Radiation therapy source wet fabrication

Abstract

A method of accumulating radium radioisotopes, the method comprising providing a first solution comprising thorium radioisotopes and a thorium-binding extractant, wherein the first solution does not bind radium; allowing a portion of the thorium radioisotopes in the first solution to decay into radium atoms; and collecting the radium atoms resulting from the decay. The collected radium atoms can be contained in a solution into which a brachytherapy source is immersed in a manner that collects the radium atoms onto the brachytherapy source.

Description

Field of the invention

[0001] The present invention relates generally to radiotherapy, and in particular to a method of preparing an alpha radiotherapy source. BACKGROUND

[0003] Alpha particles are a potent means of radiotherapy for certain types of tumors, including malignant tumors. One type of alpha radiotherapy source is a diffuse alpha emitter radiotherapy (DART) source loaded with radium-223 atoms or radium-224 atoms, which have a half-life suitable (e.g., not too long and not too short) for therapeutic purposes.

[0004] U.S. Patent 8,834,837 to Kelson describes a method of preparing an alpha DART source by positioning a source in a flux of radium-224 from a surface source of thorium-228.

[0005] U.S. Patent Publication 2015 / 0292061 describes the separation of radionuclide fission products from a proton-irradiated thorium target. SUMMARY

[0007] According to an embodiment of the present invention, there is provided a method of accumulating radium radionuclides, the method comprising providing a first solution comprising thorium radionuclides and a thorium-binding extractant, wherein the first solution does not bind radium; allowing a portion of the thorium radionuclides in the first solution to decay into radium atoms; and collecting the radium atoms resulting from the decay.

[0008] Optionally, the thorium-binding extractant comprises TOPO (trioctylphosphine oxide). Optionally, collecting the radium atoms comprises collecting the radium atoms into a second solution. Alternatively or additionally, collecting the radium atoms comprises collecting the radium atoms onto a brachytherapy source. Optionally, collecting the radium atoms comprises collecting the radium atoms into a second solution and immersing a brachytherapy source into the second solution. Optionally, providing the first solution comprises introducing the first solution into a chamber having a second solution, such that the decaying radium atoms diffuse into the second solution. Optionally, providing the first solution comprises providing a solution comprising a diluent having a low solubility level in the second solution.

[0009] Optionally, the diluent has a specific gravity that is lower than the specific gravity of water. Optionally, the diluent includes cyclohexane. Optionally, the second solution includes a salt solution. Optionally, allowing a portion of the thorium radionuclide to decay into radium atoms includes leaving the separation solution in a chamber having walls made of a material that attracts radium over a decay period, and collecting the radium atoms includes washing the radium atoms off the walls using a salt solution. Optionally, allowing a portion of the thorium radionuclide in the separation solution to decay into radium atoms includes placing the first solution in a chamber from which radium atoms are separable without using an acid having a pH lower than 4.

[0010] In some embodiments, providing the first solution includes providing a separation solution of a thorium-binding extractant and a diluent having a low solubility level, combining the prepared separation solution with an initial solution containing a thorium radionuclide such that the thorium radionuclide from the initial solution binds to the thorium-binding extractant, and separating the separation solution from the initial solution to form the first solution.

[0011] According to embodiments of the present invention, there is also provided a method of producing a brachytherapy source, the method including producing a solution containing radium atoms; and immersing a brachytherapy source into the solution in a manner that collects the radium atoms onto the brachytherapy source. Optionally, the method further includes coating the source with a protective coating that prevents the radium atoms from detaching from the source, but allows the nuclei of the radium atoms to exit the source upon decay of the radium atoms.

[0012] Optionally, coating the source with the protective coating includes coating by polysulfone or polydimethylsiloxane. Optionally, coating the source with the protective coating includes coating by aluminum oxide. Optionally, the method further includes coating the source with manganese oxide prior to immersing the source into the solution. Optionally, the method further includes, after coating the source with manganese oxide, heating the source and allowing the source to cool slowly. Optionally, the source includes a manganese oxide source. Optionally, the solution includes a salt solution or distilled water.

[0013] According to embodiments of the present invention, there is also provided an apparatus for accumulating radium radionuclides, the apparatus including: a first container containing a first solution including a thorium radionuclide and a thorium-binding extractant; a second container containing a second solution including 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 of time for collecting the radium atoms, remove the third solution from the first container and transfer the third solution to the second container.

