Wet preparation of radiation therapy sources

Abstract

This invention provides a method for preparing a proximity irradiation therapy source. [Solution] A method for accumulating radium radionuclides, comprising the steps of: providing a first solution containing a thorium radionuclide and a thorium-binding extractant, wherein the first solution is not bound to radium; decaying a portion of the thorium radionuclide in the first solution into radium atoms; and collecting the radium atoms resulting from the decay. The collected radium atoms may be included in a solution into which a proximal irradiation source is immersed, in a manner that collects the radium atoms into the proximal irradiation source.

Description

Technical Field

[0001] The present invention generally relates to methods for preparing radiation therapy sources, particularly alpha radiation therapy sources.

Background Art

[0002] Alpha particles are a powerful means for the radiation treatment of certain types of tumors, including malignant tumors. One type of alpha radiation therapy source is a Diffusion Alpha Radioactive Therapy (DART) source loaded with radium-223 or radium-224 atoms having a half-life suitable for treatment (e.g., not too long and not too short).

[0003] U.S. Patent No. 8,834,837 to Kelson (Patent Document 1) describes a method for preparing an alpha DART source by placing a source within a flux of radium-224 coming from a surface source of thorium-228.

[0004] U.S. Patent Application Publication 2015 / 0292061 (Patent Document 2) describes the separation of radionuclide fission products from a thorium target irradiated with proton beams.

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

Patent Document 2

Summary of the Invention

[0006] According to embodiments of the present invention, a method for accumulating radium radionuclides is provided, comprising the steps of: providing a first solution containing a thorium radionuclide and a thorium-binding extractant, wherein the first solution is not bound to radium; decaying a portion of the thorium radionuclide in the first solution into radium atoms; and collecting the radium atoms resulting from the decay.

[0007] The optional thorium-binding extractant is TOPO (trioctylphosphine oxide). The optional step of collecting radium atoms comprises the step of collecting radium atoms into a second solution. The optional step of collecting radium atoms comprises the step of collecting radium atoms onto a proximity irradiation therapy source. The optional step of collecting radium atoms comprises the steps of collecting radium atoms into a second solution and immersing the proximity irradiation therapy source in the second solution. The optional step of providing a first solution comprises the step of introducing the first solution into a chamber together with the second solution so that radium atoms resulting from decay diffuse into the second solution. The optional step of providing a first solution comprises the step of providing a solution containing a diluent having a low level of solubility with the second solution.

[0008] Option 1: The diluent has a specific gravity lower than that of water. Option 2: The diluent contains cyclohexane. Option 3: The second solution contains a salt solution. Option 4: The step of decaying a portion of the thorium radionuclide into radium atoms comprises leaving the separation solution in a chamber with walls made of a radium-attracting material for the duration of the decay, and the step of collecting the radium atoms comprises washing the radium atoms off the walls using a salt solution. Option 5: The step of decaying a portion of the thorium radionuclide in the separation solution into radium atoms comprises placing the first solution in a chamber in which radium atoms can be separated without using an acid with a pH lower than 4.

[0009] In some embodiments, the step of providing a first solution includes: providing a separation solution of a diluent having a low level of solubility and a thorium-binding extractant; combining the prepared separation solution with an initial solution containing a thorium radionuclide to allow the thorium radionuclide from the initial solution to bind to the thorium-binding extractant; and separating the separation solution from the initial solution to form a first solution.

[0010] According to embodiments of the present invention, a method is provided for producing a proximal irradiation therapy source, characterized by comprising the steps of: generating a solution containing radium atoms; and immersing a proximal irradiation therapy source in the solution in such a manner that radium atoms are collected in the proximal irradiation therapy source. Optionally, the method is also provided, comprising the step of coating the proximal irradiation therapy source with a protective coating that prevents the radium atoms from separating from the proximal irradiation therapy source but allows the daughter nuclei of the radium atoms to leave the proximal irradiation therapy source upon decay of the radium atoms.

[0011] As an option, the step of coating the proximity irradiation source with a protective coating comprises the step of coating with polysulfone or polydimethylsiloxane. As an option, the step of coating the proximity irradiation source with a protective coating comprises the step of coating with alumina. As an option, the step of coating the proximity irradiation source with manganese oxide before immersing the proximity irradiation source in the solution comprises the step of heating the proximity irradiation source after coating it with manganese oxide and then slowly cooling it. As an option, the proximity irradiation source comprises a manganese oxide proximity irradiation source. As an option, the solution comprises a salt solution or distilled water.

