Depend on 226 Radium production 225 Actinide method

Abstract

Liquid is irradiated in irradiation device (2) by protons, deuterium nuclei or gamma rays. 226 The radium target, and the resulting product extracted from the irradiated liquid target solution in the first extraction device (6). 225 Origin of A 226 Radium production 225 Actinium. Then, after another irradiation, it was removed. 225 Actinium liquid target solution for further production 225 Actinium. The liquid target solution is preferably circulated through the irradiation device in a closed loop (4) and through the first extraction device (6) in another closed loop (7). The advantage of this method is that the irradiated target solution does not require drying and redissolving to separate radium from the produced actinium, and no further drying and redissolving steps are needed to regenerate the liquid target from the separated radium. Therefore, radium targets can be recovered more efficiently and safely, especially considering the effects of... 226 Radon gas is continuously produced by the decay of radium.

Description

Technical Field

[0001] This invention relates to a method of... 226 Radium production 225 A method for actinginium, wherein providing an actinium-containing 226 A liquid target solution of radium, wherein the liquid target solution is irradiated in an irradiation apparatus to extract radium contained therein. 226 Radium begins to be produced in liquid target solutions. 225 Actinium; and will at least partially produce 225 Actinium and the remainder 226 Ra separation. Background Technology

[0002] 225 Actinium is an interesting radioactive nuclide that could be used in cancer treatment. 225 Actinium is a radioactive isotope that emits alpha rays with a half-life of 10 days. It can be used as a reagent in radioimmunotherapy. Due to the dense ionizing radiation from alpha particle emitters, it is a promising source of radiation for lethal irradiation of single cancer cells and micrometastases. Alpha particles are particularly advantageous for radioimmunotherapy applications because their extent in soft tissues is limited to a few cell diameters.

[0003] There are several possible methods for production. 225 Actinium, but a new and safer production method is still needed that can produce the quantity required to meet demand. 225 Actin.

[0004] For example, as disclosed in US 5,809,394, 225 Actinium can be passed 229 It is produced from the radioactive decay of thorium. This is currently the method of production for medical applications. 225 Ac's main method. This method uses 229 Th / 225 Ra / 225 AC generator (Boll 2005), among which 225 Ac is from 229 Th and its offspring 225 The radioactive inward growth of Ra's alpha decay continuously produces it. This generator produces radiochemically pure Ra every 6-8 weeks. 225 Ra and 225 Ac. 225 The maximum activity of Ac is limited by the presence of [something] in the generator. 229 Total Th. 229 Th and 225 Ra / 225 Chemical separation between Ac and Ac is typically based on ion exchange. Currently, there are three such generators in the world. ORNL (USA) provides up to 720 mCi per year.225 Ac, according to reports, the Institute of Physics and Power Engineering in Obninsk, Russia, is capable of providing a similar quantity of products, and the European Commission's G Council site in Karlsruhe maintains a relatively small one. 229 Th source, capable of producing up to 350mCi per year 225 Ac. However, the problem lies in 225 The demand for Ac has already exceeded the total output of existing generators. On the other hand, 229 Th is a rare isotope (derived from) 233 U) and the number in the world is limited. Due to 233 U and 229 Th has a relatively long half-life, even though production methods are being researched (Jost 2013). 229 Th's inventory is also unlikely to increase significantly.

[0005] Another form of production 225 Actinium methods include irradiation with protons or deuterium nuclei. 232 Thorium sputtering material for production 225 Ac. This method is based on manufacturing thick 232 Th metal targets (natural Th) are irradiated using medium-energy protons or deuterons (24-50 MeV) (Morgenstern 2006) via a cyclotron or medium- to high-energy protons (>80 MeV) in accelerator facilities (Ermalaev 2012, Weidner 2012). The use of medium-energy protons or deuterons... 225 The generation of Ac is based on 232 Th(p,4n) 229 Pa and 232 Th(d,5n) 229 Pa, subsequently via β at a lower yield of 0.48%. + Decay into isotopic purity 225 Ac. The required proton and deuteron energies are within the range of currently commercially available cyclotrons, but very high currents are needed to produce favorable yields. This requires high-energy protons. 232 The Th(p,x) reaction is directly produced. 225 Ac is not only for production 225 Ac is sensitive and produces adjacent isotopes with similarly high cross-sections. In fact, Ci levels... 225 Ac can be produced by high-energy protons in a week of irradiation (Ermolaev 2012, Griswold 2016), although direct therapeutic use may be affected by the simultaneous generation of [agents / protons]. 227 The obstacle of Ac, among which, 227 Ac is a long-lived (27 years) alpha-ray emitter (Ermolaev 2012), with a high reactivity ratio.227 Ac / 225 Ac = 0.2% produced (Griswold 2016). Due to the complex isotopic mixture present after irradiation, the chemical separation of actinium from irradiated thorium targets is quite complex and typically relies on a series of ion-exchange columns. If necessary, from... 227 Separation and purification of Ac 225 Ac isotope separation cannot be accomplished using ordinary chemical methods. It requires highly complex mass separation that can be performed online during irradiation (ISOLDE). The required proton current (>100 μA) and high proton energy (90–200 MeV) exceed the capabilities of currently commercially available cyclotrons. In fact, the number of accelerator facilities worldwide capable of producing medium- to high-energy protons with the required intensity is limited (Zhuikov 2011). Even fewer are capable of online isotope separation.

[0006] For example, production is publicly disclosed in EP 0 752 709 B1 and EP 0 962 942 B1. 225 Another method of using actinium includes through 226 Proton or deuterium irradiation of Ra 225 Ac. This method is based on manufacturing 226 A thin solid target material of Ra is placed in an airtight, water-cooled target holder and irradiated with protons (Koch 1999, Apostolidis 2004) or deuterons (Abbas 2004). Chemical separation is then performed. 225 After Ac, the remaining 226 Ra is reprocessed and recycled for the production of new targets, thus ending the radium irradiation cycle. This irradiation method has been successfully demonstrated in cyclotron irradiation experiments, where mCi levels were achieved. 225 Ac. For 226 Ra(p,2n) 225 The Ac reaction can exhibit a cross-section of 0.71 mb at 16.8 MeV protons, which is further confirmed by target dissolution and chemical separation. 225 Ac products have the following properties: 229 Th / 226 Ra / 225 AC generator produces 225 Ac has the same high radiochemical quality. (Apostolidis 2005).

[0007] However, due to 226 The complex processing of Ra solutions led to the cessation of further development and validation of this method. 226Ra is an alpha ray emitter with a fairly long lifetime and is highly radioactive, requiring shielding even when used in relatively small quantities. However, the main problem lies in... 226 Directly generated in the α decay of Ra 222 The presence of Rn (radon). In fact, without continuous separation and removal of radon, 226 Ra and 222 Rn will reach radioactive equilibrium in a few weeks, where they will have the same level of activity. Radon ( 222 Rn is an inert gas, making it very difficult to control, which leads to serious problems. Therefore, handling large quantities of Rn... 226 Ra requires low-pressure shielding facilities, such as hot chambers and glove boxes with high ventilation, and very careful and deliberate handling methods to minimize radium contamination and / or radon emissions. After solid-state irradiation... 226 Dissolution of Ra target material 225 Chemical purification of Ac and 226 The reprocessing of Ra and the production of the target material are both open processes, which makes the entire process sensitive to radon emissions.

[0008] Since irradiation is typically carried out outside the hot chamber / glove box, target handling is particularly important in such processes. The loaded target must be contaminated and airtight. Water cooling of the target and thin target window must be optimized for the proton current used to avoid target failure. A major advantage of this method is the ability to use commercially available cyclotrons for producing PET isotopes via proton irradiation. These are capable of providing optimized proton energies with appropriate currents. However, due to the aforementioned drawbacks, this promising approach... 225 Further development of the Ac production method ceased.

