RU2813760C1 - Wet method of obtaining sources for radiation therapy - Google Patents

Abstract

FIELD: radiation therapy.

SUBSTANCE: method of accumulating radium radionuclides is presented, the said method includes obtaining a first solution containing thorium radionuclides and a thorium-binding extractant, wherein the first solution does not bind radium; ensuring the possibility of decay of part of the thorium radionuclides into radium atoms in the first solution; and collection of radium atoms resulting from decay. Allowing a part of the thorium radionuclides to decay into radium atoms involves leaving the first solution for the decay period in a chamber with walls of a material that attracts radium, and where the collection of radium atoms includes washing radium atoms from the walls using a saline solution. Also, ensuring that part of the thorium radionuclides can decompose into radium atoms involves introducing a first solution into a chamber from which radium atoms are separated without the use of an acid with a pH below 4. In addition, a method of producing a brachytherapy source, a device for accumulating radium radionuclides, and a brachytherapy source are described.

EFFECT: increase in efficiency and expansion of the range of radiation therapy agents is achieved.

26 cl, 7 dwg

Description

TECHNICAL FIELD

The present invention relates generally to radiation therapy and in particular to methods for producing alpha sources for radiation therapy.

BACKGROUND ART

Alpha particles are powerful agents in radiation therapy for certain types of tumors, including malignant tumors. One type of alpha source for radiation therapy is an alpha-emitting radionuclide diffusion radiotherapy (DART) source filled with radium-223 or radium-224 atoms that has a period suitable (e.g., not too long or too short) for therapeutic purposes. half-life

Kelson's US Patent No. 8,834,837 discloses a method for producing DART alpha sources by placing the source in a radium-224 stream emanating from the surface of a thorium-228 source.

US Patent 2015/0292061 discloses the separation of radionuclide fission products from a proton-irradiated thorium target.

BRIEF DESCRIPTION OF THE INVENTION

In accordance with embodiments of the present invention, there is provided a method for accumulating radium radionuclides, including providing a first solution containing 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 collection of radium atoms resulting from decay.

Optionally, the thorium binding extractant contains TOPO (trioctylphosphine oxide). Optionally, collecting radium atoms includes collecting radium atoms into a second solution. Alternatively or additionally, collecting radium atoms includes collecting radium atoms at a source for brachytherapy. Optionally, collecting the radium atoms includes collecting the radium atoms in a second solution and immersing the brachytherapy source in the second solution. Optionally, preparing the first solution includes introducing the first solution into a chamber containing the second solution such that decaying radium atoms diffuse into the second solution. Optionally, obtaining the first solution includes obtaining a solution containing a solvent having a low degree of solubility in the second solution.

Optionally, the solvent has a specific gravity lower than that of water. Optionally, the solvent contains cyclohexane. Optionally, the second solution contains a saline solution. Optionally allowing a portion of the thorium radionuclides to decay into radium atoms involves leaving the solution to separate during the decay period in a chamber with walls of a material that attracts radium, and collecting the radium atoms involves washing radium atoms from the walls with a saline solution. Optionally, allowing a portion of the thorium radionuclides in the separation solution to decay into radium atoms involves introducing a first solution into a chamber from which the radium atoms are separated without the use of an acid with a pH below 4.

In some embodiments, producing the first solution includes preparing a solution of a separation solvent having a low degree of solubility and a thorium-binding extractant, combining the resulting separation solution with a feed solution containing thorium radionuclides such that thorium radionuclides from the feed solution are bound to thorium -binding extractant, and separating the separation solution from the original solution to form the first solution.

In accordance with embodiments of the present invention, there is further provided a method for producing a brachytherapy source, comprising: producing a solution containing radium atoms; and immersing the brachytherapy source in said solution such that radium atoms are collected onto the source. Optionally, the method further includes coating the source with a protective coating that prevents radium atoms from separating from the source but allows daughter nuclei of radium atoms to exit the source as the radium atoms decay.

Optionally, coating the source with a protective coating includes coating with polysulfone or polydimethylsiloxane. Optionally, coating the source with a protective coating includes an aluminum oxide coating. Optionally, the method further includes coating the source with manganese oxide before immersing the source in the solution. Optionally, the method, after coating the source with manganese oxide, further includes heating the source and slowly cooling it. Optionally, the source includes a source of manganese oxide. Optionally, the solution contains saline or distilled water.