[0012] According to embodiments of the present invention, an apparatus for accumulating radium radionuclides is provided, further comprising: a first container for holding a first solution containing a thorium radionuclide and a thorium-binding extractant; a second container for holding a second solution containing radium atoms; a pump; and a processor configured to control the pump to introduce a third solution into the first container, and after a sufficient period for radium atoms to be collected, to remove the third solution from the first container and transfer it to the second container.

[0013] According to embodiments of the present invention, a close-range radiotherapy source is provided, further comprising: a base of a size and shape for insertion into a human organ for close-range radiotherapy; a manganese oxide coating on the base; and radium atoms attached to the manganese oxide coating. Optionally, the base includes a metal base.

[0014] Alternatively, the base may include a nonmetallic base. Optionally, the protective coating further includes an option that prevents radium atoms from separating from the proximal irradiation source but allows daughter nuclei of the radium atoms to leave the source. Optionally, the protective coating allows daughter nuclei of the radium atoms to leave the proximal irradiation source due to energy resulting from the decay of the radium atoms. Alternatively or additionally, the protective coating allows daughter nuclei of radium to leave the proximal irradiation source due to diffusion. Optionally, the protective coating may include polysulfone or alumina. Optionally, the proximal irradiation source may not contain more than 0.1% thorium atoms compared to the radium atoms on the proximal irradiation source. Optionally, the radium atoms may be attached to a manganese oxide coating in a manner resulting from annealing. [Brief explanation of the drawing]

[0015] [Figure 1] This is a flowchart of the actions performed when manufacturing an alpha-DART proximity irradiation therapy source according to one embodiment of the present invention. [Figure 2] This is a schematic diagram of a process for producing a radium proximity irradiation therapy source according to one embodiment of the present invention. [Figure 3A-B] This figure shows a chamber system before and after the radium decay period according to one embodiment of the present invention. [Figure 4A-B] This figure shows the chamber system before and after the radium decay period according to another embodiment of the present invention. [Figure 5] This is a schematic diagram of a system for generating an alpha-DART proximity irradiation therapy source according to one embodiment of the present invention. [Modes for carrying out the invention]

[0016] One aspect of several embodiments of the present invention relates to a method for producing a solution containing radioactive radium atoms. The method comprises the steps of providing a container containing thorium atoms in a solution that attracts thorium but not radium, and decaying the thorium into radium. In some embodiments, the container further comprises a second solution that is not mixed with the thorium solution. Once a sufficient amount of radium has been collected, the radium atoms can diffuse into the second solution, which is removed from the container along with the radium atoms. In other embodiments, the radium atoms can accumulate on the walls of the container and be collected from the walls after the thorium solution has been removed from the container. The thorium includes, as an option, thorium-228. However, it should be noted that the principle of the present invention can also be used for thorium-227, for example, derived from actinium-227.

[0017] One aspect of several embodiments of the present invention relates to a method for generating a radium proximity irradiation therapy source. The method includes the step of immersing a proximity irradiation therapy source in a solution containing radium atoms, in such a manner that radium atoms are collected on the proximity irradiation therapy source.

[0018] Radium solutions are produced using the methods described above as an option. Alternatively, radium solutions are produced using other suitable methods known in the art, such as separating radium from thorium using a fractionation column.

[0019] (overview) Figure 1 is a flowchart of acts performed when manufacturing a radium brachytherapy source according to an embodiment of the present invention. Figure 2 is a schematic diagram of the process of Figure 1.

[0020] The process of Figure 1 begins, as an option, with receiving an initial solution 20 containing the thorium-228 radionuclide 22. A separation solution 30 is formed from a thorium-binding extractant that binds to thorium but not to radium, has low solubility in water (i.e., less than 0.1%), and is dissolved in a diluent having a different specific gravity from water, such as cyclohexane as an option (104). The separation solution 30 is loaded (106) into a container 40 containing the received (102) initial solution 20. After an operating time (108), the thorium radionuclide 22 from the initial solution 20 attaches to the thorium-binding extractant in the separation solution. Note that the diluent prevents the separation solution 30 from mixing with the initial solution 20.

[0021] Now the separation solution 30 containing the thorium radionuclide 22 is separated from the initial solution 20 and placed in a radium collection chamber 60 (110), where it is left for a decay period (112) sufficient for a certain proportion of the thorium radionuclide to radioactively decay into radium. After the decay period (112), the separation solution 30 is removed from the radium collection chamber 60 (114), leaving radium atoms 62 that do not bind to the separation solution 30 in the radium collection chamber 60. A liquid extraction solution 50 is used to wash away the radium atoms 62 from the radium collection chamber 60. Next, a brachytherapy source 80 is immersed in the extraction solution 50 (116) to collect the radium atoms 62 on its surface. As an option, before being immersed in the extraction solution 50 (116), the brachytherapy source 80 is coated (130) with manganese oxide suitable for attracting and / or binding the radium atoms 62 to the brachytherapy source 80.