[0009] For example, another production method is disclosed in US 2002 / 0094056 A1. 225 The method involves irradiation with neutrons or high-intensity gamma rays (achieved in US 2002 / 0094056 A1 via an electron beam, wherein a conversion material is used to convert the electron beam into gamma rays). 226 Ra to produce 225 Ac. It utilizes 226 The (y,n) or (n,2n) reaction of Ra produces 225 Ra, of which 225 Ra decays 225 Ac. The photon reaction (y,n) utilizes a hard gamma-ray intensity field, which is produced as bremsstrahlung in an electron accelerator, while neutrons are produced in a fast reactor or via spallation sources in an accelerator facility. This is achieved using an 18MV linear (medical) accelerator.226 Ra production 225 Ac, but the cross-section is too small for practical use (Melville 2007). Subsequent work described how more intense accelerators irradiate larger amounts of... 226 Ra is a feasible method (Melville 2009). In terms of radium processing, this production method has the same disadvantages as proton irradiation of solid Ra targets. 226 Ra targets do indeed require manufacturing, irradiation, dissolution, separation of actinide products, and reprocessing of radium to produce new targets. These targets will likely need to be very large (tens of grams or more). 226 Ra targets are used, but compared to proton irradiation, target technology and irradiation may be technically easier to implement because heat dissipation is not an issue, and the target window does not need to be thin. Nevertheless, photon or neutron reactions will require large facilities, such as nuclear reactors, high-intensity linear accelerators, or synchrotrons, to reach suitable production levels.

[0010] In summary, the current 225 Ac as 229 The production methods for Th decay products are not easily scaled up to meet future therapeutic needs. Actinium can be produced in commercially available cyclotrons via (p,2n) reaction irradiation of radium. However, due to its daughter product radon, 226 Ra processing is extremely challenging. The proposed techniques are based on cyclotron (proton or deuterium) or synchrotron (gamma) irradiation of solid targets, requiring target fabrication, irradiation, target dissolution, actinium separation, and finally, reprocessing the Ra into new solid targets to complete the cycle. When using charged particles (protons, deuterium) irradiation, heat dissipation (cooling) from the target and thin target window limits the particle current, thus limiting production capacity. Radon emissions will be a constant concern during such processes. For (y,n) reactions, the target window is not limited, but such processes may require large to very large quantities. 226 Ra and electron accelerator facilities. Most likely, based on 232 High-energy proton irradiation of Th requires highly complex isotope separation methods based on mass separation to remove... 227 Ac.

[0011] The method according to the invention uses a substance containing 226 Liquid target for radium solution. The use of such a liquid target is disclosed in US 2002 / 0094056 A1. In this known method, 226 Ra is converted through gamma irradiation. 225 Ra, 225 Ra has a half-life of 14.8 days, therefore subsequently... 225 Ra is converted to 225 Ac. 226Ra to 225 The conversion of Ra is achieved by guiding electrons to the conversion material that generates photons. 226 Ra can be coated onto the conversion material, but it can also flow and circulate on the conversion material in solution form until enough product is produced. 226 Ra solutions can also be placed in quartz bottles and irradiated.

[0012] by 226 The advantage of using Ra solution as a target material is that it allows for a sufficient quantity of... 226 Ra is available and does not require the production and dissolution of solid targets. However, the resulting... 225 The separation and purification of Ac still involves radioactivity. 226 The problem of handling Ra and the radon continuously generated therefrom. In the method disclosed in US 2002 / 0094056 A1, the liquid target material is actually made from... 226 A solution of radium chloride is formed. The concentration of this solution can be from about 0.5 to about 1.5 moles, for example, about 1 mole. After irradiation for about 10 to about 30 days, for example, about 20 days, the solution contains... 226 Ra and the small amount produced in the solution 225 Ra and 225 Ac. In order to be able to separate 226 Ra and 225 Ra and its products 225 Ac, the irradiated solution must be dried and the dried material must be redissolved in a 0.03 MH NO3 solution. This solution is then passed through an ion exchange column, especially... Resin chromatography column (Eichrom Industries, Inc., Darien, III.). 226 Ra and 225 Ra passes through the resin column, while 225 Ac was retained on the resin column. The bound ions were then eluted from the column using 0.35 M HNO3. 225 Ac.

[0013] Although not disclosed in US 2002 / 0094056 A1, 226 Ra and 225 Ra can be reused as a target material. Since the target material is in chloride form, the reuse of these radium isotopes requires evaporating the HNO3 solvent and then redissolving the resulting dry material in hydrochloric acid to obtain a liquid radium chloride solution of the target material.

[0014] As mentioned above, the problem with this method is that it must be carried out in a closed environment where the continuously generated radon gas is captured. This is due to the complex processing of the post-irradiation target solution to extract the produced... 225 Ac and remake contain residuals226 Ra target solution, extracted from irradiated target material 225 Before Ac, the target solution should be irradiated until it contains sufficient 225 Ac. In the method disclosed in US 2002 / 0094056 A1, more specifically, the liquid target is irradiated until maximum production capacity is reached, specifically 80%-90%. The disadvantage of such a long irradiation time is that... 225 Ac decayed after its formation, making the resulting... 225 Ac lost a significant portion of its product during the production process. Summary of the Invention

[0015] The purpose of this invention is to provide a method for irradiating a substance containing... 226 Ra's liquid target material, made of 226 Ac production 225 Ac's new method eliminates the need for drying and redissolving steps to separate the generated actinium from radium, and also eliminates the need for further drying and redissolving steps to regenerate liquid targets from the separated radium. Therefore, this new method enables the more efficient and safer recovery of radium targets after the generated actinium has been removed.

[0016] Therefore, the method according to the invention is characterized in that the separation step includes a first extraction step performed in a first extraction apparatus, wherein at least part of the separation step is performed in the first extraction apparatus. 225 Ac is extracted from the liquid target solution, while 226 Ra is maintained in a liquid target solution; and the method includes the further step of re-irradiating the portion of the target solution extracted therefrom in the irradiation apparatus. 225 Ac's liquid target solution, to be contained in the liquid target solution 226 Ra begins to be generated further in the liquid target solution. 225 Ac.

[0017] In the method of this invention, a liquid target solution is irradiated in an irradiation apparatus, and after irradiation, the same target solution is provided to a first extraction apparatus, where actinium is extracted from the liquid target solution itself. Therefore, the irradiated target solution does not require drying or redissolving. After extracting actinium from the irradiated liquid target solution, the liquid target solution is irradiated again in its original form to further produce actinium. Again, drying and redissolving steps are not required to produce the liquid target. Therefore, the cycle can be completed without any drying or redissolving of the target material.

[0018] Because the liquid target solution is used as is in the continuous irradiation and extraction steps, there is no need for drying and redissolving steps, so the production process can be easily automated and radon gas escape can be easily avoided.

[0019] The liquid target solution can be contained within a static target. This static target then needs to be emptied from the first extraction apparatus and refilled with the liquid target solution from which actinium has been extracted. The transfer of the liquid target solution into or out of the first extraction apparatus can be automated, or this single step can be easily performed in a closed environment, such as a heated chamber or glove box. For example, the actinium extracted can be extracted once daily or every few days, such as weekly.

[0020] In a first embodiment of the method according to the invention, during the irradiation step, the liquid target solution circulates through the irradiation device and the heat exchanger in a first closed loop.

[0021] In this embodiment, the target is therefore not static, but dynamic. Since the target solution circulates in a closed loop, the generated radon gas can be easily contained within the system / equipment. An advantage of this embodiment is that the circulating liquid target solution can be easily cooled to control the temperature of the target solution in the irradiation apparatus, thereby cooling the irradiation apparatus, especially the window that isolates the target solution from the outside.

