Method for Producing Actinium-225 from Radium-226

Abstract

225 Actinium is converted into liquid by proton, deuterium or gamma irradiation in the irradiation device (2). 226 The radium target is irradiated and the resulting liquid target solution in the first extractor (6) is extracted. 225 By extracting actinium, 226 It is produced from radium. 225 The liquid target solution from which actinium has been removed is irradiated again to generate more 225 The liquid target solution is preferably circulated through the irradiation device in a closed loop (4) and through the first extraction device (6) in a further closed loop (7). The advantage of such a method is that the irradiated target solution does not have to be dried and redissolved so that the produced actinium can be separated from the radium, and no further drying and redissolution steps are required to regenerate the liquid target starting from the separated radium. The radium target is therefore in particular 226 Taking into account the radon gas that is continuously produced by the decay of radium, it can be recycled in a more efficient and safe way.

Description

Technical Field

[0001] The present invention relates to 226 a method for generating 225 actinium from radium, the method comprising preparing a liquid target solution containing radium, irradiating the liquid target solution in an irradiation device, and generating actinium in the liquid target solution starting from the radium contained therein, at least a part of the generated actinium being separated from the residual 226 radium. 226 Starting from 225 radium in the liquid target solution 225 to generate 226 actinium, and

Background Art

[0002] 225 Actinium is an interesting radionuclide for use in cancer treatment. 225 Actinium is an α-emitting radioisotope with a half-life of 10 days. It can be used as an agent for radiotherapy. α-particle emitters are promising sources for the lethal irradiation of single cancer cells and micrometastases due to their high density of ionizing radiation. α-particles are particularly interesting for radiotherapy applications because their range in soft tissue is limited to only a few cell diameters.

[0003] 225 There are several possible methods for generating actinium, but there is still a need for a new and safer production method that enables the production of actinium in the amounts required to meet the demand. 225 For example, as disclosed in Patent Document 1,

[0004] actinium can be generated by 229 the radioactive decay of thorium. 225 This is the current main method for generating 225 Ac for medical use. This method involves 229 Th / 225 Ra / 225Using an Ac generator (Boll2005), 225 Ac is 229 constantly produced by the alpha decay of Th and the radioactive ingrowth from its daughter 225 Ra. The generator produces radiochemically pure 225 Ra and 225 Ac every 6 - 8 weeks. 225 The maximum activity of Ac is limited by the total amount of 229 Th present in the generator. 229 The chemical separation between Th and 225 Ra / 225 Ac is usually based on ion exchange. Currently, there are three such generators worldwide. ORNL (USA) supplies up to 720 mCi / year of 225 Ac. Similar amounts are reported to be available from the Institute of Physics and Power Engineering in Obninsk, Russia, and the European Commission directorate G in Karlsruhe maintains a smaller 229 Th source (capable of producing up to 350 mCi / year of 225 Ac). However, the problem is that 225 the demand for Ac is already higher than the total production rate from existing generators. On the other hand, 229 Th is a rare isotope ( 233 derived from 233 U) and has limited availability worldwide. 229 Due to the long half - lives of 229 U and

[0005] 225 Another method for producing actinium is 232 by proton or deuterium irradiation of a tritium target 225It consists of the production of Ac. This method is based on the production of thick 232 Th metal targets (natural Th) irradiated with medium-energy protons or deuterium (24 - 50 MeV) by a cyclotron in an accelerator facility (Ermalaev2012, Weidner2012) or medium- to high-energy protons (>80 MeV) (Morgenstern2006). For medium-energy protons or deuterium, 225 the production of Ac is 232 Th(p,4n) 229 Pa and 232 Th(d,5n) 229 Pa, followed by a low-yield 0.48% β + decay, resulting in isotopically pure 225 Ac. The required proton and deuterium energies are within the range of today's commercially available cyclotrons, but very high currents are required to obtain interesting production rates. The direct production of 232 Ac by the 225 Th(p,x) reaction is not sensitive only to the production of 225 Ac, and adjacent isotopes are produced with comparable high cross-sections. In fact, Ci-level 225 Ac can be produced by high-energy protons in a one-week irradiation (Ermolaev2012, Griswold2016), but direct therapeutic use is hampered by the co-production of the long-lived (27-year) alpha emitter 227 Ac / 225 Ac = 0.2% (Griswold2016) 227 Ac (Ermolaev2012). The chemical separation of actinium from the irradiated thorium target is quite complex due to the complex mixture of co-isotopes after irradiation and usually based on a series of ion-exchange columns. 227 From 225The separation and purification of Ac is an isotope separation if necessary and cannot be achieved using ordinary chemical methods. This requires a very complex mass separation that can be performed on-line during irradiation (ISOLDE). The required proton current (>100 μA) and high proton energy (90 - 200 MeV) exceed current commercially available cyclotrons. In fact, there are only a limited number of accelerator facilities worldwide that can produce protons with the required medium to high energies (Zhuikov 2011). Even fewer can perform isotope separation on-line.

[0006] 225 Another method for producing actinium is disclosed, for example, in Patent Document 2 and Patent Document 3, 226 and consists of the production of Ac by proton or deuterium irradiation of Ra. This method is based on the production of a thin solid target of Ra that is placed in an airtight water-cooled target holder and irradiated with protons (Koch 1999, Apostolidis 2004) or deuterium (Abbas 2004). 225 After chemical separation of Ac, the remaining 226 Ra is reprocessed and recycled for the production of new targets, thereby closing the radium irradiation cycle. The irradiation method has been successfully demonstrated in cyclotron irradiation tests where mCi levels of 225 Ac are produced. 226 For the Ra(p,2n) 225 Ac reaction, a cross-section of 0.71 mb can be demonstrated with 16.8 MeV protons, and through target dissolution and chemical separation, it has been further demonstrated that the 226 Ac product has 225 the same high radiochemical quality as the 225 Ac generated from a 229 Th / 226 Ra / 225 Ac generator (Apostolidis 2005). 225 However, further development and demonstration of this method has been halted due to the complex handling of the

[0007] Ra solution. 226 ​226 Ra is a fairly long-lived alpha emitter, highly radioactive, and requires shielding even when used in relatively small amounts. However, the main problem is that 226 Rn (radon) directly produced by the alpha decay of Ra. 222 In fact, if radon is never separated and removed, 226 Ra and 222 Rn will reach radioactive equilibrium with the same radioactivity level after a few weeks. Radon ( 222 Rn) is a noble gas and is very difficult to contain, so it has serious problems. Therefore, when handling large amounts of 226 Ra, in order to minimize radium contamination and / or radon release, shielding facilities under pressure such as hot cells and glove boxes with a large air flow, and very careful and sufficient consideration through handling approaches are required. Solid irradiation 226 dissolution of the Ra target, 225 chemical purification of Ac, and 226 reprocessing of Ra as well as target generation are all open processes that make the entire process sensitive to radon release.

[0008] In such a process, irradiation is usually carried out outside the hot cell / glove box, so the handling of the target is particularly important. The target after loading must be contamination-free and airtight. The water cooling of the target and the thin target window must be optimized for the proton current used to avoid target failure. A major advantage of this method is that commercially available cyclotrons for the production of PET isotopes by proton irradiation can be used. They can deliver the optimized proton energy at an appropriate current. However, due to the above-mentioned drawbacks, the further development of this interesting 225 method for the production of Ac has been discontinued.