[0022] In some embodiments, after the proximity irradiation therapy source 80 is removed from the extraction solution 50, the proximity irradiation therapy source is coated with a suitable coating (118) that prevents the radium atoms 62 from leaving the proximity irradiation therapy source while allowing the daughter radon nuclides to leave the proximity irradiation therapy source. In particular, the coating is, as an option, sufficient to prevent the release of radium atoms in the thermal species. Alternatively, other species methods such as gamma-ray species can be used, and in such cases, the coating can be made thinner or the coating can be dispensed with altogether. The list of all results cannot be loaded

[0023] In some embodiments, the coating comprises polysulfone, such as MED2-4213 manufactured by Solvay. Alternatively or additionally, the coating comprises polydimethylsiloxane (PDMS), such as Eviva EV-500 provided by Specialty Polymers, or parylene N. As an option, the coating has a thickness that allows the diffusion of radon through the coating. As an option, the coating has a thickness of less than 10 microns, less than 5 microns, less than 1 micron, less than 0.5 micron, or even less than 0.3 micron. In some embodiments, the coating has a thickness of at least 0.05 micron, and further at least 0.1 micron. In other embodiments, for example, when the coating consists of a PDMS coating, the coating is relatively thick and has a thickness of at least 1 micron, at least 3 microns, further at least 5 microns or at least 8 microns.

[0024] In some embodiments, the coating consists of aluminum oxide, also known as alumina. The alumina coating is, as an option, sufficiently thin to allow the outflow of radon due to radioactive recoil. As an option, the alumina coating is produced using atomic layer deposition (ALD) and has a thickness of less than 50 nanometers, less than 10 nanometers, or less than 6 nanometers.

[0025] In some embodiments, prior to coating the proximity irradiation source 80 (118), the proximity irradiation source 80 is annealed by heating and then slowly cooling it. Optionally, during annealing, the proximity irradiation source 80 is heated to at least 275°C, at least 350°C, and even at least 400°C. In some embodiments, the annealing is performed in a low-oxygen environment such as a vacuum, or in an inert gas environment.

[0026] (Details of the separation solution) Acidic solutions containing thorium-228 20 are commercially available from various providers, including Eckert-Ziegler in Germany and Oak Ridge National Laboratory (ORNL) in the United States.

[0027] The preparation of the separation solution 30 (104) is carried out using any suitable method known in the art, such as the method described in Afifi et al., "Extraction and Measurement of Thorium and Its Application to Geological Samples Using Trioctylphosphine Oxide," Arab Journal of Nuclear Science and Applications, 45(3), 2012, the disclosure of which is incorporated herein by reference.

[0028] In some embodiments, the thorium-binding extractant includes organic extractants such as TOPO (trioctylphosphine oxide), tributyl phosphate, N,N,N',N'-terahexyl succinyl amide, N-alkylamide, trialkyl-methylammonium nitrate, didodecyl phosphate, 2-ethylhexylphenyl phosphate, diisobutyl ketone, or hexaacetate calixsalen.

[0029] Alternatively or additionally, thorium-binding extractants may include one or more sulfoxides, such as dibutyl-n-sulfoxide (DBSO), as described, for example, in Khan et al., "Solvent Extraction of Thorium from Nitric Acid Solution Using Di-N-Butyl Sulfoxide (DbSO) in Xylene," Journal of Radioanalytical and Nuclear Chemistry, December 1995, col. 198, No. 2, pp. 409–421, whose disclosure is incorporated herein by reference.

[0030] In some embodiments, the thorium-binding extractant includes an extractant that binds to lead in addition to thorium, in order to reduce the amount of lead that enters the extraction solution 50 and ultimately reaches the proximity irradiation therapy source 80. Alternatively or additionally, a lead-binding material is added to the separation solution 30.

[0031] Instead of using cyclohexane as a diluent, other diluents such as benzene, carbon tetrachloride, chloroform, kerosene, toluene, dodecane, and o-xylene are used.

[0032] In some embodiments, during the operating time (108), the container 40 is shaken to induce the binding of thorium to the thorium-binding extractant. In these embodiments, the operating time (108) is at least 30 seconds, at least 1 minute, at least 3 minutes, or even at least 5 minutes. The operating time (108) is optionally less than 15 minutes, less than 10 minutes, or even less than 5 minutes.