In accordance with embodiments of the present invention, a device for accumulating radium radionuclides is further provided, including a first vessel with a first solution containing thorium radionuclides and a thorium-binding extractant, a second vessel with a second solution containing radium atoms, a pump; and a processor configured to control the pumping of the third solution into the first vessel, and after a period of time sufficient to collect the radium atoms, removing the third solution from the first vessel and transferring it to the second vessel.

In accordance with embodiments of the present invention, there is further provided a brachytherapy source, comprising a base of a size and shape suitable for insertion into a human organ for brachytherapy, a manganese oxide coating over the base; and radium atoms attached to a manganese oxide coating. Optionally, the base includes a metal base.

Alternatively, the base includes a non-metallic base. Optionally, the brachytherapy source further comprises a protective coating that prevents radium atoms from separating from the source but allows daughter nuclei of radium atoms to escape from the source. Optionally, the protective coating allows the daughter nuclei of the radium atoms to escape from the source using the energy obtained from the decay of the radium atoms. Alternatively or additionally, the protective coating allows radium daughter nuclei to escape from the source by diffusion. Optionally, the protective coating contains polysulfone and/or alumina. Optionally, the brachytherapy source does not contain thorium atoms greater than 0.1% of the radium atoms on the source. Optionally, radium atoms are attached to the manganese oxide coating by annealing.

BRIEF DESCRIPTION OF THE FIGURES

Fig. 1 is a flow chart of steps performed to produce an alpha DART source for brachytherapy in accordance with an embodiment of the invention;

Fig. 2 is a schematic illustration of a method for producing a radium source for brachytherapy in accordance with an embodiment of the invention;

In FIG. 3A-3B show a chamber system before and after a radium decay period in accordance with embodiments of the present invention;

In FIG. 4A-4B show a chamber system before and after a decay period in accordance with other embodiments of the present invention; And

Fig. 5 is a schematic illustration of a system for producing alpha DART sources for brachytherapy in accordance with an embodiment of the invention.

DETAILED DESCRIPTION OF IMPLEMENTATION OPTIONS

An aspect of some embodiments of the invention relates to a method for producing a solution containing radioactive radium atoms. The method includes providing a container containing thorium atoms in a solution that attracts thorium but not radium, and allowing the thorium to decay into radium. In some embodiments, the container further contains a second solution that is immiscible with the thorium solution. The radium atoms are allowed to diffuse into a second solution, which is removed from the container of radium atoms when sufficient radium has been collected. In other embodiments, 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. Thorium optionally contains thorium-228. However, it is noted that the principles of the present invention can also be used with thorium-227, for example, obtained from actinium-227.

An aspect of some embodiments of the invention relates to a method for producing a radium source for brachytherapy. The method includes immersing a brachytherapy source in a solution containing radium atoms such that the radium atoms are collected on the source.

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

Review

Fig. 1 is a flow chart of steps performed to produce a radium source for brachytherapy in accordance with an embodiment of the invention. Fig. 2 is a schematic illustration of the method according to FIG. 1.

The method according to Fig. 1 optionally begins with the preparation (102) of a source solution 20 containing thorium-228 radionuclides 22. A separation solution 30 is prepared (104) formed by a thorium-binding extractant that binds to thorium but does not bind to radium dissolved in a solvent having low degree of solubility (i.e. less than 0.1%) in water and optionally a specific gravity other than water, such as cyclohexane. The container 40 containing the resulting (102) initial solution 20 is loaded (106) with the separation solution 30. After the process time (108) has elapsed, thorium radionuclides 22 from the initial solution 20 are attached to the thorium-binding extractant in the separation solution 30. It should Note that the solvent prevents separation solution 30 from mixing with feed solution 20.

Separation solution 30, which now contains thorium radionuclides 22, is separated from the original solution 20 and introduced (110) into a radium collection chamber 60, in which it is left to decay (112) for a duration sufficient to allow a percentage of the thorium radionuclides to undergo radioactive decay to radium. After the decay period (112), the separation solution 30 is removed (114) from the radium 60 collection chamber, leaving radium 62 atoms not associated with the separation solution 30 inside the radium 60 collection chamber. Liquid extraction solution 50 is used to wash out the radium atoms 62 from the radium 60 collection chamber. The brachytherapy source 80 is then immersed (116) in the extraction solution 50 and radium 62 atoms are collected on its surface. Optionally, prior to immersion (116) in the extraction solution 50, the brachytherapy source 80 is coated (130) with manganese oxide suitable for attracting and/or bonding radium 62 atoms to the source 80.