[0009] has the same drawbacks as the previous production methods, but 225 Another method for producing actinium is disclosed, for example, in Patent Document 4. This method is by neutron or high-intensity gamma-ray irradiation226 By irradiation with Ra 225 consisting of the generation of Ac (this is achieved in Patent Document 4 by an electron beam converted to gamma rays by the use of a conversion material). This is 226 by utilizing the (γ, n) or (n, 2n) reaction of Ra 225 which decays to Ac 225 to generate Ra. The photon reaction (γ, n) utilizes a strong gamma-ray field generated as bremsstrahlung in an electron accelerator, while neutrons are generated in a fast reactor or by a spallation source in an accelerator facility. 226 From Ra 225 To generate Ac, a 18MV linear (medical) accelerator was used, but the cross-sectional area was too small for practical use (Melville 2007). In later research, it was stated that a more powerful accelerator irradiation of a larger amount of 226 Ra might be achievable (Melville 2009). Regarding the handling of radium, this production method has the same drawbacks as the proton irradiation of a solid Ra target. 226 The Ra target has to be actually manufactured, irradiated, dissolved, the actinium product separated, and the radium reprocessed for the production of a new target. A very large (more than several tens of grams of) 226 Ra target is likely to be required, but compared to proton irradiation, there are fewer problems with heat removal and there is no need to thin the target window, so the target technology and irradiation are probably technically easier. Nevertheless, photon or neutron reactions require large facilities such as a nuclear reactor, a high-intensity linear accelerator or a synchrotron to reach an appropriate production level.

[0010] In summary, 229 As a decay product from Th 225 The current production method of Ac cannot be easily increased or expanded to meet future demands in therapeutic treatments. Actinium can be produced with a commercial cyclotron by irradiation of radium by the (p, 2n) reaction. However, 226The handling of Ra is very difficult for its daughter radon. The proposed techniques are based on the irradiation of solid targets with cyclotrons (protons or deuterons) or synchrotrons (gamma rays), which require target production, irradiation, target dissolution, actinium separation, and finally, the reprocessing of Ra into a new solid target to close the cycle. In the irradiation of charged particles (protons, deuterons), the heat removal (cooling) of the target and the thin target window limits the particle current and thus the production capacity. Radon release will always be a concern in such processes. In the (γ, n) reaction, the target window is not limited, but such a process probably requires large to very large amounts of 226 Ra and electron accelerator facilities. 232 The method based on the high-energy proton irradiation of Th 227 may require a very complex isotope separation based on mass separation to remove Ac.

[0011] In the method according to the present invention, 226 a liquid target containing a solution of radium is used. The use of such a liquid target is disclosed in Patent Document 4. In this known method, 226 Ra is converted by gamma-ray irradiation into 225 Ra having a half-life of 14.8 days, and then 225 is converted into Ac. 226 The 225 conversion of Ra into Ra is achieved by hitting electrons on a conversion material that generates photons. 226 Ra is coated on the conversion material, but may be recycled into the flowing solution on the conversion material until sufficient product is generated. 226 The Ra solution may be contained in a quartz vial and irradiated.

[0012] As a target 226 The advantage of the Ra solution is that a sufficiently large amount of 226 Ra is available and the production and dissolution of solid targets are not required. However, the generated 225The separation and purification of Ac still pose problems in the handling of radioactive 226 Ra and the radon continuously generated thereby. In the method disclosed in Patent Document 4, the liquid target is actually 226 formed by a solution of radium chloride. This solution may have a concentration of about 0.5 to about 1.5 mol, for example, about 1 mol. After irradiation for about 10 to about 30 days, for example, about 20 days, the solution 226 contains Ra and a small amount of 225 Ra generated in the solution and 225 Ac. In order to be able to separate the generated 225 Ac from 226 Ra and 225 Ra, the irradiated solution must be dried and the dried material redissolved in a 0.03 M HNO3 solution. This solution is passed through an ion exchange column, particularly an LN (registered trademark) resin column (Eichrom Industries, Inc., Darien, III.). 226 Ra and 225 Ra pass through the column, and 225 Ac is retained on the column. Subsequently, the bound 225 Ac is eluted from the column with 0.35 M HNO3.

[0013] Although not disclosed in Patent Document 4, 226 Ra and 225 Ra can be reused as a target. Since the target is in chloride form, the reuse of these radium isotopes requires the evaporation of the nitric acid solvent and the redissolution of the dried material obtained in hydrochloric acid to obtain a radium chloride solution of the liquid target.

[0014] As described above, the problem with such a method is that it must be carried out in a sealed environment where continuously generated radon gas is trapped. Due to the complex treatment of the irradiated target solution to extract the generated 225 Ac and regenerate the remaining target solution containing 226 Ra, the target solution must be 225 sufficiently225 It should be irradiated until it contains Ac. In the method disclosed in Patent Document 4, the liquid target is irradiated even further, especially until 80 to 90% of the maximum production capacity is achieved. The drawback of such a long irradiation time is that, after being produced, 225 since Ac has already decayed, a significant portion of the produced 225 Ac is lost during its production.

Prior Art Documents

Patent Documents

[0015]

Patent Document 1

Patent Document 2

Patent Document 3

Patent Document 4

Summary of the Invention

[0016] An object of the present invention is to 226 provide a new method for producing 226 Ac from 225 Ac by irradiating a liquid target containing Ra, which does not require a drying and redissolving step to enable separation of the produced actinium from radium, and a further drying and redissolving step to regenerate the liquid target starting from the separated radium. Thus, the new method should make it possible to recycle the radium target in a more efficient and safe manner after removing the actinium produced from the radium target.

[0017] For this purpose, the method according to the present invention includes a separation step that includes a first extraction step carried out in a first extraction device, 225 wherein at least a part of the actinium is extracted from the liquid target solution while 226Radium is maintained in a liquid target solution, and the method according to the invention 225 irradiates again, in an irradiation device, the liquid target solution from which part of actinium has been extracted, so as to further 226 generate actinium in the liquid target solution starting from the radium contained therein. 225 This is characterized by including a further step of

[0018] In the method of the present invention, the liquid target solution is irradiated in an irradiation device, and after irradiation, the same target solution is supplied to a first extraction device, and the generated actinium is extracted from the liquid target solution itself. Therefore, there is no need to dry or redissolve the irradiated target solution. After extracting actinium from the irradiated liquid target solution, the liquid target solution is irradiated again as it is, and further actinium is generated in the target solution. Here too, no drying and redissolving steps are required to produce the liquid target. Therefore, the cycle is closed without requiring drying and redissolving of the target material.

[0019] Since the liquid target solution is used as it is in the continuous irradiation and extraction steps, no drying and redissolving steps are required, so the production process can be easily automated, and any leakage of radon gas can be easily avoided.

[0020] The liquid target solution may be contained in a static target. Then, in order to empty this static target in the first extraction device and refill the static target with the liquid target solution from which actinium has been extracted, some operation of this static target is required. The transfer of the liquid target solution to and from the first extraction device can be automated, or this single step can be easily performed in a closed environment such as inside a hot cell or a glove box. The extraction of the generated actinium can be carried out, for example, once a day or every few days, for example, once a week.

[0021] In a first embodiment of the method according to the invention, the liquid target solution is circulated in a first closed loop through the irradiation device and the heat exchanger during the irradiation step.

[0022] Thus, in this embodiment, the target is a dynamic target rather than a static one. Since the target solution is circulated in a closed loop, the generated radon gas can be easily confined within the system / facility. The 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 device, thereby cooling the irradiation device, particularly the window that separates the target solution from the outside.