[0022] When a radium target is irradiated with protons, the proton beam deposits its energy into the target material solution, and temperature and pressure rise during irradiation. Heat dissipation efficiency is crucial, and the target body and target window must be precisely designed to withstand the irradiation conditions. Because... 225 Ac has a relatively long half-life compared to radioactive isotopes such as PET or others produced by cyclotrons in liquid target solutions, and due to the limited solubility of radium salts in aqueous solutions, longer irradiation periods are unavoidable. To achieve suitable production levels, the highest possible proton current should be applied, which increases the thermal load on the target. However, the thermal load of a closed-volume liquid target is limited by the increased internal pressure and temperature of the liquid target. The increased thermal load can be somewhat managed in liquid targets designed with internal reflux (i.e., thermosiphon design), and is also advantageous for radium solution irradiation. However, from a safety perspective, in processing... 226 When Ra is used, it is problematic to allow for increased target temperature and pressure.

[0023] To achieve a relatively high proton current, i.e., a sufficiently high production level, in this first embodiment, the target material is preferably water-cooled, and most of the heat dissipation is achieved through external cooling of the target material solution itself. Compared to a static liquid target material, this embodiment allows for significantly higher current and heat load. The recirculated target material liquid provides effective internal cooling for the target body and the target window itself, thereby improving safety in case of target window failure.

[0024] Recycled targets have been studied for use in production. 18 F (Clarke 2004), but no regular applications have been found so far. For 18 The production of F and the recycling of the target are indeed very complex, mainly because of the technology used. 18 The volume of the O-enriched water solution is very small, only a few milliliters. This necessitates an extremely compact recirculation loop design, making the use of such a loop for cooling the liquid target material impractical. However, in the method of the present invention, the problem of an extremely compact recirculation loop design is solved by using a larger volume of target material solution with a lower concentration, resulting in a loop design with standard techniques for liquid pumping and cooling. Although a higher radium concentration in the target material solution is preferred considering the efficiency of the irradiation process, a lower radium concentration is sufficient due to the limited solubility of radium salts in aqueous solutions, especially when the aqueous solution already contains a relatively large amount of anions in acidic form. The total target material solution volume used in the production method of the present invention is particularly greater than 10 mL, more particularly greater than 20 mL, even more particularly greater than 30 mL, and even greater than 40 mL. The total target material solution volume also determines the size of the separation column, and therefore is preferably not too large, and, for example, less than 250 mL, preferably less than 150 mL. 226 The concentration of Ra is particularly low below 1 M, and even more so below 0.8 M, therefore only a relatively small amount is required. 226 Ra. 226 Ra can be dissolved in the target solution. 226 Ra salt, especially 226 Ra(NO3)2 or 226 RaCl2 is used to obtain it. Although with 226 Compared to Ra(NO3)2, using 226 RaCl2 can achieve slightly higher concentrations, but the target solution will need to contain more hydrochloric acid (which will reduce...). 226 The solubility of RaCl2 salts is considered to allow for the extraction of actinium. Therefore, 226 Ra(NO3)2 and 226 RaCl2 cannot achieve high radium concentrations in the target solution. Although only relatively low radium concentrations can be obtained, it has been found that the method according to the invention can achieve sufficiently high yields.

[0025] In a second embodiment of the method according to the invention, during the first extraction step, the liquid target solution circulates through the first extraction device in a second closed loop.

[0026] Similarly, in this second embodiment, the target solution is recirculated again in a loop design with standard techniques for liquid pumping. This is used to extract the generated actinium from the target solution. The advantage of this embodiment is that, due to the fact that the liquid target solution circulates through the first extraction device in a closed loop, the generated radon gas can be easily contained back into the system / equipment. The liquid target solution can be recirculated through the first extraction device more than once. Thus, the first extraction device can be loaded with actinium to the maximum extent, especially when the liquid target solution is contained in a container and recirculated through that container and the first extraction device.

[0027] In a third embodiment of the method according to the invention, the third embodiment is applicable to a combination of the first and second embodiments, wherein during the irradiation step, in the first closed loop, the liquid target solution circulates through the container and the irradiation device, and during the first extraction step, in the second closed loop, the liquid target solution circulates through the container and the first extraction device.

[0028] The advantage of this embodiment is that the liquid target solution does not need to be transferred from the irradiation device to the first extraction device and vice versa, but can be simply circulated through the irradiation device and the first extraction device. Since it is carried out in two closed loops, radon gas will not escape. Another advantage of this embodiment is that the irradiation step can continue during the extraction step. In other words, the generated actinium can be removed from the target solution without interrupting the irradiation step. Therefore, the generated actinium can be removed more frequently, i.e., removed more quickly after its generation, thereby reducing the actinium lost due to decay. Furthermore, the liquid target solution can be recycled through the first extraction device more than once, or even semi-continuously, i.e., mainly interrupted only during any elution or rinsing step. Thus, despite the relatively large volume of the recycled target solution, and despite the fact that the target solution leaving the first extraction device is remixed with the target solution being supplied to the first extraction device, the maximum amount of generated actinium can still be removed from the target solution.

[0029] In a fourth embodiment of the method according to the invention, the first extraction step is performed during the irradiation step.

[0030] The advantage of this implementation is that the irradiation device can be used optimally because it is not necessary to stop the irradiation process to extract the produced actinium.

[0031] In a fifth embodiment of the method according to the invention, at least a portion of the material is extracted from the liquid target solution. 225 Prior to the irradiation, the liquid target solution was irradiated for less than 16 days, preferably less than 13 days, more preferably less than 10 days, and most preferably less than 7 days.

[0032] Since actinium can be easily extracted from the liquid target solution without any drying and resolution steps, it is preferable to remove it as early as possible to reduce the decay of actinium itself during the irradiation process.

[0033] In a sixth embodiment of the method according to the invention, the first extraction step is performed with a pause time of less than 16 days, preferably less than 13 days, more preferably less than 10 days, and most preferably less than 7 days.

[0034] Furthermore, since actinium can be easily extracted from the liquid target solution without any drying and resolution steps, it is preferable to remove it as early as possible to reduce the decay of actinium itself during the irradiation process.

[0035] In a seventh embodiment of the method according to the invention, during the irradiation step, the liquid target solution is irradiated with protons or deuterium nuclei.

[0036] Through protons or deuterons, it is possible to directly and efficiently obtain... 226 Radium production 225 Actinium. A key advantage is that commercially available cyclotrons used for producing PET (Positron-Emission Tomography) isotopes via proton irradiation can be used. These accelerators are able to provide optimal proton energies with suitable currents to produce... 225 Actinium. Therefore, large facilities are not required.

[0037] In an eighth embodiment of the method according to the invention, during the irradiation step, the liquid target solution is irradiated with gamma rays to achieve the desired effect. 226 radium converted to 225 Radium and 225 radium converted to 225 Actin Production 225 Actin.

[0038] The advantage of this implementation is that, compared with proton irradiation, target technology and irradiation are technically easier to implement because heat dissipation is not an issue, and the target window does not need to be very thin.

[0039] Preferably, during the first extraction step, when extracting from the liquid target solution... 225 When, 225 Radium is retained in the liquid target solution.

[0040] The advantage of this preferred solution is that... 225 Radium is recycled, so it is immediately regenerated in the liquid target solution. 225 Actinide, without any time lag.

[0041] In a ninth embodiment of the method according to the invention, the liquid target solution comprises 226 A solution of radium salts and their corresponding acids, wherein the solution preferably contains... 226 Radium nitrate and nitric acid.

[0042] As mentioned above, although radium chloride is more soluble in water than radium nitrate, it typically requires a larger amount of the corresponding acid, HCl, in solution, which reduces the solubility of radium chloride. For example, the required HCl concentration can include approximately 5 M.