In some embodiments, after removing the brachytherapy source 80 from the extraction solution 50, the source is coated (118) with a suitable coating that prevents radium 62 atoms from escaping the source while allowing radon daughter nuclides to escape from the source 80. In particular, the coating is not necessarily sufficient to preventing the release of radium atoms during heat sterilization. Alternatively, other sterilization methods may be used, such as gamma ray sterilization, and in such cases the coating may be thinner or may not be used at all.

In some embodiments, the coating contains a polysulfone, such as MED2-4213, manufactured by Solvay. Alternatively or additionally, the coating contains polydimethylsiloxane (PDMS), such as Eviva EV-500, available from Specialty Polymers, or Parylene N. The coating does not necessarily have a thickness such that radon diffuses through the coating. The coating optionally has a thickness of less than 10 µm, less than 5 µm, less than 1 µm, less than 0.5 µm, or even less than 0.3 µm. In some embodiments, the coating has a thickness of at least 0.05 microns or even at least 0.1 microns. In other embodiments, for example, when the coating comprises a PDMS coating, the coating is relatively thin and has a thickness of at least 1 μm, at least 3 μm, or even at least 5 μm or at least 8 μm.

In some embodiments, the coating comprises aluminum oxide, also known as alumina. The aluminum oxide coating is not necessarily thin enough to allow release of radon by recoil from radioactive decay. The alumina coating is optionally obtained using atomic layer deposition (ALD) and has a thickness of less than 50 nm, less than 10 nm, or even less than 6 nm.

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

Detailed description of the separation solution

Acid solution 20 containing thorium-228 is commercially available from various suppliers, including, for example, Eckert-Ziegler in Germany and Oak Ridge National Laboratory (ORNL) in the USA.

Preparation (104) of separation solution 30 is carried out 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 description of which is incorporated herein by reference.

In some embodiments, the thorium-binding extractant contains an organic extractant such as TOPO, tributyl phosphate, N,N,N',N'-terahexylsuccinylamide, N-alkylamides, trialkylmethylammonium nitrate, didodecylphosphoric acid, 2-ethylhexylphenylphosphoric acid , diisobutyl ketone or calixarene hexaacetate.

Alternatively or additionally, the thorium-binding extractant contains 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 Solutions Using Di-N- Butyl Sulfoxide (Dbso) in Xylene”, Journal of Radioanalytical and Nuclear Chemistry, December 1995, col. 198, issue 2, pp. 409-421, the description of which is incorporated herein by reference.

In some embodiments, the thorium binding extractant contains an extractant that binds to lead, in addition to binding to thorium, to reduce the amount of lead that enters the extraction solution 50 and ultimately reaches the source 80. Alternatively or additionally to the separation solution 30 add a separate lead-binding material.

As an alternative to the use of cyclohexane as a solvent, other solvents are used, such as benzene, carbon tetrachloride, chloroform, kerosene, toluene, dodecane or o-xylene.

In some embodiments, during method (108), the container 40 is shaken to cause thorium to bind to the thorium-binding extractant. In such embodiments, the execution time of the method (108) is at least 30 seconds, at least 1 minute, at least 3 minutes, or even at least 5 minutes. The execution time of the method (108) is not necessarily less than 15 minutes, less than 10 minutes, or even less than 5 minutes.

Alternatively, the container 40 is not shaken during the method (108). According to such an alternative, the process time is long enough to allow diffusion of thorium into the thorium binding extractant, and is optionally at least 6 hours, at least 12 hours, or even at least 24 hours.

Container 40 is shown closed, which is particularly useful when shaken to cause binding. However, it should be noted that other shapes of containers can be used, including open containers.