[0023] When the radium target is irradiated with protons, the proton beam accumulates its energy in the target solution, increasing the temperature and pressure during irradiation. The efficiency of heat removal is important, and the target and the target window must be accurately designed to withstand the irradiation conditions. For example, compared with PET radioisotopes or other radioisotopes also generated by a cyclotron in a liquid target solution 225 Since the half-life of Ac is relatively long and the solubility of Ra salts in aqueous solution is limited, the irradiation inevitably has to be long. To reach an appropriate production level, it is necessary to apply the highest possible proton current to increase the heat load on the target. However, the liquid target in a closed volume has its heat load limited due to the increase in the internal pressure and temperature of the target liquid. The increase in heat load can be addressed to some extent in a liquid target designed with internal reflux, i.e., a thermosyphon design, and may also be meaningful for the irradiation of Ra solution. However, 226 Increasing the target temperature and target pressure when handling Ra is questionable from a safety perspective.

[0024] To enable a relatively high proton current, i.e., a sufficiently high production level, the target is preferably water-cooled in this first embodiment, and a significant portion of the heat removal is handled by external cooling of the target solution itself. This embodiment enables significantly higher currents and heat loads compared to static liquid targets. The recirculating target liquid provides efficient internal cooling of the target and the target window itself, thereby enhancing the safety against failure of the target window.

[0025] The recirculating target 18 has been investigated for the production of F(Clarke2004), but no conventional uses have been found so far. 18 For the production of F, the technique of recirculating the target is mainly 18 complicated in practice because the solution volume of the O-enriched water is only a few milliliters. This requires a very small recirculation loop design, so it is not obvious to use such a recirculation loop to cool the liquid target. However, in the method of the present invention, the problem of a very small recirculation loop design is solved by using a larger but less concentrated amount of target solution that enables a circulation loop design using standard techniques for liquid pumping and cooling. A higher radium concentration in the target solution is preferred from the perspective of the efficiency of the irradiation process, but 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 the form of acid, only a lower radium concentration is possible. The total volume of the target solution used in the production method of the present invention can be particularly larger than 10 ml, more specifically larger than 20 ml, even more specifically larger than 30 ml, and further larger than 40 ml. The total volume of the target solution is preferably not too large as it also determines the size of the separation column, for example, less than 250 ml, preferably less than 150 ml. The 226 Ra concentration in the target solution is relatively low, especially less than 1 M, more specifically less than 0.8 M, so only a relatively small amount of 226 Ra is required. 226Ra is 226 the Ra salt, especially 226 Ra(NO3)2 or 226 RaCl2 can be achieved in the target solution by dissolving it in the target solution. 226 Compared with Ra(NO3)2, 226 a somewhat higher concentration can be achieved with RaCl2, but in order to be able to extract actinium from the target solution, the target solution needs to contain more hydrochloric acid, 226 and the solubility of the RaCl2 salt decreases. Therefore, 226 neither Ra(NO3)2 nor 226 RaCl2 can achieve a higher radium concentration in the target solution. However, despite the relatively low radium concentration that can be achieved, the method according to the invention has been found to make it possible to obtain a sufficiently high productivity.

[0026] In a second embodiment of the method according to the invention, the liquid target solution is circulated in a second closed loop through a first extraction device during the first extraction step.

[0027] Also in this second embodiment, the recirculation of the target solution is again made possible with a circulation loop design using standard techniques for liquid pump transport. This is for extracting the generated actinium from the target solution. The advantage of this embodiment is that the generated radon gas can be easily confined again within the system / facility by circulating the liquid target solution in a closed loop through the first extraction device. The liquid target solution may be recirculated multiple times through the first extraction device. In this way, the first extraction device can be filled to the maximum with actinium, especially when the liquid target solution is contained in a container and recirculated through this container and the first extraction device.

[0028] In a third embodiment of the method according to the invention applicable to the combination of the first and second embodiments, the liquid target solution is circulated in a first closed loop through the container and the irradiation device during the irradiation step, and in a second closed loop through the container and the first extraction device during the first extraction step.

[0029] The advantage of this embodiment is that there is no need to transfer the liquid target solution from the irradiation device to the first extraction device and vice versa, and it can simply be circulated through the irradiation device and the first extraction device. Since this occurs in two closed loops, the radon gas cannot escape. A further advantage of this embodiment is that the irradiation step can be continued during the extraction step. In other words, there is no need to interrupt the irradiation step in order to be able to remove the generated actinium from the target solution. Thus, the generated actinium can be removed more frequently, i.e., more rapidly after its generation, and as a result, less actinium is lost due to decay. Also, the liquid target solution may be recirculated more than twice through the first extraction device, or semi - continuously, i.e., interrupted only mainly for any elution or rinsing step. In this way, the maximum amount of generated actinium can be removed from the target solution, despite the relatively large recirculation volume of the target solution and despite the fact that the target solution leaving the first extraction device is remixed with the target solution being fed to the first extraction device.

[0030] In a fourth embodiment of the method according to the invention, the first extraction step is carried out during the irradiation step.

[0031] The advantage of this embodiment is that the irradiation device can be used optimally because there is no need to stop the irradiation process to enable extraction of the generated actinium.

[0032] In a fifth embodiment of the method according to the invention, the liquid target solution is 225Before at least a part of the actinium is extracted from the liquid target solution, it is irradiated for less than 16 days, preferably less than 13 days, more preferably less than 10 days, and most preferably less than 7 days.

[0033] Since actinium can be easily extracted from the liquid target solution, i.e., without a drying and redissolving step, it is preferably removed early enough to reduce the decay of the actinium generated during the irradiation process itself.

[0034] In a sixth embodiment of the method according to the invention, the first extraction step is carried out with a break of less than 16 days, preferably less than 13 days, more preferably less than 10 days, and most preferably less than 7 days.

[0035] Again, since actinium can be easily extracted from the liquid target solution, i.e., without a drying and redissolving step, it is preferably removed early enough to reduce the decay of the actinium generated during the irradiation process itself.

[0036] In a seventh embodiment of the method according to the invention, the liquid target solution is irradiated with protons or deuterium during the irradiation step.

[0037] By protons or deuterium, 226 from radium 225 actinium can be generated directly and effectively. An important advantage is that commercially available cyclotrons aimed at the production of PET (positron emission tomography) isotopes by proton irradiation can be used. They can 225 deliver the optimal proton energy with a current suitable for the production of actinium. Therefore, large equipment is not required.

[0038] In an eighth embodiment of the method according to the invention, the liquid target solution is irradiated with γ irradiation during the irradiation step, 226 of radium 225 conversion to radium and 225 of radium 225By conversion to actinium 225 Actinium is produced.

[0039] The advantage of this embodiment is that, compared to proton irradiation, there are fewer heat removal problems and there is no need to thin the target window, so the target technology and irradiation can be technically easier.

[0040] Preferably, during the first extraction step 225 radium is 225 maintained in the liquid target solution when actinium is extracted from the liquid target solution.

[0041] The advantage of this preference is that 225 since radium is recycled 225 actinium is immediately regenerated again in the liquid target solution without a time lag.

[0042] In a ninth embodiment of the method according to the invention, the liquid target solution 226 comprises a solution of a radium salt and its corresponding acid, the solution preferably 226 comprises radium nitrate and nitric acid.

