells; 2) radiation emission to expose tumor cells to ionizing radiation, killing tumor cells and upregulating tumor-associated antigen presentation; 3) radiosensitization to enhance radiation-induced cell death in tumors; and 4) CAR-T to target tumor cells for an extended period of time after radiation emission and the decay of hypoxic cell radiosensitizers.

[0065] The various embodiments of the invention disclosed herein can be used for delivering cell therapies, including CAR-T. For example, in one embodiment, a method such as... Figure 1C The hollow particle method described herein involves immersing hollow spheres in CAR-T therapy, subsequently filtering them out and injecting them into the patient, or injecting them simultaneously with the particles. In some embodiments, it is also possible to use... Figure 3A The method described herein, wherein the radioactive embolic beads 1 can be constructed in layers, wherein each layer constitutes a specific form (radiation emission, drug elution, CAR-T delivery). Alternatively, it can be used with regard to... Figure 6The method involves first delivering CAR-T therapy to an arterial branch supplying the tumor, and immediately or subsequently, delivering radioembolic beads to the same arterial branch. Thus, CAR-T therapy is delivered to the tumor, and the radioembolic beads occlude the arterial lumen proximally, trapping the CAR-T therapy in place and preventing systemic migration of the modified cells. The radioembolic beads 1 can also deliver therapeutic radiation. In another embodiment, [the method may use...] Figure 7A and 7B The method described herein includes a third particle for cell therapy that can be mixed with radiation-emitting particles and drug-eluting particles.

[0066] In some embodiments, the embolic beads of the present invention disclosed herein can be used in conjunction with a variety of therapeutic agents to treat other indications or cancers. For example, in some cases, similar to the liver, the lungs are supplied with blood by two separate supplies from the pulmonary artery and the bronchial artery. Just as liver tumors are supplied by the hepatic artery, lung tumors are typically supplied by the bronchial artery. Therefore, substantially similar to the liver, branches of the bronchial artery can be embolized without damaging the remaining healthy tissue in the lungs. Furthermore, in some embodiments, this disclosure also includes applicability in the treatment of gliomas in the brain or spinal cord, as well as tumors such as the prostate. While the terms “tumor” and “tumor cells” are used herein, such terms can also refer to “solid tumor”.

[0067] The term “comprising / including” and its variations as used herein are intended to be interpreted as inclusive, not exclusive. The terms “exemplary,” “example,” and “illustrative” as used herein are intended to mean “serving as an example, instance, or illustration” and should not be construed as indicating or not indicating a preferred or advantageous configuration relative to other configurations. The terms “about,” “usually,” and “approximately” as used herein are intended to cover variations that may exist within the upper and lower limits of a range of subjective or objective values, such as variations in characteristics, parameters, sizes, and dimensions. In a non-limiting instance, the terms “about,” “usually,” and “approximately” mean plus or minus 10% or less. In a non-limiting instance, the terms “about,” “usually,” and “approximately” mean sufficiently close to be considered inclusive by one of skill in the art. As understood by one of skill, the term “substantially” as used herein refers to the complete or nearly complete range or extent of an action, feature, characteristic, state, structure, article, or result. For example, as recognized or understood by one of skill, an object being “substantially” circular means that the object is perfectly circular or nearly circular to mathematically determinable limits. In some cases, the exact permissible deviation from absolute completeness may depend on the specific context. However, in general, near-completeness will have the same full result as achieving or obtaining absolute and complete completion. As those skilled in the art will understand, the use of "substantially" is equally applicable when it is used in a negative sense to refer to the complete or near-complete lack of function, feature, characteristic, state, structure, article, or result.

[0068] In light of the foregoing description, numerous modifications and alternative embodiments of this disclosure will be apparent to those skilled in the art. Therefore, this description should be construed as illustrative only and for the purpose of teaching those skilled in the art the best mode of implementing this disclosure. The details of the structure may be significantly altered without departing from the spirit of this disclosure, and exclusive use of all modifications is reserved within the scope of the appended claims. In this specification, some embodiments have been described in a manner that enables a clear and concise description; however, it is intended, and should be understood, that various combinations or separations of embodiments may be made without departing from the invention. This disclosure is intended to be limited to the scope required by the appended claims and applicable laws and regulations.

Claims

1. An embolization particle, the particle comprising: a body having a ceramic material; a density sufficient to allow the body to move along a path; and a diameter that allows the particle to reside within a lumen at a predetermined region.

2. The particle of claim 1, wherein the body is solid, comprises a plurality of interstitial voids, a hollow lumen for containing a drug or radiosensitizing compound, or a combination thereof.

3. The particle of claim 2, for use in the treatment of at least one of the following primary or metastatic tumors: liver, lung, brain or spinal cord, prostate, breast, esophagus, upper aerodigestive tract including nasopharynx, nasal cavity, oral cavity, oropharynx, hypopharynx, larynx, neck, thyroid, lung, mediastinum, stomach, small intestine, large intestine, pancreas, spine, kidney, ureter, bladder, urethra, vagina, uterus, cervix, ovary, lymph node, muscle, and bone.

4. The particle of claim 2, wherein the body contains at least one radioisotope.

5. The particle of claim 4, wherein the radioisotope is one of yttrium-90 or holmium 166.

6. The particle of claim 4, wherein the radioisotope comprises one of a beta or gamma emitting radioisotope.

7. The particle of claim 1, wherein at least a portion of the embolization particle is radiopaque.

8. The particle of claim 1, wherein the body comprises at least one drug eluting compound layer.

9. The particle of claim 1, wherein the body comprises a plurality of interstitial voids.

10. The particle of claim 9, wherein at least a portion of the plurality of interstitial voids are interconnected with one another.

11. The particle of claim 9, wherein the density of the particle is a function of the density of the plurality of interstitial voids.

12. The particle of claim 9, wherein the body is sintered to a porosity of about 10% to 75%.

13. The particle of claim 1, wherein the body comprises a hollow lumen for containing a drug or radiosensitizing compound.

14. The particle of claim 13, further comprising: a liquid disposed within the hollow lumen.

15. The particle of claim 13, wherein the body comprises a plurality of interstitial voids disposed radially outside of the hollow lumen.

16. The particle of claim 15, wherein at least a portion of the plurality of interstitial voids are interconnected with one another.

17. The particle of claim 15, wherein at least a portion of the plurality of interstitial voids are interconnected from the hollow lumen to an outer surface of the body such that any drug or radiosensitizing compound can enter or exit the particle from the hollow lumen.

18. The particle of claim 15, wherein the density of the particle is a function of the size of the hollow lumen and the density of the plurality of interstitial voids.

19. The particle of claim 15, wherein the body is sintered to a porosity of about 10% to 75%.

20. An embolization particle, the particle comprising: a body comprising a base material and at least one radioisotope; a density sufficient to allow the body to move along a path; and a diameter that allows the particle to reside within a lumen at a predetermined region. a diameter of a lumen allowing the particle to reside at a predetermined region so that the particle emits radiation toward the predetermined region.

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