[0014] There is also provided, in accordance with an embodiment of the application, a brachytherapy source comprising a base sized and shaped for insertion into a human organ for brachytherapy; a manganese oxide coating on the base; and a radium atom attached to the manganese oxide coating. Optionally, the base comprises a metal base.

[0015] Alternatively, the base comprises a non-metal base. Optionally, the brachytherapy source further comprises a protective coating that prevents the radium atom from detaching from the source, but allows the nuclei of the radium atom to exit the source. Optionally, the protective coating allows the nuclei of the radium atom to exit the source due to energy generated by decay of the radium atom. Alternatively or additionally, the protective coating allows the nuclei of the radium to exit the source due to diffusion. Optionally, the protective coating comprises polysulfone and / or aluminum oxide. Optionally, the brachytherapy source contains no more than 0.1% of thorium atoms on the source than radium atoms. Optionally, the radium atom is attached to the manganese oxide coating in a manner resulting from annealing. BRIEF DESCRIPTION OF DRAWINGS

[0017] Figure 1 is a flowchart of actions performed in producing an alpha DART brachytherapy source, in accordance with an embodiment of the application;

[0018] Figure 2 is a schematic illustration of a process for producing a radium brachytherapy source, in accordance with an embodiment of the application;

[0019] Figures 3A-3B shows a chamber system before and after a radium decay period, in accordance with an embodiment of the application;

[0020] Figures 4A-4B shows a chamber system before and after a decay period, in accordance with other embodiments of the application; and

[0021] Figure 5 is a schematic illustration of a system for producing an alpha DART brachytherapy source, in accordance with an embodiment of the application.

[0022] DETAILED DESCRIPTION OF EMBODIMENTS

[0023] Aspects of some embodiments of the invention relate to a method of producing a solution comprising radium atoms. The method comprises providing a container comprising thorium atoms in a solution, the solution attracting thorium but not radium; and allowing the thorium to decay into radium. In some embodiments, the container further comprises a second solution that does not mix with the thorium solution. When a sufficient amount of radium has been collected, the radium atoms are allowed to diffuse into the second solution, which is removed from the container along with the radium atoms. In other embodiments, the radium atoms are allowed to accumulate on the walls of the container, and are collected from the walls after the thorium solution is removed from the container. The thorium optionally comprises thorium-228. However, it should be noted that the principles of the invention can also be used with thorium-227, for example thorium-227 produced from actinium-227.

[0024] Aspects of some embodiments of the invention relate to a method of producing a radium brachytherapy source. The method comprises immersing the brachytherapy source in a solution comprising radium atoms in a manner that collects the radium atoms onto the brachytherapy source.

[0025] The radium solution is optionally produced using the method described above. Alternatively, the radium solution is produced using any other suitable method known in the art, such as by separating radium from thorium using a fractional distillation column.

[0026] SUMMARY

[0027] Figure 1 is a flowchart of actions performed in producing a radium brachytherapy source according to embodiments of the invention. Figure 2 is Figure 1 is a schematic diagram of the process of

[0028] Figure 1 The process of is optionally initiated by receiving (102) an initial solution 20 comprising thorium-228 radionuclides 22. A separation solution 30 is prepared (104) from a thorium-binding extractant that binds to thorium but not to radium, dissolved in a diluent that has a low solubility level in water (i.e., less than 0.1%) and optionally has a specific gravity that is different than that of water, such as cyclohexane. The separation solution 30 is loaded (106) into a container 40 that contains the received (102) initial solution 20. After an operational duration (108), the thorium radionuclides 22 from the initial solution 20 attach to the thorium-binding extractant in the separation solution 30. It should be noted that the diluent prevents the separation solution 30 from mixing with the initial solution 20.

[0029] The separated solution 30 now containing thorium radionuclides 22 is separated from the initial solution 20 and placed (110) in a radium collection chamber 60, where the separated solution 30 is held for a decay period (112) of sufficient length for a percentage of the thorium radionuclides to undergo radioactive decay to radium. After the decay period (112), the separated solution 30 is removed (114) from the radium collection chamber 60, leaving radium atoms 62 unbound to the separated solution 30 in the radium collection chamber 60. A liquid extraction solution 50 is used to elute the radium atoms 62 from the radium collection chamber 60. The brachytherapy source 80 is then immersed (116) in the extraction solution 50 and collects radium atoms 62 on its surface. Optionally, prior to being immersed (116) in the extraction solution 50, the brachytherapy source 80 is coated (130) with a manganese oxide that is suitable for attracting and / or binding radium atoms 62 to the source 80.