[0033] Alternatively, container 40 is not shaken during the operating time (108). According to this alternative, the operating time is long enough to diffuse the thorium into the thorium-bound extractant, and options include at least 6 hours, at least 12 hours, or even at least 24 hours.

[0034] Container 40 is shown closed. This is particularly helpful when shaking to induce bonding. However, please note that other types of containers, including open containers, are also available.

[0035] (Details on radium collection) In some embodiments, during the decay period (112), the extraction solution 50 is contained in the radium collection chamber 60 along with the separation solution 30 and the thorium radionuclide 22 contained therein, and as a result, radium atoms 62 formed from the decay of the thorium radionuclide 22 diffuse into the extraction solution 50. Optionally, the extraction solution 50 contains distilled water. Optionally, distilled water constitutes at least 80%, at least 90%, at least 95%, or at least 99% of the extraction solution 50. The use of distilled water has been found to facilitate the transfer of radium atoms to the proximity irradiation therapy source 80 more readily than other solutions such as salt solutions. Optionally, in embodiments where the extraction solution 50 contains distilled water, the radium collection chamber 60 is formed of a material that does not readily bind to radium, such as Teflon®. Alternatively, the extraction solution 50 contains a salt solution such as potassium chloride (KCl). Salt solutions generally reduce the precipitation of radium onto the walls of the radium collection chamber 60, and therefore can be used in embodiments where the radium collection chamber 60 is made of a glass container. However, it should be noted that even in embodiments where the radium collection chamber 60 is not made of glass, but rather of another material such as Teflon®, the extraction solution 50 may contain a salt solution. As an alternative, the radium collection chamber 60 does not contain inner walls or other elements that strongly bind to the radium atoms 62 in an embodiment that requires an acid with a pH of 4 or less to extract the radium atoms 62 from the chamber. Therefore, the radium atoms 62 can be collected in a non-acidic solution, which may be more convenient for transferring the radium atoms 62 to a nearby irradiation therapy source 80.

[0036] The salt in the salt solution 50 optionally has a concentration of at least 0.001 moles or at least 0.01 moles. In some embodiments, the concentration of salt in the salt solution is less than 0.1 moles. Optionally, the pH of the salt solution is approximately 5 (±10%). Instead of the salt solution, the extraction solution 50 contains a weak acid with a pH between 2 and 3. According to this alternative, after the removal of the separation solution 30 (114) and before immersing the proximity irradiation therapy source 80 in the extraction solution 50 (116), the extraction solution 50 is optionally titrated to be suitable for transferring radium atoms 62 to the proximity irradiation therapy source 80.

[0037] In some embodiments, instead of removing the separation solution 30 from the radium collection chamber 60, the extraction solution 50 is removed to a separate container and the separation solution 30 is left in the radium collection chamber 60. The full list of results cannot be loaded.

[0038] In other embodiments, during the decay period (112), the separation solution 30 and the thorium radionuclide 22 within it are placed in the radium collection chamber 60 by themselves, and the radium atoms 62 formed by the decay settle on the walls of the radium collection chamber 60. After the decay period (112), the separation solution 30 is removed from the radium collection chamber 60, and the extraction solution 50 is passed through the radium collection chamber 60 to collect the radium atoms 62 from the walls of the chamber. In these embodiments, the extraction solution 50 optionally contains a salt solution such as potassium chloride (KCl) or a weak acid suitable for washing the radium atoms 62 from the walls of the radium collection chamber 60. Optionally, in these embodiments, the radium collection chamber 60 is configured in a shape having a large surface area, for example, in the shape of a long, narrow column. For example, the radium collection chamber 60 may have the shape of a long, narrow tube with a diameter of less than 15 millimeters, less than 10 millimeters, or even less than 5 millimeters. The length of the tube that functions as the radium collection chamber 60 is optionally selected depending on the amount of separation solution 30 used. In some embodiments, the tube has a length of at least 10 centimeters, and moreover, at least 15 centimeters. Optionally, in these embodiments, the tube has two openings, which allow the flow of the extraction solution 50 from a first opening at one end to a second opening at the other end, in a manner that washes away precipitated radium atoms 62 from the walls of the tube that functions as the radium collection chamber 60.

[0039] Instead of using the extraction solution 50, the separation solution 30 is left to stand for a sufficient amount of time (112) for some of the radionuclides to undergo radioactive decay into radium. The source 80 is then immersed in the separation solution 30 to collect radium atoms (62) from its surface. This alternative may be used, in particular, when the collection of some thorium radionuclides 22 on the source 80 is acceptable and it is not necessary to remove the thorium radionuclides 22 from the container in which the source 80 is immersed. As an option, in these embodiments, the container holding the separation solution 30 may include a material such as Teflon® that does not bond to the radium atoms 62.