Detailed description of radium collection

In some embodiments, during the decay period (112), an extraction solution 50 is located in the radium 60 collection chamber with separation solution 30 and thorium radionuclides 22 such that radium 62 atoms resulting from the decay of thorium radionuclides 22 diffuse into the extraction solution 50. Optionally, extraction solution 50 contains distilled water. Distilled water optionally makes up at least 80%, at least 90%, at least 95%, or even at least 99% of the extraction solution 50. The use of distilled water has been found to facilitate easier transfer of radium atoms to the brachytherapy source 80. than other solutions such as saline solutions. Optionally, in embodiments in which the extraction solution 50 contains distilled water, the radium collection chamber 60 is made of a material with which radium does not tend to combine, such as Teflon. Alternatively, extraction solution 50 contains a saline solution such as potassium chloride (KCl). Saline solutions generally reduce the deposition of radium on the walls of the radium 60 collection chamber and may therefore be used in embodiments in which the radium 60 collection chamber includes a glass container. However, it is noted that the extraction solution 50 may contain a saline solution even in embodiments in which the radium collection chamber 60 is not made of glass, but rather is made of other materials, such as Teflon. Optionally, the radium 60 collection chamber does not include internal walls or other elements that tightly bind the radium 62 atoms such that an acid with a pH of 4 or lower is required to extract the radium 62 atoms from the chamber. In this way, radium 62 atoms can be collected into a non-acidic solution, which may be more convenient for transferring radium 62 atoms to the brachytherapy 80 source.

The salt concentration in brine solution 50 is optionally at least 0.001 mol or even at least 0.01 mol. In some embodiments, the salt concentration in the brine solution is less than 0.1 mole. Optionally, the saline solution has a pH of about 5 (±10%). As an alternative to saline solution, extraction solution 50 contains a weak acid with a pH between 2-3. According to this alternative, after removal (114) of the separation solution 30 and before immersing (116) the brachytherapy source 80 in the extraction solution 50, the extraction solution 50 is optionally titrated to be better suited for passing atoms 62 to the brachytherapy source 80.

In some embodiments, instead of removing (114) the separation solution 30 from the radium collection chamber 60, the extraction solution 50 is removed to another container and the separation solution 30 is retained in the radium collection chamber 60.

In other embodiments, during the decay period (112), the separation solution 30 and thorium radionuclides 22 contained therein are in the radium collection chamber 60 by themselves, and the radium 62 atoms resulting 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 radium 62 atoms from the walls of the chamber. In these embodiments, the extraction solution 50 optionally contains a saline solution, such as potassium chloride (KCl), or a weak acid suitable for washing radium 62 atoms from the walls of the radium 60 collection chamber. Optionally, in these embodiments, the radium 60 collection chamber is shaped , having a large surface area, for example, the shape of a long and narrow column. For example, the radium 60 collection chamber may take the form of a long and narrow tube with a diameter of less than 15 mm, less than 10 mm, or even less than 5 mm. The length of the tube serving 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 cm, or even at least 15 cm. Optionally, in these embodiments, the tube has two holes, which allow the extraction solution 50 to flow through the tube from the first hole at one end to the second hole at the other end, thereby washing the deposited radium 62 atoms from the walls of the tube serving as a collection chamber for radium 60.

An alternative to using extraction solution 50, separation solution 30 is left on its own for sufficient time (112) for a percentage of the radionuclides to undergo radioactive decay to radium. The source 80 is then immersed in a separation solution 30 to collect radium atoms (62) onto its surface. Such an alternative may be used especially in cases where it is acceptable to collect some of the thorium radionuclides 22 at 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 separation solution container 30 contains material such as Teflon, which does not bind radium 62 atoms.

Detailed description of the source

The brachytherapy source 80 can be in essentially any form suitable for brachytherapy treatment. The brachytherapy source 80 may have, for example, a cylindrical shape, a flat surface shape, or a spherical shape. In some embodiments, the brachytherapy source 80 contains a material that attracts radium 62 atoms from the extraction solution 50. For example, the brachytherapy source 80 may contain a metal source or may be coated with a metal. These embodiments are particularly useful when the extraction solution 50 contains distilled water, which allows the radium 62 atoms to diffuse to the metal source. It is noted that in accordance with some of these embodiments, coating (130) of the brachytherapy source 80 with manganese oxide is not necessary and may be omitted.

In some embodiments, the brachytherapy source 80 contains a material that does not interfere with one or more medical imaging techniques, such as ultrasound or MRI, that will be used when the brachytherapy source 80 is implanted.

Alternatively or additionally, the brachytherapy source 80 contains a material for binding to manganese oxide, which in turn binds to the radium 62 atoms. Optionally, the brachytherapy source 80 includes a metal base that is suitable for producing a manganese oxide coating. Alternatively, the brachytherapy source 80 includes a non-metallic base that is a metal coated with a metal that sufficiently bonds to the manganese oxide coating. Alternatively, the brachytherapy source 80 includes any other material that can bind to the manganese oxide coating.