[0030] In some embodiments, after the brachytherapy source 80 is removed from the extraction solution 50, the source is coated (118) with a suitable coating that prevents the radium atoms 62 from leaving the source while allowing the daughter radon nuclides to leave the source 80. In particular, the coating is optionally sufficient to prevent release of radium atoms during heat sterilization. Alternatively, other sterilization methods can be used, such as gamma ray sterilization, and in such cases the coating can be thinner or not used at all.

[0031] In some embodiments, the coating includes a polysulfone, such as MED2-4213 produced by Solvay. Alternatively or additionally, the coating includes a polydimethylsiloxane (PDMS), such as Eviva EV-500 provided by Specialty Polymers, or Parylene N. The coating optionally has a thickness that allows radon to diffuse through the coating. The coating optionally has a thickness of less than 10 microns, less than 5 microns, less than 1 micron, less than 0.5 microns, or even less than 0.3 microns. In some embodiments, the coating has a thickness of at least 0.05 microns or even at least 0.1 microns. In other embodiments, such as when the coating includes a PDMS coating, the coating is relatively thick and has a thickness of at least 1 micron, at least 3 microns, or even at least 5 microns or at least 8 microns.

[0032] In some embodiments, the coating includes aluminum-oxide, also known as alumina. The alumina coating is optionally thin enough to allow radon to escape due to radioactive recoil. The alumina coating is optionally produced using atomic layer deposition (ALD) and has a thickness of less than 50 nanometers, less than 10 nanometers, or even less than 6 nanometers.

[0033] In some embodiments, the brachytherapy source 80 is annealed by heating and allowing it to cool slowly before it is coated (118). Optionally, in the annealing, the brachytherapy source 80 is heated to at least 275 degrees Celsius, at least 350 degrees Celsius, or even at least 400 degrees Celsius. In some embodiments, the annealing is performed in a low-oxygen environment, such as in a vacuum or in an inert gas environment.

[0034] Separation solution details

[0035] Acidic solutions 20 containing thorium-228 are commercially available from a variety of suppliers, including, for example, Eckert-Ziegler of Germany and Oak Ridge National Laboratory (ORNL) of the United States.

[0036] The preparation (104) of the separation solution 30 is performed using any suitable method known in the art, such as any of the methods described in Afifi et al. “Extraction and Determination of Thorium and its application on Geologic Samples using Trioctyl Phosphine Oxide”, Arab Journal of Nuclear Science and Applications, 45(3), 2012, the disclosure of which is incorporated herein by reference.

[0037] In some embodiments, the thorium-binding extractant includes an organic extractant, such as TOPO (trioctylphosphine oxide), tributylphosphate, N,N,N',N'- tetrahexylsuccinamide, N-alkyl amides, trialkylmethylammonium nitrate, didodecylphosphoric acid, 2-ethylhexylphenylphosphoric acid, diisobutyl ketone, or hexa acetate calixarene.

[0038] Alternatively or additionally, the thorium-binding extractant includes one or more sulfoxides, such as dibutyl-n-sulfoxide (DBSO), for example as described in Khan et al. "Solvent Extraction of Thorium From Nitric Acid Solutions Using Di-N-Butyl Sulfoxide (Dbso) in Xylene", Journal of Radioanalytical and Nuclear Chemistry, December 1995, Volume 198, Number 2, pages 409-421, the disclosure of which is incorporated herein by reference.

[0039] In some embodiments, the thorium-binding extractant includes an extractant that binds to lead in addition to binding to thorium, so as to reduce the amount of lead that enters the extraction solution 50 and ultimately reaches the source 80. Alternatively or additionally, a separate lead-binding material is added to the separation solution 30.

[0040] As an alternative to using cyclohexane as the diluent, other diluents are used, such as benzene, carbon tetrachloride, chloroform, kerosene, toluene, dodecane, or o-xylene.

[0041] In some embodiments, during the operation duration (108), the container 40 is shaken to induce binding of thorium to the thorium-binding extractant. In these embodiments, the operation duration (108) is at least 30 seconds, at least 1 minute, at least 3 minutes, or even at least 5 minutes. The operation duration (108) is optionally less than 15 minutes, less than 10 minutes, or even less than 5 minutes.