[0040] (Details of the source of close-range radiation therapy) The proximal radiotherapy source 80 can have substantially any shape suitable for proximal radiotherapy treatment. For example, the proximal radiotherapy source 80 may have a cylindrical, planar, or ball shape. In some embodiments, the proximal radiotherapy source 80 includes a material that attracts radium atoms 62 from the extraction solution 50. For example, the proximal radiotherapy source 80 may include a metal source or be coated with a metal. These embodiments are particularly useful when the extraction solution 50 includes distilled water, which allows radium atoms 62 to diffuse into the metal source. It should be noted that, according to some of these embodiments, coating (130) of the proximal radiotherapy source 80 with manganese oxide is not necessary and can be skipped.

[0041] In some embodiments, the proximity radiotherapy source 80 includes a material that does not interfere with one or more medical imaging modalities, such as ultrasound or MRI, which is used for implanting the proximity radiotherapy source 80.

[0042] Alternatively or additionally, the proximity irradiation source 80 includes a material for bonding with manganese oxide, which then bonds to radium atoms 62. Alternatively, the proximity irradiation source 80 includes a metal base suitable for receiving the manganese oxide coating. Alternatively, the proximity irradiation source 80 includes a non-metallic base metal-coated with a metal that bonds well to the manganese oxide coating. Alternatively, the proximity irradiation source 80 includes any other material that can bond to the manganese oxide coating.

[0043] Manganese oxide may include manganese dioxide (MnO2). Alternatively, manganese oxide may include other manganese oxides bonded to radium, such as manganese(IV) dioxide, manganese(II) oxide (MnO), manganese(II,III) oxide (Mn3O4), manganese(III) oxide (Mn2O3), and manganese(VII) oxide (Mn2O7), or mixtures of various manganese oxides.

[0044] Coating (130) of the proximity irradiation therapy source 80 with manganese oxide is optionally performed by immersing the proximity irradiation therapy source 80 in potassium permanganate (KMnO4). The coating (130) is optionally performed at a temperature of at least 60°C, or even at least 80°C, e.g., about 90°C. After coating the proximity irradiation therapy source 80, the proximity irradiation therapy source and the manganese oxide coating are optionally cooled slowly over at least 1 hour, or at least 6 hours. The applicant has found that slow cooling achieves a more stable coating. Alternatively, other suitable methods for coating with manganese oxide are used. In other embodiments, any other material suitable for bonding radium atoms 62 is used instead of, or in addition to, manganese oxide.

[0045] In some embodiments, before immersing the proximity irradiation therapy source 80 in the extract solution 50, the extract solution 50 is diluted, concentrated, or undergoes a chemical change. For example, as described above, the extract solution 50 may be titrated to a desired pH level, e.g., about pH 5. Dilution and / or concentration are performed as an option to bring the radium concentration in the extract solution 50 within a desired limit. As an option, the radium concentration is at least 3 microcuries per milliliter, at least 5 microcuries per milliliter, or even at least 10 microcuries per milliliter. In some embodiments, the radium concentration is less than 60 microcuries per milliliter, less than 50 microcuries per milliliter, or even lower than 40 microcuries per milliliter.

[0046] Immersion (116) of the proximity irradiation therapy source 80 into the extraction solution 50 is optionally performed for at least 1 hour, at least 5 hours, or even at least 10 hours. Alternatively, methods known in the art to facilitate the collection of radium in the proximity irradiation therapy source 80, such as shaking and / or mixing, are used. In some embodiments, the extraction solution 50 is heated to facilitate the collection of radium in the proximity irradiation therapy source 80. The extraction solution 50 is optionally heated to a temperature that generates an electric current in the solution, such as at least 50°C, at least 60°C, at least 75°C, and even at least 80°C. Alternatively, the solution is heated to a temperature of 90°C or less or 80°C or less. According to this alternative, the immersion is optionally performed for less than 3 hours, less than 1 hour, or even less than 30 minutes. The time (116) for immersing the proximity irradiation therapy source 80 in the extraction solution 50 is optionally selected according to the desired activity of the proximity irradiation therapy source and the concentration of radium in the extraction solution 50.