The manganese oxide optionally contains manganese dioxide (MnO ₂ ). Alternatively, manganese oxide contains any other manganese oxide that binds radium, such as manganese(IV) dioxide, manganese(II) oxide (MnO), manganese(II, _III ) oxide ( _Mn3O4 ), manganese(III) oxide ( Mn ₂ O ₃ ) and manganese (VII) oxide (Mn ₂ O ₇ ) or a mixture of various manganese oxides.

Coating (130) of the brachytherapy source 80 with manganese oxide is optionally accomplished by immersing the brachytherapy source 80 in potassium permanganate (KMnO ₄ ). Coating (130) is optionally carried out at a temperature of at least 60°C or even at least 80°C, for example at about 90°C. After coating the brachytherapy source 80, the source and manganese oxide coating are optionally allowed to cool slowly for at least an hour or even at least 6 hours. Applicant has found that a more stable coating is achieved by slow cooling. Alternatively, any other suitable manganese oxide coating method is used. In other embodiments, any other material suitable for binding radium 62 atoms is used instead of or in addition to manganese oxide.

In some embodiments, before the brachytherapy source 80 is immersed in the extraction solution 50, the extraction solution 50 is diluted, concentrated, or chemically altered. For example, as mentioned above, the extraction solution 50 may be titrated to a desired pH level, for example, about 5. Dilution and/or concentration is optionally performed to bring the radium concentration in the extraction solution 50 within the desired range. Optionally, the radium concentration is at least 3 μCi/ml, at least 5 μCi/ml, or even at least 10 μCi/ml. In some embodiments, the radium concentration is less than 60 μCi/ml, less than 50 μCi/ml, or even less than 40 μCi/ml.

Immersion (116) of the brachytherapy source 80 in the extraction solution 50 is optionally carried out for at least an hour, at least 5 hours, or even at least 10 hours. Alternatively, methods known in the art are used to accelerate the collection of radium to the brachytherapy source. 80, such as shaking and/or stirring. In some embodiments, the extraction solution 50 is heated to accelerate the collection of radium to the brachytherapy source 80. The extraction solution 50 is optionally heated to a temperature that creates currents in the solution, for example, at least 50°C, at least 60°C, at least 75°C or even at least 80°C. Optionally, the solution is heated to a temperature no higher than 90 °C or even no higher than 80 °C. According to such an alternative, the immersion is optionally carried out for less than 3 hours, less than an hour or even less than 30 minutes. The immersion time (116) of the brachytherapy source 80 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.

In an embodiment for large-scale production of brachytherapy source 80, the rate of production of radium 62 atoms in the radium collection chamber 60 is monitored, and when the rate is below the desired level, the separation solution 30 is replaced with another batch of separation solution 30 with a higher density of thorium. Alternatively, add the concentrated high thorium density separation solution 30 to the 30 separation solution currently in the radium 60 collection chamber. Optionally, before adding the concentrated high thorium density separation solution 30, a portion of the low thorium density separation solution 30 removed from the radium 60 collection chamber to make room for the concentrated separation solution 30. Note that, rather than monitoring the actual decay rate of thorium to radium, the rate is estimated based on the half-life of thorium and the initial concentration of thorium in separation solution 30, and accordingly the time for adding and/or replacing the separation solution 30 is selected in advance.

In the radium 60 collection chamber, the concentration of thorium in separation solution 30 is optionally at least 0.08 mCi, at least 0.1 mCi, or even at least 0.2 mCi per ml. Applicant has discovered that the use of higher concentrations of thorium can have a destructive effect on cyclohexane by causing the release of hydrogen atoms, and therefore the thorium concentration in separation solution 30 is not necessarily less than 2 mCi or even less than 1 mCi per ml. In some embodiments, upper and lower limits are determined for the concentration of thorium in separation solution 30. When the concentration reaches the lower limit, the separation solution 30 is replaced or a more concentrated thorium solution is added to the radium collection chamber 60 to bring the thorium concentration to the upper limit.

The method according to Fig. 1 is independent of the quality (eg, purity) of the source solution 20, since the radium sent to the brachytherapy source is separated from the source solution 20 before the radium is sent to the brachytherapy source. Accordingly, the resulting brachytherapy source can be produced without thorium mixed with radium, or at least with a low number of thorium atoms, such as less than one percent of the number of radium atoms in the brachytherapy source, less than 0.1% of radium atoms, or even less than 0 .01% radium atoms at the brachytherapy source. However, it is noted that in some cases a brachytherapy source containing both radium and thorium is desirable. In such cases, the desired percentage of thorium can be achieved by mixing a solution with the desired thorium concentration with the 50% extraction solution.