[0042] Alternatively, the container 40 is not shaken during the operation duration (108). According to this alternative, the operation duration is long enough to allow thorium to diffuse to the thorium-binding extractant, and is optionally at least 6 hours, at least 12 hours, or even at least 24 hours.

[0043] The container 40 is shown as being closed, which is particularly useful when it is shaken to induce binding. However, it should be noted that other forms of containers can be used, including open containers.

[0044] Radium collection details

[0045] In some embodiments, during the decay period (112), the extraction solution 50 is contained in the radium collection chamber 60 with the separation solution 30 and the thorium radionuclides 22 therein, such that radium atoms 62 formed by decay of the thorium radionuclides 22 diffuse into the extraction solution 50. Optionally, the extraction solution 50 comprises distilled water. The distilled water optionally forms at least 80%, at least 90%, at least 95%, or even at least 99% of the extraction solution 50. It is found that the use of distilled water makes it easier to transfer the radium atoms to the brachytherapy source 80 than other solutions, such as salt solutions. Optionally, in embodiments in which the extraction solution 50 comprises distilled water, the radium collection chamber 60 is formed of a material to which radium does not readily bind, such as Teflon. Alternatively, the extraction solution 50 includes a salt solution, such as potassium chloride (KCI). Salt solutions generally reduce the deposition of radium on the walls of the radium collection chamber 60, and thus can be used in embodiments in which the radium collection chamber 60 comprises a glass container. However, it should be noted that the extraction solution 50 can include a salt solution even in embodiments in which the radium collection chamber 60 is not made of glass, but of other materials, such as Teflon. Optionally, the radium collection chamber 60 does not include interior walls or other elements that strongly bind to the radium atoms 62 in a manner that requires an acid having a pH of 4 or less to extract the radium atoms 62 from the chamber. Thus, the radium atoms 62 can be collected in a non-acidic solution, which can be more convenient for transferring the radium atoms 62 to the brachytherapy source 80.

[0046] The salt in the salt solution 50 optionally has a concentration of at least 0.001 moles or even at least 0.01 moles. In some embodiments, the concentration of the salt in the salt solution is less than 0.1 moles. Optionally, the salt solution has a pH of about 5 (±10%). As an alternative to the salt solution, the extraction solution 50 includes a weak acid having a pH between 2-3. According to this alternative, after the separation solution 30 is removed (114) and before the brachytherapy source 80 is immersed (116) in the extraction solution 50, the extraction solution 50 is optionally adjusted so as to better facilitate the transfer of the radium atoms 62 to the brachytherapy source 80.

[0047] In some embodiments, instead of removing (114) the separation solution 30 from the radium collection chamber 60, the extraction solution 50 is removed to a different container, while leaving the separation solution 30 in the radium collection chamber 60.

[0048] In other embodiments, during the decay period (112), the separation solution 30 and thorium radionuclides 22 therein are themselves located in the radium collection chamber 60, and radium atoms 62 formed from the decay are deposited 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 includes a salt solution, such as potassium chloride (KCI), 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, such as the shape of a long and narrow column. For example, the radium collection chamber 60 can have the shape of a long and narrow tube having a diameter of less than 15 millimeters, less than 10 millimeters, or even less than 5 millimeters. The length of the tube used as the radium collection chamber 60 is optionally selected according to the amount of separation solution 30 used. In some embodiments, the tube has a length of at least 10 centimeters, or even at least 15 centimeters. Optionally, in these embodiments, the tube has two openings that allow the extraction solution 50 to flow through the tube from a first opening at one end to a second opening at the other end in a manner that washes the deposited radium atoms 62 off the walls of the tube used as the radium collection chamber 60.

[0049] As an alternative to using the extraction solution 50, the separation solution 30 is itself left for a sufficient time (112) for a percentage of the radionuclides to undergo radioactive decay into radium. The source 80 is then immersed into the separation solution 30 to collect the radium atoms 62 on its surface. This alternative can be particularly useful where it is acceptable to collect some thorium radionuclides 22 on the source 80, and there is no need to remove the thorium radionuclides 22 from the container in which the source 80 is immersed. Optionally, in these embodiments, the container holding the separation solution 30 includes a material that does not bind the radium atoms 62, such as Teflon.