[0043] As described above, radium chloride has a higher solubility in water than radium nitrate, but usually requires a larger amount of the corresponding acid, i.e., HCl, in solution, which reduces the solubility of radium chloride. The required concentration of HCl can include, for example, about 5M.

[0044] The advantage of using radium nitrate in combination with nitric acid is that 226 instead of extracting Ra (or even Ra if produced 225 ), there are different extraction chromatography resins that enable the extraction of actinium, and the extraction chromatography resins are from solutions having a relatively low nitric acid content (the effect on the solubility of radium nitrate is relatively small) 225 225 225An extraction chromatography resin that enables the extraction of actinium and can be eluted with a nitric acid solution having a higher nitric acid content (for example, an LN resin containing dialkylphosphoric acid), and from a solution having a relatively high nitric acid content 225 An extraction chromatography resin that enables the extraction of actinium and can be eluted with a nitric acid solution having a lower nitric acid content (for example, a DGA (diglycolamide) (for example, N,N,N’,N’-tetra-n-octyldiglycolamide or N,N,N’,N’-tetrakis-2-ethylhexyldiglycolamide) - based resin, a CMPO (that is, octylphenyl - N,N - di - isobutylcarbamoylphosphine oxide) - based TRU resin, or a diamide (for example, DMDOHEMA or DMDBTDMA) - based resin) is included. Therefore, the use of a series of these different extraction chromatography resins enables 225 the extraction of actinium from a liquid target solution, 225 the elution of actinium from the first extraction chromatography resin, 225 and the re - extraction of actinium in a purer and more concentrated form by a second extraction chromatography resin from the eluent. Depending on the nitric acid content of the liquid target solution, the series of two extraction chromatography resins can be reversed.

[0045] A further advantage of the use of radium nitrate in combination with nitric acid is that corrosion by chlorides is a much greater problem compared to corrosion problems in a nitrate medium. There are many materials that are essentially corrosion - resistant even at higher concentrations of nitric acid. There are few materials suitable for hydrochloric acid. This situation is further complicated by irradiation conditions under which reactive radicals are generated. These problems can be solved by the use of nitric acid.

[0046] In a tenth embodiment of the method according to the present invention, the first extraction device includes a first adsorbent on which 225 actinium accumulates during the first extraction step, and the method includes a first elution step, in which the 225At least a part of actinium is eluted from the first adsorbent by the first eluent.

[0047] In this embodiment, 225 Actinium accumulates on the first adsorbent during the first extraction step, so it can be easily extracted from the liquid target solution. The first extraction device is preferably an extraction chromatography device, and the first adsorbent preferably includes a carrier, preferably an inert carrier, and an extractant as a stationary phase on a support.

[0048] In an eleventh embodiment of the method according to the invention 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, while the first eluent has a pH value different from the pH value of the liquid target solution such that the 225 actinium is eluted from the first adsorbent during the first elution step.

[0049] The advantage of this embodiment is that both the liquid target solution and the first eluent can contain the same acid with only different concentrations. As a result, the acid of the target solution remaining on the first adsorbent cannot interfere with the first elution step, and vice versa. As a result, the acid of the first eluent remaining on the first adsorbent cannot interfere with the first extraction step.

[0050] In a twelfth embodiment of the method according to the invention applicable to the eleventh embodiment, the method includes a rinsing step between the first extraction step and the first elution step. In the rinsing step, the first extraction device is rinsed with a rinsing solution having a pH value different from the pH value of the first eluent such that the 225 actinium remains on the first adsorbent. The rinsing solution preferably has a pH value approximately equal to the pH value of the liquid target solution.

[0051] The advantage of this embodiment is that the radium remaining in the first adsorbent at the end of the first extraction step can be washed away before the actinium is eluted from the first adsorbent, and thus the radium remains in the system / facility without being lost and cannot form impurities in the extracted actinium. Radium, as used herein, means any radium isotope, particularly 226 radium, and optionally, if generated during the irradiation step, 225 radium also means.

[0052] Preferably, the rinse solution preferably does not mix with the liquid target solution and pushes the liquid target solution out of the first extraction device during the rinsing step, and the first eluent preferably does not mix with the rinse solution and pushes the rinse solution out of the first extraction device during the first elution step.

[0053] In a thirteenth embodiment of the method according to the invention applicable to the twelfth embodiment, the rinse solution is circulated in a third closed loop through the radium extraction device during the rinsing step, and the radium extraction device comprises a radium adsorbent on which radium rinsed from the first adsorbent by the rinse solution accumulates during the rinsing step. The method includes a radium elution step in which at least a portion of the radium accumulated on the radium adsorbent is eluted from the radium adsorbent by a radium eluent, and the radium eluent has a pH value different from the pH value of the rinse solution, particularly such that radium is eluted from the radium adsorbent during the radium elution step.

[0054] The advantage of this embodiment is that the radium rinsed from the first extraction device can be recovered. The radium can be stored in the radium eluent for a while and recovered by readjusting the radium solution to the correct acidity, concentrating it, and returning it to the target solution. Since only a small amount of radium is washed away from the first extraction device, this recovery operation only needs to be performed occasionally.

[0055] Thus, in a 14th embodiment of the method according to the invention, applicable to the 13th embodiment, 226 from the radium adsorbent 226 radium eluted during the radium elution step 226 is preferably stored and subsequently recycled to the liquid target solution.

[0056] In a 15th embodiment of the method according to the invention, applicable to any one of the 12th to 14th embodiments, the rinse solution is circulated through a first radon filter, in particular a first activated carbon filter, and radon is removed from the first extraction device.

[0057] Radon generated in the first extraction device and radon generated in the irradiation device and collected in the first extraction device can be removed from the first extraction device by the first radon filter when rinsing the first extraction device through the first radon filter. This filter is, for example, an activated carbon filter to which radon adheres. This radon then decays to 210 generate Pb, which remains in the system / facility. To enable removal of 210 Pb from the system / facility, an extraction chromatographic column containing a lead extraction device, for example Sr resin or Pb resin (Eichrome), can be provided in the system / facility, and both Sr resin and Pb resin are very efficient at removing Pb.

[0058] In a 16th embodiment of the method according to the invention, applicable to any one of the 12th to 15th embodiments, the rinse solution contains an acidic solution containing the same acid as the target solution, in particular nitric acid.

[0059] In a 17th embodiment of the method according to the invention, applicable to any one of the 10th to 16th embodiments, the first eluent contains a first acidic solution containing the same acid as the target solution, in particular nitric acid.

[0060] The liquid target solution, the rinsing solution, and the first eluent solution preferably contain the same acid, but they are not mixed because this would cause interference in the production process, especially when the production process is carried out for a relatively long time. Therefore, the volume of the rinsing solution contained in the first extraction device is preferably pushed back into its recirculation loop by the first eluent before the first eluent is recirculated through the second extraction device.