The method according to Fig. 1 also provides a high thorium recovery rate.

Optionally the method according to FIG. 1 does not require high temperatures, and in some embodiments, the entire method of FIG. 1 is carried out at temperatures below 180 °C or even below 140 °C. However, in other embodiments, one or more process steps may require high temperatures, above 250°C or even above 300°C or 350°C.

Cameras

In FIG. 3A-3B show a chamber system 300 before and after a decay period (112) in accordance with embodiments of the present invention. The camera system 300 is a possible implementation of the camera 60 described above. Chamber 310 of system 300 includes an upper plug 302 for loading separation solution 30 containing thorium radionuclides 22 into chamber 310. At the bottom, chamber 310 includes a narrow opening 304 that connects to a narrow Teflon tube 306, with an outer membrane 308 through which extraction solution 50 is introduced into the chamber 310. The membrane 308, optionally made of silicone or rubber, allows fluids to be introduced or removed by the needle without leakage.

Through the upper opening in chamber 310, which is sealed with top plug 302, separation solution 30 is introduced (110) into chamber 310. Before, after, and/or simultaneously with the addition of separation solution 30, a suitable amount of extraction solution 50 is introduced into chamber 310. through membrane 308. Extraction solution 50 fills narrow Teflon tube 306 and part of chamber 310. Because separation solution 30 is lighter than extraction solution 50, separation solution 30 floats on extraction solution 50, as shown in FIG. 3A. After the breakup period (112), extraction solution 50 is removed from chamber 310 through membrane 308 such that only separation solution 30 remains in chamber 310, as shown in FIG. 3B. It is noted that a small portion of the extraction solution 50 does not necessarily remain in the narrow Teflon tube 306, so that not all of the extraction solution 50 is extracted from the chamber system 300. This is useful to ensure that no significant portion of the separation solution 30 is present that could contaminate the extraction solution 50 , does not leave the chamber system 300 with the extraction solution 50. The size of the narrow Teflon tube 306 is optionally selected to minimize, on the one hand, the amount of extraction solution 50 remaining in the chamber system 300, and on the other hand, prevent the escape of residual separation solution 30 of the chamber system 300 with the extraction solution 50. It is noted that in place of the Teflon tubing 306, tubing of any suitable material, such as silicone or rubber, may be used. This option is particularly useful in cases where the separation solution 30 does not enter the tube and therefore there is no compatibility issue between the separation solution 30 and the tube material.

Additional extraction solution 50 can then be introduced through membrane 308 into chamber 310 to collect radium atoms from the same separation solution 30. When the concentration of thorium in separation solution 30 falls below a threshold value, additional extraction solution is introduced into chamber 310 through plug 302. separation 30 with a high concentration of thorium. Thus, the system 300 can be used to continuously produce extraction solutions 50 containing radium.

In some embodiments, the addition (110) of separation solution 30 to chamber 310 is carried out at a much lower rate than the addition of extraction solution 50 to chamber 310. For example, the addition (110) of separation solution 30 to chamber 310 may be performed once per every 10, every 100, or even every 1000 steps of introducing the extraction solution 50 into the chamber 310. Thus, introducing (110) the separation solution 30 into the chamber 310 can be considered in these embodiments as an initialization step.

In FIG. 4A-4B show a chamber system 400 before and after a decay period (112) in accordance with other embodiments of the present invention. In system 400, chamber 310 has a narrow extension 402 suitable for collecting radium atoms on its inner walls.

During the initialization of the system, separation solution 30 containing thorium radionuclides is typically loaded through the opening capped by the top plug 302 into a narrow extension 402, as shown in FIG. 4A. After the first breakup period (112), extraction solution 50 is loaded through membrane 308 and tube 306 into narrow extension 402, pushing separation solution 30 into chamber 310, as shown in FIG. 4B. Extraction solution 50 collects radium atoms from the walls of narrow extension 402 and removes it through membrane 308 along with the radium atoms. The separation solution 30 is then returned to the narrow extension 402 as shown in FIG. 4A, and another cycle of radium atom production begins.