[0050] Source details

[0051] The brachytherapy source 80 can have substantially any shape suitable for brachytherapy. The brachytherapy source 80 can have, for example, a cylindrical shape, a flat surface shape, or a spherical shape. In some embodiments, the brachytherapy source 80 includes a material that attracts radium atoms 62 from the extraction solution 50. For example, the brachytherapy source 80 can include a metal source or can be coated by a metal. These embodiments are particularly useful when the extraction solution 50 includes distilled water that allows the radium atoms 62 to diffuse to the metal source. It should be noted that, according to some of these embodiments, the coating (130) of the brachytherapy source 80 by manganese oxide is not necessary and can be skipped.

[0052] In some embodiments, the brachytherapy source 80 includes a material that does not interfere with one or more medical imaging modalities (such as ultrasound or MRI) to be used at the time of implanting the brachytherapy source 80.

[0053] Alternatively or additionally, the brachytherapy source 80 includes a material for binding with a manganese oxide, which in turn binds with the radium atoms 62. Optionally, the brachytherapy source 80 includes a metal base suitable for receiving a manganese oxide coating. Alternatively, the brachytherapy source 80 includes a non-metal base that is a metal clad metal that sufficiently binds to the manganese oxide coating. Alternatively, the brachytherapy source 80 includes any other material that can bind to the manganese oxide coating.

[0054] The manganese oxide optionally includes manganese dioxide (Mn02). Alternatively, the manganese oxide includes any other manganese oxide that binds radium, such as manganese (IV) dioxide, manganese (II) oxide (MnO), manganese (II, III) oxide (Mn304), manganese (III) oxide (Mn203), and manganese (VII) oxide (Mn207), or a mixture of manganese oxides.

[0055] Coating (130) the brachytherapy source 80 with manganese oxide is optionally performed by immersing the brachytherapy source 80 in potassium permanganate (KMn04). The coating (130) is optionally performed at a temperature of at least 60 degrees Celsius, or even at least 80 degrees Celsius, such as about 90 degrees Celsius. After coating the brachytherapy source 80, the source and manganese oxide coating are optionally slowly cooled over at least 1 hour, or even at least 6 hours. Applicant has found that slow cooling results in a more stable coating. Alternatively, any other suitable method for coating with manganese oxide is used. In other embodiments, any other material suitable for binding radium atoms 62 is used instead of or in addition to manganese oxide.

[0056] In some embodiments, the extraction solution 50 is diluted, concentrated, or undergoes a chemical change prior to immersing the brachytherapy source 80 in the extraction solution 50. For example, as mentioned above, the extraction solution 50 can be adjusted to a desired pH level, such as about 5. Dilution and / or concentration is optionally performed to bring the radium concentration in the extraction solution 50 within a desired limit. Optionally, 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 less than 40 microcuries per milliliter.

[0057] The brachytherapy source 80 is immersed (116) in the extraction solution 50, optionally for at least 1 hour, at least 5 hours, or even at least 10 hours. Alternatively, methods known in the art for accelerating the collection of radium on the brachytherapy source 80 are used, such as shaking and / or mixing. In some embodiments, the extraction solution 50 is heated in order to accelerate the collection of radium on the brachytherapy 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 degrees Celsius, at least 60 degrees Celsius, at least 75 degrees Celsius, or even at least 80 degrees Celsius. Optionally, the solution is heated to a temperature that is no higher than 90 degrees Celsius or even no higher than 80 degrees Celsius. 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 that the brachytherapy source 80 is immersed (116) in the extraction solution 50 is optionally selected according to the desired activity of the source and the concentration of radium in the extraction solution 50.

[0058] In embodiments for large scale production of the brachytherapy source 80, the rate of production of radium atoms 62 in the radium collection chamber 60 is monitored, and when this rate is below a desired level, the separation solution 30 is replaced with a different batch of separation solution 30 having a higher thorium density. Alternatively, a concentrated separation solution 30 having a high thorium density is added to the separation solution 30 currently in the radium collection chamber 60. Optionally, prior to the addition of the concentrated separation solution 30 having a high thorium density, a portion of the separation solution 30 having a low thorium density is removed from the radium collection chamber 60 in order to make room for the concentrated separation solution 30. It should be noted that rather than monitoring the actual rate of thorium decay to radium, the rate is estimated based on the half-life of thorium and the original concentration of thorium in the separation solution 30, and thus the time of addition and / or replacement of the separation solution 30 is preselected.