[0061] In an eighteenth embodiment of the method according to the invention, applicable to any one of the tenth to seventeenth embodiments, the first eluent is circulated in a fourth closed loop through the second extraction device during the first elution step, and the second extraction device contains a second adsorbent on which actinium accumulates during the first elution step. The method includes a second elution step in which at least a portion of the actinium accumulated on the second adsorbent is eluted from the second adsorbent by a second eluent. The second eluent has a pH value that is particularly different from the pH value of the first eluent such that actinium is eluted from the second adsorbent. The second eluent preferably contains a second acidic solution containing the same acid as the target solution, particularly nitric acid. 225 actinium accumulates during the first elution step. The method includes a second elution step in which at least a portion of the actinium accumulated on the second adsorbent is eluted from the second adsorbent by a second eluent. The second eluent has a pH value that is particularly different from the pH value of the first eluent such that actinium is eluted from the second adsorbent. The second eluent preferably contains a second acidic solution containing the same acid as the target solution, particularly nitric acid. 225 actinium accumulates during the first elution step. The method includes a second elution step in which at least a portion of the actinium accumulated on the second adsorbent is eluted from the second adsorbent by a second eluent. The second eluent has a pH value that is particularly different from the pH value of the first eluent such that actinium is eluted from the second adsorbent. The second eluent preferably contains a second acidic solution containing the same acid as the target solution, particularly nitric acid. 225 actinium accumulates during the first elution step. The method includes a second elution step in which at least a portion of the actinium accumulated on the second adsorbent is eluted from the second adsorbent by a second eluent. The second eluent has a pH value that is particularly different from the pH value of the first eluent such that actinium is eluted from the second adsorbent. The second eluent preferably contains a second acidic solution containing the same acid as the target solution, particularly nitric acid.

[0062] Therefore, the actinium eluted from the first extraction device can be easily collected in the second extraction device and eluted again from the second extraction device in a more concentrated and pure form. Preferably, the second eluent pushes the first eluent out of the second extraction device during the second elution step, preferably without being mixed with the first eluent.

[0063] In a nineteenth embodiment of the method according to the invention, applicable to the eighteenth embodiment, the first eluent is circulated from the first extraction device to the second extraction device through a second radon filter, particularly a second activated carbon filter, and radon is extracted from the first eluent.

[0064] The radon generated by the first extraction device, and the radon generated by the irradiation device and collected by the first extraction device, can be removed from the first extraction device by the second radon filter when the first extraction device is eluted. This filter can also be, for example, an activated carbon filter to which radon adheres. This radon then decays to 210 generate Pb, which remains within the system / facility. From the system / facility 210 To enable the removal of Pb, an extraction chromatographic column containing a lead extraction device, such as Sr resin or Pb resin (Eichrome), can be provided within the system / facility, and both Sr resin and Pb resin are very efficient in removing Pb.

[0065] In a 20th embodiment of the method according to the invention, applicable to the 18th or 19th embodiment, the second eluent is circulated in a fifth closed loop through a third extraction device during the second elution step, and the third extraction device contains a third adsorbent on which actinium eluted from the second adsorbent by the second eluent accumulates during the second elution step. The method includes a third elution step, in which at least a part of the actinium accumulated on the third adsorbent is eluted from the third adsorbent by a third eluent. The third eluent has a pH value particularly different from the pH value of the second eluent such that actinium is eluted from the third adsorbent, and the third eluent contains a third nitric acid solution. 225 actinium accumulates during the second elution step. The method includes a third elution step, in which at least a part of the 225 actinium accumulated on the third adsorbent is eluted from the third adsorbent by a third eluent. The third eluent 225 has a pH value particularly different from the pH value of the second eluent such that actinium is eluted from the third adsorbent, and the third eluent contains a third nitric acid solution.

[0066] Therefore, the actinium eluted from the second extraction device can be easily collected by the third extraction device and eluted again from the third extraction device in a more concentrated and / or pure form. Preferably, the third eluent preferably pushes the second eluent out of the third extraction device during the third elution step without being mixed with the second.

[0067] In a 21st embodiment of the method according to the invention, applicable to the 20th embodiment, the second eluent is circulated from the second extraction device through a third radon filter, in particular a third activated carbon filter, to the third extraction device, and radon is extracted from the second eluent.

[0068] Radon arriving at the second extraction device can be removed from the second extraction device by the second radon filter when the second extraction device is eluted. This filter is also, for example, an activated carbon filter to which radon adheres. This radon then decays to 210 produce Pb, which remains within the system / facility. From the system / facility 210 To enable the removal of Pb, an extraction chromatographic column containing a lead extraction device, for example Sr resin or Pb resin (Eichrome), can be provided within the system / facility, and both Sr resin and Pb resin are very efficient in removing Pb.

[0069] Further details and advantages of the present invention will become apparent from the following description of some examples of the production method according to the present invention. This description is given by way of example only and is not intended to limit the scope of the present invention as defined by the appended claims. The reference numbers used herein refer to the accompanying drawings.

Brief Description of the Drawings

[0070]

Figure 1

[0071]

Figure 2

Modes for Carrying Out the Invention

[0072] In the method of the present invention, 226Ra, and more specifically 226 A liquid target solution containing radium nitrate is prepared. This solution contains, in particular, 0.005 to 1.0 M nitric acid. It is preferably contained in a lead-shielded airtight bottle.

[0073] The facility schematically shown in FIG. 1 is specifically intended to 225 generate Ac, that is, the liquid target solution has an acidity containing, for example, 0.005 to 0.05 M HNO3. The concentration of Ra(NO3)2 in the target solution is preferably as high as possible and can be increased up to 0.4 M.

[0074] The facility includes a container 1 configured to contain the liquid target solution. The facility also includes an irradiation device 2 having a window through which the target solution can be irradiated with protons, deuterium, or gamma rays. Gamma ray irradiation can be obtained from a synchrotron or a linac, or can also be obtained by a conversion material as disclosed in US2002 / 0094056. However, the liquid target is preferably irradiated with protons (or deuterium) because 226 from Ra 225 it is the most efficient way to generate Ac. Proton irradiation can be generated by a cyclotron, for example 18 from 18 a cyclotron already commonly known for generating PET radioisotopes such as F from O.

[0075] The liquid target may be a static target, but in order to enable more efficient cooling and thus enable higher energy irradiation of the target to enhance the production capacity, the liquid target is preferably a recirculating liquid target as in the embodiment shown in FIG. 1. In this embodiment, the target solution is pumped by the pump 3 in the first closed loop 4 from the container 1 to the irradiation device 2, and then to the heat exchanger 5 and returned to the container 1. The target is also preferably cooled within the irradiation device 2 itself, especially water-cooled. The solution is preferably irradiated with protons having an incident energy of 15 to 20 MeV. During irradiation, the heat generated by stopping the protons in the target solution is completely or partially removed by the target solution itself and exchanged with the outside in the primary heat exchanger 5. The complete irradiation loop is configured such that all wetted parts are highly inert and airtight materials, typically Hastelloy, Inconel, etc., in order to avoid corrosion and ensure leak prevention. Combinations of ceramics or metals and ceramics can also be equally good choices.

[0076] During irradiation, 225 Ac is constantly building up in the target solution. When using a static target, when the irradiation is completed, the target solution is collected in an airtight target solution bottle. The static target is preferably automatically filled with an empty bottle. The recirculating liquid target can be reprocessed during the irradiation process. From there, 225 The chemical separation and purification of Ac is carried out by recycling the flow through an extraction chromatography or an ion exchange column. The conditions are set such that actinium is extracted on the column while the impurities are recycled. The size of the column, the flow rate, and the volume of the solution depend on the initial volume of the target solution.

[0077] In the case of a static target, the irradiated target solution contained in the bottle can be transferred and recycled to the first extraction device 6. In this extraction device 6, 225 Ac is extracted, while 226Ra (and, in the case of gamma-ray irradiation of the target solution, 225 Ra also) is maintained in the target solution. 226 The target solution from which Ac has been extracted is recycled back into the bottle and re-introduced into the liquid target to be irradiated.