Fig. 5 is a schematic illustration of a system 500 for producing alpha DART sources for brachytherapy in accordance with one embodiment of the invention. System 500 includes a manifold 502 that connects through valves 508 and fluid pipes 504 to various containers. The vessels include a vessel 510 for the extraction solution 50, a radium collection chamber 560 in which atoms of radium 62 (FIG. 2) formed from the decay of thorium radionuclides 22 diffuse into the extraction solution 50. The vessels optionally further include an assessment chamber 518, a vessel for radium storage 530 and a water chamber 540. In some embodiments, the manifold 502 is connected to one or more multi-chamber immersion vessels 550 that include a plurality of immersion compartments 552 arranged to receive elements to be converted into a brachytherapy source 80 by accumulating radium atoms. The robotic arm 580 is optionally used to insert and remove brachytherapy sources 80 into and out of the immersion compartments 552. A pump 536 is optionally connected to a manifold 502 and is used to move fluids between the reservoirs of the system 500. A drain 570 is connected to one of the valves 508 of the manifold 502 to receive waste fluids that are no longer required.

In some embodiments, one or more containers, such as extraction solution vessel 510, radium collection chamber 560, evaluation chamber 518, and/or water chamber 540, are placed on appropriate scales 572, which are used to monitor the amount of liquid in the containers. Alternatively or additionally, any other sensors can be used to monitor the contents of the containers.

The CPU (central processing unit) 548 optionally controls the operation of the system 500 by sending control commands to the valves 508, the pump 536, and/or the robotic arm 580. The commands from the CPU 548 are transmitted wired or wirelessly using any suitable method known in the art. Typically, closed valves 508 are opened when fluid is required to pass through a particular valve and closed again after fluid has passed.

In operation, pump 536 pumps a quantity of extraction solution 50 from vessel 510 to radium collection chamber 560. Before, in parallel, and/or after this, a separation solution 30 is introduced into the radium collection chamber 560 through the top valve 514. After a predetermined time and/or after determining that a sufficient amount of radium has been collected, the pump 536 withdraws the extraction solution 50 from the chamber to collecting 560 into an evaluation chamber 518 in which the extraction solution 50 and/or its radium content is evaluated. If the quality of extraction solution 50 is sufficient, pump 536 pumps extraction solution 50 to radium storage vessel 530. However, if the concentration of extraction solution 50 requires adjustment, pump 536 pumps the required amount of water from water chamber 540 to evaluation chamber 518. Alternatively or additionally, extraction solution 50 is returned to collection chamber 560 to obtain more radium. In parallel with the production of the radium 50 extraction solution, the radium 50 extraction solution is transferred to one or more multi-chamber immersion vessels 550 where brachytherapy sources 80 are immersed in the radium 50 extraction solution. The system 500 may include any number of collection chambers 560 connected to a single manifold 502 , for parallel production of radium solution.

As shown, valves 508 are arranged linearly along manifold 502. However, in other embodiments, tubes 504 and/or valves 508 are arranged radially on manifold 502. Optionally, manifold 502 is shaped like a half or full sphere. To transfer liquid between two containers, valve 508 connected to the source container is opened and pump 536 extracts a quantity of liquid from it into the inner chamber of the pump. Then, the valve 508 connected to the source container is closed, the valve connected to the final container is opened, and the pump is operated to push liquid from its inner chamber into the final container.

Conclusion

It should be understood that the methods and devices described above should be interpreted as including devices for carrying out said methods and methods of using said devices. It should be understood that the features and/or steps described in relation to one embodiment may sometimes be used with other embodiments, and that not all embodiments of the invention have all the features and/or steps shown in a particular figure or described in relation to one of specific embodiments. It is especially noted that although some of the dependent claims depend on only one parent claim, this is due to the formal requirements of some jurisdictions and, unless not possible or specifically stated, the present invention includes all combinations of dependent claims. The tasks are not necessarily performed in the exact order described.

It should be noted that some of the embodiments described above may include structure, actions, or details of structures and actions that may not be essential to the invention, and which are described by way of examples. The structure and actions described in the context of this invention may be replaced by equivalents performing the same function, even if the structure or actions are different, as is known in the art. The embodiments described above are given by way of example, and the present invention is not limited to what has been specifically shown and described above. That is, the scope of the present invention includes combinations and subcombinations of the various features described above, as well as variations and modifications thereof that may occur to those skilled in the art after reading the above description and which are not disclosed in the prior art. Therefore, the scope of the invention is limited only by the elements and scope used in the claims, where the terms “comprise,” “include,” “have,” and their related terms mean, when used in the claims, “including, but not necessarily limited to.”