[0043] The advantage of using radium nitrate in combination with nitric acid is that it allows for extraction. 225 Actin without extraction 226 Radium (or even in) 225 Radium is not extracted during production. 225 Different extraction chromatography resins for radium include those capable of extracting from solutions with relatively low nitric acid content (having only a minor effect on the solubility of radium nitrate). 225 Actinide, and can be extracted from solutions containing high nitric acid concentrations using extraction chromatography resins (e.g., LN resins containing dialkyl phosphates), and resins based on N,N,N',N'-tetra-n-octyl diethylene glycolamide or N,N,N',N'-tetra-2-ethylhexyl diethylene glycolamide resins (e.g., DGA (diethylene glycolamide)), CMPO-based TRU resins (i.e., octylphenyl-N,N-diisobutylcarbamoylphosphine oxide), or diamide-based resins (e.g., DMDOHEMA or DMDBTDMA), which are capable of extracting from solutions with high nitric acid concentrations. 225 Actinium can be eluted using a nitric acid solution with a lower nitric acid content. Therefore, a range of these different extraction chromatography resins can be used to extract from liquid target solutions. 225 Ac, eluted from the first extraction chromatography resin 225 Actinium, and then further extracted from the eluent using a second extraction chromatography resin to obtain a purer and more concentrated form. 225 Actinium. The order of these two extraction chromatography resins can be interchanged depending on the nitric acid content of the liquid target solution.

[0044] Another advantage of using radium nitrates in combination with nitric acid is that corrosion caused by chlorides is a much larger problem compared to corrosion in nitrate media. Many materials are essentially resistant to corrosion even at high concentrations of nitric acid. However, few materials are suitable for hydrochloric acid. This situation is further complicated by irradiation conditions that generate reactive free radicals. These problems can be addressed by using nitric acid.

[0045] In a tenth embodiment of the method according to the present invention, the first extraction device includes a first adsorbent, wherein during the first extraction step, the... 225 Actinium accumulates on the first adsorbent, and the method includes a first elution step, wherein at least a portion of the actinium already accumulated on the first adsorbent... 225 Actinium is eluted from the first adsorbent using the first eluent.

[0046] In this embodiment, the 225 Actinium can be readily extracted from the liquid target solution because it accumulates on the first adsorbent during the first extraction step. The first extraction apparatus is preferably an extraction chromatography apparatus, wherein the first adsorbent preferably comprises a support, preferably an inert support, and an extractant as a stationary phase on the support.

[0047] In an eleventh embodiment of the method according to the invention, which is applicable to the tenth embodiment, the liquid target solution has a predetermined pH value, such that the... 225 Actinium accumulates on the first adsorbent during the first extraction step, and the first eluent has a pH value different from that of the liquid target solution, so that the actinium is eluted from the first adsorbent during the first elution step. 225 Actin.

[0048] The advantage of this embodiment is that the liquid target solution and the first eluent can both contain the same acid, only at different concentrations. Therefore, any acid in the target solution retained in the first adsorbent will not interfere with the first elution step, and vice versa. Therefore, any acid in the first eluent retained in the first adsorbent will not interfere with the first extraction step.

[0049] In a twelfth embodiment of the method according to the invention, which is applicable to an eleventh embodiment, the method includes a rinsing step between the first extraction step and the first elution step, wherein the first extraction apparatus is rinsed with a rinsing solution having a pH value different from that of the first eluent, such that the... 225 Actinium is retained on the first adsorbent, and the rinsing solution preferably has a pH value substantially equal to that of the liquid target solution.

[0050] The advantage of this implementation is that any radium remaining in the first adsorbent at the end of the first extraction step can be washed off before the actinium is eluted from the first adsorbent. Therefore, the radium is not lost but retained in the system / equipment and does not form impurities in the extracted actinium. Radium in this specification refers to any radium isotope, especially... 226 Radium, and optionally, if generated during the irradiation step 225 Radium, also refers to 225 radium.

[0051] Preferably, during the rinsing step, the rinsing solution flushes the liquid target solution out of the first extraction device, preferably without mixing with the liquid target solution, and during the first elution step, the first eluent flushes the rinsing solution out of the first extraction device, preferably without mixing with the rinsing solution.

[0052] In a thirteenth embodiment of the method according to the invention, which is applicable to the twelfth embodiment, during the rinsing step, the rinsing solution circulates in a third closed loop through a radium extraction apparatus comprising a radium adsorbent, during which radium washed off from the first adsorbent by the rinsing solution accumulates on the radium adsorbent. The method includes a radium elution step, wherein at least a portion of the radium accumulated on the radium adsorbent is eluted from the radium adsorbent by a radium eluent, particularly having a pH value different from that of the rinsing solution, such that the radium is eluted from the radium adsorbent during the radium elution step.

[0053] The advantage of this implementation is that any radium washed out from the first extraction unit can be recovered. It can be stored in the radium eluent for a period of time and can be recovered by readjusting the radium solution to the correct acidity, concentrating it, and transferring it back to the target solution. Since only a small amount of radium is washed out from the first extraction unit, this recovery operation only needs to be performed occasionally.

[0054] In the fourteenth embodiment of the method according to the invention, the fourteenth embodiment is applicable to the thirteenth embodiment, and therefore preferably stored in the... 226 During the radium elution step, from the... 226 Eluting on radium adsorbent 226 Radium is then recycled back to the liquid target solution.

[0055] In a fifteenth embodiment of the method according to the invention, which is applicable to any one of the twelfth to fourteenth embodiments, the rinsing solution is circulated through a first radon filter, particularly a first activated carbon filter, to remove radon from the first extraction device.

[0056] When the first extraction unit is rinsed through a first radon filter, radon generated in the first extraction unit, as well as radon generated in the irradiation unit and collected in the first extraction unit, can be removed from it by the first radon filter. For example, this filter is an activated carbon filter, to which radon adheres. The radon then decays. 210 Pb remains in the system / device. In order to remove it from the system / device... 210 Pb can be removed by providing a lead extraction device, such as an extraction column containing, for example, Sr resin or Pb resin (Eichrome), both of which are very effective for removing Pb.

[0057] In a sixteenth embodiment of the method according to the invention, which is applicable to any one of the twelfth to fifteenth embodiments, the rinsing solution comprises an acid solution containing the same acid as the target solution, particularly nitric acid.

[0058] In a seventeenth embodiment of the method according to the invention, which is applicable to any one of the tenth to sixteenth embodiments, the first eluent comprises a first acid solution containing the same acid as the target solution, particularly nitric acid.

[0059] The liquid target solution, rinsing solution, and first elution solution preferably contain the same acid, but mixing is not permitted as it would cause interference in the production process, especially when the process is prolonged. Therefore, the volume of rinsing solution contained in the first extraction unit is preferably pushed back into its recycling loop by the first eluent before the first eluent is recycled through the second extraction unit.

[0060] In an eighteenth embodiment of the method according to the invention, which is applicable to any one of the tenth to seventeenth embodiments, during the first elution step, the first eluent circulates through a second extraction device in a fourth closed loop, the second extraction device comprising a second adsorbent, and during the first elution step, the first eluent is eluted from the first adsorbent by the first eluent. 225 Actinium accumulates on the second adsorbent, and the method includes a second elution step, wherein at least a portion of the actinium already accumulated on the second adsorbent... 225 Actinium is eluted from the second adsorbent using a second eluent, the second eluent having a different pH value than the first eluent, such that during the second elution step, the... 225 Actinium is eluted from the second adsorbent, which preferably comprises a second acid solution containing the same acid as the target solution, especially nitric acid.

[0061] Therefore, the actinium eluted from the first extraction device can be easily collected in the second extraction device and can be eluted again in a more concentrated and purer form. Preferably, during the second elution step, the second eluent flushes the first eluent out of the second extraction device, and preferably does not mix with the first eluent.

[0062] In a nineteenth embodiment of the method according to the invention, which is applicable to the eighteenth embodiment, the first eluent is circulated from the first extraction device to the second extraction device, passing through a second radon filter, particularly a second activated carbon filter, to extract radon from the first eluent.