[0078] In the facility shown in FIG. 1, 225 extracting Ac from the liquid target solution, 225 introducing the liquid target solution from which Ac has been extracted into the liquid target requires far fewer handling steps and is much easier to perform automatically. In the embodiment shown in FIG. 1, the irradiation target solution contained in container 1 is actually recycled to the first extraction device 6 in the second closed loop 7. This is done by a pump (not shown in FIG. 1).

[0079] The first extraction device includes a first adsorbent in which 225 Ac accumulates during the first extraction step. The first extraction device preferably includes, in the low-acid option, for example, a first extraction chromatography column based on LN-resin (Eichrome, HDEFIEP). When the target solution contains, for example, 0.005 - 0.05 M HNO3, for example 0.02 M HNO3, actinium is retained on the column, 226 Ra (if present 225 Ra) is recycled. The recycle volume determines the efficiency of the uptake of Ac from the target solution, and it is important to limit this volume so that breakthrough of Ac is avoided.

[0080] Loss of Ra from the target solution is preferably prevented. 226 From Ra 225 After separating Ac, it is important that most of the volume of the target solution present in the first column is pushed back into the target solution container 1.

[0081] After the initial separation, i.e., after the liquid target solution has been pumped or permeated through the column, the radium remaining in the first extraction device 6 is recovered by rinsing the column of the first extraction device 6 with the rinse solution 8. This rinse solution has a pH similar to that of the liquid target solution so that 225 Ac is retained on the column. The rinse 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 (such as DOWEX50W or Biorad50W, etc.). The radium extraction device 10 comprises a radium adsorbent on which the radium rinsed from the first adsorbent by the rinse solution 8 accumulates during the rinsing process.

[0082] To remove any radon accumulated in the first extraction device 6, the rinse solution 8 is preferably recirculated through a first activated carbon filter 11 for removing 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.

[0083] Further purification and concentration are carried out by extraction chromatography columns based on Ln resin, Sr resin, DGA resin or branched DGA resin (all Eichrome) since the column size becomes smaller, thereby reducing the elution volume as well. The change in acidity moves the actinium from one extraction column to the next, improving the purity and increasing the concentration factor each time. The last column of the process determines in which medium the actinium product leaves the process. In Figure 1, SCE (strong cation exchanger) is used and a corresponding high acidity is used to elute the actinium. An alternative would be an extraction chromatography resin selective for trivalent elements such as DGA or DGA-B (Eichrom) where the elution of actinium is carried out at a lower acidity.

[0084] In the embodiment shown in FIG. 1, the radium accumulated in the radium extraction device 10 is eluted from the radium extraction device 10 by a radium eluent 12 having a pH value or acidity different from that of the rinse solution, and thus, during the radium elution process, radium is eluted from the radium adsorbent. The rinse solution 8 may contain, for example, a 0.02M nitric acid solution, while the radium eluent 12 may contain, for example, a 2M nitric acid solution. The radium eluent 12 containing the recovered radium is stored in the airtight container 13. This container 13 is provided with a gas inlet 14 and a gas outlet 15. Therefore, in order to remove the radon gas generated in the container 13 during the storage of the radium contained in the container 13, the container 13 can be purged with a small amount of, for example, nitrogen gas. Since only a small amount is used, Rn can be captured and managed by a small activated carbon gas filter (not shown in FIGS. 1 and 2). The recovered Ra can be readjusted to the correct acidity, concentrated, and returned to the target solution as needed.

[0085] Accumulated on the first adsorbent in the first extraction device 6 225 Ac is eluted from the first adsorbent by the first eluent 16 in the first elution step after the rinsing step. This first eluent 16 has a pH value different from that of the liquid target solution so that Ac elutes during the first elution step from the first adsorbent contained in the first extraction device 6. The first eluent 16 has a lower pH, that is, a higher acidity, and may include, for example, a first nitric acid solution containing 0.5M of HNO3. With such an eluent, 225 Ac can be removed from the Ln resin. 225 Ac can be removed from the Ln resin.

[0086] The first eluent 16 is circulated in a fourth closed loop 17 passing through the first extraction device 6 and the second extraction device 18 during the first elution step, and the second extraction device 18 is eluted from the first extraction device 6 by the first eluent 16 225It contains a second adsorbent on which actinium accumulates during the first elution step. The second extraction device preferably includes a second extraction chromatography column based on, for example, DGA resin (Eichrome, TODGA) in the low acidity option shown in FIG. 1. When the first eluent 16 contains, for example, 0.5 M HNO3, actinium is retained on the DGA column and the impurities are recycled. The free column volume of the second extraction device 18 is preferably smaller than the free column volume of the first extraction device 6 so that actinium can be concentrated on the second extraction device 18 and eluted from the second extraction device 18 with a smaller amount of the second eluent 19.

[0087] To remove radon gas that may be present in the fourth closed loop 17 of the facility, the first eluent 16 is circulated from the first extraction device 6 through a second radon filter 20, particularly a second activated carbon filter, to the second extraction device 18, and radon is extracted 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.

[0088] 225 When actinium accumulates on the second adsorbent housed in the second extraction device 18, 225 Actinium is eluted from the second adsorbent by the second eluent 19 in the second elution step. The second eluent is during the second elution step from the second adsorbent contained in the second extraction column 225 It has a pH value or acidity different from that of the first eluent 8 so that actinium elutes. The second eluent 19 also preferably contains a second nitric acid solution here and contains, for example, 0.05 M HNO3 in the low acidity option shown in FIG. 1. With such a second eluent, 225 Ac can be removed from the DGA resin.

[0089] The second eluent 19 is circulated in a fifth closed loop 21 passing through the second extraction device 18 and the third extraction device 22 during the second elution step, and the third extraction device 22 is eluted from the second extraction device 18 by the second eluent 19 225It includes a third adsorbent on which actinium accumulates during the second elution step. The third extraction device 22 preferably includes a third extraction chromatography column based on Ln resin (Eichrome, HDEHEP) in the low acidity option shown in FIG. 1, for example also here. When the second eluent 19 contains, for example, 0.05 M HNO3, actinium is retained on the Ln column and the impurities are recycled. If further concentration is not required, the free column volume of the third extraction device 22 may be equal to the free column volume of the second extraction device 18.

[0090] To remove the radon gas that may be present in the fifth closed loop 21 of the facility, the second eluent 19 is circulated from the second extraction device 18 through a third radon filter 23, particularly a third activated carbon filter, to the third extraction device 22, and radon is extracted 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.

[0091] 225 When actinium accumulates on the third adsorbent contained in the third extraction device 22, 225 actinium is eluted from the third adsorbent by a third eluent 24 in the third elution step. The third eluent 24 has a pH value or acidity different from that of the second eluent 19 so that actinium elutes during the third elution step from the third adsorbent contained in the third extraction column 22. The third eluent 24 also preferably contains a third nitric acid solution here and contains, for example, 0.5 M HNO3 in the low acidity option shown in FIG. 1. With such a third eluent, 225 Ac can be removed from the Ln resin. 225 Ac can be removed from the Ln resin.

[0092] 225Further purification and optionally concentration of Ac is obtained in the embodiment of FIG. 1 by circulating the third eluent 24 in a sixth closed loop 25 through a third extractor 22 and a fourth extractor 26 during the third elution step, the fourth extractor 26 receiving the eluted Ac from the third extractor by the third eluent 24 during the third elution step. 225 The fourth extractor 26 may also comprise a DGA or DGA-B (branch) column, in which the acidity is reduced to 0.1M and in the final step 225 Actinium can be removed from the column. However, the fourth extractor 26 preferably comprises a SCE (strong cation exchanger). If the third eluent 24 comprises, for example, 0.5M HNO3, the actinium is retained in the SCE 26 and the impurities are recycled. The free column volume of the fourth extractor 26 may be equal to or less than the free column volume of the second extractor 18, 225 The second extraction device 18 may be equal to about half the free column volume to allow further concentration of Ac.