Claims (47)

1. A method for accumulating radium radionuclides, including: obtaining a first solution containing thorium radionuclides and a thorium-binding extractant, wherein the first solution does not bind radium; ensuring the possibility of decay of part of the thorium radionuclides into radium atoms in the first solution; And collection of radium atoms resulting from decay, wherein allowing a portion of the thorium radionuclides to decay into radium atoms involves leaving the first solution to decay in a chamber having walls of a material that attracts radium, and where collecting the radium atoms involves washing radium atoms from the walls with a saline solution, and where allowing a portion of the thorium radionuclides to decay into radium atoms involves introducing a first solution into a chamber from which the radium atoms are separated without the use of an acid with a pH below 4. 2. The method according to claim 1, where the thorium-binding extractant contains TOPO (trioctylphosphine oxide). 3. The method of claim 1, wherein collecting radium atoms includes collecting radium atoms into a second solution. 4. The method of claim 1, wherein collecting radium atoms includes collecting radium atoms at a brachytherapy source. 5. The method of claim 4, wherein collecting radium atoms includes collecting radium atoms in a second solution and immersing the brachytherapy source in the second solution. 6. The method of claim 1, wherein preparing the first solution comprises introducing the first solution into a chamber containing the second solution such that decaying radium atoms diffuse into the second solution. 7. The method of claim 6, wherein the preparation of the first solution comprises the preparation of a solution containing a solvent having a low degree of solubility in the second solution. 8. The method according to claim 7, where the solvent has a specific gravity lower than the specific gravity of water. 9. The method according to claim 7, where the solvent contains cyclohexane. 10. The method according to claim 6, where the second solution contains a saline solution. 11. The method according to claim 1, where obtaining the first solution includes: obtaining a solution of a separation solvent having a low degree of solubility and a thorium-containing extractant; combining the resulting solution for separation with a source solution containing thorium radionuclides, such that thorium radionuclides from the source solution are associated with a thorium-binding extractant; And separating the separation solution from the original solution to form a first solution. 12. A method for producing a source for brachytherapy, including: obtaining a solution containing radium atoms; coating the source with manganese oxide followed by heating and cooling; coating the source with a protective coating that prevents radium atoms from separating from the source but allows daughter nuclei of radium atoms to escape from the source as the radium atoms decay; And immersing a brachytherapy source in a specified solution such that radium atoms are collected on the source. 13. The method of claim 12, wherein coating the source with a protective coating includes coating with polysulfone or polydimethylsiloxane. 14. The method of claim 12, wherein coating the source with a protective coating comprises an aluminum oxide coating. 15. The method of claim 12, wherein the source includes a source of manganese oxide. 16. The method according to claim 12, where the solution contains a saline solution. 17. The method according to claim 12, where the solution contains distilled water. 18. A device for accumulating radium radionuclides, including: a first vessel with a first solution containing thorium radionuclides and a thorium-binding extractant; a second vessel containing a second solution containing radium atoms; pump; And a processor configured to control the pumping of the third solution into the first vessel, and after a period of time sufficient to collect the radium atoms, removing the third solution from the first vessel and transferring it to the second vessel. 19. Source for brachytherapy, including: a base of a size and shape suitable for insertion into a human organ for brachytherapy; manganese oxide coating over the base; a protective coating that prevents radium atoms from separating from the source but allows daughter nuclei of radium atoms to escape from the source; And radium atoms attached to a manganese oxide coating, wherein the brachytherapy source does not contain thorium atoms greater than 0.1% of the radium atoms on the source. 20. The brachytherapy source according to claim 19, wherein the base includes a metal base. 21. The brachytherapy source according to claim 19, wherein the base includes a non-metallic base. 22. The brachytherapy source according to claim 19, wherein the protective coating allows the daughter nuclei of the radium atoms to escape from the source due to the energy obtained as a result of the decay of the radium atoms. 23. The brachytherapy source according to claim 19, wherein the protective coating allows the daughter nuclei of radium atoms to escape from the source due to diffusion. 24. The source for brachytherapy according to claim 19, where the protective coating contains polysulfone. 25. The source for brachytherapy according to claim 19, where the protective coating contains aluminum oxide. 26. The brachytherapy source according to claim 19, wherein the radium atoms are attached to the manganese oxide coating by annealing.