[0063] When the first extraction unit is eluted, radon generated in the first extraction unit and radon generated in the irradiation unit and collected in the first extraction unit can be removed by a second radon filter. This filter is, for example, an activated carbon filter to which radon adheres. The radon then decays to produce... 210 Pb remains in the system / device. In order to remove it from the system / device... 210 Pb can be removed by providing a lead extraction device, such as an extraction chromatography column containing, for example, Sr resin or Pb resin (Eichrome), both of which are very effective for removing Pb.

[0064] In a twentieth embodiment of the method according to the invention, which is applicable to the eighteenth or nineteenth embodiment, during the second elution step, the second eluent circulates through a third extraction device in a fifth closed loop, the third extraction device comprising a third adsorbent, and during the second elution step, the eluent is eluted from the second adsorbent by the second eluent. 225 Actinium accumulates on a third adsorbent, and the method includes a third elution step, wherein at least a portion of the actinium already accumulated on the third adsorbent... 225 Actinium is eluted from it by a third eluent, which in particular has a pH value different from that of the second eluent, such that... 225 Actinium is eluted from the third adsorbent during the third elution step, the third eluent preferably comprising a third nitric acid solution.

[0065] Actinium eluted from the second extraction unit can therefore be easily collected in the third extraction unit and can be eluted again in a more concentrated and / or purer form. Preferably, during the third elution step, the third eluent flushes the second eluent out of the third extraction unit, and preferably does not mix with the second eluent.

[0066] In a twenty-first embodiment of the method according to the invention, which is applicable to a twenty-twentieth embodiment, the second eluent is circulated from the second extraction device to the third extraction device, passing through a third radon filter, particularly a third activated carbon filter, to extract radon from the second eluent.

[0067] When the second extraction unit is eluted, any radon that reaches it can be removed by a second radon filter. This filter is, for example, an activated carbon filter to which radon adheres. The radon then decays to produce... 210 Pb remains in the system / device. In order to remove it from the system / device... 210 Pb can be removed by providing a lead extraction device, such as an extraction chromatography column containing, for example, Sr resin or Pb resin (Eichrome), both of which can efficiently remove Pb. Attached Figure Description

[0068] Further details and advantages of the invention will become more apparent from the following description of some embodiments of a production method according to the invention. This description is provided by way of example only and is not intended to limit the scope of the invention as defined in the appended claims. Reference numerals used in this specification refer to reference numerals in the accompanying drawings, wherein:

[0069] Figure 1 This is an apparatus diagram for implementing the method according to a first embodiment of the present invention, wherein the liquid target solution contains a relatively small amount of nitric acid, particularly 0.02 M; and

[0070] Figure 2 This is an apparatus diagram for implementing the method according to a second embodiment of the present invention, wherein the liquid target solution contains a relatively large amount of nitric acid, particularly 0.5M. Detailed Implementation

[0071] In the method of the present invention, preparation containing 226 Ra, which contains more special ingredients 226 A liquid target solution of radium nitrate. This solution particularly contains nitric acid in the range of 0.005-1.0 M. Preferably, the solution is contained in a lead-shielded, airtight bottle.

[0072] Figure 1 The apparatus schematically illustrated is particularly used for producing, according to a low acidity option, wherein the liquid target solution has an acidity, for example, between 0.005 and 0.05 M HNO3. 225 Ac. The concentration of Ra(NO3)2 in the target solution is preferably as high as possible, up to 0.4 M.

[0073] The device includes a container 1 for containing a liquid target solution. It also includes an irradiation device 2 with a window through which the target solution can be irradiated with protons, deuterium nuclei, or gamma rays. The gamma rays can be obtained from a synchrotron or linear accelerator, or from the conversion materials disclosed in US 2002 / 0094056. However, it is preferable to irradiate the liquid target with protons (or deuterium nuclei) because this is because... 226 Ra generates 225 The most effective way to produce Ac is through proton irradiation. Proton irradiation can be generated by cyclotrons, for example, those known for producing radioactive isotopes of PET, such as those produced by... 18 O production 18 F's cyclotron.

[0074] Liquid targets can be static targets, but in order to cool them more effectively and thus enable higher-energy irradiation to improve production capacity, liquid targets are preferably as follows: Figure 1 The illustrated embodiment uses a recirculated liquid target. In this embodiment, the target solution is pumped from container 1 through irradiation device 2 via pump 3 in a first closed loop 4, and then returned to container 1 via heat exchanger 5. The target is preferably also cooled, particularly by water, within irradiation device 2 itself. The solution is preferably irradiated with protons, which preferably have an incident energy of 15-20 MeV. During irradiation, the generated heat is completely or partially removed by stopping protons in the target solution and externally exchanged in the primary heat exchanger 5. A complete irradiation loop is established, ensuring that all liquid-contacting components are made of highly inert, airtight materials, typically Hastelloy, CrNiFe, etc., to avoid corrosion and ensure sealing. Ceramic or a combination of metal and ceramic are also good choices.

[0075] During irradiation 225 Ac continuously accumulates in the target solution. Using a static target, the target solution is collected back into a hermetically sealed target solution bottle at the end of irradiation. The static target is preferably automatically loaded and emptied. The recycled liquid target can be reprocessed during irradiation. From this point onward, 225 The chemical separation and purification of Ac is carried out by recirculating the liquid stream through an extraction column or an ion exchange column. These conditions are set so that actinium is extracted onto the column while impurities are recycled. The column size, flow rate, and volume of the solution depend on the initial volume of the target solution.

[0076] For static targets, the irradiated target solution contained in the bottle can be transferred and recycled through the first extraction device 6. In the extraction device 6, 225 Ac is extracted from the irradiated target solution, while 226Ra (and optionally, in the case of gamma-ray irradiated target solution) 225 Ra) is retained in the target solution. Extraction has already been performed. 226 Ac's target solution was collected again in a bottle and reloaded into the liquid target for re-irradiation.

[0077] exist Figure 1 In the device shown, extraction is performed from a liquid target solution. 225 Ac will have already extracted 225 Loading the liquid target solution back into the liquid target requires fewer processing steps and is easier to implement, especially in an automated manner. Figure 1 In the illustrated embodiment, the irradiated target solution contained in container 1 is actually recirculated through the first extraction device 6 in the second closed loop 7. This is achieved through... Figure 1 This is accomplished by a pump not shown in the image.

[0078] The first extraction device includes a first adsorbent, during the first extraction step. 225 Ac accumulates on the first adsorbent. The first extraction apparatus preferably includes a first extraction column, which, in a low-acidity option, is based, for example, on LN resin (Eichrome, FIDEFIEP). For example, when the target solution contains 0.005-0.05M HNO3, such as 0.02M HNO3, actinium is retained on the column. 226 Ra (and) 225 Ra (if present) is recycled. The volume of recycling will determine the efficiency of Ac absorption from the target solution, and it is important to limit this volume to avoid actinium breakthrough.

[0079] Preferably, Ra is prevented from being lost from the target solution. It is important to... 225 Ac and 226 After Ra separation, most of the target solution volume present in the initial chromatographic column is pushed back into target solution container 1.

[0080] After the initial separation, i.e., after the liquid target solution is pumped or permeates through the column, any radium remaining in the first extraction device 6 is recovered by rinsing the column of the first extraction device 6 with rinsing solution 8. The pH of this rinsing solution is similar to that of the liquid target solution, thus facilitating the rinsing process. 225Ac remains on the chromatographic column. The wash solution is circulated in a third closed loop 9 through the first extraction device 6 and the radium extraction device 10, for example, through a strong cation exchange column (e.g., DOWEX 50W or Biorad 50W or similar). The radium extraction device 10 includes a radium adsorbent on which radium washed off by the wash solution 8 during the wash step accumulates during the wash step.

[0081] To remove all radon gas accumulated in the first extraction device 6, the rinsing solution 8 is preferably also recirculated through the first activated carbon filter 11 to remove radon gas from the first extraction device 6. The activated carbon filter 11 may be a granular activated carbon filter, but is preferably a powdered activated carbon filter.