[0059] The concentration of thorium in the separation solution 30, while in the radium collection chamber 60, is optionally at least 0.08 millicuries per milliliter, at least 0.1 millicuries per milliliter, or even at least 0.2 millicuries per milliliter. Applicant has found that the use of higher concentrations of thorium can damage the cyclohexane by causing the release of hydrogen atoms, and thus the concentration of thorium in the separation solution 30 is optionally no greater than 2 millicuries per milliliter or even no greater than 1 millicuries per milliliter. In some embodiments, both an upper limit and a lower limit 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 highly concentrated thorium solution is added to the radium collection chamber 60 to bring the thorium concentration to the upper limit.

[0060] Figure 1The method of the present application does not depend on the quality (e.g., purity) of the initial solution 20, as the radium directed onto the brachytherapy source is separated from the initial solution 20 before the radium is directed onto the brachytherapy source. Thus, the resulting brachytherapy source can be produced without thorium mixed with the radium, or at least with a small amount of thorium atoms, such as less than 1% of the number of radium atoms on the brachytherapy source, less than 0.1% of the number of radium atoms on the brachytherapy source, or even less than 0.01% of the number of radium atoms on the brachytherapy source. However, it should be noted that in some cases, a brachytherapy source including both radium and thorium is desired. In such cases, the desired percentage of thorium can be obtained by mixing a solution having the desired concentration of thorium into the extraction solution 50.

[0061] Figure 1 The method of the present application also allows for high utilization of thorium.

[0062] Optionally, Figure 1 The method of the present application does not require high temperatures, and in some embodiments, Figure 1 The entire process of the method of the present application is performed at temperatures below 180 degrees Celsius, or even below 140 degrees Celsius. However, in other embodiments, one or more stages of the method can require high temperatures above 250 degrees Celsius, or even above 300 degrees Celsius or 350 degrees Celsius.

[0063] Chamber

[0064] Figures 3A-3B A chamber system 300 is shown before and after the decay period (112) according to an embodiment of the present application. The chamber system 300 is a possible implementation of the chamber 60 discussed above. The chamber 310 of the system 300 includes an upper cork 302 for loading the separation solution 30 containing the thorium radionuclide 22 therein into the chamber 310. On the bottom side, the chamber 310 includes a narrow opening 304 which is connected to a narrow Teflon tube 306 having a distal septum 308 through which the extraction solution 50 is introduced into the chamber 310. The septum 308, which is optionally made of silicone or rubber, allows for the introduction and removal of liquids through a needle without leakage.

[0065] The separation solution 30 is placed (110) in the chamber 310 through the upper opening of the chamber 310, which is sealed by the upper cork 302. Prior to, after and / or simultaneously with the placement of the separation solution 30, a suitable amount of the extraction solution 50 is introduced into the chamber 310 through the septum 308. The extraction solution 50 fills the narrow Teflon tube 306 and a portion of the chamber 310. Because the separation solution 30 is lighter than the extraction solution 50, the separation solution 30 floats on the extraction solution 50, as shown in Figure 3Ashown. After the decay period (112), the extraction solution 50 is removed from the chamber 310 through the septum 308, so that 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 extraction solution 50 is optionally retained in the narrow Teflon tube 306, so that not all of the extraction solution 50 is extracted from the chamber system 300. This is advantageous in order to ensure that a meaningful portion of the extraction solution 50 that can be contaminated by the separation solution 30 does not exit the chamber system 300 with the extraction solution 50. The dimensions of the narrow Teflon tube 306 are optionally chosen to minimize the amount of extraction solution 50 that remains in the chamber system 300, while at the same time preventing residues of the separation solution 30 from exiting the chamber system 300 with the extraction solution 50. It should be noted that instead of a Teflon tube 306, a tube of any other suitable material such as silicon or rubber can be used. This option is particularly useful in case the separation solution 30 does not enter the tube, and thus there is no problem of incompatibility between the separation solution 30 and the material forming the tube.

[0066] Thereafter, additional extraction solution 50 can be introduced into the chamber 310 through the septum 308 in order to collect radium atoms from the same separation solution 30. When the concentration of thorium in the separation solution 30 is below a threshold value, an additional amount of separation solution 30 having a high concentration of thorium is introduced into the chamber 310 through the cork 302. Thus, the system 300 can be used to continuously produce extraction solution 50 carrying radium.

[0067] According to some embodiments, the placement (110) of the separation solution 30 in the chamber 310 is performed at a much lower rate than the introduction of the extraction solution 50 into the chamber 310. For example, the placement (110) of the separation solution 30 in the chamber 310 can be performed once for every 10, 100 or even 1000 stages of introduction of the extraction solution 50 into the chamber 310. Thus, in these embodiments, the placement (110) of the separation solution 30 in the chamber 310 can be considered as an initialization stage.