[0047] In embodiments of large-scale production of the proximity irradiation therapy source 80, the rate of radium atom 62 production in the radium collection chamber 60 is monitored, and when the rate falls below a desired level, the separation solution 30 is replaced with a different batch of separation solution 30 with a higher thorium density. Alternatively, a concentrated separation solution 30 having high-density thorium is added to the separation solution 30 currently in the radium collection chamber 60. As an alternative, before adding the concentrated separation solution 30 having high-density thorium, a portion of the separation solution 30 with a lower thorium density is removed from the radium collection chamber 60 to make room for the concentrated separation solution 30. It should be noted that instead of monitoring the actual decay rate of thorium to radium, the decay rate is estimated based on the half-life of thorium and the original concentration of thorium in the separation solution 30, and the timing of adding and / or replacing the separation solution 30 is selected accordingly.

[0048] The concentration of thorium in the separation solution 30 when it is in the radium collection chamber 60 is, as an option, at least 0.08 millicuries, at least 0.1 millicuries, or at least 0.2 millicuries per milliliter. The applicant has found that using higher concentrations of thorium can damage cyclohexane by causing the release of hydrogen atoms, and therefore the concentration of thorium in the separation solution 30 is, as an option, not more than 2 millicuries per milliliter, or even 1 millicury. In some embodiments, upper and lower limits are defined for the concentration of thorium in the separation solution 30. When the concentration reaches the lower limit, the separation solution 30 is replaced, or a higher concentration of thorium solution is added to the radium collection chamber 60 to bring the thorium concentration up to the upper limit.

[0049] The method in Figure 1 is independent of the quality (e.g., purity) of the initial solution 20 because the radium directed to the proximal irradiation source is separated from the initial solution 20 before it is directed to the proximal irradiation source. Therefore, the resulting proximal irradiation source can be prepared without mixing thorium with radium, or with at least a small amount of thorium atoms, e.g., less than 1 percent or less than 0.1% of the number of radium atoms on the proximal irradiation source. However, it should be noted that in some cases, a proximal irradiation source containing both radium and thorium is desirable. In such cases, the desired percentage of thorium can be achieved by mixing the solution with thorium of the desired concentration to obtain the extract solution 50.

[0050] The method in Figure 1 allows for high utilization of thorium. As an alternative, the method in Figure 1 does not require high temperatures, and in some embodiments, the entire process in Figure 1 is performed at temperatures below 180°C or even below 140°C. However, in other embodiments, one or more steps of the method may require temperatures above 250°C, or even higher than 300°C or 350°C.

[0051] (chamber) Figures 3A-3B show a chamber system 300 before and after the decay period (112) according to one embodiment of the present invention. The chamber system 300 is a possible implementation of the chamber 60 discussed above. The chamber 310 of system 300 is equipped with an upper cork 302 for loading the chamber 310 with a separation solution 30 containing the thorium radionuclide 22. At the bottom, the chamber 310 has a narrow opening 304 connected to a narrow Teflon® tube 306, the Teflon® tube having a distal septum 308 through which the extraction solution 50 is introduced into the chamber 310. The septum 308, optionally made of silicone or rubber, allows for leak-free introduction and removal of the liquid by a needle.

[0052] The placement (110) of the separation solution 30 into the chamber 310 is done through the upper opening of the chamber 310, which is sealed by an upper cork 302. Before, after, and / or simultaneously with the placement of the separation solution 30, an appropriate amount of extract solution 50 is introduced into the chamber 310 through the septum 308. The extract solution 50 fills a narrow Teflon® tube 306 and part of the chamber 310. Since the separation solution 30 is lighter than the extract solution 50, the separation solution 30 floats on top of the extract solution 50, as shown in Figure 3A. After a decay period (112), the extract solution 50 is removed from the chamber 310 through the septum 308, and as a result, only the separation solution 30 remains in the chamber 310, as shown in Figure 3B. It should be noted that a small portion of the extract solution 50 remains as an option in the narrow Teflon® tube 306, and not all of the extract solution 50 is extracted from the chamber system 300. This is advantageous in ensuring that no meaningful portion of the separation solution 30, which could contaminate the extraction solution 50, leaves the chamber system 300 with the extraction solution 50. The narrow size of the Teflon® tube 306 is selected as an option to minimize the amount of extraction solution 50 remaining in the chamber system 300, on the one hand, and to prevent any remaining separation solution 30 from leaving the chamber system 300 with the extraction solution 50. It should be noted that a tube of another suitable material, such as silicone or rubber, can be used instead of the Teflon® tube 306. This option is particularly useful if the separation solution 30 does not enter the tube and therefore there is no issue of incompatibility between the separation solution 30 and the material forming the tube.