[0082] Due to the reduced column size and elution volume, further purification and concentration are performed using extraction chromatography columns based on Ln resin, Sr resin, DGA resin, or branched DGA resin (all from Eichrome). Each change in acidity causes actinium to move from one extraction column to the next, thereby increasing purity and concentration factor. The final column determines the medium in which the actinium product exits the process. Figure 1 In this method, SCE (strong cation exchanger) is used with correspondingly high acidity to elute actinium. Another option is to use trivalent element-selective extraction chromatography resins, such as DGA or DGA-B (Eichrom), where actinium elution is carried out at lower acidity.

[0083] exist Figure 1 In the illustrated embodiment, more specifically, radium accumulated in the radium extraction apparatus 10 is eluted from it by a radium eluent 12, the pH or acidity of which differs from that of the rinsing solution, so that radium is eluted from the radium adsorbent during the radium elution step. The rinsing solution 8 may include, for example, a 0.02M nitric acid solution, while the radium eluent 12 may include, for example, a 2M nitric acid solution. The radium eluent 12 containing the recovered radium is stored in an airtight container 13. This container 13 is provided with a gas inlet 14 and a gas outlet 15. Therefore, a small volume of, for example, nitrogen gas can be used to purge the container 13 to remove all radon gas generated in the container 13 during radium storage. Due to the use of only a small volume, Rn can be removed by a small activated carbon gas filter ( Figure 1 and Figure 2 (Not shown in the image) Capture and manage. If necessary, the recovered Ra can be readjusted to the correct acidity, concentrated, and transferred back to the target solution.

[0084] In the first elution step following the rinsing step, the accumulated adsorbent in the first extraction device 6 is eluted from the first adsorbent using the first eluent 16. 225Ac. The pH value of the first eluent 16 is different from the pH value of the liquid target solution, so that it can be eluted from the first adsorbent contained in the first extraction device 6 during the first elution step. 225 Ac. The first eluent 16 may contain a first nitric acid solution having a low pH value, i.e., high acidity, and containing, for example, 0.5 M HNO3. Using this eluent, it is possible to remove [the substance] from the Ln resin. 225 Ac.

[0085] During the first elution step, the first eluent 16 circulates in the fourth closed loop 17 through the first extraction device 6 and the second extraction device 18, the second extraction device 18 containing a second adsorbent, which is eluted from the first extraction device 6 by the first eluent 16 during the first elution step. 225 Ac accumulates on the second adsorbent. The second extraction apparatus preferably includes a second extraction chromatographic column, in which… Figure 1 In the low-acidity options shown, for example, the second extraction column is a DGA-resin (Eichrome, TODGA) based column. When the first eluent 16 contains, for example, 0.5M HNO3, actinium is retained on the DGA column while impurities are recycled. The empty column volume of the second extraction device 18 is preferably smaller than that of the first extraction device 6, so that actinium can be concentrated thereon and eluted from it with a smaller amount of the second eluent 19.

[0086] To remove any radon gas that may be present in the fourth closed loop 17 of the device, the first eluent 16 is circulated from the first extraction unit 6 to the second extraction unit 18, passing through a second radon filter 20, particularly a second activated carbon filter, to extract radon from the first eluent 16. The second activated carbon filter 20 may be a granular activated carbon filter, but is preferably a powdered activated carbon filter.

[0087] when 225 When actinium has accumulated on the second adsorbent contained in the second extraction device 18, in the second elution step, it is removed by the second eluent 19. 225 Actinium is eluted from the second adsorbent. The pH or acidity of the second eluent differs from that of the first eluent 8, so that it is eluted from the second adsorbent contained in the second extraction column during the second elution step. 225 Actinium. The second eluent 19 preferably again comprises a second nitric acid solution, and... Figure 1 The low-acidity options shown contain, for example, 0.05M HNO3. Using this second eluent, DGA resin can be removed... 225 Ac.

[0088] During the second elution step, the second eluent 19 circulates through the second extraction device 18 in the fifth closed loop 21 and through the third extraction device 22 containing the third adsorbent. During the second elution step, the second eluent 19 is eluted from the second extraction device 18. 225 Actinium accumulates on the third adsorbent. The third extraction device 22 preferably includes a third extraction chromatographic column, in which... Figure 1 In the low-acidity options shown, for example, the third extraction column is also based on Ln resin (Eichrome, HDEHEP). When the second eluent 19 contains, for example, 0.05 M HNO3, actinium is retained on the Ln column, while impurities are recycled. If further concentration is not required, the empty column volume of the third extraction device 22 can be equal to the empty column volume of the second extraction device 18.

[0089] To remove any radon gas that may be present in the fifth closed loop 21 of the apparatus, the second eluent 19 is circulated from the second extraction unit 18 to the third extraction unit 22, passing through a third radon filter 23, particularly a third activated carbon filter, to extract radon from the second eluent 19. The third activated carbon filter 23 may be a granular activated carbon filter, but is preferably a powdered activated carbon filter.

[0090] when 225 When actinium has accumulated on the third adsorbent contained in the third extraction device 22, it is removed by the third eluent 24 in the third elution step. 225 Actinium is eluted from the third adsorbent. The pH or acidity of the third eluent 24 is different from that of the second eluent 19, so that it is eluted from the third adsorbent contained in the third extraction column 22 during the third elution step. 225 Actinium. The third eluent 24 preferably again comprises a third nitric acid solution, and in Figure 1 The low-acidity options shown contain, for example, 0.5M HNO3. Using this third eluent, it is possible to remove [the substance] from the Ln resin. 225 Ac.

[0091] exist Figure 1 In the implementation method, 225 Further purification and optional concentration of Ac are obtained by circulating a third eluent 24 through a third extraction device 22 and a fourth extraction device 26 in a sixth closed loop 25 during the third elution step. The fourth extraction device 26 contains a fourth adsorbent, which is eluted from the third extraction device 22 by the third eluent 24 during the third elution step. 225 Actinium accumulates on the fourth adsorbent. The fourth extraction device 26 may again include a DGA or DGA-B (branched) column, wherein the acidity can be as low as 0.1 M, to remove it from the adsorbent in the final step. 225Ac. However, the fourth extraction device 26 preferably comprises an SCE (strong cation exchanger). When the third eluent 24 contains, for example, 0.5 M HNO3, actinium is retained on the SCE 26, while impurities are recycled. The empty column volume of the fourth extraction device 26 can be equal to or less than the empty column volume of the second extraction device 18, and can be approximately half of its empty column volume to enable further concentration. 225 Ac.

[0092] To remove any radon gas that may be present in the sixth closed loop 25 of the device, the third eluent 24 is circulated from the third extraction unit 22 to the fourth extraction unit 26, passing through a fourth radon filter 27, particularly a fourth activated carbon filter, to extract radon from the third eluent 24. The fourth activated carbon filter 27 may be a granular activated carbon filter, but is preferably a powdered activated carbon filter.

[0093] when 225 When actinium has accumulated on the fourth adsorbent contained in the fourth extraction device 26, in the fourth elution step, it is removed by the fourth eluent 28. 225 Actinium was eluted from the fourth adsorbent.

[0094] In the case where the fourth extraction device 26 includes DGA or DGA-B resin, the pH or acidity of the fourth eluent 28 is different from that of the third eluent 24, so that elution occurs from the fourth adsorbent contained in the fourth extraction column 26 during the fourth elution step. 225 Actinium. The fourth eluent 28 preferably again comprises a fourth nitric acid solution, and... Figure 1 The low-acidity options shown contain, for example, 0.1M HNO3. This fourth eluent can be used to remove DGA or DGA-B resins. 225 Ac.

[0095] When the fourth extraction device 26 is an SCE, the fourth eluent 28 has a sufficiently high pH or acidity to elute from the SCE. 225 Ac. The fourth eluent 28 again preferably comprises a fourth nitric acid solution, in which case the fourth nitric acid solution has high acidity and contains, for example, 2M HNO3.