[0068] Figures 4A-4B A chamber system 400 according to other embodiments of the application is shown before and after a decay period (112). In the system 400, the chamber 310 has a narrow extension 402 that is adapted for collecting radium atoms on its inner walls.

[0069] In the system initialization stage, the separation solution 30 containing thorium radionuclides is typically loaded into the narrow extension 402 through the opening sealed by the upper cork 302, as shown in Figure 4A After the first decay period (112), the extraction solution 50 is loaded into the narrow extension 402 through the septum 308 and the tube 306, pushing the separation solution 30 into the chamber 310, as shown in Figure 4BAs shown. Extraction solution 50 collects radium atoms from the wall of the narrow extension 402 and removes them along with the radium atoms through diaphragm 308. Separation solution 30 is then returned to the narrow extension 402, as... Figure 4A As shown, another round of radium atom production begins.

[0070] Figure 5 This is a schematic diagram of a system 500 for generating an αDART brachytherapy source according to an embodiment of the present invention. System 500 includes a manifold 502 connected to various containers via a valve 508 and a liquid line 504. The containers include an extraction solution container 510 and a radium collection chamber 560 in which radium atoms 62 formed by the decay of thorium radioactive nuclide 22 are collected. Figure 2 The radium diffuses into the extraction solution 50. The container optionally also includes an evaluation chamber 518, a radium storage container 530, and a water chamber 540. In some embodiments, a manifold 502 is connected to one or more multi-compartment impregnation containers 550, each comprising a plurality of impregnation compartments 552 arranged to receive elements to be converted into brachytherapy sources 80 by accumulating radium atoms. A robotic arm 580 is optionally used to insert the brachytherapy sources 80 into the impregnation compartments 552 and remove them therefrom. A pump 536 is optionally connected to the manifold 502 and is used to transfer liquid between containers of the system 500. A dumping device 570 is optionally connected to one of the valves 508 of the manifold 502 to receive waste liquid that is no longer needed.

[0071] In some embodiments, one or more containers, such as extraction solution container 510, radium collection chamber 560, evaluation chamber 518, and / or water chamber 540, are placed on corresponding scales 572 for monitoring the amount of liquid in the containers. Alternatively or additionally, any other sensors for monitoring the contents of the containers may be used.

[0072] CPU 548 optionally controls the operation of system 500 by sending control commands to valve 508, pump 536, and / or robotic arm 580. Commands from CPU 548 are sent wired or wirelessly using any suitable method known in the art. Valve 508 is normally kept closed, opens when liquid needs to be passed through a specific valve, and closes again after the liquid has been transferred.

[0073] In operation, pump 536 transfers an amount of extraction solution 50 from vessel 510 to a radium collection chamber 560. Separation solution 30 is introduced to radium collection chamber 560, prior, concurrently, and / or after. After a predetermined time, and / or upon determining that sufficient radium is collected, pump 536 retrieves extraction solution 50 from collection chamber 560 to an evaluation chamber 518, where extraction solution 50 and / or its radium content is evaluated. If the quality of extraction solution 50 is sufficient, pump 536 transfers extraction solution 50 to radium storage vessel 530. However, if the concentration of extraction solution 50 needs to be adjusted, pump 536 transfers a desired amount of water from water chamber 540 to evaluation chamber 518. Alternatively or additionally, extraction solution 50 is returned to collection chamber 560 to receive more radium. In parallel to the production of radium extraction solution 50, radium extraction solution 50 is transferred to one or more multi-compartment impregnation vessels 550, where brachytherapy source 80 is immersed in radium extraction solution 50. System 500 can include any number of collection chambers 560 connected to a single manifold 502 for the parallel production of radium solutions.

[0074] As shown, valves 508 are linearly arranged along manifold 502. However, in other embodiments, tubes 504 and / or valves 508 are radially arranged on manifold 502. Optionally, manifold 502 has a semi-spherical shape or a full spherical shape. To transfer liquid between two vessels, the valve 508 connected to the source vessel is opened and pump 536 draws an amount of liquid from it into the pump's inner chamber. Then, the valve 508 connected to the source vessel is closed, the valve connected to the destination vessel is opened, and the pump is operated to push the liquid in its inner chamber to the destination vessel.