[0053] Subsequently, an additional extraction solution 50 can be introduced into the chamber 310 via the septum 308 to collect radium atoms from the same separation solution 30. When the concentration of thorium in the separation solution 30 falls below a threshold, an additional amount of separation solution 30 containing a high concentration of thorium is introduced into the chamber 310 via the cork 302. Thus, the system 300 can be used for the continuous production of radium-containing extraction solution 50.

[0054] According to some embodiments, the placement (110) of the separation solution 30 into the chamber 310 is performed at a much slower rate than the introduction of the extraction solution 50 into the chamber 310. For example, the placement (110) of the separation solution 30 can be performed every 10, 100, or even every 1000 steps of introducing the extraction solution 50 into the chamber 310. Therefore, in these embodiments, the placement (110) of the separation solution 30 into the chamber 310 can be considered an initialization step.

[0055] Figures 4A-4B show the chamber system 400 before and after the decay period (112) according to another embodiment of the present invention. In system 400, the chamber 310 has a narrow extension 402 on its inner wall that is suitable for collecting radium atoms.

[0056] During the system initialization phase, the separation solution 30 containing the radionuclide is filled into the narrow extension section 402 through an opening generally sealed with an upper cork 302, as shown in Figure 4A. After a first decay period (112), as shown in Figure 4B, the extraction solution 50 is loaded into the narrow extension section 402 through the septum 308 and tube 306, pushing the separation solution 30 into the chamber 310. The extraction solution 50 collects radium atoms from the walls of the narrow extension section 402 and is removed along with the radium atoms through the septum 308. The separation solution 30 then returns to the narrow extension section 402, as shown in Figure 4A, and another round of radium atom generation begins.

[0057] Figure 5 is a schematic diagram of a system 500 for producing an Alpha-DART proximity irradiation therapy source according to one embodiment of the present invention. The system 500 comprises a manifold 502 connected to various containers via valves 508 and liquid tubes 504. The containers include an extraction solution 50 container 510 and a radium collection chamber 560 into which radium atoms 62 (Figure 2) formed from the decay of thorium radionuclide 22 diffuse into the extraction solution 50. The containers optionally include an evaluation chamber 518, a radium storage container 530 and a water chamber 540. In some embodiments, the manifold 502 is connected to one or more multi-compartment immersion containers 550, which include a plurality of immersion compartments 552 and are arranged to receive elements that will be converted into proximity irradiation therapy sources 80 by accumulating radium atoms. Optionally, a robotic arm 580 is used to insert the proximity irradiation therapy sources 80 into the immersion compartments 552 and remove them therefrom. Optionally, a pump 536 is connected to the manifold 502 and used to transfer liquids between the containers of the system 500. As an alternative, the dump 570 is connected to one of the valves 508 on the manifold 502 to receive the waste liquid that is no longer needed.

[0058] In some embodiments, one or more containers, such as the extraction solution container 510, the radium collection chamber 560, the evaluation chamber 518, and / or the water chamber 540, are placed on their respective measuring instruments 572, which are used to monitor the volume of liquid in the containers. Alternatively or additionally, any other sensors can be used to monitor the contents of the containers.

[0059] Alternatively, the CPU 548 controls the operation of the system 500 by sending control commands to the valve 508, the pump 536, and / or the robot arm 580. Commands from the CPU 548 are transmitted wired or wirelessly using any suitable method known in the art. The valve 508 is generally kept closed and is opened when it is necessary to allow a liquid to pass through a particular valve, and then closed again after the liquid has been transferred.

[0060] During operation, pump 536 transfers a certain amount of extract solution 50 from container 510 to radium collection chamber 560. Prior to this, and / or afterward, separation solution 30 is introduced into radium collection chamber 560 via upper valve 514. After a predetermined time, and / or after it is determined that sufficient radium has been collected, pump 536 recovers the extract solution 50 from collection chamber 560 to evaluation chamber 518, where the extract solution 50 and / or its radium content is evaluated. If the quality of the extract solution 50 is sufficient, pump 536 transfers the extract solution 50 to radium storage container 530. However, if the concentration of the extract solution 50 needs to be adjusted, pump 536 delivers the required amount of water from water chamber 540 to evaluation chamber 518. Alternatively or additionally, the extract solution 50 is returned to collection chamber 560 to receive more radium. In parallel with the production of the radium extract solution 50, the radium extract solution 50 is transferred to one or more multi-compartment immersion containers 550, and the proximity irradiation therapy source 80 is immersed in the radium extract solution 50. The system 500 may include any number of collection chambers 560 connected to a single manifold 502 for parallel production of the radium solution.