[0096] The resulting purified and concentrated 225 Ac can be removed through outlet 29 of the fourth extraction device, and then dried to obtain a dried product. During the drying step, evaporation removes not only the water contained in the fourth eluent but also the acid contained therein.

[0097] For example, Figure 1 The different extraction devices and solutions used in the illustrated apparatus can have the following compositions:

[0098] Table 1: Available Figure 1 An example of the extraction device and solution composition in the illustrated apparatus.

[0099] Target solution <![CDATA[0.02M HNO3 and 0.4M 226 Ra(NO3)2]]> First extraction device 6 Ln resin (Eichrome, HDEHEP) Rinse solution 8 <![CDATA[0.02M HNO3]]> 10 radium extraction devices SCE (DOWEX 50W) Radium Eluent 12 <![CDATA[2M HNO3]]> First eluent 16 <![CDATA[0.5M HNO3]]> Second extraction device 18 DGA (Eichrome, TODGA) Second eluent 19 <![CDATA[0.05M HNO3]]> Third extraction device 22 Ln resin (Eichrome, HDEHEP) Third eluent 24 <![CDATA[0.5M HNO3]]> Fourth extraction device 26 SCE (DOWEX 50W) Fourth eluent 28 <![CDATA[2M HNO3]]>

[0100] Figure 2 Another embodiment of the method according to the invention is shown, wherein the liquid target solution has a high acidity (low pH). This high acidity option is based on the initial Ac / Ra separation performed using a DGA column. For example, the acidity of the target solution here would be a nitric acidity between 0.1M and 0.5M, and if the lower acidity is compensated by adding nitrates, such as ammonium nitrate, the target solution... 226 The Ra concentration can be as high as 0.35 M. Actinium will be removed by recirculation through a DGA column. The recirculation volume should be large enough to effectively remove Ac, but should be within the column's capacity to avoid Ac percolation. As in the low acidity option, a strong cation exchanger will carry any Ra remaining on the column after the initial actinium separation. Further purification is achieved by reducing the acidity and the uptake on the Ln resin column. The acidity is selected here to avoid co-extraction of Pb, i.e., 0.03 M–0.075 M. There are different options at this point, but subsequent purification and concentration using a DGA or DGA B column may be the preferred method.

[0101] Figure 2 The device shown is related to Figure 1 Corresponding components in the illustrated device are indicated by the same reference numerals. Figure 2 The equipment shown is the same as the one mentioned above. Figure 1 The described devices function in the same way, therefore descriptions of the functions of common components will not be repeated. Instead, the following table provides... Figure 2 A specific example of the different extraction devices and solutions used in the high-acidity equipment shown:

[0102] Table 2: Available Figure 2 An example of the extraction apparatus and solution composition in a high-acidity device is shown.

[0103] Target solution <![CDATA[0.5M HNO3 and 0.35M 226 Ra(NO3)2]]> First extraction device 6 DGA (Eichrome, TODGA) Rinse solution 8 <![CDATA[0.5M HNO3]]> 10 radium extraction devices SCE (DOWEX 50W) Radium Eluent 12 <![CDATA[2M HNO3]]> First eluent 16 <![CDATA[0.05M HNO3]]> Second extraction device 18 Ln resin (Eichrome, HDEHEP) Second eluent 19 <![CDATA[0.5M HNO3]]> Third extraction device 22 DGA (Eichrome, TODGA) Third eluent 24 <![CDATA[0.1M HNO3]]> Lead extraction device 30 Sr resin (Eichrome)

[0104] It can be seen that concentration and purification 225 Ac has been removed from the third extraction unit 22. However, in the fifth closed loop 21, an additional extraction column, namely the lead extraction unit 30, is provided between the second extraction unit 18 and the third extraction unit 22. A third radon filter 23 is provided before the lead extraction unit 30, and an additional radon filter 23' is provided after it.

[0105] The lead extraction apparatus 30 specifically includes Sr resin, which is highly effective for Pb and can be used to remove Pb from the equipment / system. Lead is produced by radon decay. Radon decays via alpha decay and causes radiation damage to the column material, which affects the column's separation performance. Therefore, it is preferable to prevent radon from migrating downstream in the process flow, thereby extending column life and avoiding radon contamination. 225 Ac products. Radon is carried by a radon filter, i.e., by a small chromatographic column containing powdered activated carbon (PAC) or granular activated carbon (GAC). Radon is absorbed / strongly delayed and decays in PAC / GAC columns. 210 Pb, a gamma emitter. 210 Pb will be eluted into the aqueous phase and included in the process flow. PAC / GAC columns can be used multiple times. Sr resin columns are highly effective for Pb and can therefore be used to remove Pb from the process flow. Sr resin columns contain a dicyclohexyl-18-crown-6 derivative as the stationary phase, which is soluble in octanol.

[0106] Also in Figure 1 In low-acidity equipment, a lead extraction unit (Sr resin column) can be easily incorporated, especially between the third extraction unit 22 and the fourth extraction unit 26. Preferably, a fourth radon filter 27 is installed before the lead extraction unit, and an additional radon filter is installed after the lead extraction unit.

[0107] Although because of the limited solubility of radium nitrate (e.g., compared to...) 68 Zinc nitrates have a solubility that is more than 10 times lower. 68 Zinc nitrates are used in liquid target materials, through... 68 Zn(p,n) 68 Ga reacts to produce 68 Ga), in the target solution 226 With a low Ra concentration, the method according to the invention enables commercially viable yields.

[0108] 225 Ac yield can be calculated. 226 Energy-dependent cross section of the Ra(p,2n) reaction (IAEA ENDF database) and containing up to 0.4 M 226 The energy-dependent stopping power of protons in the aqueous solution of Ra(NO3)2 (Nucleonica) is used to obtain the yield in a small layer of liquid target material, and the results are summed to obtain... 225 The overall formation amount of Ac. The weekly yield as a function of the proton current used is shown in Table 1.

[0109] Table 3: 225The functional relationship between Ac production and proton current. 0.35M 226 Ra, irradiation time = 7 days, cooling time = 0 days, cross section = 500mb.

[0110] Current (μA) A(Bq) A(mCi) Heat (W) 10 1.27E+09 34.4 225 20 2.54E+09 68.8 450 30 3.82E+09 103.2 675 40 5.09E+9 137.6 900 50 6.36E+9 171.9 1125 60 7.63E+9 206.3 1350 70 8.91E+9 240.7 1575 80 1.02E+10 275.1 1800 90 1.15E+10 309.5 2025 100 1.27E+10 343.9 2250

[0111] Regarding economic feasibility, assuming the use of... 225 Ac's treatment method has been approved, for 225 The demand for Ac will increase significantly. Unless for 227 Ac undergoes complex isotope separation, otherwise produced by the proposed method. 225 Ac will be more effective than proton irradiation. 232 Th target production 225 Ac is of higher quality. If allocated by production, assuming 40 weeks of production per year, the produced... 225 Ac can cover more than 25,000 treatments. Therefore, it is most likely to ensure the economic feasibility of the actinium production process.

[0112] References:

[0113] Boll,RA,Malkemus,D.,Mirzadeh,S.,Production of actinium-225for alphaparticle mediated radioimmunotherapy.Appl.Radiat.Isot.62,667-679(2005).

[0114] Jost,CU,Griswold,JR,Bruffey,SH,Mirzadeh,S.,Stracener,DW,Williams,CL,Measurement of cross sections for the 232 Th(p,4n) 229 Pa reactionat low proton energies.AIP Conference Proceedings:International Conference onApplication of Accelerators in Research and Industry.Vol.1525,pp.520-524.(2013).

[0115] Koch,L,Fuger,J,van Geel J.,Process for producing Actinium-225,EP0752709,1999.

[0116] Apostolidis,C.,Molinet,R.,McGinley,J.,Abbas,K., J.,Morgenstern,A.,Cyclotron production of Ac-225for targeted alpha therapy,Appl.Radiat.Isot.,62,383-387(2005).