[0093] To remove any radon gas that may be present in the sixth closed loop 25 of the installation, the third eluent 24 is circulated from the third extractor 22 through a fourth radon filter 27, in particular a fourth activated carbon filter, to a fourth extractor 26 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.

[0094] 225 Once the actinium has accumulated in the fourth adsorbent contained in the fourth extractor 26, 225 The actinium is eluted from the fourth adsorbent by a fourth eluent 28 in a fourth elution step.

[0095] If the fourth extraction device 26 contains a DGA or DGA-B resin, the fourth eluent 28 is eluted from the fourth adsorbent contained in the fourth extraction column 26 during a fourth elution step. 225It has a pH value or acidity different from that of the third eluent 24 so that actinium is eluted. The fourth eluent 28 also preferably contains a fourth nitric acid solution here and contains, for example, 0.1 M HNO3 in the low acidity option shown in FIG. 1. With such a fourth eluent, 225 Ac can be removed from the DGA or DGA-B resin.

[0096] When the fourth extraction device 26 is an SCE, the fourth eluent 28 has a pH or acidity high enough to elute 225 Ac from the SCE. The fourth eluent 28 preferably also contains a fourth nitric acid solution having a high acidity in this case, for example, containing 2 M HNO3.

[0097] The obtained purified and concentrated 225 Ac can be removed through the outlet 29 of the fourth extraction device and subsequently dried to obtain a dry product. In the drying process, not only water but also the acid contained in the fourth eluent can be removed by evaporation.

[0098] As an example, the different extraction devices and solutions used in the facility as shown in FIG. 1 can have the following configurations.

[0099] TIFF0007696832000001.tif94169

[0100] FIG. 2 shows an alternative embodiment of the method according to the present invention, in which the liquid target solution has a higher acidity (lower pH). This high acidity option is based on the initial Ac / Ra separation using a DGA column. Here, the acidity in the target solution is, for example, a nitric acid concentration of 0.1 M to 0.5 M, and the 226The concentration of Ra can be up to 0.35M when the lower acidity is compensated by the addition of nitrate, for example ammonium nitrate. Actinium is removed by recirculation through the DGA column. The recirculation volume should be high enough to efficiently remove Ac, but should be within the volume of the column to avoid breakthrough of Ac. As in the case of the low acidity option, a strong cation exchanger manages the Ra remaining on the column after the initial actinium separation. Further purification is carried out by reducing the acidity and the uptake on the Ln resin column. Here, the acidity is selected to avoid co-extraction of Pb (i.e., 0.03M - 0.075M). There are various options available from this point, but subsequent purification and concentration using a DGA or DGA B column is probably the preferred method.

[0101] The part of the facility shown in Figure 2 corresponding to the facility shown in Figure 1 is indicated by the same reference numerals. Since the facility shown in Figure 2 functions in the same way as the facility described above with reference to Figure 1, the description of the functions of the common parts will not be repeated. Instead, specific examples of the various extraction devices and solutions used in the high acidity facility as shown in Figure 2 are shown in the following table.

[0102] TIFF0007696832000002.tif76154

[0103] As can be seen, the concentrated and purified 225 Ac has already been removed from the third extraction device 22. However, an additional extraction column, namely the lead extraction device 30, is provided in the fifth closed loop 21 between the second extraction device 18 and the third extraction device 22. Before the lead extraction device 30, there is a third radon filter 23, and after the lead extraction device 30, there is an additional radon filter 23'.

[0104] The lead extraction device 30 contains Sr resin, which is particularly effective for Pb and can be used to remove Pb from the equipment / system. Pb is generated by the decay of radon. Radon decays by alpha decay, causing radiation damage to the column material and affecting the column separation performance. Therefore, to extend the life of the column and 225 avoid radon contamination of the Ac product, it is preferable to prevent radon from moving downstream in the process. Radon is managed by a radon filter, i.e., a small column containing powdered activated carbon (PAC) or granular activated carbon (GAC). Radon is absorbed / strongly retarded in the PAC / GAC column and decays to 210 Pb, which is a gamma emitter. 210 Pb is eluted into the aqueous phase and contained within the process. The PAC / GAC column can be used multiple times. The Sr resin column is very effective for Pb and can thus be used to remove Pb from the process. The Sr resin column contains, as the stationary phase, a dicyclohexano-18-crown-6 derivative dissolved in octanol.

[0105] Also, in the low-acidity equipment of FIG. 1, the lead extraction device (Sr resin column) can be easily incorporated, particularly between the third extraction device 22 and the fourth extraction device 26. Preferably, there is a fourth radon filter 27 before the lead extraction device and an additional radon filter after the lead extraction device.

[0106] The method according to the present invention enables achieving a commercially interesting production rate, despite the relatively low concentration of Ra in the target solution as a result of the limited solubility of radium nitrate (which is, for example, 68 Zn(p,n) 68 more than 10 times smaller than the solubility of zinc nitrate used in the liquid target to generate 68 Ga by the 68 Ga reaction). 226 The production rate of Ac can be calculated. Up to 0.4 M of

[0107] 225 ​226 Along with the energy-dependent stopping power of protons in an aqueous solution (Nucleonica) containing Ra(NO3)2 226 Using the energy-dependent cross section of the Ra(p,2n) reaction (IAEA ENDF database), the production rate of a small layer of the liquid target is obtained, and these are summed up 225 To obtain the overall formation of Ac. The weekly production rates are shown in Table 1 as a function of the proton current used.

[0108] TIFF0007696832000003.tif66167

[0109] Regarding economic feasibility, 225 Assuming that a therapeutic treatment using Ac is approved, 225 The demand for Ac will increase significantly. The 225 Ac produced by the proposed method is 227 Of higher quality than 232 Ac produced by proton irradiation of a Th target, unless complex isotope separation of Ac is carried out 225 If it is assumed that production is carried out for 40 weeks a year and distributed as produced, the 225 Ac produced can cover more than 25,000 treatments. Therefore, the economic feasibility in the actinium production process is most likely to be guaranteed.