[0061] As shown in the illustration, the valve 508 is arranged linearly along the manifold 502. However, in other embodiments, the tubes 504 and / or the valve 508 are arranged radially on the manifold 502. As an option, the manifold 502 has a half-sphere or a full sphere shape. To transfer liquid between two containers, the valve 508 connected to the source container is opened, and the pump 536 extracts a certain amount of liquid from there into the pump's internal chamber. The valve 508 connected to the source container is then closed, and the valve connected to the destination container is opened, and the pump is activated to push the liquid in its internal chamber into the destination container.

[0062] (Conclusion) It will be understood that the above methods and apparatus should be interpreted as including methods of using the apparatus and apparatus for performing the methods. Features and / or steps described in relation to one embodiment may be used in conjunction with other embodiments, and it should be understood that not all embodiments of the present invention have all features and / or steps shown in particular figures or described in relation to one particular embodiment. Some dependent claims depend on only one parent claim, which is due to the formal requirements of some jurisdictions, and it should be noted that the present invention is considered to include all combinations of dependent claims unless otherwise stated as unfeasible or specifically stated. Tasks may not necessarily be performed in the exact order described.

[0063] It should be noted that some of the embodiments described above may not be essential to the present invention and may include structures, actions, or details of structures and actions described as examples. Structures and actions described herein are interchangeable with equivalents that perform the same function, even if the structures or actions differ, as is known in the art. The embodiments described above are cited as examples and the present invention is not limited to those specifically shown and described herein. Rather, the scope of the present invention includes both combinations and subcombinations of the various features described above, as well as their variations and modifications not disclosed in the prior art, which will be recalled by those skilled in the art when reading the foregoing description. Accordingly, the scope of the present invention is limited only by the elements and limitations used in the claims, and “having,” “including,” “having,” and combinations thereof, when used in the claims, mean “including but not limited to.”

Claims

1. A first solution comprising the steps of providing a thorium radionuclide (22) and a thorium-binding extractant, wherein the first solution is not bound to radium; The steps include: decaying a portion of the thorium radionuclide in the first solution into radium atoms (62); and The steps include: collecting the radium atoms (62) produced from the decay; It has, The step of collecting the radium atoms (62) includes the step of collecting the radium atoms on a proximity irradiation therapy source (80). A method for accumulating radium radionuclides, characterized by the following:

2. The method according to claim 1, characterized in that the thorium-binding extractant has TOPO (trioctylphosphine oxide).

3. The method according to claim 1, characterized in that the step of collecting the radium atoms comprises the step of collecting the radium atoms in a second solution (50).

4. The method according to claim 1, characterized in that the step of collecting the radium atoms (62) comprises collecting the radium atoms in a second solution (50) and immersing the proximity irradiation therapy source (80) in the second solution.

5. The step of collecting the radium atoms (62) is: The steps include: diffusing the radium atoms (62) from the first solution; and The steps include: collecting the radium atoms (62) that have diffused from the first solution and are generated from the decay; The method according to any one of claims 1-4, characterized by having [a certain characteristic].

6. The method according to claim 1, characterized in that the step of providing the first solution comprises introducing the first solution, together with the second solution which is not mixed with the first solution, into a chamber (60) so that the radium atoms (62) resulting from the decay diffuse into the second solution (50).

7. The method according to 6, characterized in that the step of providing the first solution comprises providing a solution containing a diluent having a low level of solubility with the second solution (50).

8. The method according to 7, characterized in that the diluent has a specific gravity lower than that of water.

9. The method according to 7, characterized in that the diluent contains cyclohexane.

10. The method according to 6, characterized in that the second solution contains a salt solution.

11. The method according to claim 1, wherein the step of decaying a portion of the thorium radionuclide into radium atoms (62) comprises leaving the first solution in a chamber (60) having a wall made of a radium-attracting material for a decay period, and the step of collecting the radium atoms (62) comprises washing the radium atoms off the wall using a salt solution.

12. The method according to claim 1, characterized in that the step of decaying a portion of the thorium radionuclide (22) into the radium atoms (62) comprises placing the first solution in a chamber (60) in which the radium atoms can be separated without using an acid with a pH lower than 4.

13. The step of providing the first solution is: The steps include providing a separation solution (30) of a diluent having a low level of solubility and a thorium-bound extractant; The steps include: combining the prepared separation solution (30) with an initial solution (20) containing a thorium radionuclide (22) so that the thorium radionuclide (22) from the initial solution (20) binds to the thorium-binding extractant; and The steps include: separating the separation solution (30) from the initial solution (20) to form the first solution; The method according to claim 1, characterized by having the following features.

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