[0117] Abbas,K.,Apostolidis,C.,Janssens,W.,Stamm,H.,Nikula,T.,Carlos,R.,Method for producing Actinium 225,EP1455364,2004.

[0118] Apostolidis,C.,Janssens,W.,Koch,L.,Mcginley,J.,Molinet,R.,Ougier,M.,Van Geel,J., J.,Schweickert,H.,Method for producing Ac-225byirradiation of Ra-226with protons,EP062942,2004.

[0119] Morgenstern,A.,Apostolidis,C.,Molinet,R.,Lutzenkirchen,K.,Method forproducing actinium-225,US patent 20060072698,(2006).

[0120] Ermolaev,S.V.,Zhuikov,B.L.Kokhanyuk,V.M.,Matushko,V.L.,KalmykovStepan,N.,Aliev Ramiz,A.Tananaev Ivan,G.

[0121] Myasoedov,B.Production of actinium,thorium and radium isotopes fromnatural thorium irradiated with protons up to 141MeV Radiochim.Acta,100,p.223(2012).

[0122] Weidner,J.W.,Mashnik,S.G.,John,K.D.,Hemez,F.,Ballard,B.,Bach,H.,Birnbaum,E.R.,Bitteker,L.J.Couture,A.,Dry,D.,et al.Proton-induced crosssections relevant to production of 225 Ac and 223 Ra in natural thorium targetsbelow 200 MeV,Appl.Radiat.Isot.,70,pp.2602-2607,(2012).

[0123] Griswold,J.R.,Medvedev,D.G.,Engle,J.W.,Copping,R.Fitzsimmons,J.M.,Radchenko,V.,Cooley,J.C.,Fassbender,M.E.,Denton,D.L.,Murphy,K.E.,Owens,A.C.,Birnbaum,E.R.,John,K.D.,Nortier,F.M.,Stracener,D.W.,Heilbronn,L.H.,Mausner,L.F.Mirzadeh,S.,Large Scale Accelerator Production of 225 Ac:Effective CrossSections for 78-192 MeV Protons Incident on 232Th targets,Applied Radiationand Isotopes,118,366-374,(2016).

[0124] Zhuikov,B.L.,Kalmykov,S.N.,S.V.Ermolaev,S.V.,Aliev,R.A.,Kokhanyuk,V.M.,Matushko,V.L.,Tananaev,I.G.,Myasoedov B.F.,Production of 225 Ac and 223 Raby irradiation of Th with accelerated protons,Radiochemistry,53,pp.73-80,(2011).

[0125] Koch,L,Fuger,J,van Geel J.,Process for producing Actinium-225 fromradium-226,EP0752710,1999-1.

[0126] Melville,G.Meriarty,H.,Metcalfe,P.,Knittel,T.,Allen,B.J.Production ofAc-225 for cancer therapy by photon-induced transmutation of Ra-226,AppliedRadiation and Isotopes,65,1014-1022,(2007).

[0127] Melville G.,Allen,B.J.,Cyclotron and linac production of Ac-225,Applied Radiation and Isotopes,67,549-555,(2009).

[0128] Clarke,J.C.,High-Powered Cyclotron Recirculating Target forProduction of the 18 F Radionuclide,PhD Thesis,North Carolina State University(2004).

Claims

1. A kind of from 226 Separation of radium 225 The method of actinium, the method comprising the following steps: Provides 226 A liquid target solution containing radium; The liquid target solution is irradiated in the irradiation device (2) to achieve the desired effect from the components contained in the liquid target solution. 226 Radium begins to be obtained in the liquid target solution. 225 Actin; and From the remaining 226 At least a portion of the obtained radium was separated from it. 225 Actinide, Its features are, The separation step includes a first extraction step performed in the first extraction apparatus (6), wherein at least a portion of the liquid target solution is extracted from the liquid target solution. 225 Actinium, and 226 Radium is retained in the liquid target solution; and The method further includes the following steps: The portion of the substance already extracted was further extracted by irradiation in the irradiation device (2). 225 The liquid target solution of actinium, wherein the liquid target solution contains 226 Radium begins to be further obtained in the liquid target solution. 225 Actin.

2. The method according to claim 1, characterized in that, During the irradiation process, the liquid target solution circulates through the irradiation device (2) and the heat exchanger (5) in the first closed loop (4).

3. The method according to claim 2, characterized in that, During the first extraction step, the liquid target solution circulates through the first extraction device (6) in the second closed loop (7).

4. The method according to claim 3, characterized in that, During the irradiation step, the liquid target solution circulates through the container (1) and the irradiation device (2) in the first closed loop (4), and during the first extraction step, the liquid target solution circulates through the container (1) and the first extraction device (6) in the second closed loop (7).

5. The method according to claim 1, characterized in that, Extracting at least a portion of the liquid target solution from the liquid target solution 225 Prior to this, the liquid target solution was irradiated for less than 16 days.

6. The method according to claim 1, characterized in that, During the irradiation step, the liquid target solution is irradiated with protons or deuterium nuclei.

7. The method according to claim 1, characterized in that, During the irradiation step, the liquid target solution is irradiated with gamma rays to achieve the desired effect. 226 radium converted to 225 Radium and General 225 radium converted to 225 A to obtain 225 Actin.

8. The method according to claim 7, characterized in that, During the first extraction step, the 225 Radium is retained in the liquid target solution.

9. The method according to claim 1, characterized in that, The liquid target solution contains 226 Solutions of radium salts and their corresponding acids.

10. The method according to claim 9, characterized in that, The solution contains 226 Radium nitrate and nitric acid.

11. The method according to claim 1, characterized in that, The first extraction device (6) contains a first adsorbent, which, during the first extraction step, 225 Actinium accumulates on the first adsorbent, and the method includes a first elution step, wherein at least a portion of the actinium already accumulated on the first adsorbent is eluted. 225 Actinium is eluted from the first adsorbent by the first eluent (16).

12. The method according to claim 11, characterized in that, The liquid target solution has a predetermined pH value so that during the first extraction step, the... 225 Actinium accumulates on the first adsorbent, and the first eluent has a pH value different from that of the liquid target solution, so that during the first elution step... 225 Actinium is eluted from the first adsorbent.

13. The method according to claim 11, characterized in that, The first eluent (16) contains a first acid solution containing nitric acid.

14. The method according to claim 11, characterized in that, During the first elution step, the first eluent (16) circulates through the second extraction device (18) in the fourth closed loop (17), the second extraction device containing the second adsorbent, and the first eluent elutes the first adsorbent from the first adsorbent during the first elution step. 225 Actinium accumulates on the second adsorbent, and the method includes a second elution step, wherein at least a portion of the actinium already accumulated on the second adsorbent is eluted. 225 Actinium is eluted from the second adsorbent by a second eluent (19) having a different pH value than the first eluent, so that during the second elution step... 225 Actinium is eluted from the second adsorbent.

15. The method according to claim 14, characterized in that, The second eluent (19) contains a second acid solution containing nitric acid.

16. The method according to claim 14, characterized in that, The first eluent (16) is circulated from the first extraction device (6) to the second extraction device (18), passing through the second radon filter (20) to extract radon from the first eluent (16).

17. The method according to claim 14, characterized in that, During the second elution step, the second eluent (19) circulates through the third extraction device (22) in the fifth closed loop (21), the third extraction device (22) containing a third adsorbent, which, during the second elution step, elutes the adsorbent from the second adsorbent using the second eluent (19). 225 Actinium accumulates on the third adsorbent, and the method includes a third elution step, wherein at least a portion of the actinium already accumulated on the third adsorbent is eluted. 225 Actinium is eluted from the third adsorbent by a third eluent (24) having a different pH value than the second eluent (19), so that during the third elution step, the actinium... 225 Actinium is eluted from the third adsorbent.

18. The method according to claim 17, characterized in that, The third eluent comprises a third acid solution, which contains nitric acid.

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