[0110] References: Boll,R.A.,Malkemus,D.,Mirzadeh,S.,Production of actinium-225 for alpha particle mediated radioimmunotherapy.Appl.Radiat.Isot.62,667-679(2005) Jost,C.U.,Griswold,J.R.,Bruffey,S.H.,Mirzadeh,S.,Stracener,D.W.,Williams,C.L.,Measurement of cross sections for the 232 Th(p,4n) 229Pa reaction at low proton energies.AIP Conference Proceedings:International Conference on Application of Accelerators in Research and Industry.Vol.1525,pp.520-524.(2013) Koch,L,Fuger,J,van Geel J.,Process for producing Actinium-225,EP0752709,1999 Apostolidis,C.,Molinet,R.,McGinley,J.,Abbas,K.,Moellenbeck,J.,Morgenstern,A.,Cyclotron production of Ac-225 for targeted alpha therapy,Appl.Radiat.Isot.,62,383-387(2005) Abbas,K.,Apostolidis,C.,Janssens,W.,Stamm,H.,Nikula,T.,Carlos,R.,Method for produing Actinium 225,EP1455364,2004 Apostolidis,C.,Janssens,W.,Koch,L.,Mcginley,J.,Molinet,R.,Ougier,M.,Van Geel,J.,Moellenbeck,J.,Schweickert,H.,Method for producing Ac-225 by irradiation of Ra-226 with protons,EP062942,2004 Morgenstern,A.,Apostolidis,C.,Molinet,R.,Lutzenkirchen,K.,Method for producing actinium-225,US patent 20060072698,(2006) Ermolaev, S.V., Zhuikov, B.L., Kokhanyuk, V.M., Matushko, V.L., Kalmykov Stepan, N., Aliev Ramiz, A., Tananaev Ivan, G. Myasoedov, B. Production of actinium, thorium and radium isotopes from natural thorium irradiated with protons up to 141 MeV Radiochim. Acta, 100, p. 223 (2012) Weidner, J.W., Mashnik, S.G., John, K.D., Hemez, F., Ballard, B., Bach, F.I., Birnbaum, E.R., Bitteker, L.J., Couture, A., Dry, D., et al. Proton-induced cross sections relevant to production of 225 Ac and 223 Ra in natural thorium targets below 200 MeV, Appl. Radiat. Isot., 70, pp. 2602 - 2607, (2012) 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 Cross Sections for 78 - 192 MeV Protons Incident on 232Th targets, Applied Radiation and Isotopes, 118, 366 - 374, (2016) 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 c and 223 Ra by irradiation of Th with accelerated protons,Radiochemistry,53,pp.73-80,(2011) Koch,L,Fuger,J,van Geel J.,Process for producing Actinium-225 from radium-226,EP0752710,1999-1 Melville,G.Meriarty,H.,Metcalfe,P.,Knittel,T,Allen,B.J.Production of Ac-225 for cancer therapy by photon-induced transmutation of Ra-226,Applied Radiation and Isotopes,65,1014-1022,(2007) Melville G.,Allen,B.J.,Cyclotron and linac production of Ac-225,Applied Radiation and Isotopes,67,549-555,(2009) Clarke,J.C.,High-Powered Cyclotron Recirculating Target for Production of the 18 F Radionuclide,PhD Thesis,North Carolina State University(2004)

Claims

1. ２２６ From radium ２２５ A method for producing actinium, comprising: ２２６ Preparing a liquid target solution containing radium; Irradiating the liquid target solution in an irradiation device (2) to produce actinium starting from radium contained in the liquid target solution, wherein the liquid target solution is circulated in a first closed loop (4) passing through the irradiation device (2) and a heat exchanger (5) during the irradiation step; ２２６ Starting from radium ２２５ A step of generating actinium, wherein the liquid target solution is circulated in a first closed loop (4) passing through the irradiation device (2) and a heat exchanger (5) during the irradiation step; In a first extraction step performed in a first extraction device (6), separating at least a part of the generated actinium from the remaining radium; ２２５ At least a part of the actinium is separated from the remaining radium ２２６ Including a step of separating from radium; Including Said ２２５ At least a part of the actinium is extracted from the liquid target solution in the first extraction device (6) in the first extraction step, while the radium is maintained in the liquid target solution; ２２６ The radium is maintained in the liquid target solution; The liquid target solution is circulated in a first closed loop (4) passing through a container (1) and the irradiation device (2) during the irradiation step and in a second closed loop (7) passing through the container (1) and the first extraction device (6) during the first extraction step; The first extraction device (6) includes a first adsorbent on which the 225 actinium accumulates during the first extraction step, and the method includes a first elution step in which at least a part of the 225 actinium accumulated on the first adsorbent is eluted from the first adsorbent by a first eluent (16). The first eluent (16) is circulated in a fourth closed loop (17) passing through the second extraction device (18) during the first elution step, and the second extraction device (18) contains a second adsorbent in which the 225 actinium eluted from the first adsorbent by the first eluent accumulates during the first elution step. The method includes a second elution step, and in the second elution step, at least a part of the 225 actinium accumulated on the second adsorbent is eluted from the second adsorbent by a second eluent (19), and the second eluent (19) has a pH value different from the pH value of the first eluent so that the 225 actinium is eluted from the second adsorbent during the second elution step. The method comprises the ２２５ liquid target solution from which a part of the actinium has been extracted is irradiated again in the irradiation device (2) to further ２２６ generate actinium in the liquid target solution starting from the ２２５ radium contained in the liquid target solution. A method characterized by this.

2. The method according to claim 1, characterized in that the liquid target solution is irradiated for less than 16 days before at least a part of the actinium is extracted from the liquid target solution. ２２５

3. The method according to claim 1 or 2, characterized in that the liquid target solution is irradiated with protons or deuterium during the irradiation step.

4. The method according to claim 1 or 2, characterized in that the liquid target solution is irradiated with gamma rays during the irradiation step, and ２２６ radium ２２５ is converted to radium and ２２５ radium ２２５ is converted to actinium to ２２５ generate actinium.

5. During the first extraction step, the ２２５ The method according to claim 4, characterized in that radium is maintained in the liquid target solution. **Claim 6** The liquid target solution ２２６ The method according to any one of claims 1 to 5, characterized in that it contains a solution of a radium salt and its corresponding acid. **Claim 7** The solution ２２６ The method according to claim 6, characterized in that it contains radium nitrate and nitric acid. **Claim 8** The liquid target solution has a predetermined pH value such that ２２５ actinium accumulates on the first adsorbent during the first extraction step, while the first eluent has a pH value different from that of the liquid target solution such that ２２５ actinium is eluted from the first adsorbent during the first elution step. The method according to any one of claims 1 to 7. **Claim 9** The method according to any one of claims 1 to 8, characterized in that the first eluent (16) contains a first acidic solution containing nitric acid. **Claim 10** The method according to any one of claims 1 to 9, characterized in that the second eluent (19) contains a second acidic solution containing nitric acid. **Claim 11** The method according to any one of claims 1 to 9, characterized in that the first eluent (16) is circulated from the first extraction device (6), through a second radon filter (20), to the second extraction device (18), and radon is extracted from the first eluent (16). **Claim 12** The second eluent (19) is circulated in a fifth closed loop (21) passing through a third extraction device (22) during the second elution step, and the third extraction device (22) is the one eluted from the second adsorbent by the second eluent (19) ２２５including a third adsorbent on which actinium accumulates during the second elution step, the method including a third elution step, in which at least a part of the actinium accumulated on the third adsorbent is eluted from the third adsorbent by a third eluent (24), the third eluent (24) having a pH value different from the pH value of the second eluent (19) such that actinium is eluted from the third adsorbent. A method according to any one of claims 1 to 11. ２２５ at least a part of the actinium accumulated on the third adsorbent is eluted from the third adsorbent by a third eluent (24), the third eluent (24) having a pH value different from the pH value of the second eluent (19) such that actinium is eluted from the third adsorbent. A method according to any one of claims 1 to 11. ２２５ including a third adsorbent on which actinium accumulates during the second elution step, the method including a third elution step, in which at least a part of the actinium accumulated on the third adsorbent is eluted from the third adsorbent by a third eluent (24), the third eluent (24) having a pH value different from the pH value of the second eluent (19) such that actinium is eluted from the third adsorbent. A method according to any one of claims 1 to 11. **Claim 13** The method according to claim 12, characterized in that the third eluent includes a third acidic solution containing nitric acid.

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