[0075] CONCLUSION

[0076] It is to be understood that the methods and devices described above will be explained with reference to the accompanying drawings. It should be understood that the features and / or steps described with respect to one embodiment can sometimes be used with other embodiments and that not all of the features and / or steps illustrated in a specific drawing or described with respect to a specific embodiment are necessary in all embodiments of the application. It should be noted that, although some dependent claims only refer to one of the independent claims, this is only due to form requirements and is not to be interpreted as a limitation. The application is not to be interpreted as including only those features and / or steps which are explicitly described with respect to a specific embodiment. The order of the steps is not necessarily the order in which they are performed. The tasks do not necessarily have to be performed in the exact order described.

[0077] It should be noted that some of the foregoing described embodiments can include details that are not essential to the practice of the application, and are described as examples only. The structures and actions of the described embodiments can be replaced by equivalents, even if the structures or actions differ, as known in the art. The foregoing described embodiments are by way of example only and are not meant to be limiting to the application. The scope of the application is limited only by the claims as set forth herein, and the equivalents thereof, wherein the terms "comprise," "comprises," "comprising," "include," "includes," "including," and the like are meant to be broad and encompass the several features, sub-combinations, and / or equivalents thereof.

Claims

1. A method of accumulating radium radio nuclides, the method comprising: providing a first solution comprising a thorium radio nuclide and a thorium- binding extractant, wherein the first solution does not bind radium such that radium atoms produced from decay of the thorium radio nuclide diffuse out of the first solution; allowing a portion of the thorium radio nuclide in the first solution to decay into radium atoms; allowing the radium atoms to diffuse out of the first solution; and collecting radium atoms produced from decay that diffuse out of the first solution.

2. The method of claim 1, wherein the thorium-binding extractant comprises TOPO (trioctylphosphine oxide).

3. The method of claim 1, wherein collecting the radium atoms comprises collecting the radium atoms into a second solution.

4. The method of claim 1, wherein collecting the radium atoms comprises collecting the radium atoms onto a brachytherapy source.

5. The method of claim 4, further comprising coating the source with a protective coating that prevents the radium atoms from detaching from the source but allows daughter radon atoms of the radium atoms to exit the source upon decay of the radium atoms.

6. The method of claim 5, wherein coating the source with a protective coating comprises coating with a polysulfone or polydimethylsiloxane.

7. The method of claim 5, wherein coating the source with a protective coating comprises coating with aluminum oxide.

8. The method of claim 4, wherein collecting the radium atoms comprises collecting the radium atoms into a second solution and immersing the brachytherapy source into the second solution.

9. The method of claim 8, further comprising coating the source with a manganese oxide prior to immersing the source into the second solution.

10. The method of claim 9, further comprising heating the source and allowing the source to cool slowly after coating the source with a manganese oxide.

11. The method of claim 8, wherein the source comprises a manganese oxide source.

12. The method of claim 1, wherein providing the first solution comprises introducing the first solution into a chamber with a second solution that does not mix with the first solution such that decaying radium atoms diffuse into the second solution.

13. The method of claim 12, wherein providing the first solution comprises providing a solution comprising a diluent having a low solubility level in the second solution.

14. The method of claim 13, wherein the diluent has a specific gravity that is lower than water.

15. The method of claim 13, wherein the diluent comprises cyclohexane.

16. The method of claim 12, wherein the second solution comprises a salt solution.

17. The method of claim 12, wherein the first solution is lighter than the second solution. ​ 18. The method of claim 1, wherein allowing a portion of the thorium radio nuclides to decay into radium atoms comprises leaving the first solution in a chamber having walls made of a material that attracts radium over a decay period, and wherein collecting the radium atoms comprises washing the radium atoms off the walls using a salt solution.

19. The method of claim 1, wherein allowing a portion of the thorium radio nuclides to decay into radium atoms comprises placing the first solution in a chamber from which radium atoms are separable without using an acid having a pH lower than 4.

20. The method of any one of claims 1-19, wherein providing the first solution comprises: providing a separation solution of a thorium-binding extractant and a diluent having a low solubility level; combining the prepared separation solution with an initial solution comprising thorium radio nuclides, such that thorium radio nuclides from the initial solution bind to the thorium-binding extractant; and separating the separation solution from the initial solution to form the first solution.

21. The method of any one of claims 1-19, wherein the thorium radio nuclides remain in the first solution, and the radium atoms diffuse out of the first solution.

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